The Urban Environment and Childhood Asthma (URECA) birth cohort study: design, methods, and study population

James E Gern, Cynthia M Visness, Peter J Gergen, Robert A Wood, Gordon R Bloomberg, George T O'Connor, Meyer Kattan, Hugh A Sampson, Frank R Witter, Megan T Sandel, Wayne G Shreffler, Rosalind J Wright, Samuel J Arbes Jr, William W Busse, James E Gern, Cynthia M Visness, Peter J Gergen, Robert A Wood, Gordon R Bloomberg, George T O'Connor, Meyer Kattan, Hugh A Sampson, Frank R Witter, Megan T Sandel, Wayne G Shreffler, Rosalind J Wright, Samuel J Arbes Jr, William W Busse

Abstract

Background: The incidence and morbidity of wheezing illnesses and childhood asthma is especially high in poor urban areas. This paper describes the study design, methods, and population of the Urban Environment and Childhood Asthma (URECA) study, which was established to investigate the immunologic causes of asthma among inner-city children.

Methods and results: URECA is an observational prospective study that enrolled pregnant women in central urban areas of Baltimore, Boston, New York City, and St. Louis and is following their offspring from birth through age 7 years. The birth cohort consists of 560 inner-city children who have at least one parent with an allergic disease or asthma, and all families live in areas in which at least 20% of the population has incomes below the poverty line. In addition, 49 inner-city children with no parental history of allergies or asthma were enrolled. The primary hypothesis is that specific urban exposures in early life promote a unique pattern of immune development (impaired antiviral and increased Th2 responses) that increases the risk of recurrent wheezing and allergic sensitization in early childhood, and of asthma by age 7 years. To track immune development, cytokine responses of blood mononuclear cells stimulated ex vivo are measured at birth and then annually. Environmental assessments include allergen and endotoxin levels in house dust, pre- and postnatal maternal stress, and indoor air nicotine and nitrogen dioxide. Nasal mucous samples are collected from the children during respiratory illnesses and analyzed for respiratory viruses. The complex interactions between environmental exposures and immune development will be assessed with respect to recurrent wheeze at age 3 years and asthma at age 7 years.

Conclusion: The overall goal of the URECA study is to develop a better understanding of how specific urban exposures affect immune development to promote wheezing illnesses and asthma.

Figures

Figure 1
Figure 1
Hypothesized influence of genetic factors, environmental exposures and lower respiratory infections on the development of wheezing and asthma. Abbreviations: LRI, lower respiratory infection; RSV, respiratory syncytial viruses; HRV, rhinoviruses.
Figure 2
Figure 2
Screening, eligibility, and enrollment frequencies for the allergic family and non-allergic family URECA cohorts.

