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Abstract Background Severe asthma (SA) may require frequent courses or chronic use of oral corticosteroids (OCS), inducing many known side effects and complications. Therefore, it is important to identify risk factors of chronic use of OCS in SA, considering the heterogeneity of clinical and inflammatory asthma phenotypes. Another aim of the present analysis is to characterize a subpopulation of severe asthmatics, in whom blood eosinophil counts (BEC) remain elevated despite chronic OCS treatment. Methods In a cross-sectional analysis of 982 SA patients enrolled in the Belgian Severe Asthma Registry (BSAR) between March 2009 and February 2019, we investigated the characteristics of the OCS treated patients with special attention to their inflammatory profile. Results At enrollment, 211 (21%) SA patients were taking maintenance OCS (median dose: 8 [IQR: 5–10]) mg prednisone equivalent). BEC was high (> 400/mm3) in 44% of the OCS treated population. Multivariable logistic regression analysis showed that risk factors for chronic use of OCS in SA were late-onset asthma (i.e. age of onset > 40 yr), frequent exacerbations (i.e. ≥2 exacerbations in the previous year) and non-atopic asthma. Late-onset asthma was also a predictor for persistently high BEC in OCS treated SA patients. Conclusion These data showed a significant association between a persistently high BEC and late-onset asthma in OCS treated SA patients. Whether it is poor compliance to treatment or corticosteroid insensitivity the reasons for this association warrants further investigation.

Background: Nasal polyposis (NP) is a comorbidity of type 2 severe asthma (SA) which could influence response to SA biologics., Methods: We evaluated (super-) response in SA patients with (NP +) and without NP (NP-) enrolled in the Belgian Severe Asthma Registry (BSAR)., Results: 914 patients, of whom 31% NP + , were included. At enrollment, NP + patients had higher annual exacerbation rates, higher number of emergency room visits and more elevated type 2 biomarkers. In the longitudinal subanalysis of 104 patients, both groups had significant and similar asthma responses to asthma biologics, except for a greater increase in FEV 1 in the NP + group. Super-response was achieved in 33 patients (32%), irrespective of NP status or type of biologic., Conclusion: In conclusion, both NP + and NP - patients had positive treatment responses, with some able to achieve super-response. In SA patients with NP, a greater FEV 1 improvement as compared to SA patients without NP was observed., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

If multiple-breath washout (MBW)-derived acinar ventilation heterogeneity (Sacin) really represents peripheral units, the N 2 phase-III of the first MBW exhalation should be curvilinear. This is essentially due to the superposed effect of gas diffusion and convection resulting in an equilibration of N 2 concentrations between neighboring lung units throughout exhalation. We investigated this in smokers with computed tomography (CT)-proven functional small airway disease. Instantaneous N 2 -slopes were computed over 40-ms intervals throughout phase-III and normalized by mean phase-III N 2 concentration. N 2 phase-III (concave) curvilinearity was quantified as the rate at which the instantaneous N 2 -slope decreases past the phase-II peak over a 1-s interval; for a linear N 2 phase-III unaffected by diffusion, this rate would amount to 0 L -1 /s. N 2 phase-III curvilinearity was obtained on the experimental curves and on existing model simulations of N 2 curves from a normal peripheral lung model and one with missing terminal bronchioles (either 50% or 30% TB left). In 46 smokers [66 (±8) yr; 49 (±26) pack·yr] with CT-based evidence of peripheral lung destruction, instantaneous N 2 -slope decrease was compared between those with (f SAD +f Emphys ) > 20% [-0.26 ± 0.14 (SD) L -1 /s; n = 24] and those with (f SAD +f Emphys ) < 20% [-0.16 ± 0.12 (SD) L -1 /s; n = 22] ( P = 0.014). Experimental values fell in the range predicted by a realistic peripheral lung model with progressive reduction of terminal bronchioles: values of instantaneous N 2 -slope decrease obtained from model simulations were -0.09 L -1 /s (normal lung; 100% TB left), -0.17 L -1 /s (normal lung 50% TB left), and -0.29 L -1 /s (30% TB left). In smokers with CT-based evidence of functional small airway alterations, it is possible to demonstrate that Sacin really does represent the most peripheral airspaces. NEW & NOTEWORTHY In smokers with computed tomography-based evidence of functional small airway alterations by parametric response mapping, it is possible to demonstrate that the multiple-breath washout-derived Sacin, an index of acinar ventilation heterogeneity, actually does represent the most peripheral airspaces. This is done by verifying on experimental N 2 washout curves of the first breath, N 2 phase-III concavity predicted by the diffusion-convection interdependence model.

In this case study, we describe a well-resourced private school in New York City that implemented COVID-19 mitigation measures based on public health expert guidance and the lessons learned from this process. Avenues opened in New York City in 2012 and has since expanded, becoming Avenues: The World School, with campuses in São Paulo, Brazil; Shenzhen, China; the Silicon Valley, California; and online. It offers education at 16 grade levels: 2 early learning years, followed by a prekindergarten through grade 12. We describe the mitigation measures that Avenues implemented on its New York campus. We compare COVID-19 case prevalence at the school with COVID-19 case positivity in New York City, as reported by the New York State Department of Health. We also compare the school's indoor air quality to ambient indoor air quality measures reported in the literature. The school's mitigation measures successfully reduced the prevalence of COVID-19 among its students, staff, and faculty. The school also established a consistently high level of indoor air quality safety through various ventilation mechanisms, designed to reduce common indoor air pollutants. The school received positive parent and community feedback on the policies and procedures it established, with many parents commenting on the high level of trust and quality of communication established by the school. The successful reopening provides useful data for school closure and reopening standards to prepare for future pandemic and epidemic events.

