The Role of Microvascular Injury in the Evolution of Idiopathic Pulmonary Fibrosis

Abstract

Interstitial lung disease compatible with idiopathic pulmonary 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 and/or 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; 1 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 in patients with serologic evidence of active CMV infection despite the absence of cytopathic changes typical of CMV infection. Antiphospholipid antibodies, antiendothelial cell antibodies, and/or endotheliotropic viral infections related to B19 and CMV may be of pathogenetic importance to the evolution of IPF. This report underscores the potential importance of microvascular injury in the evolution of IPF.

Microscopic polyangiitis presenting as a “pulmonary‐muscle” syndrome: Is subclinical alveolar hemorrhage the mechanism of pulmonary fibrosis?

“…Two American Thoracic Society consensus state- ments on the diagnosis of idiopathic interstitial pneumonias have emphasized the importance of excluding "collagen vascular disease" through clinical and laboratory features (8,11), but neither these consensus statements nor several review articles explicitly list MPA or any other form of vasculitis in the differential diagnosis of idiopathic interstitial pneumonia (12)(13)(14). Animal models of IPF indicate that endothelial cell injury and capillary hemorrhage are linked directly to the proliferation of type II pneumocytes and the ensuing fibroplasias (15). The histopathologic features of our case raise the possibility that interstitial lung disease in MPA is caused by repeated subclinical episodes of alveolar hemorrhage.…”

Achados histológicos e sobrevida na fibrose pulmonar idiopática

“…(23) Um recente e provocativo estudo sugeriu que a fibrose pulmonar poderia decorrer de uma agressão primariamente vascular. (16) Concluímos que a avaliação da extensão dos focos fibroblásticos, do grau de faveolamento e, em especial, da obliteração resultante do leito vascular pulmonar, nas bióp-sias pulmonares de pacientes com FPI, fornece informações prognósticas de grande interesse. O estudo de uma nova coorte de pacientes, já em andamento, deverá validar os achados do presente estudo.…”

“…(15) Além disso, foi sugerido recentemente que a lesão microvascular poderia ser o evento inicial e induzir a fibrose pulmonar. (16) Remodelamento vascular extenso ocorre nas áreas de fibrose pulmonar, o que poderia indicar doença mais avançada e pior prognóstico.…”

Exertional dyspnoea in interstitial lung diseases: the clinical utility of cardiopulmonary exercise testing

“…This reversibility seems to diminish over time, as endothelial remodelling develops [24]. In addition, damage of the lung microvasculature by inflammation and fibrosis further increase exercise pulmonary vascular resistance, contributing to the evolution of pulmonary hypertension in ILD [45]. Since inadequate pulmonary blood flow increases effective dead space and leads to an exaggerated ventilator response, both V′E/V′CO 2 and VD/VT appear to be useful surrogate predictors for the presence of pulmonary hypertension [43].…”