References

    1. Asthma prevalence, health care use and mortality: United States, 2003–05
    1. Weiss KB, Gergen PJ, Crain EF. Inner-city asthma. The epidemiology of an emerging US public health concern. Chest. 1992;101:362S–367. doi: 10.1378/chest.101.6.362S.
    1. Crain EF, Weiss KB, Bijur PE, Hersh M, Westbrook L, Stein REK. An Estimate of the Prevalence of Asthma and Wheezing Among Inner-City Children. Pediatrics. 1994;94:356–362.
    1. Carr W, Zeitel L, Weiss K. Variations in asthma hospitalizations and deaths in New York City. Am J Public Health. 1992;82:59–65. doi: 10.2105/AJPH.82.1.59.
    1. Litonjua AA, Carey VJ, Weiss ST, Gold DR. Race, socioeconomic factors, and area of residence are associated with asthma prevalence. Pediatr Pulmonol. 1999;28:394–401. doi: 10.1002/(SICI)1099-0496(199912)28:6<394::AID-PPUL2>;2-6.
    1. Ernst P, Demissie K, Joseph L, Locher U, Becklake MR. Socioeconomic status and indicators of asthma in children. Am J Respir Crit Care Med. 1995;152:570–575.
    1. Morgan WJ, Crain EF, Gruchalla RS, O'Connor GT, Kattan M, Evans R, 3rd, Stout J, Malindzak G, Smartt E, Plaut M, et al. Results of a home-based environmental intervention among urban children with asthma. N Engl J Med. 2004;351:1068–1080. doi: 10.1056/NEJMoa032097.
    1. Rosenstreich DL, Eggleston P, Kattan M, Baker D, Slavin RG, Gergen P, Mitchell H, McNiff-Mortimer K, Lynn H, Ownby D, et al. The role of cockroach allergy and exposure to cockroach allergen in causing morbidity among inner-city children with asthma. N Engl J Med. 1997;336:1356–1363. doi: 10.1056/NEJM199705083361904.
    1. Matsui EC, Eggleston PA, Buckley TJ, Krishnan JA, Breysse PN, Rand CS, Diette GB. Household mouse allergen exposure and asthma morbidity in inner-city preschool children. Ann Allergy Asthma Immunol. 2006;97:514–520.
    1. Lipscomb MF, Wilder JA. Immune dysregulation as a cause for allergic asthma. Curr Opin Pulm Med. 1999;5:10–20. doi: 10.1097/00063198-199901000-00003.
    1. Umetsu DT, Dekruyff RH. Immune dysregulation in asthma. Curr Opin Immunol. 2006;18:727–732. doi: 10.1016/j.coi.2006.09.007.
    1. Prescott SL, Macaubas C, Holt BJ, Smallacombe TB, Loh R, Sly PD, Holt PG. Transplacental priming of the human immune system to environmental allergens: universal skewing of initial T cell responses toward the Th2 cytokine profile. J Immunol. 1998;160:4730–4737.
    1. Prescott SL, Holt PG. Abnormalities in cord blood mononuclear cytokine production as a predictor of later atopic disease in childhood. Clin Exp Allergy. 1998;28:1313–1316. doi: 10.1046/j.1365-2222.1998.00427.x.
    1. Williams TJ, Jones CA, Miles EA, Warner JO, Warner JA. Fetal and neonatal IL-13 production during pregnancy and at birth and subsequent development of atopic symptoms. J Allergy Clin Immunol. 2000;105:951–959. doi: 10.1067/mai.2000.106211.
    1. Gern JE, Brooks GD, Meyer P, Chang A, Shen K, Evans MD, Tisler C, Dasilva D, Roberg KA, Mikus LD, et al. Bidirectional interactions between viral respiratory illnesses and cytokine responses in the first year of life. J Allergy Clin Immunol. 2006;117:72–78. doi: 10.1016/j.jaci.2005.10.002.
    1. Ng TW, Holt PG, Prescott SL. Cellular immune responses to ovalbumin and house dust mite in egg-allergic children. Allergy. 2002;57:207–214. doi: 10.1034/j.1398-9995.2002.1o3369.x.
    1. Macaubas C, de Klerk NH, Holt BJ, Wee C, Kendall G, Firth M, Sly PD, Holt PG. Association between antenatal cytokine production and the development of atopy and asthma at age 6 years. Lancet. 2003;362:1192–1197. doi: 10.1016/S0140-6736(03)14542-4.