Background: Vaccination is vital for achieving population immunity to severe acute respiratory syndrome coronavirus 2, but vaccination hesitancy presents a threat to achieving widespread immunity. Vaccine acceptance in chronic potentially immunosuppressed patients is largely unclear, especially in patients with asthma. The aim of this study was to investigate the vaccination experience in people with severe asthma., Methods: Questionnaires about vaccination beliefs (including the Vaccination Attitudes Examination (VAX) scale, a measure of vaccination hesitancy-related beliefs), vaccination side-effects, asthma control and overall safety perceptions following coronavirus disease 2019 (COVID-19) vaccination were sent to patients with severe asthma in 12 European countries between May and June 2021., Results: 660 participants returned completed questionnaires (87.4% response rate). Of these, 88% stated that they had been, or intended to be, vaccinated, 9.5% were undecided/hesitant and 3% had refused vaccination. Patients who hesitated or refused vaccination had more negative beliefs towards vaccination. Most patients reported mild (48.2%) or no side-effects (43.8%). Patients reporting severe side-effects (5.7%) had more negative beliefs. Most patients (88.8%) reported no change in asthma symptoms after vaccination, while 2.4% reported an improvement, 5.3% a slight deterioration and 1.2% a considerable deterioration. Almost all vaccinated (98%) patients would recommend vaccination to other severe asthma patients., Conclusions: Uptake of vaccination in patients with severe asthma in Europe was high, with a small minority refusing vaccination. Beliefs predicted vaccination behaviour and side-effects. Vaccination had little impact on asthma control. Our findings in people with severe asthma support the broad message that COVID-19 vaccination is safe and well tolerated., Competing Interests: Conflict of interest: A. Bossios reports support from Novartis for attending meetings, outside the submitted work; participation on a data safety monitoring or advisory board for AstraZeneca, GSK, Novartis, Teva and Sanofi, outside the submitted work; and is a member of the Steering Committee of SHARP, Secretary of Assembly 5 (Airway Diseases, Asthma, COPD and Chronic Cough) of the European Respiratory Society and Vice-chair of the Nordic Severe Asthma Network, outside the submitted work. K. Katsoulis reports payment or honoraria for lectures presentations, speakers bureaus, manuscript writing or educational events from GSK, Novartis and AstraZeneca; and support received from Menarini and Novartis for attending meetings and/or travel, outside the submitted work. K. Kostikas reports grants or contracts from AstraZeneca, Boehringer Ingelheim, Chiesi, Innovis, ELPEN, GSK, Menarini, Novartis and NuvoAir, outside the submitted work; consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, ELPEN, GSK, Menarini, Novartis and Sanofi-Genzyme, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, Boehringer Ingelheim, Chiesi, ELPEN, GSK, Menarini, Novartis, Sanofi-Genzyme and WebMD, outside the submitted work; and is a member of the GOLD Assembly, disclosures made outside the submitted work. N. Rovina reports receiving honoraria for lectures and presentations from Chiesi, AstraZeneca, Menarini, Gilead and Baxter, outside the submitted work. K. Bieksienė reports receiving lecture honoraria from Berlin-Chemie, AstraZeneca and Norameda, outside the submitted work. A. ten Brinke reports grants from Teva and GSK, outside the submitted work; consulting fees from AstraZeneca, GSK, Novartis, Sanofi-Genzyme and Teva, outside the submitted work; and payment or honoraria for lectures received from AstraZeneca, GSK, Sanofi-Genzyme and Teva, outside the submitted work; and is Chair of the Dutch severe asthma registry RAPSODI, outside the submitted work, and ERS SHARP CRC national lead for the Netherlands. R. Chaudhuri reports grants or contracts from AstraZeneca, outside the submitted work; payment of honoraria for lectures from GSK, AstraZeneca, Teva, Chiesi, Sanofi and Novartis, outside the submitted work; support for attending meetings and/or travel from Chiesi, Sanofi and GSK, outside the submitted work; and participation in advisory board meetings for GSK, AstraZeneca, Teva, Chiesi and Novartis, outside the submitted work. H. Rupani reports grant funding from GSK and AstraZeneca, outside the submitted work; payments for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, GSK, Novartis and Teva, outside the submitted work; and is an associate editor of this journal. P. Howarth is an employee of GSK, disclosure made outside the submitted work. C. Porsbjerg reports grants or contracts from AstraZeneca, GSK, Novartis, Teva, Sanofi, Chiesi and ALK, outside the submitted work; consulting fees from AstraZeneca, GSK, Novartis, Teva, Sanofi, Chiesi and ALK, outside the submitted work; personal honoraria from AstraZeneca, GSK, Novartis, Teva, Sanofi, Chiesi and ALK, outside the submitted work; participation on a data safety monitoring or advisory board for AstraZeneca, GSK, Novartis, Teva, Sanofi, Chiesi and ALK, outside the submitted work. E.H. Bel reports research grants from GSK and Teva, outside the submitted work; and consulting fees from AstraZeneca, GSK, Sterna Biologicals, Chiesi Pharmaceuticals, Sanofi/Regeneron and Teva, outside the submitted work. M.E. Hyland reports grants or contracts from Teva outside the submitted work; and payment received from GSK for writing educational material for respiratory nurses, outside the submitted work. The remaining authors have nothing to disclose., (Copyright ©The authors 2023.)

