Descriptive epidemiology of asthma

Abstract

Asthma is a substantial health problem among children and adults worldwide, with high and increasing prevalence rates., in many countries, 1Burney PGJ Chinn S Rona RJ Has the prevalence of asthma increased in children?.in: Evidence from the national study of health and growth 1973–86. 2nd edition. BMJ. 300. 1990: 1306-1310Google Scholar a substantial morbidity-reflected in hospital admission rates, 2Halfon N Newacheck PW Trends in the hospitalisation for acute childhood asthma, 1970–84.Am J Public Health. 1986; 76: 1308-1311Crossref PubMed Scopus (122) Google Scholar use of medical services, 3Anderson HR Is the prevalence of asthma changing?.Arch Dis Child. 1989; 64: 172-175Crossref PubMed Scopus (104) Google Scholar and drug use4Klaukka T Peura S Martikainen J Why has the utilization of antiasthmatics increased in Finland?.J Clin Epidemiol. 1991; 44: 859-863Summary Full Text PDF PubMed Scopus (23) Google Scholar-and worrying trends in mortality rates in some countries.5Sears MR Epidemiology.in: Barnes PJ Rodger IW Thomson NC Asthma: basic mechanisms and clinical management. 2nd edition. Academic Press, San Diego1992: 1-19Google Scholar The incidence of asthma (the development of new disease) varies by region and by age, but the global burden of asthma can be approximated from measured prevalence rates (reflecting incidence, duration, persistence, and recurrence of disease). If 10% of children and 5% of adults have asthma, figures that are conservative for western countries1Burney PGJ Chinn S Rona RJ Has the prevalence of asthma increased in children?.in: Evidence from the national study of health and growth 1973–86. 2nd edition. BMJ. 300. 1990: 1306-1310Google Scholar but may be overestimates in some developing countries, the global burden of asthma is in the order of 130 million people. Mortality rates from asthma in almost all western countries vary between one and five per 100 000, and result in some 60 000 deaths annually, many of which occur in young people and are potentially preventables5Sears MR Epidemiology.in: Barnes PJ Rodger IW Thomson NC Asthma: basic mechanisms and clinical management. 2nd edition. Academic Press, San Diego1992: 1-19Google Scholar Central to all discussions of epidemiology of asthma is the definition or definitions of asthma, and the criteria for recognising and diagnosing asthma. Despite substantial advances in understanding the pathogenesis, genetics, and clinical characteristics of asthma, an all-encompassing definition remains difficult to construct. Recent consensus statements from national and international expert panels have built on past definitions with the addition of specific cellular functions, and describe a disorder characterised by variable airflow obstruction; symptoms of wheeze, cough, dyspnoea, and chest tightness; reversibility to bronchodilators and corticosteroids; increased airway responsiveness to a variety of stimuli; and evidence of inflammation in which eosinophils, mast cells, and lymphocytes together with a multitude of cytokines have important roles.6Global strategy for asthma management and prevention. 2nd ed. NHLBI/WHO Workshop report, March 1993. National Institutes of Health, National Heart, Lung and Blood Institute, Bethesda1995: 6Google Scholar Given the heterogeneity of the clinical forms of asthma a single definition seems remote, although genetic studies may help. Does the definition of asthma applicable to children with atopic sensitisation also adequately describe adults developing wheezing from occupational sensitisation, or after respiratory tract infections, or even after stopping smoking? Among children there exist clearly different forms of wheezing requiring different definitions and very likely having different pathologies. Martinez et al differentiated early transient wheezing with symptoms occurring before age 3 that do not persist to age 6, from wheezing with persistence beyond age 6.7Martinez FD Wright AL Taussig LM Holberg CJ Halonen M Morgan WJ Asthma and wheezing in the first six years of life.N Engl J Med. 1995; 332: 