Key Points
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Failure of symptoms to respond to β-agonists and oral steroids should prompt consideration that the symptoms are not caused by asthma but by another process.
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Cough that persists despite treatment with bronchodilators and systemic corticosteroids is often not due to asthma. Consideration of other disorders, particularly sinusitis, is imperative.
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The Asthma Action Plan is the centerpiece of asthma education, focusing the child and parents on early warning signs, when to increase treatment and when to call for advice during more severe exacerbations. The action plan is directly relevant, focussing on action not theory. An understanding of theory may be helpful when the family can focus on these details.
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Pulmonary function measures may not accurately reflect asthma severity in children, who can have an FEV 1 in the normal range even when disease is severe. The FEV 1 /FVC ratio is a much better indicator of severity of disease.
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Asthma is controllable in the vast majority of children. Even children with severe asthma can be expected fully to participate in activities. This is an important goal for children and their parents.
Asthma is the most common chronic disorder of childhood, affecting approximately 10.7% of children aged 5 to 14 years, with 6.4% of children in this age group reporting an episode of asthma or an asthma attack in the preceding 12 months. However, estimates of wheezing in this age group approach 20% or greater in some areas of the USA and in many industrialized countries, further magnifying the impact of wheezing disease on children.
Epidemiology and Etiology
Prevalence of Childhood Asthma
In the USA from 1980 to 2010 asthma prevalence in the general population increased from 3.1% to 8.4%, with increases among 5- to14-year-old children from 4.4% in 1980 to 8.2% in 1995, 9.1% in 2004, and 10.7% in 2010. Although the rise in asthma prevalence may reflect coding and classification issues, the influence of other factors, such as environmental exposures to allergens, infectious agents, endotoxin, vitamin D insufficiency and tobacco smoke, must also be considered. Place of residence appears to influence asthma prevalence. Furthermore, there appears to be an effect of gender on asthma prevalence, as the male-to-female ratio for asthma is 1.8 : 1 among children aged 2 years and under, but by puberty, asthma becomes more prevalent amongst females (M : F ratio of 0.8 : 1). The change in gender ratio represents development of new cases of asthma in females during adolescence, not a decrease in males with asthma.
Factors Influencing the Etiology of Asthma
A general pattern of factors influencing development of asthma seems to be emerging, including family history/genetics, smoking, diet, obesity and inactivity, all of which seem to influence the development of asthma and disease outcomes ( Table 34-1 ).
| Factor | Disease Development | Disease Severity |
|---|---|---|
| Atopy | ++++ | ++++ |
| Allergen exposure | ++ | ++++ |
| Rhinitis | ++ | ++ |
| Sinusitis | ? | +++ |
| Infection (viral) | + | ++++ |
| Gastroesophageal reflux | − | ++ |
| Environmental factors | ||
| Intrauterine tobacco smoke | ++ | ? |
| Passive tobacco smoke | + | ++ |
| Air pollution | − | ++ |
| Psychological factors (including stress) | + | ++++ |
| Socioeconomic status | ++ | ++++ |
| Adherence | − | ++++ |
| Obesity | Adolescent females | ++ |
| Diet | ? | ? |
| Exercise | ? | ++ * |
| Drugs (including ASA/NSAIDs) | − | ++ † |
* While exercise is a common precipitant of asthma symptoms, improved physical conditioning can reduce asthma severity.
† Consider in the context of asthma, nasal polyposis and severe sinus disease.
Socioeconomic Status
Many clinical or area studies have reported substantially higher rates of asthma prevalence, morbidity, hospitalization and mortality among racial and ethnic minorities. However, asthma is also most common among low socioeconomic groups regardless of race. While black children have higher rates of asthma than white children, most studies have found that black race is not a significant correlate of asthma after controlling for location of residence and socioeconomic status (SES). The basis for the effects of poverty and urban residence on asthma prevalence is not known. One potential factor is exposure and sensitization to allergens common in urban environments. Black children in inner city Atlanta are exposed to high levels of dust mite and cockroach allergen, and a high proportion of the children with asthma was sensitized to these allergens. Litonjua et al also concluded that a large proportion of the racial/ethnic differences in asthma prevalence can be explained by factors related to income, area of residence and level of education.
Income is a determinant of access to health care and frequently the quantity and quality of health care available. Persons who have low income, regardless of race or ethnicity, are more likely to be under- or uninsured, to encounter delays in receiving or be denied care, to rely on hospital clinics in emergency departments for health services and to receive substandard care. The usual socioeconomic indicators, education and personal or household income, serve only as surrogates for more complicated correlates of individuals within populations and multiple factors that can impact both on prevalence of asthma and adverse outcomes from the disease.
Genetics
The genetic basis of heritability has been extensively studied and while the genetic basis of asthma remains incompletely understood, studies are yielding some understanding (see Chapter 3 ). There is as of yet no established genetic pattern that predicts presence of asthma or defines its severity.
