Pulmonary Hypertension Associated with Chronic Respiratory Disease

https://doi.org/10.1016/j.ccm.2006.11.006Get rights and content

Pulmonary hypertension (PH) has long been recognized as a complication of chronic respiratory disease. Recent studies have highlighted the adverse impact PH has on the clinical course of these conditions and have cast doubt on the role of hypoxia in their pathogenesis. Clinicians should carefully consider the possibility of PH during the diagnostic evaluation of chronic respiratory disorders. The usefulness of pharmacologic therapy directed toward PH remains to be determined.

Section snippets

Chronic obstructive pulmonary disease

The exact prevalence of PH in chronic obstructive pulmonary disease (COPD) is unclear, but it is more common among patients who have severe airflow limitation. In a recent large French series of patients referred for lung volume reduction surgery or transplantation with a mean force expiratory volume in 1 second (FEV1) of 24% predicted, half had a mean pulmonary artery pressure (MPAP) greater than 25 mm Hg [8]. On average, PH is mild in severity (25–35 mm Hg MPAP) with preserved right

Connective tissue diseases

Interstitial lung disease is the most common pulmonary manifestation of scleroderma (systemic sclerosis). The impact of concomitant PH on the course of interstitial lung disease in systemic sclerosis is becoming increasingly appreciated. A typical pattern is that of mild dyspnea in the setting of stable or slowly declining pulmonary function tests over many years. An abrupt worsening of symptoms, hypoxemia, and DLCO heralds the onset of PH. A recent review of 619 patients by the Johns Hopkins

Sleep-disordered breathing

Episodic and potentially dramatic increases in pulmonary artery pressure accompany apneic episodes in obstructive sleep apnea (OSA), particularly during rapid eye movement sleep [44]. This finding has been largely attributed to hypoxia, although other factors related to large swings in intrathoracic pressure may also be important, such as increased venous return and left ventricular afterload [45]. In contrast to certain animal models, however, intermittent hypoxia does not generally produce PH

Diagnostic evaluation of pulmonary hypertension in respiratory disease

Clinicians traditionally have not aggressively pursued the diagnosis of PH in chronic respiratory diseases, largely because of the lack of specific therapy. However, the increasing array of drugs for pulmonary arterial hypertension may potentially be useful in treating these conditions. A diagnostic evaluation for PH is also clinically important to (1) identify other treatable causes for PH (eg, left heart disease, chronic thromboembolic disease), (2) help delineate the basis for symptoms, (3)

Oxygen therapy and positive pressure ventilation

Correction of hypoxemia with long-term oxygen therapy clearly improves survival in COPD, but only modest, if any, improvements in pulmonary hemodynamics occur. Long-term oxygen therapy prevents progression of PH in COPD [65], [66]. Although no data support the use of long-term oxygen therapy in other hypoxemic lung diseases [67], most clinicians prescribe it, particularly with complicating PH for which a Pao2 of less than 60 mm Hg is required for Medicare coverage, compared with less than 56 mm

Summary

PH is a common, although often overlooked, complication of chronic respiratory diseases. Although often mild and overshadowed by the underlying condition, PH and right ventricular dysfunction can dominate the clinical picture, particularly in certain interstitial lung diseases. A diagnosis of PH has important prognostic implications and helps delineate the basis for symptoms. Further research is needed to improve the diagnostic accuracy of noninvasive testing and to understand the pathogenesis

References (100)

  • S.M. Arcasoy et al.

    Characteristics and outcomes of patients with sarcoidosis listed for lung transplantation

    Chest

    (2001)
  • C.W. Atwood et al.

    Pulmonary artery hypertension and sleep-disordered breathing: ACCP evidence-based clinical practice guidelines

    Chest

    (2004)
  • A. Chaouat et al.

    Pulmonary hemodynamics in the obstructive sleep apnea syndrome. Results in 220 consecutive patients

    Chest

    (1996)
  • R. Kessler et al.

    The obesity-hypoventilation syndrome revisited: a prospective study of 34 consecutive cases

    Chest

    (2001)
  • R.T. Tan et al.

    Utility of CT scan evaluation for predicting pulmonary hypertension in patients with parenchymal lung disease. Medical College of Wisconsin Lung Transplant Group

    Chest

    (1998)
  • D.J. Riley

    Risk of surgical lung biopsy in idiopathic interstitial pneumonias

    Chest

    (2005)
  • J. Zielinski et al.

    Effects of long-term oxygen therapy on pulmonary hemodynamics in COPD patients: a 6-year prospective study

    Chest

    (1998)
  • E.C. Fletcher et al.

    Survival in COPD patients with a daytime PaO2 greater than 60 mm Hg with and without nocturnal oxyhemoglobin desaturation

    Chest

    (1992)
  • K. Fujimoto et al.

