STATE OF THE ART

INT J TUBERC LUNG DIS 19(1):10–20 Q 2015 The Union http://dx.doi.org/10.5588/ijtld.14.0446

STATE OF THE ART SERIES The global burden of chronic respiratory disease Series editor : Guy Marks Guest editor : Nils Billo NUMBER 3 IN THE SERIES

The global burden of chronic respiratory disease in adults P. Burney,* D. Jarvis,* R. Perez-Padilla† *National Heart and Lung Institute, Imperial College, London, UK; †Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico SUMMARY

With an aging global population, chronic respiratory diseases are becoming a more prominent cause of death and disability. Age-standardised death rates from chronic obstructive pulmonary disease (COPD) are highest in low-income regions of the world, particularly South Asia and sub-Saharan Africa, although airflow obstruction is relatively uncommon in these areas. Airflow obstruction is, by contrast, more common in regions with a high prevalence of cigarette smoking. COPD mortality is much more closely related to the prevalence of a low forced vital capacity which is, in turn, associated with poverty. Mortality from asthma is less common than mortality from COPD, but it is also relatively more common in poorer areas, particularly Oceania, South and South-East Asia, the Middle East

and Africa. Again this contrasts with the asthma prevalence among adults, which is highest in highincome regions. In high-income areas, mortality due to asthma, which is predominantly an adult problem, has fallen substantially in recent decades with the spread of new guidelines for treatment that emphasise the use of inhaled steroids to control the disease. Although mortality rates have been falling, the prevalence of atopy has been increasing between generations in Western Europe. Changes in the prevalence of wheeze among adults has been more varied and may have been influenced by the reduction in smoking and the increase in the use of inhaled steroids. K E Y W O R D S : chronic respiratory diseases; low income; asthma

AN AGING POPULATION is increasing both the morbidity and mortality ascribed to chronic respiratory disease. This short review can only deal with a part of the problems that affect the daily work of physicians working in this area. We have focused on those conditions for which there is most information and which are most generally prevalent. The importance of other areas, however, needs to be mentioned. Interstitial lung diseases are conditions that are less common than the obstructive diseases discussed here, are difficult to manage and are frequently associated with serious comorbidities. They are important

because they are also associated with known occupational hazards, which may be controlled; in some locations, they are much more prevalent for this reason. Other conditions, such as sleep apnoea, are of importance and are highly prevalent in some areas; however, we have relatively little information as yet on their global distribution. Other conditions are of interest to several specialties, including pulmonary hypertension and right heart failure, which may be highly prevalent in specific areas and particularly at high altitudes.

DEFINITIONS Previous articles in the series Editorial: Marks G, Billo N E. Chronic respiratory disease: the forgotten NCD? Int J Tuberc Lung Dis 2014; 18: 1261; No 1: Asher I, Pearce N. Global burden of asthma among children. Int J Tuberc Lung Dis 2014; 18: 1269–1278. No 2: Reddel H K, Jenkins C R, Partridge M R. Self-management support and other alternatives to reduce the burden of asthma and chronic obstructive pulmonary disease. Int J Tuberc Lung Dis 2014; 18: 1396–1406.

Chronic respiratory disease among adults is generally divided into obstructive and restrictive conditions, with the obstructive conditions being further divided into reversible and irreversible disease. Although definitions are based on spirometry findings, most

Correspondence to: Peter Burney, National Heart and Lung Institute, Emmanuel Kaye Building, Imperial College, 1 Manresa Road, London SW3 6LR, UK. Tel: (þ44) 207 495 7942. e-mail: [email protected] Article submitted 16 June 2014. Final version accepted 26 July 2014.

