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Early-life ozone exposure associated with asthma without sensitization in Latino children

2016; Elsevier BV; Volume: 138; Issue: 6 Linguagem: Inglês

10.1016/j.jaci.2016.03.058

1097-6825

Katherine K. Nishimura, Kensho Iwanaga, Sam S. Oh, María Pino-Yanes, Celeste Eng, Anjeni Keswani, Lindsey A. Roth, Elizabeth A. Nguyen, Shannon Thyne, Harold J. Farber, Denise Serebrisky, Kelley Meade, Michael A. LeNoir, William Rodríguez-Cintrón, Luisa N. Borrell, Kirsten Bibbins‐Domingo, Fred Lurmann, Śaunak Sen, José Rodríguez‐Santana, Emerita Brigino-Buenaventura, Pedro C. Avila, John R. Balmes, Rajesh Kumar, Esteban G. Burchard,

Indoor Air Quality and Microbial Exposure

The prevalence and risk factors of atopy vary across Latino subgroups.1Kumar R. Nguyen E.A. Roth L.A. Oh S.S. Gignoux C.R. Huntsman S. et al.Factors associated with degree of atopy in Latino children in a nationwide pediatric sample: the Genes-environments and Admixture in Latino Asthmatics (GALA II) study.J Allergy Clin Immunol. 2013; 132: 896-905.e1Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar However, few studies have been conducted on an entirely Latino population to corroborate these trends and identify reasons for potential differences. The hypothesis that traffic-related air pollution exposures increases the risk for atopy has been previously examined, with some studies supporting2Bowatte G. Lodge C. Lowe A.J. Erbas B. Perret J. Abramson M.J. et al.The influence of childhood traffic-related air pollution exposure on asthma, allergy and sensitization: a systematic review and a meta-analysis of birth cohort studies.Allergy. 2015; 70: 245-256Crossref PubMed Scopus (298) Google Scholar and others refuting3Gruzieva O. Bellander T. Eneroth K. Kull I. Mel en E. Nordling E. et al.Traffic-related air pollution and development of allergic sensitization in children during the first 8 years of life.J Allergy Clin Immunol. 2012; 129: 240-246Abstract Full Text Full Text PDF PubMed Scopus (95) Google Scholar the association. Given the mixed findings, it may be beneficial to assess this topic in minorities because they often live in or near urban areas where pollution exposures are higher.4Metzger R. Delgado J.L. Herrell R. Environmental health and Hispanic children.Environ Health Perspect. 1995; 103: 25-32Crossref PubMed Scopus (46) Google Scholar, 5Miranda M.L. Edwards S.E. Keating M.H. Paul C.J. Making the environmental justice grade: the relative burden of air pollution exposure in the United States.Int J Environ Res Public Health. 2011; 8: 1755-1771Crossref PubMed Scopus (164) Google Scholar We sought to test the hypothesis that early-life air pollution exposures were associated with atopic status among children with asthma by performing a secondary analyses on data collected from Genes-environments & Admixture in Latino Americans (GALA II) study, the largest domestic gene-environment case-control study of asthma in minority children. Briefly, 8- to 21-year-old individuals who self-identified as Latino and had 4 Latino grandparents were recruited from 5 urban regions (Chicago, Illinois; Bronx, New York; Houston, Texas; San Francisco Bay Area, California; and Puerto Rico). Participants were classified into 1 of 3 Latino subgroups: Mexican American, Puerto Rican, or Other (South American, Central American, non–Puerto Rican Caribbean, or mixed ancestry). Asthma cases had a history of physician-diagnosed asthma but no reported history of other lung disease or chronic illness. Controls had no reported history of asthma, other lung disease, chronic illness, or atopic disease (eczema, allergic rhinitis) and were 1:1 frequency matched with cases within each recruitment center. Local institutional review boards approved the study, and written informed consent was obtained from all parents/participants. A detailed description of the methods has previously been published.6Nishimura K.K. Galanter