    Benefits of oxygen on exercise performance and pulmonary hemodynamics in patients with COPD with mild hypoxemia

    Chest

    (2002)
  • A.L. Olson et al.

    The obesity hypoventilation syndrome

    Am J Med

    (2005)
  • A. Gomez et al.

    Right ventricular ischemia in patients with primary pulmonary hypertension

    J Am Coll Cardiol

    (2001)
  • S.L. Archer et al.

    A placebo-controlled trial of prostacyclin in acute respiratory failure in COPD

    Chest

    (1996)
  • H.A. Ghofrani et al.

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

    Lancet

    (2002)
  • C. Strange et al.

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

    Chest

    (2000)
  • P. Tissieres et al.

    Aerosolized iloprost as a bridge to lung transplantation in a patient with cystic fibrosis and pulmonary hypertension

    Ann Thorac Surg

    (2004)
  • R.A. Krasuski et al.

    Inhaled nitric oxide selectively dilates pulmonary vasculature in adult patients with pulmonary hypertension, irrespective of etiology

    J Am Coll Cardiol

    (2000)
  • J.A. Barbera et al.

    Worsening of pulmonary gas exchange with nitric oxide inhalation in chronic obstructive pulmonary disease

    Lancet

    (1996)
  • G.L. Yung et al.

    Outpatient inhaled nitric oxide in a patient with idiopathic pulmonary fibrosis: a bridge to lung transplantation

    J Heart Lung Transplant

    (2001)
  • I.R. Preston et al.

    Vasoresponsiveness of sarcoidosis-associated pulmonary hypertension

    Chest

    (2001)
  • S. Alp et al.

    Sildenafil improves hemodynamic parameters in COPD-an investigation of six patients

    Pulm Pharmacol Ther

    (2006)
  • B.P. Madden et al.

    A potential role for sildenafil in the management of pulmonary hypertension in patients with parenchymal lung disease

    Vascul Pharmacol

    (2006)
  • T.M. Egan et al.

    Development of the new lung allocation system in the United States

    Am J Transplant

    (2006)
  • G. Simonneau et al.

    Clinical classification of pulmonary hypertension

    J Am Coll Cardiol

    (2004)
  • A. Hyduk et al.

    Pulmonary hypertension surveillance—United States, 1980–2002

    MMWR Surveill Summ

    (2005)
  • A. Chaouat et al.

    Severe pulmonary hypertension and chronic obstructive pulmonary disease

    Am J Respir Crit Care Med

    (2005)
  • H.H. Leuchte et al.

    Brain natriuretic peptide is a prognostic parameter in chronic lung disease

    Am J Respir Crit Care Med

    (2006)
  • A.F. Shorr et al.

    Pulmonary hypertension in advanced sarcoidosis: epidemiology and clinical characteristics

    Eur Respir J

    (2005)
  • L.J. Rubin

    Pulmonary arterial hypertension

    Proc Am Thorac Soc

    (2006)
  • S. Santos et al.

    Characterization of pulmonary vascular remodeling in smokers and patients with mild COPD

    Eur Respir J

    (2002)
  • W. MacNee

    Pathophysiology of cor pulmonale in chronic obstructive pulmonary disease. Part one

    Am J Respir Crit Care Med

    (1994)
  • A.T. Dinh-Xuan et al.

    Impairment of endothelium-dependent pulmonary-artery relaxation in chronic obstructive lung disease

    N Engl J Med

    (1991)
  • J.A. Barbera et al.

    Reduced expression of endothelial nitric oxide synthase in pulmonary arteries of smokers

    Am J Respir Crit Care Med

    (2001)
  • E. Clini et al.

    Production of endogenous nitric oxide in chronic obstructive pulmonary disease and patients with cor pulmonale. Correlates with echo-Doppler assessment

    Am J Respir Crit Care Med

    (2000)
  • B.W. Christman et al.

    An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension

    N Engl J Med

    (1992)
  • A. Giaid et al.

    Expression of endothelin-1 in the lungs of patients with pulmonary hypertension

    N Engl J Med

    (1993)
  • S. Santos et al.

    Enhanced expression of vascular endothelial growth factor in pulmonary arteries of smokers and patients with moderate chronic obstructive pulmonary disease

    Am J Respir Crit Care Med

    (2003)
  • S. Eddahibi et al.

    Polymorphism of the serotonin transporter gene and pulmonary hypertension in chronic obstructive pulmonary disease

    Circulation

    (2003)
  • J.A. Barbera et al.

    Pulmonary hypertension in chronic obstructive pulmonary disease

    Eur Respir J

    (2003)
  • W. MacNee

    Pathophysiology of cor pulmonale in chronic obstructive pulmonary disease. Part two

    Am J Respir Crit Care Med

    (1994)
  • S.M. Scharf et al.

    Hemodynamic characterization of patients with severe emphysema

    Am J Respir Crit Care Med

    (2002)
  • Cited by (0)

    View full text