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Original Research: COPD |

Small Airways Dysfunction and Neutrophilic Inflammation in Bronchial Biopsies and BAL in COPD*

Thérèse S. Lapperre, MD; Luuk N. A. Willems, MD, PhD; Wim Timens, MD, PhD; Klaus F. Rabe, MD, PhD; Pieter S. Hiemstra, MSc, PhD; Dirkje S. Postma, MD, PhD; Peter J. Sterk, MD, PhD; the GLUCOLD Study Group
Author and Funding Information

Affiliations: *From the Department of Pulmonology (Drs. Lapperre, Willems, Rabe, Hiemstra, and Sterk), Leiden University Medical Center, Leiden; and Departments of Pulmonology (Dr. Postma) and Pathology (Dr. Timens), Groningen University Medical Center, Groningen and Leiden, the Netherlands.,  A list of GLUCOLD study members is given in the Appendix.

Correspondence to: Thérèse S. Lapperre, MD, Lung Function Lab, C2-P, Department of Pulmonology, Leiden University Medical Center, Albinusdreef 2, PO Box 9600, NL-2300 RC Leiden, the Netherlands; email: t.s.lapperre@lumc.nl



Chest. 2007;131(1):53-59. doi:10.1378/chest.06-0796
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Background: The single-breath N2 test (sbN2-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 (FEV1, 63 ± 8% of predicted) and sbN2-test (slope of phase III [ΔN2], 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: ΔN2 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 sbN2-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 ΔN2 and BAL NE/neutrophil ratio, and between CC/TLC and BAL neutrophil numbers remained significant when adjusting for FEV1 percentage of predicted.

Conclusions: The results of the sbN2-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.

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