Asmanet ENFUMOSA : M. Aubier AIR POLLUTION AND ASTHMA

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màj 23/07/98

ENFUMOSA
(courriel: Chanez (at) montp.inserm.fr )
The European Network For Understanding
Mechanisms of Severe Asthma
BIOMED 2 Program - European Commission

4th quaterly meeting, with the support of INSERM and
Merck Sharp & Dhome Laboratory
February 13-14th 1998 in Montpellier- France
(see programm, abstracts and experts comments )

AIR POLLUTION AND ASTHMA
Michel AUBIER
Service de Pneumologie Unité INSERM 408
Hôpital BICHAT 46 Rue Henri Huchard 75877 PARIS Cédex 18

Vendredi 13 Février 1998		Présentateurs		Modérateurs	Experts
11h30-12h30	Pollution domestique et atmosphérique Indoor and atmospheric pollution	F. de Blay (Strasbourg) M. Aubier (Paris) Discussion	15' 15' 30'	D. Charpin (Marseille) G. Pauli (Strasbourg)	J. Anto (Barcelone, E) N. Papageorgiou (Athenes, G)

Recently, several studies have shown that allergic diseases such as asthma, rhinitis, and eczema have become more comon over the last 50 years. Burr and colleagues (1), conducted two surveys 15 years apart in 12-year-old school children in South Wales (UK), and demonstrated that the number of children suffering from asthma, eczema, and hay fever increased significantly from 6% to 12%, 5% to 16%, and 9% to 15%, respectively, during this period. Similarly, three separate surveys of school-children in Aberdeen (UK), conducted by Russel and colleagues (2,3) over a 30-year period between 1964-1994, have also indicated that the prevalence of respiratory symptoms and atopy has increased, as demonstrated by increased diagnosis of asthma (from 4.1% in 1964 to 10.2% in 1989 and to 19.5% in 1994), hay fever (from 3.2% in 1964 to 11.9% in 1989 and to 12.9% in 1994), and eczema (from 5.3% in 1964 to 12% in 1989 and to 17.7% in 1994). Haahtela and colleagues (4) have analyzed records of military conscripts in Finland, over longer time spans, from 1926 to 1961 and from 1961 to 1989 and demonstrated that although the prevalence of asthma changed little (from 0.02M to 0.08%) during the first time interval, this subsequently increased 22 fold in the second interval (from 0.08% to 1.79%).

Evidence, particularly from the developed countries, suggests that the increase in the prevalence of allergic disease such as asthma may be associated with air pollution, particularly that the resulting form increased use of liquid petroleum and gas in the transport and manufacturing industries and characterized by high concentrations of atmospheric hydrocarbons, oxides of nitrogen (Nox), 03, and respirable particulate matter (PM10) (5-7).

Recent epidemiological studies have confirmed the general suspicion that air pollution plays a role in the clinical manifestations of asthma. Usetti and colleagues (8) examined an asthma outbreak in Barcelona in 1983, and found a clear correlation between oxides of nitrogen concentration and hospital admission for asthma. In a very recent study, Weeks and colleagues investigated the respiratory effects of nitrogen dioxide exposure in 62 asthmatic children aged 7-11 for 2 weeks (9). Peak expiratory flow rates (PEFR) were recorded three times daily and a symptom and a medication diary was kept. The authors found that the presence of smokers and/or gas fires in the home increased N0₂ night time levels while distance from the city center decreased it, and that day time NOz exposure correlated significantly with mean 8 am peak flow the next day. Recently, particulate air pollution has received a great deal of attention.

In Seattle, Schwartz and colleagues (10) recorded the daily emergency room visits for asthma and measured the level of respirable particulate matter or mean median diameter >10 um (PM10). A significant association was found between visits and PM10 exposure on the previous day in those under the age of 65 years. The mean of previous 4 days exposure levels of PM10, however, proved an even better predictor. Interestingly, daily PM10 concentrations never exceeded 70% of the current quality standards during the study period, suggesting that revision of current safety levels for particulate matter air pollution maybe necessary.

Although there is increasing evidence of a link between and increase in the prevalence of allergic airway disease and an increase in air pollution, the underlying mechanisms are not fully understood. It has been suggested that air pollutants may promote sensitization, and subsequent development of allergic disease, by modulating the allergenicity of airborne allergens.