Background: The subcutaneous implantable cardioverter-defibrillator (S-ICD) is an accepted alternative to transvenous (TV) ICD to provide defibrillation therapy to treat life-threatening ventricular tachyarrhythmias in high-risk patients. S-ICD outcomes by age group have not been reported., Objectives: In this study, the authors sought to report S-ICD outcomes in different age groups in a multicenter S-ICD post-approval study (PAS) involving the largest cohort of patients ever reported., Methods: Patients were prospectively enrolled in the S-ICD PAS and stratified based on age: young, aged 15-34 years; adult, aged 35-69 years; and elderly, aged ≥70 years. Patient characteristics and clinical outcomes through 3 years of follow up after implantation were compared., Results: The S-ICD PAS enrolled 1,637 patients. Elderly patients were more likely to receive an S-ICD as a replacement of a TV-ICD (15.1% elderly vs 12.3% adult vs 7.4% young). Secondary prevention indication decreased with age (32.7% young vs 22.2% adult vs 20.5% elderly). Mortality rate was significantly higher in the elderly group (24.0% elderly vs 13.0% adult vs 7.4% young; P < 0.0001), whereas the complication rate did not differ significantly (12.3% young vs 11.3% adult vs 8.1% elderly). Rates of appropriate shock (12.7% young vs 13.0% adult vs 13.8% elderly) and inappropriate shock (7.8% young vs 9.1% adult vs 8.8% elderly) rates did not differ between groups (P = 0.96 and P = 0.98, respectively)., Conclusions: Implant complications and appropriate and inappropriate shock rates were similar among age groups. S-ICD for secondary prevention was more common in the young group. Replacing a TV-ICD for an S-ICD increases with age. (S-ICD System Post-Approval Study; NCT01736618)., Competing Interests: Funding Support and Author Disclosures Dr Weiss has received compensation for services from Boston Sci Advisory honoraria; Biosense Consulting and Educational Honoraria; Abbott Consulting Honoraria; S4 Travel; and Sanofi Consulting; research grants from Boston Scientific, Abbott, Biosense, and Medtronic; and fellowship support from Boston Scientific Corporation, Abbott, Biosense, and Medtronic. Dr Knight has received consulting and speaker fees, investigator compensation, and fellowship support from Abbott, Biosense Webster, Biotronic, Boston Scientific, Medtronic, Atricure, and CVRx. Dr El-Chami has received compensation for services from Boston Scientific and Medtronic. Dr Aasbo has received consulting fees Boston Scientific and Biotronik. Dr Sadhu has received compensation for services and Speaker fees from Boston Scientific. Dr Brisben is a full-time employee of Boston Scientific. Mr Carter is a full-time employee of Boston Scientific. Dr Burke has received honoraria and research grants from Boston Scientific, Biosense Webster, and AtaCor Medical; and holds equity in AtaCor Medical. Dr Gold has received compensation for services from Boston Scientific, Medtronic, and Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

A new study finds that Schizosaccharomyces japonicus, a eukaryote that lost the ability to respire, modified its central carbon metabolism to maintain efficient ATP production, cofactor regeneration, and amino-acid production. This remarkable metabolic flexibility opens new avenues towards applications., Competing Interests: Declaration of interests K.J.V is a co-inventor on a patent application (WO2020157112A1) that identifies a gene as a major regulator of the Crabtree effect in Saccharomyces cerevisiae. Specifically, the gene regulates the balance between fermentation and respiration. Whereas the topic is related to the submitted manuscript, there is no direct interaction between the two (i.e. nothing written in this piece influences or even directly relates to the patent)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Prevalence of MRSA in patients with CF has risen over the past decades, and chronic infection with MRSA is associated with worse outcome in this patient group., Methods: This retrospective observational study investigated long-term eradication rate in pediatric and adult CF patients with chronic MRSA infection, using a 6-month eradication regimen containing 2 oral antibiotics, combined with topical decolonisation measures. Respiratory tract cultures were performed at least every three months, from the first MRSA-positive culture onwards., Results: A total of 24 patients with chronic MRSA infection were identified from our CF patient registry, of which 13 patients underwent an eradication attempt. The regimen consisted of 2 oral antibiotics: a combination of rifampicin, fusidic acid, clindamycin and co-trimoxazol, based on the sensitivity pattern of the MRSA strain. At the end of the study period (median 8.2 years), 12 out of 13 patients (92%) were MRSA negative. None of the patients interrupted treatment due to side-effects., Conclusions: Eradication of chronic MRSA infection is feasible, well-tolerated and highly successful, and can offer a long-lasting MRSA-negative status, obviating the need for patient segregation.

