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" What is epidemiology?  Epidemiology is the study of disease in populations.  Its purpose is to examine variations in disease in relation to differences in (for instance):  geography  race  age  sex  climate  time.   Epidemiological studies serve a variety of purposes.   To establish the extent of a problem, for instance to ensure that:  medical facilities match likely demand cases are not being missed by the medicalservices  cases are not being missed by screeningprogrammes.   To examine changes over time in the prevalence of disease, which might:  provide clues as to the cause  indicate efficacy of interventions, such as anti-pollutionor immunisation programmes.    To compare one area or population with another, for instance:  to identify targets for intervention  provide clues as to the cause.    Epidemiological studies provide valuable clues to the cause of disease. Classical examples include:  the link between water pollution and typhoid fever  the link between smoking and lung cancer.  It was possible to apply epidemiological techniques to these studies, because:  some people drank polluted water, and some didn&amp;#039;t  some people smoked, and others didn&amp;#039;t.  If everyone drank polluted water, or if everyone had typhoid fever, Salmonella typhi from polluted water would still be the cause of typhoid fever, but the link would not be apparent. Similarly, if everyone smoked, smoking would still be the major cause of lung cancer, but epidemiological methods would fail to demonstrate the association.  It was also possible to study these conditions because the diseases themselves were well defined. You either have typhoid or you don&amp;#039;t; carriers may cause some confusion, but during an epidemic (such as we had in Aberdeen in the &amp;#039;60s) there is seldom any doubt. Similarly, the diagnosis of lung cancer is usually unequivocal.  In contrast, the epidemiological study of asthma is difficult because:   it is widespread  it affects all groups within society most importantly, is difficult to define.  Before the extent of asthma can be discussed sensibly, two issues need to be addressed:  epidemiological terminology  what we mean by &amp;#039;asthma&amp;#039;.  Epidemiological terminology  Like all scientific disciplines, epidemiology has its own distinctive vocabulary. In particular, prevalence and incidence have quite different meanings.  Prevalence  The prevalence of a condition refers to &amp;#039;The proportion of individuals in a defined population who have that condition&amp;#039;.  Prevalence may be measured:  at a single point in time (point prevalence)  over a defined period of time (period prevalence)  over an individual&amp;#039;s entire lifetime (life-time prevalence).   Clearly, depending on the period studied, the question asked, or the test performed, entirely different answers will be obtained. Thus, the prevalence of wheeze will differ widely depending on whether the period studied is a single day, a week, a year, or the patient&amp;#039;s lifetime, and the prevalence of wheeze will not be same as the prevalence of asthma. Incidence  The incidence of a condition describes &amp;#039;The number of new cases arising in a defined population during a specified period&amp;#039;. Thus, because asthma is a chronic disorder, the incidence of new cases during a period of, say, a year, will be vastly less than the prevalence of asthma in the same population.  Incidence is also used to describe the frequency of events such as wheezing attacks and hospital admissions. At first sight these precise definitions may appear to be pedantic, but they are important. For instance, the great majority of modern asthma surveys (including the International Study of Asthma and Allergy in Childhood - ISAAC) include a question on wheezing during the past year. Some older studies, such as those from Aberdeen with which I have been involved, enquire about wheeze in the past three years, giving a higher prevalence of wheeze than studies conducted using the ISAAC protocol.  Precision is therefore all-important. Before comparing the results of different studies, it is essential to examine them in detail, to ensure that like is being compared with like. Definitions of asthma  Older readers will remember the Brains Trust that ran for many years on the BBC Home Service. One of the Brains, Professor Joad, used to play for time by prefacing every answer with the phrase, &amp;#039;It all depends what you mean by \u2026&amp;#039; This approach is particularly relevant to asthma, as there is no easily applied or widely accepted definition, and the term means different things to different people. Asthma may not even be a single disease, but the culmination in a common group of symptoms of several distinct pathological processes. There are however certain features that are widely used in defining asthma, each of which will identify a different population, highlighting the impossibility of discussing the extent of asthma with any precision.  