Natural history of asthma

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Jun 2019. | This topic last updated: May 23, 2019.

INTRODUCTIONThe natural history of asthma is variable and difficult to predict for a particular individual [1,2]. Children with asthma experience complete remission more frequently than adults; however, progression to severe disease is unusual in all age groups [3,4]. Although deaths do occur from asthma, they are rare, and asthma in the absence of other comorbid disease does not typically affect life expectancy [5,6].

The natural history of asthma from infancy to adulthood will be discussed here. The diagnosis and management of asthma, the impact of inhaled glucocorticoid treatment on the progression of childhood asthma, and the role of risk factors are discussed separately. (See «Asthma in children younger than 12 years: Initial evaluation and diagnosis» and «Diagnosis of asthma in adolescents and adults» and «Asthma in children younger than 12 years: Treatment of persistent asthma with controller medications», section on ‘Inhaled glucocorticoids’ and «An overview of asthma management» and «Risk factors for asthma».)

INFANTS AND CHILDRENMany infants wheeze early in life, but three of four school-aged children outgrow asthma by adulthood [1]. On the other hand, the majority of chronic asthma begins in the first six years of life [2,7,8]. (See «Evaluation of wheezing in infants and children».)

Wheezing during the first six years — Several studies examining the natural history of wheezing and asthma in the first six years of life support the concept that there are at least two groups of children who have wheeze and asthma-like symptoms at an early age [9-11]. One group tends to have intermittent symptoms, usually in relation to viral illnesses, and to outgrow the symptoms as the children get older. The other group, which tends to have later-onset and more persistent symptoms, is characterized by atopy, a positive family history of asthma, and an increased risk for asthma later in life. Despite identification of risk factors, prospective identification of an individual’s future asthma experience is not possible [2]. (See «Risk factors for asthma».)

One possible explanation for transient wheezing in infants is that infants have smaller airways, which predispose them to wheezing in the face of viral infections or other insults. This possibility is supported by the observation that infants who develop lower respiratory tract illnesses in the first year of life had reduced lung function prior to developing any symptoms [12].

A prospective study that followed 1623 children from before birth to age nine years examined risk factors for early transient wheeze (13 percent) and persistent wheeze (13 percent), compared with never/infrequent wheeze (74 percent) [13].

●Paternal asthma was a risk factor for persistent wheeze in boys (odds ratio [OR] 4.27, 95% CI 2.33-7.83), but not in girls.

●Maternal asthma was a risk factor for persistent wheeze in girls and boys (OR 2.13, 95% CI 1.04-4.35; OR 2.21, 95% CI 1.11-4.40, respectively).

●Black or Hispanic race/ethnicity were risk factors for persistent asthma in girls (OR 3.23, 95% CI 1.55-6.75 and OR 3.60, 95% CI 1.06-12.17, respectively).

●Bronchiolitis before age one year was a risk factor for persistent asthma in both sexes (OR 4.38, 95% CI 2.03-9.45; OR 6.49, 95% CI 3.29-12.79) in girls and boys, respectively. Atopic dermatitis was a similarly important risk factor in both sexes.

In an earlier study, 826 children were assigned to four categories according to their history of wheezing at three and six years of age: children who never wheezed; those with transient early wheezing; those with late-onset wheezing; and those with persistent wheezing [14].

●Sixty percent of children with wheezing in the first three years of life had no wheezing at six years of age. This group of transient early wheezers was distinguished from the other groups by their low pulmonary function (assessed by maximal expiratory flow at functional residual capacity [FRC]) both shortly after birth and at six years of age, even though they had «outgrown» their wheezing. The transient early wheezing and lower pulmonary function are likely due to smaller airways.

●In contrast, children with persistent wheezing had lung function values shortly after birth that were not different from those who never wheezed. However, at six years old, they had the lowest level of lung function and the highest frequency of carrying a diagnosis of asthma (46 percent) among all groups.

Risk factors for persistent wheezing and a predisposition to asthma in this population included:

●Frequent symptoms in the first year of life

●Eczema

●Elevated IgE levels

●Maternal history of asthma

●Maternal smoking

Another study, from the same group of researchers, reported results from another cohort of children [15]. A total of 786 children younger than five years of age were enrolled between 1972 and 1984 and followed for up to 11 years. The predictive power of various lower respiratory tract symptoms such as frequent cough, wheeze with and without colds, attacks of shortness of breath with wheeze (SOBWZ), chest colds, and a combination of cough, wheeze even without colds, or SOBWZ was assessed in relation to a subsequent diagnosis of asthma.

●No single lower respiratory tract symptom before the age of one year was predictive of a diagnosis of asthma at a later age.

●In logistic regression analyses, children with respiratory symptoms at one to two years but no respiratory symptoms at three to four years did not have a significantly increased risk for a new diagnosis of asthma between the ages of 5 and 11 years (OR = 1.7, 95% CI 0.5-6.0).

●In contrast, those with lower respiratory symptoms at three to four years but without symptoms at one to two years, and those with symptoms at both early age groups (ie, the groups with either late-onset symptoms or persistent symptoms), had increased risk for a new diagnosis of asthma between ages 5 and 11 years (OR = 9.2, 95% CI 3.2-26.2 and OR = 6.6, 95% CI 2.6-17.0 respectively).

Wheezing in later childhood — It has been estimated that between 30 and 70 percent of children with asthma are markedly improved or asymptomatic by early adulthood. Several studies have examined whether certain asthma characteristics during childhood predict the presence and severity of disease decades later [3,16-19]. As examples:

A retrospective cohort study of more than 13,000 newly diagnosed asthmatics, ranging in age from 5 to 44 years, used medication records to track the progression of disease over five years. Nearly half of these patients had mild asthma, while only 7 percent presented with severe disease [3]. When stratified by age, the following observations were noted:

●Patients younger than 15 years who were diagnosed with severe asthma had significantly higher five-year rates of improvement (80 versus 61 percent) and remission (23 versus 14 percent), when compared with older patients.

●Patients diagnosed with mild disease were unlikely to develop severe disease within five years, regardless of age.

A separate series of studies evaluated a cohort of 317 children with a history of wheezing to age 42, and compared them with 86 age-matched control subjects [16,17]. The prognosis depended upon the frequency of symptoms during childhood:

●86 percent of those with few symptoms at seven years of age continued to have little or no asthma.

●71 percent of those with frequent wheezing at seven years still suffered from recurrent bouts of asthma.

A four year study prospectively monitored 909 children who had been enrolled in the Childhood Asthma Management Program (CAMP) at ages 5 to 12 years [18]. Predictors of persistent asthma included atopy, low lung function, and higher airway hyperresponsiveness. Sensitization and exposure to indoor allergens were associated with three times the risk of persistent asthma. More severe asthma at study enrollment was associated with more severe asthma after four years of follow up.

Atopic sensitivity to mammalian allergens may predict persistence of asthma. In a study of 3430 Swedish children, children with persistent asthma from age 11 to 19 years were much more likely to have positive serum immunoassays for IgE specific to mammalian allergens than children without asthma (odds ratio 9.2, 95% CI 4.5-21) [20]. Dust mite sensitivity is much less common than mammalian allergen sensitivity in this area of Sweden due to the climate.

Severe asthma — Children with severe asthma tend to have marked atopy, reversible airflow limitation, high health care utilization, and a decline in lung function over time [21-23].

The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study, a three-year multicenter observational study, gathered information about the clinical course of asthma in 1261 children and adolescents with severe or difficult to control asthma [21,22,24]. Patients were managed by specialists (pulmonologists or allergists) although there was no experimental intervention.

Participants were age six or older and met one or both of the following criteria in the year before the study:

●High health care utilization (as defined as two or more unscheduled visits for asthma or two or more courses of oral glucocorticoids)

●High medication use (eg, requiring three or more medications to control asthma, long-term daily use of high dose inhaled glucocorticoids, or use of 5 mg daily or more of oral prednisone)

Approximately 60 percent were receiving three or more long-term controller medications. Despite this, 53 percent of children and 44 percent of adolescents required courses of oral prednisone and unscheduled visits within the three months prior to enrollment, indicating that asthma remained poorly controlled. Pulmonary function declined with age, particularly in adolescent boys [21]. The pre-bronchodilator percent predicted forced expiratory volume in one second (FEV₁) in boys declined from a mean of 0.91 at 6 to 8 years to 0.82 at 15 to 17 years (p<0.05). Prebronchodilator FEV₁ in girls was 0.94 at 6 to 8 years and 0.84 at 15 to 17 years (p<0.05).

Effect on future lung function — Asthma in early childhood results in decrements in pulmonary function that are persistent and detectable throughout childhood and adolescence, and even through adulthood, although the effects differ based on sex and age [25,26].

Longitudinal studies of children who developed asthma before six years of age demonstrate persistent lung function abnormalities that may be associated with reduced lung growth (lower peak FEV₁) and/or an «early decline» in lung function in adulthood.

●East Boston Study — Lung function was studied in a cohort of children from East Boston, aged five to nine years, over a 13-year period [25]. Boys with asthma experienced a larger increase in forced vital capacity (FVC) than nonasthmatic boys, whereas girls with asthma had consistently lower FEV₁ values compared with nonasthmatic girls.

●Childhood Asthma Management Program – The CAMP followed the lung function of 1041 children (420 girls and 621 boys) with mild to moderate persistent asthma, and compared it with the lung function of 5415 non-asthmatic children from the Harvard Six Cities Study [26]. In both boys and girls between the ages of 6 and 18 years, the FEV₁/FVC ratio was significantly lower and FVC was significantly greater for asthmatic children, compared with non-asthmatic children. In contrast to the East Boston study, boys had a lower FEV₁ between the ages of 10 to 18, whereas the differences in girls were not significant.

In a follow-up study, the lung function tests of 684 of the original 1041 CAMP participants who had at least one FEV₁ at the age of 23 to 30 were compared with the lung function values from individuals of the same sex, race or ethnic group, age, and height from the National Health and Nutrition Examination Survey (NHANES III) [27]. Four trajectories of lung function were observed: 170 (25 percent) had normal growth and no early decline in adulthood; 176 (26 percent) had reduced growth (lower peak FEV₁ at age 20 to 23) and an early decline in adulthood; 160 (23 percent) had reduced growth but no early decline; and 178 (26 percent) had normal growth but an early decline. Abnormal lung function in childhood and male sex were the strongest predictors of abnormal lung growth and early decline. The reduced growth and reduced growth with early decline patterns were more likely to develop into chronic irreversible airflow limitation, even in the absence of cigarette smoke exposure.

In the CAMP study, the duration of asthma also correlated with the degree of impairment in lung function. Baseline data from 1041 children with mild to moderate asthma in the CAMP study found a significant correlation between asthma duration and lower lung function, greater methacholine responsiveness, more asthma symptoms, and greater use of as-needed albuterol [28].

●Melbourne Asthma Study — Asthma in childhood continues to influence pulmonary function later in life [29-33]. The Melbourne Asthma Study followed 458 children from age seven years until age 50: 105 had never wheezed, 74 had mild wheezy bronchitis, 104 had wheezy bronchitis, 113 had asthma, and 83 had severe asthma [29]. Both the childhood asthma and severe asthma groups had deficits in mean FEV₁ and FEV₁/FVC ratio that were established by ages 7 and 10 years and persisted through age 50 years. The patterns for FVC were not reported in this study, and sex differences were not reported.

●Aberdeen — A cross-sectional, community-based study of respiratory symptoms in children was initiated in 1964 [34], with long-term follow-up of 177 participants in 2001 [35]. When adjusted for age, height, sex, and smoking status, adults with childhood asthma had diminished lung function compared with nonasthmatic controls (FEV₁ 2.45 versus 2.96 L). In addition, the rate of decline in FEV₁ was significantly greater for individuals with a history of asthma in childhood than for control subjects (-0.75 versus -0.59 L per year).

Effect on future airway responsiveness — Airway responsiveness can vary over time and is affected by factors such as puberty and duration of asthma. Among children with mild to moderate asthma followed in the CAMP trial described above, airway responsiveness increased after puberty in girls, but decreased after puberty in boys, independent of baseline FEV₁ [36]. In addition, after controlling for multiple variables, methacholine responsiveness increased (ie, the provocative concentration causing a 20 percent decrease in FEV₁ decreased) with longer duration of asthma [28].

ADULTSAdults are less likely than children to experience a complete remission from asthmatic symptoms [3,4]. However, the risk of progressive clinical deterioration is small, and asthma in the absence of other comorbidities does not appear to decrease life expectancy [5,6]. It is not clear which factors determine the course of asthma in adulthood, although some potential risk factors have been identified.

Adult onset asthma — «New onset» asthma in adulthood sometimes has its origin in undiagnosed childhood asthma. For those without evidence of prior asthma, new onset asthma at age 22 is twice as likely to occur in women as men. Among women, the rate of adult onset asthma is increased in the perimenopausal years.

The characteristics of adults aged 22 years who have a new diagnosis of asthma after age six were examined as part of a longitudinal study of asthma (Tucson Children’s Respiratory Study) that followed 1246 healthy newborns for 22 years [11]. Although subjects with new onset asthma at age 22 had no prior clinician diagnosis of asthma, 37 percent had reported wheezing during study visits in childhood and 19 percent had bronchial hyperresponsiveness by cold air bronchoprovocation at age 6.

Sex also appears to play a role in the age of onset of asthma, although the mechanism is unclear [36]. In the Tucson Children’s Respiratory Study, newly diagnosed asthma at age 22 was twice as likely in women compared with men [21].

Menopause may be another life phase associated with an increased frequency of new onset asthma. A longitudinal Northern European study assessed respiratory health in 2322 women at baseline and again at follow-up 10 to 12 years later when the women were age 45 to 65 years [37]. The odds of new-onset asthma were increased in women who were perimenopausal (odds ratio [OR] 2.40, 95% CI 1.09-5.30), early postmenopausal (OR 2.11, 95% CI 1.06-4.20), and late postmenopausal (OR 3.44, 95% CI 1.31-9.05) at follow-up compared with nonmenopausal women. Approximately 53 percent were current or former cigarette smokers, but adjustment for smoking status did not affect the results. Further study is needed to confirm these observation in other populations.

Symptoms and progression — Asthma severity appears to remain stable over several years, based on cohort studies that have assessed asthma severity in intervals of 5 to 23 years.

In the retrospective, medication-based cohort study of more than 13,000 newly diagnosed asthmatics described above (see ‘Wheezing in later childhood’ above), patients who received asthma therapy consistent with mild asthma were unlikely to progress clinically over the next five years [3]. Only 3 percent of patients diagnosed at age 15 or older with mild disease required treatment for severe disease five years later. (See «Diagnosis of asthma in adolescents and adults» and «Evaluation of wheezing illnesses other than asthma in adults».)

Similar results were noted in a follow up-study of 738 incoming college students who were initially evaluated by interview, physical examination, skin testing, and questionnaire [38]. When contacted 23 years later, 84 alumnae with a history of asthma completed symptom questionnaires, and the following observations were noted:

●40 (48 percent) were asymptomatic at follow-up, most of whom had been asymptomatic for more than 5 years.

●44 (52 percent) had ongoing symptoms of asthma. Within this group, 22 noted decreasing severity, 18 were unchanged, and only 4 experienced progression.

●The risk of developing asthma during this 23 year interval was small. Only 36 of 738 respondents (5.2 percent) reported a new diagnosis of asthma, corresponding to an incidence of 0.23 percent per year.

An unanswered question is whether inhaled glucocorticoids or other newer modalities of therapy can reduce airways remodeling and alter the natural history of asthma [39]. When assessed in children, inhaled glucocorticoids did not alter the natural history of asthma; benefits of inhaled glucocorticoids on asthma symptoms and lung function waned after discontinuation. These studies are discussed separately. (See «Asthma in children younger than 12 years: Treatment of persistent asthma with controller medications», section on ‘Impact on disease progression’.)

Severe asthma — Severe and difficult-to-treat asthma comprises a small portion of asthma patients, but a large portion of asthma morbidity.

The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study was a three-year multicenter observational study of 4756 patients, of whom 3489 (73 percent) were ≥18 years old [24]. The entrance criteria are described above. (See ‘Severe asthma’ above.)

Between 50 and 60 percent of patients were receiving three or more long-term controller medications. Despite this, 40 to 50 percent required courses of oral prednisone and unscheduled visits within the three months prior to interview, indicating that symptoms were not controlled in many.

Among TENOR participants age 65 and older, lung function was significantly more impaired than among younger adults in the study, although their health care utilization for asthma was lower [40]. The prebronchodilator forced expiratory volume in one second (FEV₁) was 66 ± 23 percent predicted in older patients and 76 ± 23.2 percent predicted in younger patients (p<0.001).

Effect on lung function — The majority of studies of adult asthma have found that the rate of loss of lung function appears greater in patients with more severe symptoms and those with newly diagnosed asthma, compared with individuals without asthma.

●Asthma versus healthy controls — Longitudinal studies demonstrate that patients with asthma have a more rapid decline in lung function than those without asthma [41,42]. In one report, for example, 1095 asthmatics were compared with 16,411 normal subjects using data collected over 15 years [41]. The participants with asthma had a greater rate of decline in FEV₁ (38 mL/year) compared with nonasthmatic participants (22 mL/year). The effect of asthma was present in men and women and among smokers and nonsmokers, although the decline was most rapid among smokers with asthma.

●Severity of symptoms — The rate of loss of lung function appears to be related to the severity of symptoms. In a study of young adults between the ages of 21 and 28 years, those with the most severe symptoms had the most rapid rate of decline in the FEV₁/forced vital capacity (FVC) ratio compared to controls and patients with less severe asthma [31].

●Recently diagnosed asthma — The rate of decline in lung function may be greatest in those with new onset asthma. One group studied 10,952 persons who were part of an ongoing longitudinal study, the Copenhagen City Heart Study, to analyze the rate of decline in lung function of adults with asthma [43]. Over a five-year period, 159 subjects were identified who were self-reported asthmatics at initial study and follow-up and 185 subjects who reported no asthma on initial encounter but developed asthma during the study. Those with new onset asthma had the largest loss of lung function; the excess decline, on average, was 39 mL/year in men and 11 mL/year in women when compared with declines in those without asthma. However, after controlling for the initial level of FEV₁, the rates of decline were not different between the groups.

