Summary:
The Tucson Children’s Respiratory Study (TCRS) is the longest ongoing birth cohort study centered on the early origins of asthma and chronic obstructive lung disease worldwide. It was started in 1980 with the goal of exploring the early life origins of asthma. Between 1980 and 1984, 1246 healthy infants were enrolled in the study at birth making the TCRS a population-based, non-selected, prospective birth cohort study.
The CRS has been continuously funded by the National Institutes of Health through the present. Starting at birth, samples and questionnaires have been collected from the enrolled children at regular intervals. There have been 7 “In Depth” Evaluations completed at ages 6, 11, 16, 22, 26, 32 and 36 years. At each In Depth Evaluation, the participants performed pulmonary function testing (PFT), bronchial hyper-responsiveness testing (methacholine or cold air challenge), allergy skin prick tests to local aeroallergens. In some of the evaluations, peak flow variability testing, exhaled nitric oxide measurement and sputum induction were also included in the protocols. In addition, blood samples were collected for complete blood cell counts, DNA extraction, and total immunoglobulin E measurement. Blood samples were collected at birth (umbilical cord) and ,at 9 months of age and all In Depth visits. Additional respiratory health questionnaires were completed at ages 2, 3, 8, 13, 18, 24, and 29 years. At In Depth 6 a subset of participants also completed impulse oscillometry, plethysmography and lung clearance index testing.
One of the strengths of the TCRS study is the detailed information collected about lower respiratory illnesses (LRI) during the first 3 years of life (bronchiolitis, pneumonia, croup and others). In case of symptoms compatible with LRI, children were seen by a pediatrician and symptoms as well as viral or bacterial etiology of each LRI were determined. Parents and siblings also completed respiratory questionnaires, pulmonary function testing, allergy skin prick testing and a blood sample collection.
Of the 1246 TCRS participants, 821 have adult respiratory data between ages 22 and 36 years. Our main measure of asthma is derived from the questionnaires and is defined as a physician diagnosis of asthma with episodes or attacks of asthma and/or wheeze during the previous year. We define frequent asthma as four or more episodes during the previous year and infrequent asthma as 1-3 episodes during the previous year. As adults, 12% (n=97) of the CRS participants have frequent asthma and 18% have infrequent asthma (n=148). In addition, 6% (n=47) report frequent wheeze without a diagnosis of asthma and 24% (n=195) report infrequent wheeze without a diagnosis of asthma. Overall, 41% (n=334) of TCRS participants do not report asthma and wheeze symptoms as adults.
Data Access Request (DAR):
To request data access complete the CRS Data Access Request Form and email it to ChildrensRespiratoryStudy@email.arizona.edu
Researchers:
Anne Wright, PhD
Fernando Martinez, MD
Marilyn Halonen, PhD
Stefano Guerra, MD, PhD, MPH
Wayne J. Morgan, MD
Dean Billheimer, PhD
Darren Cusanovich, PhD
Tara Carr, MD
Floyd "Ski" Chilton, PhD
Research Specialties:
Allergy
Asthma
Genetics
Immunology
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Wright AL, Holberg CJ, Taussig LM, Martinez FD. Factors influencing the relation of infant feeding to asthma and recurrent wheeze in childhood. Thorax. 2001;56(3):192-7. Epub 2001/02/22. PubMed PMID: 11182011
Wright AL, Stern DA, Halonen M. The association of allergic sensitization in mother and child in breast-fed and formula-fed infants. Advances in experimental medicine and biology. 2001;501:249-55. Epub 2002/01/15. PubMed PMID: 11787688
Ball TM, Holberg CJ, Aldous MB, Martinez FD, Wright AL. Influence of attendance at day care on the common cold from birth through 13 years of age. Archives of pediatrics & adolescent medicine. 2002;156(2):121-6. Epub 2002/02/09. PubMed PMID: 11814371