133-138Crossref PubMed Scopus (3283) Google Scholar The former children have smaller airways and are more at risk from maternal cigarette smoking than maternal asthma or allergy, whereas risk factors for the latter include family history, serum IgE, and other manifestations of atopy. Does one definition of asthma apply equally to both? In the absence of a single easily recognised diagnostic marker of the presence or absence of asthma, the diagnosis in a clinical setting usually relies on the combination of a history of characteristic symptoms, and objective evidence of airway lability, demonstrated by spontaneously variable or reversible airflow obstruction with 15% or greater change in flow rate, a bronchoconstrictor response to histamine or methacholine, or daily or diurnal variability in peak expiratory flow.8Sears MR The definition and diagnosis of asthma.Allergy. 1993; 48: 12-16Crossref PubMed Scopus (37) Google Scholar In earlier epidemiological studies, reliance was largely placed on questionnaire responses to determine “probable asthma” and “possible asthma”, but these were unverified diagnoses. Most studies have found that 50% or fewer of those with recurrent wheezing consistent with asthma have been given that diagnosis, and that those so diagnosed generally have more severe disease. More recent epidemiological studies have added functional measurements, with abbreviated validated methacholine or histamine challenge protocols to demonstrate airway hyperresponsiveness and peak flow monitoring over 1-2 weeks to confirm or negate the symptom history suggesting variable airflow obstruction.9Sears MR Jones DT Holdaway MD et al.Prevalence of bronchial reactivity to inhaled methacholine in New Zealand children.Thorax. 1986; 41: 283-289Crossref PubMed Scopus (165) Google Scholar Other ancillary investigations used in epidemiology, including the presence of atopy as determined by serum IgE levels or allergen skin prick test responses, facilitate the characterisation of asthma rather than the certainty of the diagnosis.10Sears MR Herbison GP Holdaway MD Hewitt CJ Flannery EM Silva PA The relative risks of sensitivity to grass pollen, house dust mite and cat dander in the development of childhood asthma.Clin Exp Allergy. 1989; 19: 419-424Crossref PubMed Scopus (476) Google Scholar In both adult and childhood studies, a proportion of subjects have been identified with clinical histories that suggest asthma but in whom challenge tests to histamine or methacholine are negative, whereas others are symptom-free but have increased airway responsiveness to these agents.5Sears MR Epidemiology.in: Barnes PJ Rodger IW Thomson NC Asthma: basic mechanisms and clinical management. 2nd edition. Academic Press, San Diego1992: 1-19Google Scholar, 9Sears MR Jones DT Holdaway MD et al.Prevalence of bronchial reactivity to inhaled methacholine in New Zealand children.Thorax. 1986; 41: 283-289Crossref PubMed Scopus (165) Google Scholar, 11Enarson DA Vedal S Schluzer M Dybuncio A Chan-Yeung M Asthma, asthma-like symptoms, chronic bronchitis, and the degree of bronchial hyperresponsiveness in epidemiological surveys.Am Rev Respir Dis. 1987; 136: 613-617Crossref PubMed Scopus (120) Google Scholar Hence the usefulness of bronchoconstrictor challenge testing as the gold standard for asthma diagnosis has been questioned, although there remains a high correlation between diagnosed asthma and airway hyperresponsiveness in clinical and population studies. Studies of inflammatory characteristics of asthma, particularly sputum differential cell counts that use non-invasive induction methods with saline inhalation, have shown promise in establishing the diagnosis of asthma.12Pizzichini E Pizzichini MMM Efthimiadis A et al.Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements.Am J Respir Crit Care Med. 1996; 154: 308-317Crossref PubMed Scopus (847) Google Scholar The usefulness of these markers of inflammation in epidemiology is currently under investigation in small pilot studies. Until we have a more precise method of determining whether individual participants in an epidemiological study do or do not have asthma, the population epidemiology of asthma remains an uncertain science. Toelle et al proposed a definition of asthma for use in epidemiological studies, especially for comparisons between studies, describing “current asthma” as a history of wheezing symptoms within the previous 12 months in combination with airway hyperresponsiveness to challenge testing.13Toelle BG Peat JK Salome CM Mellis CM Woolcock AJ Toward a definition of asthma for epidemiology.Am Rev Respir Dis. 1992; 146: 633-637Crossref PubMed Scopus (254) Google Scholar This definition excludes some symptomatic subjects without airway hyperresponsiveness on the day of the study, as well as those with symptom-free hyperresponsiveness, some of whom also show variability of airflow consistent with asthma despite the lack of symptoms. Investigators have sought to determine the prevalence of asthma in local or national surveys, with many different sampling frames and questionnaires, and highly variable results which may reflect the limitations and biases of the methodology as much as true regional differences in prevalence.5Sears MR Epidemiology.in: Barnes PJ Rodger IW Thomson NC Asthma: basic mechanisms and clinical management. 2nd edition. Academic Press, San Diego1992: 1-19Google Scholar In general terms, higher prevalence rates have been found among children from “westernised” countries than in developing countries in Asia and Africa, in warmer climates compared with cooler regions such as Scandinavia, and in certain countries such as Australia and New Zealand compared with the USA and Canada despite similar living conditions. These differences may be real, or may reflect study methodology. International comparisons of prevalence and characteristics of asthma have been greatly facilitated by the completion of two major initiatives in asthma epidemiology, the European Commission Respiratory Health Study (ECRHS)14Burney P Chinn S Luczynska C Jarvis D Lai E Variations in the prevalence of respiratory symptoms, self-reported asthma attacks, and use of asthma medication in the European Community Respiratory Health Survey (ECRHS).Eur Respir J. 1996; 9: 687-695Crossref PubMed Scopus (952) Google Scholar and the International Study of Asthma and Allergies in Childhood (ISAAC).15Pearce N Weiland S Keil U et al.Self-reported prevalence of asthma symptoms in children in Australia, England, Germany and New Zealand: an international comparison using the ISAAC protocol.Eur Respir J. 1993; 6: 1455-1461PubMed Google Scholar Preliminary data from both studies (Table 1, Table 2) show two-fold to five-fold differences in crude prevalence rates in different regions depending on the symptoms compared. The analysis of complementary objective data from bronchial challenge studies in the adult ECRHS study may help clarify the meaning of these large symptom differences. Objective data are not available in phase 1 of the ISAAC study, but are planned in phase 2. Further analyses of these studies, which used internationally standardised questionnaires and (in adults) objective measurements of lung function and atopy, should resolve the true magnitude of regional differences in prevalence. Factors associated with higher prevalence rates, and factors that are protective against development of asthma, may be identifiable from these data.Table 1Distribution of responses from 46-48 centres that responded to questions in ECRHS study questionnaire14Percent prevalenceMinimum25th centileMedian75th centileMaximumWheeze in past 12 months4.114.920.725.232.0Wheeze with breathlessness1.47.79.813.916.3Wheeze without a cold2.09.312.716.221.6Waking with tightness in chest6.29.713.517.520.5Waking with breathlessness1.54.77.38.911.4Waking with cough6.025.627.929.542.6Attack of asthma1.32.63.14.59.7Treatment for asthma0.62.43.55.09.8Nasal allergies and hyfever9.516.620.928.240.9 Open table in a new tab Table 2Prevalence (%) of childhood asthma and wheezing among 13-14 year olds with ISAAC questionnaireLocation everAsthma everWheeze 12 monthsWheeze pastReferenceAdelaide, Australia22402915Pearce N Weiland