Diaz-Sanchez and colleagues have investigated the direct effect of diesel exhaust particles (DEP) on the local immune response in normal healthy volunteers undergoing nasal challenge with several doses of DEP (11). These authors demonstrated that DEP led to significant increase in IgE, but not IgG, IgA, or IgM, when compared with saline challenge. Additionally, they demonstrated that DEP led to significant increase in IgE-secreting cells and a concomitant increase in epsilon mRNA production in the lavage cells. Studies of animals exposed to pollutants have also demonstrated that specific IgE may be synthesized to adducts of pollutants such as 0s (12,13) and diesel exhaust particulates (14).

Taken together, these findings provide evidence that exposure to air pollutants generated from petrol and diesel burning engines are likely to precipitate attacks of asthma and rhinitis and possibly contribute to the increase in prevalence of these disorders.

Ref (1): Burr ML, Butland BK, King S, Vaughan-Williams E: Changes in asthma prevalence: Two surveys 15 years apart. Arch Dis Child 1989; 64: 1452-1456. (partial abstract from http://www.healthy.net/library/search/medline.htm )

Author : Burr ML; Butland BK; King S; Vaughan-Williams E
Address : MCR Epidemiology Unit, Cardiff.
Source : Arch Dis Child, 64(10):1452-6 1989 Oct
Abstract : In 1973 a survey was conducted among 12 year old children living in a defined area of South Wales. In 1988 the survey was repeated in the same area, again among 12 year old children. Questionnaires were completed for all 965 children in the population sample; peak expiratory flow rates were performed on them all, and repeated (except for five children) after an exercise provocation test. The prevalence of a history of wheeze at any time had increased from 17% to 22%, while that of a history of asthma at any time had increased from 6% to 12%. Current asthma had increased from 4% to 9%, but wheezing in the past year not attributed to asthma had remained at 6%. The exercise provocation tests suggested that both mild and severe asthma had become more common. Increases had also occurred in the frequencies of a history of eczema (from 5% to 16%) and of hay fever (from 9% to 15%). It seems that the prevalence of asthma has risen, and that this cannot be wholly explained by a greater readiness to diagnose the disease.

Ref (2): Ninan TK, Russell G. Respiratory symptoms and atopy in Aberdeen schoolchildren: Evidence from two surveys 25 years apart. Br Med J 1992; 304: 873-875. (partial abstract from http://www.healthy.net/library/search/medline.htm )

Author : Ninan TK; Russell G
Address : Department of Child Health, University of Aberdeen.
Source : BMJ, 304(6831):873-5 1992 Apr 4
Abstract : OBJECTIVE--To estimate changes in the prevalence of respiratory symptoms and the reported diagnoses of asthma, eczema, and hay fever in primary school children in Aberdeen between 1964 and 1989. DESIGN--Determination of incidence prevalence and prevalence from survey data. SETTING--Aberdeen, Scotland. PARTICIPANTS--2743 primary school children (aged 8-13) from 1964 and 4003 [corrected] from 1989. MAIN OUTCOME MEASURES--Survey data on whether, according to the parent or guardian, the child wheezed or was troubled with shortness of breath; the number of episodes of breathlessness in the past year; and whether asthma, eczema, or hay fever had ever been diagnosed. RESULTS--Questionnaires were completed by the parents of 2510 children in 1964 and 3403 children in 1989. The prevalence of wheeze rose from 10.4% in 1964 to 19.8% in 1989, and the prevalence of episodes of shortness of breath increased from 5.4% to 10.0%. In both surveys wheeze and shortness of breath were more prevalent in boys than in girls. The reported diagnosis of asthma rose from 4.1% to 10.2%, hay fever from 3.2% to 11.9%, and eczema from 5.3% to 12%. The proportion of boys suffering from eczema rose from 47.7% to 60.0%. Hay fever showed a similar increase, from 49.4% to 60.1%, in boys over the 25 year period. Though the parents of a higher proportion of children with wheeze were aware of the diagnosis of asthma in 1989, because of the increased prevalence of wheeze the absolute number of parents of wheezy children who were not aware of a diagnosis of asthma increased from 7.4% to 9.6% of the population studied....