Purpose: Previous studies in patients with breast cancer have shown acute radiation therapy-induced reductions of pulmonary diffusing capacity, essentially owing to lung volume restriction. We aimed to assess the long-term effect of 2 radiation therapy regimens, which differed in terms of radiation technique and dose fractionation, on lung function., Methods and Materials: From a randomized controlled trial comparing conventional 3-dimensional conformal radiation therapy (CR) and hypofractionated tomotherapy (TT), 84 patients with breast cancer (age at inclusion 54 ± 10 [standard deviation] years) could be assessed at baseline, after 3 months, and after 1, 2, 3, and 10 years. Measurements included forced vital capacity, total lung capacity (TLC), and diffusing capacity (TLco)., Results: Radiation therapy-induced lung function changes over 10 years (Δ) were similar for both treatment arms, and in a patient subgroup with negligible history of respiratory disease or smoking (n = 57) these averaged: Δ forced vital capacity = -13 (± 9) percent predicted; ΔTLco = -14 (± 12) percent predicted; and ΔTLC = -11 (± 9) percent predicted. The only significant correlation was between V20 (lung volume exposed to dose exceeding 20 Gy) and ΔTLco (rho = -0.36; P = .007). In this subgroup, as well as in the entire patient cohort, the incurred pulmonary restriction in terms of TLC and TLco showed a greater decline at 3 months for CR versus TT. However, at 10 years, no significant difference could be detected between CR and TT (P = .9 for TLC and P = .2 for TLco in the entire patient cohort). Of the patients with normal TLC and TLco at baseline (ie, above lower limits of normal), respectively 94% and 96% were still normal 10 years later., Conclusions: In women with breast cancer, conventional 3-dimensional conformal radiation therapy and hypofractionated tomotherapy induce similar restrictive lung patterns during the course of a 10-year period, despite some treatment-dependent differences in the first 3 months. The large majority of women with normal lung function at baseline maintained a normal lung function status 10 years after radiation therapy, irrespective of treatment arm., (Copyright © 2022 Elsevier Inc. All rights reserved.)

There are many different inhaler devices and medications on the market for the treatment of asthma and chronic obstructive pulmonary disease, with over 230 drug-delivery system combinations available. However, despite the abundance of effective treatment options, the achieved disease control in clinical practice often remains unsatisfactory. In this context, a key determining factor is the match or mismatch of an inhalation device with the characteristics or needs of an individual patient. Indeed, to date, no ideal device exists that fits all patients, and a personalized approach needs to be considered. Several useful choice-guiding algorithms have been developed in the recent years to improve inhaler-patient matching, but a comprehensive tool that translates the multifactorial complexity of inhalation therapy into a user-friendly algorithm is still lacking. To address this, a multidisciplinary expert panel has developed an evidence-based practical treatment tool that allows a straightforward way of choosing the right inhaler for each patient., (© 2022. The Author(s).)

Background: Asthmatics have accelerated lung function decline over time compared with healthy individuals., Objective: To evaluate risk factors for accelerated lung function decline., Methods: In a longitudinal analysis on severe asthmatics enrolled in the Belgian Severe Asthma Registry with at least 2 visits a minimum of 12 months apart, we compared characteristics of patients with and without decline (loss of post-bronchodilation forced expiratory volume in 1 s [FEV 1 ] (% predicted)/y greater than zero) over time. Multiple linear regression was applied to study the factors independently associated with FEV 1 decline., Results: In the overall population (n = 318), median annual FEV 1 decline was 0.27 (-4.22 to 3.80) % predicted/y over a period of 23 months (12-41 months). Asthma was less controlled at baseline in nondecliners than in decliners (53%). Lung function and residual volume at baseline were higher in the declining group. Decliners presented with increased bronchial reactivity (ie, a lower provocative concentration of methacholine causing a 20% fall in FEV 1 ) at baseline. Twenty-five percent of nondecliners were started on anti-interleukin-5 (anti-IL-5) for severe eosinophilic asthma during the study compared with 10% of decliners. The multivariable model suggested that Asthma Control Questionnaire score at baseline, late-onset asthma, and addition of anti-IL-5 during follow-up were associated with lower FEV 1 decline, independently from other variables such as evolution in exacerbations, smoking status, inhaled corticosteroids or oral corticosteroids dose, or add-on anti-immunoglobulin E over time, whereas reversibility to salbutamol and higher FEV 1 were associated with accelerated FEV 1 decline., Conclusions: Add-on therapy with anti-IL-5 in severe eosinophilic asthma was associated with an attenuated FEV 1 decline. The causality of this observation should, however, be confirmed in future prospective controlled studies., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Dry powder inhaler (DPI) use requires sufficient peak inspiratory flow over the DPI internal resistance (PIFR)., Objectives: We examined whether spirometric peak inspiratory flow (PIFspiro) could serve to predict PIFR in patients with obstructive lung disease., Method: Thirty healthy nonsmokers and 140 stable outpatients (70 COPD, 70 asthma) performed spirometry according to the 2019 ERS/ATS spirometry update, yielding PIFspiro. Using a PIFR measurement device with varying orifices, all subjects' PIFR values were recorded for 5 predefined resistance levels, characterized by 5 orifice cross sections (SR). A test group including all healthy subjects, 30 of the asthma, and 30 of the COPD patients was used to establish the relationship between PIFR and both PIFspiro and SR by multiple regression. A validation group including the remaining 40 asthma and 40 COPD patients, served to verify whether their predicted PIFR value corresponded to the measured PIFR for each resistance level., Results: The asthma (FEV1 = 78 ± 17 [SD] %pred) and COPD (FEV1 = 46 ± 17 [SD] %pred) patients under study had varying airway obstruction. In the test group, PIFR could be predicted by ln[PIFspiro] (p < 0.0001), SR (p < 0.0001), and SR2 (p = 0.006), with an adjusted R2 = 0.71. In the validation group, estimated PIFR did not significantly differ from measured PIFR (p > 0.05 for the 5 resistance levels)., Conclusions: We propose a simple method to predict PIFR for a range of common DPI resistances, based on the device characteristics and on the patient's characteristics reflected in PIFspiro. As such, routine spirometry can serve to estimate a patient's specific PIFR without the need for additional testing., (© 2022 S. Karger AG, Basel.)

