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Differential distribution of inflammatory cells in large and small airways in smokers
  1. Salvatore Battaglia1,
  2. Thais Mauad1,3,
  3. Annemarie M van Schadewijk1,
  4. Antonia M Vignola2,
  5. Klaus F Rabe1,
  6. Vincenzo Bellia2,
  7. Peter J Sterk1,
  8. Pieter S Hiemstra1
  1. 1Department of Pulmonology, Leiden University Medical Centre (LUMC), Leiden, The Netherlands
  2. 2Dipartimento di Medicina, Pneumologia, Fisiologia e Nutrizione Umana (DIMPEFINU), Sezione di Pneumologia e Medicina, Università di Palermo, Palermo, Italy
  3. 3Department of Pathology, Sao Paulo University Medical School, Sao Paulo, Brazil
  1. Correspondence to:
 Dr P S Hiemstra
 Department of Pulmonology, C3-P, Leiden University Medical Centre (LUMC), PO Box 9600, NL-2300 RC Leiden, The Netherlands;p.s.hiemstra{at}


Background: Smoking induces structural changes in the airways, and is considered a major factor in the development of airflow obstruction in chronic obstructive pulmonary disease. However, differences in inflammatory cell distribution between large airways (LA) and small airways (SA) have not been systematically explored in smokers.

Hypothesis: The content of cells infiltrating the airway wall differs between LA and SA.

Aims: To compare the content of neutrophils, macrophages, lymphocytes and mast cells infiltrating LA and SA in smokers who underwent surgery for lung cancer.

Methods: Lung tissue from 15 smokers was analysed. Inflammatory cells in the lamina propria were identified by immunohistochemical analysis, quantified by digital image analysis and expressed as number of cells per surface area.

Results: The number of neutrophils infiltrating the lamina propria of SA (median 225.3 cells/mm2) was higher than that in the lamina propria of LA (median 60.2 cells/mm2; p<0.001). Similar results were observed for mast cells: 313.3 and 133.7 cells/mm2 in the SA and LA, respectively (p<0.001). In contrast, the number of CD4 cells was higher in LA compared with SA (median 217.8 vs 80.5 cells/mm2; p = 0.042). Conclusions: These findings indicate a non-uniform distribution of neutrophils and mast cells throughout the bronchial tree, and suggest that these cells may be involved in the development of smoking-related peripheral lung injury.

  • COPD, chronic obstructive pulmonary disease
  • LA, large airways
  • SA, small airways

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  • Published Online First 17 August 2006

  • Funding: This study was funded by the Università di Palermo and Leiden University Medical Centre, Valeas Italy and Italian Nitric Oxide Club.

  • Competing interests: SB has received unrestricted educational grants from Valeas Italy, GlaxoSmithKline and AstraZeneca. TM has no competing interests. AMvS has no competing interests. KFR has been consulting for participated in advisory board meetings of and received lecture fees from AstraZeneca, Boehringer, Pfizer, Novartis, ALTANA Pharma, MSD and GlaxoSmithKline. VB has participated in advisory board meetings of and received lecture fees from GlaxoSmithKline. The Department of Pulmonology (LUMC) and KFR, PSH and PJS as staff members have received grants from ALTANA Pharma, Novartis, Bayer, AstraZeneca, Pfizer, MSD, Exhale Therapeutics and GSK from 2001 to 2004. The Dipartimento di Medicina, Pneumologia, Fisiologia e Nutrizione Umana (DIMPEFINU) and AMV and VB as staff members have received grants from Bayer, Rhone Poulenc, AstraZeneca, MSD and Aventis Pharma from 2001 to 2004.

  • Professor Vignola died in December 2004.