REVIEW
Pulmonary Hypertension in Patients With Interstitial Lung Diseases

https://doi.org/10.4065/82.3.342Get rights and content

Pulmonary hypertension (PH) in patients with interstitial lung diseases (ILDs) is not well recognized and can occur in the absence of advanced pulmonary dysfunction or hypoxemia. To address this topic, we identified relevant studies in the English language by searching the MEDLINE database (1966 to November 2006) and by individually reviewing the references of identified articles. Connective tissue disease-related ILD, sarcoidosis, idiopathic pulmonary fibrosis, and pulmonary Langerhans cell histiocytosis are the ILDs most commonly associated with PH. Pulmonary hypertension is an underrecognized complication in patients with ILDs and can adversely affect symptoms, functional capacity, and survival. Pulmonary hypertension can arise in patients with ILDs through various mechanisms, including pulmonary vasoconstriction and vascular remodeling, vascular destruction associated with progressive parenchymal fibrosis, vascular inflammation, perivascular fibrosis, and thrombotic angiopathy. Diagnosis of PH in these patients requires a high index of suspicion because the clinical presentation tends to be nonspecific, particularly in the presence of an underlying parenchymal lung disease. Doppler echocardiography is an essential tool in the evaluation of suspected PH and allows ready recognition of cardiac causes. Right heart catheterization is needed to confirm the presence of PH, assess its severity, and guide therapy. Management of PH in patients with ILDs is guided by identification of the underlying mechanism and the clinical context. An increasing number of available pharmacologic agents in the treatment of PH allow possible treatment of PH in some patients with ILDs. Whether specific treatment of PH in these patients favorably alters functional capacity or outcome needs to be determined.

Section snippets

PREVALENCE

The overall prevalence of PH in ILD is not fully known and varies among the ILDs. In a prospective observational study, Leuchte et al19 reported that 31.8% of 88 consecutive patients with various ILDs undergoing right heart catheterization had significant PH (defined as mean PAP >35 mm Hg). Data are available regarding the prevalence of PH in several specific ILDs (Table 1). Perhaps the best known association is with PLCH. Pulmonary Langerhans cell histiocytosis (also known as histiocytosis X,

PATHOGENESIS

The pathogenesis of PH in ILD is incompletely understood and may involve multiple diverse mechanisms, some of which are peculiar to specific forms of ILD, as discussed subsequently. In advanced lung disease, PH generally results from chronic hypoxic pulmonary vasoconstriction and vascular remodeling.4, 48, 49 This vascular remodeling involves all layers of the pulmonary arterial wall and includes intimal thickening and medial hypertrophy. However, PH can be seen in the absence of hypoxemia in

DIAGNOSIS

Because exertional dyspnea is the most common symptom associated with both PH and ILD, the presence of coexisting PH could easily be overlooked in patients with ILD. Furthermore, the development of both PH and ILD is typically insidious and associated with minimal symptoms and signs in earlier stages. Advanced stages of PH are easier to recognize and are associated with symptoms of leg swelling, abdominal bloating and distention, anorexia, plethora, and profound fatigue as right ventricular

TREATMENT

Management of PH in patients with ILD is guided by the clinical context, mechanism underlying PH, severity of PH, and results of vasoreactivity testing performed during right heart catheterization. To a certain extent, PH in ILD is treatable whether one is addressing the PH itself, the underlying ILD, or both (Table 2). Some of the vasomodulating agents used in the treatment of pulmonary arterial hypertension, eg, bosentan, may have beneficial effects on the underlying parenchymal lung disease,

PROGNOSIS

Pulmonary hypertension causes disability and premature death in patients with or without underlying lung disease. Prognosis in patients with ILD and PH is affected by both PH and underlying ILD. The presence of PH in patients with ILD correlates with worse prognosis.11, 12, 13, 14, 16, 17, 114 For example, an increasing PH correlated with worse survival in patients with IPF; those with systolic PAP greater than 50 mm Hg had a median survival of less than 1 year.14 Whether vasomodulator therapy

CONCLUSION

Pulmonary hypertension is an underrecognized complication in patients with ILDs and may arise through multiple mechanisms. The prevalence and clinical implications of PH in patients with ILDs require further clarification. Although some themes may be similar in the pathogenesis of PH in patients with ILDs, there are likely mechanisms peculiar to specific ILDs, and these need to be studied. The presence of PH adds to the symptoms, functional impairment, morbidity, and mortality in these

REFERENCES (114)

  • RW Battle et al.

