***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Acute exposure to ozone has been related to a wide spectrum of health effects in susceptible individuals . Genetic factors may influence interindividual variation in ozone response . The current authors investigated the relationships between common polymorphisms in two genes involved in response to oxidative stress , i.e. glutathione S-transferases M1 ( GSTM1 ) and P1 ( GSTP1 ) , and both respiratory symptoms and lung function in response to ozone among childhood asthmatics . A total of 151 asthmatic children , who were participants in a r and omised controlled trial of antioxidant vitamin supplementation in Mexico City , were studied . Children were genotyped using PCR methods and followed from October 1998–April 2000 . Increases in reported breathing difficulty were associated with ozone exposure in children with GSTM1 null ( 8 % , 95 % confidence interval ( CI ) 1–15 % , per 20-ppb increase in 1-h maximum daily average over 7 days ) or GSTP1 Valine/Valine ( Val/Val ) genotypes ( 14 % , 95 % CI 5–25 % ) . In children with both GSTM1 null and GSTP1 Val/Val genotypes , the increase in breathing difficulty associated with a 20-ppb increase in ozone exposure was even greater ( 21 % , 95 % CI 5–39 % ) . GSTP1 genotypes were not significantly associated with ozone-related lung function changes . In conclusion , asthmatic children with glutathione S-transferase M1 null and glutathione S-transferase P1 Valine/Valine genotypes appear more susceptible to developing respiratory symptoms related to ozone exposure BACKGROUND We recently reported that antioxidant supplementation with vitamins C and E mitigated ozone related decline in forced expiratory flow ( FEF(25 - 75 ) ) in 158 asthmatic children in an area with high ozone exposure in Mexico City . METHODS A study was undertaken to determine whether deletion of glutathione S-transferase M1 ( GSTM1 null genotype ) , a gene involved in response to oxidative stress , influences ozone related decline in FEF(25 - 75 ) and the benefit of antioxidant supplementation . RESULTS GSTM1 null children receiving placebo had significant ozone related decrements in FEF(25 - 75 ) ( percentage change per 50 ppb of ozone 2.9 ( 95 % CI -5.2 to -0.6 ) , p=0.01 ) ; GSTM1 positive children did not . Conversely , the effect of antioxidants  was stronger in children with the GSTM1 null genotype . CONCLUSIONS Asthmatic children with a genetic deficiency of GSTM1 may be more susceptible to the deleterious effects of ozone on the small airways and might derive greater benefit from antioxidant supplementation RATIONALE Although it is widely assumed that the incidence of childhood respiratory allergies to common aeroallergens is directly related to allergen exposure in early life , few longitudinal studies have investigated this issue , and available data are scarce and mainly limited to high-risk groups . OBJECTIVES To assess , in a prospect i ve manner and in a general population , the role of early life exposures to Der p1 and Fel d1 on the inception of sensitization and asthma . METHODS Pregnant women and their children were recruited for the Asthma Multicentre Infant Cohort Study . Overall , 1,611 newborns were initially enrolled in three cohorts in the United Kingdom and Spain .  Der p1 and Fel d1 allergens were measured in household dust sample s at 3 months of age for 1,474 ( 91.5 % ) participants , and skin prick tests were performed at 6 years of age on 1,182 ( 80.2 % ) participants . Wheeze and diagnosed asthma were reported in yearly question naires . MEASUREMENTS AND MAIN RESULTS Exposure to Der p1 early in life was not related to a positive specific prick test or to asthma or persistent wheeze at 6 years of age . Fel d1 showed an association with all these outcomes ( third vs. first tertile ; odds ratio , 4.43 for positive specific prick test and 2.6 for diagnosed asthma ) . CONCLUSIONS Dose-response relationships between allergen exposure and sensitization or asthma may be allergen specific and nonlinear ; a minimum threshold level is needed to induce sensitization , but no dose-response relationship exists above this level . The effect of a particular allergen seems to be similar on atopy and asthma inception RATIONALE Secondh and tobacco smoke ( SHS ) and traffic-related air pollutants are associated with asthma and allergy . Diesel exhaust particles ( DEPs ) and SHS can interact with allergens in exacerbating allergic airway diseases through generation of reactive oxygen species . Glutathione S-transferases ( GSTs ) metabolize reactive oxygen species and detoxify electrophilic xenobiotics present in SHS and DEPs . OBJECTIVES We tested the hypotheses that functional GSTM1-null genotype and GSTP1 codon 105 variants ( Ile105 and Val105 ) are determinants of allergic responses to SHS , and that responses to SHS and DEPs are correlated . METHODS AND MEASUREMENTS In a r and omized , placebo-controlled crossover trial , 19 ragweed allergen-sensitive subjects who had previously participated in a DEP trial were challenged intranasally with allergen after having been exposed to either clean air or SHS at separate visits .  Nasal allergen-specific IgE , histamine , IL-4 , and IFN-gamma levels were measured before and after allergen challenge . MAIN RESULTS Individuals with GSTM1-null or GSTP1 Ile105 genotypes showed larger nasal responses to allergens with SHS compared with clean air . GSTM1-null subjects had a larger increase in IgE than GSTM1-present subjects ( median , 173.3 vs. 46.7 U/ml ; p = 0.03 ) , and the Ile105 GSTP1 genotype subjects had increased histamine ( median , 10.2 vs. 4.6 nM ; p = 0.01 ) after SHS plus allergen challenge . Responses to SHS and DEPs were correlated . Enhancement of IgE and histamine was greatest in the subjects with both the GSTM1-null and GSTP1 Ile/Ile genotypes . CONCLUSIONS GSTM1 and GSTP1 are important cytoprotective factors that reduce SHS and DEP exacerbation of allergic responses We determined the prevalence of GSTP1-Ile105 and GSTP1-Val105 alleles in patients with bronchial asthma and atopic dermatitis and healthy children of 2 groups ( r and omized and nonatopic control ) . The GSTP1-Ile105/Val105 genotype determines the resistance to atopic dermatitis ( odds ratio=0.51 ; 95 % confidence interval : 0.28 - 0.92 ; p=0.023 ) . However , both homozygotes are at high risk of developing atopic dermatitis ( near-significant differences ) The impact of domestic exposure to cat allergen ( Fel d1 ) and house dust mite ( Der p1 ) on  wheezing from birth to the age of 4 years was investigated in a multicenter prospect i ve birth cohort ; 1,611 mothers were recruited before delivery in Ashford , Engl and , and Barcelona and Menorca , Spain . Exposures were gathered via dust sample collection at children 's home in their first year of life . Families provided complete outcome data ( wheezing status in all 4 years ) for 1,289 children . Domestic allergen levels varied substantially between centers . Six hundred three ( 47 % ) children never wheezed during their first 4 years of life . Der p1 did not correlate with any type of wheezing outcome . Fel d1 significantly increased the risk of wheezing in 3- and 4-year-olds in comparison to 1-year-olds . Distinct risk profiles were found for wheezing at different ages . Multivariate analysis revealed an interaction between Fel d1 and maternal asthma among children who wheeze in Year 4 ( relative risk = 2.77 ; 95 % confidence interval = 1.19 - 6.46 ) . Our data support the idea that several patterns of wheezing with different risk profiles exist among young children . The effect of Fel d1 exposure varied according to age and maternal asthma 
    Output:
    
Meta- analysis of GSTP1 Ile105Val ( n = 17 ) and asthma suggested a possible protective effect of the Val allele , but heterogeneity was extreme .
Few studies evaluated wheezing and BHR and most reported no associations , although weak evidence was found for positive associations of GSTM1 null and GSTP1 Val allele with wheezing and a negative association of GSTP1 Val allele with BHR .
CONCLUSIONS Our findings do not support a substantial role of GST genes alone in the development of asthma .