Associated Pulmonary Hypertension Is an Independent Contributor to Exercise Intolerance in Chronic Fibrosing Interstitial Pneumonias

Abstract

Background: Associated pulmonary hypertension (APH) is frequently observed in fibrosing interstitial pneumonias (FIP), such as idiopathic pulmonary fibrosis (IPF). APH is associated with worse prognosis, but it remains unclear whether it is associated with greater functional impairment. Six-minute walk distance (6MWD) is widely used to assess functional capacity in pulmonary hypertension and FIP. Objectives: To investigate if APH independently contributes to exercise intolerance in FIP, irrespective of the extent of underlying fibrosis. Methods: Patients diagnosed with FIP (September 2009 to June 2017) were included in the study if they underwent right heart catheterization, high-resolution chest computed tomography (HRCT), and 6MWD within 3 months. Recruitment was not limited only to patients undergoing lung transplant assessment. APH was defined as mean pulmonary artery pressure (mPAP) ≥25 mm Hg. The extent of fibrosis was quantified on HRCT using a visual fibrosis score by 2 separate observers. Results: Seventy-two patients (60 with IPF) were identified. Fifty-five patients had APH. mPAP was not significantly different in subgroups stratified according to the extent of fibrosis on HRCT. Pulmonary vascular resistance (PVR) was the strongest predictor of 6MWD on both univariate and stepwise regression analyses, and remained so considering only patients with normal wedge pressure (< 15 mm Hg) (n = 61). HRCT fibrosis score and pulmonary function tests did not significantly correlate with 6MWD. Conclusions: In patients with FIP, PVR is a significant contributor of 6MWD, independently from the extent of fibrosis on HRCT. These results strengthen both the rationale to use 6MWD as endpoint in FIP and to target APH with specific therapies.

Longitudinal functional changes with clinically significant radiographic progression in idiopathic pulmonary fibrosis: are we following the right parameters?

“…The overall extent of pulmonary fibrosis was evaluated with a quantitative visual score [9,25]. Two chest radiologists from different institutions, with specific interstitial lung disease expertise and > 20 years experience (G.S., M.Z.…”

“…Several methods exist to evaluate the extent of lung fibrosis on HRCT and to assess disease progression. These include visual scores [6,9] and automated methods [10][11][12][13]. One recognized limit in the use of HRCT in interstitial lung disease is interobserver variability in terms of pattern recognition [14,15].…”

Pathogenesis, clinical features, and phenotypes of pulmonary hypertension associated with interstitial lung disease: A consensus statement from the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative ‐ Group 3 Pulmonary Hypertension

“…In another study of ILD patients with and without PH, the PVR was able to independently predict the distance walked in the 6MWT. 89 The difference in distance walked during the 6MWT might be even more relevant in severe PH (mPAP >35 mmHg), 90 in comparison to patients without PH or those with mild PH. It is very likely that the impairment of exercise tolerance in ILD‐PH patients is multifactorial being that the parenchymal lung disease, the pulmonary vascular dysfunction, comorbidities, and deconditioning all may play varying roles.…”

Exercise Testing in Idiopathic Pulmonary Fibrosis: Expanding Our Options

“…Although STSTs tests may not fully capture the depth of desaturation seen with the 6MWT in subjects with IPF, they may nevertheless expand our options of exercise testing in fibrosing ILDs. From this perspective, the study of Degano et al[21]sets an interesting framework of research: can STSTs represent a surrogate exercise test for 6MWT to monitor the clinical course of the disease? Can the present results be applied to a wider range of ILDs?…”

“…Can the present results be applied to a wider range of ILDs? Can STSTs capture the significant impact of associated pulmonary hypertension on exercise capacity in fibrosing ILDs [20] [21]?…”