Featured Report:
Childhood Asthma: Emerging Patterns
and Prospects for Novel Therapies (A-02) Full Text

Background

Methods

Childhood Asthma Morbidity and Mortality in the United States
Prevalence
Hospitalizations
Mortality

Trends in Sex- and Race/Ethnic-Specific Childhood Asthma
Gender Differences in Asthma Mortality and Morbidity
Racial and Ethnic Disparities in Asthma Mortality and Morbidity

Plausible Explanations for Recent Trends in Childhood Asthma

An "Epidemic" of Childhood Asthma?

Prospects for Novel Therapies

Recommendations (Adopted AMA Policies and Directives)

References

Table. Basic Elements of Population-based Medicine

Background

Asthma is the most common chronic illness of childhood and is one of the most frequent reasons for visits to pediatricians.^1-3 Data from the last three decades also suggest that childhood asthma is increasing in prevalence^{1,2, 4-8} and in severity, as demonstrated by increasing rates of hospitalizations and mortality due to asthma.^{1, 2, 7-15} Asthma also negatively affects children during critical periods of growth and development^16-22 and the annual cost of treating childhood asthma in the United States is more than $2 billion.^2,3,18,25 As a result, studies have increasingly identified pediatric asthma as an important public health concern. A better understanding of thepathophysiology of childhood asthma has resulted in a wider range of treatment options and better management of the disease.^15,24 However, assessment of childhood asthma is still made problematic by the lack of a universally accepted definition.^1,8,25 Furthermore, despite better knowledge of its pathophysiology, childhood asthma continues to be underdiagnosed and undertreated.^26-29 Evaluation of the effectiveness of treatment is further restricted by limitations in our understanding of the epidemiology of the disease.^1,30 Clearly, more needs to be known about the condition before it can be effectively treated in this age group.

This report examines some of the basic epidemiologic patterns underlying much of the recent interest in childhood asthma. Specifically, it examines trends in the prevalence of childhood asthma morbidity and mortality in the United States, briefly reviews some of the factors associated with these emerging patterns, and explores therapeutic interventions to reduce childhood asthma. Because of limitations in scope, this report does not examine the full range of possible risk factors important in the etiology of childhood asthma. Back to Top

Methods

A systematic review of the literature was conducted using the MEDLINE database for the years 1980 to 2001. English-language articles were selected based on their ability to provide information on (1) the definition and diagnosis of childhood asthma; (2) trends in the morbidity and mortality of childhood asthma; and (3) the epidemiology of childhood asthma. Further relevant articles and books were selected from the reference listings of the primary journal articles. Other sources included the National Center for Health Statistics, the President’s Task Force on Environmental Health Risks and Safety Risks to Children, and the Epidemiology and Statistics Unit of the American Lung Association. Back to Top

Childhood Asthma Morbidity and Mortality in the United States

Difficulties in diagnosing asthma are directly related to problems in the determination of childhood asthma prevalence or in the trends of childhood asthma. Despite these problems, there are a number of measures of childhood asthma morbidity currently under surveillance in the United States, including prevalence estimates, hospitalizations, and mortality.

Prevalence. Ideally, an understanding of childhood asthma would most benefit from an examination of asthma incidence (the number of new cases of a disease over a period of time), because incidence rates can be used to estimate the probability that healthy people will develop the disease during a specified period of time.³¹ In practice, however, asthma incidence is very difficult to measure, both because of the intensive long-term monitoring required and because of the difficulty of establishing the date of onset of the condition.^1,32 For these reasons, most studies of childhood asthma report prevalence (the number of cases of asthma existing in the population at the time the study was conducted). Asthma prevalence reflects both the incidence of asthma and the average duration of the condition.³¹

National estimates of childhood asthma are typically derived from the National Health Interview Survey (NHIS), a multi-purpose health survey conducted by the National Center for Health Statistics (NCHS). In 1997 the NHIS questionnaire was redesigned in an effort to lower response burden, making it impossible to compare current asthma estimates with previous estimates.⁸ The revised questionnaire evaluates both period (lifetime diagnosis of asthma by a health care professional) and point (asthmatic attack or episode in the past 12 months) prevalence of childhood asthma. In contrast, the earlier surveys simply asked respondents whether they had asthma in the past 12 months.