Patients with cystic fibrosis have increased risk for gastrointestinal cancer, lymphoid leukemia and testicular carcinomas. Chronic inflammation does not seem to be the only contributing factor. Mutations and epigenetic alterations in the CFTR gene may alter susceptibility to develop cancer. Lung cancer is up to now not frequently observed in CF patients. In lung cancer patients without CF low CFTR expression is significantly associated with advanced staging, lymph node metastasis. As the management and life expectancy of patients with cystic fibrosis have improved substantially in recent years, we expect an increased number of these patients diagnosed with lung cancer. In addition, it is possible that they, as a result of CFTR-dysfunction, will present with more aggressive lung tumors. Treating cancer in CF patients is a challenge because of multi-organ involvement and chronic colonization by resistant pathogens. The effectiveness and safety of immunotherapy in this population needs to be further evaluated.

We present the case of a 45-year-old woman, working as a silver polisher since 11 years, complaining of dyspnea on exertion and dry cough. Intensive diagnostic workup, including high-resolution CT scan of the chest and lung biopsy by VATS led to the diagnosis of pulmonary siderosis. Pulmonary siderosis is a benign, non-fibrotic type of pneumoconiosis caused by inhalation of iron oxide, which is generally asymptomatic (except in concurrent smoking or concurrent silicosis). Combination of relevant exposure and the typical findings on CT-imaging (centrilobular nodules without cranio-caudal gradient) usually strongly suggest the diagnosis, but this should always be discussed at a multidisciplinary consultation. This includes discussing whether to perform a lung biopsy for histological confirmation. Cessation of the causative exposure is the only-treatment one can take and then radiological features can improve and even disappear of time. Unfortunately, this treatment has an enormous impact on patient's life because it implies changing profession. Preventive measures can be taken by employers (respiratory equipment and ventilation). This case illustrates that physicians should stay vigilant about occupational exposures in clinical practice as well as the need for multidisciplinary consult in patients suspected of having interstitial lung disease.

Introduction: Most post COVID-19 follow-up studies are limited to a follow-up of 3 months. Whether a favorable evolution in lung function and/or radiological abnormalities is to be expected beyond 3 months is uncertain., Materials and Methods: We conducted a real-life follow-up study assessing the evolution in lung function, chest CT and ventilation distribution between 10 weeks and 6 months after diagnosis of COVID-19 pneumonia., Results: Seventy-nine patients were assessed at 6 months of whom 63 had chest CT at both follow-up visits and 46 had multiple breath washout testing to obtain lung clearance index (LCI). The study group was divided into a restrictive (n = 39) and a non-restrictive subgroup (n = 40) based on TLC z-score. Restriction was associated with a history of intubation, neuromuscular blockade use and critical illness polyneuropathy. Restriction significantly improved over time, but was not resolved by 6 months (median TLC z-score of -2.2 [IQR: -2.7; -1.5] at 6 months versus -2.7 [IQR: -3.1; -2.1] at 10 weeks). LCI did not evolve between both follow-up visits. Symptoms and chest CT score improved irrespective of restriction., Conclusion: We observed a disconnect between the improvement of COVID-19 related symptoms, chest CT lesions, and corresponding lung function. While CT imaging is almost normalized at 6 months, a further reduction of pulmonary restriction may be hoped for beyond 6 months in those patients showing restriction at their first follow-up visit., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Patients with severe asthma require high-dose inhaled corticosteroids, with or without add-on treatments, to maintain asthma control. Because symptom control remains unsatisfactory in some patients despite these therapies, maintenance therapy with oral corticosteroids (OCS) remains considered a treatment option by physicians. Besides physician-diagnosed exacerbations, many patients intermittently self-medicate with OCS during episodes of worsening symptoms or as a prevention of such episodes. However, long-term OCS use is associated with several comorbidities that may decrease health-related quality of life, worsen prognosis, and should ideally require monitoring and management. In this review, we discuss the adverse effects of OCS use, the OCS-sparing effect of biologics in severe asthma, and the need for optimal referral pathways to ensure the best outcomes for those at-risk asthma patients., Data Sources: PubMed., Study Selection: Studies with results on the OCS-sparing effect of biologics in adult severe asthma were selected., Results: Chronic and intermittent OCS use in asthma is associated with considerable adverse effects in asthma. Omalizumab, mepolizumab, benralizumab, and dupilumab reduce the need for OCS in severe asthma, while also reducing the exacerbation rate and improving several patient-related outcomes., Conclusion: Targeted biologic therapies have revolutionized the treatment of uncontrolled severe asthma by reducing or even eliminating the need for OCS and improving other major outcomes. Novel agents are now rapidly increasing the therapeutic armamentarium, but additional efforts are needed to optimize referral pathways in order to ensure sustainable access to these therapies.

