Effect of 5 weeks of oral acetazolamide on patients with pulmonary vascular disease: A randomized, double-blind, cross-over trial.

BACKGROUND: The carbonic anhydrase inhibitor acetazolamide stimulates ventilation through metabolic acidosis mediated by renal bicarbonate excretion. In animal models, acetazolamide attenuates acute hypoxia-induced pulmonary hypertension (PH), but its efficacy in treating patients with PH due to pulmonary vascular disease (PVD) is unknown. METHODS: 28 PVD patients (15 pulmonary arterial hypertension, 13 distal chronic thromboembolic PH), 13 women, mean±SD age 61.6±15.0 years stable on PVD medications, were randomised in a double-blind crossover protocol to 5 weeks acetazolamide (250mg b.i.d) or placebo separated by a ≥2 week washout period. Primary endpoint was the change in 6-minute walk distance (6MWD) at 5 weeks. Additional endpoints included safety, tolerability, WHO functional class, quality of life, arterial blood gases, and hemodynamics (by echocardiography). RESULTS: Acetazolamide had no effect on 6MWD compared to placebo (treatment effect: mean change [95%CI] -18 [-40 to 4]m, p=0.102) but increased arterial blood oxygenation through hyperventilation induced by metabolic acidosis. Other measures including pulmonary hemodynamics were unchanged. No severe adverse effects occurred, side effects that occurred significantly more frequently with acetazolamide vs. placebo were change in taste (22/0%), paraesthesia (37/4%) and mild dyspnea (26/4%). CONCLUSIONS: In patients with PVD, acetazolamide did not change 6MWD compared to placebo despite improved blood oxygenation. Some patients reported a tolerable increase in dyspnoea during acetazolamide treatment, related to hyperventilation, induced by the mild drug-induced metabolic acidosis. Our findings do not support the use of acetazolamide to improve exercise in patients with PVD at this dosing. GOV IDENTIFIER: NCT02755298.

[Pulmonary hypertension in connective tissue disease]. / Pulmonale Hypertonie bei Kollagenosen.

Pulmonary arterial hypertension (PAH) is a major complication of systemic sclerosis (SSc) and screening is recommended for a timely initiation of disease-targeted drug therapy to modify disease progression. Patients with SSc-PAH have a better prognosis when detected and treated early. The PAH can occur in all disease stages and subsets of SSc. Regular screening tests, which are indicative for PAH, e.g. echocardiography, diffusion capacity, brain natriuretic protein (BNP) and a 6-min walking test, are recommended to enhance the suspicion, since clinical symptoms are unspecific and occur late in the course of PAH. In patients with suspected PAH, the diagnosis should be confirmed by right heart catheterization. A multidisciplinary approach in expert centres including rheumatologists and respiratory physicians and cardiologists specialized in pulmonary hypertension is mandatory for management of patients with SSc at risk for or with manifest pulmonary arterial hypertension.

[Bilaterale pneumonia after myocardial infarction]. / Bilaterale Pneumonie nach Myokardinfarkt.

A 63-year-old man was admitted with fever and bilateral pulmonary infiltrates accompanied by pleural effusion a few days after ST-segment elevation myocardial infarction treated with primary angioplasty and stent implantation. The diagnosis of early postmyocardial infarction syndrome (Dressler's syndrome) with pulmonary infiltrates was made after ruling out possible differential diagnosis such as pneumonia and congestive heart failure. Infiltrates and markers of inflammation resolved rapidly with systemic steroid therapy. Etiology, diagnosis and treatment of this immunological reaction with inflammation of pericardium, pleura and often pulmonary parenchyma are discussed.

Thalassaemia in Azerbaijan.

beta thalassaemia is present throughout the southern regions of the former USSR. We have defined the clinical picture of the disorder, the spectrum of beta thalassaemia mutations, and the role of customary consanguineous marriage in Azerbaijan, where thalassaemia presents a public health problem of the same order as that in Greece. Contrary to earlier suggestions, we found that the common form of the disorder is typically severe. Typical Turkish, Mediterranean, Azeri, Kurdish, and Asian Indian mutations were found, consistent with the history of the region. The common Mediterranean beta 0 thalassaemia mutation (codon 39) was not found. Three mutations (codon 8-AA, IVS2-1 and IVS1-110) account for over 80% of beta thalassaemia genes. Consanguineous marriage appears to contribute relatively little to the frequency of affected births. These observations provide the basis for a thalassaemia prevention programme in Azerbaijan.