Idiopathic Pulmonary Fibrosis and Pulmonary Hypertension

Abstract

Idiopathic pulmonary fibrosis (IPF) has a poor prognosis and a course that is unpredictable. Pulmonary hypertension may complicate the course of IPF and potentially impact prognosis. There are multiple factors that might influence the onset and severity of pulmonary hypertension in IPF. The relationship between the physiologic and pathobiologic manifestations of the progressive fibrotic process and interceding pulmonary hypertension has not been well defined. This article serves to explore these relationships and to hypothesize about the possible linkage between these entities. From a prognostic standpoint, recent evidence suggests this to be important to assess for pulmonary hypertension in patients with IPF. The appropriate triggers for evaluating for pulmonary hypertension and the best method of detection require further study. Despite the relative ease of noninvasive methods, such as echocardiography, right-heart catheterization remains the best diagnostic test. The appeal of pulmonary hypertension in IPF is that it may be an enticing therapeutic target in a disease that otherwise does not have any proven effective therapies. Which agent(s) might be useful and when they should be implemented mandate the appropriate studies being performed. Some of the data presented in this article have previously been reported in abstract form only.

Development of pulmonary fibrosis through a pathway involving the transcription factor Fra-2/AP-1

“…However, a recent report has positively correlated pulmonary arterial changes with fibrosis in IPF (12). This report and other findings have raised the question whether the pathogenesis of pulmonary fibrosis and pulmonary hypertension may possibly be linked (11,25). In humans, pulmonary arterial hypertension does not necessarily cause pulmonary fibrosis (25), but additional factors could indeed link vascular disease and fibrosis.…”

“…More recent data have proposed that IPF is an epithelial/mesenchymal disease resulting from repeated epithelial cell injury and aberrant wound healing (8,9). Besides aberrant matrix production by mesenchymal cells, vascular remodeling of pulmonary arteries and pulmonary arterial hypertension have been identified as potential prognostic factors in IPF (10), but the relevance of these findings for the pathogenesis remains unclear (11,12).…”

Automated quantification of radiological patterns predicts survival in idiopathic pulmonary fibrosis

“…In fact, the threshold of 10% decline in FVC is below the degree of normal intraindividual variability, as suggested by recent guidelines [15]. Secondly, physiological measures provide only indirect estimates of the progression of fibrosis, and may be affected by coexisting emphysema and/or pulmonary hypertension that are frequently associated with IPF [7,8]. Lastly, PFTs may not be sensitive enough to detect subclinical progression of fibrosis: FVC decline as defined by current thresholds is a relatively rare event in IPF clinical trials, which has led some authors to suggest that marginal declines in FVC may be more sensitive, though less specific [16].…”

“…decline in forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO) over 6-12 months [2,5,6]. However, the utility of such longitudinal physiological indices for individual patient management is still significantly limited by substantial intra-individual variability, perhaps with confounding by coexisting conditions, such as emphysema or pulmonary hypertension [7,8].…”

Pulmonary hypertension related to pulmonary diseases or hypoxia and its treatment

“…Erken evrede yapılan çalışmalarda PH prevalansı daha düşük çıkmaktadır. 39 olgunun dahil edildiği bir çalışmada olgulara SKK ile yapılan ölçümde PH %33 bulunurken transplantasyon öncesi ölçümlerde bu oran %85'e yükselmiştir (29,30). PH solunum fonksiyon testlerinden DLCO ile ters orantılıdır.…”