In a subsequent report of 15 years of follow-up data from the same group, the more rapid decline in lung function of asthmatics was confirmed [41]. The decline in FEV₁ among subjects with asthma was 38 mL per year, compared with 22 mL per year in those without asthma.

Another study of adults greater than 60 years of age also noted a rapid decline in lung function around the time of diagnosis [44]. Rates of decline in FEV₁were almost twice as high in subjects with newly diagnosed asthma as in other subjects. This phenomenon may reflect the fact that the decline in lung function was what led the patients to seek medical attention. Alternatively, it may reflect submaximal therapy, although it is uncertain that optimal treatment can modify the rapid rates of decline in asthmatics. (See «Diagnosis and management of asthma in older adults».)

●Cigarette smoking — Cigarette smoking may contribute to a more rapid rate of decline in lung function in patients with asthma. In the Copenhagen City Heart Study, participants with asthma who smoked had the greatest rate of lung function decline compared with nonasthmatics and nonsmoking asthmatics [41].

In contrast to the above studies, the Melbourne Asthma Study, which followed patients with persistent childhood asthma up to age 50 (see ‘Effect on future lung function’ above), did not find a significant difference in the rate of decline between the asthmatic groups and the non-asthmatics [29]. However, this observation may be due to the relatively small number of subjects and the substantial deficits in lung function at a young age that did not leave much room for further decline in lung function. Similarly, data from the Childhood Asthma Management Program (CAMP) suggest that reduced lung growth due to early onset persistent childhood asthma has a greater impact on adult lung function than decline in lung function. (See ‘Effect on future lung function’ above.)

SOCIETY GUIDELINE LINKSLinks to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See «Society guideline links: Asthma in children» and «Society guideline links: Asthma in adolescents and adults».)

INFORMATION FOR PATIENTSUpToDate offers two types of patient education materials, «The Basics» and «Beyond the Basics.» The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on «patient info» and the keyword(s) of interest.)

●Beyond the Basics topics (see «Patient education: Asthma treatment in adolescents and adults (Beyond the Basics)» and «Patient education: Trigger avoidance in asthma (Beyond the Basics)»)

SUMMARY

●Wheezing in young children is a heterogeneous condition characterized by relatively low pre-illness lung function compared to that in healthy children. No single lower respiratory tract symptom before the age of one year is predictive of a diagnosis of asthma at a later age. (See ‘Wheezing during the first six years’ above.)

●For most children, wheezing before the age of six years is probably a benign condition reflecting smaller airways that will improve or resolve in a few years. (See ‘Wheezing during the first six years’ above.)

●A subgroup of children with wheezing before age six will have persistence of symptoms and will eventually develop clinical asthma. This subgroup is characterized by the atopic state, relatively severe and persistent symptoms at a young age, and a maternal history of asthma. Maternal smoking may also contribute. (See ‘Wheezing during the first six years’ above.)

●Children with more severe symptoms tend to have lower lung function than those with less severe symptoms; deficits in lung function that are established by six to seven years often persist into adult life. (See ‘Severe asthma’ above.)

●Wheezing and asthma in adolescence is associated with a high rate of persistence into adulthood (approximately 75 percent). Similarly, adults with wheezing are more likely than children to experience persistent asthma. However, adolescents and adults are unlikely to experience progressive worsening of asthma in the absence of other comorbidities. (See ‘Wheezing in later childhood’ above and ‘Adults’ above.)

●«New onset» asthma in adulthood sometimes has its origin in undiagnosed childhood asthma. For those without evidence of prior asthma, adult onset asthma is more likely to occur in women than men. The frequency of new onset asthma in women increases during the perimenopausal years. (See ‘Adult onset asthma’ above.)

●Among patients with severe asthma, older adults (≥65 years) have significantly more impaired lung function than younger adults, although their health care utilization for asthma is lower. (See ‘Severe asthma’ above.)

●Compared with healthy adults, the rate of loss of lung function is greater among adults with asthma, those with more severe asthma symptoms, and those with newly diagnosed asthma. (See ‘Effect on lung function’ above.)

Use of UpToDate is subject to the Subscription and License Agreement.

Topic 567 Version 22.0

Diagnosis of asthma in adolescents and adults

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Jun 2019. | This topic last updated: Jun 13, 2019.

INTRODUCTIONThe «classic» signs and symptoms of asthma are intermittent dyspnea, cough, and wheezing. Although typical of asthma, these symptoms are nonspecific, making it sometimes difficult to distinguish asthma from other respiratory diseases. The definitive diagnosis of asthma requires the history or presence of respiratory symptoms consistent with asthma, combined with the demonstration of variable expiratory airflow obstruction [1-3].

Tools used in the diagnosis of asthma include history, physical examination, pulmonary function testing, and other laboratory evaluations. This topic review describes these tools, followed by several specific strategies for making the diagnosis of asthma in adolescents and adults.

The diagnosis of asthma in children and older adults and an overview of asthma management are discussed separately. (See «Asthma in children younger than 12 years: Initial evaluation and diagnosis» and «Diagnosis and management of asthma in older adults» and «An overview of asthma management».)

DEFINITIONWhile asthma is readily recognized in its classic presentation, with intermittent cough, wheeze, and shortness of breath brought on by characteristic triggers and relieved by bronchodilating medications, it is difficult to provide a definition that distinguishes asthma from similar and overlapping conditions. In the absence of a definitive laboratory test or biomarker, asthma has defied precise definition, one acceptable to all disciplines (including clinicians, physiologists, and pathologists). Clinically, its symptoms are non-specific. Physiologically, asthma is characterized by bronchial hyperresponsiveness, the tendency of airways to narrow excessively in response to a variety of stimuli that provoke little or no bronchoconstriction in persons without airway disease, but bronchial hyperresponsiveness is not unique to asthma. Pathologically, asthma may be described broadly as «a chronic inflammatory disorder of the airways» [1]. However, this description omits the characteristic waxing and waning of airflow obstruction in asthma and fails to distinguish asthma from other inflammatory airways disorders, such as chronic bronchitis or bronchiolitis.

A more precise definition combines the central roles of inflammation and bronchial hyperresponsiveness with the characteristic clinical symptoms. Towards this end, asthma has been defined by the Expert Panel 3 of the National Asthma Education and Prevention Program as «a common chronic disorder of the airways that is complex and characterized by variable and recurring symptoms, airflow obstruction, bronchial hyperresponsiveness, and an underlying inflammation. The interaction of these features of asthma determines the clinical manifestations and severity of asthma and the response to treatment» [1]. This definition is descriptive of key features of the disease, but it lacks utility for patients and clinicians.

The Global Initiative for Asthma defines asthma as follows [2]: «Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation. It is defined by the history of respiratory symptoms such as wheeze, shortness of breath, chest tightness, and cough that vary over time and in intensity, together with variable expiratory airflow limitation.»

Many of the features described above for asthma overlap with chronic obstructive pulmonary disease (COPD). Sometimes the distinction between asthma and COPD is clear: chronic exercise limitation and persistent airflow obstruction in a middle-aged or older person with a history of more than 20 pack-years of cigarette smoking point to a diagnosis of COPD. In COPD, pre- and post-bronchodilator pulmonary function testing may confirm little or no reversibility of the airflow obstruction. At other times, however, the distinction is less clear, such as when patients with COPD exhibit episodic symptoms and a large reversible component to their airflow obstruction. Recognition of these overlapping features of both asthma and COPD in some patients has led to description of the asthma-COPD overlap syndrome, discussed below. (See ‘Differential diagnosis’ below and «Chronic obstructive pulmonary disease: Definition, clinical manifestations, diagnosis, and staging», section on ‘Definitions’.)

«Reactive airways disease» is an imprecise term that has been used to describe transient symptoms of cough and wheeze when confirmation of a diagnosis of asthma is lacking. Although it may be appropriate as a description of intermittent wheezing in very young children in whom a diagnosis of asthma cannot yet be definitively ascertained, it should be avoided in adolescents and adults in whom additional testing is available to confirm or exclude a diagnosis of asthma [4]. «Reactive airways dysfunction syndrome (RADS)» refers to an airway disorder resulting from an intense exposure to an inhaled chemical irritant or noxious gas. It is characterized by asthma-like features of bronchial hyperresponsiveness and airflow obstruction. (See «Reactive airways dysfunction syndrome and irritant-induced asthma».)

CLINICAL FEATURESAsthma is diagnosed before the age of seven years in approximately 75 percent of cases [5]. As a result, clinicians treating adolescents and adults will often encounter patients whose diagnosis of asthma was made years earlier. Many children experience a remission of asthma symptoms around the time of puberty, with potential recurrence years later. Asthma may develop at any age, although new-onset asthma is less frequent in older adults compared to other age groups. Occupational asthma, aspirin-sensitive asthma (aspirin-exacerbated respiratory disease), and eosinophilic asthma are distinct syndromes that typically have their onset in adulthood.

History — A pattern of respiratory symptoms that occur following exposure to triggers (eg, allergen, exercise, viral infection) and resolve with trigger avoidance or asthma medication is typical of asthma. Some patients will report all three of the classic symptoms of asthma, while others may report only one or two:

●Wheeze (high-pitched whistling sound, usually upon exhalation)

●Cough (often worse at night)

●Shortness of breath or difficulty breathing

«Wheezing» does not have a standard meaning for patients and may be used by those without a medical background to describe a variety of sounds, including upper airway noises emanating from the nose or throat. Cough may be dry or productive of clear mucoid or pale yellow sputum (made discolored by the presence of eosinophils). Asthma is a potential cause of unexplained chronic cough. (See «Evaluation of subacute and chronic cough in adults».)

Some patients describe chest tightness, a band-like constriction, or the sensation of a heavy weight on the chest. In contrast, sharp chest pain is rarely used to describe the sensation of asthma.

Because the symptoms of asthma are also seen in several other respiratory diseases, it is difficult to be certain of the diagnosis of asthma based upon history alone [6-8]. However, certain historical features heighten the probability of asthma:

●Episodic symptoms – Asthmatic symptoms characteristically come and go, with a time course of hours to days, resolving spontaneously with removal from the triggering stimulus or in response to anti-asthmatic medications. Patients with asthma may remain asymptomatic for long periods of time. Report of symptoms that occur or worsen at night is often a feature of asthma.

●Characteristic triggers – Respiratory symptoms triggered by exercise, cold air, and exposure to inhaled allergens (aeroallergens) are suggestive of asthma. A list of questions that can help elicit a history of asthma triggers is provided in the table (table 1).

Exercise-triggered symptoms typically develop 5 to 15 minutes after a brief (eg, five minutes) period of exertion or about 15 minutes into prolonged exercise and resolve with rest over approximately 30 to 60 minutes. This time-course is distinct from simple exertional dyspnea, which typically begins shortly after the onset of exertion and abates within five minutes of stopping exercise. In asthma, exercise-induced symptoms occur more commonly and are more intense when the inhaled air is cold. (See «Exercise-induced bronchoconstriction», section on ‘Clinical manifestations’.)

Allergens that commonly trigger asthmatic symptoms include dust mites, molds, furry animals, cockroaches, and pollens (table 1) [1]. The acute onset of lower respiratory tract symptoms reliably precipitated by exposure to a cat or dog is virtually pathognomonic of asthma. Allergenic foods very rarely cause isolated asthma symptoms without other simultaneous allergic manifestations, such as angioedema, urticaria, hypotension, or gastrointestinal distress. Symptoms brought on by irritant-type exposures (eg, cigarette smoke, strong fumes, changes in weather, airborne chemicals or dusts) are non-specific and do not favor a diagnosis of asthma over other respiratory diseases. Viral infections are common triggers for asthma, although they can provoke exacerbations in other chronic respiratory conditions as well. Moreover, acute viral bronchitis in the absence of asthma may at least transiently cause respiratory symptoms that mimic asthma. Unique to asthma is the onset of cough, wheeze, and/or chest tightness 30 to 120 minutes following ingestion of aspirin or any cyclooxygenase-1 inhibitor (referred to as «aspirin-sensitive asthma» or «aspirin-exacerbated respiratory disease»), but this sensitivity occurs in only a small minority (3 to 5 percent) of asthmatic patients. (See «Trigger control to enhance asthma management» and «Aspirin-exacerbated respiratory disease».)

Other rare but characteristic sensitivities that may occasionally be reported by persons with asthma include symptoms triggered by ingestion of sulfites or certain food dyes. (See «Allergic and asthmatic reactions to food additives».)

●Work-related exposures — It is estimated that as many as 10 percent of cases of new-onset asthma in the adult are due to workplace-related exposures (occupational asthma). The diagnosis may be suspected based on a characteristic history of asthmatic symptoms temporally associated with work-related exposures, especially in occupations in which there is exposure to known sensitizing agents. The diagnosis can be confirmed by demonstration of variable airflow obstruction before and after a work shift, and in some cases the diagnosis is supported by identification of IgE-specific antibodies in the blood to the offending sensitizer [9]. (See «Occupational asthma: Clinical features, evaluation, and diagnosis».)

●Personal or family history of atopy – A strong family history of asthma and allergies or a personal history of atopic diseases (eg, atopic dermatitis, seasonal allergic rhinitis and conjunctivitis) favors a diagnosis of asthma in a patient with suggestive respiratory symptoms. (See «Risk factors for asthma», section on ‘Atopy and allergens’ and «Genetics of asthma».)

●History of asthmatic symptoms as a child – As previously mentioned, recollection of childhood symptoms of chronic cough, nocturnal cough in the absence of respiratory infections, or a childhood diagnosis of «recurrent bronchitis» or «wheezy bronchitis» favors asthma, but may also be reported in someone with bronchiectasis or simply frequent childhood respiratory infections.

Certain historic features lessen the prior probability of asthma. These include:

●Lack of improvement following anti-asthmatic medications – Patients who have tried an inhaled bronchodilator and obtained no relief of their symptoms are less likely to have asthma. Similarly, lack of dramatic improvement with a course of oral glucocorticoids suggests a diagnosis other than asthma. (See ‘Differential diagnosis’ below.)

●Onset of symptoms after age 50 – In middle-aged and older patients, other respiratory and cardiovascular diseases with overlapping manifestations become the more likely explanation for these symptoms although the new onset of asthma remains a possibility. The evaluation of asthma in older adults is discussed separately. (See «Diagnosis and management of asthma in older adults».)

●Concomitant symptoms such as chest pain, lightheadedness, syncope, or palpitations suggest an alternate diagnosis such as pulmonary vascular disease, cardiomyopathy, early coronary artery disease, or pericardial disease. (See «Evaluation of the adult with dyspnea in the emergency department» and «Approach to the adult patient with syncope in the emergency department».)

●History of cigarette smoking – In patients with more than 20 pack-years of cigarette smoking, the likely etiology of cough, wheeze, and shortness of breath shifts away from asthma toward chronic obstructive pulmonary disease, although the two diseases can co-exist. (See «Chronic obstructive pulmonary disease: Definition, clinical manifestations, diagnosis, and staging».)

Physical findings — Widespread, high-pitched, musical wheezes are a characteristic feature of asthma, although wheezes are not specific for asthma and are usually absent between asthma exacerbations. Wheezes are heard most commonly on expiration, but can also occur during inspiration. Asthmatic wheezing usually involves sounds of multiple different pitches, starting and stopping at various points in the respiratory cycle and varying in tone and duration over time. It is different from the monophasic wheezing of a local bronchial narrowing (eg, due to an aspirated foreign body or bronchogenic cancer), which has single pitch and repeatedly begins and ends at the same point in each respiratory cycle.

Expiratory noises transmitted from the upper airway (eg, larynx, pharynx) can mimic wheezing and are often described as wheezing by patients. However, these upper airway noises are typically loudest over the neck and greatly diminished over the chest in contrast to true wheezes that are typically louder over the chest. Patients may be able to identify respiratory noises as inspiratory rather than expiratory. Clinicians can usually distinguish the low-pitched wheezes (also called «rhonchi») that clear with cough, a sign of increased airway secretions as may be seen in bronchitis or bronchiectasis, from the typical high-pitched expiratory wheezes of asthma. (See «Evaluation of wheezing illnesses other than asthma in adults».)

Physical findings that suggest severe airflow obstruction in asthma include tachypnea, tachycardia, prolonged expiratory phase of respiration (decreased I:E ratio), and a seated position with use of extended arms to support the upper chest («tripod position») [1,2]. Use of the accessory muscles of breathing (eg, sternocleidomastoid) during inspiration and a pulsus paradoxus (greater than 12 mmHg fall in systolic blood pressure during inspiration) are usually found only during severe asthmatic attacks. However, these signs are insensitive manifestations of severe airflow obstruction; their absence does not exclude the possibility of a severe asthmatic attack. (See «Examination of the arterial pulse» and «Acute exacerbations of asthma in adults: Emergency department and inpatient management», section on ‘Clinical findings’.)

Importantly, the presence or absence of wheezing on physical examination is a poor predictor of the severity of airflow obstruction in asthma. Wheezing may be heard in patients with mild, moderate, or severe airway narrowing, while widespread airway narrowing may be present in individuals without wheezing. Thus, the presence of wheezing alerts one to the likely presence of airway narrowing, but not its severity.

Extrapulmonary physical findings in patients with asthma that can provide evidence in support of or against a diagnosis of asthma include the following:

●Pale, swollen membranes on examination of the nasal cavities with an otoscope and a cobblestone appearance to the posterior pharyngeal wall suggest associated allergic rhinitis, a common condition among patients with allergic asthma. (See «Allergic rhinitis: Clinical manifestations, epidemiology, and diagnosis».)

