title: Distal airway dysfunction identifies pulmonary inflammation in asymptomatic smokers.
abstract: Smoking induced inflammation leads to distal airway destruction. However, the relationship between distal airway dysfunction and inflammation remains unclear, particularly in smokers prior to the development of airway obstruction. Seven normal controls and 16 smokers without chronic obstructive pulmonary disease (COPD) were studied. Respiratory function was assessed using the forced oscillation technique (FOT). Abnormal FOT was defined as elevated resistance at 5 Hz (R5). Parameters reflecting distal lung function included frequency dependence of resistance (R5-20) and dynamic elastance (X5). Inflammation was quantified in concentrated bronchoalveolar lavage utilising cell count differential and cytokines expressed as concentration per mL epithelial lining fluid. All control subjects and seven smokers had normalR5. Nine smokers had elevatedR5with abnormalR5-20andX5, indicating distal lung dysfunction. The presence of abnormal FOT was associated with two-fold higher lymphocyte and neutrophil counts (p<0.025) and with higher interleukin (IL)-8, eotaxin and fractalkine levels (p<0.01). Reactivity ofR5-20andX5correlated with levels of IL-8, eotaxin, fractalkine, IL-12p70 and transforming growth factor-α (r>0.47, p<0.01). Distal airway dysfunction in smokers without COPD identifies the presence of distal lung inflammation that parallel reported observations in established COPD. These findings were not evident on routine pulmonary function testing and may allow the identification of smokers at risk of progression to COPD.
authors.affiliation: André Cournand Pulmonary Laboratory, Bellevue Hospital Center, New York, NY, USA; Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, New York University School of Medicine, New York, NY, USA.
authors.forename: Kenneth I
authors.initials: KI
authors.lastname: Berger
authors.affiliation: André Cournand Pulmonary Laboratory, Bellevue Hospital Center, New York, NY, USA; Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, New York University School of Medicine, New York, NY, USA.
authors.forename: Deepak R
authors.initials: DR
authors.lastname: Pradhan
authors.affiliation: André Cournand Pulmonary Laboratory, Bellevue Hospital Center, New York, NY, USA; Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, New York University School of Medicine, New York, NY, USA.
authors.forename: Roberta M
authors.initials: RM
authors.lastname: Goldring
authors.affiliation: André Cournand Pulmonary Laboratory, Bellevue Hospital Center, New York, NY, USA; Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, New York University School of Medicine, New York, NY, USA.
authors.forename: Beno W
authors.initials: BW
authors.lastname: Oppenheimer
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, New York University School of Medicine, New York, NY, USA.
authors.forename: William N
authors.initials: WN
authors.lastname: Rom
authors.affiliation: André Cournand Pulmonary Laboratory, Bellevue Hospital Center, New York, NY, USA; Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, New York University School of Medicine, New York, NY, USA.
authors.forename: Leopoldo N
authors.initials: LN
authors.lastname: Segal