title: Biologic mechanisms of environmental tobacco smoke in children with poorly controlled asthma: results from a multicenter clinical trial.
abstract: BACKGROUND
  Environmental tobacco smoke (ETS) negatively affects children with asthma. The prevalence of ETS exposure among children with poor asthma control may be changing. Importantly, the mechanisms by which ETS worsens asthma control are poorly understood.
  
  
  OBJECTIVE
  We describe how ETS affects gastroesophageal reflux (GER), respiratory infections, and leukotriene production among children with poor asthma control.
  
  
  METHODS
  We analyzed data from 306 children between 6 and 17 years of age with poorly controlled asthma enrolled in a 6-month clinical trial. We evaluated prevalence and determinants of ETS exposure by interview, questionnaire, and urinary cotinine and the association of ETS exposure on leukotriene production, respiratory infections, GER, lung function, and asthma control. We used multivariable linear, logistic, and Poisson regressions to assess outcomes.
  
  
  RESULTS
  ETS prevalence estimates ranged from 6% to 30%. Children with domestic indoor exposure had worse asthma control (c-Asthma Control Test, 17.8 vs 21.5; P = .04), worse FEV1 % predicted (84.1 vs 90.7; P = .02), and a trend for increased mean urinary leukotriene E4. ETS from any setting was associated with increased symptomatic respiratory infections (adjusted incidence rate ratio: 1.30; P = .02). However, children exposed to ETS did not have symptoms or pH probe results, suggestive of heightened GER.
  
  
  CONCLUSIONS
  Domestic smoking exposure was associated with both higher rates of symptomatic respiratory infection and poorer asthma control despite generally intensive controller therapy. ETS exposure is common among asthmatic children with poor control and may worsen asthma control by promoting respiratory infections. Further investigation is required to elucidate ETS mechanisms in poor asthma control.
authors.affiliation: Division of Pulmonary & Sleep Medicine, Nemours Children's Hospital, Orlando, Fla; Center for Pharmacogenomics & Translational Research, Nemours Children's Clinic, Jacksonville, Fla. Electronic address: jelang@nemours.org.
authors.forename: Jason E
authors.initials: JE
authors.lastname: Lang
authors.affiliation: Division of Pediatric Pulmonology, New York Medical College, Valhalla, NY.
authors.forename: Allen J
authors.initials: AJ
authors.lastname: Dozor
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Md.
authors.forename: Janet T
authors.initials: JT
authors.lastname: Holbrook
authors.affiliation: Center for Pharmacogenomics & Translational Research, Nemours Children's Clinic, Jacksonville, Fla.
authors.forename: Edward
authors.initials: E
authors.lastname: Mougey
authors.affiliation: Division of Pediatric Pulmonology, New York Medical College, Valhalla, NY.
authors.forename: Sankaran
authors.initials: S
authors.lastname: Krishnan
authors.affiliation: Center for Pharmacogenomics & Translational Research, Nemours Children's Clinic, Jacksonville, Fla.
authors.forename: Shawn
authors.initials: S
authors.lastname: Sweeten
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Md.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wise
authors.affiliation: University of Virginia School of Medicine, Charlottesville, Va.
authors.forename: W Gerald
authors.initials: WG
authors.lastname: Teague
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Md.
authors.forename: Christine Y
authors.initials: CY
authors.lastname: Wei
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Md.
authors.forename: David
authors.initials: D
authors.lastname: Shade
authors.affiliation: Center for Pharmacogenomics & Translational Research, Nemours Children's Clinic, Jacksonville, Fla.
authors.forename: John J
authors.initials: JJ
authors.lastname: Lima
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000209:etiology*; D002648:Child; D005260:Female; D005764:Gastroesophageal Reflux / Q000209:etiology; D006801:Humans; D015289:Leukotrienes / Q000096:biosynthesis; D016015:Logistic Models; D008297:Male; D016012:Poisson Distribution; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D015289:Leukotrienes; D014028:Tobacco Smoke Pollution
keywords: Asthma; Children; Environmental tobacco smoke; Gastroesophageal reflux; Leukotriene; Spirometry; respiratory infection