●Nasal polyps, which appear as glistening, gray, mucoid masses within the nasal cavities, should prompt questioning about concomitant aspirin sensitivity, anosmia, and chronic sinusitis (picture 1). Since aspirin-exacerbated respiratory disease (asthma, nasal polyps, and aspirin sensitivity) is uncommon in childhood, the finding of nasal polyps in an adolescent with lower respiratory tract symptoms should lead to consideration of alternative diagnoses, specifically cystic fibrosis. (See «Aspirin-exacerbated respiratory disease» and «Cystic fibrosis: Clinical manifestations and diagnosis».)

●Atopic dermatitis with typical lichenified plaques in a flexural distribution, especially of the antecubital and popliteal fossae, volar aspect of the wrists, ankles, and neck (picture 2 and picture 3), may accompany asthma in adults. In early childhood it is a risk factor for the later development of asthma, with as many as a third of children with atopic dermatitis progressing to asthma. (See «Atopic dermatitis (eczema): Pathogenesis, clinical manifestations, and diagnosis» and «Risk factors for asthma», section on ‘Atopy and allergens’.)

●Clubbing is not a feature of asthma; its presence should direct the clinician toward alternative diagnoses such as interstitial lung disease, lung cancer, and diffuse bronchiectasis, including cystic fibrosis. (See «Approach to the adult with interstitial lung disease: Clinical evaluation» and «Cystic fibrosis: Clinical manifestations and diagnosis».)

EVALUATIONThe laboratory evaluation of a patient with suspected asthma is predominantly focused on pulmonary function testing. Other laboratory studies, including chest radiography, blood tests, and tests for allergy, are useful in selected patients but cannot of themselves establish or refute a diagnosis of asthma.

Pulmonary function testing — Tests of airflow limitation are critical tools in the diagnosis of asthma. A detailed discussion of a wider range of pulmonary function tests used in the diagnosis of asthma and other causes of shortness of breath is presented separately. (See «Pulmonary function testing in asthma».)

Spirometry — Spirometry, in which a maximal inhalation is followed by a rapid and forceful complete exhalation into a spirometer, includes measurement of forced expiratory volume in one second (FEV₁) and forced vital capacity (FVC) [10]. These measurements provide information that is essential to the diagnosis of asthma [1]. We obtain baseline spirometry in virtually all patients with a suspected diagnosis of asthma. (See «Office spirometry» and «Pulmonary function testing in asthma».)

The results of spirometry can be used to determine the following:

●Determine whether baseline airflow limitation (obstruction) is present (reduced FEV₁/FVC ratio)

●Assess the reversibility of the obstructive abnormality by repeating spirometry after administration of a bronchodilator

●Characterize the severity of airflow limitation (based on the FEV₁ as a percentage of the normal predicted value)

●For patients with normal airflow (normal FEV₁/FVC ratio), identify a restrictive pattern as an alternate explanation for dyspnea (eg, FVC <80 percent predicted)

An obstructive pattern on spirometry is identified numerically by a reduction in the ratio of FEV₁ to FVC [11]. When FEV₁/FVC is reduced below normal (less than 0.70 or less than the lower limit of normal [LLN], which is the cut-off at the fifth percentile of the confidence interval provided electronically by modern computerized spirometers), airflow obstruction is present. When the FEV₁/FVC ratio is normal or increased, there is no expiratory airflow obstruction. (See «Pulmonary function testing in asthma» and «Selecting reference values for pulmonary function tests».)

Having identified the presence of airflow obstruction by a reduction in FEV₁/FVC, the severity of airflow obstruction is then categorized by the degree of reduction of the FEV₁ below normal. The severity of airflow obstruction based on spirometry is graded as borderline, mild, moderate, and severe as shown in the figure (figure 1), although other grading systems can be used [11,12]. These categories are used for pulmonary function interpretation and are NOT the same as categories used by the National Asthma Education and Prevention Program (NAEPP) guidelines to stage asthma severity (table 2) [1].

An obstructive pattern can also be identified visually by inspection of the shape of the expiratory flow-volume curve that is often provided by modern spirometry equipment. A scooped, concave appearance to the expiratory portion of the flow-volume loop signifies diffuse intrathoracic airflow obstruction, typical of asthma and many other obstructive lung diseases (figure 2). Inspection of the inspiratory and expiratory portions of the flow-volume loop can also be useful in identifying the characteristic patterns seen in upper airway obstruction (figure 3). (See «Overview of pulmonary function testing in adults», section on ‘Flow-volume loop’ and «Flow-volume loops».)

Bronchodilator response — We assess bronchodilator reversibility in almost all adult and adolescent patients with airflow limitation on their baseline spirometry, as recommended by the NAEPP guidelines [1]. Acute reversibility of airflow obstruction is tested by administering 2 to 4 puffs of a quick-acting bronchodilator (eg, albuterol), preferably with a valved holding-chamber («spacer»), and repeating spirometry 10 to 15 minutes later. Measurements can also be made before and after administration of nebulized bronchodilator. An increase in FEV₁ of 12 percent or more, accompanied by an absolute increase in FEV₁ of at least 200 mL, can be attributed to bronchodilator responsiveness with 95 percent certainty.

The presence of a bronchodilator response, in isolation, is not sufficient to make the diagnosis of asthma, however. Bronchodilator responsiveness may be seen with other conditions, such as chronic obstructive pulmonary disease (COPD), cystic fibrosis, non-cystic fibrosis bronchiectasis, and bronchiolitis. Asthma is typically distinguished from these other conditions by the capacity for a «large» increase in FEV₁. The definition of a large bronchodilator response is not standardized; investigators generally classify a large response as at least 15 or 20 percent. However, there is no precise cutoff value that defines an «asthmatic» bronchodilator response.

Occasionally, patients with asthma will have airflow obstruction on spirometry but fail to exhibit a 12 percent or greater increase in FEV₁ following bronchodilator (a «false negative» response). Reasons for false negatives include the following:

●Inadequate inhalation of the bronchodilator due to problems using the metered-dose inhaler correctly

●Recent use of a quick-acting bronchodilator or other anti-asthmatic medications (eg, long-acting bronchodilators), resulting in near-maximal bronchodilation prior to testing

●Minimal airflow obstruction at the time of testing (FEV₁ already close to 100 percent)

●In some patients with asthma, the presence of irreversible airways obstruction due to chronic airways inflammation or scarring

Changes in the forced expiratory flow between 25 and 75 percent of the vital capacity (FEF_25-75) observed over time or in response to bronchodilator are not used to diagnose asthma in adults; nor are decreases in the FEF_25-75 used to characterize the severity of asthma.

Bronchoprovocation testing — Bronchoprovocation testing is available in most pulmonary function testing laboratories and is a useful tool for diagnosing asthma in patients with normal baseline airflow. Bronchoprovocation testing can be used to identify or exclude airway hyperresponsiveness in patients with atypical presentations (eg, normal baseline spirometry, no variability in airflow limitation with serial spirometry or peak flow) or isolated symptoms of asthma, especially cough. (See ‘History’ above.)

A provocative stimulus (eg, inhaled methacholine, inhaled mannitol, exercise, or hyperventilation of dry air) is used to stimulate bronchoconstriction. People with asthma are more sensitive (hyperresponsive) to such stimuli than those without asthma (figure 4). When paradoxical vocal cord motion is being considered in the differential, an inspiratory and expiratory flow volume loop and sometimes also direct laryngoscopy are performed during bronchoprovocation testing to identify an upper airway response mimicking asthma. (See «Paradoxical vocal fold motion», section on ‘Pulmonary function tests’.)

The technical aspects of performing this type of testing, interpreting the results, and identifying the causes of false positive and false negative results are presented separately. A positive test (indicating bronchial hyperresponsiveness) is not entirely specific for asthma. Using a cut point of 8 mg/mL of methacholine or less to indicate the presence of hyperresponsiveness, as many as 5 percent of the normal population and a greater percentage of non-asthmatic persons with rhinitis will exhibit positive results. However, false negative results are uncommon, and a negative test (no significant decline in FEV₁ at the highest dose of methacholine administered) performed in a patient off controller therapy for asthma reliably excludes the diagnosis of asthma. (See «Bronchoprovocation testing», section on ‘Pharmacologic challenge’.)

Other specialized provocation testing can be used when further evaluation of the role of a specific precipitating factor is needed. Typical examples include measuring lung function before and after exercise when a diagnosis of exercise-induced bronchoconstriction related to asthma is suspected and evaluation of possible occupational asthma by FEV₁ or PEF measurements made before and after the work shift. (See «Exercise-induced bronchoconstriction» and «Bronchoprovocation testing», section on ‘Exercise challenge’ and «Occupational asthma: Clinical features, evaluation, and diagnosis».)

Peak expiratory flow — The peak expiratory flow (PEF) is measured during a brief, forceful exhalation, using a simple and inexpensive device (approximately $20). We typically use PEF measurements to monitor patients with a known diagnosis of asthma or to assess the role of a particular occupational exposure or trigger, rather than as a tool for the primary diagnosis of asthma [1]. In contrast to spirometry, applying quality control to peak flow measurements is difficult because of the lack of graphic display to ensure appropriate technique and maximal patient effort and the lack of ability to calibrate different peak flow meters.

●Technique – The PEF maneuver can be performed sitting or standing. Proper technique involves taking a maximally large breath in, putting the peak flow meter quickly to the mouth, sealing the lips around the mouthpiece, and blowing out as hard and fast as possible into the meter. For PEF, the effort does not need to be sustained beyond one to two seconds. The maneuver is performed three times and the highest of the three measurements is recorded (table 3and figure 5). (See «Peak expiratory flow monitoring in asthma» and «Patient education: How to use a peak flow meter (Beyond the Basics)».)

●Normal values – Average normal values for men and women are based upon height and age (calculator 1) (table 4A-B). Average normal values for adolescents are based upon height (table 5). The range of normal values around the mean is up to 80 to 100 L/min.

●Interpretation of PEF – A single peak flow determination made in the doctor’s office at the time that a patient is experiencing respiratory symptoms, if reduced from the normal predicted value, is suggestive of asthma. However, it is not diagnostic because a reduced peak flow is not specific for airflow obstruction and can be seen with other pulmonary processes. On the other hand, a reduced peak flow that improves by more than 20 percent approximately 10 to 20 minutes after administration of a quick-acting bronchodilator (eg, inhaled albuterol) provides supportive evidence favoring the diagnosis of asthma.

PEF measurements may vary as much as 15 to 20 percent from one measurement to the next in patients with asthma but without symptoms and in individuals without asthma. PEF results that vary little over time (less than 20 percent of the maximal value) argue against the diagnosis of asthma, particularly if reported symptoms are associated with unchanging peak flow measurements. In contrast, peak flow values that repeatedly fall by more than 20 percent when symptoms are present and return to baseline as symptoms resolve are consistent with asthma.

●Limitations of PEF – PEF measurement has several shortcomings as a diagnostic tool for asthma, including [1,10,11,13-16]:

•Peak flow values often underestimate the severity of airflow obstruction (figure 6). Significant airflow obstruction may be present on spirometry when the peak flow is within the normal range.

•Reduced peak flow measurements may be seen in both obstructive and restrictive diseases. Spirometry and sometimes measurement of lung volumes are necessary to distinguish the two.

•Peak flow measurements are not sufficient to distinguish upper airway obstruction (eg, vocal cord dysfunction) from asthma. Spirometry with a flow volume loop is needed for evaluation of upper airway obstruction. (See «Overview of pulmonary function testing in adults», section on ‘Flow-volume loop’.)

•The validity of PEF measurements depends entirely upon patient effort and technique. Errors in performing the test frequently lead to underestimation of true values, and occasionally to overestimation.

•Home PEF monitoring is unsupervised. Patients may produce higher values in the clinician’s office with appropriate coaching to ensure a maximal effort.

•Peak flow meters cannot be routinely calibrated, unlike spirometers. Thus, results and percent predicted values will vary somewhat between different instruments.

Exhaled nitric oxide — The measurement of nitric oxide in a patient’s exhaled breath (eNO) can be utilized as a method to aid in the diagnosis of asthma, but it is not widely available. The test is based on the observation that the eosinophilic airway inflammation associated with asthma leads to up-regulation of nitric oxide synthase in the respiratory mucosa, which in turn generates increased amounts of nitric oxide gas in the exhaled breath. Carefully calibrated equipment is designed to differentiate the concentration (in parts per billion) of nitric oxide in the exhaled breath of persons with asthma from the low levels of nitric oxide present in the exhaled breath of normal individuals. Use of oral and/or inhaled glucocorticoids reduces airway inflammation and levels of exhaled nitric oxide. Further studies are required to define better the sensitivity and specificity of exhaled nitric oxide as a diagnostic test for asthma, particularly among persons with other, potentially confounding respiratory diseases. (See «Exhaled nitric oxide analysis and applications».)

Blood tests — No blood tests are available that can determine the presence or absence of asthma or gauge its severity. However, a complete blood count (CBC) with differential white blood cell analysis to screen for eosinophilia or significant anemia may be helpful in certain cases. We typically obtain a CBC and differential when asthma symptoms are severe, the patient presents to the hospital with an exacerbation, nasal polyposis is present, the chest radiograph is abnormal (eg, suggestive of eosinophilic pneumonia or eosinophilic granulomatosis with polyangiitis [Churg Strauss]), or a parasitic infection is suspected.

●Markedly elevated eosinophil percentages (>15 percent) or counts (>1500 eosinophils/microL) may be due to allergic asthma, but should prompt consideration of alternative or additional diagnoses, including parasitic infections (eg, Strongyloides), drug reactions, and syndromes of pulmonary infiltrates with eosinophilia. Novel therapies utilizing anti-interleukin 5 monoclonal antibodies are now available to treat severe asthma with persistent eosinophilia (eg, mepolizumab and reslizumab). (See «Approach to the patient with unexplained eosinophilia» and «Overview of pulmonary eosinophilia».)

●Significant anemia can cause dyspnea that is unresponsive to asthma therapies and would require further evaluation to determine the causative process.

For the lifelong non-smoker with persistent and irreversible airflow obstruction, a one-time measurement of the serum alpha-1 antitrypsin level is recommended to exclude emphysema due to homozygous alpha-1 antitrypsin deficiency, which is in the differential of chronic and largely irreversible airflow limitation. (See «Clinical manifestations, diagnosis, and natural history of alpha-1 antitrypsin deficiency».)

Tests for allergy — Allergy tests are not useful for the diagnosis of asthma, but they can be helpful to confirm sensitivity to suspected allergic triggers of respiratory symptoms and to guide on-going management of asthma. We usually perform allergy testing in selected patients with a history of symptoms that occur upon exposure to particular aeroallergen(s) (table 1), persistent symptoms and suspicion of exposure to relevant allergens in the home environment (eg, pet animals, dust, cockroaches, or mice), and/or moderate-to-severe asthma symptoms despite conventional therapies. In addition to the peripheral blood eosinophil count mentioned above, the main tests for allergy are the total serum immunoglobulin E (IgE) level and the tests for specific allergic sensitization, which include blood testing for specific IgE antibody to inhalant allergens and skin testing with extracts of inhalant allergens.

Measurement of total serum IgE levels is indicated in patients with moderate-to-severe persistent asthma when considering treatment with anti-IgE monoclonal antibody (omalizumab) or when allergic bronchopulmonary aspergillosis is suspected on the basis of eosinophilia, a positive skin test to aspergillus, or radiographic evidence of mucus plugging or central bronchiectasis. An elevated total IgE level may occur in the absence of asthma (eg, in allergic rhinitis or eczema), and allergic asthma may be present in the absence of an elevated total IgE level, which may not fully reflect the levels of mast cell-bound IgE in airway tissue. Very high total IgE levels (>1000 IU/mL) are typically found in persons with allergic bronchopulmonary aspergillosis, certain parasitic infections, and sometimes eczema. (See «The biology of IgE», section on ‘Increased total IgE’ and «Clinical manifestations and diagnosis of allergic bronchopulmonary aspergillosis» and «Atopic dermatitis (eczema): Pathogenesis, clinical manifestations, and diagnosis».)

Allergic sensitivity to specific allergens in the environment can be assessed using either of two methods: blood tests for allergen-specific IgE or allergy skin tests.

●Blood tests for allergen-specific IgE most commonly utilize enzyme-linked immunosorbent assays (ELISA) to measure minute quantities of IgE antibody specifically directed at particular allergens (as opposed to the total serum IgE discussed above). This type of blood test is often referred to as RAST, although the radioallergosorbent assay method has been replaced with a non-radioactive detection reagent, called an immunoassay. Based on the aeroallergens in the patient’s geographic location and household, a panel of immunoassays is ordered. Aeroallergens (eg, house dust mite antigen, cat and dog danders, cockroach antigen, mouse and rat antigens, pollens, and mold spores) are the types of allergens most commonly implicated in asthma. Orally ingested food allergens rarely cause isolated asthmatic symptoms; inhaled food particles (eg, fish cooking, peanut dust on airplane) occasionally trigger asthma symptoms. By asking relatively few specific questions, clinicians can often elicit a potential relationship between allergen exposure and asthmatic symptoms that will guide the choice of which antigens to assess by immunoassay (table 1). When ordering these blood tests, one can select specific antigens for testing or choose among pre-grouped panels of antigens. The technique and accuracy of immunoassays are discussed separately. (See «Overview of in vitro allergy tests», section on ‘Immunoassays’.)

●Allergy skin tests are performed to a panel of indoor and outdoor aeroallergens. The negative predictive value of skin testing (using prick and intradermal techniques) is very high, such that skin testing can exclude allergy with relative certainty. Skin testing should be performed by a trained allergy technician and interpreted by an allergy specialist. The indications, contraindications, technique, and interpretation of allergy skin tests are presented in detail separately. (See «Overview of skin testing for allergic disease».)

The advantages of in vitro testing over skin testing are that no trained technician is needed to apply the test, antihistamines and other medications do not interfere with the results, and there is no risk of adverse reactions (eg, inducing asthmatic reactions or anaphylaxis). The disadvantages are the greater cost and somewhat lesser sensitivity of immunoassays compared with skin testing and lack of the immediate and often powerful visual feedback for the patient that occurs with a positive skin test reaction.