J.M. Roth L.A. Oh S.S. Thakur N. Nguyen E.A. et al.Early-life air pollution and asthma risk in minority children: the GALA II and SAGE II studies.Am J Respir Crit Care Med. 2013; 188: 309-318Crossref PubMed Scopus (193) Google Scholar Atopic sensitization was defined as demonstrating at least 1 positive allergy skin test reaction to a panel of 14 environmental allergens using the Multi-Test II device (Lincoln Diagnostics, Decatur, Ill). The allergy skin test was considered valid if the histamine positive control had surrounding erythema and its wheal diameter was at least 3 mm greater than the wheal diameter of the saline negative control. A reaction to a specific allergen was considered positive if the allergen caused erythema surrounding the wheal with a diameter that was at least 3 mm greater than the diameter of the negative control wheal. Those with allergy skin tests who failed to pass quality control measures were excluded from the analysis. Measurements for ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), and particulate matter with aerodynamic diameter of 10 μm or less (PM10) and 2.5 μm or less (PM2.5) were obtained from the US Environmental Protection Agency Air Quality System.7Air Quality System (AQS). Available at: https://www.epa.gov/aqs. Accessed June 7, 2011.Google Scholar Individual exposures were estimated by calculating the inverse distance-squared weighted average of all available values from the 4 closest monitoring stations (within 50 km) of where the subject resided during the first year of life. If the child moved during the first year of life, a weighted average of the pollution estimates was based on the number of months spent at each residence. The distribution of pollution exposures is available in Table E1 in this article's Online Repository at www.jacionline.org. To reduce bias due to the case-control study design, statistical analyses were restricted to asthma cases only. Chi-square tests compared the proportion of atopy between Latino subgroups. Multivariate logistic regressions were used to evaluate associations between each first year of life pollution exposure and atopic status. All regressions were controlled for age, sex, ethnicity, recruitment region, percent of African genetic ancestry, maternal in utero smoking, and socioeconomic status. Analyses were performed using Stata13 (StataCorp, College Station, Tex) and R (R Foundation for Statistical Computing, Vienna, Austria). The GALA II study enrolled 4157 children from 2006 to 2011. After excluding controls (n = 2135), those missing essential covariates (n = 468), those with invalid allergy skin test results (n = 392), and those missing air pollution estimates (n = 130), the final sample included 1032 children with asthma (Table I). There were no substantial differences in the percent of atopy between the 4 mainland US recruitment sites (ranging from 72% in the San Francisco Bay Area, Calif, to 79% in Houston, Tex) or between mainland Latino subgroups (ranging from 75% in Mexican Americans to 81% in Other Latinos). However, the prevalence of atopy was significantly lower among Puerto Ricans who were living in Puerto Rico (52%). Although these differences were statistically significant, 55% of allergy skin test results from Puerto Rico were invalid because of poor responses to the histamine positive control and the results must be interpreted with caution.Table IEligible participants in the GALA II studyVariableAsthma cases, n (%)Total1032 (100)Recruitment region Chicago, Ill232 (22.5) Houston, Tex151 (14.6) Bronx, NY177 (17.2) Puerto Rico264 (25.6) San Francisco Bay Area, Calif208 (20.2)Age (y), mean ± SD12.5 ± 3.2Sex Male585 (56.7) Female447 (43.3)Latino subgroup Mexican American427 (41.4) Puerto Rican359 (34.8) Other Latino∗Other Latino includes those with self-reported ethnicity of South American, Central American, non–Puerto Rican Caribbean, or mixed Latino.246 (23.8)SES composite score†SES composite score is based on the level of maternal education, annual household income, and the type of medical insurance. 