Background: While peak in- and expiratory flow rates offer valuable information for diagnosis and monitoring in respiratory disease, these indices are usually considered too variable to be routinely used for quantification in clinical practice., Objectives: The aim of the study was to obtain reproducible measurements of maximal inspiratory flow rates and to construct reference equations for peak in- and expiratory flows (PIF and PEF)., Method: With coaching for maximal effort, 187 healthy Caucasian subjects (20-80 years) performed at least 3 combined forced inspiratory and expiratory manoeuvres, until at least 2 peak inspiratory flow measurements were within 10% of each other. The effect on PIF preceded by a slow expiration instead of a forced expiration and PIF repeatability over 3 different days was also investigated in subgroups. Reference values and limits of normal for PIF, mid-inspiratory flow, and PEF were obtained according to the Lambda-Mu-Sigma statistical method., Results: A valid PIF could be obtained within 3.3 ± 0.6(SD) attempts, resulting in an overall within-test PIF variability of 4.6 ± 3.2(SD)%. A slow instead of a forced expiration prior to forced inspiration resulted in a significant (p < 0.001) but small PIF increase (2.5% on average). Intraclass correlation coefficient for between-day PIF was 0.981 (95% CI: 0.960-0.992). Over the entire age range, inter-subject PIF variability was smaller than in previous reports, and PIF could be predicted based on its determinants gender, age, and height (r2 = 0.53)., Conclusions: When adhering to similar criteria for the measurement of effort-dependent portions of inspiratory and expiratory flow-volume curves, performed according to current ATS/ERS standards, it is possible to obtain reproducible PIF and PEF values for use in routine clinical practice., (© 2021 S. Karger AG, Basel.)

Introduction: Since studies about clinical status after COVID-19 are scarce, we conducted a cross sectional study with assessment of residual symptoms, lung function and chest CT., Materials and Methods: During an outpatient follow-up visit, chest CT, pulmonary function and COVID-19 related symptoms were assessed approximately 10 weeks after diagnosis. Demographics, baseline (time of diagnosis) CT score and blood results were collected from patient files. Association between lung function and clinical characteristics (baseline), blood markers (baseline), chest CT (baseline and follow-up) and symptom score (followup) was analysed. Mann-Whitney U tests and Chi squared tests were used for statistical comparison between subgroups with and without restriction., Results and Discussion: Two hundred-twenty subjects were evaluated at a median follow-up of 74±12 (SD) days. Median symptom and median CT score at follow-up were 1(IQR=0- 2) and 2(IQR=0-6) respectively. Forty-six percent of patients had normal lung function, while TLC and TLCO below the lower limit of normal were observed in 38% and 22% of subjects respectively. This restrictive pulmonary impairment was associated with length of hospital stay (8 vs 6 days; p=0.003), admission to the intensive care unit (27% vs 13%;p=0.009), and invasive mechanical ventilation (10% vs 0.7%;p=0.001), but not with symptom score or CT score at baseline and follow-up., Conclusions: Fifty-four percent of COVID-19 survivors had abnormal lung function 10 weeks after diagnosis. Restriction was the most prevalent pulmonary function, with the more critically ill patients being more prone to this condition. Yet, restriction could not be linked with abnormal imaging results or residual symptoms., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: This study evaluated spontaneous arrhythmias and clinical outcomes in the S-ICD System PAS (Subcutaneous Implantable Cardioverter-Defibrillator Post Approval Study) cohort., Background: The U.S. S-ICD PAS trial patient population more closely resembles transvenous ICD cohorts than earlier studies, which included many patients with little structural heart disease and few comorbidities. Early outcomes and low peri-operative complication rates were demonstrated in the S-ICD PAS cohort, but there are no data detailing spontaneous arrhythmias and clinical outcomes., Methods: The S-ICD PAS prospective registry included 1,637 de novo patients from 86 U.S. centers. Descriptive statistics, Kaplan-Meier time to event, and multivariate logistic regression were performed using data out to 365 days., Results: Patients (68.5% men; mean ejection fraction of 32.0%; 42.9% ischemic; 13.4% on dialysis) underwent implantation for primary (76.6%) or secondary prevention indication. The complication-free rate was 92.5%. The appropriate shock (AS) rate was 5.3%. A total of 395 ventricular tachycardia (VT) or fibrillation (VF) episodes were appropriately sensed, with 131 (33.2%) self-terminating. First and final shock efficacy (up to 5 shocks) for the 127 discrete AS episodes were 91.3% and 100.0%, respectively. Discrete AS episodes included 67 monomorphic VT (MVT) and 60 polymorphic VT (PVT)/VF, with first shock efficacy of 95.2% and 86.7%, respectively. There were 19 storm events in 18 subjects, with 84.2% conversion success. Storm episodes were more likely PVT/VF (98 of 137)., Conclusions: In the first year after implantation, a predominantly primary prevention population with low ejection fraction demonstrated a high complication-free rate and spontaneous event shock efficacy for MVT and PVT/VF arrhythmias at rapid ventricular rates. (Subcutaneous Implantable Cardioverter-Defibrillator System Post Approval Study [S-ICD PAS; NCT01736618)., Competing Interests: Author Relationship With Industry This study was supported by Boston Scientific. Dr. Burke has been a consultant and has received honoraria from Boston Scientific and AtaCor Medical; has received research grants from Boston Scientific, Medtronic, and St. Jude Medical; and holds equity in AtaCor Medical. Dr Aasbo has been a consultant and has received honoraria from Boston Scientific and Biotronik. Dr. El-Chami has received honoraria for consulting for Medtronic and Boston Scientific. Dr. Dinerman has received consulting fees from Boston Scientific, Medtronic, and Abbott. Dr. Hanon has received compensation for services from Boston Scientific. Dr. Weiss has received honoraria for speaking and serving as a consultant from Boston Scientific, Medtronic, Biotronic, and Biosense Webster. Dr. Gold has received honoraria and consulting fees from Boston Scientific and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Because device-related thrombus (DRT) portends a poor prognosis after left atrial appendage closure with the Watchman device, surveillance transesophageal echocardiography (TEE) is recommended at 45 days and 1 year. However, oral anticoagulants are just discontinued at 45 days, rendering this early TEE unlikely to detect DRT. Indeed, DRT is most likely to occur after instituting aspirin monotherapy., Objective: The purpose of this study was to evaluate the alternative strategy of first TEE imaging (or computed tomography) at 4 months post-Watchman implantation., Methods: After Food and Drug Administration approval, consecutive patients undergoing Watchman implantation at 2 centers received TEE or CT at 4 months and 1 year, along with a truncated drug regimen: 6 weeks of an oral anticoagulant (or clopidogrel in a subset) plus aspirin, then 6 weeks of dual antiplatelet therapy, and finally aspirin monotherapy., Results: Of the 530-patient cohort (mean age 78.7±7.9 years; 65.5% (n = 347) male; CHA 2 DS 2 -VASc score 4.5±1.4), 465 patients (87.7%) received 4-month imaging: 83.0% (440 of 530) TEE and 4.7% (25 of 530) computed tomography. Over a median follow-up of 12 months, 16 ischemic strokes (ISs), 8 transient ischemic attacks, and 1 systemic embolization occurred. Importantly, no IS occurred between 45 days and 4 months; the sole transient ischemic attack in this period (at ∼2 months) occurred 1 week after transcatheter aortic valve replacement. DRT was detected in 2.4% (11 of 465) at 4 months and 0.9% (2 of 214) at 1 year. No IS, but 1 leg embolization, was observed after DRT detection., Conclusion: Delaying the first imaging post-Watchman implantation to 4 months was associated with no IS between 45 days and 4 months, the "vulnerable" period of this follow-up strategy., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Severe asthma (SA) may require frequent courses or chronic use of oral corticosteroids (OCS), inducing many known side effects and complications. Therefore, it is important to identify risk factors of chronic use of OCS in SA, considering the heterogeneity of clinical and inflammatory asthma phenotypes. Another aim of the present analysis is to characterize a subpopulation of severe asthmatics, in whom blood eosinophil counts (BEC) remain elevated despite chronic OCS treatment., Methods: In a cross-sectional analysis of 982 SA patients enrolled in the Belgian Severe Asthma Registry (BSAR) between March 2009 and February 2019, we investigated the characteristics of the OCS treated patients with special attention to their inflammatory profile., Results: At enrollment, 211 (21%) SA patients were taking maintenance OCS (median dose: 8 [IQR: 5-10]) mg prednisone equivalent). BEC was high (> 400/mm 3 ) in 44% of the OCS treated population. Multivariable logistic regression analysis showed that risk factors for chronic use of OCS in SA were late-onset asthma (i.e. age of onset > 40 yr), frequent exacerbations (i.e. ≥2 exacerbations in the previous year) and non-atopic asthma. Late-onset asthma was also a predictor for persistently high BEC in OCS treated SA patients., Conclusion: These data showed a significant association between a persistently high BEC and late-onset asthma in OCS treated SA patients. Whether it is poor compliance to treatment or corticosteroid insensitivity the reasons for this association warrants further investigation.

