Profiling cellular and inflammatory changes in the airway wall of mild to moderate COPD

Respirology. 2017 Aug;22(6):1125-1132. doi: 10.1111/resp.13021. Epub 2017 Mar 22.

Abstract

Background and objective: The objective of this study was to enumerate total cells and the number of inflammatory cell differentials in large airways (LAs) versus small airways (SAs) of mild-moderate COPD, and against appropriate controls.

Methods: For LA, we used endobronchial biopsies and for SA resected lung tissues. Immunostaining was enumerated (cells per mm2 ) for macrophages, neutrophils, CD4 and CD8 T cells in the lamina propria (LP) up to 150 µM deep for LA and full wall thickness for SA.

Results: We confirmed hypocellularity in the LA and in the SA wall in smokers and COPD (P < 0.001). LA cellularity was least in current smokers with COPD (COPD-CS) (P < 0.01), while SA cellularity was similar across smoker/COPD groups. LA neutrophils were decreased in COPD-CS (P < 0.01), while SA neutrophil counts were unchanged. Compared with controls, LA macrophage numbers in COPD were significantly lower (P < 0.05), with SA macrophage numbers unchanged. A significant increase was observed in SA CD8+ cells in both normal smokers (P < 0.01) and COPD-CS (P < 0.001) but not in LA.

Conclusion: These unique data indicate that the current model for airway wall inflammation in COPD is oversimplified, and contrast with innate inflammatory activation in the lumen, at least in mild-moderate disease. Any abnormalities in airway wall cell differentials are small, although exaggerated in percentage terms.

Keywords: airways; chronic obstructive pulmonary disease; inflammation; inflammatory cells; lung tissue.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bronchi / pathology
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes*
  • CD8-Positive T-Lymphocytes*
  • Female
  • Humans
  • Inflammation / immunology
  • Inflammation / pathology*
  • Lung / pathology
  • Macrophages*
  • Male
  • Middle Aged
  • Neutrophils*
  • Pulmonary Disease, Chronic Obstructive / immunology
  • Pulmonary Disease, Chronic Obstructive / pathology*
  • Respiratory Mucosa / pathology*
  • Tobacco Smoking / pathology
  • Young Adult