The global burden of CRD in adults

patients with a diagnosis will never have had their lung function tested. The Global Initiative on Obstructive Lung Disease (GOLD) has recommended that obstruction should be defined as the ratio of the forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) of ,70%.1 Although other definitions also use FEV1/FVC, a measure of flow adjusted for the approximate size of the lung, they use different criteria. The main criticism of the fixed ratio has been that the value naturally falls with age, so that for very young adults 70% is too low and for the elderly it is too high, and too large a proportion of the normal population come to be included in the diseased group as they age.2 The most common alternative is the use of the lower limit of normal (LLN), set at the value that defines the lowest 5% of the non-smoking population with no overt respiratory disease. This value is adjusted for age. The ‘normal’ value for FEV1/FVC appears to be fairly constant across ethnic groups.3 Measuring restriction is more contentious. By convention, restriction is defined by low FVC, although strictly speaking this should ideally be the total lung capacity (TLC). The difference between the two is residual volume, i.e., the air left in the lung at the end of a forced expiration. This may increase in severe obstruction, lowering FVC even where the TLC is unchanged or even increased. In surveys of general populations, this is probably not a major problem, except among the elderly.4 A greater difficulty is that normal values vary widely as measured, with values in populations of European origin being higher than elsewhere. As FVCs are also higher in more prosperous populations, it is unclear to what extent these variations are driven by genetic differences between populations or by economic conditions (see below). Reversibility is sometimes measured in the clinic and defined by different indices, including a 12% change in FEV1 and an increase of 200 ml in FEV1 following a dose of 400 lg salbutamol. 5 For epidemiological studies in what are generally normal participants a dose of 400 lg is probably excessive, with too many unwanted side effects, and 200 lg is generally regarded as adequate. The upper limit of the normal value (5th centile) of percentage change in FEV following 200 lg salbutamol among healthy non-smokers appears to be relatively constant, at 12% of initial FEV1 or 10% of expected FEV1 wherever it is measured.6 As those with reversible airflow obstruction often have, by definition, normal lung function, this is not a good measure in surveys, and epidemiologists often use challenge tests to look for hyper-responsiveness rather than reversibility. In adults, this is more usually tested using challenge with pharmacological agents, which may stimulate the airways either directly, such as methacholine or histamine, or indirectly by releasing mediators, such

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as adenosine monophosphate or non-isotonic solutions of saline or mannitol. An alternative is to record serial peak flow measurements and calculate the diurnal variation.7 Chronic bronchitis is defined as chronic production of excess bronchial mucus. Its measurement has been standardised by the British Medical Research Council Questionnaire as increased cough with sputum for .3 months of the year for at least 2 consecutive years.8 Chronic bronchitis is a symptom, not a disease, and is associated with asthma as well as chronic irritation of the airway by cigarette smoke, occupational exposures or air pollution and other conditions of the airways.

PREVALENCE OF POST-BRONCHODILATOR OBSTRUCTION Reviewing the prevalence of post-bronchodilator airflow obstruction is made more difficult in part by the scarcity of surveys that have used bronchodilators and have reported the FEV1/FVC ratio, and also by the use of a wide variety of methods for reporting the ratio which have often used the fixed ratio, a measure that is highly dependent on the age group studied.9 Using data from the Burden of Lung Disease (BOLD) and Platino studies provides comparable data that have used a standard protocol.10,11 Defining obstruction as a post-bronchodilator FEV1/FVC of less than the LLN defined by the United States National Health and Nutrition Examination Survey (NHANES) shows that the prevalence varies from ,5% (the figure that would be expected in a nonsmoking population with no overt respiratory disease) among women in Sousse, Tunisia, Tartu, Estonia and Manila, the Philippines, to .20% among men in Cape Town, South Africa and women in Salzburg, Austria.12 Prevalence is low in the poorer regions of the world, and rises as the mean pack years smoked increases (Figure 1).13 This is compatible with the hypothesis that airflow obstruction is predominantly a condition associated with smoking.

PREVALENCE OF LOW FVC Using the same surveys, low FVC prevalence has a very different distribution. This ranges from less than 10% in most of Europe to over 60% in both men and women in Mumbai and Pune.13 The interpretation of this has been controversial. The wealthier regions of the world—Europe, North America and Australasia in particular—are largely populated by people of European origin, and some regard the higher FVC in these populations as physiological and linked to race and genetics rather than poverty. This controversy will be impossible to resolve until a good understanding of the genetics of lung function is achieved. At present, there is very little knowledge of specific

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Figure 1 Prevalence of airflow obstruction (FEV1/FVC , LLN) by mean pack-years smoked in the BOLD sites. Redrawn from Burney et al.13 FEV1 ¼ forced expiratory volume in 1 s; FVC ¼ forced vital capacity; LLN ¼ lower limit of normal; BOLD ¼ Burden of Lung Disease.