    Prevalence of pulmonary hypertension in limited and diffuse scleroderma

    Chest

    (1996)
  • CE Cox et al.

    Sarcoidosis

    Med Clin North Am

    (2005)
  • R Sulica et al.

    Distinctive clinical, radiographic, and functional characteristics of patients with sarcoidosis-related pulmonary hypertension

    Chest

    (2005)
  • T Handa et al.

    Incidence of pulmonary hypertension and its clinical relevance in patients with sarcoidosis

    Chest

    (2006)
  • JH Ryu et al.

    Idiopathic pulmonary fibrosis: current concepts

    Mayo Clin Proc

    (1998)
  • CS Glazer et al.

    Occupational interstitial lung disease

    Clin Chest Med

    (2004)
  • RM Tuder et al.

    The pathobiology of pulmonary hypertension: endothelium

    Clin Chest Med

    (2001)
  • G Cella et al.

    Plasma markers of endothelial dysfunction in pulmonary hypertension

    Chest

    (2001)
  • MR MacLean

    Endothelin-1 and serotonin: mediators of primary and secondary pulmonary hypertension?

    J Lab Clin Med

    (1999)
  • Y Braun-Moscovici et al.

    Endothelin and pulmonary arterial hypertension

    Semin Arthritis Rheum

    (2004)
  • SA Yousem

    The pulmonary pathologic manifestations of the CREST syndrome

    Hum Pathol

    (1990)
  • RM Tuder et al.

    Histopathology of pulmonary hypertension

    Chest

    (1998)
  • LJ Smith et al.

    Vascular sarcoidosis: a rare cause of pulmonary hypertension

    Am J Med Sci

    (1983)
  • TE Damuth et al.

    Major pulmonary artery stenosis causing pulmonary hypertension in sarcoidosis

    Chest

    (1980)
  • R Bargout et al.

    Sarcoid heart disease: clinical course and treatment

    Int J Cardiol

    (2004)
  • J Gagermeier et al.

    Abnormal vascular phenotypes in patients with idiopathic pulmonary fibrosis and secondary pulmonary hypertension

    Chest

    (2005)
  • RT Tan et al.

    Utility of CT scan evaluation for predicting pulmonary hypertension in patients with parenchymal lung disease

    Chest

    (1998)
  • E Bossone et al.

    Pulmonary arterial hypertension: the key role of echocardiography

    Chest

    (2005)
  • C Tei et al.

    Doppler echocardiographic index for assessment of global right ventricular function

    J Am Soc Echocardiogr

    (1996)
  • TC Yeo et al.

    Value of a Doppler-derived index combining systolic and diastolic time intervals in predicting outcome in primary pulmonary hypertension

    Am J Cardiol

    (1998)
  • PJ Currie et al.

    Continuous wave Doppler determination of right ventricular pressure: a simultaneous Doppler-catheterization study in 127 patients

    J Am Coll Cardiol

    (1985)
  • DB Badesch et al.

    Medical therapy for pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines

    Chest

    (2004)
  • KK Brown et al.

    Medical treatment for pulmonary fibrosis: current trends, concepts, and prospects

    Clin Chest Med

    (2004)
  • JH Ryu et al.

    Diagnostic approach to the patient with diffuse lung disease

    Mayo Clin Proc

    (2002)
  • DM Rodman et al.

    Successful treatment of sarcoidosis-associated pulmonary hypertension with corticosteroids

    Chest

    (1990)
  • O Sanchez et al.

    Immunosuppressive therapy in connective tissue diseases-associated pulmonary arterial hypertension

    Chest

    (2006)
  • H Kubo et al.