3-4184 (17.8%) 5-6543 (52.6%) 7-9305 (23.8%)Family history of atopy‡Family history of atopy is defined as having 1 or more parent ever being diagnosed with allergic rhinitis, eczema, or asthma. Yes546 (52.9) No486 (47.1)Atopic (based on allergy skin tests) Yes726 (70.4) No306 (29.7)Percent African genetic ancestry, mean ± SD13.1 ± 12.7Maternal in utero smoking No976 (94.6) Yes56 (5.4)Lung function, mean SD§Lung function was measured in asthma cases only. FEV1 (L)2.5 ± 0.9 FVC (L)2.9 ± 1.0 FEV1/FVC (%)84.0 ± 7.4 FEF25-75 (L/s)2.6 ± 1.1Birth state same as current state Yes978 (94.8) No54 (5.2)FEF25-75, Forced expiratory flow between 25% and 75% of vital capacity (L/s); FVC, forced vital capacity (L); SES, socioeconomic status.∗ Other Latino includes those with self-reported ethnicity of South American, Central American, non–Puerto Rican Caribbean, or mixed Latino.† SES composite score is based on the level of maternal education, annual household income, and the type of medical insurance.‡ Family history of atopy is defined as having 1 or more parent ever being diagnosed with allergic rhinitis, eczema, or asthma.§ Lung function was measured in asthma cases only. Open table in a new tab FEF25-75, Forced expiratory flow between 25% and 75% of vital capacity (L/s); FVC, forced vital capacity (L); SES, socioeconomic status. First year of life exposures to NO2, PM10, PM2.5, or SO2 were not associated with atopic status (Table II). However patients with asthma without allergic sensitization were more likely to be exposed to higher levels of ozone during their first year of life compared with those with atopic asthma (adjusted odds ratio, 1.32; 95% CI, 1.11-1.57; P = .002). For every 5-ppb increase in average ozone exposure during the first year of life, the odds for having asthma without sensitization increased by 32%. The odds ratio was not significantly changed in sensitivity analyses when the following subsets were excluded: (1) patients with asthma recruited from Puerto Rico, (2) patients with asthma who had moved away from their birth state, and (3) pollution outliers (patients with asthma with the top and bottom 5% of exposure values).Table IIAdjusted ORs for the association between atopic status and first year of life exposure to air pollutionPollutantOR95% CIP valuen24-h NO2 (ppb)1.060.89-1.26.529378-h O3 (ppb)1.32∗Results at a significant Bonferroni-corrected α value of 0.01.1.11-1.57∗Results at a significant Bonferroni-corrected α value of 0.01..002∗Results at a significant Bonferroni-corrected α value of 0.01.768∗Results at a significant Bonferroni-corrected α value of 0.01.24-h PM10 (μg/m3)1.020.89-1.78.77102724-h PM2.5 (μg/m3)0.890.42-1.87.7639224-h SO2 (ppb)0.990.92-1.07.85989Reference group = atopic (allergic sensitization as demonstrated by at least 1 positive allergy skin test reaction to a panel of 14 environmental allergens). Comparison group = nonatopic (no positive allergy skin test results).Models are adjusted for age, sex, SES, ethnicity, recruitment region, proportion of global African ancestry, and maternal in utero smoking. All pollutants are scaled to represent a 5-unit change in exposure, except SO2 (1-ppb change).OR, Odds ratio; SES, socioeconomic status.∗ Results at a significant Bonferroni-corrected α value of 0.01. Open table in a new tab Reference group = atopic (allergic sensitization as demonstrated by at least 1 positive allergy skin test reaction to a panel of 14 environmental allergens). Comparison group = nonatopic (no positive allergy skin test results). Models are adjusted for age, sex, SES, ethnicity, recruitment region, proportion of global African ancestry, and maternal in utero smoking. All pollutants are scaled to represent a 5-unit change in exposure, except SO2 (1-ppb change). OR, Odds ratio; SES, socioeconomic status. Our findings suggest that children with asthma without allergic sensitization were more likely to be exposed to higher levels of ozone pollution during their first year of life compared with children with atopic asthma. Experimental studies in those with asthma have shown that acute exposure to ozone stimulates airway neutrophilia,8Drews A.C. Pizzichini M.M.M. Pizzichini E. Pereira M.U. Pitrez P.M. Jones M.H. et al.Neutrophilic airway inflammation is a main feature of induced sputum in nonatopic asthmatic children.Allergy. 