Efficacy and safety of direct switch to indacaterol/glycopyrronium in patients with moderate COPD: the CRYSTAL open-label randomised trial.

BACKGROUND: Dual bronchodilation combining a long-acting ß2-agonist (LABA) and a long-acting muscarinic antagonist (LAMA) is the preferred choice of treatment recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 guidelines for the management of patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). The once-daily (q.d.) fixed-dose combination (FDC) of LABA, indacaterol 110 µg and LAMA, glycopyrronium 50 µg (IND/GLY 110/50 µg q.d.) demonstrated superior improvements in lung function, dyspnoea and overall health status and better tolerability against LABA or LAMA monotherapies and combination of LABA and inhaled corticosteroid (ICS) in more than 11,000 patients with moderate-to-severe COPD in several randomised controlled clinical trials. METHODS: The CRYSTAL study was the first, 12-week, randomised, open-label trial that evaluated the efficacy and safety of a direct switch from previous treatments to IND/GLY 110/50 µg q.d. on lung function and dyspnoea in patients with moderate COPD and a history of up to one exacerbation in the previous year. Patients were divided into 2 groups according to their background therapy and symptom scores and were randomised (3:1) to IND/GLY or to continue with their previous treatments. RESULTS: The study included 4389 randomised patients, of whom 2160 were in groups switched to IND/GLY (intention-to-treat population). The effect of IND/GLY was superior to LABA + ICS on trough forced expiratory volume in 1 s (FEV1; treatment difference, Δ = +71 mL) and transition dyspnoea index (TDI; [Δ = 1.09 units]), and to LABA or LAMA on trough FEV1 (Δ = +101 mL) and a TDI (Δ = 1.26 units). Improvements in health status and lower rescue medication use were also observed with IND/GLY. The safety profile of the study medication was similar to that observed in previous studies. CONCLUSIONS: IND/GLY demonstrated superior improvements in lung function and dyspnoea after direct switch from previous treatments. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT01985334 .

Early bronchodilator action of glycopyrronium versus tiotropium in moderate-to-severe COPD patients: a cross-over blinded randomized study (Symptoms and Pulmonary function in the moRnING).

BACKGROUND: Morning symptoms associated with COPD have a negative impact on patients' quality of life. Long-acting bronchodilators with rapid onset may relieve patients' symptoms. In the Symptoms and Pulmonary function in the moRnING study, we prospectively compared the rapid onset bronchodilator profile of glycopyrronium (GLY) and tiotropium (TIO) during the first few hours after dosing in patients with moderate-to-severe COPD. METHODS: Patients were randomized (1:1) to receive either once-daily GLY (50 µg) or TIO (18 µg) and corresponding placebos in a cross-over design for 28 days. The primary objective was to demonstrate the superiority of GLY versus TIO in area under the curve from 0 to 4 hours (AUC0-4h) forced expiratory volume in 1 second (FEV1) after the first dose. The secondary objective was to compare GLY versus TIO using the patient reported outcomes Morning COPD Symptoms Questionnaire 3 hours post-inhalation. RESULTS: One-hundred and twenty-six patients were randomized (male 70.2%; mean age 65.7 years) and 108 patients completed the study. On Day 1, GLY resulted in significantly higher FEV1 AUC0-4h after the first dose versus TIO (treatment difference [Δ], 0.030 L, 95% confidence interval 0.004-0.056, P=0.025). Improvements in morning COPD symptoms from baseline at Days 1 and 28 were similar between GLY and TIO. Post hoc analysis of the FEV1 AUC0-4h by time point on Day 1 showed significant improvements in patients receiving GLY versus TIO at 5 minutes (Δ=0.029 L, P=0.015), 15 minutes (Δ=0.033 L, P=0.026), and 1 hour (Δ=0.044 L, P=0.014). Safety results were comparable between both treatments. CONCLUSION: The SPRING study demonstrates the superiority of GLY versus TIO in terms of superior bronchodilation in the first 4 hours after administration, thus extending the clinical data that support a faster onset of action of GLY versus TIO.

Association between resting energy expenditure, psychopathology and HPA-axis in eating disorders.

AIM: To investigate the complex relationships between resting energy expenditure (REE), eating psychopathology, and Hypothalamus Pituitary Adrenal axis functioning in patients with eating disorders. METHODS: The study was designed as a cross-sectional survey, and it was planned by the Clinic for Eating Disorders of the University of Florence (Italy). The protocol was approved by the Ethics Committee of the Institution. Twenty two anorexia nervosa and twenty one Bulimia Nervosa patients were assessed by means of a clinical interview and the structured clinical interview for diagnostic and statistical manual of mental disorders, fourth edition. Eating attitudes and behaviour were specifically investigated by means of the eating disorder examination questionnaire (EDE-Q). Patients were also evaluated by means of the symptom checklist (SCL 90-R), REE was measured by means of indirect calorimetry, and blood cortisol morning levels were evaluated. RESULTS: Both anorexia nervosa and bulimia nervosa patients showed a reduced REE as compared with predicted REE. Body mass index (BMI) was positively associated with resting energy expenditure in Bulimics, whereas a strong, negative association between BMI and REE was observed in Anorectics. The pattern of associations between variables supported a mediation model, where shape concern accounted for variations in REE and cortisol levels (mediator), and variations in the mediator significantly accounted for variations in REE. When these associations where taken into account together, the relationship between shape concern and REE was no longer significant, whereas the association between cortisol levels and REE retained its significance, showing strong evidence for a single, dominant mediator. Anorectics and Bulimics showed an opposite pattern of association between BMI and REE. In Anorectics only, a higher REE was associated with a more severe eating disorder specific psychopathology, and cortisol levels represent a possible mediating factor for this relationship. CONCLUSION: The data supported a mediation model where cortisol levels mediated the relationship between eating psychopathology (concern about body shape) and REE.

Non-contact detection of breathing using a microwave sensor.

In this paper the use of a continuous-wave microwave sensor as a non-contact tool for quantitative measurement of respiratory tidal volume has been evaluated by experimentation in seventeen healthy volunteers. The sensor working principle is reported and several causes that can affect its response are analyzed. A suitable data processing has been devised able to reject the majority of breath measurements taken under non suitable conditions. Furthermore, a relationship between microwave sensor measurements and volume inspired and expired at quiet breathing (tidal volume) has been found.