Ref (3): Omran M, Russell G. Continuing rise in the prevalence of asthma-like symptoms and diagosed atopic disease in Aberdeen school children. Eur Respir J 1995; 8: 495s. (partial abstract from http://www.healthy.net/library/search/medline.htm )

Author : Haahtela T; Lindholm H; Björkstén F; Koskenvuo K; Laitinen LA
Address : Department of Allergic Diseases, University Central Hospital, Helsinki, Finland.
Source : BMJ, 301(6746):266-8 1990 Aug 4
Abstract : OBJECTIVE--To determine the prevalence of asthma in cohorts of Finnish young men in the period 1926-89. DESIGN--A retrospective analysis using reports and statistics of Finnish defence forces. SETTING--Call up examinations of candidates for military conscription and examination of conscripts discharged because of poor health. SUBJECTS--Roughly 900,000 men--that is, 98% of men of conscription age--examined in 1966-89 and a proportional but unknown number examined in 1926-61. MAIN OUTCOME MEASURES--Asthma recognised at call up examination, exemption from military service, and discharge from military service because of asthma. RESULTS--During 1926-61 the prevalence of asthma recorded at call up examinations remained steady at between 0.02% and 0.08%. Between 1961 and 1966, however, a continuous, linear rise began, the prevalence increasing from 0.29% in 1966 to 1.79% in 1989--that is, representing a sixfold increase. Compared with 1961 the rise was 20-fold. From 1966 to 1989 the sum of exemptions and discharges from military service due to asthma increased analogously sixfold. CONCLUSIONS--If the apparent increase in asthma detected in Finnish young men was due entirely to improved diagnostic methods and other confounding effects then some 95% of cases must have gone undiagnosed in the years before 1966....

Ref (6): Department of Health Advisory Group on the Medical Aspects of Air Pollution Episodes. Second Report - Sulphur dioxide, acid aerosols and particulates. London: HMSO, 1992. (partial abstract from http://www.healthy.net/library/search/medline.htm )

Ref (7): Department of Health Advisory Group on the Medical Aspects of Air Pollution Episodes. Third Report - Oxides of nitrogen. London: HMSO, 1993. (partial abstract from http://www.healthy.net/library/search/medline.htm )

Ref (8): Usetti P, Roca J, Agusti AGN, Montserrat JM, Rodrigues-Roisin R, AugustiVidal A. Another asthma outbreak in Barcelona: Role of oxides of nitrogen. Lancet 1984; i: 156. (partial abstract from http://www.healthy.net/library/search/medline.htm )

Ref (9): Weeks J, Oliver J, Carswell F. Respiratory effects of nitrogen dioxide exposure in asthmatic children. Eur Respir J 1995; 8: 286s (abstract). (partial abstract from http://www.healthy.net/library/search/medline.htm )

Ref (10): Schwartz J, Slater D, Larson TV, Pierson WE, Koening JQ. Particulate air pollution and hospital emergency room visits for asthma in Seattle. Am Rev Respir Dis 1993; 147; 826-831 (partial abstract from http://www.healthy.net/library/search/medline.htm )

Author : Schwartz J; Slater D; Larson TV; Pierson WE; Koenig JQ
Address : U.S. Environmental Protection Agency, Washington, D.C.
Source : Am Rev Respir Dis, 147(4):826-31 1993 Apr
Abstract : Recent studies have associated short-term exposure to respirable particulate matter (PM10) exposure with peak flow decrements, increased symptoms of respiratory irritation, increased use of asthma medications, and increased hospitalization for asthma. Increased mortality from chronic respiratory disease has also been reported. To help confirm whether PM10 exposure is a risk factor for the exacerbation of asthma, we compiled daily records of asthma emergency room visits from eight hospitals in the Seattle area. In Poisson regressions controlling for weather, season, time trends, age, hospital, and day of the week, the daily counts of emergency room visits for persons under age 65 were significantly associated with PM10 exposure on the previous day. The mean of the previous 4 days' PM10 was a better predictor (p < 0.005). The relative risk for a 30 micrograms/m3 increase in PM10 was 1.12 (95% confidence interval 1.20 to 1.04). Daily PM10 concentrations never exceeded 70% of the current ambient air quality standards during the period. The consistency of investigations of the health effects of PM10 suggest that increased attention should be given to the control of particulate matter air pollution.