genetic polymorphisms influencing lung development. Interpretation depends on whether a whole population can be ‘abnormal’ because of its environment. Whatever may be normal in the sense of usual, African Americans, who also have a low FVC compared with white Americans of the same age, sex and height, have a mortality that is increased to the same extent as for a white American with the same FVC. This is one argument for not regarding the low average FVC generally found in poor regions as ‘normal’ in the sense of ‘not disadvantageous’.14,15

MORTALITY DUE TO COPD Deaths due to COPD are now the third most common cause of death in the world.16 This is in part because it is a condition of old age, and the world population is aging. As COPD deaths tend to occur later in life, it is ninth on the list of causes of years of life lost, being third in East Asia, fourth in high-income North America and fifth in South Asia. Age-specific death rates from COPD are, by contrast, falling in almost all areas. The recorded age-standardised mortality rates are higher in absolute terms in the poorer areas of the world in East, South and South-East Asia and in sub-Saharan Africa. Given that these places have relatively low smoking rates and relatively low levels of airflow obstruction, this seems at first sight paradoxical. However, the distribution is very similar to the prevalence of low FVC, and there is evidence from the Atherosclerosis Risk in Communities (ARIC) study in the United States that mortality is much more strongly associated with low FVC than it is with a low FEV1/FVC ratio.17 As very few people undergo lung function testing, the precise nature of

the disease that causes death is largely unknown; furthermore, the certification procedure has relatively few options for coding. The conditions generally associated with restrictive defects are rare and are unlikely to explain the widespread distribution of low levels of FVC in poorer regions. Low lung function, generally reported as a low FEV1, is highly correlated with the FVC, and is associated with high all-cause mortality and with cardiovascular mortality in particular.18 Not only has mortality been shown to be more closely associated with low FVC and low TLC than with a low FEV1/ FVC ratio,17,19 a low FVC is also strongly associated with a range of other disorders, including hypertension, glucose insensitivity and atherosclerosis. How these common comorbidities influence the recorded mortality rates due to COPD is unknown. While total mortality rates due to COPD are rising in most parts of the world due to the aging of the population, age-specific mortality rates have been in long-term decline, at least in England and Wales20 and Australia.21,22 This is consistent with limited data that suggest that lung function has been improving over the long term.23 In England and Wales, a longterm decline started just after the end of the First World War and continued until the 1940s (Figure 2), after which rates rose again; however, these rates never reached the levels that were recorded in the first decade of the twentieth century, and they began to decline again in the 1970s.20

DISABILITY DUE TO COPD In an exercise undertaken for the Global Burden of Disease programme,24 the disability associated with

The global burden of CRD in adults

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Figure 2 Changes in age-specific mortality due to COPD among males aged 15–24, 25–34, 25–44, 45–54, 55–64 and 65–74 years, England and Wales, 1901–1997. Redrawn from Marks and Burney.20 COPD ¼ chronic obstructive pulmonary disease.

different conditions was assessed in a standard way, and moderate COPD (FEV1/FVC ratio ,LLN and FEV1 ,80% predicted for age, sex and height) was scored at 0.192, more severely than severe angina (0.167) or severe heart failure (0.186). Severe COPD (FEV1/FVC ratio ,LLN and FEV1 ,50% predicted for age, sex and height) was scored 0.383, more severe than the long-term effects of a moderate stroke with impaired cognition (0.312). The combined effects of premature mortality and the disability experienced when living with the condition before death is summarised in the disability-adjusted lifeyears lost due to the condition. COPD ranks ninth in the world among the causes of years of life lost in full health. In some regions, it is even more important in its relative contribution, being ranked second in highincome North America, third in East Asia and Australasia and fifth in South Asia.25

RISK FACTORS FOR IRREVERSIBLE AIRWAY OBSTRUCTION Although family studies have suggested that .40% of the variations in lung function may be due to genetic differences,18 it has been very difficult to identify specific polymorphisms to account for this. The genes that have been found have been either rare variants, such as defects in the a1-antitrypsin gene, or variants in the nicotine receptors presumably regulating the craving for tobacco. Of all the risk factors that have been identified, by far the most common cause of