Recurrent wheeze  Wheeze is the hallmark of asthma, but:  not all asthmatics wheeze  some asthmatics have cough-variant asthma, in which the principal symptom is cough.   Recurrent wheeze is often interpreted as asthma, but asthma is by no means the only cause of wheeze. Other causes include:  chronic bronchitis  emphysema cystic fibrosis  virus-associated wheeze in pre-school children.  Some patients may be difficult to classify, and doctors may resort to such non-diagnoses as &amp;#039;asthmatic bronchitis&amp;#039;. Professor Joad would certainly have said, &amp;#039;It all depends what you mean by wheeze.&amp;#039;  Wheeze is a whistling noise.  It comes from the chest.  It is most marked on expiration.  It has been shown by workers in both London [1] and Sheffield that the general public has great difficulty in distinguishing between these noises and wheeze, with the result that the prevalence of wheeze tends to be overestimated. Vibratory, rattling or purring noises arising in the larynx or larger airways are not wheeze, but are widely but wrongly interpreted as wheeze. Stridor, though whistling, is a mainly inspiratory noise resulting from obstruction to the flow of air through the larynx. Doctor-diagnosed asthma  Many epidemiological surveys include a question on whether or not the subject has ever been diagnosed by a doctor as suffering from asthma. On the face of it, this might seem to be a perfectly reasonable means of ascertaining the prevalence of a disease, but asthma is both underdiagnosed and overdiagonsed.  The response to this question is more likely to reflect the diagnostic fashions of the time than the true prevalence of asthma. Thus, in Aberdeen, the prevalence of doctor-diagnosed asthma [2] has increased twice as fast as the prevalence of wheeze, reflecting the increasing tendency to offer a diagnosis of asthma to explain wheezing and coughing in childhood. Asthma has now become such a popular diagnosis that one of the main tasks at hospital asthma clinics is to &amp;#039;undiagnose&amp;#039; it. For instance, the diagnosis is often made in patients with:   recurrent cough  wheeze caused by other pathology  shortness of breath due to cardiovascular unfitness, that is wrongly attributed to exercise-induced asthma.  Doctor-diagnosed asthma is therefore a heavily tarnished gold standard for the diagnosis of asthma. Nevertheless, individuals whose symptoms are severe enough for medical help to be sought are more likely to be suffering from asthma than those with milder wheeze. Reversible airways obstruction This definition of asthma depends on the demonstration of a positive response to a bronchodilator drug.  The peak flow or other lung function test is measured before and after inhaling salbutamol.  A convincing improvement indicates reversible airways obstruction.  This definition demands that the patient should be wheezy when seen; otherwise there will be nothing to reverse.  It is useful in clinical practice, when the patient can be asked to report back next time he or she is wheezy.  It is much less useful in epidemiological studies, which seldom have the resources for repeated examinations.  Bronchial hyper-reactivity This implies the development of bronchospasm in response to a defined stimulus, such as the inhalation of:  histamine  methacholine  water mist  cold air.  Such tests are:  usually positive in more severe asthmatics, so they tend to identify individuals whose asthma is clinically important. sometimes positive in individuals who are apparently completely well.  Disadvantages of tests of bronchial reactivity include:  the same individual may react differently on different occasions. the presence of an upper respiratory tract infection commonly increases bronchial hyper-reactivity. they are time-consuming (and therefore expensive), and are thus less suitable for application in large population surveys.  An exception is the &amp;#039;free-running exercise test&amp;#039;, which exposes the bronchi to cold air that has not been humidified by passage through the nose. Such exercise tests have been widely used to support the diagnosis of asthma in children, though they lack diagnostic precision [3]. In clinical practice, bronchial challenge tests have their advocates [4] and their critics [5].  Allergic airways disease  Many asthmatics show signs of allergy such as:  eczema  hay fever.  Their symptoms may be triggered by exposure to allergens such as:  house dust mite  cat saliva  pollens  moulds  feathers  foods such as dairy products.   