Pulmonary hypertension complicating pulmonary sarcoidosis

Pulmonary hypertension (PH) is a severe complication of sarcoidosis, with an unknown prevalence. The aetiology is multifactorial, and the exact mechanism of PH in the individual patient is often difficult to establish. The diagnostic work-up and treatment of PH in sarcoidosis is complex, and should therefore be determined by a multidisciplinary expert team in a specialised centre. It is still a major challenge to identify sarcoidosis patients at risk for developing PH. There is no validated algorithm when to refer a patient suspected for PH, and PH analysis itself is difficult. Until present, there is no established therapy for PH in sarcoidosis. Besides optimal treatment for sarcoidosis, case series evaluating new therapeutic options involving PH-targeted therapy are arising for a subgroup of patients. This review summarises the current knowledge regarding the aetiology, diagnosis and possible treatment options for PH in sarcoidosis.     

Pulmonary hypertension associated with sarcoidosis

Pulmonary involvement is common in sarcoidosis, an immune-mediated inflammatory disorder that is characterized by non-caseating granulomas in tissue. Sarcoid patients with advanced pulmonary disease, especially end-stage pulmonary fibrosis, risk developing pulmonary hypertension (World Health Organization group III pulmonary hypertension secondary to hypoxic lung disease). Increased levels of endothelin (ET)-1 in plasma and bronchoalveolar lavage of some sarcoid patients suggest that ET-1 may be driving pulmonary fibrosis and sarcoidosis-associated pulmonary hypertension. Although a relationship between raised levels of ET-1 and clinical phenotype is yet to be identified, early evidence from studies of ET-1 blockade with drugs such as bosentan is encouraging. Such therapy possibly could be combined with standard anti-inflammatory agents to improve outcome.     

Pulmonary function in asthmatic patients in remission.

Thirty-five asthmatic patients (average age 28 years) who attended a pulmonary function laboratory when their mean ratio of forced expiratory volume in one second: forced vital capacity was 81 per cent (within the normal range for their age group) had arterial hypoxaemia and hypocapnia. These were probably secondary to lung hyperinflation and pulmonary ventilation/perfusion imbalance. The pulmonary abnormalities of bronchial asthma are not always detected by simple spirometric tests and the results of such tests should be interpreted cautiously.     

Enigmas in sarcoidosis.

Sarcoidosis is a multisystem granulomatous disorder of unknown cause that presents most frequently in young adults with bilateral hilar adenopathy, pulmonary infiltrates, and skin or eye lesions. The multisystem clinical manifestations of this disease are a diagnostic challenge to all physicians. Although the clinical and pathologic characteristics of sarcoidosis are well described, the decision to treat and the optimal therapy are less well defined. This review focuses on the natural history, clinical manifestations, controversies in therapy, including steroid-sparing agents, and current concepts of how the disease''s activity can be monitored.     

Pulmonary function changes in ozone-interaction of concentration and ventilation.

A total of 28 healthy young subjects have been exposed for 2 h to ozone (0.37-0.75 ppm) under conditions of either rest or intermittent light exercise (sufficient to increase the respiratory minute volume by a factor of 2.5). All pulmonary function tests (vital capacity, forced expiratory volume, maximum expiratory flow-volume curve, slope of phase III of alveolar nitrogen plateau) showed a significant deterioration relative to parallel control experiments. Responses were related to the dose of ozone as calculated from the product of concentration, exposure time, and respiratory minute volume during exposure, changes at 1 h averaging approximately one-half those seen at 2 h.