Imaging — In the absence of comorbid illness, the chest radiograph is almost always normal in patients with asthma. However, many clinicians, including ourselves, obtain a chest radiograph for new-onset moderate-to-severe asthma in adults over age 40 to exclude the occasional alternative diagnosis that may mimic asthma (eg, the mediastinal mass with tracheal compression or heart failure). The cost-effectiveness of this approach has not been evaluated.

In contrast, chest radiographs are routinely recommended when evaluating severe or «difficult-to-control» asthma and when co-morbid conditions (eg, allergic bronchopulmonary aspergillosis, eosinophilic pneumonia, or atelectasis due to mucus plugging) are suspected based on history, physical examination, and/orother laboratory data.

In addition, chest radiography is indicated in patients presenting with features that are atypical for asthma, including any of the following:

●Fever

●Chronic purulent sputum production

●Persistently localized wheezing

●Hemoptysis

●Weight loss

●Clubbing

●Inspiratory crackles

●Significant hypoxemia (eg, pulse oxygen saturation less than approximately 94 percent) in the absence of an acute asthmatic attack

●Moderate or severe airflow obstruction that does not reverse with bronchodilators

High resolution computed tomography (HRCT) scanning is performed when abnormalities seen on conventional chest radiography need clarification or when other processes are suspected, such as bronchiectasis, bronchiolitis obliterans, tracheomalacia, or vascular anomalies compromising central airways (eg, right sided aortic arch and aberrant left subclavian artery). (See ‘Differential diagnosis’ below and «Bronchiolitis in adults» and «Clinical manifestations and diagnosis of bronchiectasis in adults» and «Vascular rings and slings», section on ‘Right aortic arch with aberrant left subclavian artery and left-sided ductus arteriosus/ligamentum’.)

DIAGNOSISA history of intermittent symptoms typical of asthma plus the finding on physical examination of characteristic musical wheezing (present in association with symptoms and absent when symptoms resolve) strongly point to a diagnosis of asthma. Confirmation of the diagnosis of asthma is based on two key additional elements [1,2]:

●The demonstration of variable expiratory airflow limitation, preferably by spirometry

●Exclusion of alternative diagnoses (see ‘Differential diagnosis’ below)

Spirometry is the primary method for confirming variable airflow limitation; variability may be demonstrated by testing before and after bronchodilator, from one office visit to another, or before and after bronchoprovocation challenge. Use of pulmonary function testing in this manner helps to prevent both over- and under-diagnosis of asthma [17]. The importance of confirming reversible airflow limitation was illustrated by a study of 701 randomly selected adults with a physician diagnosis of asthma in the previous five years [18]. Upon careful review by a panel of experts, the diagnosis of asthma was excluded in 33 percent and among these, less than half had had previous testing to confirm airflow limitation. (See ‘Pulmonary function testing’ above.)

The results of initial spirometry are used to guide the diagnostic approach, as described in the following sections.

Initial spirometry shows airflow limitation — A symptom pattern suggestive of asthma AND airflow limitation on initial spirometry, which completely reverses to normal following bronchodilator, virtually clinch the diagnosis of asthma. Likewise, typical symptoms and a large reversibility of airflow obstruction on spirometry (increase in FEV₁ >15 percent) generally confirm the diagnosis of asthma. (See ‘Bronchodilator response’ above.)

As an example, reversible airflow obstruction in the patient with chronic cough but without other chest symptoms or wheezing on examination would assist in making the correct diagnosis of asthma. On the other hand, finding little or no reversibility does not necessarily exclude asthma, as the airflow limitation can be caused by concomitant airway inflammation that will only reverse with anti-inflammatory medication (eg, inhaled or oral glucocorticoids) or removal from exposure to an aeroallergen. However, incomplete or absent reversibility should raise the possibility of an alternate diagnosis. (See ‘Differential diagnosis’ below.)

Initial spirometry is normal — Patients with asthma who are asymptomatic at the time of evaluation often have normal lung function. For these patients, the following strategies can be used to confirm the clinical diagnosis [2]:

●Repeat spirometry at subsequent office visits when the patient is symptomatic

●Patient-recorded serial measurements of PEF over time (eg, morning and evening, with symptoms and then repeated again after administration of bronchodilator) using a portable device

●Bronchoprovocation testing, such as methacholine, mannitol, or exercise challenge (see ‘Bronchoprovocation testing’ above)

Serial measurements of lung function over time — One useful strategy for diagnosing asthma in patients with normal lung function on initial spirometry is to ask the patient to use a portable hand-held device to measure FEV₁ or PEF and record readings obtained twice a day for two weeks or with and without symptoms. The diagnosis of asthma is confirmed by a reliable series of recordings that document more than 20 percent variability in FEV₁ or PEF over time (especially when these reductions are associated with asthmatic symptoms). Individuals without asthma experience little variability (10 percent or less) in their PEF, even when respiratory symptoms are present [2].

Similar data collection can take place in the clinician’s office by recording spirometry or PEF at each patient visit. This method is less dependent on the reliability of the patient independently making self-measurements, although multiple visits may be required.

Serial patient-recorded measurements of FEV₁ (using a small, electronic, hand-held device) or PEF can be combined with a «therapeutic trial» of a bronchodilator [19]. Significant decreases in PEF that reverse within minutes of use of an inhaled beta-adrenergic agonist typify asthma. In individuals without asthma or other chronic airway disease, the increase in PEF following bronchodilator administration would be expected to be less than 20 percent.

Bronchoprovocation — The presence of airways hyperresponsiveness, a key feature of asthma, can be confirmed with bronchoprovocation testing, usually in the form of a methacholine or mannitol inhalation challenge. This diagnostic strategy is particularly useful for patients with atypical symptoms or an atypical response to medications. Given the test’s high negative predictive value, it is especially useful when exclusion of a diagnosis of asthma is helpful in patient management. Bronchoprovocation testing is a relatively costly diagnostic strategy and relies on the expertise of sophisticated pulmonary function laboratories. (See ‘Bronchoprovocation testing’ above and «Bronchoprovocation testing», section on ‘Diagnosis of asthma’.)

A positive methacholine provocation challenge (eg, a 20 percent decrease in FEV₁ at a methacholine concentration of 8 mg/mL or less) is indicative of airways hyperresponsiveness. While airways hyperresponsiveness is most commonly due to asthma, other diseases, such as COPD, cystic fibrosis, and allergic rhinitis, can cause a «false positive» methacholine challenge. (See «Bronchoprovocation testing», section on ‘Interpretation’.)

Diagnosis based on history and clinical course — In some instances, the history and clinical course are strongly suggestive of asthma, and a treatment trial is initiated as part of the diagnostic process. The combination of a typical presentation (eg, repeated episodes of typical symptoms triggered by typical stimuli), musical wheezes on auscultation, and a prompt response to anti-asthma medication may be used to make a presumptive diagnosis, as might occur for new-onset asthma presenting in an acute care setting. However, we agree with the NAEPP guidelines that the clinical diagnosis of asthma should be validated with objective data, whenever possible. For patients with less typical or more persistent or refractory symptoms, formal spirometric data are essential to ensure that the correct diagnosis is identified [20].

DIFFERENTIAL DIAGNOSISCough, wheeze, shortness of breath, and chest tightness, while characteristic of asthma, are also symptoms of a number of other respiratory diseases affecting both the upper and lower respiratory tracts. Some of these diseases can also result in airflow obstruction on spirometry. In addition, certain non-respiratory conditions (eg, heart failure, gastroesophageal reflux) may mimic asthma symptoms, and several common conditions (eg, chronic rhinosinusitis, laryngopharyngeal esophageal reflux) may coexist with asthma and increase its severity.

Conditions causing similar symptoms — Alternative diagnoses that may cause cough, wheeze, or shortness of breath include the following:

●Wheeze ─ Wheezing may be generated by luminal narrowing anywhere along the respiratory tract, including nares, pharynx, glottis, trachea, and bronchi. Inspiratory upper airway sounds, including stridor, are usually distinguishable from asthma. Expiratory wheezes emanating from the upper airway (eg, vocal cord dysfunction syndrome) are often readily audible without a stethoscope but sound distant on auscultation of the lower chest. However, at times these upper airway sounds may be transmitted widely throughout the chest, making differentiation from asthma difficult. A focal, monophonic wheeze (eg, bronchogenic carcinoma or foreign body aspiration) should not be confused with asthma. The full spectrum of disorders that can cause wheezing is presented elsewhere. (See «Clinical presentation, diagnostic evaluation, and management of central airway obstruction in adults» and «Evaluation of wheezing illnesses other than asthma in adults».)

●Cough ─ When persistent cough is the presenting complaint and lung function and chest radiograph are normal, the differential includes rhinitis or rhinosinusitis, gastroesophageal reflux disease (GERD), post-viral tussive syndrome, eosinophilic bronchitis, cough induced by angiotensin converting enzyme inhibitors, and infection with Bordetella pertussis («whooping cough»). (See «Evaluation of subacute and chronic cough in adults».)

A chronic cough with mucoid sputum production in a long-term cigarette smoker (generally more than 10 pack-years) points to a diagnosis of chronic bronchitis. Chronic bronchitis may develop in the presence or absence of airflow limitation on pulmonary function tests and may be partially alleviated by treatments for asthma.

●Dyspnea ─ Dyspnea has a broad differential, but common causes that are in the differential of asthma in the adult are COPD, heart failure, pulmonary embolism, and sarcoidosis. (See «Approach to the patient with dyspnea» and «Evaluation of the adult with dyspnea in the emergency department».)

Obesity can cause a pattern of dyspnea that mimics asthma [17]. In a study of patients with an elevated body mass index (BMI >30 kg/m²) and a doctor diagnosis of asthma, formal testing for bronchial hyperresponsiveness was negative in 36 percent [21]. This observation underscores the need for a definitive initial diagnosis of asthma. Obesity can also add to the severity of dyspnea in patients with asthma. (See «Risk factors for asthma».)

In patients with asthma-like symptoms, the diagnostic considerations vary in part by age:

●In adolescents and young to middle-aged adults, the principal considerations include recurrent bouts of bronchitis, bronchiolitis, bronchiectasis, paradoxical vocal cord motion, pulmonary embolism, GERD, panic disorder, and sarcoidosis. (See «Bronchiolitis in adults» and «Clinical manifestations and diagnosis of bronchiectasis in adults» and «Paradoxical vocal fold motion» and «Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism» and «Gastroesophageal reflux and asthma» and «Clinical manifestations and diagnosis of pulmonary sarcoidosis».)

●In older-aged patients, especially cigarette smokers, additional considerations include COPD, left-ventricular heart failure, sarcoidosis, tumors involving central airways, and recurrent oropharyngeal aspiration. (See «Chronic obstructive pulmonary disease: Definition, clinical manifestations, diagnosis, and staging» and «Evaluation of the patient with suspected heart failure».)

Conditions producing obstructive patterns on spirometry

●COPD typically presents in patients with a substantial smoking history (eg, >20 pack years). The symptoms of dyspnea on exertion and cough with or without sputum production can mimic adult-onset asthma. Variable airflow obstruction over time and an improvement on post-bronchodilator spirometry can be seen, similar to asthma, although the improvement in postbronchodilator spirometry is generally less pronounced in COPD and does not achieve normal values. (See «Chronic obstructive pulmonary disease: Definition, clinical manifestations, diagnosis, and staging».)

●Asthma-COPD overlap syndrome (ACOS) is characterized by persistent airflow limitation (may be partially reversible) in patients with features of both asthma (atopy and large variability in airflow limitation) and COPD (history of cigarette smoking and a component of irreversible airflow obstruction) [2,22]. While patients are typically age 40 or older, they may have had asthma symptoms since childhood. Aeroallergen sensitivity is common, as is a family history of asthma and allergy. Symptoms are typically persistent, but variable. Research suggests a distinct natural history and perhaps genetic predisposition compared to COPD without asthmatic features. (See «Chronic obstructive pulmonary disease: Definition, clinical manifestations, diagnosis, and staging».)

●Bronchiectasis, a condition of abnormal widening of the bronchi due to airway wall injury associated with chronic or recurrent infection, shares many clinical features with asthma, including inflamed airways, obstruction to airflow, and exacerbations characterized by increased dyspnea and sputum production. Bronchiectasis is suspected on the basis of prominent symptoms of cough with mucopurulent sputum production, recurrent chest infections, and sometimes hemoptysis. The diagnosis is usually established radiographically based on characteristic findings of bronchial wall thickening and luminal dilatation seen on chest computed tomographic (CT) scans. (See «Clinical manifestations and diagnosis of bronchiectasis in adults».)

●Constrictive bronchiolitis, also known as bronchiolitis obliterans, is characterized by submucosal and peribronchiolar fibrosis that causes concentric narrowing of the bronchiolar lumen. Constrictive bronchiolitis is most commonly seen following viral illness, inhalation injury, transplantation (eg, bone marrow, lung), or in the context of rheumatoid lung or inflammatory bowel disease (table 6). Symptoms include progressive onset of cough and dyspnea associated with hypoxemia at rest or with exercise. Crackles may be present. Pulmonary function tests show a progressive and irreversible airflow limitation. Findings on CT scan may include centrilobular bronchial wall thickening, bronchiolar dilation, tree-in-bud nodularity, and a mosaic pattern of attenuation of lung tissue density. (See «Bronchiolitis in adults» and «Bronchiolitis in adults», section on ‘Diagnosis’.)

●Central airway obstruction can be caused by numerous benign and malignant processes and can mimic asthma with dyspnea on exertion that may progress to dyspnea with minimal activity. Monophonic wheezing or stridor may be present. Symptoms are minimally, if at all, improved by inhaled bronchodilator. A high index of suspicion is needed as conventional chest radiographs are rarely diagnostic. Flow-volume loops can show the characteristic changes of flow limitation due to upper airway obstruction (figure 3 and figure 7). A high resolution CT scan with three-dimensional airway reconstruction can be helpful. The gold standard for diagnosis is direct visualization of the central airways via bronchoscopy. (See «Flow-volume loops» and «Clinical presentation, diagnostic evaluation, and management of central airway obstruction in adults», section on ‘Diagnostic evaluation and initial management’.)

Co-existent conditions — Certain illnesses commonly co-exist with asthma and may exacerbate its course. These illnesses are discussed separately. (See «Evaluation of severe asthma in adolescents and adults», section on ‘Comorbidities’.)

●Allergic rhinitis is present in most patients with allergic asthma and in at least 50 percent of those with non-allergic asthma [23]. The frequency with which rhinitis and asthma co-exist has prompted formation of the «integrated airway hypothesis,» which proposes that the two conditions are essentially one disorder, involving both the upper and lower airways in most patients [24]. Post-nasal drip associated with any form of chronic rhinitis or sinusitis can also worsen asthma symptoms. (See «Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis».)

●Both obesity and GERD can mimic asthma and can worsen pre-existent asthma. (See «Gastroesophageal reflux and asthma».)

●Patients with obesity and mild asthma may perceive more severe dyspnea than would be anticipated on the basis of spirometry. (See «Risk factors for asthma».)

INDICATIONS FOR REFERRALConsultation with an asthma specialist, either a pulmonologist or an allergist, is warranted when the diagnosis of asthma is uncertain, when the asthma is difficult-to-control, medication side effects are intolerable, or when a patient has frequent exacerbations. Pulmonologists may be most helpful if alternative pulmonary diseases are suspected or if further pulmonary testing or bronchoscopy may be needed. Referral to an allergist may be most helpful if allergic triggers need further evaluation or if concomitant nasal and ocular allergy symptoms are difficult-to-control.

SOCIETY GUIDELINE LINKSLinks to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See «Society guideline links: Asthma in adolescents and adults».)

INFORMATION FOR PATIENTSUpToDate offers two types of patient education materials, «The Basics» and «Beyond the Basics.» The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on «patient info» and the keyword(s) of interest.)

●Beyond the Basics topics (see «Patient education: Asthma treatment in adolescents and adults (Beyond the Basics)» and «Patient education: Trigger avoidance in asthma (Beyond the Basics)» and «Patient education: How to use a peak flow meter (Beyond the Basics)»)

SUMMARY AND RECOMMENDATIONS

●Asthma may develop at any age, although the majority of people with asthma are diagnosed in childhood. Obtaining the clinical history in an adult should include questions about the presence of symptoms earlier in life. Other historic clues that are highly suggestive of asthma include recurring, episodic symptoms, the presence of typical triggers (especially exercise, cold air, or allergen exposure), and personal or family history of allergic disease (table 1). (See ‘History’ above.)

●The physical examination may be normal in asthma. The presence of abnormal findings (such as wheezing) is suggestive of asthma, although not specific. Asthmatic wheezing is typically composed of multiple high-pitched sounds audible most prominently during expiration. Nasal examination should be included to check for the pale, swollen mucosa of associated allergic rhinitis or nasal polyps, which raise the possibility of aspirin-exacerbated respiratory disease. (See ‘Physical findings’ above.)

●The pulmonary function tests most helpful in diagnosing asthma are spirometry pre and post bronchodilator, bronchoprovocation testing (usually with methacholine), and peak expiratory flow (PEF) monitoring. Expiratory airflow obstruction with a reversible reduction in the forced expiratory volume in one second (FEV₁), heightened sensitivity to bronchoprovocative agents such as methacholine or exercise, and variability over time of >20 percent in PEF are findings consistent with asthma. (See ‘Pulmonary function testing’ above.)

●Other laboratory studies are sometimes indicated to identify potential asthma triggers and exclude alternative diagnoses, including blood tests (eg, allergen immunoassays), skin testing for environmental allergies, and a chest radiograph. (See ‘Evaluation’ above.)

●The diagnosis of asthma is based upon the presence or history of symptoms consistent with asthma (most commonly episodic cough, wheezing, or dyspnea provoked by typical triggers), combined with the demonstration of variable expiratory airflow obstruction. The strategies for using pulmonary function testing vary based on the results of baseline spirometry. (See ‘Definition’ above and ‘Diagnosis’ above.)