If evidence of allergy is insisted upon for a diagnosis of asthma, then this will exclude many non-allergic individuals who have exactly the same symptoms and signs, and who respond to anti-asthma therapy. It is however perfectly reasonable to classify asthma as:  non-allergic (&amp;#039;intrinsic&amp;#039;) allergic (&amp;#039;extrinsic&amp;#039;).   A fuller discussion on the relationship between asthma and allergy appears in a recent review in the British Medical Journal [6]. Chronic inflammatory airways disease  The mucous membrane lining the bronchial tree is inflamed in asthma, and the demonstration of such inflammation is perhaps the most robust method of diagnosis. Unfortunately, this involves obtaining a sample of the mucous membrane, and/or secretions from the lung, an invasive procedure followed by expensive laboratory tests. Such an approach is not practicable for epidemiological purposes.  Simpler tests are becoming available, and may soon reach the stage when they can be applied to populations rather than patients. A gene-environment interaction  Both academia and the drug industry are currently committing large amounts of money and effort to the search for genes that predispose a person to asthma. Such genes (of which there are likely to be many) will identify potential asthmatics who:   under appropriate circumstances, will manifest the disease  under a different set of environmental conditions may remain perfectly well.  Summary of asthma diagnosis  It is apparent that it really does depend on what you mean by asthma, and that in the absence of a gold standard diagnostic test, the precise extent of asthma is inevitably uncertain. Nevertheless, we do have a vast amount of information about the prevalence of doctor-diagnosed asthma, and of symptoms suggestive of asthma, and while the data may lack precision, we know a great deal about the epidemiology of asthma. Asthma in the past  A long time ago, asthma was probably quite uncommon, but in the absence of properly conducted surveys, it is difficult to be sure.  In Victorian times, Hyde Salter, a London physician with a special interest in asthma, felt that it was underdiagnosed, although he made no guess as to its true prevalence. A century later, medical papers written in the 1950s and 1960s identified it as the commonest chronic disorder of childhood, the commonest cause of absence from school, and a major cause of absence from the workplace. By the 1970s it was apparent that asthma was badly underdiagnosed in the UK. In the past, this would not have mattered, as there was little treatment to offer milder cases. However, the late 60s and early 70s saw the development of:  selective beta2 bronchodilators, eg salbutamol (Ventolin)  sodium cromoglicate (Intal)  inhaled corticosteroids, eg beclometasone (Becotide).   With these safe and effective therapies available, underdiagnosis became important because now the associated undertreatment really mattered.  The 70s and 80s also saw significant increases in the numbers of patients, particularly children, admitted to hospital with a diagnosis of asthma.  It was unclear at the time if these increased admissions reflected:  a change in hospital diagnostic practice  a change in GP referral habits  a true increase in the prevalence of asthma in the community at large.  Because of the previous underdiagnosis of asthma, which remains a problem [7], my own suspicion at the time was that the hospital statistics reflected nothing more than a change in diagnostic labelling of wheezing episodes. Others (rightly, as it turned out) were persuaded that asthma was becoming more common. There then followed large numbers of asthma surveys, and in the remainder of this article I will try to summarise the findings from these studies. Changes in the prevalence of asthma  It is now quite clear that, over the past 30 years or so, there has been an increase in doctor-diagnosed asthma, particularly in the younger age groups [8]. This increase has attracted a great deal of media attention, with talk of:  an asthma epidemic  the asthma generation.   This increase reflects:  changes in the diagnostic labelling of patients with wheeze  Increases in the prevalence of symptoms suggestive of asthma, particularly wheeze [9]  increases in conditions commonly associated with asthma, such as eczema and hay fever.   Numerous studies have now presented data confirming the increase in the prevalence of asthma [10].  No study has shown a decline.  There are some hints that the prevalence might now be stabilising.  