Impact of bronchoscopic lung volume reduction with endobronchial valves on dynamic hyperinflation: Results from the PIERCE study.

BACKGROUND AND OBJECTIVE: Dynamic hyperinflation (DH) is a major marker of exertional dyspnoea in severe emphysema. We hypothesized that bronchoscopic lung volume reduction (BLVR) using endobronchial valves (EBVs) decreases DH. METHODS: In this prospective bi-centre study from both Toulouse and Limoges Hospitals, we assessed DH during an incremental cycle ergometry before and 3 months after EBVs treatment. The primary objective was to observe the change in inspiratory capacity (IC) at isotime. Target lobe volume reduction (TLVR) and changes in residual volume (RV), forced expiratory volume in one-second (FEV1 ), mMRC, 6 minutes walking distance (6MWD), BODE and other dynamic measures like tele-expiratory volume (EELV) were also analysed. RESULTS: Thirty-nine patients were included, of whom thirty-eight presented DH. IC and EELV at isotime significantly improved (+214 mL, p = 0.004; -713 mL, p Ë‚ 0.001, respectively). Mean changes were +177 mL for FEV1 (+19%, p < 0.001), -600 mL for RV (p < 0.0001), +33 m for 6MWD (p < 0.0001), respectively. Patients who responded on RV (>430 mL decrease) and FEV1 (>12% gain) had better improvements compared to non-responders (+368 mL vs. +2 mL; +398 mL vs. -40 mL IC isotime, respectively). On the opposite, in patients who responded on DH (>200 mL IC isotime increase), changes in TLV (-1216 mL vs. -576 mL), FEV1 (+261 mL vs. +101 mL), FVC (+496 mL vs. +128 mL) and RV (-805 mL vs. -418 mL) were greater compared to non-responders. CONCLUSIONS: DH decreases after EBVs treatment, and this improvement is correlated with static changes.

Auto-adjusted versus fixed positive airway pressure in patients with severe OSA: A large randomized controlled trial.

BACKGROUND AND OBJECTIVE: Continuous positive airway pressure (CPAP) in the treatment of severe obstructive sleep apnoea (OSA) can be used in fixed CPAP or auto-adjusted (APAP) mode. The aim of this prospective randomized controlled clinical study was to evaluate the 3 month-efficacy of CPAP used either in fixed CPAP or APAP mode. METHODS: Eight hundred one patients with severe OSA were included in twenty-two French centres. After 7 days during which all patients were treated with APAP to determine the effective pressure level and its variability, 353 and 351 patients were respectively randomized in the fixed CPAP group and APAP group. After 3 months of treatment, 308 patients in each group were analysed. RESULTS: There was no difference between the two groups in terms of efficacy whatever the level of efficient pressure and pressure variability (p = 0.41). Exactly, 219 of 308 patients (71.1%) in the fixed CPAP group and 212 of 308 (68.8%) in the APAP group (p = 0.49) demonstrated residual apnoea hypopnoea index (AHI) <10/h and Epworth Score <11. Tolerance and adherence were also identical with a similar effect on quality of life and blood pressure evaluation. CONCLUSION: The two CPAP modes, fixed CPAP and APAP, were equally effective and tolerated in severe OSA patients.

Efficiency of a phone coaching program on adherence to continuous positive airway pressure in sleep apnea hypopnea syndrome: a randomized trial.

BACKGROUND: Continuous Positive Airway Pressure (CPAP) remains the reference treatment for moderate to severe forms of the Sleep Apnea/Hypopnea Syndrome (SAHS). Compliance to the treatment appears to be a key factor to improving health status of these patients. METHODS: We conducted a multicenter, prospective, randomized, controlled, parallel group trial of standard support completed or not within 3 months of coaching sessions for newly diagnosed SAHS patients starting CPAP therapy. This study has been recorded by AFSSAPS with the RCB number: 2009-A01127-50 and received favourably by the Human Studies Committee in France. The coaching session consisted of 5 sessions of telephone-based counselling by competent staff. The primary outcome was the proportion of patients using CPAP more than 3 h per night for 4 months; the secondary outcome was mean hours of CPAP usage in the 2 groups. RESULTS: Three hundred and seventy-nine patients fulfilled the inclusion criteria and were randomized. The percentage of patients using CPAP more than 3 h per night for 4 months was 65 % for the standard support group and 75 % for the coached group. This difference reached a statistical significance (χ2 = 3.97). The mean CPAP usage was increased in the coached group versus standard group. A difference of 26 min was observed (4 h34+/-2 h17 and 4 h08+/-2 h25 respectively, p = 0.04). CONCLUSION: This study shows that SAHS patients who benefit from phone coaching are statistically more compliant to CPAP than a standard support group is. A simple phone coaching procedure based on knowledge of the disease and reinforcement messages about treatment benefits helps to improve CPAP adherence in SAHS patients. TRIAL REGISTRATION: NCT02435355.

