Towards prevention

Abstract

The results of serial prevalence studies with identical methods suggest that a substantial increase in the prevalence of wheeze and asthma has occurred over the past decades in many western countries.1Anderson HR Butland BK Strachan DP Trends in prevalence and severity of childhood asthma.BMJ. 1994; 308: 1600-1604Crossref PubMed Scopus (237) Google Scholar, 2Gergen PJ Mullally DI Evans III, R National survey of prevalence of asthma among children in the United States, 1976 to 1980.Pediatrics. 1988; 81: 1-7PubMed Google Scholar, 3Manfreda J Becker AB Wang P-Z Roos LL Anthonisen NR Trends in physician-diagnosed asthma prevalence in Manitoba between 1980 and 1990.Chest. 1993; 103: 151-157Crossref PubMed Scopus (96) Google Scholar This change has been accompanied by increasing hospital admission rates for childhood asthma4Mitchell EA International trends in hospital admission rates for asthma.Arch Dis Child. 1985; 60: 376-378Crossref PubMed Scopus (160) Google Scholar and increasing prevalence rates of bronchial hyperresponsiveness, hay fever, and atopic eczema in affluent countries.5Gergen PJ Weiss KB Changing patterns of asthma hospitalization among children: 1979 to 1987.JAMA. 1990; 264: 1688-1692Crossref PubMed Scopus (375) Google Scholar, 6Omran M Russell G Continuing increase in respiratory symptoms and atopy in Aberdeen schoolchildren.BMJ. 1996; 312: 34Crossref PubMed Scopus (146) Google Scholar, 7Burr 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 (752) Google Scholar, 8Peat JK van den Berg RH Green WF Mellis CM Leeder SR Woolcock AJ Changing prevalence of asthma in Australian children.BMJ. 1994; 308: 1591-1596Crossref PubMed Scopus (492) Google Scholar Although a hereditary component in the pathogenesis of asthma and allergic diseases has been shown, the increase in the prevalence of atopic diseases in recent years and the relatively low concordance among homozygotic twins clearly indicates that environmental factors have a major influence in determining which subjects will develop asthma and allergic symptoms. This implies that once environmental risk factors that determine the manifestation of childhood asthma are identified interventions can be designed to reverse these trends and reduce the incidence of asthma.Primary preventionEnvironmental risk factorsWhich environmental risk factors can be identified that causally affect the incidence of childhood asthma and are not intermediate steps in the pathogenesis of the disease? The distinction between risk factor and precursor is not always apparent, but depends on the concept of disease that is applied. An association between the increased occurrence of upper respiratory tract infections, for example, and the subsequent development of asthma may indicate a causal relation, but may also be due to an inherent characteristic of asthma that confers susceptibility to viral infections early in life.Childhood asthma is a complex syndrome that cannot easily be defined. Because of the heterogeneity of this disease it has been suggested that characteristics which are known to be related to asthma such as bronchial hyperresponsiveness and atopy may be more amenable to prevention. However, the relation between these features and the outcome of interest needs to be defined precisely. Atopy has been linked to asthma in a multitude of studies, some investigators using a summary estimate of atopy and others studying specific sensitisations. There is evidence that asthma is related to perennial allergens, but there is less consistent evidence with respect to seasonal allergens. It has furthermore been shown that the level of allergen exposure is strongly related to the development of sensitisation towards that specific allergen.9Lau S Falkenhorst G Weber A et al.High mite allergen exposure increases the risk of sensitization in atopic children and young adults.J Allergy Clin Immunol. 1989; 84: 718-725Summary Full Text PDF PubMed Scopus (328) Google Scholar, 10Kuehr J Frischer T Meinert R et al.Mite allergen exposure is a risk for the incidence of specific sensitization.J Allergy Clin Immunol. 1994; 94: 44-52Summary Full Text Full Text PDF PubMed Scopus (222) Google Scholar Whether environmental allergen exposure affects the initiation of asthma in similar ways remains to be elucidated. The high prevalence of asthma in those who are sensitive to indoor allergens or alternaria may reflect one of two underlying mechanisms. Environmental factors that drive the development of IgE antibodies towards these allergens may also determine the development of asthma. Alternatively, an increased immunological response towards perennial allergens may be a characteristic of asthmatic subjects with the extent of environmental allergen exposure determining the type of sensitisation that they develop, but not the start of her/his disease. The nature of the relation between sensitisation to