The burden of asthma with specific reference to the United States

Transcription

1 The burden of asthma with specific reference to the United States Richard Beasley, MBChB, FRACP, DM, FAAAI Wellington, New Zealand During the second half of the 20th century, the increasing prevalence, morbidity, economic burden, and, in some countries, mortality from asthma have generated worldwide concern. The prevalence in the United States and other Englishspeaking countries is higher than that in most other countries, but worldwide variations cannot be explained by current knowledge of recognized risk or protective factors. According to hospital admission rates, asthma morbidity rates have also risen throughout the world during the past 40 years. These trends are likely due to many different factors, including an increase in the prevalence of severe asthma. Asthma mortality rates gradually declined in the United States during the 1960s and 1970s but have exhibited a substantial, progressive increase during the past 20 years. This trend stands in contrast to those in most other western countries, where asthma mortality rates have generally been decreasing during the 1990s. In both western and developing countries, the considerable economic burden of asthma disproportionately affects individuals with severe disease. This observation illustrates the potential for reducing the costs associated with asthma through management approaches that have been proven to reduce morbidity and mortality. (J Allergy Clin Immunol 2002;109:S482-9.) Key words: Asthma, β-agonists, inhaled corticosteroids Since the second half of the 20th century, the increasing prevalence, morbidity, mortality, and economic burden associated with asthma have generated worldwide concern. This concern has been based not only on the magnitude of the increases but also on an inadequate understanding of the underlying causes. A closer examination of these trends, particularly in the United States, may help shed greater light on the basis for such trends. PREVALENCE International trends Most studies that have assessed changes in the prevalence of asthma symptoms with standardized methods in the same community at different times over the past 40 years have reported that asthma prevalence has increased. 1 This increase has been observed in a wide range of countries with differing lifestyles and, in some From the Department of Medicine, Wellington School of Medicine, Wellington, New Zealand. Dr Beasley is a consultant for GlaxoSmithKline and is a member of the speakers bureau for GlaxoSmithKline and AstraZeneca. He also receives grant support from GlaxoSmithkline, AstraZeneca, and Novartis. Reprint requests: Richard Beasley, MBChB, FRACP, DM, FAAAI, Department of Medicine, Wellington School of Medicine, PO Box 7343, Wellington, New Zealand Mosby, Inc. All rights reserved /2002/$ /0/ doi: /mai S482 Abbreviations used ECRHS: European Community Respiratory Health Survey ISAAC: International Study of Asthma and Allergies in Childhood countries, has been of considerable magnitude (Table I). Interpretation of these studies is limited by the lack of objective markers of asthma, and the findings may in part be attributed to greater patient awareness of symptoms or greater physician awareness of diagnostic criteria. Nonetheless, the few studies that have examined changes in the prevalence of bronchial hyperreponsiveness in children have demonstrated increases over this period. 2 The rise in asthma prevalence appears to have begun in the early 1960s, has occurred in both children and adults, and has increased progressively since this time. 1-4 Asthma prevalence has also been shown to increase when communities move from a rural to an urban environment; indeed, up to a 50-fold higher prevalence has been observed in children of the same racial background in rural areas compared urban areas in Africa. 5 Another observation is that other atopic disorders, such as allergic rhinitis, atopic eczema, and urticaria, are becoming more common throughout the world, although these conditions, like asthma, are poorly defined and are prone to changes in recognition of symptoms and diagnosis. 2 The magnitude of these increases is similar to that associated with asthma prevalence, although the time course may be different, with the increase in asthma prevalence predating, by at least 10 years, the subsequent increase in the prevalence of allergic rhinitis and atopic eczema. 6 Although it is recognized that the worldwide increase in asthma prevalence is due to changes in environmental risk factors, there is no adequate explanation of the relative importance of the numerous factors that have been implicated. US trends The increase in the prevalence of asthma symptoms in US children and adults has been similar in magnitude to that in other western countries. When data from either standardized national or regional surveys are used, the increase in the prevalence of diagnosed asthma or of asthma symptoms in children and adolescents has been reported to range between 25% and 75% per decade during the period from 1960 to Another consistent feature of these and other studies has been the higher prevalence rates in children of color as compared with white children, and in urban compared with rural areas. 8,12,13

