title: Relation between circulating CC16 concentrations, lung function, and development of chronic obstructive pulmonary disease across the lifespan: a prospective study.
abstract: BACKGROUND
  Low concentrations of the anti-inflammatory protein CC16 (approved symbol SCGB1A1) in serum have been associated with accelerated decline in forced expiratory volume in 1 s (FEV1) in patients with chronic obstructive pulmonary disease (COPD). We investigated whether low circulating CC16 concentrations precede lung function deficits and incidence of COPD in the general population.
  
  
  METHODS
  We assessed longitudinal data on CC16 concentrations in serum and associations with decline in FEV1 and incidence of airflow limitation for adults who were free from COPD at baseline in the population-based Tucson Epidemiological Study of Airway Obstructive Disease ([TESAOD] n=960, mean follow-up 14 years), European Community Respiratory Health Survey ([ECRHS-Sp] n=514, 11 years), and Swiss Cohort Study on Air Pollution and Lung Diseases in Adults ([SAPALDIA] n=167, 8 years) studies. Additionally, we measured circulating CC16 concentrations in samples from children aged 4-6 years in the Tucson Children's Respiratory Study (n=427), UK Manchester Asthma and Allergy Study (n=481), and the Swedish Barn/children, Allergy, Milieu, Stockholm, Epidemiological survey (n=231) birth cohorts to assess whether low CC16 concentrations in childhood were predictive for subsequent lung function.
  
  
  RESULTS
  After adjustment for sex, age, height, smoking status and intensity, pack-years, asthma, and FEV1 at baseline, we found an inverse association between CC16 concentration and decline in FEV1 in adults in TESAOD (4·4 mL/year additional FEV1 decline for each SD decrease in baseline CC16 concentration, p=0·0014) and ECRHS-Sp (2·4 mL/year, p=0·023); the effect in SAPALDIA was marginal (4·5 mL/year, p=0·052). Low CC16 concentration at baseline was also associated with increased risk of incident stage 2 airflow limitation (ratio of FEV1 to forced expiratory volume [FEV1/FVC] less than 70% plus FEV1 % predicted less than 80%) in TESAOD and ECRHS-Sp. In children, the lowest tertile of CC16 concentrations was associated with a subsequent FEV1 deficit of 68 mL up to age 16 years (p=0·0001), which was confirmed in children who had never smoked by age 16 years (-71 mL, p<0·0001).
  
  
  CONCLUSIONS
  Low concentrations of CC16 in serum are associated with reduced lung function in childhood, accelerated lung function decline in adulthood, and development of moderate airflow limitation in the general adult population.
  
  
  BACKGROUND
  National Heart, Lung, and Blood Institute and European Union Seventh Framework Programme.
authors.affiliation: Arizona Respiratory Center, University of Arizona, Tucson, AZ, USA; Centre for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra, and CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. Electronic address: stefano@email.arizona.edu.
authors.forename: Stefano
authors.initials: S
authors.lastname: Guerra
authors.affiliation: Arizona Respiratory Center, University of Arizona, Tucson, AZ, USA.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Halonen
authors.affiliation: Arizona Respiratory Center, University of Arizona, Tucson, AZ, USA; Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA.
authors.forename: Monica M
authors.initials: MM
authors.lastname: Vasquez
authors.affiliation: Arizona Respiratory Center, University of Arizona, Tucson, AZ, USA.
authors.forename: Amber
authors.initials: A
authors.lastname: Spangenberg
authors.affiliation: Arizona Respiratory Center, University of Arizona, Tucson, AZ, USA.
authors.forename: Debra A
authors.initials: DA
authors.lastname: Stern
authors.affiliation: Arizona Respiratory Center, University of Arizona, Tucson, AZ, USA.
authors.forename: Wayne J
authors.initials: WJ
authors.lastname: Morgan
authors.affiliation: Arizona Respiratory Center, University of Arizona, Tucson, AZ, USA.
authors.forename: Anne L
authors.initials: AL
authors.lastname: Wright
authors.affiliation: Centre for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra, and CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
authors.forename: Iris
authors.initials: I
authors.lastname: Lavi
authors.affiliation: Centre for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra, and CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
authors.forename: Lluïsa
authors.initials: L
authors.lastname: Tarès
authors.affiliation: Centre for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra, and CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain; IMIM Hospital del Mar Medical Research Institute, Barcelona, Spain.
authors.forename: Anne-Elie
authors.initials: AE
authors.lastname: Carsin
authors.affiliation: ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Carlota
authors.initials: C
authors.lastname: Dobaño
authors.affiliation: Pulmonology Department-Muscle and Respiratory System Research Unit (URMAR), IMIM-Hospital del Mar and CIBER de Enfermedades Respiratorias (CIBERES), Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Barreiro
authors.affiliation: Centre for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra, and CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
authors.forename: Jan-Paul
authors.initials: JP
authors.lastname: Zock
authors.affiliation: Servicio de Neumología del Complejo Hospitalario Universitario de Albacete, and Servicio de Salud de Castilla-La Mancha, Albacete, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Martínez-Moratalla
authors.affiliation: Pneumology Service, Galdakao-Usánsolo Hospital, Bizkaia, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Urrutia
authors.affiliation: Centre for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra, and CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain; IMIM Hospital del Mar Medical Research Institute, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Sunyer
authors.affiliation: Swiss Tropical and Public Health Institute, and University of Basel, Basel, Switzerland.
authors.forename: Dirk
authors.initials: D
authors.lastname: Keidel
authors.affiliation: Swiss Tropical and Public Health Institute, and University of Basel, Basel, Switzerland.
authors.forename: Medea
authors.initials: M
authors.lastname: Imboden
authors.affiliation: Swiss Tropical and Public Health Institute, and University of Basel, Basel, Switzerland.
authors.forename: Nicole
authors.initials: N
authors.lastname: Probst-Hensch
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, and Sachs' Children and Youth Hospital, Stockholm, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Hallberg
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, and Sachs' Children and Youth Hospital, Stockholm, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Melén
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, and Sachs' Children and Youth Hospital, Stockholm, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Wickman
authors.affiliation: Department of Respiratory Diseases, University Hospital, Montpellier, France; Respiratory and Environmental Epidemiology Team, INSERM 1018, CESP Centre, Villejuif, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Bousquet
authors.affiliation: Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, University of Manchester and University Hospital of South Manchester, Manchester, UK.
authors.forename: Danielle C M
authors.initials: DC
authors.lastname: Belgrave
authors.affiliation: Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, University of Manchester and University Hospital of South Manchester, Manchester, UK.
authors.forename: Angela
authors.initials: A
authors.lastname: Simpson
authors.affiliation: Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, University of Manchester and University Hospital of South Manchester, Manchester, UK.
authors.forename: Adnan
authors.initials: A
authors.lastname: Custovic
authors.affiliation: Centre for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra, and CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain; IMIM Hospital del Mar Medical Research Institute, Barcelona, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Antó
authors.affiliation: Arizona Respiratory Center, University of Arizona, Tucson, AZ, USA.
authors.forename: Fernando D
authors.initials: FD
authors.lastname: Martinez
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D001249:Asthma / Q000150:complications; D002648:Child; D002675:Child, Preschool; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008137:Longitudinal Studies; D008168:Lung / Q000503:physiopathology*; D008173:Lung Diseases, Obstructive / Q000097:blood* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012129:Respiratory Function Tests; D012131:Respiratory Insufficiency / Q000150:complications; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013997:Time Factors; D014598:Uteroglobin / Q000097:blood*; D055815:Young Adult
chemical_list: C556389:SCGB1A1 protein, human; D014598:Uteroglobin