Allergy
Studies of school children in Melbourne, Australia by Williams and McNicol have indicated increases in both the incidence of asthma and asthma severity with increases in number of positive skin tests and total serum IgE. The relationship between allergy and asthma has more recently been highlighted by the importance of aeroallergen sensitivity in the progression of frequent intermittent wheezing to persistent asthma in young children. Several large epidemiological studies have clearly indicated the importance of aeroallergen sensitization in asthma development among populations at risk. Sensitization to house dust mite and mold was a predictor of asthma in rural Chinese individuals selected on the basis of having at least two siblings with physician-diagnosed asthma. In a similar study, total serum IgE levels and positive skin tests to aeroallergens were correlated with current wheezing. This association was present in children from nonatopic, asymptomatic probands, as well as in the expected atopic asthmatic probands, suggesting that much of the increase in asthma prevalence is associated with specific IgE sensitization and is occurring in persons previously considered to be at low risk for developing asthma or atopy.
Demographic and Environmental Factors
Studies comparing the populations of East and West Germany showed the prevalence of hay fever and asthma to be significantly higher in West German children, suggesting that environmental factors may explain the difference in prevalence in these ethnically similar populations. Early exposure to infections (e.g. being in a daycare environment early in life) or exposure to endotoxin or other bacterial products (e.g. growing up on a farm with close exposure to the farm animals) is associated with a decreased prevalence of asthma. In contrast, growing up in an urban environment or generally with an increased standard of living is associated with an increased prevalence of asthma. Such correlates are also present for atopic diseases other than asthma. In fact, Strachan, who noted that prevalence of hay fever was inversely related to family size, was the first to recognize the importance of early exposures on atopic disease. In the USA, asthma is more prevalent in African-Americans and Puerto Ricans. These findings are not explained by the observations on the role of social class in European studies. Given the ethnic differences between African-Americans and whites, these studies may represent gene-environment interaction producing varied phenotypic outcomes.
Gene-Environment Interaction
Genetic factors alone cannot explain the rise in asthma prevalence, morbidity or mortality. However, a small change in the prevalence of relevant environmental exposures could explain a significant rise in disease prevalence among genetically susceptible individuals. Gene-environment interaction, defined as the co-participation of genetic and environmental factors, is particularly relevant to the etiology of asthma morbidity, particularly in individuals who experience a disproportionate burden of environmental exposures, and may exert its effect through epigenetic mechanisms. Relevant exposures include smoking, stress, nutritional factors, infections, allergens and occupational exposures. In addition, racial/ethnic variability in the distribution of genetic polymorphisms can potentially modify the response to pharmacotherapeutic agents, such as the β 2 -adrenergic agonists.
Stress
Negative family characteristics such as family conflict and family dysfunction discriminated children who died of asthma from children with equally severe asthma who did not die. Parenting difficulties have been associated with a higher risk for the development of asthma early in life. In addition, children with the highest risk of developing early-onset asthma were those in families with both parenting problems and high stress. Evidence for a link between stress and asthma has been gained from temporal studies, as experiencing an acute negative life event increased children’s risk for an asthma attack 4 to 6 weeks after the occurrence of the event. Moreover, the combination of chronic and acute stress plays a role in the temporal association. Experiencing an acute life event among children who had ongoing chronic stress in their lives shortened the time frame in which they were at risk for an asthma attack to within 2 weeks of the acute event. The experience of daily life stressors is associated with same-day lower peak expiratory flow (PEF) rate and greater self-report of asthma symptoms. Further, high levels of stress have been associated with detrimental biological profiles, such as greater inflammatory responses after antigen challenge or in vitro stimulation of immune cells among children with or at risk for asthma.
Children with asthma have been found to have higher rates of clinically significant family stress compared with healthy children. Children whose families are more cohesive are more likely to have controlled, rather than uncontrolled, asthma. Additionally, parenting difficulties early in a child’s life, particularly during times of high stress, have been found to predict the onset of asthma in childhood. Thus, strain in the family, both in terms of conflicts among family members and impact of illness on family relationships, could be associated with both increased asthma prevalence and poor asthma outcomes.
One psychological pathway that has been suggested to explain associations of SES with asthma is the differential experiences of stress faced by children of low and high SES. In healthy children, low SES has been associated with more frequent exposure to stressful life events, and children who live in low SES neighborhoods are more likely to report witnessing incidences of violence. Low SES also has been associated with more negative stress appraisals.
Obesity
Obesity is linked with the development and severity of asthma in both children and adults, and weight reduction improves asthma severity and symptoms. Similar to the results in industrialized countries, Celedon and colleagues found an association between overweight and presence of asthma or airway hyperresponsiveness among adults in China with either physician-diagnosed asthma or airway responsiveness to methacholine. They also found an association between underweight (body mass index [BMI) 16 kg/m 2 or less) and asthma, which could be the result of an effect of asthma symptoms on nutrition or an effect of previous weight loss and development of asthma.