More severe asthma may be declining due to:   In the forefront of these research endeavours have been workers in the academic Department of Public Health Medicine at St George&amp;#039;s Hospital Medical School, where a Lung and Asthma Information Agency (LAIA) website is maintained. Current prevalence of asthma  The LAIA factsheet on the prevalence of asthma in Great Britain provides data on childhood asthma and shows:   the increase in asthma has been much greater than the increase in wheeze  the proportion of wheezy children diagnosed as asthmatic has risen from well under a half in the 60s to about two-thirds in the 80s.   The true prevalence of asthma probably lies somewhere between the figure for asthma and the figure for wheeze.  Since that factsheet was produced, there have been further rises in the prevalence of wheezing illness in both adults and children. The prevalence of asthma is probably:   at least 15 per cent in children  about half that proportion in adults.   Given the difficulties in obtaining reliable estimates of the prevalence of asthma, these figures are approximate. Data from the European Respiratory Health Survey suggest that in the UK:  about one quarter of adults between 20 and 44 suffer from wheeze  in 15 per cent there was wheeze with breathlessness  the prevalence of doctor-diagnosed asthma was around 7 per cent.   In this age group, young enough to make the diagnosis of COPD unlikely, the principal cause of wheeze with breathlessness is asthma. The wide discrepancy between the prevalence of wheeze with breathlessness, and of asthma, illustrates the difficulty in giving precise figures. Absolute numbers are therefore unreliable. Despite these problems, there is still a great deal that epidemiology can tell us about asthma. Sex differences influence the prevalence of asthma  In childhood there is a clear sex difference in the prevalence of asthma.   In middle childhood, the male:female ratio may be as high as 2:1, though the male preponderance has been somewhat less in more recent studies.  At puberty, this ratio reverses.   In adults there is a female preponderance.  The role of sex hormones is also indicated by:   the effects of pregnancy on asthma - in some women asthma improves and in other women asthma worsens.  the effects of the monthly hormonal cycle on asthma - there is often pre-menstrual worsening.   Environmental effects on the prevalence of asthma  The effect of environmental factors have been studied extensively, but with few consistent results.  Area of residence  No difference between Newcastle and Cumbria.  No difference between Scottish Highlands and urban areas.  Asthma is more common in rural than in urban settings and in the inner cities than in suburbia.   Increased asthma in association with deprivation   Partly due to environmental tobacco smoke exposure.   Protective effect from being brought up on a farm  A very different matter from simply having an address in the country.  May reflect early exposure to soil bacteria.   Atmospheric pollution   Little or no effect on the prevalence of asthma.  Marked effect on the incidence of attacks of asthma.  Environmental tobacco smoke exposure   Prevalence of asthma in children is about 25 per cent higher in smoking than in non-smoking families.  Intrauterine exposure has an adverse effect that is independent of the effects of exposure after birth.  In adults, the effects of passive smoking on the prevalence of asthma are less dramatic but still important.  Exposure to passive smoking is also an important avoidable factor that can precipitate asthma attacks.  There is a strong association between smoking and deprivation.   Diet  The effects of anti-oxidants:   vitamins A, C and E protect against oxidising chemicals present in the atmosphere.  anti-oxidant consumption has fallen during the period when asthma has been increasingly so dramatically.  the development of asthma in adults is associated with low anti-oxidant levels.  The effects of fatty acids:   studies from Australia have found a protective effect of eating oily fish supplementing omega-3 polyunsaturated fatty acids given in a special margarine had no beneficial effect.   Infant feeding:   possible protective role of breastfeeding - a controversial topic, with studies showing increased, decreased and unchanged prevalence of asthma.  a recent study demonstrated a beneficial effect [11].   Physical activity and fitness  Risk factors for asthma include both:   obesity  physical inactivity.   During the period when asthma has become more prevalent:  the average weight of children has increased  the average weight of adults has increased  cardiovascular unfitness has become widespread.  Statistically, there is increasing evidence in this chicken and egg situation that asthma may be the egg.  Weight reduction has a beneficial effect on lung function is obese asthmatics [12].  Season of birth  Season of birth affects age of first exposure to seasonal allergens such as grass pollens.  Generally, asthma is increased in children born in the Spring and Summer months.   