S Keil U et al.Self-reported prevalence of asthma symptoms in children in Australia, England, Germany and New Zealand: an international comparison using the ISAAC protocol.Eur Respir J. 1993; 6: 1455-1461PubMed Google ScholarSydney, Australia26453015Pearce N Weiland S Keil U et al.Self-reported prevalence of asthma symptoms in children in Australia, England, Germany and New Zealand: an international comparison using the ISAAC protocol.Eur Respir J. 1993; 6: 1455-1461PubMed Google ScholarSussex, UK15482915Pearce N Weiland S Keil U et al.Self-reported prevalence of asthma symptoms in children in Australia, England, Germany and New Zealand: an international comparison using the ISAAC protocol.Eur Respir J. 1993; 6: 1455-1461PubMed Google ScholarBochum, Germany4332015Pearce N Weiland S Keil U et al.Self-reported prevalence of asthma symptoms in children in Australia, England, Germany and New Zealand: an international comparison using the ISAAC protocol.Eur Respir J. 1993; 6: 1455-1461PubMed Google ScholarWellington, NZ18442815Pearce N Weiland S Keil U et al.Self-reported prevalence of asthma symptoms in children in Australia, England, Germany and New Zealand: an international comparison using the ISAAC protocol.Eur Respir J. 1993; 6: 1455-1461PubMed Google ScholarHamilton, Canada19443016Pizzichini MMM Taylor B Habbick B Senthilselvan A Rennie D Sears MR Prevalence of childhood asthma in two age groups in two regions of Canada: the ISAAC study.Am J Respir Crit Care Med. 1997; 155: A75Crossref Scopus (236) Google ScholarSaskatoon, Canada12362316Pizzichini MMM Taylor B Habbick B Senthilselvan A Rennie D Sears MR Prevalence of childhood asthma in two age groups in two regions of Canada: the ISAAC study.Am J Respir Crit Care Med. 1997; 155: A75Crossref Scopus (236) Google ScholarBay of Plenty, NZ2230..17Moyes CD Waldon J Ramadas D Crane J Pearce N Respiratory symptoms and environmental factors in schoolchildren in the Bay of Plenty.N Z Med J. 1995; 108: 358-361PubMed Google ScholarSingapore21291018Goh DYT Chew FT Quek SC Lee BW Prevalence and severity of asthma, rhinitis, and eczema in Singapore schoolchildren.Arch Dis Child. 1996; 74: 131-135Crossref PubMed Scopus (162) Google ScholarHong Kong..201219Lai CKW Douglass C Ho SS Chan J Lau J Wong G Asthma epidemiology in the Far East.Clin Exp Allergy. 1996; 26: 5-12Crossref PubMed Scopus (60) Google ScholarNZ=New Zealand.=Not sought. Open table in a new tab NZ=New Zealand.=Not sought. Although the ECRHS and ISAAC studies provide cross-sectional snapshots of well-defined populations, and hence enable comparisons within and between countries that may help identify specific risk factors for current asthma, neither study will answer questions on changes in prevalence or severity of asthma with time, unless subsequent studies with the same methodology are undertaken in future years. However, there have been a number of epidemiological studies repeated in more or less the same population with the same or similar methods, suggesting asthma prevalence and severity have increased. In Aberdeen in the UK, essentially identical studies were undertaken in children 25 years apart.20Ninan TK Russell G Respiratory symptoms and atopy in Aberdeen schoolchildren: evidence from two surveys 25 years apart.BMJ. 1992; 304: 873-875Crossref PubMed Scopus (587) Google Scholar In 1989, the prevalence of wheeze and of diagnosed asthma had doubled compared with 1964. The prevalences of eczema and hayfever had also substantially increased, suggesting the increase in asthma related primarily to an increase in the prevalence of allergy (figure 1). That study also provided evidence that the recognition of asthma had increased, as in 1989 the label of “asthma” was used in 52% of subjects with wheeze compared with only 21% in 1964. Among 12-year-old children in south Wales, 21Burr ML Butland BK King S Vaughan-Williams E Changes in asthma prevalence: two surveys 15 years apart.Arch Dis Child. 