The relationship between obesity and asthma observed in adults has also been most often observed in adolescent females, but not in males. Girls who were overweight or obese at age 11 years were more likely to have current wheezing at ages 11 and 15 years, but not at ages 6 to 8 years. The relationship between obesity and asthma is strongest among females beginning puberty before age 11 years. Females who become overweight or obese between 6 and 11 years are seven times more likely to develop new asthma symptoms at age 11 and 13 years. The mechanism of increased asthma with obesity is not clear. The strong gender differences observed suggest that overweight status itself does not produce the asthma, as a direct effect of weight is not seen in both boys and girls. Longitudinal studies suggest that there is a more fundamental relationship, as most of the asthma in obese adolescent girls was new-onset asthma. In a study of young adults with asthma, a lower level of physical activity did not explain the association between the incidence of asthma and gain in weight. Poor asthma control in obese children with asthma may be overestimated since obesity is associated with enhanced perception of nonspecific symptoms such as dyspnea that results from altered mechanical properties of the chest wall.
Infection
Viral respiratory infections are present in up to 85% of children with exacerbated asthma. In addition to worsening asthma, there may be a more fundamental relationship between infection and the development of asthma. Such a relationship has been suggested by the finding of a higher than expected incidence of bronchial hyperresponsiveness in children who had whooping cough, croup or bronchiolitis in their early years of life. Children hospitalized with respiratory syncytial virus bronchiolitis are at increased risk for asthma at school age, and this risk appears to persist to early adulthood. In addition, wheezing in the context of rhinovirus infection during the preschool years is also a significant risk factor for asthma at school age.
The role of Mycoplasma pneumoniae or Chlamydia pneumoniae infections in the underlying pathogenesis of asthma has been suggested (see Chapter 31 ). A conclusive association between development of C. pneumoniae or M. pneumoniae infection and onset of asthma, or even an association between the presence of the organism and more severe disease, remains to be established in large prospective studies.
Diet
Several studies have identified relationships between maternal and infant diets and subsequent asthma risk. Studies in birth cohorts have found that higher maternal intakes of vitamin D during pregnancy from both foods and supplements were associated with an almost 60% reduction of asthma and recurrent wheezing in 3- to 5-year-old children. Other studies identified a relationship between a high dietary intake of vitamins C, A, and E with higher levels of lung function. A longitudinal analysis of decline in forced expiratory volume in 1 second (FEV 1 ) over a 9-year period in adults found the decline to be lower amongst those with a higher average vitamin C intake, but no relationship to magnesium or vitamins A or E. The relationship between diet and atopy is not clearly understood, although there is some evidence for a relationship between concentrations of vitamin E and both allergen skin sensitization and IgE concentrations.
Natural History of Asthma
Persistence and Progression of Disease into Adulthood
The course of asthma through childhood and adolescence is variable. More severe asthma is likely to persist from childhood into adulthood without remission, with only 15% of children with severe asthma experiencing remission by age 50 years. Another important tendency in the natural history is for symptoms to remit in adolescence only to return again in adulthood. In general, the amount of wheezing in early adolescence seems to be a guide for severity in early adult years, with 73% of those with few symptoms at age 14 years continuing to have little or no asthma at age 28 years. Similarly, 68% of those with frequent wheezing at 14 years still experienced recurrent asthma at age 28 years. Most subjects with frequent wheezing at 21 years continued to have comparable asthma at 28 and 50 years. In addition to the importance of symptoms, the childhood degree of bronchial responsiveness combined with a low FEV 1 was also related to the outcome of asthma in adulthood. While many children become asymptomatic in adolescence, pulmonary function deficits associated with asthma and wheeze increase throughout childhood, and a significant proportion of children free of symptoms and with normal FEV 1 and even FEV 1 /forced vital capacity (FVC) ratios, continue to have increases in bronchial reactivity. This bronchial hyperresponsiveness is an independent risk factor for development of a low FEV 1 and associated symptoms in early adulthood. What is perhaps most concerning about the persistence of childhood disease into adulthood is the development of chronic airflow obstruction, with loss of bronchodilator responsiveness and a decline in FEV 1 over time, that is greater in adults with asthma than in asymptomatic peers. These findings suggest that asthma, even uncomplicated by cigarette smoking, may be a precursor of a chronic obstructive pulmonary disease (COPD)-like syndrome in adults.
Duration of Disease is Associated with Degree of Abnormality in Pulmonary Function
Longer duration of asthma was associated with lower levels of lung function in children with mild-to-moderate asthma aged 5 to 12 years. This association was independent of levels of atopy, presence of household allergens and prior use of anti-inflammatory medications. Duration of asthma was associated with lower levels of both pre- and post-bronchodilator values for FEV 1 and FEV 1 /FVC ratio. While the values for FEV 1 both pre- and post-bronchodilation were well within the normal range for children (93.9% predicted and 102.8% predicted, respectively), more than 50% of children with asthma had low FEV 1 /FVC ratios, suggesting that airway obstruction is present and worsens even with relatively mild-to-moderate asthma. The degree of bronchial hyperresponsiveness in these children was also related to the duration of disease. Since level of pulmonary function and degree of bronchial hyperresponsiveness are independent predictors of abnormal levels of lung function in adults who had childhood asthma, it is apparent that longer duration of disease in childhood and its associated abnormalities of lung function predispose adults to disease.
Morbidity and Mortality
In 2010, 6.4% of US children experienced a self-reported asthma attack, with no significant decrease in incidence since 1997 in spite of the much improved therapies available. Between 2001 and 2009, the rate of outpatient office visits remained relatively stable at 351 visits/10,000 population/year.
