Advertisement

Exposure to bisphenols and asthma morbidity among low-income urban children with asthma

      Background

      Bisphenol A (BPA) has been linked with pediatric asthma development and allergic airway inflammation in animal models. Whether exposure to BPA or its structural analogs bisphenol S (BPS) and bisphenol F (BPF) is associated with asthma morbidity remains unknown.

      Objective

      We examined associations between bisphenols and morbidity due to pediatric asthma.

      Methods

      We quantified concentrations of BPA, BPS, and BPF in 660 urine samples from 148 predominantly low-income, African American children (aged 5-17 years) with established asthma. We used biobanked biospecimens and data on symptoms, health care utilization, and pulmonary function and inflammation that were collected every 3 months over the course of a year. We used generalized estimating equations to examine associations between concentrations or detection of urinary bisphenols and morbidity outcomes and assessed heterogeneity of associations by sex.

      Results

      We observed consistent positive associations between BPA exposure and measures of asthma morbidity. For example, we observed increased odds of general symptom days (adjusted odds ratio [aOR] = 1.40 [95% C = 1.02-1.92]), maximal symptom days (aOR = 1.36 [95% CI = 1.00-1.83]), and emergency department visits (aOR = 2.12 [95% CI =1.28-3.51]) per 10-fold increase in BPA concentration. We also observed evidence of sexually dimorphic effects; BPA concentrations were associated with increased odds of symptom days and health care utilization only among boys. Findings regarding BPS and BPF did not consistently point to associations with asthma symptoms or health care utilization.

      Conclusion

      We found evidence to suggest that BPA exposure in a predominantly low-income, minority pediatric cohort is associated with asthma morbidity and that associations may differ by sex. Our findings support additional studies, given the high pediatric asthma burden and widespread exposure to BPA in the United States.

      Graphical abstract

      Key words

      Abbreviations used:

      aOR (Adjusted odds ratio), BPA (Bisphenol A), BPF (Bisphenol F), BPS (Bisphenol S), BMI (Body mass index), ED (Emergency department), EDC (EDC endocrine-disrupting compound), Feno (Fraction of exhaled nitric oxide), GM (Geometric mean), ICC (Intraclass correlation coefficient), LOD (Limit of detection), MAACS (Mouse Allergen and Asthma Cohort Study), NHANES (National Health and Nutrition Examination Survey)
      To read this article in full you will need to make a payment

