Gaining insights into pulmonary hypertension in respiratory diseases

Abstract

@ERSpublications Pulmonary hypertension associated with respiratory disease is a difficult to manage condition with significant burden http://ow.ly/S1COQPulmonary hypertension (PH) associated with respiratory diseases, group 3 in the current classification [1], is one of the most frequent presentations of PH. Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are the two most common respiratory disorders associated with PH. In these conditions the presence of PH is associated with shorter survival [2,3] and worse clinical course [4]. Yet, much is still unknown about group 3 PH regarding its prevalence in the whole disease spectrum, noninvasive markers that might facilitate its recognition and, most importantly, how to treat it.The majority of studies assessing prevalence of PH in chronic respiratory diseases have been conducted in patients with advanced disease [5,6]. Little is known about moderate disease stages. Recent studies report a prevalence of PH among COPD patients in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 2 and 3 of 7% and 25%, respectively [7,8], and among 8-15% of patients with IPF at their diagnostic evaluation [3,9]. Regarding treatment of PH, only a few trials have assessed the effects of targeted therapy in patients with chronic respiratory diseases, most of them with negative results [10][11][12][13]. For this reason current guidelines do not recommend such treatment until more evidence on its efficacy is available [1,6]. Two articles in this issue of the European Respiratory Journal provide further insights into group 3 PH [14,15], particularly regarding its prevalence and response to treatment. RAGHU et al. [14] report the characteristics and outcomes of patients with IPF and PH that participated in the ARTEMIS-IPF trial, a randomised, placebo-controlled study to evaluate the effectiveness and safety of ambrisentan in IPF. The trial was terminated prematurely because ambrisentan-treated patients were at increased risk for disease progression and respiratory hospitalisations [16]. The ARTEMIS-IPF study enrolled 494 patients with mild-to-moderate IPF and all patients underwent right heart catheterisation (RHC) at baseline. At the time of study termination, 117 patients had undergone a second RHC after 48 weeks, allowing the investigators to document prevalence and progression of PH in a large cohort of patients with mild-to-moderate IPF. Their results show that precapillary PH was present in 14% of patients. The reported prevalence concurs with that seen in patients with IPF at their initial evaluation [3,9] and contrasts with that observed in patients with advanced IPF candidates for lung transplantation, where it is 2-3 times higher [17]. Prevalence of PH in mild-to-moderate IPF is also similar to that observed in GOLD stage 2 and 3 COPD [7,8]. PH was of mild severity in the majority of patients and only 4% had severe PH [6]. 4% of patients developed PH at the follow-up RHC, with an estimated progression of pulmonary artery press...

Chronic use of PAH‐specific therapy in World Health Organization Group III Pulmonary Hypertension: a systematic review and meta‐analysis

“…[1][2][3][4][5][6][7][8][9] PH in COPD and ILD increases symptomatic burden, costs, and reduces survival. [1][2][3][4][5][6][7][8][9][10] Although not extensively studied in the WHO Group III PH population, many providers are using pulmonary arterial hypertension (PAH)-specific therapy for WHO Group III PH patients. In fact, a recent study showed 80% of PH referral centers in the USA use PAH-specific therapy in WHO Group III PH patients.…”

“…11 Use of PAH-specific therapy in WHO Group III PH patients is controversial as these medications are only approved for WHO Groups I and IV patients, and there is theoretical concern that the pulmonary vasodilation could result in ventilation perfusion (V/Q) mismatch and subsequently worsen hypoxemia. 10 However, small clinical trials in COPD-PH and ILD-PH patients showed PAH-specific medications were safe, but the therapeutic benefit was unclear. [12][13][14][15][16][17][18][19][20][21] In order to gain better insight into the utility of PAH-specific therapy in WHO Group III PH, we conducted a systematic review and meta-analysis.…”

Survival in pulmonary hypertension due to chronic lung disease: Influence of low diffusion capacity of the lungs for carbon monoxide

“…Pulmonary hypertension (PH) in the setting of chronic lung disease or World Health Organization (WHO) Group 3 PH is the second most common cause of PH after left heart disease. 1,2 Group 3 patients have a high symptom burden 3 and poor long-term outcomes with a median survival of only 2 to 5 years after diagnosis. 2,4–8 Furthermore, there are no approved treatments for Group 3 PH, and pulmonary vasodilator therapy does not improve exercise capacity or reduce symptom burden.…”

Progenitor cell mobilisation and recruitment in pulmonary arteries in chronic obstructive pulmonary disease

“…Pulmonary vascular abnormalities, as shown by alterations in vessel structure, abnormal cell growth, endothelial dysfunction and resistance to apoptosis, are characteristic features in COPD [4, 5]. An altered pulmonary vascular function in COPD patients may predispose to pulmonary hypertension, which is associated with adverse outcomes [6]. Growing evidence suggests that endothelial cell damage found in pulmonary vessels of COPD patients is an initial and important triggering factor that promotes pulmonary vascular remodelling [5].…”