Emergency department visits among children aged 5 to 14 years increased by approximately 8% from 2001 to 2009, with nearly 10% of children aged 5 to 14 years seeking emergency department care yearly. Rates among blacks are almost 3-fold higher than rates for whites. Asthma is the leading admitting diagnosis to children’s hospitals, and blacks have greater than 3-fold more hospitalizations than whites. Rates of hospitalizations in 5- to 14-year-old children remained stable from 1980 to 2009, and were more than 3-fold lower than for younger children. A significant proportion of hospitalizations are repeat hospitalizations, with rehospitalizations accounting for 20% to 25% of hospitalizations in a signal year and up to 43% of hospitalizations in one urban children’s hospital within a 5- to 10-year period. A lifetime history of hospitalizations was associated with family impacts (greater family strain and family conflict, greater financial strain), as well as caregiver characteristics of greater personal strain and beliefs about not being able to manage one’s child’s asthma. Individual characteristics of the caregiver (lower sense of mastery, being less emotionally concerned by asthma) predicted greater likelihood of future asthma hospitalizations.
The rate of deaths due to asthma in 5- to 14-year-old children increased more than 2-fold from 1980 (1.8 per million) to 1995 (3.4 per million) before stabilizing through 2002 (2.4 per million) and then increasing in 2004 to 2.6 per million and 2.8 per million in 2009. Blacks have many more deaths from asthma than whites (2.9-fold in 2009). While the death rate in children is relatively small compared to that in other age groups, physicians find that many, if not most, of these deaths are preventable, with the major reason for death being late arrival to health care associated with poor use of oral corticosteroids. Late arrival is often associated with psychological problems in the family or child, but can be associated with shortcomings in availability of medical care.
While there have been significant efforts toward understanding the reasons for the occurrence of fatal and near-fatal asthma episodes, the identification of patients at risk for dying remains an art with no single set of criteria able to identify all patients who will die. Prior history of severe events, especially respiratory failure requiring intubation, is an obvious risk factor. However, while as many as 25% of patients with a history of respiratory failure die in a 3- to 5-year follow-up, most patients who die have not had a previous episode of respiratory failure. Most studies indicate that a high proportion of patients who have died have had severe asthma, but the number of patients with severe disease is large and only 1% to 3% will die over an extended follow-up period. The importance of psychological factors in poor outcomes from asthma indicates that patient and family factors resulting in psychological dysfunction need to be identified as well.
There are certain time intervals when risk of fatality is increased. For example, patients may need extra care and communication in periods following hospitalization, as enhanced bronchial hyperresponsiveness persists after hospitalization much longer than abnormalities in spirometry, and oral steroids will be being weaned, further increasing risk. Hospitalizations that occur in spite of optimally prescribed therapy are of special concern.
Differential Diagnosis of Asthma
The differential diagnosis of cough and wheeze is extensively reviewed in Chapters 27 , 32 , and 37 .
Evaluation
Figure 34-1 presents an algorithm for evaluation of a school-age child or adolescent who presents with chest symptoms of cough, wheeze, shortness of breath, chest tightness or chest pain.
History
Historical elements should include specific symptoms, their frequency and severity, triggering factors and response to therapy. Age of onset of symptoms is important, as 80% of patients with asthma experience symptoms within the first 5 years of life. Thus, the adolescent presenting with recent onset of symptoms without a prior history warrants further evaluation of alternative diagnoses. Since asthma is a disorder characterized by repeated episodes of at least partially reversible airflow obstruction, failure of symptoms to improve with treatment including bronchodilators and corticosteroids should prompt evaluation for other processes, either a nonasthma diagnosis or a co-morbid condition complicating underlying asthma.
A short series of questions focussing on recent symptom frequency is extremely informative in assessing the child with asthma. The Asthma Control Test (ACT) serves this purpose, and when completed at each follow-up asthma visit, can serve as a rapid appraisal of asthma control over time.
Additional history should focus on identification of other co-morbid conditions that may worsen asthma severity, including allergen exposure, rhinitis, sinusitis and gastroesophageal reflux. Furthermore, an assessment of underlying psychosocial factors and adherence to the medical regimen may provide valuable clues as to barriers in delivery and receipt of asthma care.
Physical Examination
Findings may include an increased anteroposterior chest diameter in severe disease and expiratory wheezes and prolongation of the expiratory phase during exacerbation. Presence of nasal polyposis should prompt an evaluation for cystic fibrosis, regardless of the age of the child, as cystic fibrosis remains the leading cause of polyps in childhood. The primary focus of the exam should include careful evaluation to assure absence of findings suggestive of other diseases, such as the presence of crackles, digital clubbing and hypoxemia, as well as to uncover factors that worsen disease, including nasal and sinus disease.
