Epidemiology

The World Health Organization (WHO) estimates that 300 million people have asthma worldwide, producing significant morbidity and interfering with daily activities and quality of life. During the year 2009, 250,000 people died from this condition in low- to middle-income countries. Furthermore, asthma is the most frequent chronic respiratory condition among children worldwide, and its prevalence is increasing. The Centers for Disease Control and Prevention (CDC) has estimated a significant rise in asthmatic patients of 12.3% since 2001 in the United States. Statistical figures for 2009 show that 24.6 million people had asthma, compared with 20.3 million at the beginning of the decade. This increase has come with a cost to society of $56 billion dollars in medical expenses and lost productivity. No clear explanation for this increased prevalence, however, has emerged, especially in view of the overall reduction in smoking and in second-hand smoke exposure with the implementation of laws banning smoking. The same situation is described outside the United States. From a metaanalysis of data obtained through routine statistics and population surveys, Anderson and co-workers concluded that asthma prevalence increased in the United Kingdom from 1955 to 2004.

Despite a large number of research studies, the reasons for why some people develop asthma and others do not and why asthma has emerged as a public health problem in some populations earlier than in others are not well understand. The main problem in focusing on the epidemiology of asthma is to address a proper operational definition in an attempt to unify the large conclusions of many epidemiologic studies from different areas of the world. The need to derive a practical and tangible definition of asthma for use in large-scale questionnaire-based epidemiologic research has led to a focus on asthma symptoms and their highly subjective expressions as part of the results. In questionnaire surveys, the presence of asthma often is defined on the basis of responses to questions about symptoms of wheeze in the past weeks or months, “wheeze ever,” and doctor-diagnosed asthma. This approach has been shown to have good short-term repeatability but may lack specificity, particularly in children, because other causes of wheezing illness, such as viral infection, may be misdiagnosed as asthma. With a focus on symptoms, the most common clinical presentation is one of breathlessness, wheezing, chest tightness, and cough, especially at night, coexisting with asymptomatic periods. Because of the nonspecificity and variability inherent in personal perception of respiratory difficulty, implementation of vital patient educational programs and pharmacologic treatment of asthma symptoms may be delayed. Clinical symptoms vary from one person to another, so a severe asthma exacerbation that necessitates urgent medical attention may not be recognized at first, and consequent delay in getting required treatment may lead to a poorer outcome.

Reported prevalence rates for asthma are widely variable. Despite the difficulty in obtaining a consensus on epidemiologic data, several studies have shown that asthma prevalence is increasing worldwide, with at least 7% to 10% of the population affected. Inclusion of data obtained using nonstandardized methods (questionnaires versus definition agreement) in a majority of the epidemiologic studies to determine asthma prevalence underlies the notable differences in global rates published in contemporary literature. This particular finding has no significance for geographic distribution of asthma, rates for which remain very low in many rural villages, in contrast with data reported for Western populations. Pollution in industrialized civilizations acts like a silent predator on the susceptible airway, leading to asthma in persons with certain respiratory diseases. A “hygiene hypothesis” has been proposed to explain an increased risk in children for the development of asthma that may reflect reduced microbe exposure in early life.

In a morbidity and mortality report from the CDC for the period 2006 to 2008, asthma prevalence was estimated as 7.8% for the U.S. population (Table 38-1). Current asthma prevalence was higher among the multiracial (14.8%), Puerto Rican Hispanics (14.2%), and non-Hispanic blacks (9.5%) than among non-Hispanic whites (7.8%). Current asthma prevalence also was higher among children (9.3%) than among adults (7.3%), among females (8.6%) than among males (6.9%), and among the poor (11.2%) than among the near-poor (8.4%) and nonpoor (7.0%).

Table 38-1 Prevalence of Current Asthma Among Children and Adults by Sex, Race/Ethnicity, and Economic Status–Poverty Level*

With respect to the worldwide variability in reported prevalence rates for asthma, different studies have examined the impact on asthma care in two of the most ethnically diverse nations, such as the United Kingdom and the United States. Emigrational cohorts of Mexican Hispanics have demonstrated a lower rate of asthma than that in U.S.-born Hispanics. Moreover, in a comparison of U.K.-born persons of the same ethnic group with those already settled after emigration, the second group demonstrated a lower rate of physician visits for asthmatic symptoms. Nevertheless, Westernization does not explain this variance, and the inequalities also may be influenced by differences in genetics, environmental risk factors, and social activities.

