Abstract
Recently, several reports suggest differences in the vascularization of the various histopathologic patterns of parenchymal remodeling seen in usual interstitial pneumonia (UIP). In this study, we sought to validate the importance of vascular remodeling in patients with idiopathic pulmonary fibrosis (IPF) and to examine the relationship between vascular remodeling and parenchymal remodeling or pulmonary function. Open lung biopsies were performed in 57 patients with IPF, and vascular changes in alternating areas of parenchymal remodeling (UIP histologic patterns) were studied. Quantitative analysis of the internal area, internal perimeter, wall thickness, and surrounding cellularity of medium or large pulmonary arteries, as well as their distribution according to air/parenchymal ratios, was performed. Semiquantitative analysis also was used to determine the grade of vascular occlusion. An inverse association was found between vascularization and UIP parenchymal remodeling (p < 0.05); that is, the decreased internal luminal area and perimeter as well as the increased wall thickness run in parallel with progression from alveolar collapse toward severe mural-organizing fibrosis with honeycombing. Vascular regression (diminished internal area and perimeter of vessels) was also associated with higher FEV1, FVC, and RV values (r = 0.48, p< 0.05), reflecting a tight relationship between vascular remodeling and pulmonary function. A progressive regression of vascularization, reflected by different degrees of luminal occlusion after vascular remodeling, coincided with parenchymal remodeling (alveolar collapse, mural-organizing fibrosis, and honeycombing). This vascular regression may be responsible for the impaired wound healing and progressive fibroproliferation found in patients with IPF. Further studies are needed to determine whether this relationship is causal or consequential.
Similar content being viewed by others
References
American Thoracic Society (2000) Idiopathic Pulmonary Fibrosis: diagnosis and treatment. International Consensus Statement. Am J Respir Crit Care Med 161:646–664
American Thoracic Society/European Respiratory Society (2002) International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonia. Am J Respir Grit Care Med 165:277–304
Basset F, Ferrans VJ, Soler P, Takemura T, Fukuda Y, Crystal RG (1986) Intraluminal fibrosis in interstitial lung disorders. Am J Pathol 122:443–461
Coalson JJ (1982) The ultrastructure of human fibrosing alveolitis. Virchows Arch A Pathol Anat Hist 395:181–199
Cutaia M, Rounds S (1990) Hypoxic pulmonary vasoconstriction: physiologic significance, mechanism, and clinical relevance. Chest 97:706–718
Demedts M, Costabel U (2002) ATS/ERS international multidisciplinary consensus classification of the idiopathic interstitial pneumonias. Eur Respir J 19:794–796
Fukuda Y, Ferrans VJ, Schoenberger CI, Rennard SI, Crystal RG (1985) Patterns of pulmonary structural remodeling after experimental paraquat toxicity. The morphogenesis of intraalveolar fibrosis. Am J Pathol 118:452–475
Fukuda Y, Ishizaki M, Masuda Y, Kimura G, Kawanami O, Masugi Y (1987) The role of intraalveolar fibrosis in the process of pulmonary structural remodeling in patients with diffuse alveolar damage. Am J Pathol 126:171–182
Heath D, Edwards JE (1958) The pathology of hypertension pulmonary vascular disease. A description of six grades of structural changes in the pulmonary arteries with special reference to congenital cardiac defects. Circulation 18:533–547
Katzenstein AL (1985) Pathogenesis of “fibrosis” in interstitial pneumonia. An electron microscopic study. Hum Pathol 16:1015–1024
Katzenstein AL, Myers JL, Mazur MT (1986) Acute interstitial pneumonia A clinicopathologic, ultrastructural, and cell kinetic study. Am J Respir Grit Care Med 10:256–267
Katzenstein AL, Myers JL (1998) Idiopathic pulmonary fibrosis. Clinical relevance of pathologic classification. Am J Respir Crit Care Med 157:1301–1315
Norusis MJ (2002) SPSS for Windows [10.0]. SPSS Inc., Chicago, IL
Peao MND, Aguas AP, DeSa CM, Grande NR (1994) Neoformation of blood vessels in association with rat lung fibrosis induced by bleomycin. Anat Rec 238:57–67
Renzoni EA, Walsh DA, Salmon M, Wells AU, Sestini P, Nicholson AG, et al (2003) Interstitial vascularity in fibrosing alveolitis. Am J Respir Crit Care Med 167:438–443
Salmon M, Lui YC, Mark JC, Rousell J, Huang TJ, Hisada T, et al (2000) Contribution of upregulation airway endothelin–1 expression to airway smooth muscle and epithelial cell DNA synthesis after repeated allergen exposure of sensitized Brown–Norway rats. Am J Respir Cell Mol Biol 23:618–625
Turner–Warwick M (1963) Precapillary systemic-pulmonary anastomoses. Thorax 18:225–237
Wiebe BM, Laursen H (1998) Lung morphometry by unbiased methods in emphysema: bronchial and blood vessel volume, alveolar surface area and capillary length. APMIS 106(6):651–656
Acknowledgments
This study was supported by the following Brazilian agencies: the National Council for Scientific and Technological Development [CNPq 300430/95-7]; the Foundation for the Support of Research of the State of São Paulo [FAPESP 2000/14336-0, 2001/14566-9 and 2003/00162-9]; and the Laboratories for Medical Research [LIM 05], Clinicas Hospital, School of Medicine, University of São Paulo.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Parra, E.R., David, Y.R., Costa, L.R.S.d. et al. Heterogeneous Remodeling of Lung Vessels in Idiopathic Pulmonary Fibrosis. Lung 183, 291–300 (2005). https://doi.org/10.1007/s00408-004-2542-z
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s00408-004-2542-z