Isavuconazole Kinetic Exploration for Clinical Practice.

BACKGROUND: Isavuconazole is a new antifungal prodrug for the treatment of invasive aspergillosis and mucormycosis. As no clear pharmacokinetic-pharmacodynamic relationship has been established for patients, therapeutic drug monitoring is not currently required. However, as isavuconazole is a new drug, clinicians are sometimes sceptical about the exposure achieved in their patients and seek pharmacokinetic exploration. A minimal response consists of determining that the patient's pharmacokinetic profile agrees with profiles reported by Desai et al. using concentrations from the SECURE study. METHODS: Based on one concentration and Desai et al.'s population-pharmacokinetic model, it is possible to estimate a patient's most likely pharmacokinetic profile. If a patient's pharmacokinetic profile is close to the profiles reported by Desai et al., therapeutic drug monitoring is not required. In contrast, when the pharmacokinetic profile differs from the Desai et al. profiles, isavuconazole concentration monitoring and pharmacokinetic profile modeling are the only methods for obtaining information on a patient's exposure and the efficacy of isavuconazole. RESULTS: Four patients presented with surprising pharmacokinetic profiles, unexplained by drug interactions or cytochrome P450 3A4/5 polymorphisms. For two of them, a drug dosage adjustment was proposed and applied by clinicians, together with a check for a new pharmacokinetic profile a few days later. CONCLUSIONS: Collecting one blood sample just before the first maintenance dose to make an early estimation of the patient's most likely pharmacokinetic profile is one method of identifying patients with outlier pharmacokinetic behavior.

Differential effects of low and high-dose estradiol on airway reactivity in ovariectomized rats.

The aim of this animal study was to test the hypothesis that low and high doses of 17beta-estradiol (E2) may differentially influence airway responsiveness. Ovariectomized female rats received either placebo or E2 (10 or 100 microg/kg per day) for 21 days. The concentration of inhaled acetylcholine (ACh) required to double pulmonary resistance (EC200 RL) was calculated as the in vivo index of airway responsiveness. Ex vivo airway responsiveness was evaluated by the cumulative concentration-response curve (CCRC) of isolated tracheal segments. Rats treated with low-dose E2 were less responsive to ACh than rats given either placebo or high-dose E2 (P=0.003). Ex vivo, low-dose E2 treatment decreased (P=0.01) and high-dose E2 increased the potency of ACh (P<0.001) compared to placebo. E2 treatment did not alter smooth muscle cross-sectional area or epithelium thickness. Accumulation of liquid within the tracheal mucosa was moderately enhanced by high-dose E2 treatment compared with animals given either placebo or low-dose E2 (P=0.03). We conclude that E2 treatment has differential, dose-dependent effects on airway responsiveness to acetylcholine.

Mediastinal teratoma and trichoptysis.

We report the case of a 22-year-old woman suffering from mature mediastinal teratoma, revealed by trichoptysis, which is an exceptional, but pathognomonic symptom of intrathoracic teratomas. Only eight cases of trichoptysis are reported, none of them involved a mediastinal localization. We present the endoscopic and radiologic presentation, its surgical management, and histologic particularities.

A study of experimental acute lung injury in pigs on zero end-expiratory pressure.

OBJECTIVES: Tidal expiratory flow limitation (EFL) has been reported in humans with acute lung injury (ALI) and assumed to be associated with small airway closure. Detection of EFL is important because by selecting positive end-expiratory pressure at such a level that EFL is no longer present in the tidal breath, the repeated opening and closure of small airways can be prevented. The objective of this study was to investigate the occurrence of EFL in two experimental models of ALI. ANIMALS: Ten female piglets. METHODS: Animals were anaesthetized, tracheotomized and mechanically ventilated on zero end-expiratory pressure. Acute lung injury was induced by oleic acid (OA) (n = 5) or saline lavage (SL) (n = 5). Tidal EFL was assessed by the negative expiratory pressure test. Lung and chest wall mechanics were partitioned using an oesophageal balloon. Resistance and static elastance were assessed by a rapid airway occlusion technique at baseline ventilatory settings. RESULTS: There was no EFL at any time before and after ALI in both models. This may be due to an increased elastance which promoted higher expiratory flow after ALI and to a decreased chest wall to lung static elastance ratio which could favour small airways patency. The similar increase in total lung resistance, in the two models, after ALI was mostly due to an increased airway resistance in the OA model and to the lung tissue resistance in the SL model. CONCLUSIONS AND CLINICAL RELEVANCE: Tidal EFL was not detected in experimental ALI. This finding casts some doubt about the usefulness of some experimental models of ALI to mimic some reported findings in human ALI.