airflow obstruction is cigarette smoking.11,26,27 The relation of smoking to deaths attributed to COPD and to the prevalence of poor lung function has been shown many times.28,29 COPD is not, however, the only or even the most important adverse effect of smoking. Cardiovascular deaths due to smoking are more common, and lung cancer is more specifically linked to smoking than is death due to COPD. In addition to active smoking, there is evidence of obstruction also being associated with passive smoking, which suggests that sidestream smoke is particularly toxic.27 It would be natural to assume that if passive smoking was a cause of obstruction, then other sources of exposure to particulate air pollution would also have similar effects, but these have been difficult to demonstrate. It has been suggested that exposure to biomass burning, which is common in low-income countries, particularly among women, might be an explanation for the high mortality due to COPD in low-income countries where women rarely smoke.30 The BOLD Study, however, was able to show little evidence for this,27 and found little evidence of obstruction in areas that did not have a substantial smoking history. More recently, a much larger study of a large number of non-smoking people in China has also been unable to show any convincing evidence of an association between low lung function and the burning of biomass in the home,31 and this study only showed a relatively small effect from burning coal. Although increases in hospital admissions for

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Figure 3 Cross-sectional relation of lung function to age in asymptomatic controls, participants with diagnosed asthma and participants who had smoked 2 pack-years. Estimates are modelled, adjusting for sex, height, smoking, skin tests and diagnosis. Drawn from Obaseki et al.46

respiratory diseases have been associated with episodes of outdoor air pollution,32,33 and older studies have reported lower lung function in areas with more severe air pollution,34 the most recent estimates from Western Europe show little measurable effect from current levels of outdoor pollution on the prevalence of airflow obstruction.35 Systematic reviews of observational studies suggest that occupational exposures may have an important influence on lung function.36,37 Some of the industrial exposures that are associated with reduced lung function, notably working with silica dust, can cause restrictive lung disease, while others, associated, for example, with cotton milling, have been linked to obstruction. However, the BOLD study did not show that exposure to vapours, dust or fumes in the workplace was associated with a major decrease in lung function.27 Although these alternative sources of particulate air pollution have not been found to be strongly associated with increased airway obstruction, a history of tuberculosis (TB) has been associated with obstructive airway disease in earlier studies and in both the PLATINO and BOLD studies.27,38 These studies depend on a history of TB, which probably implies a history of treatment and, because TB is relatively rare, it probably cannot explain much of the variation in the prevalence of airflow obstruction. Finally, there is evidence to suggest that diet affects the prevalence of obstruction, although this may be restricted in some cases to people who are at particular risk. The main dietary components that have been examined are antioxidants in the diet. This is based on the general hypothesis that one principle mechanism is related to oxidant damage. Both crosssectional and longitudinal studies have suggested

associations between diet and lung function,39–43 and that the protective effect of a ‘healthy’ diet is most marked in those who smoke.39,40,42,44 There has been some debate in the literature over the relation of asthma to COPD. It is a common clinical finding that patents with longstanding asthma appear to develop irreversible airflow obstruction, but this could represent a biased selection in clinics among those who did (for whatever reason) develop chronic obstruction. In an American cohort of subjects, Burrows et al. found that those who had a diagnosis of asthma, had never smoked and had evidence of sensitisation to allergens had a good prognosis, while those who had smoked and had no evidence of sensitisation had a rapid decline in lung function, with mixed groups having intermediate results.45 More recently, in a large European study, Obaseki et al. have shown that there is a greater decline in lung function between age groups among those with asthma, similar to that of people who had smoked one pack of cigarettes per day for 10 years (Figure 3). This was independent of both smoking and objective markers of sensitisation to allergens.46

RISK FACTORS FOR LOW FVC There is much less information on the risk factors for low FVC, and the subject remains controversial. Although the FEV1/FVC ratio is generally regarded as being equivalent for all ethnic groups,3 there are large differences in ‘normal’ FVC values from one place to another and from one ethnic group to another living in the same country.12,47,48 There have been attempts to separate out the effects of ethnicity and poverty, which suggest that each is independently important.49 Quantification of this conclusion, however, is hampered by imprecise definitions of both ethnicity and social disadvantage. Family studies suggest that up to 40% of the variations in FVC may be attributable to genetic differences;18 however, to date very little of the variation in lung function has been attributable to differences in the prevalence of specific genetic polymorphisms.50 Poverty is associated with low FVC,51 an observation that may be reflected in the greater prevalence of low FVC in countries with lower gross national income/head, particularly where this is below about US$15 000 per annum (Figure 4).13 Whether this is as important in populations where the whole population is above a minimum level is less certain. Some of the variation in FVC is explained by differences in birth weight.52–55 Low birth weight babies grow up to have lower FVC (Figure 5), and babies that put on weight more slowly in the first year of life also have lower FVC in later life. This has given an impetus to ‘life course’ explanations of lung function. However, although they explain an impor-

