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Background: Although the psychometric properties of patient-reported outcome measures (e.g. the 22-item Sino-nasal Outcomes Test [SNOT-22]) in chronic rhinosinusitis with nasal polyps (CRSwNP) have been defined, these definitions have not been extensively studied in patients with very severe CRSwNP, as defined by recurrent disease despite ≥ 1 previous surgery and a current need for further surgery. Therefore, the psychometric properties of the symptoms visual analogue scales (VAS) were evaluated, and meaningful within-patient change thresholds were calculated for VAS and SNOT-22. Methods: SYNAPSE (NCT03085797), a randomized, double-blind, placebo-controlled, 52-week trial, assessed the efficacy and safety of 4-weekly mepolizumab 100 mg subcutaneously added to standard of care in very severe CRSwNP. Enrolled patients (n = 407) completed symptom VAS (six items) daily and SNOT-22 every 4 weeks from baseline until Week 52. Blinded psychometric assessment of individual and composite VAS was performed post hoc, including anchor-based thresholds for meaningful within-patient changes for VAS and SNOT-22, supported by cumulative distribution function and probability density function plots. The effect of mepolizumab versus placebo for 52 weeks on VAS and SNOT-22 scores was then determined using these thresholds using unblinded data. Results: Internal consistency was acceptable for VAS and SNOT-22 scores (Cronbach's α-coefficients ≥ 0.70). Test–retest reliability was demonstrated for all symptom VAS (Intra-Class Correlation coefficients > 0.75). Construct validity was acceptable between individual and composite VAS and SNOT-22 total score (r = 0.461–0.598) and between individual symptom VAS and corresponding SNOT-22 items (r = 0.560–0.780), based upon pre-specified ranges. Known-groups validity assessment demonstrated generally acceptable validity based on factors associated with respiratory health, with all VAS responsive to change. Mepolizumab treatment was associated with significantly increased odds of meeting or exceeding meaningful within-patient change thresholds, derived for this very severe cohort using six anchor groups for individual VAS (odds ratio [OR] 2.19–2.68) at Weeks 49–52, and SNOT-22 (OR 1.61–2.96) throughout the study. Conclusions: Symptoms VAS and SNOT-22 had acceptable psychometric properties for use in very severe CRSwNP. Mepolizumab provided meaningful within-patient improvements in symptom severity and health-related quality of life versus placebo, indicating mepolizumab provides substantial clinical benefits in very severe CRSwNP. Plain English summary: Patients with chronic rhinosinusitis (CRS) often have blocked or runny noses, and loss of sense of smell. They can also have sac-like growths in their nose called nasal polyps, which often require surgical removement. The symptoms of CRS with nasal polyps can affect quality of life. In a clinical study named SYNAPSE, a new treatment option called mepolizumab reduced the size and severity of nasal polyps in patients suffering from very severe CRS with nasal polyps, compared with placebo. Mepolizumab also reduced the need for nasal polyp surgery. The SYNAPSE study also measured if 1 year of mepolizumab treatment improved patients' symptoms and quality of life. This was evaluated by asking patients to complete two separate tasks. These tasks were rating symptoms on a visual analogue scale (VAS) and completing a quality of life questionnaire called SNOT-22. The objective of this analysis was to see if these questionnaires accurately assessed a patient's quality of life. The analysis also assessed how many patients had major improvements in their symptoms with mepolizumab. Overall, data from 407 patients in the SYNAPSE study was analyzed. Results showed that both the VAS and SNOT-22 questionnaires accurately captured CRS symptoms and quality of life. In addition, patients treated with mepolizumab for 1 year had improvements in quality of life compared with placebo. In conclusion, these findings suggest that the VAS and SNOT-22 questionnaires are appropriate evaluation tools for patients with very severe CRS with nasal polyps. The findings also show that mepolizumab treatment is beneficial for these patients. [ABSTRACT FROM AUTHOR]

Objectives: The primary objective of the ADVANTAGE study was to compare device-naïve chronic obstructive pulmonary disease (COPD) patients' perception of the Breezhaler® and Ellipta® devices' feedback mechanisms of dose delivery confirmation. The secondary objective was to assess comfort with the inhalers' mouthpiece in terms of ease to form a tight seal around the mouthpiece. These objectives were achieved by using a novel, patient perception of inhaler questionnaire developed and tested during cognitive interviews of patients by Evidera, London, United Kingdom.Methods: Ten COPD patients were interviewed to collect feedback on the interpretation, relevance and language of the questionnaire. This questionnaire was then used in ADVANTAGE to compare patients' perception (n = 100) of both devices. Patients completed the questionnaire after a single inhalation of placebo through each inhaler.Results: Using the final questionnaire, patients reported being more confident of the feedback mechanism of Breezhaler than that of the Ellipta device (mean score 4.3 versus 3.6 respectively, estimated difference [95% CI]: 0.75 [0.51, 0.99], p < .0001). Patients also reported better comfort (ease to form a tight seal with the lips) with the Breezhaler mouthpiece than the Ellipta mouthpiece (mean score 4.3 versus 3.9 respectively, estimated difference [95% CI]: 0.41 [0.21, 0.61], p < .0001). There were no safety concerns associated with either device.Conclusion: COPD patients showed greater preference for the Breezhaler over the Ellipta inhaler for confidence of dose delivery and comfort of the mouthpiece.Trial Registration: The trial is registered at ClinicalTrials.gov (ClinicalTrials.gov number NCT02551224). [ABSTRACT FROM AUTHOR]

