BackgroundAdult patients with cystic fibrosis (CF) frequently have reduced exercise tolerance, which is multifactorial but mainly due to bronchial obstruction. The aim of this retrospective analysis was to determine the mechanisms responsible for exercise intolerance in patients with mild-to-moderate or severe disease.MethodsCardiopulmonary exercise testing with blood gas analysis at peak exercise was performed in 102 patients aged 28 ± 11 years: 48 patients had severe lung disease (FEV1 < 50%, group 1) and 54 had mild-to-moderate lung disease (FEV1 ≥ 50%, group 2). VO2 peak was measured and correlated with clinical, biological, and functional parameters.ResultsVO2 peak for all patients was 25 ± 9 mL/kg/min (65 ± 21% of the predicted value) and was < 84% of predicted in 82% of patients (100% of group 1, 65% of group 2). VO2 peak was correlated with body mass index, C-reactive protein, FEV1, FVC, RV, DLCO, VE/VCO2 peak, VD/VT, PaO2, PaCO2, P(A-a)O2, and breathing reserve. In multivariate analysis, FEV1 and overall hyperventilation during exercise were independent determinants of exercise capacity (R2 = 0.67). FEV1 was the major significant predictor of VO2 peak impairment in group 1, accounting for 31% of VO2 peak alteration, whereas excessive overall hyperventilation (reduced or absent breathing reserve and VE/VCO2) accounted for 41% of VO2 alteration in group 2.ConclusionExercise limitation in adult patients with CF is largely dependent on FEV1 in patients with severe lung disease and on the magnitude of the ventilatory response to exercise in patients with mild-to-moderate lung disease.

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La longue activité explosive du Mont Dore (3,8 à 0,3 Ma), la variété et la dissémination importante de ses téphras en font un stratovolcan d'intérêt majeur pour la corrélation téphrochronologique des formations plio-quaternaires du Massif Central français. Une étude de terrain détaillée et de nombreuses analyses minéralogiques et géochimiques permettent de proposer une nouvelle synthèse téphrostratigraphique calée par rapport aux datations radiométriques existantes (K-Ar et Ar-Ar). Il est ainsi montré que : (1) l'activité explosive commence avec des téphras trachytiques de faible volume ; (2) le cycle plio-pléistocène débute vers 3 Ma par des pyroclastites rhyolitiques distinctes de l'émission majeure de la «Grande Nappe» ; (3) le cycle trachytique moyen (2,6 à 1,5 Ma) regroupe un minimum de S phases pyroclastiques caractérisées par de nombreuses coulées et retombées ; (4) le cycle pléistocène du Sancy (1 à 0,25 Ma) comporte au moins 5 phases d'émissions ponceuses étalées entre 1 et 0,3 Ma. La mise en évidence : (a) de coulées latitiques riches en plagioclases et ferromagnésiens, (b) de coulées trachytiques à feldspaths alcalins, biotite et sphène, (c) de pyroclastites sous-saturées en silice à amphibole brune calcique, augite brune calcique et/ou zircons pyramidaux et (d) de pyroclastites rhyolitiques sans quartz, consacre de nouveaux types, alors que la grande variété des formations souligne la multiplicité des corrélations possibles.

IMPORTANCEThe prevalence of pulmonary embolism in patients with chronic obstructive pulmonary disease (COPD) and acutely worsening respiratory symptoms remains uncertain.OBJECTIVE To determine the prevalence of pulmonary embolism in patients with COPD admitted to the hospital for acutely worsening respiratory symptoms. DESIGN, SETTING, AND PARTICIPANTSMulticenter cross-sectional study with prospective follow-up conducted in 7 French hospitals. A predefined pulmonary embolism diagnostic algorithm based on Geneva score, D-dimer levels, and spiral computed tomographic pulmonary angiography plus leg compression ultrasound was applied within 48 hours of admission; all patients had 3-month follow-up. Patients were recruited from January 2014 to May 2017 and the final date of follow-up was August 22, 2017.EXPOSURES Acutely worsening respiratory symptoms in patients with COPD. MAIN OUTCOMES AND MEASURESThe primary outcome was pulmonary embolism diagnosed within 48 hours of admission. Key secondary outcome was pulmonary embolism during a 3-month follow-up among patients deemed not to have venous thromboembolism at admission and who did not receive anticoagulant treatment. Other outcomes were venous thromboembolism (pulmonary embolism and/or deep vein thrombosis) at admission and during follow-up, and 3-month mortality, whether venous thromboembolism was clinically suspected or not. RESULTS Among 740 included patients (mean age, 68.2 years [SD, 10.9 years]; 274 women [37.0%]), pulmonary embolism was confirmed within 48 hours of admission in 44 patients (5.9%; 95% CI, 4.5%-7.9%). Among the 670 patients deemed not to have venous thromboembolism at admission and who did not receive anticoagulation, pulmonary embolism occurred in 5 patients (0.7%; 95% CI, 0.3%-1.7%) during follow-up, including 3 deaths related to pulmonary embolism. The overall 3-month mortality rate was 6.8% (50 of 740; 95% CI, 5.2%-8.8%). The proportion of patients who died during follow-up was higher among those with venous thromboembolism at admission than the proportion of those without it at admission (14 [25.9%] of 54 patients vs 36 [5.2%] of 686; risk difference, 20.7%, 95% CI, 10.7%-33.8%; P < .001). The prevalence of venous thromboembolism was 11.7% (95% CI, 8.6%-15.9%) among patients in whom pulmonary embolism was suspected (n = 299) and was 4.3% (95% CI, 2.8%-6.6%) among those in whom pulmonary embolism was not suspected (n = 441).CONCLUSIONS AND RELEVANCE Among patients with chronic obstructive pulmonary disease admitted to the hospital with an acute worsening of respiratory symptoms, pulmonary embolism was detected in 5.9% of patients using a predefined diagnostic algorithm. Further research is needed to understand the possible role of systematic screening for pulmonary embolism in this patient population.

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Theranostic assays are based on single-gene testing, but the ability of next-generation sequencing (NGS) to interrogate numerous genetic alterations will progressively replace single-gene assays. Although NGS was evaluated to screen for theranostic mutations, its usefulness in clinical practice on large series of samples remains to be demonstrated. NGS performance was assessed following guidelines. TaqMan probes and NGS were compared for their ability to detect EGFR and KRAS mutations, and NGS mutation profiles were analyzed on a large series of non-small-cell lung cancers (n = 1343). The R correlation between expected and measured allelic ratio, using commercial samples, was >0.96. Mutation detection threshold was 2% for 10 ng of DNA input. κ Scores for TaqMan versus NGS were 0.99 (95% CI, 0.97-1.00) for EGFR and 0.98 (95% CI, 0.97-1.00) for KRAS after exclusion of rare EGFR (n = 40) and KRAS (n = 60) mutations. NGS identified 693 and 292 mutations in validated and potential oncogenic drivers, respectively. Significant associations were found between EGFR and PI3KCA or CTNNB1 and between KRAS and STK11. Potential oncogenic driver mutations or gene amplifications were more frequent in validated oncogenic driver nonmutated samples. This work is a proof of concept that targeted NGS is accessible in routine screening, including large screening, at reasonable cost. Clinical data should be collected and implemented in specific databases to make molecular data meaningful for direct patients' benefit.

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