Severe Pulmonary Hypertension in Histiocytosis X

Abstract

Diminished exercise capacity in advanced pulmonary histiocytosis X does not appear to be related to ventilatory limitation but may be related to pulmonary vascular dysfunction. Pulmonary hemodynamics and respiratory function were studied in 21 consecutive patients with advanced pulmonary histiocytosis X, and compared with parameters of patients with other severe chronic lung diseases (29 patients with chronic obstructive pulmonary disease and 14 patients with idiopathic pulmonary fibrosis). All patients with pulmonary histiocytosis X displayed severe pulmonary hypertension: mean pulmonary arterial pressure, 59 +/- 4 mm Hg; cardiac index, 2.6 +/- 0.8 L/min/m(2); and total vascular pulmonary resistance, 25 +/- 3 IU/m(2) (p < 0.05, as compared with patients with other chronic lung diseases). Pa(O(2)) was similar in the three groups, whereas FEV(1) was lower in patients with other chronic lung diseases (p < 0.05). In contrast to other chronic lung diseases, the degree of pulmonary hypertension was not related to variables of pulmonary function in pulmonary histiocytosis X. Histopathology was available for 12 patients with pulmonary histiocytosis X and revealed proliferative vasculopathy involving muscular arteries and veins, with prominent venular involvement. Two consecutive lung samples (taken before and after the occurrence of pulmonary hypertension) were available for six patients with pulmonary histiocytosis X, and showed that pulmonary vasculopathy worsened, whereas parenchymal and bronchiolar lesions remained relatively unchanged. These results indicate that pulmonary hypertension in pulmonary histiocytosis X might be related to an intrinsic pulmonary vascular disease, in which the pulmonary circulation is involved independent of small airway and lung parenchyma injury.

Pulmonary Langerhans'-Cell Histiocytosis

“…Retrospective studies have failed to show correlation between the severity of pulmonary hypertension and impairment in pulmonary function parameters, except for one study showing an inverse relation with forced vital capacity [99]. In contrast to other chronic lung diseases, the pulmonary hypertension in PLCH is associated with a primary pulmonary vasculopathy, which may be observed histopathologically as intimal fibrosis and remodeling of both venous and arterial systems [68]. Progressive vascular involvement may occur in a minority of patients despite relative stability of pulmonary parenchymal lesions.…”

“…Accumulation of pigmented alveolar macrophages in small airways and distal airspaces is also very commonly seen [10,31]. In addition to bronchiolar nodular inflammation and varying degrees of alveolar macrophage infiltration, some cases are associated with extensive vascular involvement resulting in a vasculopathy that may be observed in both arteries and veins [68]. The characteristic cystic lesions form as the peribronchial lesions destroy the cellular and connective tissue components of the bronchiolar walls, resulting in progressive dilatation of the lumina of small airways which are eventually surrounded by fibrous tissue [10,31,69].…”

“…It is increasingly appreciated that the incidence and severity of pulmonary hypertension in PLCH is higher than that observed in other chronic lung diseases such as idiopathic pulmonary fibrosis, and is associated with poor survival [68,98,99]. Retrospective studies have failed to show correlation between the severity of pulmonary hypertension and impairment in pulmonary function parameters, except for one study showing an inverse relation with forced vital capacity [99].…”

“…When pulmonary hypertension is present, therapy with vasodilators including phosphodiesterase inhibitors or endothelin receptor antagonists may be of substantial benefit, and may result in objective reduction in pulmonary artery pressure and improved exercise capacity (unpublished observations). Epoprostenol (prostacyclin) can cause severe pulmonary edema and should be used very cautiously in this patient population given the prominent venous involvement and higher incidence of veno-occlusive disease [68,100]. In addition to appropriate trials of vasodilator therapy, patients with moderate to severe pulmonary hypertension may benefit from anticoagulation and supplemental oxygen to correct underlying hypoxemia.…”

Pulmonary veno-occlusive disease: advances in clinical management and treatments

“…PVOD can also occur in conditions usually associated with pulmonary hypertension including connective tissue diseases [11][12][13], sarcoidosis [14], pulmonary Langerhans cell histiocytosis [7,15,16] and, more rarely, HIV infection [17][18][19].…”