    1. Bufford JD, Reardon CL, Li Z, Roberg KA, DaSilva D, Eggleston PA, Liu AH, Milton D, Alwis U, Gangnon R, et al. Effects of dog ownership in early childhood on immune development and atopic diseases. Clin Exp Allergy. 2008;38:1635–1643. doi: 10.1111/j.1365-2222.2008.03018.x.
    1. Neaville WA, Tisler C, Bhattacharya A, Anklam K, Gilbertson-White S, Hamilton R, Adler K, Dasilva DF, Roberg KA, Carlson-Dakes KT, et al. Developmental cytokine response profiles and the clinical and immunologic expression of atopy during the first year of life. J Allergy Clin Immunol. 2003;112:740–746. doi: 10.1016/S0091-6749(03)01868-2.
    1. Copenhaver CC, Gern JE, Li Z, Shult PA, Rosenthal LA, Mikus LD, Kirk CJ, Roberg KA, Anderson EL, Tisler CJ, et al. Cytokine response patterns, exposure to viruses, and respiratory infections in the first year of life. Am J Respir Crit Care Med. 2004;170:175–180. doi: 10.1164/rccm.200312-1647OC.
    1. Jackson DJ, Gangnon RE, Evans MD, Roberg KA, Anderson EL, Pappas TE, Printz MC, Lee WM, Shult PA, Reisdorf E, et al. Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children. Am J Respir Crit Care Med. 2008;178:667–672. doi: 10.1164/rccm.200802-309OC.
    1. Kusel MM, de Klerk NH, Kebadze T, Vohma V, Holt PG, Johnston SL, Sly PD. Early-life respiratory viral infections, atopic sensitization, and risk of subsequent development of persistent asthma. J Allergy Clin Immunol. 2007;119:1105–1110. doi: 10.1016/j.jaci.2006.12.669.
    1. Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ, Graeber M, Evaluator Group tE The eczema area and severity index (EASI): assessment of reliability in atopic dermatitis. Exp Dermatol. 2001;10:11–18. doi: 10.1034/j.1600-0625.2001.100102.x.
    1. Silkoff PE, McClean PA, Slutsky AS, Furlott HG, Hoffstein E, Wakita S, Chapman KR, Szalai JP, Zamel N. Marked flow-dependence of exhaled nitric oxide using a new technique to exclude nasal nitric oxide. Am J Respir Crit Care Med. 1997;155:260–267.
    1. American Thoracic Society Recommendations for standardized procedures for the on-line and off-line measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide in adults and children-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. Am J Respir Crit Care Med. 1999;160:2104–2117.
    1. Shreffler WG, Visness CM, Burger M, Cruikshank WW, Lederman HM, de la Morena M, Grindle K, Calatroni A, Sampson HA, Gern JE. Standardization and performance evaluation of mononuclear cell cytokine secretion assays in a multicenter study. BMC Immunol. 2006;7:29. doi: 10.1186/1471-2172-7-29.
    1. Lee WM, Grindle K, Pappas T, Marshall DJ, Moser MJ, Beaty EL, Shult PA, Prudent JR, Gern JE. High-throughput, sensitive, and accurate multiplex PCR-microsphere flow cytometry system for large-scale comprehensive detection of respiratory viruses. J Clin Microbiol. 2007;45:2626–2634. doi: 10.1128/JCM.02501-06.
    1. Crain EF, Walter M, O'Connor GT, Mitchell H, Gruchalla RS, Kattan M, Malindzak GS, Enright P, Evans R, 3rd, Morgan W, et al. Home and allergic characteristics of children with asthma in seven U.S. urban communities and design of an environmental intervention: the Inner-City Asthma Study. Environ Health Perspect. 2002;110:939–945.
    1. Gold DR, Burge HA, Carey V, Milton DK, Platts-Mills T, Weiss ST. Predictors of repeated wheeze in the first year of life: the relative roles of cockroach, birth weight, acute lower respiratory illness, and maternal smoking. Am J Respir Crit Care Med. 1999;160:227–236.
    1. Alwis KU, Milton DK. Recombinant factor C assay for measuring endotoxin in house dust: comparison with LAL, and (1 --> 3)-beta-D-glucans. Am J Ind Med. 2006;49:296–300. doi: 10.1002/ajim.20264.