Ref (11): Diaz-Sanchez D, Dotson AR, Takenaka H, Saxon A. Diesel exhaust particles induce local IgE production in vivo and after the pattern of IgE messenger RNA isoforms. J Clin Invest 1994; 94: 1417-1425. (partial abstract from http://www.healthy.net/library/search/medline.htm )

Author : Diaz-Sanchez D; Dotson AR; Takenaka H; Saxon A
Address : Hart and Louise Lyon Laboratory, Department of Medicine, UCLA School of Medicine, University of California 90024-1680.
Source : J Clin Invest, 94(4):1417-25 1994 Oct
Abstract : Diesel exhaust particles (DEP) have been implicated in the increased incidence of allergic airway disorders. We investigated the effects of DEP on localized immunoglobulin production by performing nasal challenges with varying doses of DEP and analyzing the local immune response in nasal lavages obtained before and after. A significant rise in nasal IgE but not IgG, IgA, IgM, or albumin was observed in subjects 4 d after challenge with 0.30 mg DEP, equivalent to exposure on an average Los Angeles day. Direct evidence for DEP-enhanced local production of IgE was that challenge increased the number of IgE-secreting cells in lavage fluid from < 1 in 2,000,000 to > 1 in 100,000 but did not alter the number of IgA-secreting cells. There was a concomitant increase in epsilon mRNA production in the lavage cells. Additionally, DEP altered the relative amounts of five different epsilon mRNAs generated by alternative splicing, mRNAs that code for different IgE proteins. These results show that DEP exposure in vivo causes both quantitative and qualitative changes in local IgE production. The implication is that natural exposure to DEP may result in increased expression of respiratory allergic disease.

Ref (12): Osebold JW, Owens SL, Zee YC, Dotson WM, La Barre DD. Imunological alterations in the lungs of mice following ozone exposure: Changes in immunoglobin levels and antibody containing cells. Arch Environ Health 1979 ; 34: 258-265. (partial abstract from http://www.healthy.net/library/search/medline.htm )

Ref (13): Biagini RE, Moorman WJ, Lewis TR, Bernstein IL. Ozone enchancement of platinum asthma in a primate model. Am Rev Respir Dis 1986; 134: 179-725. (partial abstract from http://www.healthy.net/library/search/medline.htm )

Author : Biagini RE; Moorman WJ; Lewis TR; Bernstein IL
Source : Am Rev Respir Dis, 134(4):719-25 1986 Oct
Abstract : Three groups of adult male cynomolgus monkeys (Macaca fascicularis) were exposed to either 200 micrograms/m3 ammonium hexachloroplatinate [(NH4)2PtCl6], 200 micrograms (NH4)2PtCl6 concurrently with 1 ppm ozone (O3), or to 1 ppm O3 only. The animals were exposed by inhalation for 6 h per day, 5 days per week for 12 wk. The experimental design included methacholine preexposure and Na2PtCl6 bronchoprovocation challenge evaluations, Na2PtCl6 threshold skin tests, and sera for analyses of antibodies. Two weeks after the 12-wk exposures, these same indices were reevaluated. Baseline pulmonary function was not significantly affected by the exposure regimens; however, the combination of exposure to O3 and (NH4)2PtCl6 significantly reduced the concentration of platinum (Pt) salt and methacholine necessary to increase average pulmonary flow resistance (RL) 200% (EC200 RL). Ozone or Pt exposure alone had no significant effect on these parameters. Platinum and methacholine EC200 RL values were highly correlated for both Pt-exposed groups after exposure. These data indicated that combined O3 and Pt exposure significantly increased specific (Pt) and nonspecific (methacholine) bronchial hyperreactivity more often than did exposure to either O3 or the Pt salt alone. Combined O3 plus Pt exposure also significantly increases the incidence of positive Pt skin tests when compared with the other exposure groups. Similar to the human experience, radioallergosorbent testing (RAST) for Pt-specific antibodies was not as sensitive as direct skin testing in identifying allergic persons.