Between 1980 and 1994 the overall prevalence rate of asthma in the United States increased 75%, with the most substantial increases occurring among children aged 0-4 years (160%, from 22.2 per 1,000 to 57.8 per 1,000) and children aged 5-14 years (74%, from 42.8 per 1,000 to 74.4 per 1,000).^6,33-34 Between 1997 and 1998 the period prevalence for asthma diagnosis (all ages) increased from 25.7 million to 26.3 million people.⁸ The highest period prevalence rate was observed for children 5-17 years of age in both years: 130.1 per 1,000 in 1997 and 135.0 per 1,000 in 1998. The period prevalence rates of asthma also increased for children aged 0-4 years (from 70.9 per 1,000 to 82.6 per 1,000). Between 1997 and 1998 the asthma attack rate (point prevalence) in children under 5 years increased 12.9%, from 41.2 per 1,000 to 46.5 per 1,000.⁸ Children aged 5-17 years had the highest prevalence rates in both years (59.5 and 55.6 per 1,000). Overall, an estimated 3.8 million children under age 18 years had an asthma attack or episode in 1998, the last year the data are available.⁸ Evidence also suggests considerable regional variation in asthma prevalence, with rates highest among children in the western region of the United States and in urban areas.^6,34-36

Hospitalizations. Hospitalizations reflect another dimension of asthma morbidity, as they typically represent acute events associated with asthma exacerbation.³⁰ The NCHS monitors hospitalizations using the National Hospital Discharge Survey (NHDS), a survey of noninstitutional hospitals in the United States, excluding military and Department of Veterans Affairs hospitals. Hospitalizations for asthma are identified using the first listed diagnosis; i.e., the first listed diagnosis is the diagnosis identified as the principal diagnosis or listed first on the medical record.

Initially, first listed hospital discharges for asthma increased along with prevalence rates. Between 1970 and 1987, there was a dramatic increase in the rate of hospitalizations attributable to asthma among children 0-14 years of age, from 5.8 per 10,000 discharges to 28.4 per 10,000 discharges. Much of this increase was limited to younger children, aged 0 to 4 years.^10,37 Although changes in survey methodology in 1988 make direct comparisons with earlier years impossible, there is evidence that the rate of hospitalizations for childhood asthma continued to increase into the mid-1990s, peaking at 36.7 per 10,000 in 1996.⁸ Since 1996, rates of hospitalizations for childhood asthma have declined, to 27.7 per 10,000 in 1998.⁸ However, the occurrence of asthma discharges remains very common among the pediatric population. Despite accounting for only 22% of the total population in the United States, children under 15 years accounted for more than 39% of all asthma discharges in 1998.⁸ Geographic variation in asthma hospitalizations mirrored those identified previously, with increases in childhood hospitalizations for asthma more likely in metropolitan areas.³⁸

Mortality. The NCHS also monitors U.S. vital statistics, including data on all live births, deaths, and fetal deaths. The death certificate, in particular, is an important source of disease-related data, providing information on the immediate cause of death (the disease or injury that directly causes death) as well as the underlying cause of death (the disease or injury that initiated the train of morbid events leading to death). Causes of death are coded according to revisions of the International Classification of Disease – Eighth Revision (ICD-8) for 1968 through 1978 and Ninth Revision (ICD-9) for later years. Asthma mortality is defined as any person with an underlying cause of death assigned an ICD code of 493.0 through 493.9 according to either ICD-8 or ICD-9.³⁹ Several studies suggest that the accuracy of the diagnosis of asthma as an underlying cause of death is approximately 95% for deaths of persons less than 35 years of age.^40-41

Despite revisions to the ICD coding system, increases in mortality have been consistent since 1979.¹⁴ Overall, the age-adjusted death rate for asthma mortality rose from 0.9 per 100,000 in 1979 to 1.4 per 100,000 in 1998, a 55.6% increase. The overall increase in asthma mortality was due primarily to increased mortality rates in the population subgroup aged 65 years and older.^6,42 Between 1979 and 1998, mortality rates for children less than 5 years remained relatively constant at 0.2 per 100,000. The rate for children 5-14 years of age, however, increased from 0.1 per 100,000 (39 deaths) in 1979 to 0.4 per 100,000 (149 deaths) in 1996. After 1996, the asthma mortality rate for children 5-14 years of age actually declined somewhat to 0.3 per 100,000 (131 deaths) in 1998, the last year data are available.⁸ As expected, risk of mortality is associated with disease severity^43-45 and most asthma deaths occurred in urban areas.^14,43,46 For example, New York City; Cook County, Illinois; Fresno County, California; and Maricopa County, Arizona, accounted for a majority of asthma deaths in the 1980s.^14,47 During this period, the five counties of New York City and Cook County, Illinois, together accounted for more than 20% of all U.S. asthma deaths in individuals 5 to 34 years of age.⁴⁶Back to Top