perennial allergens and asthma will eventually determine whether specific allergen-avoidance strategies will reduce only atopic sensitisation to that specific allergen, or both specific sensitivity and the risk of asthma.Population at riskWhat is the population at risk and who should benefit from preventive measures? In relation to cardiovascular research Geoffrey Rose proposed and discussed two basic prevention strategies: the “high-risk” and the “population-based” strategies (see panel).11Rose G The strategy of preventive medicine. Oxford University Press, Oxford1992Google Scholar The high-risk strategy is close to clinical practice, and involves the patient taking responsibility to reduce risk.Panel 1Basic approaches to prevention strategiesTabled 1High-risk strategyPopulation-based strategyIdentify subjects at riskIdentify the target populationApply to subjects at risk onlyApply to the population as a wholeReduces the incidence of a given disease in subjects at riskReduces the incidence of a given disease within that populationThe benefit is limited to subjects at riskThe benefit may be large and shift a population's characteristics Open table in a new tab With regard to asthma, risk may be translated to genetic predisposition for asthma. Since the genes for asthma remain unknown surrogates may be used. A positive family history of asthma or atopy may be due to shared genetic factors or to factors relating to the shared environment of family members enhancing or suppressing the manifestation of the disease in that particular family. A positive family history of asthma is a relatively specific, but not sensitive, parameter to detect offspring who will develop asthma later in life. Parents who are not affected may still transmit the asthmatic genes to their children.Therefore, markers have been sought that allow early identification of children at risk. Cord blood IgE has not proved a satisfying index.12Martinez FD Wright AL Taussig LM et al.Asthma and wheezing in the first six years of life.N Engl J Med. 1995; 332: 133-138Crossref PubMed Scopus (3256) Google Scholar, 13Koning H Baert MR Oranje AP Savelkoul HF Neijens HJ Development of immune functions related to allergic mechanisms in young children.Pediatr Res. 1996; 40: 363-375Crossref PubMed Scopus (38) Google Scholar Studies investigating the early immunological responses to allergens in uter14Miles EA Warner JA Jones AC Colwell BM Bryant TN Warner JO Peripheral blood mononuclear cell proliferative responses in the first year of life in babies born to allergic patients.Clin Exp Allergy. 1996; 26: 780-788Crossref PubMed Scopus (109) Google Scholar, 15Warner JA Miles EA Jones AC Quint DJ Colwell BM Warner JO Is deficiency of interferon gamma production by allergen triggered cord blood cells a predictor of atopic eczema?.Clin Exp Allergy. 1994; 24: 423-430Crossref PubMed Scopus (338) Google Scholar may open new avenues into recognition of infants at risk. Sensitivity to egg white in the first years of life has furthermore been proposed as a predictor for later asthma.16Wahn U Bergmann R Bergmann K et al.Development of atopic disease during the first years of life.in: Van Moerlbeke D Cohort study on the development of atopy and asthma in infancy and early childhood. The UCB Institute of Allergy, Braine-I'Alleud, Belgium1997Google Scholar The length of the vulnerable period in which environmental factors decisively influence the manifestation of asthma is, however, unknown. If indeed this “window of opportunity” is limited to early life as the results of recent studies suggest,17Warner JA Jones AC Miles EA Colwell BM Warner JO Maternofetal interaction and allergy.Allergy. 1996; 51: 447-451Crossref PubMed Scopus (49) Google Scholar, 18von Mutius E Weiland SK Fritzsch C Duhme K Keil U Increasing prevalence of atopy in East Germany.Am J Respir Crit Care Med. 1997; 155: A248Google Scholar then recognition of subjects at risk and preventive strategies must start early.The population-based strategy is based on the observation that a small decrease in the mean level of exposure to a risk factor may significantly reduce the incidence of a given disease within that population.” Hence, small but widespread -lifestyle changes may cumulate to produce substantial changes in public health. The increase in the prevalence of atopic diseases in many populations of affluent western countries over the past decades may point towards one or several factors whose distribution may have shifted towards higher exposure levels. If these factors were known, prevention as a mass approach to lower the distribution of the risk variable by some measure in which all participate might revert these trends. Rudolph Virchow's observation. “Epidemics appear, and often disappear without traces, when a new culture period has started;… The history of epidemics is therefore the history of disturbances of human culture"19Ackerknecht EH Therapie von den Primitiven bis zum 20. Enke, Jahrhundert. Stuttgart1970Google Scholar is still relevant.Primary prevention studies in childrenWhat have we learned from prevention studies? Most studies have addressed the relation between breast milk or hypoallergenic formula feeds and the development of atopic diseases in infancy and early childhood. In prospective studies breastfeeding has been found to have a transient beneficial effect on the incidence of eczema, food allergy, atopic sensitisation, and early wheezing illnesses in the first 1-3 years of life.20Chandra RK Prospective studies of the effect of breast feeding on incidence of infection and allergy.Acta Paediatr Scand. 