Ball TM, Holberg CJ, Martinez FD, Wright AL. Is there a common cold constitution? Ambulatory pediatrics : the official journal of the Ambulatory Pediatric Association. 2002;2(4):261-7. Epub 2002/07/24. PubMed PMID: 12135399
Karakoc F, Remes ST, Martinez FD, Wright AL. The association between persistent eosinophilia and asthma in childhood is independent of atopic status. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2002;32(1):51-6. Epub 2002/05/11.PubMed PMID: 12002737
Taussig LM, Wright AL, Holberg CJ, Halonen M, Morgan WJ, Martinez FD. Tucson Children's Respiratory Study: 1980 to present. The Journal of allergy and clinical immunology. 2003;111(4):661-75; quiz 76. Epub 2003/04/22. PubMed PMID: 12704342
Crestani E, Guerra S, Wright AL, Halonen M, Martinez FD. Parental asthma as a risk factor for the development of early skin test sensitization in children. The Journal of allergy and clinical immunology. 2004;113(2):284-90. Epub 2004/02/10. doi: 10.1016/j.jaci.2003.11.009. PubMed PMID: 14767443
Guerra S, Carla Lohman I, LeVan TD, Wright AL, Martinez FD, Halonen M. The differential effect of genetic variation on soluble CD14 levels in human plasma and milk. Am J Reprod Immunol. 2004;52(3):204-11. Epub 2004/09/18. doi: 10.1111/j.1600-0897.2004.00207.x. PubMed PMID: 15373760
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Wright AL, Stern DA, Kauffmann F, Martinez FD. Factors influencing gender differences in the diagnosis and treatment of asthma in childhood: the Tucson Children's Respiratory Study. Pediatric pulmonology. 2006;41(4):318-25. Epub 2006/02/16. doi: 10.1002/ppul.20373. PubMed PMID: 16477658
Guilbert TW, Stern DA, Morgan WJ, Martinez FD, Wright AL. Effect of breastfeeding on lung function in childhood and modulation by maternal asthma and atopy. American journal of respiratory and critical care medicine. 2007;176(9):843-8. Epub 2007/08/11. doi: 10.1164/rccm.200610-1507OC.PubMed PMID: 17690333
Stern DA, Guerra S, Halonen M, Wright AL, Martinez FD. Low IFN-gamma production in the first year of life as a predictor of wheeze during childhood. The Journal of allergy and clinical immunology. 2007;120(4):835-41. Epub 2007/08/11. doi: 10.1016/j.jaci.2007.05.050. PubMed PMID: 17689598
Stern DA, Morgan WJ, Wright AL, Guerra S, Martinez FD. Poor airway function in early infancy and lung function by age 22 years: a non-selective longitudinal cohort study. Lancet. 2007;370(9589):758-64. Epub 2007/09/04. doi: S0140-6736(07)61379-8 [pii] 10.1016/S0140-6736(07)61379-8.PubMed PMID: 17765525
Stern DA, Morgan WJ, Halonen M, Wright AL, Martinez FD. Wheezing and bronchial hyper-responsiveness in early childhood as predictors of newly diagnosed asthma in early adulthood: a longitudinal birth-cohort study. Lancet. 2008;372(9643):1058-64. Epub 2008/09/23. doi: 10.1016/S0140-6736(08)61447-6. PubMed PMID: 18805334
Tebow G, Sherrill DL, Lohman IC, Stern DA, Wright AL, Martinez FD, et al. Effects of parental smoking on interferon gamma production in children. Pediatrics. 2008;121(6):e1563-9. Epub 2008/06/04. doi: 10.1542/peds.2007-2795. PubMed PMID: 18519461
Custovic A, Rothers J, Stern D, Simpson A, Woodcock A, Wright AL, et al. Effect of day care attendance on sensitization and atopic wheezing differs by Toll-like receptor 2 genotype in 2 population-based birth cohort studies. The Journal of allergy and clinical immunology. 2011;127(2):390-7 e1-9. Epub 2011/02/02. doi: 10.1016/j.jaci.2010.10.050. PubMed PMID: 21281869
Sherrill DL, Guerra S, Wright AL, Morgan WJ, Martinez FD. Relation of early childhood growth and wheezing phenotypes to adult lung function. Pediatric pulmonology. 2011;46(10):956-63. Epub 2011/04/27. doi: 10.1002/ppul.21470. PubMed PMID: 21520441
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Marri PR, Stern DA, Wright AL, Billheimer D, Martinez FD. Asthma-associated differences in microbial composition of induced sputum. The Journal of allergy and clinical immunology. 2013;131(2):346-52 e1-3. Epub 2012/12/26. doi: 10.1016/j.jaci.2012.11.013. PubMed PMID: 23265859