2 J ALLERGY CLIN IMMUNOL VOLUME 109, NUMBER 5 Beasley S483 Worldwide prevalence patterns and comparative US rates With the standardized international asthma prevalence data published by the European Community Respiratory Health Survey (ECRHS) 14 and the International Study of Asthma and Allergies in Childhood (ISAAC), 15,16 it is now possible to make comparisons of the prevalence of asthma symptoms between countries. These studies have shown wide variations in asthma prevalence in both children and adults that cannot be explained by current knowledge of the recognized risk or protective factors for the development of asthma (Fig 1). One of the features of these studies is that the prevalence of asthma symptoms and diagnosed asthma in the United States is among the highest in the world for both children and adults The US rates are similar to those in other English-speaking countries such as the United Kingdom, Australia, and New Zealand and are higher than in most other countries. This overall pattern is maintained when the data are elicited by video questionnaire, suggesting that differences in language or labeling of symptoms are unlikely to explain the major international patterns, at least in children. In the United States, the prevalence of self-reported wheezing in the previous 12 months was 22%, and a positive response to the question of whether the individual ever had asthma was 16% for 13- to 14-year-old children in the ISAAC study. 15,16 The corresponding figures were 26% and 7%, respectively, for adults from the United States in the ECRHS. 14 The lower rate for diagnosed asthma in adults possibly relates to poor recall of childhood conditions. 17 Alternatively, these findings would represent a cohort effect (the 2 surveys had a mean age difference of about 20 years) with an increase in reported asthma prevalence over time, because of either a change in diagnostic practice or an actual increase in prevalence. MORBIDITY International trends Available data also suggest a worldwide increase in asthma morbidity, if the rate of hospital admissions is considered an acceptable surrogate measure. International trends have indicated an increasing number of hospital admissions for asthma, beginning in the 1960s and being most pronounced in young children. 18 These trends cannot be completely explained by an increase in re-admissions, diagnostic transfer from related disease categories, or changes in medical practice (such as the threshold for hospital admission); rather, they likely reflect an increase in the prevalence of severe asthma The observation that hospital admission rates in England have risen approximately evenly in all age groups within successive generations is compatible with a cohort effect caused by an increase in the prevalence of severe asthma, as well as with changes in service use. 2,22 During the 1990s, the hospital admission rates stabilized or decreased in several countries, including the United Kingdom 19 and New Zealand. 23 TABLE I. Changes in prevalence of asthma or asthma symptoms in children and young adults US trends Asthma prevalence First study Second study Country Period (%) (%) Australia Canada * England Finland France Germany 1991/2-1995/ Hong Kong Israel Italy / Japan New Zealand Norway Papua, New Guinea Scotland Singapore Sweden Tahiti Taiwan United States Vietnam Wales Adapted with permission from J Allergy Clin Immunol 2000;105: Asthma or asthma symptom prevalence data for a country are included only if the same method was used on 2 occasions. Many different methods were used to define asthma or asthma symptoms in studies from the different countries; as a result, comparisons of the asthma prevalence rates between countries should be avoided. *Men. Women. Incidence rates per 1000 person-years. Similar to the international trends, in the United States, hospital admissions for asthma have exhibited a marked increase during recent decades. 11,20,24,25 Between the mid 1960s and the mid 1980s, hospitalization rates for asthma increased by more than 200% in children and 50% in adults. 25 Since the 1980s, a more modest increase in asthma hospitalization rates has been apparent in children and young adults, with a reduction in older adults. 24 Several observations suggest that the increase in hospitalization rates reflects a real increase in the prevalence of severe disease, rather than simply greater use of hospital care or