    Anticoagulant therapy for idiopathic pulmonary fibrosis

    Chest

    (2005)
  • K Jones et al.

    Pulmonary vasodilation with prostacyclin in primary and secondary pulmonary hypertension

    Chest

    (1989)
  • C Strange et al.

    Hemodynamic effects of epoprostenol in patients with systemic sclerosis and pulmonary hypertension

    Chest

    (2000)
  • HA Ghofrani et al.

    Sildenafil for treatment of lung fibrosis and pulmonary hypertension: a randomised controlled trial

    Lancet

    (2002)
  • G Simonneau et al.

    Clinical classification of pulmonary hypertension

    J Am Coll Cardiol

    (2004)
  • R Naeije

    Pulmonary hypertension and right heart failure in chronic obstructive pulmonary disease

    Proc Am Thorac Soc

    (2005)
  • KW Presberg et al.

    Pathophysiology of pulmonary hypertension due to lung disease

    Curr Opin Pulm Med

    (2003)
  • R Kessler et al.

    “Natural history” of pulmonary hypertension in a series of 131 patients with chronic obstructive lung disease

    Am J Respir Crit Care Med

    (2001)
  • Nocturnal Oxygen Therapy Trial Group

    Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial

    Ann Intern Med

    (1980)
  • Report of the Medical Research Council Working Party

    Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema

    Lancet

    (1981)
  • K Ashutosh et al.

    Early effects of oxygen administration and prognosis in chronic obstructive pulmonary disease and cor pulmonale

    Am Rev Respir Dis

    (1983)
  • RM Timms et al.

    Hemodynamic response to oxygen therapy in chronic obstructive pulmonary disease

    Ann Intern Med

    (1985)
  • JP Maloney

    Advances in the treatment of secondary pulmonary hypertension

    Curr Opin Pulm Med

    (2003)
  • S Shapiro

    Management of pulmonary hypertension resulting from interstitial lung disease

    Curr Opin Pulm Med

    (2003)
  • Cited by (86)

    • Pulmonary hypertension due to silicosis and right upper pulmonary artery occlusion with bronchial anthracofibrosis

      2021, Respiratory Medicine Case Reports
      Citation Excerpt :

      It is usually not associated with artery occlusion. On the other hand, pulmonary hypertension (PH) can occur with pneumoconiosis, which is associated with interstitial lung disease and hypoxic vasoconstriction [4]. Here, we report a rare case of PH due to silicosis and right upper pulmonary artery occlusion with bronchial anthracofibrosis.

    • Acute Respiratory Failure in Interstitial Lung Disease Complicated by Pulmonary Hypertension

      2020, Respiratory Medicine
      Citation Excerpt :

      Shorr et al. (2005) reported ~75% of pre-transplant patients with advanced sarcoidosis had PH on RHC [17]. The reported incidence of PH in systemic sclerosis (SSc) patients is up to 45% [22,26] and moderate to severe PH is reported in 17.9% of SSc patients [19]. The prevalence of PH in SSc-ILD has been estimated at 12% and is associated with increased risk of overall mortality [27].

    • Increasing Opportunity for Lung Transplant in Interstitial Lung Disease With Pulmonary Hypertension

      2018, Annals of Thoracic Surgery
      Citation Excerpt :

      The use of ECMO as BTT is increasing as outcomes for its use improve for a wide variety of conditions [6–8]. A significant proportion of patients with ILD have associated PH, and the PH in these patients is an independent risk factor for pretransplant mortality [10, 11]. There is a notably different response to mechanical circulatory support in patients with end-stage ILD-PH, which may be in part due to the presence of right ventricular strain and reduced cardiac output.

    • Pulmonary hypertension

      2018, Cardiac Intensive Care
    View all citing articles on Scopus
    1

    Dr Krowka has received grant support from CoTherix, Inc. Dr McGoon is a consultant for Medtronic, Inc, a steering committee member for CoTherix, Inc, and Myogen, a data safety and monitoring committee member for United Therapeutics, and a central event committee member for Actelion; he has received grant/research support from Medtronic, Inc, CoTherix, Inc, and Myogen.

    View full text