Voraphani N, Stern DA, Wright AL, Guerra S, Morgan WJ, Martinez FD. Risk of current asthma among adult smokers with respiratory syncytial virus illnesses in early life. American journal of respiratory and critical care medicine. 2014;190(4):392-8. Epub 2014/06/14. doi: 10.1164/rccm.201311-2095OC. PubMed PMID: 24927374
Beamer PI, Lothrop N, Lu Z, Ascher R, Ernst K, Stern DA, et al. Spatial clusters of child lower respiratory illnesses associated with community-level risk factors. Pediatric pulmonology. 2015. Epub 2015/10/06. doi: 10.1002/ppul.23332. PubMed PMID: 26436763
Beamer PI, Lothrop N, Stern DA, Billheimer D, Wright AL, Martinez FD. Increased wheezing risk with diesel exposure among children of younger mothers. The European respiratory journal. 2015;46(3):853-5. Epub 2015/04/18. doi: 10.1183/09031936.00227214. PubMed PMID: 25882808
Chan JY, Stern DA, Guerra S, Wright AL, Morgan WJ, Martinez FD. Pneumonia in childhood and impaired lung function in adults: a longitudinal study. Pediatrics. 2015;135(4):607-16. Epub 2015/03/04. doi: peds.2014-3060 [pii] 10.1542/peds.2014-3060. PubMed PMID: 25733757
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Martinez FD. The origins of asthma and chronic obstructive pulmonary disease in early life. Proc Am Thorac Soc. 2009 May 1;6(3):272-7. PMCID: PMC2677402 PubMed PMID: 19387029
Voraphani N, Martinez FD. Postnatal Growth and the Heterogeneity of Preschool Wheeze. J Pediatr. 2015 Feb;166(2):226-8. Epub 2014 Nov 4. PMID: 25466678 PubMed PMID: 25466678
Martinez FD. Early-Life Origins of Chronic Obstructive Pulmonary Disease. N Engl J Med. 2016 Sep 1;375(9):871-8. PMID: 27579637 PubMed PMID: 27579637
JYC Chan, DA Stern, S Guerra, AL Wright, WJ Morgan, FD Martinez: “Pneumonia in Childhood and Impaired Lung Function and Asthma in Adults: A Longitudinal Study”. Pediatrics 2015, 135: 607-616. PMID 25733757; PMCID: PMC4379462. PubMed PMID: 25733757
CE Berry, D Billheimer, IC Jenkins, ZJ Lu, DA Stern, LB Gerald, TF Carr, S Guerra, MJ Halonen, W Morgan, AL Wright, FD Martinez: “A distinct low lung function trajectory from childhood to the fourth decade of life”. The American Journal of Respiratory and Critical Care Medicine 2016, 194: 607-612.PubMed PMID: 27585385
Early life risk factors for chronic sinusitis: a longitudinal birth cohort study Eugene H Chang MD1,2, Debra A Stern MS2, Amanda L Willis MSC1,2, Stefano Guerra MD, PhD2, Anne L Wright PhD2, and Fernando D Martinez MD2 PubMed PMID: 27923563
FD Martinez & S Guerra: “Early Origins of Asthma: Role of Microbial Dysbiosis and Metabolic Dysfunction”. The American Journal of Respiratory and Critical Care Medicine PubMed PMID: 29048927
Martinez FD. Beyond the Paradigm of Asthma as an Inflammatory Disease. A Summary of the 2015 Aspen Lung Conference. Annals of the American Thoracic Society. 2016;13 Suppl 1:S91-4. Epub 2016/03/31. doi: 10.1513/AnnalsATS.201510-677MG. PubMed PMID: 27027960.
Oren E, Gerald L, Stern DA, Martinez FD, Wright AL. Self-Reported Stressful Life Events During Adolescence and Subsequent Asthma: A Longitudinal Study. The journal of allergy and clinical immunology In practice. 2017;5(2):427-34 e2. Epub 2016/11/07. doi: 10.1016/j.jaip.2016.09.019. PubMed PMID: 27815066; PMCID: 5591640
Chang EH, Stern DA, Willis AL, Guerra S, Wright AL, Martinez FD. Early life risk factors for chronic sinusitis: A longitudinal birth cohort study. The Journal of allergy and clinical immunology. 2018;141(4):1291-7 e2. Epub 2018/01/23. doi: 10.1016/j.jaci.2017.11.052. PubMed PMID: 29355680; PMCID: 5937937
Gerhart KD, Stern DA, Guerra S, Morgan WJ, Martinez FD, Wright AL. Protective effect of breastfeeding on recurrent cough in adulthood. Thorax. 2018;73(9):833-9. Epub 2018/05/23. doi: 10.1136/thoraxjnl-2017-210841. PubMed PMID: 29786547; PMCID: 6473807.