2009; 64: 1597-1601Crossref PubMed Scopus (54) Google Scholar, 9Basha M.A. Gross K.B. Gwizdala C.J. Haidar A.H. Popovich J. Bronchoalveolar lavage neutrophilia in asthmatic and healthy volunteers after controlled exposure to ozone and filtered purified air.Chest. 1994; 106: 1757-1765Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar a characteristic though not necessarily a specific feature of asthma without sensitization. Because our analysis used data from a case-control study, our samples may not be representative of the underlying population or generalizable to the population of US Latinos. It is not immediately clear whether ozone exposure in subsequent years might have contributed to risk for sensitization. Nevertheless, our study benefits from analyzing a very large and diverse Latino population recruited from multiple regions in the United States. Although additional studies are needed to confirm these findings, our results suggest that ozone air pollution may partially account for the prevalence of asthma without sensitization in Latino children. These controversial findings might have emerged from interactions with the assessed geographic areas or neighborhoods. Because minorities such as various Latino subgroups often live in or near urban areas where they are disproportionally impacted by air pollution, they should be studied separately and reducing exposures in Latino communities may prevent similar asthma cases. We acknowledge the families and patients for their participation and thank the numerous health care providers and community clinics for their support and participation in the GALA II study. In particular, we thank the study coordinator Sandra Salazar, and the study recruiters: Duanny Alva, Gaby Ayala-Rodriguez, Ulysses Burley, Lisa Caine, Elizabeth Castellanos, Jaime Colon, Denise DeJesus, Iliana Flexas, Blanca Lopez, Brenda Lopez, Louis Martos, Vivian Medina, Juana Olivo, Mario Peralta, Esther Pomares, Jihan Quraishi, Johanna Rodriguez, Shahdad Saeedi, Dean Soto, Ana Taveras, and Emmanuel Viera. Table E1First year of life air pollution exposures among eligible participants compared with the EPA air quality standardsPollutantGALAEPA NAAQSNO2, ppb (24-h average)53∗Annual mean. Mean ± SD21.8 ± 8.7 25th15.5 50th21.5 75th28.6O3, ppb (8-h maximum)NAS Mean ± SD29.5 ± 6.6 25th25.5 50th28.3 75th33.5PM10 (μg/m3) (24-h average)NAS Mean ± SD29.2 ± 6.0 25th24.8 50th28.4 75th33.1PM2.5 (μg/m3) (24-h average)12†Annual mean, over 3 years. Mean ± SD12.9 ± 3.6 25th10.4 50th12.9 75th15.6SO2 (ppb) (24-h average)30∗Annual mean. Mean ± SD5.0 ± 3.8 25th2.2 50th4.0 75th5.7Data from US-EPA (United States Environmental Protection Agency, National Ambient Air Quality Standards: http://www.epa.gov/air/criteria.html).EPA NAAQS, US Environmental Protection Agency National Ambient Air Quality Standards; NAS, no annual standard; ppb, parts per billion; PM10, particulate matter with aerodynamic diameter of ≤10 μm; PM2.5, particulate matter with aerodynamic diameter of ≤2.5 μm.∗ Annual mean.† Annual mean, over 3 years. Open table in a new tab Data from US-EPA (United States Environmental Protection Agency, National Ambient Air Quality Standards: http://www.epa.gov/air/criteria.html). EPA NAAQS, US Environmental Protection Agency National Ambient Air Quality Standards; NAS, no annual standard; ppb, parts per billion; PM10, particulate matter with aerodynamic diameter of ≤10 μm; PM2.5, particulate matter with aerodynamic diameter of ≤2.5 μm.