      References

      1. Biomonitoring summary: bisphenol A. US Centers for Disease Control and Prevention National Biomonitoring Program.
        (Available at:) (Accessed August 13, 2019)
        • Vandenberg L.N.
        • Colborn T.
        • Hayes T.B.
        • Heindel J.J.
        • Jacobs Jr., D.R.
        • Lee D.H.
        • et al.
        Regulatory decisions on endocrine disrupting chemicals should be based on the principles of endocrinology.
        Reprod Toxicol. 2013; 38: 1-15
        • Ruiz D.
        • Becerra M.
        • Jagai J.S.
        • Ard K.
        • Sargis R.M.
        Disparities in environmental exposures to endocrine-disrupting chemicals and diabetes risk in vulnerable populations.
        Diabetes Care. 2018; 41: 193-205
        • Nelson J.W.
        • Scammell M.K.
        • Hatch E.E.
        • Webster T.F.
        Social disparities in exposures to bisphenol A and polyfluoroalkyl chemicals: a cross-sectional study within NHANES 2003-2006.
        Environ Health. 2012; 11: 10
      2. Fourth report on human exposure to environmental chemicals. Updated tables. January 2019. US Centers for Disease Control and Prevention (CDC).
        (Available at:) (Accessed August 13, 2019)
        • von Goetz N.
        • Wormuth M.
        • Scheringer M.
        • Hungerbuhler K.
        Bisphenol A: how the most relevant exposure sources contribute to total consumer exposure.
        Risk Anal. 2010; 30: 473-487
        • Larson N.I.
        • Story M.T.
        • Nelson M.C.
        Neighborhood environments: disparities in access to healthy foods in the U.S.
        Am J Prev Med. 2009; 36: 74-81
        • Chalubinski M.
        • Kowalski M.L.
        Endocrine disrupters--potential modulators of the immune system and allergic response.
        Allergy. 2006; 61: 1326-1335
        • Koike E.
        • Yanagisawa R.
        • Win-Shwe T.T.
        • Takano H.
        Exposure to low-dose bisphenol A during the juvenile period of development disrupts the immune system and aggravates allergic airway inflammation in mice.
        Int J Immunopathol Pharmacol. 2018; 322058738418774897
        • Yan H.
        • Takamoto M.
        • Sugane K.
        Exposure to bisphenol A prenatally or in adulthood promotes T(H)2 cytokine production associated with reduction of CD4CD25 regulatory T cells.
        Environ Health Perspect. 2008; 116: 514-519
        • Lee M.H.
        • Chung S.W.
        • Kang B.Y.
        • Park J.
        • Lee C.H.
        • Hwang S.Y.
        • et al.
        Enhanced interleukin-4 production in CD4+ T cells and elevated immunoglobulin E levels in antigen-primed mice by bisphenol A and nonylphenol, endocrine disruptors: involvement of nuclear factor-AT and Ca2+.
        Immunology. 2003; 109: 76-86
        • Sawai C.
        • Anderson K.
        • Walser-Kuntz D.
        Effect of bisphenol A on murine immune function: modulation of interferon-gamma, IgG2a, and disease symptoms in NZB X NZW F1 mice.
        Environ Health Perspect. 2003; 111: 1883-1887
        • Tian X.
        • Takamoto M.
        • Sugane K.
        Bisphenol A promotes IL-4 production by Th2 cells.
        Int Arch Allergy Immunol. 2003; 132: 240-247
        • Wang Y.X.
        • Liu C.
        • Shen Y.
        • Wang Q.
        • Pan A.
        • Yang P.
        • et al.
        Urinary levels of bisphenol A, F and S and markers of oxidative stress among healthy adult men: variability and association analysis.
        Environ Int. 2019; 123: 301-309
        • Xin F.
        • Jiang L.
        • Liu X.
        • Geng C.
        • Wang W.
        • Zhong L.
        • et al.
        Bisphenol A induces oxidative stress-associated DNA damage in INS-1 cells.
        Mutat Res Genet Toxicol Environ Mutagen. 2014; 769: 29-33
        • Cho Y.S.
        • Moon H.B.
        The role of oxidative stress in the pathogenesis of asthma.
        Allergy Asthma Immunol Res. 2010; 2: 183-187
        • Scioscia G.C.G.
        • Lacedonia D.
        • Cotugno G.
        • Santamaria S.
        • Venuti M.
        • Depalo A.
        • Colanardi M.
        • Barbaro M.
        Searching for inflammatory and oxidative-stress markers capable of clustering severe asthma [abstract].
        Eur Respir J. 2018; 52OA3584
        • Kuiper G.G.
        • Lemmen J.G.
        • Carlsson B.
        • Corton J.C.
        • Safe S.H.
        • van der Saag P.T.
        • et al.
        Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta.
