In chronic obstructive pulmonary disease (COPD), the sympathetic nervous system, as well as the renin-angiotensin system, is activated with possible negative systemic effects on skeletal muscles. Angiotensin II type-1 receptor blockers inhibit the sympathetic and reninangiotensin systems and might improve skeletal and respiratory muscle strength in patients in whom these systems are activated.The effects of the angiotensin receptor blocker irbesartan given over 4 months was evaluated in 60 patients with COPD and a forced expiratory volume in one second of ,50% of the predicted value and without obvious cardiovascular disease that would necessitate the administration of an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker.Irbesartan was well tolerated, but did not exert a significant effect on the primary end-point maximum inspiratory pressure. Spirometric results were not affected, but total lung capacity was reduced. Irbesartan led to a significant decrease in haematocrit (46.4¡3.6 to 43.9¡4.3% versus 47.5¡2.4 to 48.7¡3.0% with placebo).In conclusion, respiratory muscle strength in chronic obstructive pulmonary disease patients was not influenced by angiotensin II receptor blockade. However, the changes in haematocrit and total lung capacity following irbesartan raise the possibility that well-known cardiovascular drugs can produce unanticipated beneficial effects in chronic obstructive pulmonary disease patients.

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Background: MET amplifications occur in human tumors, including non-small cell lung cancer (NSCLC).MET inhibitors have demonstrated some clinical activity in MET amplified NSCLC, presumably with a gene dose effect. However, the definition of MET positivity or MET amplification as a potential oncogenic driver is still under debate. In this study, we aimed to establish the molecular subgroup of NSCLC with the highest unequivocal MET amplification level and to describe the prevalence, and histologic and clinical phenotype of this subgroup.Methods: A total of 373 unselected patients with NSCLC were consecutively tested for MET gene copy number (GCN) by FISH. Mean GCN, MET/CEN7 ratio and other FISH parameters were identified and correlated with morphological and molecular pathological characteristics of the tumors as well as with clinical data.Results: Based on the variability of obtained data a top-level category of MET amplification was newly defined (>90th percentile of average GCN; ≥10 MET gene copies per tumor cell). This criterion was fulfilled in 2% of analyzed tumors. These tumors were exclusively poorly differentiated adenocarcinomas with a predominant solid subtype and pleomorphic features. Rarely, co-alterations were detected (KRAS mutation or MET exon 14 skipping mutation). In this top-level group, there were no EGFR mutations or ALK or ROS1 alterations. The most important clinical feature was a significantly shortened overall survival (HR 3.61; median OS 8.2 vs. 23.6 months). Worse prognosis did not depend on initial stage or treatment. Conclusions:The newly defined top-level category of MET amplification in NSCLC defines a specific subgroup of pulmonary adenocarcinoma with adverse prognosis and characteristic morphological features.Lower levels of MET gene copy number seem to have probably no specific value as a prognostic or predictive biomarker.

The examinations revealed a high prevalence of curable stage SPM in HNSCC patients. Adapting a surveillance scheme including a chest CT is recommended.

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