1979; 68: 691-694Crossref PubMed Scopus (50) Google Scholar, 21Fergusson DM Horwood JL Shannon FT Taylor B Breast feeding, gastrointestinal and lower respiratory illness in the first two years.Aust Paediatr J. 1981; 17: 191-195PubMed Google Scholar, 22Wright AL Holberg CJ Martinez FD et al.Breast feeding and lower respiratory tract illness in the first year of life.BMJ. 1989; 299: 946-949Crossref PubMed Google Scholar, 23Zeiger RS Heller S The development and prediction of atopy in high-risk children: follow-up at age seven years in a prospective randomized study of combined maternal and infant food allergen avoidance.J Allergy Clin Immunol. 1995; 95: 1179-1190Summary Full Text Full Text PDF PubMed Scopus (500) Google Scholar, 24Chandra RK Puri S Hamed A Influence of maternal diet during lactation and use of formula feeds on development of atopic eczema in high risk infants.BMJ. 1989; 299: 228-230Crossref PubMed Google Scholar Furthermore, infectious respiratory and gastrointestinal diseases may be prevented by breastfeeding.22Wright AL Holberg CJ Martinez FD et al.Breast feeding and lower respiratory tract illness in the first year of life.BMJ. 1989; 299: 946-949Crossref PubMed Google Scholar No consistent protective effect of breastfeeding or hypoallergenic formulas on the subsequent development of childhood asthma has been found.In the Isle of Wight Study infants born to mothers with a strong family history of atopy were prenatally randomised into prophylactic (n=58) and control (n=62) groups.25Hide DW Matthews S Tariq S Arshad SH Allergen avoidance in infancy and allergy at 4 years of age.Allergy. 1996; 51: 89-93Crossref PubMed Scopus (274) Google Scholar Children in the prophylactic group were either breastfed with their mothers excluding foods regarded as highly allergenic from their diet, or were given a soy base protein hydrolysate. In addition, reduction of exposure to house-dust mites was achieved by encasing the child's mattress and treating the home with an acaricide four times within the first 9 months of age. A significant decrease in the prevalence of eczema (a summary measure of atopic illness) and of sensitisation to both dietary and aeroallergens at the age of 2 and 4 years was found for infants in the prophylactic group. At the age of 4 years the prevalence of doctor-diagnosed asthma was 24·1% in the prophylactic group compared with 35·5% in the controls. This difference did not, however, reach statistical significance even after controlling for confounding factors (see table).TableIsle of Wight Study: effect of avoidance strategies on expression of allergy at 1, 2, and 4 years of age25Hide DW Matthews S Tariq S Arshad SH Allergen avoidance in infancy and allergy at 4 years of age.Allergy. 1996; 51: 89-93Crossref PubMed Scopus (274) Google Scholar, 26Hide DW Matthews S Matthews L et al.Effect of allergen avoidance in infancy on allergic manifestations at age two years.J Allergy Clin Immunol. 1994; 93: 842-846Summary Full Text PDF PubMed Scopus (219) Google Scholar, 27Arshad SH Matthews S Gant C Hide DW Effect of allergen avoidance on development of allergic disorders in infancy.Lancet. 1992; 339: 1493-1497Summary PubMed Scopus (430) Google ScholarAsthmaRhinitisEczemaPositive skin-prick testAt 1 year4.13 (1.1-15.5)..3.6 (1.0-12.5)..At 2 yearsNSNS9.5 (1.8-50.1)10.3(1.6-66.7)At 4 yearsNSNS3.4 (1.2-10.1)3.7(1.3-10.0)Unadjusted odds ratio (95% Cl) for the control group is shown. NS= Not significant..= Not determined. Open table in a new tab A definite diagnosis of asthma is difficult to establish in preschool children since many wheezing infants lose their symptoms in the first years of life.12Martinez FD Wright AL Taussig LM et al.Asthma and wheezing in the first six years of life.N Engl J Med. 1995; 332: 133-138Crossref PubMed Scopus (3256) Google Scholar The follow-up of these infants to school age will provide important information about the effectiveness of combined allergen avoidance on the subsequent development of childhood asthma. However, further carefully designed, prospective, long-term studies with larger numbers of children are needed to identify early risk factors potentially operating in utero or postnatally that affect the development of