Immunohistochemical and morphometric evaluation of COX 1 and COX-2 in the remodeled lung in idiopathic pulmonary fibrosis and systemic sclerosis.
OBJECTIVE
To study the expression of COX-1 and COX-2 in the remodeled lung in systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF) patients, correlating that expression with patient survival.


METHODS
We examined open lung biopsy specimens from 24 SSc patients and 30 IPF patients, using normal lung tissue as a control. The histological patterns included fibrotic nonspecific interstitial pneumonia (NSIP) in SSc patients and usual interstitial pneumonia (UIP) in IPF patients. We used immunohistochemistry and histomorphometry to evaluate the expression of COX-1 and COX-2 in alveolar septa, vessels, and bronchioles. We then correlated that expression with pulmonary function test results and evaluated its impact on patient survival.


RESULTS
The expression of COX-1 and COX-2 in alveolar septa was significantly higher in IPF-UIP and SSc-NSIP lung tissue than in the control tissue. No difference was found between IPF-UIP and SSc-NSIP tissue regarding COX-1 and COX-2 expression. Multivariate analysis based on the Cox regression model showed that the factors associated with a low risk of death were younger age, high DLCO/alveolar volume, IPF, and high COX-1 expression in alveolar septa, whereas those associated with a high risk of death were advanced age, low DLCO/alveolar volume, SSc (with NSIP), and low COX-1 expression in alveolar septa.


CONCLUSIONS
Our findings suggest that strategies aimed at preventing low COX-1 synthesis will have a greater impact on SSc, whereas those aimed at preventing high COX-2 synthesis will have a greater impact on IPF. However, prospective randomized clinical trials are needed in order to confirm that.
University of São Paulo, School of Medicine, São Paulo, Brazil.
Edwin Roger
ER
Parra
University of São Paulo, School of Medicine, São Paulo, Brazil.
Flavia
F
Lin
University of São Paulo, School of Medicine, São Paulo, Brazil.
Vanessa
V
Martins
University of São Paulo, School of Medicine, São Paulo, Brazil.
Maristela Peres
MP
Rangel
University of São Paulo, School of Medicine, Department of Pathology, São Paulo, Brazil.
Vera Luiza
VL
Capelozzi
D000328:Adult; D000367:Age Factors; D000368:Aged; D056151:Airway Remodeling; D001706:Biopsy; D051545:Cyclooxygenase 1 / Q000032:analysis*; D051546:Cyclooxygenase 2 / Q000032:analysis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D007150:Immunohistochemistry; D008168:Lung / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011650:Pulmonary Alveoli / Q000503:physiopathology; D012129:Respiratory Function Tests; D012595:Scleroderma, Systemic / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate
D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2