        Endocrinology. 1998; 139: 4252-4263
        • Hiroi H.
        • Tsutsumi O.
        • Momoeda M.
        • Takai Y.
        • Osuga Y.
        • Taketani Y.
        Differential interactions of bisphenol A and 17beta-estradiol with estrogen receptor alpha (ERalpha) and ERbeta.
        Endocr J. 1999; 46: 773-778
        • Welshons W.V.
        • Nagel S.C.
        • vom Saal F.S.
        Large effects from small exposures. III. Endocrine mechanisms mediating effects of bisphenol A at levels of human exposure.
        Endocrinology. 2006; 147: S56-S69
        • Uemura Y.
        • Liu T.Y.
        • Narita Y.
        • Suzuki M.
        • Matsushita S.
        17 Beta-estradiol (E2) plus tumor necrosis factor-alpha induces a distorted maturation of human monocyte-derived dendritic cells and promotes their capacity to initiate T-helper 2 responses.
        Hum Immunol. 2008; 69: 149-157
        • Bonds R.S.
        • T M-H
        Estrogen effects in allergy and asthma.
        Curr Opin Allergy Clin Immunol. 2013; 13
        • Bonefeld-Jorgensen E.C.
        • Long M.
        • Hofmeister M.V.
        • Vinggaard A.M.
        Endocrine-disrupting potential of bisphenol A, bisphenol A dimethacrylate, 4-n-nonylphenol, and 4-n-octylphenol in vitro: new data and a brief review.
        Environ Health Perspect. 2007; 115: 69-76
        • Donohue K.M.
        • Miller R.L.
        • Perzanowski M.S.
        • Just A.C.
        • Hoepner L.A.
        • Arunajadai S.
        • et al.
        Prenatal and postnatal bisphenol A exposure and asthma development among inner-city children.
        J Allergy Clin Immunol. 2013; 131: 736-742
        • Kim K.N.
        • Kim J.H.
        • Kwon H.J.
        • Hong S.J.
        • Kim B.J.
        • Lee S.Y.
        • et al.
        Bisphenol A exposure and asthma development in school-age children: a longitudinal study.
        PLoS One. 2014; 9e111383
        • Wang I.J.
        • Chen C.Y.
        • Bornehag C.G.
        Bisphenol A exposure may increase the risk of development of atopic disorders in children.
        Int J Hyg Environ Health. 2016; 219: 311-316
        • Bloom B.
        • Jones L.
        • Freeman G.
        Summary Health Statistics for U.S. Children: National Health Interview Survey, 2012. National Center for Health Statistics.
        Vital Health Stat. 2013; 10: 1-81
        • Milligan K.L.
        • Matsui E.
        • Sharma H.
        Asthma in urban children: epidemiology, environmental risk factors, and the public health domain.
        Curr Allergy Asthma Rep. 2016; 16: 33
        • Clark E.
        Sulfolane and sulfones.
        John Wiley & Sons, New York2012
      3. Biomonitoring California: p,p’-Bisphenols and Diglycidyl Ethers of p,p’-Bisphenols. Office of Environmental Health Hazards Assessment.
        (Available at:)
        • Liao C.
        • Kannan K.
        A survey of alkylphenols, bisphenols, and triclosan in personal care products from China and the United States.
        Arch Environ Contam Toxicol. 2014; 67: 50-59
        • Liao C.
        • Liu F.
        • Kannan K.
        Bisphenol S, a new bisphenol analogue, in paper products and currency bills and its association with bisphenol a residues.
        Environmental science & technology. 2012; 46: 6515-6522
        • Liao C.
        • Kannan K.
        Concentrations and profiles of bisphenol A and other bisphenol analogues in foodstuffs from the United States and their implications for human exposure.
        J Agric Food Chem. 2013; 61: 4655-4662
        • Michalowicz J.
        • Mokra K.
        • Bak A.
        Bisphenol A and its analogs induce morphological and biochemical alterations in human peripheral blood mononuclear cells (in vitro study).
        Toxicol In Vitro. 2015; 29: 1464-1472
        • Qiu W.
        • Shao H.
        • Lei P.
        • Zheng C.
        • Qiu C.
        • Yang M.
        • et al.
        Immunotoxicity of bisphenol S and F are similar to that of bisphenol A during zebrafish early development.
        Chemosphere. 2018; 194: 1-8
      4. National Asthma Educationand Prevention Program Expert Panel Report 3. Guidelines for the diagnosis and management of asthma. NIH Publication No. 08-5846. National Heart, Lung, and Blood Institute. Available at: https://www.nhlbi.nih.gov/files/docs/guidelines/asthsumm.pdf. In: U.S. Department of Health and Human Services. National Institues of Health NH, Lung, and Blood Institute, editor 2007. Accessed August 13, 2019.

