Abstract Despite the availability of vasodilating compounds, pulmonary hypertension (PH) of various origins remains a disease with a poor prognosis. In recent years, pulmonary arterial hypertension (PAH) has been recognized as a predominantly proliferative process. Everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), inhibits cellular protein synthesis and growth not only in lymphocytes but also in cells of the vascular wall. Ten patients suffering from PAH ([Formula: see text]) or chronic thromboembolic PH ([Formula: see text]) with progressive disease despite therapy with at least 2 vasodilating drugs were included in a prospective open-label pilot study. All patients were treated with everolimus in addition to their prior medication. Safety and tolerability were observed throughout the study. Pulmonary vascular resistance (PVR) and 6-minute walk distance (6MWD) were considered coprimary end points. In 2 patients, study medication was stopped prematurely because of an adverse event. One patient had acute bronchitis, and the other had right heart decompensation. The remaining 8 patients exhibited a significant 31% decrease in PVR (median [interquartile range], 1,012 [688-1,344] vs. 663 [546-860] dyn s cm(-5); [Formula: see text]) and an increase in 6MWD (median [interquartile range], 236 [139-350] vs. 298 [207-450] m; [Formula: see text]) after 6 months of treatment with everolimus. In conclusion, in this pilot study antiproliferative therapy with everolimus was well tolerated in patients with PH. The observed improvements in PVR and 6MWD may stimulate further consideration of mTOR inhibition with everolimus for the treatment of PH.
Although asthma is listed as an indication for lung transplantation, only 2 cases have been reported to date. Here, we describe a 42-year-old woman with progressive, severe, persistent bronchial asthma resistant to high-dose oral steroids and adjuvant immunosuppressive therapy. Because conventional and experimental therapeutic strategies failed, the patient was listed for bilateral lung transplantation and received a transplant shortly thereafter. At 12 months after transplantation, her lung function parameters are normal and an asthma attack has not occurred since.
Asthma/surgery , Lung Transplantation , Adrenal Cortex Hormones/therapeutic use , Adult , Asthma/diagnosis , Asthma/drug therapy , Female , Humans , Immunosuppressive Agents/therapeutic use , Oxygen Inhalation Therapy , Respiratory Function Tests , Treatment Outcome
We describe a patient who underwent thoracic radiation therapy for biopsy-proven pulmonary spindle cell sarcoma in the left lower lobe, 15 months after birth. At the age of 37 she developed shoulder pain, fatigue, and progressive exertion dyspnoea. Chest X-ray revealed a pulmonary mass in the left lower lobe due to a cytology-proven malignant tumour.The patient underwent left pneumonectomy. Histology revealed a myosarcoma of the lung, similar to the previous sarcoma. Furthermore, the patient was diagnosed to have Turner syndrome mosaic and chromosomal analysis revealed a translocation t(1;13) in 3/50 metaphases. However a germline mutation of the p53 tumour suppressor gene was excluded. After 2 years of follow-up the patient is stable and there are no signs of recurrence of the tumour.We conclude a re-occurrence of this very rare malignant disorder of the lung after a 36-year interval in a patient with Turner syndrome mosaic. Following initial curative radiation therapy, with a remission over 36 years, lung resection was now successfully performed.