childhood asthma. Since in infants and toddlers asthma may not easily be separated from other wheezing illnesses follow-up must at least continue up to school age. Other potential risks such as passive smoke exposure, 28von Mutius E. The application of modern epidemiological methods to paediatric respiratory disorders. Eur Respir J (in press).Google Scholar which emerge consistently from different epidemiological surveys, may be considered targets for future primary prevention studies.Primary prevention in adultsAsthma may be acquired during adulthood, particularly at the workplace and this is amenable to prevention. There is uncertainty about what proportion of cases of adult-onset asthma is attributable to occupational causes, and about the relative importance of different causes. The importance of atopy and tobacco smoking varies according to the type of sensitising agent. Satisfactory discriminating tests for the identification of workers at risk and adequate primary prevention strategies are lacking, Asthma epidemics, however, when the point source of the outbreaks can be identified and subsequently removed, as in the soy bean asthma epidemic in Barcelona,29Anto JM Sunyer J Rodriguez-Roisin R Suarez-Cervera M Vazquez L Community outbreaks of asthma associated with inhalation of soybean dust: Toxicoepidemiological Committee.N Engl J Med. 1989; 320: 1097-1102Crossref PubMed Scopus (243) Google Scholar, 30Anto JM Sunyer J Reed CE et al.Preventing asthma epidemics due to soybeans by dust-control measures.N Engl J Med. 1993; 329: 1760-1763Crossref PubMed Scopus (99) Google Scholar are amenable to preventive measures.Secondary and tertiary preventionApart from primary prevention strategies that have the potential to reduce rates of acquisition of asthma and atopic sensitisation, secondary prevention is needed once asthma is established to reduce morbidity and mortality. Environmental risk factors that aggravate the disease or favour the persistence of asthma-related health problems in adolescence, a period of low activity of the disease in many asthmatic subjects, should be minimised.Allergen avoidanceIt has long been recognised that acute asthma attacks can be triggered by several allergens. Furthermore, the role of different allergens in determining the severity of the clinical course of asthma has been established. Particular emphasis has been laid on the importance of indoor allergens such as house-dust mites and cats for a deterioration in the condition of asthmatic patients.31Duff AL Platts-Mills TAE Allergens and asthma.Pediatr Clin North Am. 1992; 39: 1277-1291PubMed Google Scholar, 32Van Metre TE Marsh DG Adkinson NF Dose of cat (felis domesticus) allergen 1 (Fel d 1) that induces asthma.J Allergy Clin Immunol. 1986; 78: 62-75Summary Full Text PDF PubMed Scopus (86) Google Scholar Early studies by Platts-Mills and co-workers33Platts-Mills TAE Tovey ER Mitchell EB Moszoro H Nock P Wilkins SR Reduction of bronchial hyperreactivity during prolonged allergen avoidance.Lancet. 1982; ii: 675-677Summary Scopus (561) Google Scholar have shown the effectiveness of allergen avoidance in asthmatics sensitised to house-dust mite by moving these patients to a mite-free environment. These findings have been corroborated by others showing that residence in high altitude where house-dust mite allergen concentrations are low improves asthma control in those sensitive to house-dust mite.34Boner AL Peroni DG Piacentini GL Venge P Influence of allergen avoidance at high altitude on serum markers of eosinophil activation in children with asthma.Clin Exp Allergy. 1993; 23: 1021-1026Crossref PubMed Scopus (88) Google ScholarSince then alternative mite allergen avoidance strategies that are more easily applicable in daily life have been studied. House-dust mites thrive well in places with sufficient humidity and their reproduction can be prevented by depriving them of moisture. Humidity levels indoors can be decreased by dehumidifiers and by increased ventilation. Allergen concentrations in beds can be reduced by encasing mattresses with occlusive covers and by regular washing of covers, blankets, and duvets. In mite-sensitive asthmatics encasing the mattress was found to significantly reduce symptoms and bronchial hyperresponsiveness.35Ehnert B Lau-Schadendorf S Weber A Buettner P Schou C Wahn U Reducing domestic exposure to dust mite allergen reduces bronchial hyperreactivity in sensitive children with asthma.J Allergy Clin Immunol. 1992; 90: 135-138Summary Full Text PDF PubMed Scopus (359) Google Scholar Acaricides have been used to remove house-dust mite allergens from floors and furnishings, but their effect on long-term reduction of allergens is uncertain.Cat allergens remain airborne for long periods and, after eviction of a cat, it can take more than 6 months36Wood RA Chapman MD Adkinson NF Eggleston PA The effect of cat removal on allergen contact in household dust samples.J Allergy Clin Immunol. 