        • Ahluwalia S.K.
        • Peng R.D.
        • Breysse P.N.
        • Diette G.B.
        • Curtin-Brosnan J.
        • Aloe C.
        • et al.
        Mouse allergen is the major allergen of public health relevance in Baltimore City.
        J Allergy Clin Immunol. 2013; 132: 830-835.e1-2
        • Lu K.D.
        • Breysse P.N.
        • Diette G.B.
        • Curtin-Brosnan J.
        • Aloe C.
        • Williams D.L.
        • et al.
        Being overweight increases susceptibility to indoor pollutants among urban children with asthma.
        J Allergy Clin Immunol. 2013; 131 (23 e1-3): 1017-1023
        • Matsui E.C.
        • Simons E.
        • Rand C.
        • Butz A.
        • Buckley T.J.
        • Breysse P.
        • et al.
        Airborne mouse allergen in the homes of inner-city children with asthma.
        J Allergy Clin Immunol. 2005; 115: 358-363
        • McCormack M.C.
        • Breysse P.N.
        • Matsui E.C.
        • Hansel N.N.
        • Peng R.D.
        • Curtin-Brosnan J.
        • et al.
        Indoor particulate matter increases asthma morbidity in children with non-atopic and atopic asthma.
        Ann Allergy Asthma Immunol. 2011; 106: 308-315
        • Morgan W.J.
        • Crain E.F.
        • Gruchalla R.S.
        • O'Connor G.T.
        • Kattan M.
        • Evans 3rd, R.
        • et al.
        Results of a home-based environmental intervention among urban children with asthma.
        N Engl J Med. 2004; 351: 1068-1080
        • Quanjer P.H.
        • Stanojevic S.
        • Cole T.J.
        • Baur X.
        • Hall G.L.
        • Culver B.H.
        • et al.
        Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations.
        Eur Respir J. 2012; 40: 1324-1343
        • American Thoracic Society, European Respiratory Society
        ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005.
        Am J Respir Crit Care Med. 2005; 171: 912-930
        • Cabaton N.
        • Zalko D.
        • Rathahao E.
        • Canlet C.
        • Delous G.
        • Chagnon M.C.
        • et al.
        Biotransformation of bisphenol F by human and rat liver subcellular fractions.
        Toxicol In Vitro. 2008; 22: 1697-1704
        • Dumont C.
        • Perdu E.
        • de Sousa G.
        • Debrauwer L.
        • Rahmani R.
        • Cravedi J.P.
        • et al.
        Bis(hydroxyphenyl)methane-bisphenol F-metabolism by the HepG2 human hepatoma cell line and cryopreserved human hepatocytes.
        Drug Chem Toxicol. 2011; 34: 445-453
        • Ji K.
        • Hong S.
        • Kho Y.
        • Choi K.
        Effects of bisphenol S exposure on endocrine functions and reproduction of zebrafish.
        Environ Sci Technol. 2013; 47: 8793-8800
        • Gramec Skledar D.
        • Troberg J.
        • Lavdas J.
        • Peterlin Masic L.
        • Finel M.
        Differences in the glucuronidation of bisphenols F and S between two homologous human UGT enzymes, 1A9 and 1A10.
        Xenobiotica. 2015; 45: 511-519
        • Hanioka N.
        • Naito T.
        • Narimatsu S.
        Human UDP-glucuronosyltransferase isoforms involved in bisphenol A glucuronidation.
        Chemosphere. 2008; 74: 33-36
        • Calafat A.M.
        • Koch H.M.
        • Swan S.H.
        • Hauser R.
        • Goldman L.R.
        • Lanphear B.P.
        • et al.
        Misuse of blood serum to assess exposure to bisphenol A and phthalates.
        Breast Cancer Res. 2013; 15: 403
        • Koch H.M.
        • Kolossa-Gehring M.
        • Schroter-Kermani C.
        • Angerer J.
        • Bruning T.
        Bisphenol A in 24 h urine and plasma samples of the German Environmental Specimen Bank from 1995 to 2009: a retrospective exposure evaluation.
        J Expo Sci Environ Epidemiol. 2012; 22: 610-616
        • Lehmler H.J.
        • Liu B.
        • Gadogbe M.
        • Bao W.
        Exposure to bisphenol A, bisphenol F, and bisphenol S in U.S. adults and children: the National Health and Nutrition Examination Survey 2013-2014.
        ACS Omega. 2018; 3: 6523-6532
        • Ye X.
        • Wong L.Y.
        • Kramer J.
        • Zhou X.
        • Jia T.
        • Calafat A.M.
        Urinary concentrations of bisphenol A and three other bisphenols in convenience samples of U.S. adults during 2000-2014.