●The preferred approach to the diagnosis of asthma is the use of spirometry to identify reversible airflow obstruction. An obstructive pattern with an increase in FEV₁ of more than 12 percent from the baseline measurement, following administration of 2 to 4 puffs of a quick-acting bronchodilator, is suggestive of asthma, especially if post-bronchodilator spirometry is normal. (See ‘Spirometry’ above.)

●An alternative approach is to obtain serial measurements of FEV₁ or PEF over time at home or in the office. Patients can track the results in a peak flow diary (figure 5). A variability of >10 percent that corresponds to symptoms is strongly suggestive of asthma. PEF measurement can be combined with a therapeutic trial of inhaled bronchodilator. (See ‘Peak expiratory flow’ above and ‘Serial measurements of lung function over time’ above.)

●Bronchoprovocation testing, such as with a methacholine, mannitol, or exercise challenge, is typically reserved for patients in whom the baseline spirometry is normal and the diagnosis remains uncertain. (See ‘Bronchoprovocation testing’ above and «Bronchoprovocation testing».)

●For clinical settings in which neither spirometry nor peak flow measurement is available, a diagnosis of probable asthma can be made based upon history alone, provided the patient has typical symptoms that respond promptly and completely to therapy. History-based diagnosis is also appropriate for urgent care settings when patients respond to asthma therapies as expected. Peak flow measurements are appropriate in these office-based and urgent care settings to supplement history and exam. (See ‘Diagnosis based on history and clinical course’ above.)

●The differential diagnosis of asthma includes respiratory and non-respiratory conditions that may cause similar symptoms, wheezing, and/or an obstructive pattern on spirometry. Evaluation should include assessment for conditions that may co-exist with asthma and worsen its severity. (See ‘Differential diagnosis’above.)

●The classification of asthma severity (table 2) and a step-wise approach to asthma management are provided separately. (See «An overview of asthma management».)

Use of UpToDate is subject to the Subscription and License Agreement.

Topic 543 Version 25.0

Asthma in children younger than 12 years: Initial evaluation and diagnosis

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Jun 2019. | This topic last updated: Nov 16, 2018.

INTRODUCTIONAsthma is a significant health problem worldwide, and it is one of the most common chronic diseases of childhood in many countries [1,2]. The prevalence in different countries ranges from 1 to 18 percent. In the United States, for example, over nine million children have been ever told they had asthma, and over six million still have asthma [3]. Establishing a diagnosis of asthma involves a careful process of history taking, physical examination, and diagnostic studies. The differential diagnosis of wheezing must be carefully considered, particularly in infants and very young children, for whom testing for reversible airflow obstruction is not done routinely.

The epidemiology, initial evaluation, and diagnosis of childhood asthma are reviewed here. The assessment of severity/control and monitoring, and treatment of childhood asthma are discussed separately. (See «Asthma in children younger than 12 years: Initiating therapy and monitoring control» and «Asthma in children younger than 12 years: Treatment of persistent asthma with controller medications» and «Asthma in children younger than 12 years: Rescue treatment for acute symptoms».)

The pathogenesis, genetics, risk factors, and natural history of asthma are also reviewed separately. (See «Pathogenesis of asthma» and «Genetics of asthma»and «Risk factors for asthma» and «Wheezing phenotypes and prediction of asthma in young children» and «Natural history of asthma».)

EPIDEMIOLOGYA wide global variation exists in the prevalence of asthma, with higher rates typically seen in higher-income countries [4]. Asthma is the most common chronic disease in childhood in resource-rich countries. A significant increase in the estimated prevalence of asthma was seen in resource-rich countries in the 1980s and 1990s, with slower rates of increase in the 2000s and a plateau thereafter [5]. Approximately 8.3 percent of US children had asthma in 2016, down from 9.4 percent in 2010 and 8.7 percent in 2001. However, asthma prevalence continues to increase in other countries such as China [6]. Possible causes for the increase in asthma prevalence are reviewed in detail separately. (See «Increasing prevalence of asthma and allergic rhinitis and the role of environmental factors».)

Prevalence rates for current asthma in children under age 18 years increased in the United States from 2001 to 2009 (8.7 to 9.7 percent), then plateaued, with a prevalence of 8.3 percent in 2013 and 2016 [7,8]. Disparities in prevalence remained, with increasing prevalence seen in poor children and those living in the Southern US and the highest prevalence still seen in Puerto Rican and non-Hispanic black children, particularly for those living in inner cities. Before the onset of puberty, boys have a higher current prevalence of asthma than girls (9.2 versus 7.4 percent) [3,9]. This trend reverses in adolescence. Lifetime asthma prevalence for children was 12.7 percent in 2013 and 2016. The prevalence of asthma appears to have plateaued in other countries as well [10-14].

Asthma exacerbation rates among children with current asthma in the United States decreased from a rate of 62 percent among children <18 years old in 2001 to 48 percent in 2014 but increased in 2016 to 54 percent [3,8].

HISTORYThe history in a child with suspected asthma should focus on the presence of symptoms, typical symptom patterns, precipitating factors or conditions (ie, atopy), and known asthma risk factors (table 1).

Additional history that should be obtained in a child with established asthma who presents for disease monitoring includes previous and current therapy (controller and quick-relief medication use), exposure to triggers, utilization of health care services (emergency department [ED], hospital, unscheduled clinic visits), school attendance and performance, and participation in physical activity. Review of an asthma questionnaire such as the Asthma Control Test may provide additional useful information. (See «Asthma in children younger than 12 years: Initiating therapy and monitoring control», section on ‘Assessment of control’.)

The evaluation of a child who presents with an acute asthma exacerbation is discussed separately. (See «Acute asthma exacerbations in children younger than 12 years: Emergency department management».)

Symptoms — Approximately 80 percent of children with asthma develop symptoms before five years of age, but the disease is frequently misdiagnosed or not suspected, particularly in infants and toddlers [15]. Evaluating the presence of asthma symptoms is an important first step in establishing a proper diagnosis.

Coughing and wheezing are the most common symptoms of childhood asthma. Breathlessness, chest tightness or pressure, and chest pain also are reported. Poor school performance and fatigue may indicate sleep deprivation from nocturnal symptoms.

Cough — The presence of a nocturnal cough, a cough that recurs seasonally, a cough in response to specific exposures (eg, cold air, exercise, laughing, allergen exposure, or crying), or a cough that lasts more than three weeks should raise the suspicion for asthma [16]. Although wheezing is considered the hallmark of childhood asthma, cough is frequently the sole presenting complaint [17]. The most common cause of chronic cough in children older than three years is asthma, even if it is not accompanied by wheezing. The cough is typically dry and hacking but may be productive; when the cough is productive, clear or whitish sputum may be expectorated (which often contains eosinophils). It is not unusual for chronic cough lasting more than three weeks to be labeled «bronchitis» and to be treated with medications, such as cough suppressants, decongestants, or antibiotics. However, these types of cough may be manifestations of asthma and are likely to respond to asthma therapy. (See «Approach to chronic cough in children».)

Wheeze — Wheezing is a high-pitched, musical sound produced when air is forced through narrow airways. The wheezing of asthma tends to be polyphonic (varied in pitch), reflecting the heterogeneous distribution of affected airways. When airflow obstruction becomes severe, wheezing can be heard on both inspiration and expiration. In contrast to asthma, central airway obstruction may cause a harsh expiratory monophonic wheeze, as occurs with tracheomalacia. Upper airway obstruction (eg, vocal cord dysfunction) should be suspected if an inspiratory monophonic (of single pitch) wheeze (typically called stridor) is the only audible sound during an exacerbation. (See «Assessment of stridor in children».)

A silent chest in the context of an asthma exacerbation implies airflow limitation of such severity that audible wheezes cannot be produced; this represents a medical emergency. (See «Acute asthma exacerbations in children younger than 12 years: Emergency department management».)

Seasonal symptoms — Symptoms that are worse in certain pollen seasons are characteristic of atopic asthma. Trees in temperate climates pollinate in early spring, grasses in summer, and weeds in the fall. Children who are sensitive to molds tend to wheeze or cough during rainy seasons or if they are exposed to flooding or indoor dampness. Other allergic symptoms, such as rhinitis, conjunctivitis, or eczema, may flare concurrently with the chest complaints. (See «Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis» and «Allergic conjunctivitis: Clinical manifestations and diagnosis» and «Atopic dermatitis (eczema): Pathogenesis, clinical manifestations, and diagnosis».)

Symptom patterns — Chronic asthma symptoms assume several typical patterns:

●Intermittent exacerbations superimposed upon an asymptomatic baseline

●Chronic symptoms punctuated by periods of worsening symptoms

●Morning «dipping» (an accentuation of the physiologic cycle of pulmonary function in normal individuals, characterized by worsening of symptoms and decreased peak flow in the early morning, with improvement as the day progresses)

Precipitating factors — Wheezing or cough may occur at any time, but certain patterns and precipitating factors (table 2) are typical. Depending upon the type and intensity of the provocative agent, most acute asthma exacerbations have a slow onset over several days. Uncommonly, severe attacks may occur suddenly and with minimal warning, resulting in life-threatening exacerbations [18-22]. (See «Acute asthma exacerbations in children younger than 12 years: Emergency department management» and «Trigger control to enhance asthma management».)

Respiratory tract infections — Viral upper respiratory infections (URIs) are the most important triggering factor for patients with asthma of all ages, including infants and young children [23]. Clustering of asthma attacks between fall and spring suggests viral illness-induced phenomena [24,25]. Among children who are hospitalized for wheezing, respiratory syncytial virus, influenza virus, and rhinovirus are most common in those younger than three years (depending upon the season); rhinovirus is most common among older children [24]. (See «Role of viruses in wheezing and asthma: An overview».)

One study found that clusters of asthma hospitalizations in school-aged children in Canada occurred predictably after they returned to school following summer vacation and other breaks [26]. Specifically, there was a «September asthma epidemic» approximately 18 days after Labor Day (the first Monday of September), with a lesser increase in attacks two days later in preschool children and six days later in adults. Viral infections were the presumed cause, although a reduction in daily asthma medication use (eg, therapeutic holiday) during the summer months has also been implicated.

Chronic sinusitis (which is often bacterial) and respiratory infections due to Mycoplasma pneumoniae and Chlamydia pneumoniae may precipitate worsening of asthma [27-31]. (See «Pneumonia caused by Chlamydia pneumoniae in children» and «Mycoplasma pneumoniae infection in children», section on ‘Clinical features’.)

Exercise — Exercise-induced bronchospasm (EIB) may be the only manifestation of asthma in children [32]. It occurs in up to 90 percent of children with asthma [33].

Typical symptoms are shortness of breath, chest tightness, and cough. Exercise-triggered symptoms typically develop several minutes into prolonged exercise. Symptoms usually resolve with rest over 30 to 60 minutes. Lung function changes little or may even improve somewhat during most of the actual period of exercise. Lung function may begin to deteriorate towards the end of the exercise period and can fall quite markedly in some patients. The major fall in lung function normally occurs 5 to 10 minutes after stopping the exercise. Lung function then normally returns spontaneously to baseline over 30 to 45 minutes. A late-phase reaction occurs in a small proportion of patients with asthma [34], and some patients have both an immediate and a late-phase response to exercise [35]. (See «Exercise-induced bronchoconstriction».)

Certain types of exertion (eg, swimming) appear to be less provocative of asthma than others (eg, running, skating), probably because they produce less airway cooling and drying, which are thought to be provocative of EIB [32]. In a systematic review, patients with stable asthma who participated in swimming training had improved lung function and physical fitness, with no change in asthma symptoms or exacerbations [36]. However, there is an ongoing debate about potential lung damage caused by repeated respiratory exposure to chlorine byproducts in recreational swimmers [37-40]. We allow our patients to swim and only advise against it if chlorine appears to be an irritant trigger in a particular patient.

Short bursts of activity tend to be better tolerated than prolonged exercise. Repeated short periods of exercise tend to result in diminishing EIB with each episode. Nonetheless, children with asthma do not need to be steered toward particular sports, since they can participate in sports at any level (including the Olympics) with proper treatment, and improved exercise tolerance leads to lower respiratory rates with the same level of activity.

If untreated, longstanding EIB may result in poor overall fitness, decreased exercise stamina, a preference for a sedentary lifestyle, and exercise avoidance due to the distress brought on by physical activity. EIB that is difficult to control often indicates inadequately controlled underlying asthma.

Weather — Cold air; hot, humid air; changes in barometric pressure; rain; thunderstorms; or wind may be provocative factors for asthma in individual patients. (See «Trigger control to enhance asthma management», section on ‘Temperature and weather’.)

Tobacco smoke — Exposure to secondhand cigarette smoke is the single, most common, external risk factor for the development and progression of asthma symptoms in children [41-43]. (See «Secondhand smoke exposure: Effects in children».)

Allergens — Indoor and outdoor allergens are an important trigger of childhood asthma for the 80 percent of children with asthma and allergies, particularly those older than three years of age (see «Allergen avoidance in the treatment of asthma and allergic rhinitis»). These include [44]:

●House dust mites, cockroaches, and rodents [45-48]

●Pet exposures; cats and dogs are especially provocative, but other furry animals (gerbils, rabbits, hamsters, etc) may be suspect, especially if symptoms only occur in settings where these animals reside [49]

●Pollens [50]

●Molds

Irritant exposures — Asthma symptoms that occur after prolonged time indoors (eg, winter months or during periods of inclement weather) should raise a suspicion of sensitivity to indoor exposures to allergens (see ‘Allergens’ above) or inhaled airway irritants, such as [44,51]:

●Nitrogen dioxide (from gas stoves) [52]

●Particulates and smoke from wood fires, pellet stoves, or kerosene space heaters

●Propellant cleaning sprays

●Perfumes, hair sprays

●Paint

●Room deodorizers

●Cleaning products with strong odors

Stress — Various types of stress can trigger or exacerbate asthma [53], although asthma can also cause stress. However, asthma symptoms and exacerbations should not be attributed to stress unless all other exacerbating factors have been excluded. In addition, asthma should be sufficiently well controlled to allow patients to tolerate stressful situations and other unavoidable triggers without asthma exacerbations.

Additional history — Additional history that should be obtained in children with suspected asthma includes a personal history of other atopic diseases, family history of asthma or other atopic diseases (eg, allergic rhinitis, atopic dermatitis, and food allergy), environmental history, past medical history, medication use, medical utilization, school attendance, and psychosocial factors.

Allergic history — Allergic disease is associated with the development, severity, and persistence of asthma. As an example, up to 80 percent of children with atopic dermatitis develop asthma and/or allergic rhinitis later in childhood [54]. Approximately 30 percent of children with food allergy have asthma and respiratory allergy compared with 10 percent of children without food allergy [55]. Food allergy is also a risk factor for life-threatening asthma, as evidenced by a substantially higher rate of food allergy in children requiring intubation for asthma compared with a control group of asthmatic children [56]. Sensitivity to many mold allergens is associated with increased asthma severity and persistence [57,58]. (See «Role of allergy in atopic dermatitis (eczema)» and «Allergen avoidance in the treatment of asthma and allergic rhinitis» and «Risk factors for asthma», section on ‘Atopy and allergens’.)

In a study of children who were hospitalized for wheezing (cases), total serum immunoglobulin E (IgE) concentrations in the subgroup <3 years of age were similar to hospitalized children without wheezing (controls) but were significantly elevated among the cases in the subgroup >3 years old [24]. In addition, a higher percentage of cases were sensitized to at least one inhaled allergen (84 versus 33 percent).

In atopic infants, sensitization to common foods, such as egg white and cow’s milk, may occur and peaks at approximately eight months of age [59]. IgE antibodies to inhalant allergens generally appear beginning at two years of age and increase throughout childhood [59]. Food allergy and eczema are the most common manifestations of atopy in early life, whereas asthma and allergic rhinitis are more common in older children. (See «Atopic dermatitis (eczema): Pathogenesis, clinical manifestations, and diagnosis» and «Clinical manifestations of food allergy: An overview» and «Food allergy in children: Prevalence, natural history, and monitoring for resolution».)

Sensitization to foods and the presence of atopic dermatitis represent an atopic diathesis, whereas sensitization to airborne allergens also represents a trigger for asthma exacerbations.

Family history — The influence of genetics in the development of asthma has not been fully defined [43,60-66]. Because families also share environments, determining the influence of the genetic contribution to asthma is complicated. Nonetheless, a family history of asthma or other atopic disease (ie, allergic rhinitis, atopic dermatitis, or food allergy) certainly strengthens the likelihood that a child with a compatible history has asthma.

Children with one asthmatic parent are 2.6 times more likely to have asthma; with two asthmatic parents, the odds ratio rises to 5.2 [60]. Maternal asthma appears to make a bigger contribution than paternal asthma to asthma in offspring, although this finding is inconsistent [62-64].

Environment — A thorough review of all regular environments, including home, school, daycare, and relatives’ homes, is essential to evaluate possible provocative situations in the child with asthma. The table outlines some questions that may be helpful in obtaining this history (table 3). A strategy to avoid asthma triggers is one of the essential elements for managing the disease. (See «Trigger control to enhance asthma management» and «Allergen avoidance in the treatment of asthma and allergic rhinitis».)

Past medical history — A careful survey of all aspects of the child’s medical history is critical to formulate a differential diagnosis of the child’s complaint. Questions about the neonatal course, early respiratory symptoms, and the coexistence of systemic symptoms (failure to thrive, fever, developmental delay, recurrent infections) may point toward other diagnoses. Additional questioning may reveal evidence of comorbid conditions, such as obstructive sleep apnea (OSA), gastroesophageal reflux, or chronic rhinosinusitis.

