Mast cell infiltration discriminates between histopathological phenotypes of chronic obstructive pulmonary disease.
BACKGROUND
COPD is a complex disease with heterogeneous manifestations. Attempts have been made to define different phenotypes that could guide toward better disease understanding. We described before that smokers can develop either panlobular (PLE) or centrilobular emphysema (CLE). The latter has worse small airways remodeling and narrowing, which account for the airflow obstruction similar to asthma.


OBJECTIVE
Because of the small airways involvement in CLE similar to asthma, we hypothesized a role for mast cells in CLE but not in PLE. Hence, we investigated mast cell infiltration, along with overall inflammation, and their relation with hyperreactivity and emphysema type in COPD.


METHODS
We studied lung function, emphysema type, mast cells, and overall inflammation in small airways and alveolar walls, along with alveolar wall thickening in 67 subjects undergoing lung resection (59 smokers, 8 nonsmokers).


RESULTS
Twenty-seven smokers had CLE, 24 had PLE, and 8 had no emphysema. Mast cells were significantly increased in CLE compared with PLE and control subjects. Especially relevant was the mast cell increase in airway smooth muscle in CLE, which related significantly to airway hyperreactivity. CD4(+)T cells, neutrophils, and macrophages, but not eosinophils and CD8(+)T cells, were significantly higher in CLE than PLE. Alveolar wall thickness was increased in all smokers, but significantly more in CLE.


CONCLUSIONS
The pathological phenotypes of COPD CLE and PLE show important differences in their overall inflammation with a protagonism of mast cells, which are related to airway reactivity. These findings highlight the distinctness of these COPD phenotypes and the role of mast cells in the pathophysiology of COPD.
Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova, Padova, Italy.
Andrea
A
Ballarin
Erica
E
Bazzan
Rafael Hernandez
RH
Zenteno
Graziella
G
Turato
Simonetta
S
Baraldo
Dora
D
Zanovello
Elena
E
Mutti
James C
JC
Hogg
Marina
M
Saetta
Manuel G
MG
Cosio
D000368:Aged; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation / Q000150:complications / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000648:ultrastructure; D008297:Male; D008407:Mast Cells / Q000276:immunology* / Q000648:ultrastructure*; D008875:Middle Aged; D010641:Phenotype; D011650:Pulmonary Alveoli / Q000276:immunology / Q000648:ultrastructure; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000276:immunology* / Q000473:pathology; D011656:Pulmonary Emphysema / Q000150:complications / Q000276:immunology / Q000473:pathology; D012129:Respiratory Function Tests; D012907:Smoking / Q000276:immunology