“Natural History” of Pulmonary Hypertension in a Series of 131 Patients with Chronic Obstructive Lung Disease

Abstract

The prognostic value and the evolution of pulmonary hypertension (PH) in patients with markedly hypoxemic chronic obstructive pulmonary disease (COPD), treated or not with long-term oxygen therapy (LTOT), has been extensively investigated. However, little is known in patients with mildly or moderately hypoxemic COPD not requiring LTOT. Therefore, we assessed the evolution of pulmonary hemodynamics in 131 patients with stable COPD by performing two right heart catheterizations at a mean (+/- SD) time interval of 6.8 +/- 2.9 yr. At inclusion (T0), no patient had PH (i.e., the mean pulmonary artery pressure [Ppa] at rest was < 20 mm Hg). Group 1 included 55 patients without exercising PH and group 2 included 76 patients with exercising PH, defined by a pulmonary arterial pressure (Ppa) > 30 mm Hg during a steady-state 40-W exercise. Group 2 patients compared with group 1 patients had a significantly higher resting Ppa (16 +/- 3 mm Hg versus 14 +/- 2 mm Hg, p = 0.001). At the second catheterization, 33 (25%) patients (9 of 55 in group 1, 24 of 76 in group 2, p = 0.048) showed a resting Ppa > 20 mm Hg, but PH was generally mild, ranging from 20 to 42.5 mm Hg. The mean Ppa at second evaluation was 16 +/- 5 mm Hg in group 1 and 19 +/- 7 mm Hg in group 2 (p = 0.01). The patients who developed resting PH at the second catheterization (T1) had higher resting and exercising Ppa (p = 0.001 and p = 0.002, respectively), and significantly lower resting and exercising Pa(O(2)) (p = 0.005 and p = 0.012, respectively) at T0. Logistic regression analysis showed that resting and exercising Ppa were independent predictors (at T0) for the subsequent development of PH (p = 0.029 and p = 0.027, respectively). The patients who developed resting PH (T1) had a significantly worsening of Pa(O(2)) (from 63.5 mm Hg at T0 to 60 mm Hg at T1, p = 0.047), whereas the Pa(O(2)) as a mean was stable in the remainder (69.5 mm Hg at T0 and T1). These results show the following. The progression of Ppa over time in patients with COPD with mild to moderate hypoxemia is rather slow, the average change for the group as a whole being of + 0.4 mm Hg/yr. Only about 25% of patients with COPD with mild to moderate hypoxemia and without resting PH at the onset will develop PH during a 6-yr follow-up. The patients with exercising PH at the onset have a significantly increased risk of developing PH over time. Only resting and exercising Ppa at the onset are independently related to the subsequent development of PH. However, in individual cases, the models of linear or logistic regression do not allow a pertinent prediction of the level of Ppa or the presence of PH at the second right heart catheterization.

Extrapulmonary comorbidities in chronic obstructive pulmonary disease: state of the art

“…COPD-associated PH is increasingly common in more severe disease, and tends to progress slowly [48] and reduce survival [26]. The overall prevalence in the modern era is likely to be lower than data from before the widespread use of long-term oxygen therapy (LTOT), as PH in COPD is generally driven by hypoxia-induced vascular remodeling, although endothelial dysfunction may play a part in milder stages of the disease.…”

Pathology of Pulmonary Hypertension

“…We will frame this review on the pathology of PH within the functional categories proposed previously i.e., that PH can be broadly divided into mild/moderate vs. severe based on pulmonary artery pressures, their impact on right ventricular performance, and overall mortality [1] (Tables 1 and 2). Many non neoplastic lung diseases with intima thickening or medial hypertrophy, such as idiopathic interstitial pneumonias (IPF) [2] and chronic obstructive pulmonary diseases (COPD) [3], present with mild/moderate PH. On the other hand, conditions associated with endothelial cell proliferative lesions (including plexiform lesions), marked intima fibrosis (such as idiopathic pulmonary arterial hypertension (IPAH) and scleroderma), or medial and intimal smooth muscle cell growth (as observed in a fraction of IPF or COPD lungs) cause severe PH.…”

Exercise‐induced pulmonary hypertension associated with systemic sclerosis: Four distinct entities

“…Abnormal exercise physiology has been recognized in SSc, idiopathic PAH, idiopathic pulmonary fibrosis (IPF), and chronic obstructive pulmonary disease (21,28,(34)(35)(36)(37)(38)(39)(40). Studies have described exerciseinduced PH in 46-59% of patients with scleroderma spectrum disorders, characterized by Doppler echocardiogram pulmonary artery systolic pressure Ͼ40 mm Hg during exercise (23,41,42).…”

“…Few studies have used right heart catheterization to address whether an mPAP Ͼ30 mm Hg during exercise represents an aberrant pulmonary vascular system in "at-risk" populations (19,21,28,34,38,39,43). Recently, Tolle and coworkers evaluated a large cohort of non-SSc symptomatic patients who underwent simultaneous cardiopulmonary exercise testing and right heart catheterization (21).…”