3 S484 Beasley J ALLERGY CLIN IMMUNOL MAY 2002 FIG 1. Twelve-month prevalence of self-reported asthma symptoms in 13- to 14-year-old children. (Reprinted with permission from ISAAC Steering Committee. Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC. Lancet 1998;351: Copyright by The Lancet Ltd ) a shift in diagnostic coding for asthma as the reason for the admission. For example, there has been an increase in the proportion of patients with asthma admitted to the hospital who require intubation, 20,21 even as the total number of hospitalizations for respiratory disease has decreased during this period. 11,20 Hospitalization rates for patients of color compared with white patients were reported to be 50% higher in adults and 150% higher in children. 25 Although numerous reasons may explain this racial difference, including the higher prevalence of asthma in communities of color, this trend is likely to be primarily related to poverty rather than race per se. 26 International comparisons Even though trends in country-specific asthma hospitalization rates are a useful measure of changes in asthma morbidity within a country, they are less useful for comparing morbidity rates between countries because of the numerous factors, including the availability and use of health care resources, that can influence hospital admission rates. An alternative approach is to compare the prevalence of symptoms of severe asthma, such as nocturnal awakenings or severe attacks affecting speech, as indicators of morbidity. The prevalence of self-report-

4 J ALLERGY CLIN IMMUNOL VOLUME 109, NUMBER 5 Beasley S485 FIG 2. International patterns of asthma mortality (deaths per 100,000 persons) in individuals aged 5 to 34 years, 1960 to 1994, showing the different trends. (Reprinted from Ref. 29, p , by courtesy of Marcel Dekker, Inc.) ed symptoms of severe asthma, based on the standardized international data, can then be compared between countries Such analyses indicate that the prevalence of severe asthma in the United States is among the highest recorded throughout the world for both children and adults. In a general population of 13- to 14-year-old children from the United States, 4% and 10% reported wheezing that disturbed sleep or limited speech, respectively, 16 and 8% of all adults reported waking with breathlessness within the preceding 12 months. 14 Morbidity in the United States A more detailed assessment of asthma-associated morbidity was provided by the Asthma in America Survey, which documented the frequency and severity of symptoms and the requirement for emergency care in a national sample of more than 2500 adults with asthma or parents of children with asthma. 27 This survey showed that approximately half of children with asthma and one quarter of adults with asthma missed school or work in the previous 12-month period because of their disease. Furthermore, 30% of patients with asthma reported awakening with breathing problems at least once a week. With respect to health care use within a 12-month period, 9% of persons with asthma were hospitalized, 23% required emergency department visits, and 29% had other unscheduled asthma-related emergency visits to a physician s office or clinic. In total, 41% of all adults with asthma and 54% of children with asthma were hospitalized or treated in an emergency department or required other urgent care for their asthma within the previous 12 months. By comparing these data with those from a control group, it was possible to determine that patients with asthma had, on average, 75% more sick days than the general public. Similarly, almost two thirds of adults with asthma, but only one quarter of control subjects, reported that their activities were limited by their health. MORTALITY International trends Many different patterns of asthma mortality were observed throughout the 20th century. 28,29 After asthma mortality rates had remained relatively stable during the first half of the century, a gradual increase was apparent in the 5- to 34-year-old age group in many countries during the last half of the century. Several possible reasons, including increases in asthma prevalence, have been proposed to explain this trend, but their relative contributions in different countries are uncertain. Another pattern was a sudden marked increase in asthma mortality rates in at least 7 countries during the 1960s and in New Zealand in the 1970s (Fig 2). 29 Available evidence indicates that the major cause of these epidemics was the use of high-dose preparations of 2 specific β- agonist drugs, isoproterenol and fenoterol. Both agents are relatively nonselective potent full agonists that have both greater long-term and immediate adverse effects than other β-agonists. It is likely that the regular use of these agonists led to worsening asthma control and that their overuse for treatment of life-threatening asthma attacks led to an increased risk of death as the result of adverse cardiac effects in the presence of severe hypoxia. These epidemics ended after the withdrawal of isoproterenol and fenoterol from the markets in the 1970s and 1990, respectively. Since the late 1980s, asthma mortality rates have fallen gradually in some, but not all, countries in which accurate mortality statistics are available. This reduction may have been related to changes in management, in particular the greater use of inhaled corticosteroid therapy However, the time-trend evidence is not conclusive in this regard, and other factors may account for some of the recent decline in mortality rates.