Sleep disordered breathing, for example, was associated with a 3.6-fold increased risk of severe asthma in one study [67]. Another large, observational study found an improvement in asthma control (eg, decreased exacerbations, hospitalizations, and medication use) following adenotonsillectomy [68]. The latter results did not show, however, that adenotonsillectomy caused a reduction in the severity of childhood asthma. It is possible that the children who underwent adenotonsillectomy shared another unknown factor that led to improvements in their asthma over time, such as a reduction in upper respiratory tract infections. (See ‘Differential diagnosis’ below and «Evaluation of severe asthma in adolescents and adults», section on ‘Comorbidities’.)

Medications — A careful review of prior and present medications (including over-the-counter and alternative remedies) provides information on adherence to therapy, drug efficacy, drug delivery systems in use, accuracy of diagnosis, and control of asthma. Response to treatment with albuterol, as demonstrated by a decreased respiratory rate, diminished retractions, increased aeration, and/or decreased cough or wheezing, can be helpful in making the diagnosis of asthma, particularly in children unable to perform spirometry. The onset of action is within 20 minutes, and the benefits should last four to six hours.

Common reasons for poor response to asthma medications include:

●Nonadherence to the prescribed regimen. Parents and children often over-report adherence with controller medications; objective measures (eg, an inhaler with a dose counter) may be necessary to verify adherence [69]. Overuse of quick-relief medications (eg, short-acting beta agonists) with resultant tolerance can also be an issue. (See «Enhancing patient adherence to asthma therapy» and «Beta agonists in asthma: Acute administration and prophylactic use», section on ‘Tolerance’.)

●Improper inhaler technique. Since the efficacy of many asthma medications depends upon their deposition in the lung, inhalation technique figures strongly in the success or failure of inhaled therapies. Metered dose inhalers (MDIs) require a significant degree of coordination for optimal drug delivery, and there is considerable evidence that many patients and health care professionals do not regularly perform or teach proper inhalation technique [70,71]. Errors also can be made with dry powder inhalers (DPIs). Patient education materials, use of spacers (with MDIs), and frequent reappraisal of technique contribute to greater success with this form of therapy. Spacers with masks are especially helpful to the very young child. (See «Delivery of inhaled medication in children» and «The use of inhaler devices in children».)

●Ineffective drug dose or dosing interval. (See «Asthma in children younger than 12 years: Treatment of persistent asthma with controller medications».)

●Complicating medical problems (eg, chronic sinusitis, vocal cord dysfunction, gastroesophageal reflux, environmental allergies) [72,73]. (See «Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis» and «Paradoxical vocal fold motion» and «Clinical manifestations and diagnosis of gastroesophageal reflux disease in children and adolescents» and «Relationships between rhinosinusitis and asthma».)

●Complicating psychosocial factors (which can interfere with regularly obtaining and properly using medications).

●Inappropriate treatment (eg, antibiotics, antitussives, over-the-counter or alternative medications).

●Different response to controller medications depending upon the child’s intrinsic characteristics [74-77].

Health care utilization — The degree of asthma control is usually linked to health care utilization, such that more severe or poorly controlled patients with asthma tend to be treated more often in EDs or doctors’ offices. A history of more than a few such interventions is often indicative of poorly controlled asthma, regardless of the level of chronic symptoms [78]. In addition, a history of prior hospitalizations, ED visits, or exacerbations requiring oral glucocorticoids confers an increased risk for future asthma exacerbations.

School attendance — One-third of children with asthma suffer noticeable disability [79]. Interference with regular school attendance or achievement is a good measure of disability from childhood asthma. A pattern of significant numbers of lost days from school and a deteriorating academic performance should prompt more aggressive asthma management.

Nearly 14 million school days are missed each year due to asthma, although the percent of children with asthma who reported one or more missed school days declined significantly from 2003 to 2013 (61.4 versus 49 percent) [3] and held steady at 49 percent in 2016 [8]. Childhood asthma is also a major cause of parental work absenteeism [80,81].

Physical activity — Most children with asthma can have symptoms brought on by intensive activity; therefore, many children limit their level of exertion. In one study, children with newly diagnosed, untreated asthma were less fit and spent less time in vigorous activity than their healthy peers [82]. However, physical activities need not be restricted. Rather, appropriate treatment should allow full participation, which should be encouraged. With appropriate therapy, children with asthma can participate in all activities, including sports at every level up to and including participation in the Olympics [83], without restriction.

Psychosocial profile — Chronic asthma may create or exacerbate psychosocial problems for patients and their families. Conversely, psychosocial factors can affect asthma symptoms and health behaviors [84]. Stressors surrounding asthma can include:

●Anxiety about the often sudden, life-threatening nature of attacks

●Fear of dying

●Fear of peer rejection because of being «different»

●Concern regarding the adverse effects of asthma drugs (particularly glucocorticoids, also called corticosteroids)

●Sleep deprivation due to nocturnal symptoms

●Poor school performance

●Financial consequences

●Disruption in family routines

●Siblings’ resentment of the patient’s special status within the family

●Limitation of social or geographic venues because of potential triggering of asthma (eg, cannot visit places where environmental tobacco smoke or allergen exposure is likely)

●Family discord over asthma treatment

Predictive tools — Parents often ask if their young child with recurrent cough or wheeze has asthma and if he or she might outgrow it. Various predictive models or clinical indicators of risk have been studied to help the clinician identify young children who will continue wheezing later in childhood, although these tools were primarily designed to enrich study populations rather than actually predict asthma. These models have employed various risk factors associated with the development of asthma in longitudinal epidemiologic studies, such as parental history of allergic sensitization and asthma, wheezing history, atopic disease in the child, IgE levels, and cytokine secretion profiles. However, none of these clinical tools have been validated in populations different from the study group. These tools and risk factors are discussed in greater detail separately. (See «Wheezing phenotypes and prediction of asthma in young children», section on ‘Predictive tools in children with wheezing’ and «Natural history of asthma», section on ‘Infants and children’.)

PHYSICAL EXAMINATIONExamination findings during an acute exacerbation include tachypnea, hypoxia, wheezing, accessory muscle use, retractions, and prolonged expiratory phase. These findings are discussed in detail separately. (See «Acute asthma exacerbations in children younger than 12 years: Emergency department management».)

Physical examination of a child with asthma is generally normal if performed when the patient does not have an acute exacerbation. Abnormal findings in the absence of an acute exacerbation may suggest severe disease, suboptimal control, or associated atopic conditions. Abnormalities that may be observed include [78]:

●Decreased air entry or wheezing on auscultation

●A prolonged expiratory phase on auscultation

●Dry cough

●Signs of rhinitis, conjunctivitis, and sinusitis (nasal discharge, inflamed nasal mucosa, sinus tenderness, dark circles under the eyes) (see «Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis»)

●Signs of an acute respiratory infection

●A transverse nasal crease due to frequent itching (allergic salute)

●Halitosis due to chronic rhinitis, sinusitis, and mouth breathing

●Eczema/atopic dermatitis

●Nasal polyps (picture 1 and picture 2) (glistening, gray, mucoid masses within the nasal cavities, which may be associated with asthma and aspirin sensitivity in adolescents and adults, but should prompt evaluation for cystic fibrosis in children of any age) (see «Cystic fibrosis: Clinical manifestations and diagnosis»)

●An increased anterior-posterior diameter of the chest due to air trapping

Obesity — Results are conflicting regarding the relationship between obesity and asthma severity [67,85-88]. Obesity and higher percent body fat are associated with an increased incidence of asthma [89] and are more commonly seen in children with newly diagnosed, untreated asthma than their healthy peers [82]. Higher body mass index (BMI) is also associated with greater asthma severity [85,89]. However, biologic causality has not been proven, and reverse causation may also occur (ie, asthma limiting physical activity leading to obesity). (See «Risk factors for asthma» and «Evaluation of severe asthma in adolescents and adults», section on ‘Comorbidities’.)

DIAGNOSISA history of intermittent or chronic symptoms typical of asthma plus the finding on physical examination of characteristic musical wheezing (present in association with symptoms and absent when symptoms resolve) strongly point to a diagnosis of asthma (see ‘History’ above and ‘Physical examination’ above). Confirmation of the diagnosis of asthma is based on three key additional elements [78,90,91]:

●The demonstration of variable expiratory airflow limitation, preferably by spirometry, when possible

●Documentation of reversible obstruction

●Exclusion of alternative diagnoses (see ‘Differential diagnosis’ below)

Evidence of airway obstruction on spirometry, especially if acutely reversible with a bronchodilator, strongly supports the diagnosis of asthma. However, normal spirometry, or the lack of reversibility of obstruction in the setting of an acute exacerbation, does not exclude the diagnosis. A trial of asthma medication is warranted in patients with symptoms suggestive of asthma who have normal or near-normal spirometry or who are unable to perform spirometry due to age or other factors. Improvement on medications is sufficient to make the diagnosis in these patients. If a trial of asthma medication fails to improve symptoms, bronchoprovocation testing with methacholine, cold air, or exercise may be warranted. (See ‘Spirometry’ below and ‘Medications’ above and ‘Ancillary studies’below.)

Spirometry — Demonstration of reversible airflow obstruction establishes the diagnosis of asthma and facilitates the assessment of severity (figure 1) [78]. Spirometry is the preferred method of diagnosis of airflow obstruction. The National Asthma Education and Prevention Program (NAEPP) expert panel recommends performing spirometry in patients five years of age and older if a diagnosis of asthma is suspected [78]. (See «Overview of pulmonary function testing in children».)

Spirometry measurements include forced vital capacity (FVC) and the forced expiratory volume in one second (FEV₁). Airflow obstruction is defined as FEV₁reduced to less than 80 percent predicted and an FEV₁/FVC ratio of less than 0.85 (85 percent) (table 4A). Reference values are based on age, height, sex, and race [92]. FEV₁/FVC appears to be a more sensitive measure of impairment than FEV₁, whereas FEV₁ may be a more useful measure of risk for future exacerbations [78,93-96] (see «Asthma in children younger than 12 years: Initiating therapy and monitoring control», section on ‘Assessment of control’). Forced expiratory flow between 25 and 75 percent of vital capacity (FEF25-75) less than 65 percent correlates with reversible airflow obstruction in children with normal FEV₁ and may be a useful measure in this subgroup, although further studies are needed [97].

Spirometry should be performed before and after administration of a bronchodilator to assess for reversibility (bronchodilator response [BDR]) even in children with a normal baseline FEV₁ because many of these children will still have a BDR (both within the normal range and sometimes also supranormal) after treatment. Significant reversibility is indicated by an increase in FEV₁ of ≥12 percent from baseline after administration of a short-acting bronchodilator. This definition for BDR positivity was established primarily in adults. An increase in FEV₁ of ≥8 percent may be a better definition for BDR in children [98-100]. (See «Overview of pulmonary function testing in children».)

There is some evidence from cross-sectional studies to suggest that the NAEPP criteria for percent predicted FEV₁ (table 4A-B) do not accurately categorize asthma severity in children and that symptom frequency and rescue medication use may be more sensitive measures [93,94,101-103]. In the Childhood Asthma Management Program (CAMP) study, for example, the mean FEV₁ of all children studied was 94 percent predicted [94], although this study included only children with mild-to-moderate asthma based upon symptoms, use of medications, and response to methacholine [104]. Nonetheless, percent predicted FEV₁ remains a useful measure because it is strongly associated with the risk of asthma exacerbation in the 12 months after measurement [95,96].

Another potential spirometric measure of risk for asthma severity and poor control (asthma instability) is the air-trapping obstruction phenotype, defined as a FVC z score of <-1.64 (equivalent to fifth percentile in a healthy population) or a ≥10 percent change in the predicted value of FVC after bronchodilation. In a study of 560 children aged 6 to 17 years from low-income, urban areas who had physician-diagnosed asthma, the risk of ≥2 asthma exacerbations during the 12-month study period was more than fourfold higher (odds ratio 4.41, 95% CI 2.37-8.21) in those with this phenotype compared with those without any evidence of obstruction on spirometry [105]. Children with the air-trapping obstruction phenotype also had higher Composite Asthma Severity Index scores and asthma treatment steps, as well as greater sensitivity to methacholine challenge and variability in FEV₁ over time.

Measurements of peak expiratory flow using a peak flow meter are more variable and effort dependent. In addition, there is wide variability in the published predicted peak expiratory flow reference values and in the reference values from brand to brand [78]. Thus, peak flow measurements alone should not be used to diagnose asthma. Peak flow measurements may be more useful in monitoring a patient’s symptoms and response to therapy over time, although serial spirometry is preferred (table 4B) [78]. (See «Peak expiratory flow monitoring in asthma».)

Children <5 years — In infants and children younger than five years of age, the diagnostic steps should remain the same as described above, except that spirometry often cannot be performed in this age group. A trial of asthma medications may help to establish the diagnosis in these children. Reversal of symptoms and signs in the time expected for albuterol to work is suggestive of the diagnosis of asthma. Impulse oscillometry (IOS) is an alternative to spirometry in younger children since it only requires passive cooperation [106,107]. However, it is not readily available to most clinicians treating children with asthma, limiting its clinical utility [108]. IOS measurements at baseline and postbronchodilator differed significantly between children aged three to six years with and without asthma, whereas no significant differences were seen with traditional spirometry. IOS may detect alterations in respiratory mechanics not seen with spirometry even in older children [109-111]. (See ‘Diagnosis’ above and ‘Medications’ above.)

Debate is ongoing regarding how to best classify infants and young children with recurrent wheezing. The terms asthma, reactive airway disease, wheezy bronchitis, bronchiolitis, asthmatic bronchitis, wheezing-associated respiratory illness, and postinfectious bronchial hyperreactivity have all been employed. This jargon reflects an attempt to describe and define a subgroup of wheezing children with a more benign prognosis than is implied by «asthma,» which is, by definition, chronic. «Wheezy bronchitis» usually defines nonatopic babies or toddlers with recurrent, virus-induced wheezing (the majority of this group of wheezing young children) that tends to disappear by five years of age [112,113]. Asthma, on the other hand, has been taken to mean a chronic condition, frequently associated with atopy, provoked by a number of triggers in addition to viruses, and carrying a poorer prognosis for spontaneous resolution. (See «Diagnosis of asthma in adolescents and adults», section on ‘Definition’ and «Natural history of asthma», section on ‘Infants and children’ and «Wheezing phenotypes and prediction of asthma in young children» and «Role of viruses in wheezing and asthma: An overview» and «Evaluation of wheezing in infants and children» and «Approach to chronic cough in children».)

Ancillary studies — The history and physical examination, in conjunction with spirometry, are usually adequate to establish the diagnosis of asthma. Ancillary studies are most helpful to exclude competing diagnoses or to identify comorbid conditions.

Allergy testing — Allergy testing, done either by skin or in vitro testing, is helpful even in the very young child when used selectively. Specifically, when the environmental history uncovers exposure to furry animals (pets or pests), molds, cockroaches, or dust mites, it is worthwhile to test for these or other limited allergens to formulate proper avoidance strategies. Outdoor aeroallergens are unusual triggers in infants and very young children but may be triggers in older children. Food allergy testing is not helpful unless there is a sound history of gastrointestinal complaints, worsening eczema, urticaria, or asthma that is temporally associated with the ingestion of certain foods. Children with this type of history should be evaluated by a clinician familiar with food allergies and prescribed epinephrine since ingestion of a food allergen can be life threating in a patient with food allergies, particularly in a patient with concomitant asthma. In addition, when indicated testing reveals the presence of IgE antibody to any allergen, an atopic diathesis is demonstrated, increasing the likelihood that chest symptoms are due to asthma. (See «Overview of skin testing for allergic disease».)

Bronchoprovocation testing — We advise performing bronchoprovocation testing (with methacholine, cold air, or exercise) when the clinical features are suggestive of asthma but spirometry is normal and there is no response to asthma medications. An exercise challenge of sufficient magnitude may provoke symptoms in children with asthma [114-116]. A negative bronchoprovocation study may also be useful in reducing the likelihood that a child has asthma, although it cannot be used to exclude the diagnosis. For safety reasons, these tests should be conducted in a specialized facility with trained technicians and should not be performed if a patient has severe airflow limitation (FEV₁ <50 percent predicted) [117]. Exercise challenge has a high specificity, whereas methacholine challenge had a high sensitivity. Bronchial challenge tests are discussed in greater detail separately. (See «Overview of pulmonary function testing in children» and «Bronchoprovocation testing».)

Chest radiograph — We advise performing a chest radiograph (chest x-ray [CXR]) only in children who do not respond to initial therapy. In those children, the chest radiograph may display findings suggestive of causes for wheezing other than asthma including congenital malformations (eg, a right aortic arch suggestive of a vascular ring); evidence of airspace disease consistent with aspiration or cystic fibrosis; or findings consistent with asthma, such as hyperinflation, peribronchial thickening, and mucoid impaction with atelectasis.

Sweat chloride test — A sweat chloride test below established cut-off values reduces the likelihood of the diagnosis of cystic fibrosis in children with respiratory complaints in association with frequent foul-smelling stools or other evidence of malabsorption (eg, undigested food or oil), recurrent pneumonia, edema, and/or failure to thrive. There should be a low threshold to perform this test in children with this clinical picture, even if prenatal maternal screening or newborn screening was negative, since identifying a patient with cystic fibrosis has major implications for the patient, the family, and future reproductive decisions. Mutation analysis should be performed even if the sweat chloride is below established cut-off values if the suspicion for cystic fibrosis remains high. (See «Cystic fibrosis: Clinical manifestations and diagnosis».)

Barium swallow — A modified barium swallow should be included in the diagnostic evaluation if swallowing dysfunction with aspiration is a consideration. (See «Clinical manifestations and diagnosis of gastroesophageal reflux disease in children and adolescents» and «Evaluation of wheezing in infants and children».)

Exhaled nitric oxide — Exhaled nitric oxide testing is not recommended. (See «Exhaled nitric oxide analysis and applications», section on ‘Clinical use in asthma’.)