Birth weight   Children who, at birth, were relatively heavy for their length have a slightly increased prevalence of asthma.   Family position and size  Asthma is more common in firstborn than subsequent children.   May reflect protective effects of upper respiratory tract infection.  Younger children in a family are exposed to additional respiratory viruses brought into the household by older children.   Infection  The allergic reaction is an immune reaction.   Normally stimulated by parasites such as worms.  Th2 reaction involving the production of Immunoglobulin E (IgE).   Lack of parasitic infestation might explain some of the increase in allergies during the past 30 years.  Th2 reaction diverted towards innocuous foreign proteins such as the house dust mite.   &amp;#039;Ordinary&amp;#039; infections stimulate Th1 reaction with production of Immunoglobulin G (IgG).  Lack of IgG stimulation might divert the immune system from Th1 to Th2 reaction (IgG to IgE).  Lack of contact with soil organisms called mycobacteria might be an important factor underlying the increase in asthma.   Infection not entirely benign.  Respiratory virus infection in infancy can precipitate recurrent wheezing.  Upper respiratory tract infection is the most common trigger of asthma attacks.   Immunisation  Pertussis vaccine has been associated with a predisposition to asthma, but other studies have shown no effect.  BCG immunisation (against tuberculosis, using a mycobacterium) may have a protective effect.  These data are insufficiently robust to recommend any change in immunisation practice.   Asthma in athletes  Asthma is more common among elite athletes - females more so than males.  Particularly associated with rigorous training (&amp;amp;gt;20 hours a week). Prolonged exercise might predispose to asthma.  &amp;#039;Western&amp;#039; lifestyle   Asthma is more common in countries with what a Western lifestyle.  Asthma is less common in developing countries.  No evidence that asthma can be reduced by changes in lifestyle.  Factors that have been implicated include:  wall-to-wall carpeting, sealed glazing units and central heating, which together conspire to produce an environment conducive to the reproduction of house mites. modern furniture materials that release fumes such as formaldehyde. wall coverings of PVC and other materials containing plasticisers. reinforced concrete as a building material. moulds in central heating and air conditioning vents. use of beds with mattresses, pillows and blankets.  increased cleanliness. reduced breastfeeding. use of pesticides and other agrochemicals.  use of bottled gas, kerosene and other heating fuels.  damp housing conditions. use of gas for cooking. use of pre-prepared foods. exposure to cockroach allergens.  increasing pet ownership, particularly of cats.   It can be seen that many of these factors are associated not only with the western lifestyle, but specifically with the lifestyle of many of the more deprived members of western societies. Yet, in Ireland, children from gypsy families have less than half the prevalence of asthma and wheezing disorders seen in controls, suggesting that poverty and urban deprivation may have significantly different effects. Although we know a great deal about who gets asthma, and have some suspicions as to why, we are not yet in a position to recommend lifestyle or environmental changes with a view to preventing asthma. Intervention studies will be expensive, but are badly needed.  Environmental influences on the incidence of asthmatic attacks  The factors precipitating attacks of asthma, often known as triggers, are quite different from those that predispose to the development of the asthmatic condition. Upper respiratory tract infection   By far the most common factor that triggers asthmatic attacks.  An important cause of diagnostic confusion, leading to inappropriate and unnecessary prescription of antibiotics.  Exercise  A common problem that interferes with many everyday activities. The mechanism is described below.  Normal nasal breathing at rest warms and humidifies the inspired air, so that the air reaching the bronchi is more or less fully saturated and at body temperature. During exercise, the lungs are presented with a much greater volume of air than normal, and mouth breathing ensures that this air is drier and cooler than usual. Drying and cooling of the airways trigger reflex bronchospasm, and the result is an asthma attack.  Consumption of chilled and acid drinks  Chilled drinks and those with a low pH (especially cola drinks).  Commoner in non-Europeans, and presumably reflects a reflex from oesophageal (gullet) stimulation.  Nocturnal asthma  Asthma often worst in the small hours of the night. Shutting down for the night involves:  Exposure to dust mites in the bedding may also play a part.  