1989; 83: 730-734Summary Full Text PDF PubMed Scopus (224) Google Scholar for cat allergens to return to concentrations similar to cat-tree homes. Ownership of furry pets has been shown37Gelber LE Seltzer LH Bouzoukis JK Pollart SM Chapman MD Platts-Mills TAAD Sensitization and exposure to indoor allergens as risk factors for asthma among patients presenting to hospital.Am Rev Respir Dis. 1993; 147: 573-578Crossref PubMed Scopus (466) Google Scholar to relate to severe asthma in adolescence, yet compliance with cat removal from homes of asthmatic children is poor.Avoidance of environmental pollutionIndoor tobacco smoke exposure has consistently been found to trigger symptoms and exacerbations of asthma.38Chilmonczyk BA Salmun LM Megathlin KN et al.Association between exposure to environmental tobacco smoke and exacerbations of asthma in children.N Engl J Med. 1993; 328: 1665-1669Crossref PubMed Scopus (440) Google Scholar Increases in the number of emergency department visits, in the use of asthma medication, and in the degree of bronchial hyperresponsiveness of asthmatics have all been reported. Yet little public action has been taken in Europe compared with the USA to decrease the frequency of cigarette smoking in the population and thereby reduce an important risk factor for both the acquisition and aggravation of asthma in children and adults.Several studies have shown an increased frequency of emergency department visits and hospital admission rates for acute respiratory illnesses and asthma with increasing air pollution.39Anderson HR Holgate ST Asthma and outdoor air pollution: Committee on the Medical Effects of Air Pollutants. HM Stationery Office, London1995Google Scholar The evidence appears strongest for the type of summer haze pollution that affects Canada and the eastern part of the USA, whereas most of the episodes of increased sulphur dioxide exposure in winter have not been shown to induce exacerbations in asthmatic patients. However, particulate pollution was found by several authors to affect asthma hospital admissions and emergency department visits. It remains, however, uncertain to what extent asthma morbidity as assessed by daily symptom frequency, medication use, peak flow variability, or school and work absenteeism is affected by ambient air pollution. Thus, the attributable risk of outdoor air pollution remains to be established, and the extent to which reduction of air pollution levels would reduce morbidity of asthmatic children and adults remains unknown.Use of drugs in preventionNational and international consensus statements40Meijer RJ Kerstjens HAM Postma DS Comparison of guidelines and self-management plans in asthma.Eur Respir J. 1997; 10: 1163-1172Crossref PubMed Scopus (51) Google Scholar provide recommendations for therapy according to asthma' severity with a view to improving bronchodilatation and reducing mediator-induced inflammation. However, very little is known about the impact of different treatment strategies on the long-term outcome of asthmatic patients. The time course of airway remodelling that may start early in the course of disease and eventually leads to irreversible loss of pulmonary function is not well understood. The potential of anti-inflammatory drugs, particularly the early administration of topical steroids, to prevent this process remains to be elucidated. Furthermore, the relative importance of novel therapies such as leukotriene antagonists and lipoxygenase synthesis inhibitors needs careful evaluation in children and in adults.ConclusionsMany environmental factors have been proposed as risk factors for the development of childhood and adult-onset asthma. Yet in many instances results of different studies have yielded conflicting results or the precise relation between these risk factors and the disease has not clearly been established. Therefore, substantial uncertainty about identification of subjects at risk and effective prevention strategies remains. However, carefully designed prevention studies with randomised allocation of exposure might help to understand both the relative importance of different risk factors for the development of asthma and the benefit that can be gained by implementing these avoidance strategies. The results of serial prevalence studies with identical methods suggest that a substantial increase in the prevalence of wheeze and asthma has occurred over the past decades in many western countries.1Anderson HR Butland BK Strachan DP Trends in prevalence and severity of childhood asthma.BMJ. 1994; 308: 1600-1604Crossref PubMed Scopus (237) Google Scholar, 2Gergen PJ Mullally DI Evans III, R National survey of prevalence of asthma among children in the United States, 1976 to 1980.Pediatrics. 1988; 81: 1-7PubMed Google Scholar, 3Manfreda J Becker AB Wang P-Z Roos LL Anthonisen NR Trends in physician-diagnosed asthma prevalence in Manitoba between 1980 and 1990.Chest. 