        Environ Sci Technol. 2015; 49: 11834-11839
        • Zhou X.
        • Kramer J.P.
        • Calafat A.M.
        • Ye X.
        Automated on-line column-switching high performance liquid chromatography isotope dilution tandem mass spectrometry method for the quantification of bisphenol A, bisphenol F, bisphenol S, and 11 other phenols in urine.
        J Chromatogr B Analyt Technol Biomed Life Sci. 2014; 944: 152-156
        • Lubin J.H.
        • Colt J.S.
        • Camann D.
        • Davis S.
        • Cerhan J.R.
        • Severson R.K.
        • et al.
        Epidemiologic evaluation of measurement data in the presence of detection limits.
        Environ Health Perspect. 2004; 112: 1691-1696
        • Mahalingaiah S.
        • Meeker J.D.
        • Pearson K.R.
        • Calafat A.M.
        • Ye X.
        • Petrozza J.
        • et al.
        Temporal variability and predictors of urinary bisphenol A concentrations in men and women.
        Environ Health Perspect. 2008; 116: 173-178
        • Bhandari R.
        • Xiao J.
        • Shankar A.
        Urinary bisphenol A and obesity in U.S. children.
        Am J Epidemiol. 2013; 177: 1263-1270
        • Liu B.
        • Lehmler H.J.
        • Sun Y.
        • Xu G.
        • Sun Q.
        • Snetselaar L.G.
        • et al.
        Association of bisphenol A and its substitutes, bisphenol F and bisphenol S, with obesity in United States children and adolescents.
        Diabetes Metab J. 2019; 43: 59-75
        • Trasande L.
        • Attina T.M.
        • Blustein J.
        Association between urinary bisphenol A concentration and obesity prevalence in children and adolescents.
        JAMA. 2012; 308: 1113-1121
        • Mohanan S.
        • Tapp H.
        • McWilliams A.
        • Dulin M.
        Obesity and asthma: pathophysiology and implications for diagnosis and management in primary care.
        Exp Biol Med (Maywood). 2014; 239: 1531-1540
      5. Defining childhood obesity 2017 [updated May 3, 2017. US Centers for Disease Control and Prevention.
        (Available at:) (Accessed August 13, 2019)
        • Arasi S.
        • Porcaro F.
        • Cutrera R.
        • Fiocchi A.G.
        Severe asthma and allergy: a pediatric perspective.
        Front Pediatr. 2019; 7: 28
        • Wang H.X.
        • Zhou Y.
        • Tang C.X.
        • Wu J.G.
        • Chen Y.
        • Jiang Q.W.
        Association between bisphenol A exposure and body mass index in Chinese school children: a cross-sectional study.
        Environ Health. 2012; 11: 79
        • Chen Y.
        • Fang J.
        • Ren L.
        • Fan R.
        • Zhang J.
        • Liu G.
        • et al.
        Urinary bisphenol analogues and triclosan in children from south China and implications for human exposure.
        Environ Pollut. 2018; 238: 299-305
        • Teitelbaum S.L.
        • Britton J.A.
        • Calafat A.M.
        • Ye X.
        • Silva M.J.
        • Reidy J.A.
        • et al.
        Temporal variability in urinary concentrations of phthalate metabolites, phytoestrogens and phenols among minority children in the United States.
        Environ Res. 2008; 106: 257-269
        • Hoepner L.A.
        • Whyatt R.M.
        • Just A.C.
        • Calafat A.M.
        • Perera F.P.
        • Rundle A.G.
        Urinary concentrations of bisphenol A in an urban minority birth cohort in New York City, prenatal through age 7 years.
        Environ Res. 2013; 122: 38-44
        • Cooper J.E.
        • Kendig E.L.
        • Belcher S.M.
        Assessment of bisphenol A released from reusable plastic, aluminium and stainless steel water bottles.
        Chemosphere. 2011; 85: 943-947
        • Carwile J.L.
        • Luu H.T.
        • Bassett L.S.
        • Driscoll D.A.
        • Yuan C.
        • Chang J.Y.
        • et al.
        Polycarbonate bottle use and urinary bisphenol A concentrations.
        Environ Health Perspect. 2009; 117: 1368-1372
        • Makris K.C.
        • Andra S.S.
        • Jia A.
        • Herrick L.
        • Christophi C.A.
        • Snyder S.A.
        • et al.
        Association between water consumption from polycarbonate containers and bisphenol A intake during harsh environmental conditions in summer.