DIFFERENTIAL DIAGNOSISAlthough wheezing is most commonly caused by asthma, it is not a pathognomonic finding. The lack of objective measures of pulmonary function in very young children and the relatively high prevalence of congenital and inherited disorders that present with wheezing make it imperative to consider the differential diagnosis of wheezing illnesses before making a diagnosis of asthma solely on the basis of wheezing (table 5 and table 6). In particular, other causes of wheezing in children must be excluded if there is a failure to respond to asthma therapy or if the history and/or physical examination suggest alternative diagnoses. Cough is the primary manifestation in some children with asthma; therefore, the differential diagnosis for chronic cough in children should also be considered (table 7 and algorithm 1). Clinical features suggestive of a diagnosis other than asthma are seen in the table (table 8) and are discussed in detail separately. (See «Evaluation of wheezing in infants and children» and «Approach to chronic cough in children» and «Causes of chronic cough in children».)

INDICATIONS FOR REFERRALConsultation with an asthma specialist, either a pulmonologist or an allergist, is warranted when the diagnosis of asthma is uncertain, the asthma is difficult to control, medication side effects are intolerable, or a patient has frequent exacerbations. Pulmonologists may be most helpful if alternative pulmonary diseases are suspected or if further pulmonary testing or bronchoscopy may be needed. Referral to an allergist may be most helpful if allergic triggers need further evaluation or if concomitant nasal and ocular allergy symptoms are difficult to control.

SOCIETY GUIDELINE LINKSLinks to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See «Society guideline links: Asthma in children».)

INFORMATION FOR PATIENTSUpToDate offers two types of patient education materials, «The Basics» and «Beyond the Basics.» The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on «patient info» and the keyword(s) of interest.)

●Basics topic (see «Patient education: Cough in children (The Basics)»)

●Beyond the Basics topics (see «Patient education: Asthma symptoms and diagnosis in children (Beyond the Basics)» and «Patient education: Asthma treatment in children (Beyond the Basics)»)

SUMMARY AND RECOMMENDATIONS

●Establishing a diagnosis of asthma involves a careful process of history taking, physical examination, and diagnostic studies; other causes of wheezing must be excluded. (See ‘Introduction’ above.)

●The history in a child with suspected asthma centers on the presence of symptoms (cough and wheeze are the most common), precipitating factors or conditions (table 1 and table 2), typical symptom patterns, and response to asthma therapy. (See ‘History’ above.)

●Additional history that should be obtained in children with suspected asthma includes a history of atopy, family history of asthma, environmental history, and past medical history. (See ‘Additional history’ above.)

●Important aspects of the history in a child with asthma who presents for monitoring include previous and current therapy, exposure to triggers, medical utilization, school attendance and performance, comorbidities, and psychosocial stressors. (See ‘Additional history’ above.)

●Physical examination of an asthmatic child is generally normal if performed in the absence of an acute exacerbation. Abnormal findings may suggest severe disease, suboptimal control, or associated atopic conditions. (See ‘Physical examination’ above.)

●Other causes of wheezing in children must be excluded if there is a failure to respond to asthma therapy or if the history and/or physical examination suggest alternative diagnoses (table 5 and table 6 and table 7 and algorithm 1 and table 8). (See ‘Differential diagnosis’ above and «Evaluation of wheezing in infants and children».)

●The diagnosis of asthma requires a history of episodic symptoms of airflow obstruction or bronchial hyperresponsiveness, demonstration (with spirometry if possible) that airflow obstruction is reversible, and exclusion of alternate diagnoses. If spirometry cannot be performed, a trial of medications may help to establish reversibility. (See ‘Diagnosis’ above.)

Use of UpToDate is subject to the Subscription and License Agreement.

Topic 5742 Version 36.0

An overview of asthma management

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Jun 2019. | This topic last updated: Oct 05, 2017.

INTRODUCTIONThis overview topic presents the components and goals of asthma management. It is applicable to both children and adults. The information herein is consistent with «The National Asthma Education and Prevention Program: Expert Panel Report 3, Guidelines for the Diagnosis and Management of Asthma – Full Report 2007» [1]. Similar guidelines have been published by the Global Initiative for Asthma (GINA) [2].

The diagnosis of asthma and more detailed management issues are reviewed elsewhere. (See «Diagnosis of asthma in adolescents and adults» and «Asthma in children younger than 12 years: Initial evaluation and diagnosis» and «Asthma in children younger than 12 years: Treatment of persistent asthma with controller medications» and «Treatment of intermittent and mild persistent asthma in adolescents and adults» and «Treatment of moderate persistent asthma in adolescents and adults».)

COMPONENTS OF ASTHMA MANAGEMENTThe successful management of patients with asthma includes four essential components:

●Routine monitoring of symptoms and lung function

●Patient education to create a partnership between clinician and patient

●Controlling environmental factors (trigger factors) and comorbid conditions that contribute to asthma severity

●Pharmacologic therapy

GOALS OF ASTHMA TREATMENTThe goals of chronic asthma management may be divided into two domains: reduction in impairment and reduction of risk [1].

Reduce impairment — Impairment refers to the intensity and frequency of asthma symptoms and the degree to which the patient is limited by these symptoms. Specific goals for reducing impairment include:

●Freedom from frequent or troublesome symptoms of asthma (cough, chest tightness, wheezing, or shortness of breath)

●Minimal need (≤2 days per week) of inhaled short acting beta agonists (SABAs) to relieve symptoms

●Few night-time awakenings (≤2 nights per month) due to asthma

●Optimization of lung function

●Maintenance of normal daily activities, including work or school attendance and participation in athletics and exercise

●Satisfaction with asthma care on the part of patients and families

Reduce risk — The 2007 NAEPP guidelines introduced the concept of risk to encompass the various adverse outcomes associated with asthma and its treatment [1]. These include asthma exacerbations, suboptimal lung development (children), loss of lung function over time (adults), and adverse effects from asthma medications. Proper asthma management attempts to minimize the patient’s likelihood of experiencing these outcomes. Specific goals for reducing risk include:

●Prevention of recurrent exacerbations and need for emergency department or hospital care

●Prevention of reduced lung growth in children, and loss of lung function in adults

●Optimization of pharmacotherapy with minimal or no adverse effects

MONITORING PATIENTS WITH ASTHMACurrently, the majority of medical visits for asthma are for urgent care. Effective asthma management, however, requires a proactive, preventative approach, similar to the treatment of hypertension or diabetes. Routine follow-up visits for patients with active asthma are recommended, at a frequency of every one to six months, depending upon the severity of asthma. These visits should be used to assess multiple aspects of the patient’s asthma and to discuss steps that patients can take to intervene early in asthma exacerbations (an asthma «action plan») [3]. The aspects of the patient’s asthma that should be assessed at each visit include the following: signs and symptoms, pulmonary function, quality of life, exacerbations, adherence with treatment, medication side effects, and patient satisfaction with care.

By consensus from panels of asthma experts, well-controlled asthma is characterized by daytime symptoms no more than twice per week and nighttime symptoms no more than twice per month. SABAs for relief of asthma symptoms should be needed less often than three days out of the week, and there should be no interference with normal activity (preventative use of a SABA, such as prior to exercise, is acceptable even if used in this way on a daily basis). Peak flow should remain normal or near-normal. Oral glucocorticoid courses and/or urgent care visits should be needed no more than once per year [4]. Assessment of control in patients of different ages is summarized in the tables (table 1A-C).

Symptom assessment — Symptoms over the past two to four weeks should be assessed at each visit. Assessment should address daytime symptoms, nighttime symptoms, frequency of use of SABAs to relieve symptoms, and difficulty in performing normal activities and exercise. Several quick and validated questionnaires addressing these specific measures of asthma control, like the Asthma Control Test, have been published (form 1 and figure 1) [5-15].

Assessment of impairment — The following questions are representative of those used in validated questionnaires to assess asthma control:

●Has your asthma awakened you at night or in the early morning?

●How often have you been needing to use your quick-acting relief medication to relieve symptoms of cough, shortness of breath, or chest tightness?

●Have you needed any unscheduled care for your asthma, including calling in, an office visit, or an emergency department visit?

●Have you been able to participate in school/work and recreational activities as desired?

●If you are measuring your peak flow, has it been lower than your personal best? Home monitoring of peak flow measurements is reviewed in detail separately. (See «Peak expiratory flow monitoring in asthma».)

●Have you had any side effects from your asthma medications?

Assessment of risk — The following questions can be used to address the most important risk factors for future exacerbations [1]. A discussion of the risk factors for fatal and near-fatal asthma is provided separately. (See «Identifying patients at risk for fatal asthma», section on ‘Identifying high-risk patients’.)

●Have you taken oral glucocorticoids («steroids») for your asthma in the past year?

●Have you been hospitalized for your asthma? If yes, how many times have you been hospitalized in the past year?

●Have you been admitted to the intensive care unit or been intubated because of your asthma? If yes, did this occur within the past five years?

●Do you currently smoke cigarettes?

●Have you ever noticed an increase in asthma symptoms after taking aspirin or a nonsteroidal antiinflammatory agent (NSAID)?

Monitoring pulmonary function — Peak expiratory flow rate (PEFR) (performed in the office and/or at home) and spirometry (performed in the office) are the two most commonly employed modalities for monitoring pulmonary function in children older than five years of age and in adults. The 2007 NAEPP guidelines state a preference for use of spirometry in medical offices, when available [1]. Children older than five years of age are usually able to perform the peak flow or spirometric maneuver.

Office monitoring — Measurement of PEFR can be a useful indicator of airflow obstruction, the hallmark finding of asthma. PEFR can be measured with handheld peak flow meters in settings not equipped with a spirometer. Average normal values for men, women, and children are listed in the tables (table 2A-C). Adolescents have values closer to children than to adults [1].

It is important to understand the limitations of PEFR. A reduced peak flow is not synonymous with airway obstruction; spirometry is needed to distinguish conclusively an obstructive from restrictive abnormality [16]. Also, the accuracy of a single peak flow measurement to detect the presence of airflow obstruction is limited, given the large variability of PEFR among healthy individuals of the same age, height, and gender (±20 percent) [17-19]. Nonetheless, repeated measurements of PEFR in an individual patient are useful for determining relative changes or trends in asthma control [17,20-24]. PEFR monitoring is best used in patients in whom the diagnosis of asthma has been previously established with a more complete evaluation. The use of PEFR monitoring and its limitations are presented in more detail elsewhere. (See «Peak expiratory flow monitoring in asthma».)

Spirometry, which additionally measures forced expiratory volume in one second (FEV₁) and forced vital capacity (FVC), can be used to document airflow obstruction (by demonstration of a reduced FEV₁/FVC ratio) and provides additional information that is useful in monitoring asthma, such as risk for exacerbations, by detecting important reductions in lung function in patients who have few symptoms or physical findings of asthma [16,25]. Spirometry can detect airflow obstruction in the presence of a normal peak expiratory flow. As mentioned previously, the 2007 NAEPP and GINA guidelines recommend the use of spirometry in practices that are regularly caring for patients with asthma [1,2]. (See «Office spirometry» and «Pulmonary function testing in asthma».)

Home monitoring — Home monitoring of the peak expiratory flow rate (PEFR) may be helpful in patients with moderate to severe asthma. It is also useful in patients who poorly perceive limitations in airflow. These individuals cannot be easily identified at the outset of care, although over time they display a lack of awareness of increasing impairment, and typically seek care for exacerbations only after symptoms have become severe [26,27].

Peak flow meters for individual use are widely available, inexpensive (approximately $20), and easy to use. However, the resulting measurements are highly dependent upon the patient’s technique. It is therefore important that the clinician periodically checks the patient’s use of the meter, and corrects any mistakes in technique. Instructions for patients are provided. (See «Patient education: How to use a peak flow meter (Beyond the Basics)».)

The patient should be instructed in how to establish a baseline measure of peak flow when feeling entirely well: the «personal best» peak flow value. The personal best PEFR is then used to determine the normal PEFR range, which is between 80 and 100 percent of the patient’s personal best. Readings below this normal range indicate airway narrowing, a change that may occur before symptoms are perceived by the patient. (See ‘Asthma action plan’ below.)

Novel forms of monitoring — Measurements of lung function such as peak flow and spirometry assess asthma control based on airway diameter. However, it would also be desirable to measure airway inflammation directly. Quantitative analysis of expectorated sputum for eosinophilia and measurement of the concentration of nitric oxide in exhaled breath are two modalities currently being explored for this purpose. Studies have reached conflicting conclusions about whether regularly measuring these markers could help optimize asthma management. Nitrogen oxide analyzers are commercially available, but their use has been mostly limited to referral centers and hospital-based pulmonary function laboratories. The use of expectorated sputum eosinophilia and exhaled nitric oxide analysis in the management of asthma are discussed in more detail separately. (See «Evaluation of severe asthma in adolescents and adults», section on ‘Airway inflammation’ and «Exhaled nitric oxide analysis and applications».)

PATIENT EDUCATIONClinicians should enable patients to become active partners in managing their asthma. Ideally, this would occur through direct education in the office, as well as adjunctive education by other members of the health care team, emergency department providers, pharmacists, and organized programs [3]. The effectiveness of direct one-on-one education by the primary clinician, in particular, is well supported by evidence [1].

Patient education decreases hospitalizations due to asthma, improves daily function, and improves patient satisfaction [28-30]. A well-informed and motivated patient can assume a large measure of control over his or her asthma care.

Patients must learn how to monitor their symptoms and pulmonary function; they must understand what triggers their asthma attacks and how to avoid or decrease exposure to these triggers; and they must understand what medicine to take and how to use inhalers properly (table 3 and table 4 and table 5). If they have difficulty taking the medications regularly, they need help devising methods to improve compliance. The specific information that should be conveyed to the patient is reviewed in detail separately. (See «Asthma education and self-management».)

Asthma action plan — The patient’s normal PEFR value can be used to construct a personalized «asthma action plan» (form 2). Symptom-based plans appear to be equally effective. The asthma action plan provides specific directions for daily management and for adjusting medications in response to increasing symptoms or decreasing PEFR. Instructions and forms for asthma action plans are presented elsewhere. (See «Asthma education and self-management».)

CONTROLLING TRIGGERS AND CONTRIBUTING CONDITIONSThe identification and avoidance of asthma «triggers» is a critical component of successful asthma management, and successful avoidance or remediation may reduce the patient’s need for medications. Directed questions can identify specific triggers and contributing conditions (table 6). (See «Trigger control to enhance asthma management».)

Adults should be questioned about symptoms not only in the home, but also in the workplace, as asthma can be exacerbated by both irritant and allergen exposures in occupational settings. Patterns of symptoms that suggest occupational triggers are presented in the table (table 7) [1]. (See «Occupational asthma: Definitions, epidemiology, causes, and risk factors».)

Some triggers are mostly unavoidable, such as upper respiratory tract illnesses, physical exertion, hormonal fluctuations, and extreme emotion, and patients should be taught to adjust their management accordingly.

Other triggers, however, should be identified and specifically addressed or treated [5,31]:

●Inhaled allergens – The patient should be questioned about symptoms triggered by common inhaled allergens, at home, daycare, school, or work (table 6and table 7). Indoor allergens, such as dust mites, animal danders, molds, mice, and cockroaches, are of particular importance. Food allergy rarely causes isolated asthma symptoms, although wheezing and cough can be symptoms of food-induced anaphylaxis.

If the history suggests the patient has allergic triggers, basic avoidance measures can be advised, and evaluation by an allergy specialist should be considered. The assessment and management of allergen exposure in patients with asthma are reviewed in detail separately. (See «Allergen avoidance in the treatment of asthma and allergic rhinitis».)

●Respiratory irritants – Inhaled irritants include tobacco smoke, wood smoke from stoves or fireplaces, strong perfumes and odors, chlorine-based cleaning products, and air pollutants. Patients should be cognizant of avoiding irritants, and avoid exertion outdoors on days when levels of air pollution are elevated. (See «Trigger control to enhance asthma management».)

Smoking cessation and avoidance of environmental tobacco smoke are reviewed in detail elsewhere. (See «Control of secondhand smoke exposure» and «Secondhand smoke exposure: Effects in adults» and «Secondhand smoke exposure: Effects in children» and «Overview of smoking cessation management in adults».)

●Comorbid conditions – Clinicians should be vigilant for comorbid conditions in patients with poorly-controlled asthma. In adults, these conditions include chronic obstructive pulmonary disease/emphysema (COPD), allergic bronchopulmonary aspergillosis, gastroesophageal reflux, obesity, obstructive sleep apnea, rhinitis/sinusitis, vocal cord dysfunction, and depression/chronic stress. These conditions are reviewed separately. (See «Clinical manifestations and diagnosis of allergic bronchopulmonary aspergillosis» and «Gastroesophageal reflux and asthma» and «Clinical presentation and diagnosis of obstructive sleep apnea in adults» and «An overview of rhinitis» and «Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis».)

In young children, potential alternative or comorbid conditions include respiratory syncytial virus infection, foreign body aspiration, bronchopulmonary dysplasia, cystic fibrosis, and obesity [1].

●Medications – Non-selective beta-blockers can trigger severe asthmatic attacks, even in the minuscule amounts that are absorbed systemically from topical ophthalmic solutions. Selective beta-1 blockers can also aggravate asthma in some patients, especially at higher doses. (See «Treatment of hypertension in asthma and COPD».)

Aspirin and non-steroidal anti-inflammatory drugs can trigger asthma symptoms in approximately 3 to 5 percent of adult asthmatic patients. The incidence of aspirin-exacerbated respiratory disease is higher among asthmatic patients with nasal polyposis (constituting «triad asthma» or Samter’s triad). Aspirin-sensitive asthma is uncommon in children. (See «Aspirin-exacerbated respiratory disease».)

●Complications of influenza – Annual administration of influenza vaccine is recommended for patients with asthma because they are at increased risk for complications of influenza infection. This recommendation is supported by a systematic review in which vaccination of persons with asthma reduced the rates of influenza infection and asthma attacks [32], although randomized trial data are limited. Indications for vaccination against influenza are reviewed separately. (See «Seasonal influenza vaccination in adults» and «Seasonal influenza in children: Prevention with vaccines», section on ‘Target groups’.)

