Treatment of Pulmonary Hypertension Associated with Interstitial Lung Disease Using Inhaled Iloprost

Miao Iwai^*
*Correspondence: Miao Iwai, Department of Quantitative Health Sciences, Yale University, New Haven, CT 06520, USA, Email:

Introduction

Pulmonary Hypertension (PH) associated with Interstitial Lung Disease (ILD) is a serious condition that worsens the prognosis of patients with ILD. Management of PH in these patients is complex due to the interdependence of both diseases, limiting treatment options. This case report describes a patient with PH secondary to ILD who was successfully treated with inhaled iloprost, a prostacyclin analogue. This treatment resulted in marked clinical improvement, providing evidence for the efficacy and safety of inhaled iloprost in this population. The following case illustrates its potential use as a treatment option in similar cases. Pulmonary Hypertension (PH) is a condition characterized by elevated Pulmonary Arterial Pressure (PAP), which can complicate various underlying diseases, including Interstitial Lung Disease (ILD). The co-existence of ILD and PH worsens the prognosis, contributing to a more rapid decline in lung function, exercise capacity, and overall survival.

Description

PH in ILD is multifactorial, with chronic hypoxemia, pulmonary vascular remodeling, and the effects of lung fibrosis contributing to increased pulmonary vascular resistance. The combination of these two conditions presents a significant therapeutic challenge, as treatments targeting one condition may adversely affect the other. For instance, therapies aimed at dilating pulmonary vessels may lead to worsened ventilation-perfusion mismatch and oxygenation in patients with ILD. Despite these challenges, targeted therapies for PH, such as inhaled prostanoids, have shown promise in certain cases. Iloprost is a prostacyclin analogue that acts as a potent vasodilator with antiproliferative and anti-inflammatory properties. Inhaled iloprost allows selective pulmonary vasodilation, potentially reducing the systemic side effects seen with intravenous or oral vasodilators. This report discusses a case of PH secondary to ILD successfully managed with inhaled iloprost, demonstrating its potential utility in similar clinical contexts [1].

A 58-year-old female with a five-year history of Idiopathic Pulmonary Fibrosis (IPF), a type of ILD, presented to the outpatient pulmonary clinic with worsening dyspnea on exertion, fatigue, and peripheral edema over the past three months. The patient had been on long-term oxygen therapy for chronic hypoxemia and was receiving antifibrotic therapy with nintedanib. She had no significant cardiovascular history and was compliant with her treatment regimen. On physical examination, the patient was in mild respiratory distress, with a resting oxygen saturation of 88% on 4 liters per minute of supplemental oxygen. Auscultation revealed bilateral inspiratory crackles at the lung bases and a loud P2 heart sound. Peripheral edema was present in both lower extremities. A High-Resolution Computed Tomography (HRCT) of the chest confirmed extensive bilateral fibrotic changes consistent with progressive ILD. Pulmonary Function Testing (PFT) showed a further decline in Forced Vital Capacity (FVC) to 55% of the predicted value, compared to 62% six months prior. Arterial blood gas analysis demonstrated hypoxemia with a partial pressure of oxygen (PaO2) of 58 mmHg [2].

Transthoracic echocardiography revealed right ventricular enlargement and an estimated right ventricular systolic pressure (RVSP) of 60 mmHg, suggestive of PH. The patient subsequently underwent right heart catheterization, which confirmed the diagnosis of PH with a mean pulmonary arterial pressure of 36 mmHg, a Pulmonary Vascular Resistance (PVR) of 4 Wood units, and a normal Pulmonary Capillary Wedge Pressure (PCWP), ruling out left-sided heart failure. Given the diagnosis of PH associated with ILD, therapeutic options were discussed. Due to concerns about worsening gas exchange with systemic vasodilators, inhaled iloprost was selected as a targeted therapy. The patient was started on inhaled iloprost at a dose of 5 mcg, administered six times daily using a nebulizer device. Over the course of three months, the patient demonstrated significant clinical improvement. Dyspnea on exertion improved, and she was able to walk longer distances with reduced symptoms of fatigue. Oxygen saturation levels stabilized, and the requirement for supplemental oxygen remained unchanged, with no worsening of hypoxemia [3].