Atmospheric pollution   Urban smog precipitates asthmatic attacks.  Hospital Accident and Emergency departments report marked rises in asthma-related attendances during periods of high pollution.  At its most extreme, this rise can be as much as seven times the level seen during open, breezy weather.  In the north of England, children living near open cast mines consult their doctors about respiratory conditions more often than controls.  Within the home, in addition to tobacco smoke, exposure to a wide variety of chemicals such as paints, furniture polish and cosmetics can precipitate asthma attacks.  Allergens   Best known is pollen asthma.  Asthma can also occur following exposure to animals, such as horses, cats and dogs.  Asthma may also occur on bed-making due to house dust mite .  Asthma can also occur following exposure to foods such as eggs and cow&amp;#039;s milk.   Seasonality  On children&amp;#039;s units a dip in asthma admissions is seen every summer. This is then followed by an autumn epidemic. Asthma mortality is also increased in the autumn.  In adults there is a similar pattern, though the peaks and troughs are less dramatic.  The reasons for these variations are numerous:  the weather itself may play a part  variations in the concentrations of various aero-allergens. In particular, the house dust mite thrives in the moist, warm conditions of the autumn.   Weather  Many asthmatics identify specific weather conditions that they feel upset their asthma.  Thunderstorms are frequently implicated:  association has been confirmed by epidemiological studies  association weak, and the risk to asthmatics before, during and after thunderstorms is slight.  Psychological and other stressors   Stress can aggravate asthma.  At one time many doctors thought that psychological factors were paramount. There is a danger in these days when medical therapy is so effective, that this aspect of asthma may be overlooked.  Occupational asthma  A serious problem for both employers and employees. Numerous substances used in the workplace can trigger allergic reactions, ranging from solder flux to the urine of laboratory animals [6].  Usually clues, though these are often missed:   Aspirin   Aspirin hypersensitivity relatively uncommon, but important not to miss.  In addition to asthma, these individuals also have nasal polyps.  Conclusions  We are unclear about exactly what we mean by asthma. We do know that it is becoming more common, especially in children.  Other allergic disorders are also becoming more common - the increase is not confined to asthma.  We know quite a lot about who gets asthma, but not really why, and although we have some ideas of how to avoid getting asthma, we don&amp;#039;t know if these ideas work in practice.  References 1. Cane SR, Ranganathan SC, McKenzie SA. What do parents of wheezy children understand by &amp;quot;wheeze&amp;quot;? Arch Dis Child 2000; 82: 327-332.  2. Omran M, Russell G. Continuing increase in respiratory symptoms and atopy in Aberdeen schoolchildren. BMJ 1996; 312: 34.  3. Pattemore PK, Asher MI, Harrison AC et al. The interrelationship among bronchial hyperresponsiveness, the diagnosis of asthma, and asthma symptoms. Am Rev Respir Dis 1990; 142(3): 549-54.  4. D Robin Taylor. Making the diagnosis of asthma (editorial). BMJ 1997; 315: 4-5.  5. Pavord ID. Making the diagnosis of asthma (letter). BMJ 1998; 316:150.  6. Newman Taylor AJ. Asthma and allergy. BMJ 1998; 316: 997.  7. Siersted HC, Boldsen J, Hansen HS, Mostgaard G, Hyldebrandt N. Population based study of risk factors for underdiagnosis of asthma in adolescence: Odense schoolchild study. BMJ 1998; 316: 651-657.  8. Kaur B, Anderson HR, Austin J et al. Prevalence of asthma symptoms, diagnosis, and treatment in 12-14 year old children across Great Britain (international study of asthma and allergies in childhood, ISAAC UK). BMJ 1998; 316: 118-124.  9. Whincup PH, Cook DG, DP Strachan and Papacosta O. Time trends in respiratory symptoms in childhood over a 24 year period. Arch Dis Child, Vol 68, 729-734.  10. Upton MN, McConnachie A, McSharry C et al. Intergenerational 20 year trends in the prevalence of asthma and hay fever in adults: the Midspan family study surveys of parents and offspring. BMJ 2000; 321: 88-92.  11. Oddy WH, Holt PG, Sly PD et al. Association between breast feeding and asthma in 6 year old children: findings of a prospective birth cohort study. BMJ 1999; 319: 815-819.  12. Brita Stenius-Aarniala B, Poussa T, Kvarnstr\u00F6m J et al. Immediate and long term effects of weight reduction in obese people with asthma: randomised controlled study. BMJ 2000; 320: 827-832.   Last updated 01.06.2001 "^^<http://www.w3.org/2001/XMLSchema#string>
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