    1. Carver CS. You want to measure coping but your protocol's too long: consider the brief COPE. International journal of behavioral medicine. 1997;4:92–100. doi: 10.1207/s15327558ijbm0401_6.
    1. Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc Behav. 1983;24:385–396. doi: 10.2307/2136404.
    1. Cox JL, Holden JM, Sagovsky R. Detection of postnatal depression. Development of the 10-item Edinburgh Postnatal Depression Scale. Br J Psychiatry. 1987;150:782–786. doi: 10.1192/bjp.150.6.782.
    1. Lobel M, Dunkel-Schetter C, Scrimshaw SC. Prenatal maternal stress and prematurity: a prospective study of socioeconomically disadvantaged women. Health Psychol. 1992;11:32–40. doi: 10.1037/0278-6133.11.1.32.
    1. Wright RJ, Mitchell H, Visness CM, Cohen S, Stout J, Evans R, Gold DR. Community violence and asthma morbidity: the Inner-City Asthma Study. Am J Public Health. 2004;94:625–632. doi: 10.2105/AJPH.94.4.625.
    1. Rinas U, Horneff G, Wahn V. Interferon-gamma production by cord-blood mononuclear cells is reduced in newborns with a family history of atopic disease and is independent from cord blood IgE-levels. Pediatr Allergy Immunol. 1993;4:60–64. doi: 10.1111/j.1399-3038.1993.tb00068.x.
    1. Keil T, Kulig M, Simpson A, Custovic A, Wickman M, Kull I, Lodrup Carlsen KC, Carlsen KH, Smit HA, Wijga AH, et al. European birth cohort studies on asthma and atopic diseases: I. Comparison of study designs – a GALEN initiative. Allergy. 2006;61:221–228. doi: 10.1111/j.1398-9995.2006.00989.x.
    1. Morgan WJ, Stern DA, Sherrill DL, Guerra S, Holberg CJ, Guilbert TW, Taussig LM, Wright AL, Martinez FD. Outcome of asthma and wheezing in the first 6 years of life: follow-up through adolescence. Am J Respir Crit Care Med. 2005;172:1253–1258. doi: 10.1164/rccm.200504-525OC.
    1. Lemanske RF., Jr The childhood origins of asthma (COAST) study. Pediatr Allergy Immunol. 2002;13:38–43. doi: 10.1034/j.1399-3038.13.s.15.8.x.
    1. Williams LK, McPhee RA, Ownby DR, Peterson EL, James M, Zoratti EM, Johnson CC. Gene-environment interactions with CD14 C-260T and their relationship to total serum IgE levels in adults. J Allergy Clin Immunol. 2006;118:851–857. doi: 10.1016/j.jaci.2006.07.007.
    1. Gold DR, Tager IB, Weiss ST, Tosteson TD, Speizer FE. Acute lower respiratory illness in childhood as a predictor of lung function and chronic respiratory symptoms. Am Rev Respir Dis. 1989;140:877–884.
    1. Maas T, Dompeling E, Van Schayck CP, Muris JWM, Schonberger H, Wesseling G, Platts-Mills T, Knottnerus JA. Birth cohort studies on asthma development. Pediatr Asthma Allergy Immunol. 2005;18:201–215. doi: 10.1089/pai.2005.18.201.
    1. DeNavas-Walt C, Proctor BD, Smith J. Income, poverty, and health insurance coverage in the United States: 2006. U.S. Census Bureau, Current Population Reports, P60-233, U.S. Government Printing Office, Washington, DC; 2007.
    1. Martin JA, Hamilton BE, Sutton PD, Ventura SJ, Menacker F, Kirmeyer S. Births: final data for 2004. Natl Vital Stat Rep. 2006;55:1–101.
    1. Litonjua Augusto A, Carey Vincent J, Burge Harriet A, Weiss Scott T, Gold Diane R. Parental History and the Risk for Childhood Asthma. Does Mother Confer More Risk than Father? Am J Respir Crit Care Med. 1998;158:176–181.
    1. Miles EA, Warner JA, Lane AC, Jones AC, Colwell BM, Warner JO. Altered T lymphocyte phenotype at birth in babies born to atopic parents. Pediatr Allergy Immunol. 1994;5:202–208. doi: 10.1111/j.1399-3038.1994.tb00240.x.
    1. Prescott SL, Macaubas C, Smallacombe T, Holt BJ, Sly PD, Holt PG. Development of allergen-specific T-cell memory in atopic and normal children. Lancet. 1999;353:196–200. doi: 10.1016/S0140-6736(98)05104-6.

Source: PubMed

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