Laboratory Evaluation
Peripheral blood eosinophilia and/or elevated serum IgE levels are often found in children with asthma and can be helpful in the evaluation of severe disease. Laboratory evaluation is helpful in excluding entities that comprise the differential diagnosis of asthma. Serum immunoglobulin levels (IgG, IgM and IgA) may be helpful in evaluating for defects in humoral immunity predisposing to recurrent lower respiratory tract illness. Sweat chloride analysis is required to exclude cystic fibrosis. Children with bronchiectasis along with chronic otitis media and sinusitis may warrant an evaluation of ciliary structure and function. A purified protein derivative (PPD) skin test is helpful in excluding mycobacterial infection.
Assessment for Allergic Sensitization
Evaluation for allergen-specific IgE, either by percutaneous skin testing or in vitro testing, should be part of the evaluation of all children with persistent asthma, as proper identification of allergic sensitivities and instruction in environmental control measures may provide significant clinical benefit.
Radiology
All children with recurrent episodes of cough and/or wheeze should have a chest radiograph (anteroposterior and lateral views) to aid in exclusion of other diagnostic entities. Radiographic findings that may be seen with asthma include hyperexpansion, increased anteroposterior diameter, peribronchial cuffing and/or areas of atelectasis (any lobe or subsegment can be involved). Findings of chronic changes, including bronchiectasis, should lead to further evaluation of alternate diagnoses.
Pulmonary Function Tests
With the help of well-trained and experienced pulmonary function technicians, children as young as 4 to 5 years of age should be capable of performing spirometry. Spirometry measures FVC, FEV 1 , the ratio of FEV 1 /FVC, as well as other measures of airflow including the forced expiratory flow between 25% and 75% of FVC (FEF 25–75 ). The FEV 1 is the most commonly used and reproducible measure of pulmonary function, whereas the FEF 25–75 demonstrates much more intrapatient variability. Standards are widely available for most spirometric measures and allow for correction for patient age, gender, race and height. The FEV 1 /FVC ratio is an indicator of airflow obstruction and may be more sensitive in identifying airflow abnormalities in asthma than the FEV 1 , as most children with asthma have an FEV 1 within the normal range, even in the presence of severe disease (see section on Classification of asthma severity).
Asthma is characterized by airflow obstruction that is at least partially reversible by a bronchodilator. Thus, spiromety is often performed before and 20 minutes following administration of a bronchodilator such as albuterol. An increase in the FEV 1 of at least 12% is considered to represent a significant change and exceeds that seen in nonasthmatic individuals, although recent evidence suggests that lower levels of bronchodilator response (≥8–9%) may be more appropriate cut-offs in identifying asthma in children.
Particular attention should be given to the inspiratory and expiratory flow-volume loops, as they are extremely helpful in excluding other patterns of airway obstruction. For example, fixed airway obstruction (abnormalities on both the expiratory and inspiratory loops) can be seen with a mediastinal mass compressing a large airway or variable extrathoracic airway obstructive process (abnormalities just on the inspiratory loop) is seen with vocal cord dysfunction (VCD). Asthma produces variable intrathoracic obstruction (abnormalities on just the expiratory loop). Patients with VCD without asthma do not demonstrate intrathoracic airway obstruction, but may show blunting or truncation of the inspiratory loop consistent with variable extrathoracic obstruction. Variability between spirometric trials is not uncommon in patients with VCD, often consisting of normal and abnormal inspiratory loops during a single session.
In addition to spirometry, other tests of pulmonary function may aid in the evaluation of the child with asthma that is difficult to diagnose or control. Patients with asthma generally demonstrate normal total lung capacity (TLC) on lung volume testing by plethysmography, but may demonstrate evidence of air trapping as shown by elevated residual volumes (RV) and RV/TLC ratio. Measurement of diffusing capacity of carbon monoxide (DL CO ) is normal in patients with asthma, and abnormalities in DL CO should prompt evaluation for interstitial lung diseases.
Fractional exhaled nitric oxide (FeNO) is a noninvasive marker related to asthmatic airway inflammation as reflected by bronchial wall inflammation, sputum eosinophila and airway hyperresponsiveness. FeNO levels increase as asthma control deteriorates and decrease with treatment with agents which reduce airway inflammation, including inhaled corticosteroids (ICSs) and leukotriene receptor antagonists (LTRAs).
Challenge Testing
Some children present with atypical features of asthma and may pose greater challenges in confirming an asthma diagnosis. Thus, use of bronchial challenges with agents that provoke bronchoconstriction may be helpful in the diagnosis and management of the child with atypical symptoms, poor response to asthma medications or lack of a response to a bronchodilator during spirometry. Agents used for bronchoprovocation challenges include methacholine, mannitol, histamine, adenosine, allergen, cold air and exercise. Methacholine challenge has been widely used in epidemiological and clinical trials of childhood asthma and has demonstrated an excellent safety record. Challenge studies should be performed in laboratories familiar with such procedures.
Bronchoscopy
In children with particularly severe disease or with poor response to conventional therapy, direct visualization of the airways along with bronchoalveolar lavage (BAL) may provide important clinical information. Such examinations may reveal the presence of previously undiagnosed foreign body aspiration or other intrinsic airway mass, infection, extrinsic airway compression, evidence of chronic aspiration, as well as indicators of airway inflammation (such as eosinophilia or neutrophilia).