One of the main objectives of the European Community Respiratory Health Survey (ECRHS) was to estimate the variation in prevalence of asthma, asthma-like symptoms, atopic sensitization, and bronchial hyperreactivity, predominantly in Western Europe and many other countries (Figure 38-1). The highest rates in Europe were in the United Kingdom (15.2%), and the lowest were in Georgia (0.28%). Another important ongoing multicenter study, the International Study of Asthma and Allergies in Children (ISAAC), had as its main aim to determine the asthma prevalence in children. A comparative survey conducted in Canadian children between 2 and 7 years of age showed an asthma prevalence of 9.8% overall, with a 4.6% higher rate in boys than in girls (Figure 38-2). GINA embraced the results of both of these valuable studies in the Global Burden of Asthma report and estimated that by 2025, 400 million people around the world will have a diagnosis of asthma. In the same way, this increase in prevalence is directly related to the augmented rates of rhinitis, eczema, and other atopic disorders.

Figure 38-1 Prevalence of asthma in Europe.

(Courtesy European Community Respiratory Health Survey I Centers. Available at: http://www.ecrhs.org/ECRHS%20I.htm.)

Figure 38-2 Annual changes in worldwide prevalence of asthma symptoms among children 6 to 7 years of age and those 13 to 14 years of age, over a mean of 7 years after phase I of the International Study of Asthma and Allergies in Childhood (which in most participating countries was conducted between 1991 and 1993). Blue triangles, locations where prevalence was reduced by at least 1 standard error (SE) per year; green squares, locations where there was little change in prevalence (i.e., change of less than 1 SE per year); red triangles, locations where prevalence increased by at least 1 SE per year.

(From Subbarao P, Mandhane PJ, Sears MR: Asthma: epidemiology, etiology and risk factors, CMAJ 181:E181–E190, 2009.)

In relation to mortality, asthma accounts for an estimated 250,000 annual deaths worldwide. Statistical data show large differences between countries, and asthma death rates do not parallel prevalence rates (Figure 38-3). Mortality seems to be high in countries where access to essential drugs is low. According to the WHO, many asthma-related deaths are preventable, being a result of suboptimal long-term medical care and delay in obtaining help during the final, fatal attack. In many areas of the world, people with asthma do not have access to basic asthma medications and health care. Nations with the highest death rates are those in which controller medications are not available. In many countries, deaths due to asthma have declined recently as a result of better asthma management. Considerable evidence points to an overall trend of decreasing mortality. For instance, mortality rates in Australia registered by the Australian Institute of Health and Welfare decreased by approximately 70% between 1989 and 2006. Persons older than 65 years of age and people of lower socioeconomic status were at higher risk for dying from asthma, mainly secondary to respiratory infections during winter. Overall, asthma-related mortality in Australia remains uncommon, accounting for 402 (0.30%) in the year 2006 of all deaths (Australian Centre for Asthma Monitoring: Asthma in Australia 2008, AIHW Asthma Series no. 3, Cat. no. ACM 14, Canberra, Australian Institute of Health and Welfare, 2008) (Figure 38-4).

Figure 38-3 World map of asthma case-fatality rates: asthma deaths per 100,000 people with asthma in the 5- to 34-year-old age group.

(From Masoli M, Fabian D, Holt S, Beasley R; Global Initiative for Asthma [GINA] Program: The global burden of asthma: executive summary of the GINA Dissemination Committee Report, Allergy 59:469–478, 2004.)

Figure 38-4 Changes in prevalence of diagnosed asthma (A) and asthma symptoms (B) over time among children and young adults.

(From Eder W, Ege MJ, von Mutius E: The asthma epidemic, N Engl J Med 355:2226–2235, 2006.)

It is worth emphasizing that many of the deaths secondary to asthma are preventable, and that the high economic costs attributable to this disease can be diminished. The elevated prevalence and mortality rates are associated with not inconsideable consumption of health-related resources, placing an additional economic load on health care services.

Pathogenesis

Asthma is an inflammatory disorder of the airways in which multiple mediators and several types of inflammatory cells are involved. This pattern of inflammation is strongly associated with airway hyperresponsiveness and classic asthma symptoms of wheezing, breathlessness, chest tightness, and coughing.

A genetic predisposition to develop specific immunoglobulin E (IgE) antibodies directed against common environmental allergens, or atopy, is the strongest identifiable risk factor for the development of asthma. Intrinsic abnormalities in airway smooth muscle and airway remodeling in response to injury and inflammation add to the effects of airway inflammation in creating the clinical presentation of asthma (Figure 38-5).

Figure 38-5 Natural history of asthma.

(From Szefler SJ: The natural history of asthma and early intervention, J Allergy Clin Immunol 109:S550, 2002. Adapted from Holgate ST: The cellular and mediator basis of asthma in relation to natural history, Lancet 350[Suppl 2]:5–9, 1997.)