INTRODUCTION — The 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 "Asthma in adolescents and adults: Evaluation and diagnosis" and "Asthma in children younger than 12 years: Management of persistent asthma with controller therapies", section on 'Inhaled glucocorticoids' and "An overview of asthma management" and "Risk factors for asthma".)
INFANTS AND CHILDREN — Many 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 male (odds ratio [OR] 4.27, 95% CI 2.33-7.83), but not female children.
●Maternal asthma was a risk factor for persistent wheeze in both sexes (OR 2.13, 95% CI 1.04-4.35 [males]; OR 2.21, 95% CI 1.11-4.40 [females]).
●Race and ethnicity were risk factors for persistent asthma in female children (OR 3.23, 95% CI 1.55-6.75 [Black versus all others] and OR 3.60, 95% CI 1.06-12.17[Hispanic versus nonhispanic]).
●Bronchiolitis before age one year was a risk factor for persistent asthma in both sexes (OR 4.38, 95% CI 2.03-9.45 [females]; OR 6.49, 95% CI 3.29-12.79[males]). 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 [3,16-20]. 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) [21]. 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 [22-24].
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 [22,23,25]. 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 males [22]. The prebronchodilator percent predicted forced expiratory volume in one second (FEV1) in males declined from a mean of 0.91 at six to eight years to 0.82 at 15 to 17 years (p<0.05). Prebronchodilator FEV1 in female children was 0.94 at six to eight 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 [26,27].
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 [26]. Male children with asthma experienced a larger increase in forced vital capacity (FVC) than nonasthmatic males, whereas female children with asthma had consistently lower FEV1 values compared with nonasthmatic females.
●Childhood Asthma Management Program – The CAMP followed the lung function of 1041 children (420 female and 621 male) with mild to moderate persistent asthma, and compared it with the lung function of 5415 nonasthmatic children from the Harvard Six Cities Study [27]. 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 nonasthmatic children. In contrast to the East Boston study, males had a lower FEV1 between the ages of 10 to 18, whereas the differences in females 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) [28]. 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 [29].
●Melbourne Asthma Study - Asthma in childhood continues to influence pulmonary function later in life [30-34]. 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 [30]. 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 [35], with long-term follow-up of 177 participants in 2001 [36]. 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 females, but decreased after puberty in males, independent of baseline FEV1 [37]. 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 [29].
ADULTS — Adults 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 females as males. Among the female population, 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 [37]. In the Tucson Children's Respiratory Study, newly diagnosed asthma at age 22 was twice as likely in females compared with males [22].
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 female participants at baseline and again at follow-up 10 to 12 years later when they were age 45 to 65 years [38]. The odds of new-onset asthma were increased in those 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 the nonmenopausal group. 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 25 years [3,39,40].
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 "Asthma in adolescents and adults: Evaluation and diagnosis" 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 [39]. 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 in adults [41]. 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: Management of persistent asthma with controller therapies", section on 'Inhaled glucocorticoids'.)
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 [25]. 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 [42]. 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 [43,44]. In one report, for example, 1095 asthmatics were compared with 16,411 normal subjects using data collected over 15 years [43]. 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 among smokers and nonsmokers of both sexes, 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 [32].
●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 [45]. 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 male patients and 11 mL/year in female patients 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 [43]. 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 [46]. Rates of decline in FEV1 were 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 [43].
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 [30]. 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 LINKS — Links 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 PATIENTS — UpToDate 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 5th to 6th 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 10th to 12th 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
●Natural history of wheezing in young children – 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.
•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.
●Childhood asthma – Between 30 and 70 percent of children with asthma are markedly improved or asymptomatic by early adulthood. 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 'Wheezing in later childhood' above and 'Severe asthma' above and 'Effect on future lung function' above.)
●Adult-onset asthma – "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 female patients than male patients. The frequency of new onset asthma is highest during the perimenopausal years. (See 'Adult onset asthma' above.)
●Progression of adolescent or adult asthma – 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.)
•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.)