Background: Blood eosinophil counts (BEC) were recently included in the 2019 Global Initiative for Obstructive Lung Disease (GOLD) guideline as an easily accessible theragnostic biomarker for Chronic Obstructive Pulmonary Disease (COPD). However, the stability of BEC remains insufficiently studied., Methods: We conducted a retrospective study in six primary care practices in Belgium on data from Electronic Health Records of stable COPD patients, to characterise the stability of blood eosinophils over time. We report the percentage of patients with BEC persistently below or above the 2019 GOLD guideline thresholds (100 and 300 cells/μL). For each patient the mean, standard deviation (SD) and relative standard deviation (RSD) of the BEC were calculated to determine the intra-patient variability., Results: Ninety-eight patients were included, yielding 1082 eosinophil measurements (median 8 measurements/patient), with BEC ranging between 0 and 1504 cells/μL. Four (4.1%) patients had BEC persistently below 100 cells/μL, 34 (34.7%) had measurements persistently above this threshold. Approximately half of the patients (51.0%) had BEC persistently below 300 cells/μL and 3 (3.1%) patients had counts persistently above this threshold. 28.6% of patients crossed both threshold values throughout the registration period. The mean BEC per patient ranged between 15 and 846 cells/μL with an intra-patient SD between 5 and 658 cells/μL. The mean intra-patient RSD was 0.46. There was a significant strong positive correlation (Pearson analyses) between the mean BEC and SD (r = 0.765; n = 98). Simple linear regression was used to further describe the influence of the mean eosinophil count on the SD (B = 0.500; 95%CI 0.415-0.586; n = 98; p < 0.001)., Conclusion: BEC can be variable in individual COPD patients. Therefore, the use of a single measurement to guide therapeutic decisions remains debatable. Further prospective research remains necessary to validate the reproducibility of this biomarker.

