title: Ambient air pollution, lung function, and airway responsiveness in asthmatic children.
abstract: BACKGROUND
  Although ambient air pollution has been linked to reduced lung function in healthy children, longitudinal analyses of pollution effects in asthmatic patients are lacking.
  
  
  OBJECTIVE
  We sought to investigate pollution effects in a longitudinal asthma study and effect modification by controller medications.
  
  
  METHODS
  We examined associations of lung function and methacholine responsiveness (PC20) with ozone, carbon monoxide (CO), nitrogen dioxide, and sulfur dioxide concentrations in 1003 asthmatic children participating in a 4-year clinical trial. We further investigated whether budesonide and nedocromil modified pollution effects. Daily pollutant concentrations were linked to ZIP/postal code of residence. Linear mixed models tested associations of within-subject pollutant concentrations with FEV1 and forced vital capacity (FVC) percent predicted, FEV1/FVC ratio, and PC20, adjusting for seasonality and confounders.
  
  
  RESULTS
  Same-day and 1-week average CO concentrations were negatively associated with postbronchodilator percent predicted FEV1 (change per interquartile range, -0.33 [95% CI, -0.49 to -0.16] and -0.41 [95% CI, -0.62 to -0.21], respectively) and FVC (-0.19 [95% CI, -0.25 to -0.07] and -0.25 [95% CI, -0.43 to -0.07], respectively). Longer-term 4-month CO averages were negatively associated with prebronchodilator percent predicted FEV1 and FVC (-0.36 [95% CI, -0.62 to -0.10] and -0.21 [95% CI, -0.42 to -0.01], respectively). Four-month averaged CO and ozone concentrations were negatively associated with FEV1/FVC ratio (P < .05). Increased 4-month average nitrogen dioxide concentrations were associated with reduced postbronchodilator FEV1 and FVC percent predicted. Long-term exposures to sulfur dioxide were associated with reduced PC20 (percent change per interquartile range, -6% [95% CI, -11% to -1.5%]). Treatment augmented the negative short-term CO effect on PC20.
  
  
  CONCLUSIONS
  Air pollution adversely influences lung function and PC20 in asthmatic children. Treatment with controller medications might not protect but rather worsens the effects of CO on PC20. This clinical trial design evaluates modification of pollution effects by treatment without confounding by indication.
authors.affiliation: University of Groningen, Department of Epidemiology, University Medical Center Groningen, Groningen, The Netherlands; Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: d.ierodiakonou@euc.ac.cy.
authors.forename: Despo
authors.initials: D
authors.lastname: Ierodiakonou
authors.affiliation: Environmental Epidemiology and Risk Program, Harvard T.H. Chan School of Public Health, Boston, Mass.
authors.forename: Antonella
authors.initials: A
authors.lastname: Zanobetti
authors.affiliation: Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Mass.
authors.forename: Brent A
authors.initials: BA
authors.lastname: Coull
authors.affiliation: Environmental Epidemiology and Risk Program, Harvard T.H. Chan School of Public Health, Boston, Mass.
authors.forename: Steve
authors.initials: S
authors.lastname: Melly
authors.affiliation: Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, Groningen, The Netherlands; University of Groningen, Department of Pulmonology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.affiliation: University of Groningen, Department of Epidemiology, University Medical Center Groningen, Groningen, The Netherlands; Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: H Marike
authors.initials: HM
authors.lastname: Boezen
authors.affiliation: University of Groningen, Department of Epidemiology, University Medical Center Groningen, Groningen, The Netherlands; Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Judith M
authors.initials: JM
authors.lastname: Vonk
authors.affiliation: Department of Pediatrics, School of Medicine, University of Washington, Seattle, Wash.
authors.forename: Paul V
authors.initials: PV
authors.lastname: Williams
authors.affiliation: Department of Pediatrics, School of Medicine, University of Washington, Seattle, Wash.
authors.forename: Gail G
authors.initials: GG
authors.lastname: Shapiro
authors.affiliation: Department of Respiratory Medicine, St Vincent University Hospital, Dublin, Ireland.
authors.forename: Edward F
authors.initials: EF
authors.lastname: McKone
authors.affiliation: Department of Pulmonary and Critical Care, School of Medicine, University of Washington, Seattle, Wash.
authors.forename: Teal S
authors.initials: TS
authors.lastname: Hallstrand
authors.affiliation: Department of Environmental Health, School of Medicine, University of Washington, Seattle, Wash.
authors.forename: Jane Q
authors.initials: JQ
authors.lastname: Koenig
authors.affiliation: Department of Biostatistics, School of Medicine, Vanderbilt University, Nashville, Tenn.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Schildcrout
authors.affiliation: Department of Statistics, University of Auckland, Auckland, New Zealand.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lumley
authors.affiliation: Channing Laboratory, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, Mass.
authors.forename: Anne N
authors.initials: AN
authors.lastname: Fuhlbrigge
authors.affiliation: Environmental Epidemiology and Risk Program, Harvard T.H. Chan School of Public Health, Boston, Mass.
authors.forename: Petros
authors.initials: P
authors.lastname: Koutrakis
authors.affiliation: Environmental Epidemiology and Risk Program, Harvard T.H. Chan School of Public Health, Boston, Mass.
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
authors.affiliation: Channing Laboratory, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, Mass.
authors.forename: Scott T
authors.initials: ST
authors.lastname: Weiss
authors.affiliation: Environmental Epidemiology and Risk Program, Harvard T.H. Chan School of Public Health, Boston, Mass; Channing Laboratory, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, Mass. Electronic address: diane.gold@channing.harvard.edu.
authors.forename: Diane R
authors.initials: DR
authors.lastname: Gold
mesh_terms: D000367:Age Factors; D000393:Air Pollutants / Q000032:analysis; D000397:Air Pollution / Q000009:adverse effects*; D000704:Analysis of Variance; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D052638:Particulate Matter / Q000032:analysis; D012129:Respiratory Function Tests; D013147:Spirometry
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter
keywords: Asthma; airway hyperresponsiveness; ambient air pollution; inhaled corticosteroids; lung function