5 S486 Beasley J ALLERGY CLIN IMMUNOL MAY 2002 TABLE II. Comparison of asthma mortality rates with prevalence rates of severe asthma in 12 countries Country Asthma mortality rate* Prevalence of severe asthma Ratio Australia Canada England Finland France Italy Japan New Zealand Sweden United States Wales West Germany Reprinted from Ref. 29, p , by courtesy of Marcel Dekker, Inc. Note: Mortality and prevalence data are not available in the same age group. *Asthma mortality rate (per 100,000) in persons aged 5 to 34 years in Asthma prevalence rates defined as self-reported episodes of wheezing sufficient to limit speech in previous 12 months in 13- to 14-year-old children, 1993 to US trends The asthma mortality rate in the United States was low (<0.5 per 100,000 in the 5- to 34-year-old age group) during the first half of the 20th century and did not increase during the 1940s and 1950s, as was the case in other western countries. 28,35 No epidemics of asthma mortality occurred during the 1960s through the 1980s because the high-dose preparations of isoproterenol and fenoterol were not approved for use in the United States. 28,29,36,37 After a gradual decline in asthma mortality rates in the 1960s and 1970s, rates have increased progressively during the past 2 decades. 24,35 The magnitude of the increase has been substantial such that the rate of asthma mortality in the mid 1990s was approximately double that in the mid 1970s. This trend contrasts with the trends in most other western countries, in which the rate of asthma mortality decreased during the 1990s after the progressive increase through the 1980s. The underlying reasons, including the role of management, will require further investigation if strategies are to be implemented successfully to reduce asthma mortality rates in the United States. International comparisons It is necessary to consider the prevalence of severe asthma in the countries being compared to enable meaningful comparisons of international asthma mortality rates. With the use of such prevalence data from the ISAAC study, it is possible to devise crude national case fatality rates, defined by the ratio of the asthma mortality rates to prevalence rates of severe asthma for each country. In this way, an indication of national case fatality rates can be achieved, providing a different perspective on the international differences in asthma mortality than that obtained from the absolute mortality rates (Table II). Mortality in the United States The international comparisons suggest that case fatality rates in the United States are broadly within the range of those in similar western countries. However, this interpretation must be qualified by the circumstantial data suggesting substantial underreporting of asthma as a cause of death in the United States. This possibility is based on the observation that more than half the deaths from asthma in the United States are reported to occur in the hospital, compared with fewer than 20% in other western countries Furthermore, a US study of the accuracy of death certification in asthma in Rochester, New York, over a period of 20 years showed a 33% underestimation of asthma-related deaths in the population. 41 As a result, these data suggest that the rate of mortality from asthma in the United States may be considerably higher than currently recognized. Investigations of asthma-related deaths in the United States have shown that rates are greater in disadvantaged groups, such as black and Hispanic populations, as well as in those who are poorly educated, live in large cities, or are poor. 35,39,40,42 The reasons for these findings are likely multifactorial, including differences in prevalence, in risk factors for severe disease, and in asthma management (including access to medical care). Seasonal trends in asthma mortality have also been observed in the United States, with patterns similar to those in other countries. 43 The asthma mortality rate in the 5- to 34-year-old age group is highest during the summer months, whereas the peak occurs during the winter in older age groups. This trend in the younger age group is likely to be related to reduced access to medical care during the summer holidays, in view of the associated reduction in hospital admissions during this period.

