Pulmonary hypertension associated with lung diseases

Abstract

Pulmonary hypertension (PH) associated with chronic lung disease (CLD) is both common and underrecognised. The presence of PH in the setting of lung disease has been consistently shown to be associated with worse outcomes. Recent epidemiological studies have advanced understanding of the heterogeneity of this patient population and shown that defining both the specific type of CLD as well as the severity of PH (i.e. deeper phenotyping) is necessary to inform natural history and prognosis. A systematic diagnostic approach to screening and confirmation of suspected PH in CLD is recommended. Numerous uncontrolled studies and one phase 3 randomised, controlled trial have suggested a benefit in treating PH in some patients with CLD, specifically those with fibrotic interstitial lung disease (ILD). However, other studies in diseases such as COPD-PH showed adverse outcomes with some therapies. Given the expanding list of approved pharmacological treatments for pulmonary arterial hypertension, developing a treatment algorithm for specific phenotypes of CLD-PH is required. This article will summarise existing data in COPD, ILD and other chronic lung diseases, and provide recommendations for classification of CLD-PH and approach to the diagnosis and management of these challenging patients.

FIGURE 1

Major components of the updated classification of group 3 pulmonary hypertension (PH). Chronic lung diseases (CLDs) encompass a wide range of parenchymal processes which often have unique pathogenetic mechanisms and clinical presentations. Recent literature demonstrates that there are important pathogenic differences contributing to PH complicating different CLDs, which is likely to impact how these entities respond to therapy. These considerations led to a change in classification of group 3 PH that placed COPD, interstitial lung disease (ILD), combined pulmonary fibrosis emphysema (CPFE) and other parenchymal lung diseases in different categories, in addition to developmental lung diseases, nonparenchymal restriction and hypoxia without lung disease (which are not represented on the figure). Making a diagnosis of CLD-PH requires a multimodal approach, with particular emphasis on a high-quality radiographic assessment.

FIGURE 2

Diagnostic algorithm for pulmonary hypertension (PH) in the setting of COPD and interstitial lung disease (ILD). The decision to perform a right heart catheterisation should be predicated by a clinical or research need that would impact management and/or provide prognostic information, such as considerations of disease phenotyping and therapeutic interventions, clinical trial enrolment, pre-operative clearance/assistance with perioperative management, evaluation for lung transplantation and, in COPD, assessment for lung volume reduction therapy. A multimodal assessment, including lung function, functional, radiographic and echocardiographic data is recommended to determine when to proceed with haemodynamic assessment. Given that in patients with chronic lung diseases the performance characteristics of transthoracic echocardiography are worse due to poor windows, altered location of the heart in the chest cavity and interference due to the lung tissue overlying the heart, in patients with moderate or high clinical suspicion for PH, right heart catheterisation can be considered irrespective of the transthoracic echocardiography findings (as indicated by the dotted line). RV: right ventricular; PFTs: pulmonary function tests; D_LCO: diffusion capacity of the lung for carbon monoxide; K_CO: carbon monoxide transfer coefficient; FVC: forced vital capacity; 6MWT: 6-min walk test; 6MWD: 6-min walk distance; S_aO2: arterial haemoglobin oxygen saturation; HRR: heart rate recovery; P_aO2: arterial partial pressure of oxygen; CPET: cardiopulmonary exercise testing; BNP: brain natriuretic peptide; NT-proBNP: N-terminal pro-BNP; RH: right heart. ^#: in idiopathic pulmonary fibrosis; ^¶: especially in severe PH.

FIGURE 3

Framework for management of patients with interstitial lung disease (ILD)-associated pulmonary hypertension (PH). This figure represents a framework for management of PH in patients with ILD. The columns “Favours PH therapy” and “Does not favour PH therapy” are not prescriptive and are meant to guide providers in selecting appropriate patients for treatment. Each patient needs to be evaluated in the context of their disease and their treatment needs to be individualised. Please refer to the text for further details. PVR: pulmonary vascular resistance; WU: Wood units; mPAP: mean pulmonary arterial pressure; FEV₁: forced expiratory volume in 1 s; FVC: forced vital capacity; BNP: brain natriuretic peptide; NT-proBNP: N-terminal pro-BNP; CT: computed tomography; CTD: connective tissue disease. ^#: inhaled treprostinil where approved; off-label use of other PH drugs such as phosphodiesterase-5 inhibitors in an individualised manner (ambrisentan is contraindicated in idiopathic pulmonary fibrosis and riociguat is contraindicated in idiopathic interstitial pneumonia-PH).