The global burden of CRD in adults

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Figure 4 Prevalence of a low FVC (FVC,LLN) in BOLD sites by gross national income of the country. Redrawn from Burney et al.13 FVC ¼ forced vital capacity; LLN ¼ lower limit of normal; BOLD ¼ Burden of Lung Disease.

tant part of the variation, this still explains only a minority of the variation. Diet is also likely to be a major source of variation; however, the assessment of FVC, rather than FEV1 or FEV1/FVC, has been relatively ignored. There is nevertheless, evidence to suggest that diet does affect FVC,56 as well air flow obstruction.

MORTALITY DUE TO ASTHMA Asthma is a much rarer cause of death than COPD, as it affects a younger age group. Death from asthma nevertheless increases markedly with age and is much more common in older adults than in children, where it should be rare. Asthma is estimated to be the 42nd cause of years of life lost, but is relatively more important in Oceania (13th) and in some of the poorer parts of the world such as South-East Asia (25th),

Figure 5 Relation of FEV1 to birth weight in 9 studies. Reproduced with permission from Lawlor et al.53 FEV1 ¼ forced expiratory volume in 1 s;

South Asia (26th), North Africa and the Middle East (30th) and South, West and Central sub-Saharan Africa (32nd, 33rd and 34th, respectively).16 Asthma in the 5–34 year age range has been designated an ‘avoidable death’ suitable for use as a marker of poor health services,57 although death rates overall also reflect the prevalence and severity of the condition. Audits of asthma deaths repeatedly find a high prevalence of patients who have not been prescribed or have failed to take inhaled corticosteroids or have been over-reliant on short-term beta-agonists. This may be due to poor access to health care or problems with self management, including mental health problems such as depression.58–60

PREVALENCE OF ASTHMA Comparable information on asthma prevalence in adults comes from the European Community Respiratory Health Survey (ECRHS) (mostly in Western Europe)61 and the World Health Survey,62 which used similar questions. Large-scale surveys have depended on questionnaires, and their interpretation raises several difficulties. First, the translation of symptoms is often difficult, as the term ‘wheeze’ used in English surveys does not have an equivalent word in several languages. Second, there has been a tendency recently to define all wheezy illness as asthma, and this may obscure important distinctions. It is probably more informative to take more stringent definitions (‘severe’ asthma in the terminology of the International Study of Asthma and Allergies in Childhood survey) when describing the distribution of the disease. The World Health Survey used questions derived from the ECRHS on wheezing and on diagnosed

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income (,US$3000), to 59% (10/17) among countries with intermediate incomes (US$3000– US$7999), and to 73% (22/30) among countries with incomes .US$8000. In Western Europe, the prevalence of sensitisation to allergens has been increasing between generations over the last half century at least.63,64 In Sweden, repeat adult surveys in three different parts of the country have suggested that while the prevalence of diagnosed asthma has increased over the last 20 years, the prevalence of symptoms commonly associated with asthma has remained stable or even fallen.65–67 This is very similar to the pattern of change seen in adult cohorts followed over the same period,68 and may in part be due to changes in smoking,69 as well as increases in the use of inhaled steroids. Elsewhere, however, Italy has seen a steady increase in symptoms of asthma.70

DISABILITY DUE TO ASTHMA As a cause of disability, ‘controlled’ asthma was estimated by the exercise conducted on behalf of the Global Burden of Disease programme to cause very little disability, scoring 0.009, whereas partially controlled asthma scored 0.027, slightly above a mild stroke (0.021), and uncontrolled asthma scored 0.132, above the long-term consequences of a ‘moderate’ stroke.24 Due to the generally earlier onset and high prevalence of disease, asthma is a more important cause of disability relative to other causes than it is of mortality. As a cause of loss of years in full health, it ranks 28th among all the causes listed. It is ranked much higher in the causes of disabilityadjusted years of life lost in Oceania (8th), Australasia and tropical Latin America (15th) and the Caribbean (19th).25