Rationale: Azithromycin prevents acute exacerbations of chronic obstructive pulmonary disease (AECOPDs); however, its value in the treatment of an AECOPD requiring hospitalization remains to be defined. Objectives: We investigated whether a 3-month intervention with low-dose azithromycin could decrease treatment failure (TF) when initiated at hospital admission and added to standard care. Methods: In an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial, patients who had been hospitalized for an AECOPD and had a smoking history of ≥10 pack-years and one or more exacerbations in the previous year were randomized (1:1) within 48 hours of hospital admission to azithromycin or placebo. The study drug (500 mg/d for 3 d) was administered on top of a standardized acute treatment of systemic corticosteroids and antibiotics, and subsequently continued for 3 months (250 mg/2 d). The patients were followed for 6 months thereafter. Time-to-first-event analyses evaluated the TF rate within 3 months as a novel primary endpoint in the intention-to-treat population, with TF defined as the composite of treatment intensification with systemic corticosteroids and/or antibiotics, a step-up in hospital care or readmission for respiratory reasons, or all-cause mortality. Measurements and Main Results: A total of 301 patients were randomized to azithromycin ( n  = 147) or placebo ( n  = 154). The TF rate within 3 months was 49% in the azithromycin group and 60% in the placebo group (hazard ratio, 0.73; 95% confidence interval, 0.53-1.01; P  = 0.0526). Treatment intensification, step-up in hospital care, and mortality rates within 3 months were 47% versus 60% ( P  = 0.0272), 13% versus 28% ( P  = 0.0024), and 2% versus 4% ( P  = 0.5075) in the azithromycin and placebo groups, respectively. Clinical benefits were lost 6 months after withdrawal. Conclusions: Three months of azithromycin for an infectious AECOPD requiring hospitalization may significantly reduce TF during the highest-risk period. Prolonged treatment seems to be necessary to maintain clinical benefits.

Background: Aim: Despite the availability of effective treatments for asthma, many patients still suffer from uncontrolled asthma. This study evaluates whether a single educational session could improve asthma control assessed by Asthma Control Test (ACT) score as well as knowledge of the inhaler device, knowledge of medication and inhalation technique., Methods: This prospective single blinded randomized controlled trial of 160 adults with asthma, examined the effectiveness of a single standardized, educational intervention, performed by a respiratory nurse specialist. The education provided to the intervention group consisted of basic information about asthma treatment and instructions on inhalation technique for about 10min. This additional education was not offered to the control group. In both groups ACT scores, knowledge of medication, knowledge of inhaler device and inhalation technique were assessed at baseline and after three months. Asthma was considered well-controlled when the ACT score exceeded 19., Results: At baseline there were no significant differences in patient demographics, degree of asthma control, knowledge of medication or device and inhalation technique between the intervention group and the control group. In the intervention group the educational session resulted in a significantly higher proportion of well-controlled asthma patients with an ACT>19 (43% versus 77%) (p < 0.001) after three months. In the control group this proportion remained similar (57% versus 67%) (p > 0.1). We also observed improvements in knowledge of medication (p < 0.001), knowledge of device (p < 0.001) and inhalation technique (p = 0.004) in the intervention group and not in the control group., Conclusion: A single 10 min, educational session provided by a respiratory nurse specialist can substantially improve asthma control determined by the ACT score after three months., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Platypnea-orthodeoxia syndrome (POS) is an uncommon disorder characterized by dyspnea (=platypnea) and desaturation (=orthodeoxia) in upright position and improvement of symptoms and blood oxygenation in supine position. Clinical presentation is heterogeneous and often confuses the clinician., Objectives: The present case report illustrates a complicated presentation of the underlying syndrome., Methods: Description of a POS case in a 73-year-old female with thorough workup and tailored treatment., Results: In this case report, we describe a rather unusual presentation of POS, with posture-dependent hypoxemic-induced psychiatric symptoms. Further investigations revealed the presence of a patent foramen ovale with atrial septum aneurysm, an aortic root dilatation up to 41 mm and bilateral lower lobe lung emboli. The ventilation-perfusion mismatch aggravated the desaturation in upright position. Since the patient remained symptomatic after treatment of the functional trigger, we choose for the percutaneous closure of the anatomical defect. We used an Occlutech Figulla Flex II UNI 33/33 mm occluder resulting in a perfect closure of the defect., Conclusion: Abnormal shunting in upright position may be the result of different underlying conditions, requiring a thorough workup and a tailored treatment. In case of serious co-morbid conditions, an endovascular procedure to close a patent foramen ovale, after unsuccessful treatment of precipitating conditions, should be considered.

Purpose: To assess the effect of radiation therapy on lung function over the course of 3 years., Methods and Materials: Evolution of restrictive and obstructive lung function parameters was investigated in 108 breast cancer participants in a randomized, controlled trial comparing conventional radiation therapy (CR) and hypofractionated tomotherapy (TT) (age at inclusion ranging 32-81 years). Spirometry, plethysmography, and hemoglobin-corrected diffusing capacity were assessed at baseline and after 3 months and 1, 2, and 3 years. Natural aging was accounted for by considering all lung function parameters in terms of percent predicted values using the most recent reference values for women aged up to 80 years., Results: In the patients with negligible history of respiratory disease or smoking (n=77), the greatest rate of functional decline was observed during the initial 3 months, this acute decrease being more marked in the CR versus the TT arm. During the remainder of the 3-year follow-up period, values (in terms of percent predicted) were maintained (diffusing capacity) or continued to decline at a slower rate (forced vital capacity). However, the average decline of the restrictive lung function parameters over a 3-year period did not exceed 9% predicted in either the TT or the CR arm. Obstructive lung function parameters remained unaffected throughout. Including also the 31 patients with a history of respiratory disease or more than 10 pack-years showed a very similar restrictive pattern., Conclusions: In women with breast cancer, both conventional radiation therapy and hypofractionated tomotherapy induce small but consistent restrictive lung patterns over the course of a 3-year period, irrespective of baseline respiratory status or smoking history. The fastest rate of lung function decline generally occurred in the first 3 months., (Copyright © 2016 Elsevier Inc. All rights reserved.)