●Complications of pneumococcal infection – Administration of pneumococcal vaccination is recommended for adults whose asthma is severe enough to require controller medication and for children with asthma who require chronic oral glucocorticoid therapy (table 8 and table 9) [2,33]. (See «Pneumococcal vaccination in adults», section on ‘Indications’ and «Pneumococcal vaccination in children», section on ‘Immunization of high-risk children and adolescents’.)

●Dietary sulfites – Sulfite compounds are used in the food industry to prevent discoloration. Fewer than 5 percent of patients with asthma note significant and reproducible exacerbations following ingestion of sulfite-treated foods and beverages, such as beer, wine, processed potatoes, dried fruit, sauerkraut, or shrimp (table 10). Affected patients typically have severe asthma. (See «Trigger control to enhance asthma management», section on ‘Food allergens’.)

PHARMACOLOGIC TREATMENTPharmacologic treatment is the mainstay of management in most patients with asthma [34]. The 2007 National Asthma Education and Prevention Program (NAEPP) Expert Panel Report presented a stepwise approach to pharmacologic therapy, which is reflected in this review [1]. These guidelines were intended to support, rather than dictate, care that is based upon the clinician’s clinical judgment.

The stepwise approach to pharmacotherapy is based on increasing medications until asthma is controlled, and decreasing medications when possible to minimize side effects. Adjustment of the patient’s management should be considered at every visit.

The first step in determining appropriate therapy for patients who are not already on a controller medication is classifying the severity of the patient’s asthma. For patients already taking one or more controller medications, treatment options are guided by an assessment of asthma control rather than asthma severity.

Categories of asthma severity — Asthma severity is determined by considering the following factors [1]:

●Reported symptoms over the previous two to four weeks

●Current level of lung function (PEFR or FEV₁ and FEV₁/FVC values)

●Number of exacerbations requiring oral glucocorticoids in the previous year

The use of these three elements to determine severity in adolescents over the age of 12 years and in adults is graphically presented in the figure (table 11).

The classification of severity in children aged 5 to 11 years is similar to that in adults (table 12). Severity in children under the age of four years, however, is classified somewhat differently (table 13). Initiating long-term controller medications in children under the age of 12 years is reviewed separately. (See «Asthma in children younger than 12 years: Treatment of persistent asthma with controller medications».)

Intermittent — Intermittent asthma is characterized by the following (table 11). The criteria for adolescents and adults are utilized in this discussion [1]:

●Daytime asthma symptoms occurring two or fewer days per week

●Two or fewer nocturnal awakenings per month

●Use of short-acting beta agonists to relieve symptoms two or fewer days per week

●No interference with normal activities between exacerbations

●FEV₁ measurements between exacerbations that are consistently within the normal range (ie, ≥80 percent of predicted normal)

●FEV₁/FVC ratio between exacerbations that is normal (based on age-adjusted values)

●One or no exacerbations requiring oral glucocorticoids per year

If any of the features of a patient’s asthma is more severe than those listed here, the asthma should be categorized as persistent, with its severity based on the most severe element. Patients experiencing two or more exacerbations of asthma requiring oral glucocorticoids in the past year are considered to have persistent asthma.

In addition, a person using a SABA to prevent exercise-induced asthmatic symptoms might fit into this category of intermittent asthma even if exercising more than twice per week. Others in whom asthmatic symptoms arise only under certain infrequently occurring circumstances (eg, upon encountering a cat or during viral respiratory tract infections) are also considered to have intermittent asthma. (See «Exercise-induced bronchoconstriction».)

Equivalent schema for classifying asthma in children 0 to 4 years and 5 to 11 years are provided (table 13 and table 12).

Mild persistent — Mild persistent asthma is characterized by the following (table 11):

●Symptoms more than twice weekly (although less than daily)

●Approximately three to four nocturnal awakenings per month due to asthma (but fewer than every week)

●Use of SABAs to relieve symptoms more than two days out of the week (but not daily)

●Minor interference with normal activities

●FEV₁ measurements within normal range (≥80 percent of predicted normal) and normal FEV₁/FVC ratio

●Two or more exacerbations requiring oral glucocorticoids per year

Asthma is considered to be mild persistent if any of the above features is present (lung function measured in the absence of an asthmatic exacerbation may be normal in both intermittent and mild persistent asthma). If any of the features of a patient’s asthma is more severe than those listed here, their asthma should be categorized according to the most severe element.

Equivalent figures for asthma in children 0 to 4 years and 5 to 11 years are provided (table 13 and table 12).

Moderate persistent — The presence of any of the following is considered an indication of moderate disease severity (table 11):

●Daily symptoms of asthma

●Nocturnal awakenings more than once per week

●Daily need for SABAs for symptom relief

●Some limitation in normal activity

●FEV₁ between 60 and 80 percent of predicted and FEV₁/FVC below normal

Equivalent figures for asthma in children 0 to 4 years and 5 to 11 years are provided (table 13 and table 12).

Severe persistent — Patients with severe persistent asthma experience one or more of the following (table 11):

●Symptoms of asthma throughout the day

●Nocturnal awakenings nightly

●Need for SABAs for symptom relief several times per day

●Extreme limitation in normal activity

●FEV₁ <60 percent of predicted and FEV₁/FVC below normal

Equivalent figures for asthma in children 0 to 4 years and 5 to 11 years are provided (table 13 and table 12).

Initiating therapy during an acute exacerbation — Patients with acute exacerbations of asthma often require systemic glucocorticoids. Treatment of asthma exacerbations is reviewed separately. (See «Acute exacerbations of asthma in adults: Home and office management» and «Acute asthma exacerbations in children younger than 12 years: Emergency department management».)

Initiating therapy in previously untreated patients — The initiation of asthma therapy in a stable patient who is not already receiving medications is based upon the severity of the individual’s asthma (table 11).

Initiating long-term controller medications in young children is reviewed separately. (See «Asthma in children younger than 12 years: Treatment of persistent asthma with controller medications».)

Adjusting medication in patients already on controller therapy — In patients already taking controller asthma therapy, medication is adjusted according to asthma control. Control is assessed based on impairment over the past two to four weeks (as determined by history or a validated questionnaire), current FEV₁ or peak flow, and estimates of risk (table 14) [1,35]. Adjusting therapy in children younger than 12 years is reviewed in more detail separately. (See ‘Monitoring patients with asthma’ above and «Asthma in children younger than 12 years: Treatment of persistent asthma with controller medications».)

In patients with well controlled asthma, medications can be continued unchanged or potentially reduced in step-wise fashion. In patients with poorly controlled asthma, treatment should be «stepped up» along the 6-step protocol described below. In patients with very poorly controlled asthma, it may be necessary to escalate therapy rapidly, then «step-down» again once good control is achieved.

Therapy should be reassessed at each visit, because asthma is an inherently variable condition, and the management of asthma is a dynamic process that changes in accordance with the patient’s needs over time.

Intermittent (Step 1) — Patients with mild intermittent asthma are best treated with a quick-acting inhaled beta-2-selective adrenergic agonist, taken as needed for relief of symptoms (figure 2 and figure 3 and figure 4) [36-38]. Patients for whom triggering of asthmatic symptoms can be predicted (eg, exercise-induced bronchoconstriction) are encouraged to use their inhaled beta agonist approximately 10 minutes prior to exposure in order to prevent the onset of symptoms. (See «Beta agonists in asthma: Acute administration and prophylactic use» and «Exercise-induced bronchoconstriction».)

The pharmacologic management of mild intermittent asthma is discussed in more detail separately. (See «Treatment of intermittent and mild persistent asthma in adolescents and adults» and «Asthma in children younger than 12 years: Rescue treatment for acute symptoms».)

Mild persistent (Step 2) — The distinction between intermittent and mild persistent asthma is important, because current guidelines for mild persistent asthma call for initiation of daily long-term controller medication. For mild persistent asthma, the preferred long-term controller is a low dose inhaled glucocorticoid (GC) (figure 2 and figure 3 and figure 4 and table 15). Regular use of inhaled glucocorticoids reduces the frequency of symptoms (and the need for SABAs for symptom relief), improves the overall quality of life, and decreases the risk of serious exacerbations [39-41]. Regular use of inhaled glucocorticoids has not been shown to prevent progressive loss of lung function over time.

Alternative strategies for treatment of mild persistent asthma in the 2007 NAEPP guidelines included leukotriene receptor antagonists, theophylline, and cromoglycates (figure 2). Among these alternatives, we favor the leukotriene blockers. Patients receiving long-term controller therapy should continue to use their SABA as needed for relief of symptoms and prior to exposure to known triggers of their symptoms.

The pharmacologic management of mild persistent asthma is presented in greater detail elsewhere. (See «Treatment of intermittent and mild persistent asthma in adolescents and adults» and «Asthma in children younger than 12 years: Treatment of persistent asthma with controller medications».)

Moderate persistent (Step 3) — For moderate persistent asthma, the preferred therapies are either low-doses of an inhaled glucocorticoid plus a long-acting inhaled beta agonist (LABA), or medium doses of an inhaled glucocorticoid (figure 2 and figure 3 and figure 4 and table 15). The former combination has proven more effective in controlling asthmatic symptoms than an increased dose of inhaled GCs. While potential risks of adverse outcomes have been reported in association with LABAs, safety data regarding the use of combination inhalers containing inhaled glucocorticoid and a LABA are reassuring. (See «Beta agonists in asthma: Controversy regarding chronic use», section on ‘Long–acting beta-agonists’.)

Alternative strategies include adding a leukotriene modifier (leukotriene receptor antagonist or lipoxygenase inhibitor) or theophylline to low-dose inhaled GCs. We favor use of leukotriene modifiers and rarely initiate theophylline in the modern treatment of asthma. The pharmacologic management of moderate asthma is presented in more detail elsewhere. (See «Treatment of moderate persistent asthma in adolescents and adults».)

Severe persistent (Step 4 or 5) — For severe persistent asthma, the preferred treatments are medium (Step 4) or high (Step 5) doses of an inhaled glucocorticoid, in combination with a long-acting inhaled beta-agonist (figure 2 and figure 3 and figure 4 and table 15). In treating severe asthma, many providers add a leukotriene modifier to the combination inhaled GC and LABA, so-called «triple-controller therapy.» When severe asthma remains poorly controlled, oral glucocorticoids may be needed on a daily or alternate-day basis. Severe asthma is reviewed in more detail separately. (See «Treatment of severe asthma in adolescents and adults».)

For patients whose asthma is inadequately controlled on high-dose inhaled GCs and LABAs, the anti-IgE therapy omalizumab may be considered if there is objective evidence of sensitivity to a perennial allergen (by allergy skin tests or in vitro measurements of allergen-specific IgE) and if the serum IgE level is within the established target range. (See «Anti-IgE therapy».)

Monoclonal antibodies (mepolizumab and reslizumab) against interleukin-5 (IL-5), a potent chemoattractant for eosinophils, are available for patients with eosinophilic severe asthma. They are indicated for the treatment of severe eosinophilic asthma poorly controlled with conventional therapy. (See «Treatment of severe asthma in adolescents and adults», section on ‘Anti-IL-5 therapy’.)

Bronchial thermoplasty is a device-based intervention available to treat severe asthma. Utilizing a special catheter introduced via a fiberoptic bronchoscope, thermal energy is applied to bronchial walls in an effort to impair bronchial smooth muscle contractility. The role of bronchial thermoplasty in managing severe asthma remains debated. (See «Treatment of severe asthma in adolescents and adults», section on ‘Bronchial thermoplasty’.)

EFFICACY OF ASTHMA MANAGEMENTThe stepwise approach to asthma management that forms the foundation of guideline-based asthma management has been shown to reduce symptoms and improve health-related quality of life [1,2]. A prospective, randomized trial applied the management recommendations of previous NAEPP guidelines to approximately 1500 patients with all severities of asthma over the course of one year [42]. Guideline-based management resulted in significant improvement in health-related quality of life in most patients, regardless of disease severity. In this study, subjects who required inhaled GCs were randomly assigned to receive either fluticasone propionate (FP) alone or the combination of fluticasone propionate and salmeterol (FP + S). Subjects were evaluated every three months and medications were stepped up as needed (although the protocol did not allow for stepping down of therapy). With both treatments, the majority of patients achieved well-controlled or totally-controlled asthma; good control was achieved slightly more often with FP + S. The greatest improvements occurred in the first few months of therapy.

WHEN TO REFERBoth pulmonologists and allergists/immunologists have specialty training in asthma care. Referral for consultation or comanagement is recommended when any of the following circumstances arise [1]:

●The patient has experienced a life-threatening asthma exacerbation

●The patient has required hospitalization or more than two bursts of oral glucocorticoids in a year

●The adult and pediatric patient older than five years requires step 4 care or higher or a child under five requires step 3 care or higher

●Asthma is not controlled after three to six months of active therapy and appropriate monitoring

●The patient appears unresponsive to therapy

●The diagnosis of asthma is uncertain

●Other conditions are present which complicate management (nasal polyposis, chronic sinusitis, severe rhinitis, allergic bronchopulmonary aspergillosis, COPD, vocal cord dysfunction, etc)

●Additional diagnostic tests are needed (skin testing for allergies, bronchoscopy, complete pulmonary function tests)

●Patient may be a candidate for allergen immunotherapy (see «Subcutaneous immunotherapy for allergic disease: Indications and efficacy»)

●Patient is a potential candidate for therapy with biologics (omalizumab, mepolizumab, reslizumab) or bronchial thermoplasty.

Other possible indications for referral include [1]:

●The adult and pediatric patient older than five years who requires step 3 care or higher or a child under five who requires step 2 care or higher

●Patients with potential occupational triggers

●Patients in whom psychosocial or psychiatric problems are interfering with asthma management and in whom referral to other appropriate specialists may be required

SOCIETY GUIDELINE LINKSLinks to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See «Society guideline links: Asthma in adolescents and adults».)

INFORMATION FOR PATIENTSUpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

●Basics topics (see «Patient education: How to use your child’s dry powder inhaler (The Basics)» and «Patient education: Asthma in children (The Basics)» and «Patient education: How to use your child’s metered dose inhaler (The Basics)» and «Patient education: Asthma and pregnancy (The Basics)» and «Patient education: How to use your dry powder inhaler (adults) (The Basics)» and «Patient education: How to use your metered dose inhaler (adults) (The Basics)»and «Patient education: How to use your soft mist inhaler (adults) (The Basics)» and «Patient education: Asthma in adults (The Basics)» and «Patient education: Avoiding asthma triggers (The Basics)» and «Patient education: Medicines for asthma (The Basics)» and «Patient education: Coping with high drug prices (The Basics)» and «Patient education: Inhaled corticosteroid medicines (The Basics)»)

●Beyond the Basics topics (see «Patient education: Asthma inhaler techniques in children (Beyond the Basics)» and «Patient education: Asthma treatment in children (Beyond the Basics)» and «Patient education: Asthma and pregnancy (Beyond the Basics)» and «Patient education: Asthma symptoms and diagnosis in children (Beyond the Basics)» and «Patient education: How to use a peak flow meter (Beyond the Basics)» and «Patient education: Asthma inhaler techniques in adults (Beyond the Basics)» and «Patient education: Asthma treatment in adolescents and adults (Beyond the Basics)» and «Patient education: Exercise-induced asthma (Beyond the Basics)» and «Patient education: Trigger avoidance in asthma (Beyond the Basics)» and «Patient education: Coping with high drug prices (Beyond the Basics)»)

SUMMARY AND RECOMMENDATIONS

●The four essential components of asthma management are: routine monitoring of symptoms and lung function, patient education, control of trigger factors and amelioration of comorbid conditions, and pharmacologic therapy. (See ‘Components of asthma management’ above.)

●The goals of asthma treatment are to reduce impairment from symptoms, minimize risk of the various adverse outcomes associated with asthma (eg, hospitalizations, loss of lung function), and minimize adverse effects from asthma medications. (See ‘Goals of asthma treatment’ above.)

●Effective asthma management requires a preventative approach, with regularly scheduled visits during which symptoms are assessed, pulmonary function is monitored, medications are adjusted, and ongoing education is provided. (See ‘Monitoring patients with asthma’ above.)

●Patients should learn to monitor asthma control at home (eg, frequency and severity of dyspnea, cough, chest tightness, and short-acting beta agonist [SABA] use). Patients with moderate to severe asthma and those with poor perception of increasing asthma symptoms may also benefit from assessment of their peak expiratory flow rate at home. A personalized asthma action plan should be provided with detailed instructions on how to adjust asthma medications based upon changes in symptoms and/or lung function (form 2). (See ‘Patient education’ above.)

●Environmental triggers and co-existing conditions that interfere with asthma management should be identified and addressed for each patient. (See ‘Controlling triggers and contributing conditions’ above.)

●Pharmacologic therapy varies according to asthma severity and asthma control. Asthma control can be judged, irrespective of medication use, based on the current level of symptoms, FEV₁ or PEFR values, and number of exacerbations requiring oral glucocorticoids per year (table 11 and table 12 and table 13). (See ‘Categories of asthma severity’ above and «Asthma in children younger than 12 years: Treatment of persistent asthma with controller medications».)

●A stepwise approach to therapy is recommended, in which the dose of medication, the number of medications, and/or the frequency of administration are increased as necessary and decreased when possible (figure 2 and figure 3 and figure 4). (See ‘Initiating therapy in previously untreated patients’ above.)

●At each return visit, the patient’s asthma control is evaluated (table 14). If the asthma is not well-controlled, therapy should be «stepped-up.» If the asthma is well-controlled, therapy can be continued or possibly «stepped-down» to minimize medication side effects. (See ‘Adjusting medication in patients already on controller therapy’ above and «Asthma in children younger than 12 years: Treatment of persistent asthma with controller medications».)

●Guidelines for when to refer a patient to a pulmonologist or an allergist/immunologist are provided. (See ‘When to refer’ above.)

Use of UpToDate is subject to the Subscription and License Agreement.

Topic 547 Version 42.0