Evaluation and Management of Factors which Increase the Severity of Disease
Overview
The most common precipitating factors are respiratory infections and weather changes. Drawing attention to these factors can prompt patients to start increased treatment early in an exacerbation, as they will be looking for increasing symptoms that occur as an infection starts or as weather is changing rapidly. Exercise is also commonly identified as an exacerbating factor. Interestingly, although it is known that exposure to allergens and irritants can worsen asthma, such exposures are much less commonly recognized as important.
Exposure to Inhalant Allergens
Exposure and allergic sensitization to cockroach allergen was associated with a significantly greater risk of asthma hospitalization and greater healthcare utilization among 476 children aged 4 to 9 years who participated in the National Cooperative Inner-City Asthma Study. Allergic sensitization to the mold Alternaria has been identified as a significant allergen in terms of increasing airway hyperresponsiveness and was associated with a nearly 200-fold increased risk of respiratory arrest due to asthma, emphasizing the importance of determining underlying allergic sensitivities in patients with asthma and providing patients with accurate and practical advice on allergen avoidance techniques.
The Childhood Asthma Management Program, comprised of 1,041 children aged 5 to 12 with mild-to-moderate asthma, found that allergic sensitization to tree pollen, weed pollen, Alternaria , cat dander, dog dander or indoor molds was associated with greater airway hyperresponsiveness to methacholine, although only sensitivity to dog and cat dander and the outdoor fungus Alternaria had independently significant relationships. A cross-sectional analysis of a birth cohort of 562 children studied at 11 years of age found that bronchial hyperresponsiveness significantly correlated with higher levels of total serum IgE. Burrows and co-workers found a close relationship between total serum IgE and both the severity and persistence of bronchial responsiveness in a longitudinal study of adolescents and adults. Together these findings further the importance of control of these allergens in attenuating asthma symptoms.
A number of studies have followed children with asthma through childhood and adolescence into adulthood. Conclusions from the study in Melbourne, Australia indicate that severity of asthma in adulthood is related to the presence of increased levels of atopy in childhood, with the presence of an atopic condition in childhood shifting the risk of asthma in later life toward more severe outcomes.
There is a clear association between sensitization to pets and current wheezing and bronchial hyperresponsiveness. Dharmage and co-workers found that a high level of cat allergen in floor dust was associated both with an increased risk of being sensitized to cats and the presence of current asthma. In the Childhood Asthma Management Program (CAMP) population, children sensitized to dog and exposed to high levels of dog allergen and sensitized to cat and exposed to high levels of cat allergen had a clearly increased risk of nocturnal awakenings.
In contrast, there is evidence of a lower risk of asthma among children exposed to pets in early life compared with unexposed children. Other studies find that individuals living with a pet have significantly less asthma or less severe bronchial hyperresponsiveness. Studies showing protection from pet ownership are confounded by the likelihood that subjects with less severe asthma can keep the pets, whereas subjects with more severe disease are unable to hold pets.
Rhinitis
Rhinitis is common in children with asthma, with estimates of up to 80% of patients with asthma reporting upper airway symptoms. Whereas most rhinitis that worsens asthma is allergic, perennial rhinitis in nonatopic subjects can be a risk factor for more severe asthma. Topical nasal steroid therapy for allergic rhinitis has also been shown to attenuate the increase in bronchial hyperresponsiveness during the grass pollen season, as well as decrease the risk of emergency department visits or hospitalizations for asthma. Thus, treatment plans for patients with asthma and allergic rhinitis should consist of optimal management of concomitant allergic rhinitis (see Chapter 24 ).
Sinusitis
Sinusitis is often discovered in the search for factors responsible for an overall worsening of asthma unexplained by changes of environment or other obvious historical features. Although many patients present with symptoms of upper airway disease along with asthma, some have sinusitis as a significant contributor to difficult-to-control asthma but with a paucity of symptoms suggestive of sinusitis.
Radiographic examination of the paranasal sinuses in children hospitalized for acute asthma exacerbations is positive in 30% to 60% of children, partly depending upon the diagnostic technique used (Water’s view radiograph or computed tomography of the sinuses). The effect of antibiotic treatment of bacterial sinusitis on asthma control has been examined in several clinical studies and shown to reduce asthma medication use, decrease asthma symptoms and improve bronchial hyperresponsiveness. (see Chapter 26 ). Duration of antibiotic treatment should be individualized, but should continue until the patient is symptom-free for at least 7 days.
Gastroesophageal Reflux
Gastroesophageal reflux (GER) is common among patients with asthma. In adults with asthma the estimated prevalence of GER approaching 80%. Studies of the prevalence of GER in pediatric patients with asthma are limited, but a reported 64% incidence of a positive pH probe study in a group of 25 children with asthma suggests that GER may also be common among children with asthma.
In our experience most young children and even adolescents with GER do not report symptoms classically associated with GER in adults, including heartburn, chest pain, dysphagia or hoarseness. In fact, children rarely complain of symptoms even in the presence of significant GER demonstrated by pH probe studies. Thus, a high level of suspicion of underlying GER is necessary in the evaluation of the child with severe asthma, especially uncontrolled asthma associated with nocturnal symptoms. However, a recent trial in children with persistent asthma without symptoms of GER did not demonstrate a benefit of gastric acid suppression with omeprazole in terms of asthma symptom control, even among children with evidence of GER by pH probe study.