RISK FACTORS FOR ASTHMA

Figure 6 Prevalence of asthma among adults according to the World Health Survey. Reproduced with permission from Sembajwe et al.62

asthma to estimate the prevalence of asthma in adults aged .18 years on six continents (Figure 6).62 The prevalence of diagnosed asthma ranged from 2% in Viet Nam to 33% in Australia. The lowest mean prevalence was found in the middle-income countries, but the percentage of sites with .10% prevalence rose from 19% (4/21) in the countries with the lowest

Asthma has long been recognised as a condition with a strong genetic component, although more recent studies have suggested that this may be stronger in childhood disease than in disease of later onset.71 It is also well established that the genetic component for sensitisation to allergen that is often associated with asthma is independent of the inheritance of another specific component associated with the airway.72–74 More recent evidence suggests that there is a further genetic link between the atopic diseases, asthma, eczema and hay fever, that is independent of the link to allergy.75 In considering the risks of asthma, the risks of allergy and of asthma need to be disentangled, as the risks are not entirely correlated. In a large study of Swedish conscripts, those who had been born prematurely were less likely to have allergic rhinitis, but those with higher birth weights were likely to

The global burden of CRD in adults

have more asthma, those with older siblings were more likely to have asthma but less likely to have allergic rhinitis, and those born to younger mothers were more likely to have developed asthma but were less likely to have allergic rhinitis. Only being a multiple birth (such as a twin) conferred protection against both conditions.76 Other exposures later in life also have paradoxical effects on asthma and allergy in adult life. Both a larger sibship size and attending school early if there were no siblings are protective against rhinitis, but are associated with more wheeze in early adult life.77 The lack of rhinitis in those from large families led to the hypothesis that early exposure to infectious agents might be protective against sensitisation,78 and this has been used to explain the apparently paradoxical effects of being brought up on a farm on allergy and atopic disease. In this case, both sensitisation (judged from skin tests) as well as symptoms of both rhinitis and asthma are all reduced,79 and this protection is preserved in later life, even among those who move away from the countryside.80,81 On the other hand, sensitisation (measured as a positive specific immunoglobulin E [IgE] to common allergens such as house dust mite) is very high in rural Africa, where there are very high levels of exposure to animals.82,83 A more recent extension to this hypothesis is that biodiversity might be protective beyond the effects of exposure to a diverse microbiota, although this has not yet been widely tested in low-income settings.84 A related hypothesis has been that allergic disease might be suppressed by exposure to parasites. It was initially thought that the production of very large quantities of polyclonal IgE might block the IgE sites on mast cells and prevent sensitised people from responding to the allergen when exposed.85 It has recently been shown that parasites may elicit strong interleukin-10 responses that may in turn reduce the response of the immune system to allergen exposure.86 The protective effect of parasites appears to be associated with those that have a systemic phase in their lifecycle.87 Attempts to moderate atopic responses by infecting people with hookworm, however, have not been successful,88 and some have speculated that a common genetic tendency toward a strong IgE response could explain a low prevalence of parasites and a high prevalence of atopy.89 There is again evidence that allergy and wheezy illness are not influenced in the same direction. Calvert and Burney found a slightly lower prevalence of positive skin tests among those with Ascaris infestations; however, a higher prevalence of exercise induced bronchoconstriction.83 The other risk factor that has been widely investigated is a possible association with diet, and several components of diet, including anti-oxidants and omega-3 fatty acids. There are theoretical

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reasons for believing that both anti-oxidants and changes in the lipid content of the diet could influence asthma. Several potential anti-oxidants have been investigated, including vitamins—particularly vitamins C and E, selenium and flavonoids. One difficulty with the observational studies, however, is ascribing causality to any association. Dietary components tend to be correlated with each other and with other lifestyle factors, which make them difficult to disentangle. Although many associations have been reported, experimental studies have generally not been able to show efficacy. This does not mean that diet is unimportant, but it does mean that it may be difficult to replicate dietary change by offering supplements of individual nutrients. In adult life, the distribution of asthma changes in two important respects. Boys suffer more frequently from asthma than girls; however, during adolescence and adulthood, asthma seems to be a more serious problem among women, while late onset ‘non-atopic’ asthma seems to be a more important component around or after the menopause. Second, occupational asthma becomes an important cause of adult onset asthma and of asthma exacerbations. Approximately 5–10% of adults with asthma aged 20–44 years, but approximately 10–20% of new cases of asthma at this age, have an occupational cause or an occupational reason for exacerbations of disease.90,91 Among the most common of these causes, and largely unrecognised until recently, has been exposure to occupation as a cleaner. Household cleaning has also been found to be associated with asthma among householders who use cleaners in a domestic, nonprofessional environment.92

