Pulmonary hypertension associated with interstitial lung disease

Patients with pulmonary arterial hypertension associated with collagen vascular diseases (CVD, e.g. scleroderma) are classified as PAH based on the actual WHO classification. Many of these patients have a minor to moderate degree of interstitial lung disease. While clinical efficacy of specific PAH treatment has been proven in CVD associated PAH this has not yet been shown in other forms of interstitial lung disease associated pulmonary hypertension. Interstitial lung diseases lead to dyspnea of the patient due to a combination of restrictive changes of the parenchyma and gas-exchange deterioration. Relevant pulmonary hypertension may develop and significantly contribute to dyspnea at rest or under exercise. The molecular and cellular mechanisms that trigger and expedite the development of pulmonary hypertension in interstitial lung diseases are not well understood. Historical observations suggested a correlation of vital capacity and DLCO with severity of pulmonary hypertension in IPF patients.

Recent data no longer supports a direct correlation of lung function tests to the existence of pulmonary hypertension, which implicates the necessity of focused diagnostic procedures (echocardiography, right heart catheter) to rule out pulmonary hypertension in patients with interstitial lung disease. Elevated levels of brain natriuretic peptide may be a useful plasma marker to detect patients with pulmonary hypertension in this collective . Pulmonary hypertension has an impact on mortality in idiopathic pulmonary fibrosis and interstitial lung disease associated with scleroderma.

Therefore, manifest pulmonary hypertension in patients with ILD warrants treatment in order to improve exercise capacity, dyspnea and survival. Due to the pre-existing gas-exchange problems of these patients, the ideal drug to treat pulmonary hypertension should introduce an intrapulmonary selective vasodilatation, i.e. vasodilatation selectively in well ventilated areas of the lung in order to maintain optimal gas exchange. In patients with idiopathic pulmonary fibrosis, inhaled nitric oxide – the prototype of an intrapulmonary selective vasodilator – and sildenafil were shown to act as intrapulmonary selective vasodilators, whereas intravenous prostacyclin leads to increase in shunt flow fraction and increased hypoxemia. Comparable pulmonary and intrapulmonary selective vasodilatation was shown for inhaled iloprost. Comparable data does not yet exist for the endothelin receptor antagonist bosentan. Long term clinical experience with bosentan does not suggest a negative impact on gas exchange as this drug is supposed to lack acute vasodilatory capacity.

Controlled trials addressing the use of these drugs in pulmonary hypertension associated with interstitial lung disease are still missing. In cases where severity of pulmonary hypertension appears to be inappropriate to the extension of ILD, specific treatments for PAH may be used in the attempt to improve symptoms. However, due to lack of controlled clinical trials, specific treatment currently cannot be generally recommended.

This article was published in Indian Expressnewspaper on 11th May’22 (Mumbai edition - Page 7)on World Pulmonary Hypertension Day.