Review Article
Pulmonary Hypertension Idiopathic Pulmonary Fibrosis: A Dastardly Duo

https://doi.org/10.1097/MAJ.0b013e31827871dcGet rights and content

Abstract

Pulmonary hypertension (PH) is a well-recognized complication of interstitial lung disease, including idiopathic pulmonary fibrosis (IPF). The underlying pathogenesis was initially hypothesized to be inflammatory but now is characterized as an over exuberant fibroproliferative process. The prevalence of PH in the setting of IPF has not been well described in the literature, with a reported occurrence from 32% to 85%. Diagnostically, recognizing underlying PH in the setting of IPF remains challenging because of nonspecific clinical symptoms and unrevealing ancillary testing. A high degree of clinical suspicion is paramount. The only reliable diagnostic tool for PH is right heart catheterization. The treatment of PH, in patients with IPF, is based on multiple factors, including disease severity, functional status and degree of hypoxemia. Medications currently approved to treat PH have been administered for PH in the setting of IPF, such as phosphodiesterase-5 inhibitors, nonselective endothelin receptor antagonists and prostacyclin analogues. The treatment of PH in the setting of IPF may also be difficult due to worsening ventilation-perfusion mismatch induced by selective pulmonary artery vasodilator therapy. Lung transplantation should be considered with patients refractory to pharmacological treatment. Identification of PH in IPF patients is crucial, as functional status and prognosis are greatly reduced. Given the high mortality rate and propensity for acute decompensation, IPF and PH patients should be evaluated for transplant early in their disease course.

Section snippets

PREVALENCE

The prevalence of PH in the setting of IPF has not been well described in the literature, with a reported occurrence from 32% to 85%.5 This wide range is hypothesized to be because of RHC timing in the patients’ disease course. This disparity was addressed in a retrospective review of 39 IPF patients, where serial RHC was performed. Initial readings revealed a prevalence of 33%, whereas the second and third readings obtained closer to time of lung transplantation revealed an 85% prevalence.6 A

PATHOGENESIS

The pathogenesis of PH in the setting of IPF is complex and largely undefined. Several pathologic mechanisms have been implicated, including reduced endothelial cell prostacyclin production, elevated endothelin levels from enhanced production and reduced clearance, decreased nitric oxide synthase expression, decreased pulmonary vascular smooth muscle voltage-gated potassium channels, increase of proinflammatory cytokines and development of a prothrombotic state.9 Each of these processes favor

DIAGNOSIS

Diagnosis of PH in the setting of IPF can be challenging, relying on a high index of clinical suspicion as both signs and symptoms of each disease process share numerous clinical features, such as dyspnea, palpitations and chest discomfort. To date, there is no validated standardized clinical approach to evaluate an IPF patient who is suspected to have developed concurrent PH. The physical examination may provide the first clues. Patients may have an accentuated P2 component of the second heart

TREATMENT

The treatment of PH in patients with IPF is based on multiple factors, including disease severity, functional status and level of hypoxemia. Medications currently approved to treat PAH have been administered for PH in the setting of IPF, such as phosphodiesterase-5 inhibitors, nonselective endothelin receptor antagonists and prostacyclin analogues. PH experts and guidelines state that patients with more advanced PH including high-risk features should be considered for parenteral prostacyclin

CONCLUSIONS

IPF and PH convey a dismal prognosis in isolation and when combined, portend even worse outcomes. Diagnostically, recognizing underlying PH in the setting of IPF remains challenging because of nonspecific clinical symptoms and unrevealing ancillary testing. A high degree of clinical suspicion is paramount, as underlying PH will remain undetected. Currently, the only reliable diagnostic tool for PH is RHC, which is both invasive and costly. However, to make the correct diagnosis, RHC is

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Curt J. Daniels is receiving grant funding outside of the submitted work. The remaining authors have no financial or other conflicts of interest to disclose.

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