The role of microvascular injury in the evolution of idiopathic pulmonary fibrosis

Interstitial lung disease compatible with idiopathicpulmonary fibrosis (IPF) developed in 19 previously healthy patients. Although interstitial and/or honeycomb parenchymal fibrosis was present in all, there were patchy areas of paucicellular septal capillary injury along with corroborative direct immunofluorescent evidence of a humorally mediated microvascular injury syndrome. Significantly elevated factor VIII levels were seen in 17 of 18 patients tested. Antiphospholipids were present in all 18 patients tested, comprising antibodies of phosphatidylethanolamine, beta-2 glycoprotein, phosphatidylcholine, and/or phosphatidylserine. Anti-Ro andlor anti-ribonucleoprotein (RNP) antibodies were seen in 4 patients. Serologic evidence of infection with cytomegalovirus (CMV) was found in 9 patients and parvovirus B19 (B19) in 9 patients; I patient was not tested. Molecular studies revealed B19 DNA in 6 of 6 B19-seropositive patients. In situ hybridization studies revealed CMV RNA in pulmonary cells inpatients with serologic evidence of active CMV infection despite the absence of cytopathic changes typical of CMV infection. Antiphospholipid antibodies, antiendothelial cell antibodies, andlor endotheliotropic viral infections related to B19 and CMV may be of pathogenetic importance to the evolution of IPE This report underscores the potential importance of microvascular injury in the evolution of IPF.