Environmental Exposures (Including Tobacco Smoke)
Passive exposure to tobacco smoke is a clear exacerbating factor in asthma, with increases in asthma prevalence and asthma severity among children exposed to parental smoking. Maternal smoking is associated with small but statistically significant, and probably clinically important, deficits in pulmonary function among school children. Since most smokers begin smoking during the adolescent years, active personal tobacco smoke exposure must be considered in all adolescents with asthma, especially when the clinical course becomes more severe. Cigarette smoking has been reported to be associated with mild airway obstruction and slowed growth of lung function in adolescents without asthma. Furthermore, asthma has been linked to an accelerated rate of decline in FEV 1 over time, and this rate is even greater among asthmatic individuals who smoke.
Many patients report that their asthma is triggered by ‘weather changes.’ Weather changes may be accompanied by changes in airborne allergen exposures. However, multiple studies have failed to find a definitive link between airborne outdoor allergen levels (except for an occasional mold) and worsening asthma symptoms. Thus, the true link between weather changes and asthma attacks remains unknown. In addition to allergen exposure, epidemiological studies suggest an association between levels of air pollutants, including ozone, nitrogen oxides, carbon monoxide and sulfur dioxide, and symptoms or exacerbations of asthma.
Vocal Cord Dysfunction
Vocal cord dysfunction (VCD), a functional respiratory tract disorder resulting from paradoxical adduction of the vocal cords, complicates the diagnosis and management of common respiratory tract problems, including asthma. The recognition of VCD in a patient with atypical or difficult-to-control asthma is critical in minimizing symptoms and potential side-effects associated with treatment of severe asthma. The symptoms of VCD are not unique to the disorder and include cough, wheeze, stridor, dyspnea, hoarseness and choking. Some patients report difficulty swallowing or tightness in the chest or throat. Patients with VCD often report difficulty ‘getting air in’ due to paradoxical adduction of the vocal cords during inspiration, in contrast to difficulty with exhalation as reported by asthmatics. However, patients with significant exacerbation of asthma do have diffuse airway narrowing and can have significant inspiratory limitation, which can dominate their perception of breathing difficulties. Cough is a common feature of VCD and must be differentiated from cough due to asthma or from postnasal drainage due to rhinosinusitis. Patients with VCD frequently complain of tightness in the throat and/or chest and may speak in a hoarse voice. Nocturnal symptoms are uncommon in uncomplicated VCD, but may occur in patients with both VCD and asthma. Exercise is a frequent precipitant of both VCD and asthma.
Upon presentation in an emergency department, increased work of breathing and decreased aeration caused by VCD can be difficult to distinguish from asthma. A report provides evidence that a normal level of oxygen saturation can be a clue that the cause of the distress is VCD rather than asthma.
Spirometry and inhaled provocation challenges assist in the differentiation between VCD and asthma. Asthma typically produces abnormalities in the expiratory phase of the flow-volume loop, whereas VCD results in inspiratory loop abnormalities, such as blunting or truncation of the inspiratory loop due to variable extrathoracic airflow obstruction. Respiratory impedance during inspiration, as assessed by impulse oscillometry, has been reported to differentiate between patients with VCD and normal controls. Provocation challenges, either pharmacological (methacholine or histamine) or exercise, are helpful in determining the presence or absence of airways hyperresponsiveness, a feature characteristic of asthma. Exercise challenges frequently reproduce clinical symptoms and spirometric abnormalities consistent with VCD. If this approach fails to establish the diagnosis or if the patient does not respond to appropriate therapy, direct visualization of paradoxical vocal cord movement during symptomatic periods may be helpful in confirming the diagnosis of VCD. Characteristic findings include adduction of the true vocal cords during inspiration with a diamond-shaped opening at the posterior aspect of the glottis. Once the diagnosis of VCD has been established, attention should focus on reassurance, maneuvers directed at laryngeal relaxation (from speech therapy) and discovering underlying stress that is often involved in producing or exacerbating the problem (from psychology). In our experience, a combination of speech therapy and psychological evaluation is necessary for successful therapy for VCD. Maintenance therapy for VCD includes minimization of medication use for co-morbid conditions frequently confused with VCD (i.e. asthma).
Psychological Factors
Psychological factors may be as, or even more, important than medical factors in determining outcomes of asthma, particularly in children with more severe asthma. In a group of children with severe asthma, 50% had levels of fitness in the significantly abnormal range. Psychological functioning as determined by structured interviews significantly correlated with cardiopulmonary function, but medical characteristics did not. Similar to the findings in studies of fitness levels, school performance and gross and fine motor coordination, while generally in a normal range (in contrast to the findings of fitness), overall correlated with psychological functioning but not the medical characteristics of the asthma. Depression symptoms, cigarette smoking and cocaine use occurred more frequently in youth reporting current asthma than in youth without asthma. These results indicate a need to screen adolescents with asthma for depression.