This document constitutes a summary of the clinical practice guidelines (CPGs) prepared at the initiative of the Latin American Thoracic Society (ALAT). Due to new evidence in the treatment of severe asthma, it was agreed to select six clinical questions, and the corresponding recommendations are provided herein. After considering the quality of the evidence, the balance between desirable and undesirable impacts and the feasibility and acceptance of procedures, the following recommendations were established. 1) We do not recommend the use of an inhaled corticosteroid (ICS) plus formoterol as rescue medication in the treatment of severe asthma. 2) We suggest performing many more high-quality randomised studies to evaluate the efficacy and safety of tiotropium in patients with severe asthma. 3) Omalizumab is recommended in patients with severe uncontrolled allergic asthma with serum IgE levels above 30 IU. 4) Anti-interleukin (IL)-5 drugs are recommended in patients with severe uncontrolled eosinophilic asthma (cut-off values above 150 cells·µL -1 for mepolizumab and above 400 cells·µL -1 for reslizumab). 5) Benralizumab is recommended in adult patients with severe uncontrolled eosinophilic asthma (cut-off values above 300 cells·µL -1 ). 6) Dupilumab is recommended in adult patients with severe uncontrolled allergic and eosinophilic asthma and in adult patients with severe corticosteroid-dependent asthma., Competing Interests: Conflict of interest: G. García reports research grants from Novartis, GSK, Boehringer Ingelheim, AstraZeneca and Sanofi, and acting as a consultant/advisor/speaker for GSK, Astra Zeneca, Novartis and Sanofi. Conflict of interest: M. Bergna reports research grants from Novartis, GSK, Boehringer Ingelheim, Roche, AstraZeneca and Sanofi, and acting as a consultant/advisor/speaker for GSK, AstraZeneca and Novartis. Conflict of interest: J.C. Vazquez reports acting as a consultant/advisor/speaker for GSK, AstraZeneca, Novartis and Boehringer Ingelheim. Conflict of interest: M.C. Cano Salas reports acting as a consultant/advisor/speaker for GSK, AstraZeneca, Novartis and Boehringer Ingelheim. Conflict of interest: J.L. Miguel reports acting as a consultant/advisor/speaker for GSK, AstraZeneca, Novartis and Boehringer Ingelheim. Conflict of interest: C. Celis Preciado reports research grants from Novartis and AstraZeneca. Conflict of interest: A. Acuña Izcaray reports acting as a consultant/advisor/speaker for GSK, AstraZeneca, Novartis and Boehringer Ingelheim. Conflict of interest: M. Barros Monge reports research grants from Novartis, GSK, Boehringer Ingelheim and AstraZeneca, and acting as a consultant/advisor/speaker for GSK, AstraZeneca and Novartis. Conflict of interest: N. Garcia Batista reports acting as a consultant/advisor/speaker for AstraZeneca and Novartis. Conflict of interest: I. Zabert has nothing to disclose. Conflict of interest: J.L. Mayorga has nothing to disclose. Conflict of interest: R. Casanova Mendoza has nothing to disclose. Conflict of interest: M. Gutierrez has nothing to disclose. Conflict of interest: M.F. Montero Arias reports research grants from Novartis. Conflict of interest: L. Utrecho Perez has nothing to disclose. Conflict of interest: M. Antunez reports acting as a consultant/advisor/speaker for GSK, AstraZeneca, Novartis and Boehringer Ingelheim. Conflict of interest: V. Williams Derby has nothing to disclose. Conflict of interest: A. Villatoro Azméquita has nothing to disclose. Conflict of interest: L. Motiño has nothing to disclose. Conflict of interest: M.A. De Oliveira has nothing to disclose. Conflict of interest: D. Rey Sanchez has nothing to disclose. Conflict of interest: M. Arroyo has nothing to disclose. Conflict of interest: M. Rodriguez has nothing to disclose., (Copyright ©ERS 2021.)

Objectives: The primary objective of the ADVANTAGE study was to compare device-naïve chronic obstructive pulmonary disease (COPD) patients' perception of the Breezhaler ® and Ellipta ® devices' feedback mechanisms of dose delivery confirmation. The secondary objective was to assess comfort with the inhalers' mouthpiece in terms of ease to form a tight seal around the mouthpiece. These objectives were achieved by using a novel, patient perception of inhaler questionnaire developed and tested during cognitive interviews of patients by Evidera, London, United Kingdom., Methods: Ten COPD patients were interviewed to collect feedback on the interpretation, relevance and language of the questionnaire. This questionnaire was then used in ADVANTAGE to compare patients' perception (n = 100) of both devices. Patients completed the questionnaire after a single inhalation of placebo through each inhaler., Results: Using the final questionnaire, patients reported being more confident of the feedback mechanism of Breezhaler than that of the Ellipta device (mean score 4.3 versus 3.6 respectively, estimated difference [95% CI]: 0.75 [0.51, 0.99], p < .0001). Patients also reported better comfort (ease to form a tight seal with the lips) with the Breezhaler mouthpiece than the Ellipta mouthpiece (mean score 4.3 versus 3.9 respectively, estimated difference [95% CI]: 0.41 [0.21, 0.61], p < .0001). There were no safety concerns associated with either device., Conclusion: COPD patients showed greater preference for the Breezhaler over the Ellipta inhaler for confidence of dose delivery and comfort of the mouthpiece., Trial Registration: The trial is registered at ClinicalTrials.gov (ClinicalTrials.gov number NCT02551224).