Trends in Sex- and Race/Ethnic-Specific Childhood Asthma

Gender Differences in Asthma Mortality and Morbidity.  Among children 0 through 11 years of age, the prevalence rate of asthma is higher but statistically similar for boys and girls, although among children 12 through 17 years of age, asthma is significantly more prevalent among boys.^1,28,48 Boys also have much higher rates of hospitalization for asthma.¹⁰ In contrast, among children less than 15 years of age, females and males had similar mortality rates independent of year and race.^14,33,47 This finding is somewhat paradoxical given the higher prevalence and hospitalization rates for asthma among males compared with females. It is possible that the proportion of severe asthma cases is similar among females and males, resulting in similar asthma mortality rates.³³ Another explanation is that the greater prevalence of asthma morbidity among males may be due to a greater proportion of mild to moderate disease being diagnosed.

Racial and Ethnic Disparities in Asthma Mortality and Morbidity.  Asthma prevalence varies among racial/ethnic groups in the United States, with black children more likely to have asthma than whites.^1,6,38,48-52 For example, the period prevalence rate (lifetime diagnosis) for black children <5 years is almost twice that for white children (134.4 per 1,000 vs. 70.5 per 1,000 persons in 1998).⁸ Similar – although less disparate – increases were also noted for children 5-17 years of age (131.6 per 1,000 vs. 160.7 per 1,000 in 1998).⁸ Blacks are also reported to have a higher proportion of undiagnosed asthma.^29,53 While there are fewer studies of Hispanic populations, evidence does suggests that Puerto Rican children living in the United States have a higher prevalence than nonHispanic whites or blacks and that Mexican-American children report lower rates.⁵⁴ The effects of race and ethnicity appear to be even greater with respect to asthma hospitalizations and mortality.^{10,12,33,48,55-56} For example, from 1993 to 1995, black children were 3.3 times more likely than whites to be hospitalized for asthma^10,57 and were more than twice as likely to die from asthma. Although fewer, studies also suggest that the hospitalization and death rate among Hispanic children is similar to that noted for blacks.^38,46

The etiologies of racial and ethnic differences in childhood asthma morbidity and mortality remain unclear. Cited reasons include biologic factors (e.g., genetic differences) and sociodemographic factors such as socioeconomic status, indoor and outdoor air quality, and differences in the quality of care for asthma.^56,58-59Back toTop

Plausible Explanations for Recent Trends in Childhood Asthma

While a detailed discussion of the epidemiology of childhood asthma is beyond the scope of this report, it is important to understand whether the trends noted are real or simply an artifact of the way asthma is diagnosed, recorded, or analyzed.³⁰ It is possible that all or part of the increases in prevalence may be related to changes in diagnostic recognition and accuracy resulting from improvements in both physician and public awareness of the signs and symptoms of asthma.^1,45 The trends may also be the result of changes in diagnostic transfer (i.e., the way in which another disease is reclassified as asthma). For example, researchers have proposed that the substitution of asthma for bronchitis is artificially inflating estimates of asthma.^10,60 Changes in ICD coding for asthma may have also resulted in higher rates of childhood asthma.⁴ Finally, there may have been changes in risk factors associated with recent asthma trends.^11,14

All these possibilities have been examined to some extent. While data suggest that changes in diagnostic recognition and accuracy may affect prevalence rates, it is apparent that improved diagnostic recognition, changes in diagnostic transfer, or changes in ICD coding fail to account for all of the recent change in childhood asthma rates, suggesting that a true increase in disease burden is occurring.³⁰ It is more likely that the United States is experiencing real changes in risk factors associated with childhood asthma morbidity and mortality. However, an understanding of the relative impact of identified risk factors is far from complete.³⁰ Some of the more promising explanations focus on changes in the medical care environment (e.g., access to care, pharmacotherapy)^30,61-63 and indoor air quality (e.g., smoking, aeroallergens, viral agents, molds, and irritant gases).^30,64-75 Other factors have been suggested, including gastroesophageal reflux disease,⁷⁶ low birth weight,⁷⁷ and short duration of breastfeeding.⁷⁸ However, the evidence is inconclusive and more research is needed before firm conclusions can be drawn about the epidemiology of childhood asthma.Back to Top

An "Epidemic" of Childhood Asthma?