At the six-month follow-up, repeat echocardiography showed a reduction in RVSP to 45 mmHg, indicating a partial response to therapy. The patient’s quality of life improved, and there was no further decline in PFT results. No significant side effects or complications related to the inhaled iloprost therapy were reported during the treatment period. PH is a common and severe complication of ILD, affecting up to 40% of patients with advanced lung fibrosis. It is associated with worse clinical outcomes, including reduced exercise capacity, frequent hospitalizations, and increased mortality. The presence of PH in ILD creates a complex therapeutic dilemma, as treatments that target pulmonary vasculature may compromise gas exchange, especially in the context of severe lung fibrosis. The pathogenesis of PH in ILD is multifactorial. Chronic hypoxia is a key driver of pulmonary vasoconstriction and vascular remodeling, leading to increased PAP and right heart strain. Additionally, fibrotic destruction of lung parenchyma leads to obliteration of pulmonary capillaries, further increasing vascular resistance. This combination of factors results in elevated PAP and PVR, placing a significant burden on the right ventricle.

Management of PH in patients with ILD is challenging due to the delicate balance between improving pulmonary hemodynamics and maintaining adequate oxygenation. Systemic vasodilators, such as endothelin receptor antagonists and phosphodiesterase-5 inhibitors, have shown limited benefit in this population and may worsen ventilation-perfusion mismatch by dilating poorly ventilated areas of the lung, leading to increased shunt and hypoxemia. Inhaled therapies, however, offer a more targeted approach. Inhaled prostanoids, such as iloprost, selectively dilate the pulmonary vasculature without significant systemic effects. By limiting vasodilation to well-ventilated areas of the lung, inhaled iloprost reduces the risk of worsening gas exchange, making it a viable option for patients with PH secondary to ILD. Iloprost, a synthetic analogue of prostacyclin, works by binding to prostacyclin receptors on pulmonary arterial smooth muscle cells, inducing vasodilation. Inhaled iloprost has been shown to improve exercise capacity and hemodynamics in patients with PH, including those with PH secondary to lung diseases [4].

The inhaled route of administration allows for targeted delivery to the lungs, reducing the risk of systemic hypotension and other side effects associated with systemic vasodilators. In this case, the use of inhaled iloprost led to significant improvements in symptoms and hemodynamics without worsening hypoxemia, supporting its safety in patients with PH and ILD. This case highlights the potential benefits of inhaled iloprost in treating PH associated with ILD. While treatment options for this population are limited, inhaled iloprost offers a promising approach by improving pulmonary hemodynamics while minimizing the risk of worsening oxygenation. Further research, including randomized controlled trials, is needed to establish the long-term efficacy and safety of inhaled iloprost in patients with PH and ILD. There are several limitations to the use of inhaled iloprost in this population. The need for frequent administration (up to six to nine times daily) can be burdensome for patients, and adherence to the regimen may be challenging. Additionally, while this case demonstrates clinical improvement with inhaled iloprost, it is unclear whether long-term use will alter disease progression or survival in patients with PH associated with ILD [5].

Conclusion

Pulmonary hypertension in the setting of interstitial lung disease presents significant therapeutic challenges, as both conditions exacerbate each other and limit treatment options. Inhaled iloprost offers a promising therapy for patients with PH associated with ILD by providing targeted pulmonary vasodilation without compromising oxygenation. In this case, inhaled iloprost resulted in symptomatic and hemodynamic improvement, supporting its use in similar cases. However, larger studies are necessary to confirm its efficacy and establish long-term outcomes in this patient population.

Acknowledgement

None.

Conflict of Interest

None.

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