1993; 103: 151-157Crossref PubMed Scopus (96) Google Scholar This change has been accompanied by increasing hospital admission rates for childhood asthma4Mitchell EA International trends in hospital admission rates for asthma.Arch Dis Child. 1985; 60: 376-378Crossref PubMed Scopus (160) Google Scholar and increasing prevalence rates of bronchial hyperresponsiveness, hay fever, and atopic eczema in affluent countries.5Gergen PJ Weiss KB Changing patterns of asthma hospitalization among children: 1979 to 1987.JAMA. 1990; 264: 1688-1692Crossref PubMed Scopus (375) Google Scholar, 6Omran M Russell G Continuing increase in respiratory symptoms and atopy in Aberdeen schoolchildren.BMJ. 1996; 312: 34Crossref PubMed Scopus (146) Google Scholar, 7Burr 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 (752) Google Scholar, 8Peat JK van den Berg RH Green WF Mellis CM Leeder SR Woolcock AJ Changing prevalence of asthma in Australian children.BMJ. 1994; 308: 1591-1596Crossref PubMed Scopus (492) Google Scholar Although a hereditary component in the pathogenesis of asthma and allergic diseases has been shown, the increase in the prevalence of atopic diseases in recent years and the relatively low concordance among homozygotic twins clearly indicates that environmental factors have a major influence in determining which subjects will develop asthma and allergic symptoms. This implies that once environmental risk factors that determine the manifestation of childhood asthma are identified interventions can be designed to reverse these trends and reduce the incidence of asthma. Primary preventionEnvironmental risk factorsWhich environmental risk factors can be identified that causally affect the incidence of childhood asthma and are not intermediate steps in the pathogenesis of the disease? The distinction between risk factor and precursor is not always apparent, but depends on the concept of disease that is applied. An association between the increased occurrence of upper respiratory tract infections, for example, and the subsequent development of asthma may indicate a causal relation, but may also be due to an inherent characteristic of asthma that confers susceptibility to viral infections early in life.Childhood asthma is a complex syndrome that cannot easily be defined. Because of the heterogeneity of this disease it has been suggested that characteristics which are known to be related to asthma such as bronchial hyperresponsiveness and atopy may be more amenable to prevention. However, the relation between these features and the outcome of interest needs to be defined precisely. Atopy has been linked to asthma in a multitude of studies, some investigators using a summary estimate of atopy and others studying specific sensitisations. There is evidence that asthma is related to perennial allergens, but there is less consistent evidence with respect to seasonal allergens. It has furthermore been shown that the level of allergen exposure is strongly related to the development of sensitisation towards that specific allergen.9Lau S Falkenhorst G Weber A et al.High mite allergen exposure increases the risk of sensitization in atopic children and young adults.J Allergy Clin Immunol. 1989; 84: 718-725Summary Full Text PDF PubMed Scopus (328) Google Scholar, 10Kuehr J Frischer T Meinert R et al.Mite allergen exposure is a risk for the incidence of specific sensitization.J Allergy Clin Immunol. 1994; 94: 44-52Summary Full Text Full Text PDF PubMed Scopus (222) Google Scholar Whether environmental allergen exposure affects the initiation of asthma in similar ways remains to be elucidated. The high prevalence of asthma in those who are sensitive to indoor allergens or alternaria may reflect one of two underlying mechanisms. Environmental factors that drive the development of IgE antibodies towards these allergens may also determine the development of asthma. Alternatively, an increased immunological response towards perennial allergens may be a characteristic of asthmatic subjects with the extent of environmental allergen exposure determining the type of sensitisation that they develop, but not the start of her/his disease. The nature of the relation between sensitisation to perennial allergens and asthma will eventually determine whether specific allergen-avoidance strategies will reduce only atopic sensitisation to that specific allergen, or both specific sensitivity and the risk of asthma.Population at riskWhat is the population at risk and who should benefit from preventive measures? In relation to cardiovascular research Geoffrey Rose proposed and discussed two basic prevention strategies: the “high-risk” and the “population-based” strategies (see panel).11Rose G The strategy of preventive medicine. Oxford University Press, Oxford1992Google Scholar The high-risk strategy is close to clinical practice, and involves t