1989; 64: 1452-1456Crossref PubMed Scopus (759) Google Scholar the prevalence of a history of wheezing at any time increased from 17% in 1973 to 22% in 1988, and a history of asthma at any time from 6% to 12%. Exercise provocation testing suggested both mild and severe asthma had increased. As in Aberdeen, the prevalence rates of eczema and hayfever also rose over that 15-year period, from 5% to 16%, and 9% to 15%, respectively. In an adult Australian population, the prevalence of wheezy breathing in the past year increased from 21·0% in 1987 to 25·1% in 1990, and current asthma from 5·6% to 8·0%.22Campbell DA Ruffin RE McEvoy RD Crockett AJ South Australian asthma symptom prevalence survey.Aust N Z J Med. 1991; 21: 658Crossref Google Scholar In two UK birth cohorts, born in 1958 and 1970, the prevalences at age 16 of asthma or wheezy bronchitis in the past 12 months were 3·8% and 5·9%, respectively.23Lewis S Butland B Strachan D et al.A comparison of the prevalence and severity of childhood wheezing illness in 1974 and 1986 using two nationally representative British birth cohorts.Am J Respir Crit Care Med. 1994; 149: A574Google Scholar It is noteworthy that no study has shown a decrease in prevalence over time. Reasons for increased prevalence of asthma, or increased allergy, may include changes in housing allowing greater proliferation of house-dust mites, therefore increasing both sensitisation and exposure, 24Sporik R Chapman MD Platts-Mills TAE House dust mite exposure as a cause of asthma.Clin Exp Allergy. 1992; 22: 897-906Crossref PubMed Scopus (257) Google Scholar effects of environmental factors including both outdoor and more pertinently indoor pollutants (the impact of passive smoking being the best documented5Sears MR Epidemiology.in: Barnes PJ Rodger IW Thomson NC Asthma: basic mechanisms and clinical management. 2nd edition. Academic Press, San Diego1992: 1-19Google Scholar), and perhaps changes in diet.25Hodge L Salome CM Peat JK Haby MM Xuan W Woolcock AJ Consumption of oily fish and childhood asthma risk.Med J Aust. 1996; 164: 137-140PubMed Google Scholar The impact of early childhood infections, and their treatment, on the development of the immune system (and therefore on allergy) is currently of major interest. Asthma has a low mortality compared with other chronic lung diseases, in part because most asthma is in young people and because asthmatic airway obstruction is substantially reversible, but over the 1970s and 1980s there was a steady increase in asthma mortality especially among young people in many countries.5Sears MR Epidemiology.in: Barnes PJ Rodger IW Thomson NC Asthma: basic mechanisms and clinical management. 2nd edition. Academic Press, San Diego1992: 1-19Google Scholar In addition, two well-defined epidemics of mortality occurred among young people.25Hodge L Salome CM Peat JK Haby MM Xuan W Woolcock AJ Consumption of oily fish and childhood asthma risk.Med J Aust. 1996; 164: 137-140PubMed Google Scholar Revisions in coding of airway diseases according to the International Classification of Diseases has made interpretation of trends in older subjects less precise, especially the change from ICD8 to ICDQ in which death from “bronchitis with mention of asthma”, formerly coded as death from bronchitis, was, now coded as death from asthma. The effect of this revision was a 30–35% increase in asthma mortality rates between 1978 and 1979, but in 5–34 year olds the impact was minimal. As the accuracy of certification of asthma as a cause of death is greater in this younger age group, population trends in mortality are generally best followed in 5–34 year olds, although it must be appreciated that most deaths coded to asthma are in older subjects in whom accuracy of diagnosis of asthma and certification of cause of death is less precise.27Sears MR Rea HH de Boer G et al.Accuracy of certification of deaths due to asthma: a national study.Am J Epidemiol. 1986; 124: 1004-1011PubMed Google Scholar In many but not all countries with reliable statistics, asthma mortality in 5–34 year olds increased from the mid-1970s to the second half of the 1980s, but reached a plateau and has subsequently declined in most countries.5Sears MR Epidemiology.in: Barnes PJ Rodger IW Thomson NC Asthma: basic mechanisms and clinical management. 