CONCLUSIONS As the population of the world ages, the burden from chronic lung diseases will continue to increase, with a larger number of people disabled by these conditions and a greater number of deaths attributable to them. This is likely to be a problem for all regions of the world; however, these changes are likely to be much more rapid and much more difficult to address in low-resource countries, where a major investment in research to understand why these conditions are responsible for such a large proportion of the burden of disease in these countries and to find appropriate models of care that are cost effective, affordable and acceptable to the local population is required. Conflicts of interest: none declared.

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The global burden of CRD in adults

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RESUME

A mesure que la population mondiale vieillit, les maladies respiratoires chroniques deviennent une cause de d´ec`es et de handicap de plus en plus importante. Les taux de d e´ ce` s standardis e´ s par age ˆ dus aux bronchopneumopathies chroniques obstructives (BPCO) sont les plus e´ lev´es dans les r´egions du monde a` faible revenu, particuli`erement en Asie du Sud et en Afrique sub-saharienne, bien que l’obstruction du flux d’air soit relativement rare dans ces r´egions. Cette obstruction est par contre plus fr´equente dans les r´egions ou` les fumeurs de cigarettes sont nombreux. La mortalit´e par BPCO est bien plus e´ troitement li´ee a` la pr´evalence d’une faible capacit´e vitale forc´ee, qui est a` son tour li´ee a` la pauvret´e. La mortalit´e par asthme est moins fr´equente que la mortalit´e par BPCO, mais elle est e´ galement relativement plus fr´equente dans les zones

plus pauvres, surtout en Oc´eanie, en Asie du Sud et du Sud Est, au Moyen Orient et en Afrique. Ceci contraste a` nouveau avec la pr´evalence de l’asthme chez les adultes, qui est la plus e´ lev´ee dans les zones a` haut revenu. Dans ces r´egions, la mortalit´e par asthme, qui est surtout un probl`eme d’adultes, a consid´erablement diminu´e au cours des derni`eres d´ecennies grace ˆ a` la diffusion de nouvelles directives de traitement qui mettent l’accent sur le recours aux st´ero¨ıdes inhal´es pour controler ˆ la maladie. Bien que le taux de mortalit´e ait diminu´e, la pr´evalence de l’atopie a augment´e d’une g´en´eration a` l’autre en Europe de l’Ouest. Les modifications de la pr´evalence de respiration sifflante chez les adultes a e´ t´e plus variable et a peut-eˆ tre e´ te´ influence´ e par la diminution de la consommation de tabac et l’augmentation du recours aux st´ero¨ıdes inhal´es. RESUMEN

Las enfermedades respiratorias cronicas ´ se han hecho ma´s prominentes como causa de muerte e incapacidad con la presencia una poblaci on ´ que envejece progresivamente. La tasa estandarizada de mortalidad por la enfermedad pulmonar obstructiva cr onica ´ (EPOC) es alta en regiones con bajos ingresos, particularmente el sur de Asia y la Africa subsahariana, aunque en estas a´reas la obstruccion ´ al flujo a´ereo es poco comun ´ no as´ı en las regiones con alta prevalencia de tabaquismo. La mortalidad atribuida a EPOC se relaciona en estudios internacionales ma´s estrechamente a la prevalencia de una capacidad vital forzada baja que a su vez se asocia con pobreza. La mortalidad por asma bronquial es menos comun ´ que por

EPOC, pero prevalece en zonas pobres, particularmente de Ocean´ıa, el sur y sureste asia´ticos, el medio oriente y Africa. De nuevo esto contrasta con el asma en adultos, ma´s comun ´ en regiones de altos ingresos economicos ´ pero donde la mortalidad, problema de adultos primordialmente, ha caido substancialmente en las d´ecadas recientes a partir de la diseminacion ´ de gu´ıas de manejo que enfatizan el uso de esteroides inhalados. La atopia va´ en aumento en Europa Occidental aunque la tasa de mortalidad atribuible ha caido. El cambio en la prevalenca de sibilancias en adultos ha sido ma´s heterog´eneo quiza bajo la influencia de la disminucion ´ en el tabaquismo y el uso creciente de esteroides inhalados.