Hiranrattana A, Stern DA, Guerra S, Halonen M, Wright AL, Daines M, Martinez FD, Morgan WJ. Alternaria sensitisation at age 6 years is associated with subsequent airway hyper-responsiveness in non-asthmatics. Thorax. 2018;73(12):1170-3. Epub 2018/03/23. doi: 10.1136/thoraxjnl-2017-210325. PubMed PMID: 29563159; PMCID: 6410363
Martinez FD, Guerra S. Early Origins of Asthma. Role of Microbial Dysbiosis and Metabolic Dysfunction. American journal of respiratory and critical care medicine. 2018;197(5):573-9. Epub 2017/10/20. doi: 10.1164/rccm.201706-1091PP. PubMed PMID: 29048927; PMCID: 6005239.
Zhai J, Stern DA, Sherrill DL, Spangenberg AL, Wright AL, Morgan WJ, Halonen M, Martinez FD, Guerra S. Trajectories and Early Determinants of Circulating CC16 from Birth to Age 32 Years. American journal of respiratory and critical care medicine. 2018;198(2):267-70. Epub 2018/02/28. doi: 10.1164/rccm.201712-2398LE. PubMed PMID: 29485918; PMCID: 6058982
Beamer PI, Furlong M, Lothrop N, Guerra S, Billheimer D, Stern DA, Zhai J, Halonen M, Wright AL, Martinez FD. CC16 Levels into Adult Life are Associated with Nitrogen Dioxide Exposure at Birth. American journal of respiratory and critical care medicine. 2019. Epub 2019/02/23. doi: 10.1164/rccm.201808-1488OC. PubMed PMID: 30789752.
Carr TF, Stern DA, Halonen M, Wright AL, Martinez FD. Non-atopic rhinitis at age 6 is associated with subsequent development of asthma. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2019;49(1):35-43. Epub 2018/09/17. doi: 10.1111/cea.13276. PubMed PMID: 30220097; PMCID: 6310646
Lombardi E, Stern DA, Sherrill D, Morgan WJ, Wright AL, Garcia-Aymerich J, Serra Pons I, Guerra S, Martinez FD. Peak flow variability in childhood and body mass index in adult life. The Journal of allergy and clinical immunology. 2019;143(3):1224-6 e9. Epub 2018/11/12. doi: 10.1016/j.jaci.2018.10.035. PubMed PMID: 30414860
Martinez FD. Childhood Asthma Inception and Progression: Role of Microbial Exposures, Susceptibility to Viruses and Early Allergic Sensitization. Immunology and allergy clinics of North America. 2019;39(2):141-50. Epub 2019/04/08. doi: 10.1016/j.iac.2018.12.001. PubMed PMID: 30954166; PMCID: 6613822
Zhai J, Insel M, Addison KJ, Stern DA, Pederson W, Dy A, Rojas-Quintero J, Owen CA, Sherrill DL, Morgan W, Wright AL, Halonen M, Martinez FD, Kraft M, Guerra S, Ledford JG. Club Cell Secretory Protein Deficiency Leads to Altered Lung Function. American journal of respiratory and critical care medicine. 2019;199(3):302-12. Epub 2018/12/14. doi: 10.1164/rccm.201807-1345OC. PubMed PMID: 30543455; PMCID: 6363971.
Guerra S, Lombardi E, Stern DA, Sherrill DL, Gilbertson-Dahdal D, Wheatley-Guy CM, Snyder EM, Wright AL, Martinez FD, Morgan WJ. Fetal Origins of Asthma: A Longitudinal Study from Birth to Age 36 Years. American journal of respiratory and critical care medicine. 2020. Epub 2020/07/11. doi: 10.1164/rccm.202001-0194OC. PubMed PMID: 32649838.
Chang EH, Willis AL, Romanoski CE, Cusanovich DA, Pouladi N, Li J, Lussier YA, Martinez FD. Rhinovirus Infections in Individuals with Asthma Increase ACE2 Expression and Cytokine Pathways Implicated in COVID-19. American journal of respiratory and critical care medicine. 2020;202(5):753-5. Epub 2020/07/11. doi: 10.1164/rccm.202004-1343LE. PubMed PMID: 32649217; PMCID: PMC7462393.