Small airways dysfunction and neutrophilic inflammation in bronchial biopsies and BAL in COPD.
BACKGROUND
The single-breath N(2) test (sbN(2)-test) is closely related to small airways pathology in resected lung specimens of smokers. We investigated whether uneven ventilation and airway closure are associated with specific markers of airway inflammation as obtained by bronchial biopsies, BAL, and induced sputum in patients with manifest COPD.


METHODS
Fifty-one patients with stable COPD not receiving corticosteroids were examined in a cross-sectional study (43 men; mean [SD] age, 63 +/- 8 years; exsmokers and smokers; median pack-years, 41 [interquartile range, 31 to 51 pack-years]). Postbronchodilator spirometry (FEV(1), 63 +/- 8% of predicted) and sbN(2)-test (slope of phase III [DeltaN(2)], closing capacity [CC]/total lung capacity [TLC] percentage of predicted) were performed. Inflammatory cell counts were assessed in bronchial biopsies, BAL (only in the first half of patients), and induced sputum. Neutrophil elastase (NE), secretory leukocyte proteinase inhibitor (SLPI), and interleukin-8 levels were determined in BAL fluid.


RESULTS
DeltaN(2) increased with subepithelial neutrophil numbers in bronchial biopsies (rs = 0.337, p = 0.017) and with NE levels (rs = 0.443, p = 0.039), NE/neutrophil ratio (rs = 0.575, p = 0.005) and SLPI levels (rs = 0.484, p = 0.022) in BAL. CC/TLC was associated with BAL neutrophil numbers (rs = 0.448, p = 0.048). The sbN(2)-test was not associated with any other inflammatory cell type in BAL or biopsies, nor with inflammatory cell counts in sputum. Of importance, the correlations between DeltaN(2) and BAL NE/neutrophil ratio, and between CC/TLC and BAL neutrophil numbers remained significant when adjusting for FEV(1) percentage of predicted.


CONCLUSIONS
The results of the sbN(2)-test are associated with neutrophilic inflammation in bronchial biopsies and BAL in patients with COPD. Our findings support a role of neutrophilic inflammation in the pathogenesis of small airways dysfunction in COPD.
Lapperre
Thérèse S
TS
Department of Pulmonology, Leiden University Medical Center, Albinusdreef 2, PO Box 9600, NL-2300 RC Leiden, the Netherlands. t.s.lapperre@lumc.nl
Willems
Luuk N A
LN
Timens
Wim
W
Rabe
Klaus F
KF
Hiemstra
Pieter S
PS
Postma
Dirkje S
DS
Sterk
Peter J
PJ
D001706:Biopsy; D001944:Breath Tests; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D001993:Bronchodilator Agents / Q000627:therapeutic use; D001999:Bronchoscopy; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D013147:Spirometry; D013183:Sputum / Q000276:immunology*
D001993:Bronchodilator Agents; D018836:Inflammation Mediators