Original contributionPulmonary vascular lesions in end-stage idiopathic pulmonary fibrosis: histopathologic study on lung explant specimens and correlations with pulmonary hemodynamics
Introduction
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease of unknown origin generally developing in patients older than 50 years. The disease is usually nonreactive to usual therapeutics such as corticosteroids or immunosuppressive drugs, and the usual evolution is toward a progressive worsening of the respiratory condition leading to death within a median duration of 3 years [1], [2], [3]. In the course of IPF, the patients are prone to develop pulmonary hypertension (PH) at rest as well as at exercise, particularly at the advanced stage of the disease [2], [4]. When present at rest, PH is, in general, of mild to moderate severity [5], [6], [7] but may also sometimes be severe as underlined by a recent study [8]. Chronic alveolar hypoxia with subsequent vascular remodeling is probably involved in the pathogenesis of PH in this setting, but the most prominent mechanism is thought to be the reduction of the pulmonary vascular bed due to the extension of fibrosis [9]. In particular, vascular changes are reported as frequent in the scarred areas. They include intimal proliferation and medial thickening of muscular pulmonary arteries and pulmonary veins [10], [11], [12], [13]. However, whether vascular changes in the intervening patches of normal lung are present or absent remains not well known. Moreover, the correlation between histopathologic pulmonary vascular features and pulmonary hemodynamics is not available.
For more than 15 years, our center has developed a lung transplantation (LT) program. For that reason, patients with IPF are frequently referred to our center for consideration of LT. All of them undergo a heart catheterization of the right side (hereafter referred to as RHC) during the selection process, and in those who are transplanted, the explanted lung is available for histopathologic analysis. Therefore, we designed a retrospective study on lung explant specimens from patients who underwent LT for IPF to (1) describe and compare vascular lesions in areas of dense fibrosis and in preserved lung regions, and (2) correlate the histopathologic findings with pulmonary hemodynamics.
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Patients
All the patients with the diagnosis of pulmonary fibrosis who underwent LT at our center between February 1988 and December 2003 were screened for potential inclusion in the study. To homogenize our group of fibrotic patients, we restricted our analysis to the patients with a firm diagnosis of IPF (see hereinbelow). Twenty-six patients who satisfied these inclusion criteria form the basis of the study. The explanted lung specimens of these patients, obtained at the time of LT, were examined
Results
The main demographic, functional, and hemodynamic characteristics of the 26 patients are featured in Table 1.
Discussion
The main results of our study concerning 26 patients transplanted for IPF in our center are the following: (1) Besides the well-known arterial involvement in the dense fibrotic areas, the pulmonary circulation was also affected in the architecturally preserved lung particularly with a lesion of occlusive venopathy in 65% of the patients. (2) The degree of lung fibrosis on macroscopic evaluation was related to PAPm.
The involvement of the pulmonary circulation in IPF is a well-known phenomenon.
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