At the level of characteristics of the individual caregiver, the beliefs that parents hold about their ability to manage their child’s asthma and the quality of life that they maintain while caring for a child with asthma may be associated with asthma hospitalizations. A health education intervention study conducted to improve asthma management skills and to build family self-confidence in the ability to manage asthma found that families that participated in the intervention reported better attack management strategies and preventive strategies compared to a control group. Adults with asthma who have greater confidence or trust in the care they receive from their doctor report having better controlled asthma and are more likely to have mild, as opposed to severe, asthma. Thus, parents who believe strongly that they cannot adequately care for their child’s asthma may be more likely to bring their child to the hospital repeatedly for acute episodes.
Poor Adherence to the Medical Regimen
Most patients receive suboptimal benefit from any given prescribed asthma regimen. This is often reflected as inadequate asthma control, and often leads to prescription of higher doses or additional controller medications based upon the assumption that the medication prescribed accurately reflects the medication the patient actually takes. However, since most patients miss substantial amounts of medications, even when participating in research studies examining medication adherence, practitioners must focus on patient education regarding the importance of asthma medication use as directed and provision of a written plan of action which is practical for the patient. Complex regimens consisting of several medications given frequently during the day are less likely to be followed when compared to simple regimens with less frequent dosing requirements. When discussing asthma-related information and setting appropriate and achievable short- and long-term goals, excellence in communication and development of a partnership between healthcare providers and patients is essential in establishing the foundation for asthma care and adherence to the recommended treatment approach.
The developmental level of the child complicates adherence in the pediatric population. Children’s understanding of their asthma and the steps necessary to control the disease evolve over time. Thus, the action plan for each child must be individualized based upon the child’s developmental stage. While children begin to acquire basic asthma decision-making abilities by the ages of 8 years, they remain unable to manage their asthma independently until about 16 years of age.
Obesity
Weight reduction in obese patients with asthma has been associated with improvement of lung function and other indicators of lung status. Similar to the importance of monitoring height in children with asthma, both as an indicator of general wellness and the effects of medications used to treat asthma, comprehensive care in children with asthma includes monitoring weight acquisition and encouraging weight reduction. Recognition that obesity may produce respiratory symptoms that mimic but do not actually represent asthma is essential to avoid inappropriate and unnecessary escalations of asthma therapy.
Exercise
Exercise-induced asthma (EIA) may lead to decreased participation in physical activities due to either exertional limitation or fear of symptom development. This may explain the finding that children with asthma are less physically fit than their nonasthmatic peers. Despite these facts, asthma should not be perceived as a limitation on physical fitness, as evidenced by the prevalence of asthma among Olympic athletes approximating twice that of the general population. Increased aerobic fitness decreases EIA, as better conditioned individuals require smaller increases in heart rate and ventilation for a given task. Thus, although EIA may still occur, more physical work can be done before it begins (see Chapter 36 ).
Classification of Asthma Severity and Control
Asthma severity is currently classified as either intermittent or persistent disease ( Table 34-2 ). While the distinction between intermittent and persistent disease, and even between the various levels of persistent disease, is arbitrary, it serves as a framework for severity classification and ultimately treatment recommendations. Asthma severity is most easily assessed in a patient not receiving long-term control therapy as this reflects the intrinsic intensity of the disease process. The assessment of asthma severity requires determination of morbidity in the domains of impairment and risk, where impairment reflects the frequency and intensity of symptoms and functional limitation experienced, and risk reflects the likelihood of asthma exacerbations. Four major features of asthma – daytime symptom frequency, nocturnal symptom frequency, interference with exercise and pulmonary function – define levels of severity in the impairment domain, and exacerbations requiring systemic corticosteroids define severity in the risk domain. Nocturnal symptoms are a particularly important marker of more severe disease.
| Component of Severity | CLASSIFICATION OF ASTHMA SEVERITY FOR DIFFERENT AGE GROUPS | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| INTERMITTENT | PERSISTENT | ||||||||
| MILD | MODERATE | SEVERE | |||||||
| 5–11 Years | ≥12 Years | 5–11 Years | ≥12 Years | 5–11 Years | ≥12 Years | 5–11 Years | ≥12 Years | ||
| Impairment | Symptoms | ≤2 days/week | ≤2 days/week | >2 days/week but not daily | >2 days/week but not daily | Daily | Daily | Throughout the day | Throughout the day |
| Nighttime awakenings | 0 | 0 | 1–2×/month | 1–2×/month | 3–4×/month | 3–4×/month | >1×/week | >1×/week | |
| Short-acting β2-agonist use for symptom control | ≤2 days/week | ≤2 days/week | >2 days/week but not daily | >2 days/week but not daily | Daily | Daily | Several times per day | Several times per day | |
| Interference with normal activity | None | None | Minor limitation | Minor limitation | Some limitation | Some limitation | Extremely limited | Extremely limited | |
| Lung Function |
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| Risk | Exacerbations (consider frequency and severity) | 0–2/year | >2 exacerbations in 1 year | ||||||
| Relative annual risk may be related to FEV 1 Frequency and severity may fluctuate over time Exacerbations of any severity may occur in patients in any severity category | |||||||||
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