2nd edition. Academic Press, San Diego1992: 1-19Google Scholar Exceptions to this decline are the USA and Japan, which are still experiencing increasing asthma mortality trends in young people or have just reached a plateau. Reasons for these trends have been vigorously debated. Evidence from the two epidemics of asthma mortality in young people, occurring in the UK, Australia, and New Zealand in the mid-1960s, and in New Zealand alone commencing in 1977, strongly suggest that mortality increased with introduction of high-dose formulations of inhaled beta-agonist26Sears MR Taylor DR The B2-agonist controversy: observations, explanations and relationship to asthma epidemiology.Drug Saf. 1994; 11: 259-283Crossref PubMed Scopus (124) Google Scholar (figure 2). The recent abrupt fall in morbidity and mortality in New Zealand following the withdrawal of the most potent beta-agonist provides compelling evidence that the severity of asthma was influenced by use of this medication28Sears MR Epidemiological trends in asthma.Can Respir J. 1996; 3: 261-268Google Scholar (figure 3). Hence the question arises as to whether the non-epidemic increases in asthma mortality may also be in part related to treatment of the disease. Studies in national and urban settings have added understanding of many risk factors that relate to long-term and short-term care of asthma, access to medical help, ethnic and socioeconomic factors, and psychological and personal factors that may increase the risk that an episode of severe asthma in an individual may be fatal.30Rea HH Sears MR Beaglehole R et al.Lessons from the national asthma mortality study: circumstances surrounding death.N Z Med J. 1987; 100: 10-13PubMed Google Scholar, 31Strunk RC Mrazek DA Furhmann GSW LaBrecque JF Physiologic and psychological characteristics associated with deaths due to asthma in childhood: a case-controlled study.JAMA. 1985; 254: 1193-1198Crossref PubMed Scopus (292) Google Scholar Over and above these circumstantial factors, however, is the question of why an individual has asthma of such severity to be at risk of a fatal attack, and whether this may relate to chronic treatment.Figure 3Abrupt decrease in asthma morbidity and mortality among New Zealand M-44 year olds between 1989 and 1990 following withdrawal of fenoterol28Sears MR Epidemiological trends in asthma.Can Respir J. 1996; 3: 261-268Google ScholarShow full captionA=Case-control study published.29Crane J Pearce N Flatt A et al.Prescribed fenoterol and death from asthma in New Zealand, 1981–83: case-control study.Lancet. 1989; i: 918-922Google Scholar B=Fenoterol regulated in New Zealand.View Large Image Figure ViewerDownload Hi-res image Download (PPT) A=Case-control study published.29Crane J Pearce N Flatt A et al.Prescribed fenoterol and death from asthma in New Zealand, 1981–83: case-control study.Lancet. 1989; i: 918-922Google Scholar B=Fenoterol regulated in New Zealand. More precise information on population-based epidemiology of asthma will emerge as study methodologies are standardised (already in progress with the ECRHS and ISAAC studies), objective methods for determining the presence of the condition “asthma” are refined or added (more specific challenge tests, measurements of airway inflammation by sputum differential cell counts, determination of exhaled nitric oxide as a marker of asthmatic inflammation, as possible examples), and the genotype rather than merely the phenotype of asthma is determined. Improved population sampling and statistical techniques to reduce selection and response bias may increase accuracy of prevalence estimates, while continuing case-control and longitudinal cohort studies will provide information on risk factors for the development, persistence, and remission of asthma. Studies in occupational settings may clarify factors resulting in sensitisation or irritant asthma, with new insights into pathogenetic mechanisms, while cellular and molecular research may also enhance the recognition of asthma if the results can be applied in epidemiological studies.