        Environ Sci Technol. 2013; 47: 3333-3343
        • Harley K.G.
        • Aguilar Schall R.
        • Chevrier J.
        • Tyler K.
        • Aguirre H.
        • Bradman A.
        • et al.
        Prenatal and postnatal bisphenol A exposure and body mass index in childhood in the CHAMACOS cohort.
        Environ Health Perspect. 2013; 121: 514-520
        • Larsson K.
        • Ljung Bjorklund K.
        • Palm B.
        • Wennberg M.
        • Kaj L.
        • Lindh C.H.
        • et al.
        Exposure determinants of phthalates, parabens, bisphenol A and triclosan in Swedish mothers and their children.
        Environ Int. 2014; 73: 323-333
        • Spanier A.J.
        • Kahn R.S.
        • Kunselman A.R.
        • Hornung R.
        • Xu Y.
        • Calafat A.M.
        • et al.
        Prenatal exposure to bisphenol A and child wheeze from birth to 3 years of age.
        Environ Health Perspect. 2012; 120: 916-920
        • Whyatt R.M.
        • Rundle A.G.
        • Perzanowski M.S.
        • Just A.C.
        • Donohue K.M.
        • Calafat A.M.
        • et al.
        Prenatal phthalate and early childhood bisphenol A exposures increase asthma risk in inner-city children.
        J Allergy Clin Immunol. 2014; 134: 1195-1197.e2
        • Xie M.Y.
        • Ni H.
        • Zhao D.S.
        • Wen L.Y.
        • Li K.S.
        • Yang H.H.
        • et al.
        Exposure to bisphenol A and the development of asthma: a systematic review of cohort studies.
        Reprod Toxicol. 2016; 65: 224-229
        • Lin T.J.
        • Karmaus W.J.J.
        • Chen M.L.
        • Hsu J.C.
        • Wang I.J.
        Interactions between bisphenol A exposure and GSTP1 polymorphisms in childhood asthma.
        Allergy Asthma Immunol Res. 2018; 10: 172-179
        • Quiros-Alcala L.
        • Hansel N.N.
        • McCormack M.C.
        • Matsui E.C.
        Paraben exposures and asthma-related outcomes among children from the U.S. general population.
        J Allergy Clin Immunol. 2019; 143: 948-956.e4
        • Ku H.Y.
        • Su P.H.
        • Wen H.J.
        • Sun H.L.
        • Wang C.J.
        • Chen H.Y.
        • et al.
        Prenatal and postnatal exposure to phthalate esters and asthma: a 9-year follow-up study of a taiwanese birth cohort.
        PLoS One. 2015; 10e0123309
        • Habib M.R.
        • Karim M.R.
        Antimicrobial and cytotoxic activity of di-(2-ethylhexyl) phthalate and anhydrosophoradiol-3-acetate isolated from Calotropis gigantea (Linn.) flower.
        Mycobiology. 2009; 37: 31-36
        • Buckley J.P.
        • Quirós-Alcalá L.
        • Teitelbaum S.L.
        • Calafat A.M.
        • Wolff M.S.
        • Engel S.M.
        Associations of prenatal environmental phenol and phthalate biomarkers with respiratory and allergic diseases among children aged 6 and 7 years.
        Environment Int. 2018; 115: 79-88
        • Ahmed S.A.
        The immune system as a potential target for environmental estrogens (endocrine disruptors): a new emerging field.
        Toxicology. 2000; 150: 191-206
        • Card J.W.
        • Zeldin D.C.
        Hormonal influences on lung function and response to environmental agents: lessons from animal models of respiratory disease.
        Proc Am Thorac Soc. 2009; 6: 588-595
        • DeWitt C H.P.
        Endocrine disruptors and the developing immune system.
        Curr Opin Toxicol. 2018; 10: 31-36
        • Kuo C.H.
        • Yang S.N.
        • Kuo P.L.
        • Hung C.H.
        Immunomodulatory effects of environmental endocrine disrupting chemicals.
        Kaohsiung J Med Sci. 2012; 28: S37-S42
        • Miller M.D.
        • Marty M.A.
        Impact of environmental chemicals on lung development.
        Environ Health Perspect. 2010; 118: 1155-1164
        • DeBoer M.D.
        • Phillips B.R.
        • Mauger D.T.
        • Zein J.
        • Erzurum S.C.
        • Fitzpatrick A.M.
        • et al.
        Effects of endogenous sex hormones on lung function and symptom control in adolescents with asthma.
        BMC Pulm Med. 2018; 18: 58
        • Fuseini H.
        • Newcomb D.C.
        Mechanisms driving gender differences in asthma.
        Curr Allergy Asthma Rep. 2017; 17: 19