The data do suggest that the United States may be facing an epidemic of childhood asthma, especially in urban areas and among minority children. When analyzed separately, trends in asthma prevalence, hospitalizations, and mortality, all point to a general increase in childhood asthma over the last 30 years. High levels of hospitalizations and/or mortality as a percentage of prevalence among children also suggest a high level of disease severity among children of all ages. Furthermore, all indications suggest that the prevalence of childhood asthma and severe childhood asthma will continue to rise. Even if prevalence rates were to stabilize, childhood asthma would continue to be a profound problem affecting individuals, families, and society.

While clearly a public health concern, definitive assessment of a potential epidemic of childhood asthma is limited by the available data. As already noted, prevalence data can be affected by changes in diagnostic recognition and accuracy.³⁰ Prevalence estimates are generally believed to reflect an underestimate of true asthma prevalence among children, since studies have indicated that many are undiagnosed.^1,8 Crude hospital discharge rates also vary considerably by state of residence and population characteristics.³⁷ The NHDS has another important limitation in that it samples only discharge events and not individuals, making it impossible to differentiate between an increase in the disease due to first admissions from new asthmatic patients vs. repeat admissions. It is likely that both changing prevalence and repeat admissions contribute to the observed trends in hospitalizations for childhood asthma.^37,79-81 Finally, while the certification of death due to asthma may be accurate, the quality of mortality data in general is poorer for certain racial and ethnic minorities.^82-83

Lack of consensus on the definition also impedes the assessment of childhood asthma in the United States.^1,25,84-85 Asthma is generally defined as a chronic or recurring inflammatory disease of the airways in which bronchial hyperresponsiveness (BHR) is associated with reversible airway obstruction.^{83, 86-87} This definition is embodied in the Expert Panel Report II: Guidelines for the Diagnosis and Treatment of Asthma put forth by the National Heart, Lung, and Blood Institute’s (NHLBI) National Asthma Education and Prevention Program (NAEPP).⁸⁸ Unfortunately, difficulties arise when this definition is applied to young children.^83,87,89 Authors have noted the lack of evidence for persistent inflammatory processes in the airways of wheezy children, the lack of data connecting BHR to wheezy children (compared to non-wheezy children), and the limited information regarding variability of airway obstruction in young children.^83,87 These issues are compounded by the nonspecific nature of symptoms of airway obstruction in young children^26,90 and from the complex interrelationships between BHR, the diagnosis of asthma, and asthma symptoms in this population.^91-92 One study even suggests that BHR and clinical asthma may not always coexist in children, calling into question the use of BHR as the gold standard for the diagnosis of childhood asthma.⁹³

Problems in definition also make the classification (and treatment) of childhood asthma more difficult^29,83,87 and may influence physician compliance with the NHLBI asthma guidelines. While pediatricians are generally aware of the guidelines, poor adherence is well documented.^94-96 In an effort to improve compliance with evidence-based recommendations, the American Academy of Allergy, Asthma and Immunology, the American Academy of Pediatrics, and the NHLBI translated the NAEPP guidelines into recommendations that can be easily used by pediatricians.⁹⁷ These revised guidelines also acknowledge the differences in assessment and management that exist for younger children with asthma (i.e., age <= 5 years). The AMA’s Physician Consortium for Performance Improvement (The Consortium), comprised of methodological and data experts and representatives from more than 50 national medical specialty societies, is developing performance measures for asthma care based on the NHLBI guidelines. The Consortium is also developing tools that will allow physicians to collect information prospectively on asthma patients to improve the consistency with which asthma symptoms are assessed, encourage the classification of asthma severity, and promote appropriate treatment in accordance with the evidence-based recommendations.Back to Top

Prospects for Novel Therapies

The complexity of childhood asthma disease makes it unlikely that it could be addressed using a single clinical or public health intervention. However, a number of promising strategies exist that may be employed by clinicians to treat the condition. One example is population-based medicine (PBM). Population-based medicine is a clinical strategy that attempts to manage the health care of a population as a whole, placing the individual patient within the context of a larger community of both sick and well individuals.^98-101 Basic elements of PBM include:

• Identifying the health and disease states that are likely to be responsive to population-based care;
• Applying principles of epidemiology to define the population of interest;
• Assembling a multidisciplinary team; and
• Building information systems to support ongoing surveillance of population-based care.

Also see the Table.