6 J ALLERGY CLIN IMMUNOL VOLUME 109, NUMBER 5 Beasley S487 TABLE III. Ten-year changes in US costs of asthma from Category 1985 estimates adjusted to 1994 dollars (in millions of dollars) 1994 total costs (in millions of dollars) Direct medical expenditures Hospital care Inpatient* ED Outpatient Physicians services Inpatient Outpatient Medications All direct expenditures Indirect costs School days lost Work days lost Outside employment Housekeeping only Mortality All indirect costs All costs ,748.3 Reprinted with permission from J Allergy Clin Immunol 2000;106: ED, Emergency department *Number of bed days. Number of medications prescribed. Number of actual deaths. ECONOMIC BURDEN OF ASTHMA General observations Another way of characterizing the burden of asthma in a community is to calculate the economic costs of the illness. This is normally undertaken by calculating the direct costs (those associated with the medical treatments for the illness) together with indirect costs (those associated with nonmedical output losses resulting from the consequences of the illness). 44 In terms of costs to the individual, a number of studies have provided estimates of the financial burden on patients with asthma in different Western countries, ranging from $300 to $1300 per patient per year (adjusted to 1990 US dollars). 45 However, the economic burden of asthma disproportionately affects those with the most severe disease. In both western and developing countries, patients with severe asthma account for the majority of both direct and indirect costs. Estimates have shown that patients with severe asthma are responsible for approximately 50% of all direct medical costs and a similar proportion of the total asthma-related costs, even though they represent only up to 10% of the population with asthma (depending on the criteria used to define severe asthma) In contrast, the 70% of patients with asthma that can be classified as mild are responsible for only approximately 20% of the total asthma costs. In general, indirect costs are of a magnitude similar to that of direct medical costs, and the major components of the direct medical costs are hospital admissions. It is evident that the overall economic burden can be reduced by changing the proportion of direct and indirect costs. In this way, an increase in direct medical costs could lead to a reduced total cost of care if it led to a disproportionately greater reduction in indirect costs as the result of improved clinical outcomes. Management regimens that have been shown to reduce hospital admissions and time lost from work or school, particularly in the patients with the most severe disease, would thus have the greatest potential for reducing the economic burden of asthma. Economic burden in the United States The economic burden of asthma in the United States in 1990 was assessed in detail by using data from the National Center for Health Statistics. 49 This analysis calculated that the cost of asthma in 1990 was approximately $6.2 billion, representing $3.6 billion of direct medical expenditures for asthma and $2.6 billion of indirect economic losses attributed to the disease. Inpatient hospital services represented the largest single direct medical expenditure for asthma, approaching $1.6 billion. This and a subsequent study based on 1987 data, 50 which estimated that hospitalizations accounted for more than half of all expenditures, illustrated the potential for effective intervention

7 S488 Beasley J ALLERGY CLIN IMMUNOL MAY 2002 programs to reduce costs associated with asthma if there was a shift from more expensive hospital care to ambulatory care. This latter study calculated that more than 80% of the resources were used by 20% of the population with asthma, defined as the high-cost patients. A similar analysis of the trends between 1985 and 1994 showed that total adjusted asthma costs increased by approximately 50%, primarily because of an increase in indirect economic costs (Table III). 51 In terms of direct medical expenditures, the proportion of costs as a result of hospital inpatient care decreased significantly, primarily because of shorter lengths of stay (23% reduction) as opposed to a decrease in the total number of admissions (3% reduction). During this same period, hospital admissions for all conditions decreased by 11%, and annual total bed days decreased by nearly 25%. In 1994, medications replaced hospital admissions as the largest component of direct medical expenditure, up from 30% to 40%. The marked increase in indirect economic costs was primarily due to the increase in the total number of days lost from work and the costs attributed to the 40% increase in the mortality rate. CONCLUSIONS In summary, there is worldwide concern about the increasing burden of asthma over recent decades, in terms of increasing prevalence, morbidity, and economic costs, and in some countries, mortality. Although the magnitude of the increases has been variable, the overall pattern of an increasing burden from asthma is broadly consistent between countries with differing lifestyles and medical practices. Also of concern is the incomplete understanding of the underlying causative factors that are responsible for the international trends. 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