Despite the limitations of the epidemiological studies reviewed in this report, many utilize methods to identify and stratify child and adolescent populations at risk of the disease (e.g., utilization of health care facilities, utilization of pharmacotherapy). It is clear, for example, that urban and minority children suffer disproportionately from asthma. Another starting point for a population-based intervention strategy is a clear body of evidence-based literature suggesting that a disease state can be managed using a population-based approach. Here, again, asthma care benefits from the existence of well-accepted national practice guidelines. Furthermore, the revised guidelines acknowledge the differences in assessment and management of asthma in younger children. While incomplete, the epidemiology of childhood asthma also offers the opportunity to identify subpopulations of interest (e.g., those at risk for morbidity and amenable to intervention) within a patient population. Genetics clearly plays a role in the epidemiology of childhood asthma.^84,102 Also important, however, are the emergent risk factors mentioned earlier. For instance, the relationship between indoor air quality and asthma may prompt a clinician to screen young children in his/her practice who are enrolled in day care for asthma. The tools being developed by The Consortium could then be used to monitor progress.

That PBM to treat childhood asthma is not simply an academic exercise is demonstrated by the success of population-based asthma management programs. One example is the Central Pediatric Asthma Program (CPAP) conducted at Harvard Pilgrim Health Care in Boston.^103-104 Discussed more thoroughly by Weiss,¹⁰⁰ patients enrolled in CPAP receive coordinated asthma care from primary care physicians, asthma specialists, and asthma nurses, with the level of care dictated by the severity of the disease. The Joint Commission on Accreditation of Healthcare Organizations also recently awarded it first disease-specific care certificate to the Los Angeles County Department of Health Services Clinical Resource Management (CRM) Program for its population-based work in pediatric asthma. In the CRM program, multidisciplinary teams of health care professionals, including physicians, nurses, and respiratory therapists, use a network of mobile clinics to reduce barriers to care and bring preventive health care to children at their school sites.^{105Back to Top}

RECOMMENDATIONS (Adopted AMA Policy and Directives)

The following statements, recommended by the Council on Scientific Affairs, were adopted by the AMA House of Delegates as AMA policy and directives at the 2002 AMA Interim Meeting:

1. The AMA encourages the Centers for Disease Control and Prevention; the American Lung Association; the National Heart, Lung, and Blood Institute; the American Academy of Pediatrics; the American Academy of Family Physicians; and others to work together to develop a comprehensive and uniform definition of childhood asthma. (Directive)
2. The AMA will educate physicians using existing communication channels on the problem of childhood asthma in the United States, including basic epidemiologic patterns underlying much of the recent interest in the environmental and demographic disparities in the prevalence of childhood asthma. (Directive)
3. The AMA encourages the National Center for Health Statistics, the American Lung Association, and others to develop better data on the incidence and prevalence of childhood asthma morbidity and mortality, including complete demographic, environmental, and socioeconomic information. (Directive)
4. The AMA encourages physicians to make use of guidelines for the treatment of childhood asthma, including those contained in the Expert Panel Report II: Guidelines for the Diagnosis and Management of Asthma, released by the National Heart, Lung, and Blood Institute, and the Promoting Best Practice Guide for Management of Asthma in Children, released by the American Academy of Allergy, Asthma and Immunology. (Policy)
5. The AMA will continue to support the efforts of the Physician Consortium for Performance Improvement (The Consortium) to develop evidence-based performance measures for asthma care. Furthermore, the AMA encourages The Consortium to explore the feasibility of performance measures for asthma care of children less than 5 years of age. (Directive)
6. The AMA encourages physicians to (a) educate parents of children with asthma on the assessment and reduction of known risk factors for childhood asthma; and (b) where necessary refer patients and their families to comprehensive asthma education programs based on evaluated models. (Policy)
7. The AMA encourages and supports public health departments to examine risk factors for childhood asthma and work with medicine to develop appropriate treatment and educational resources for physicians and for families with asthmatic children. (Policy) Back to Top 

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Table. Basic Elements of Population-based Medicine^*

* Adapted from Weiss¹⁰⁰

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Resolution 412 (I-01)

Resolution 412, introduced by the American Academy of Child and Adolescent Psychiatry, American Academy of Allergy, Asthma and Immunology, American College of Preventive Medicine, and American Psychiatric Association, and adopted by the AMA House of Delegates at the 2001 American Medical Association (AMA) Annual Meeting, asked: "That the AMA Board of Trustees through the Council on Scientific Affairs prepare a report reviewing the scientific literature concerning the increased incidence of childhood asthma, including the relationship between asthma and socioeconomic status, psychosocial factors, air pollution, and exposure to environmental toxins; and develop recommendations, based on the scientific literature, for specific public policy, public education, and/or legislation designed to reduce the incidence of childhood asthma."

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