Exploring immediate cardiorespiratory responses: low-intensity blood flow restricted cycling vs. moderate-intensity traditional exercise in a randomized crossover trial.

PURPOSE: Blood-flow restriction (BFR) endurance training may increase endurance performance and muscle strength similar to traditional endurance training while requiring a lower training intensity. We aimed to compare acute cardiorespiratory responses to low-intensity interval exercise under BFR with moderate-intensity traditional interval exercise (TRA). METHODS: We conducted a randomized crossover study. The protocol involved three cycling intervals interspersed with 1 min resting periods. With a 48-h washout period, individuals performed the protocol twice in random order: once as BFR-50 (i.e., 50% incremental peak power output [IPPO] and 50% limb occlusion pressure [LOP]) and once as TRA-65 (65% IPPO without occlusion). TRA-65 intervals lasted 2 min, and time-matched BFR-50 lasted 2 min and 18 s. Respiratory parameters were collected by breath-by-breath analysis. The ratings of perceived breathing and leg exertion (RPE, 0 to 10) were assessed. Linear mixed models were used for analysis. RESULTS: Out of the 28 participants initially enrolled in the study, 24 healthy individuals (18 males and 6 females) completed both measurements. Compared with TRA-65, BFR-50 elicited lower minute ventilation (VE, primary outcome) (-3.1 l/min [-4.4 to -1.7]), oxygen consumption (-0.22 l/min [-0.28 to -0.16]), carbon dioxide production (-0.25 l/min [-0.29 to -0.20]) and RPE breathing (-0.9 [-1.2 to -0.6]). RPE leg was significantly greater in the BFR-50 group (1.3 [1.0 to 1.7]). CONCLUSION: BFR endurance exercise at 50% IPPO and 50% LOP resulted in lower cardiorespiratory work and perceived breathing effort compared to TRA at 65% IPPO. BFR-50 could be an attractive alternative for TRA-65, eliciting less respiratory work and perceived breathing effort while augmenting perceived leg muscle effort. TRIAL REGISTRATION: NCT05163600; December 20, 2021.

Sex-Differences in Alpha-1 Antitrypsin Deficiency: Data From the EARCO Registry.

BACKGROUND: Sex and gender influence many aspects of chronic obstructive pulmonary disease (COPD). Limited data are available on this topic in alpha-1 antitrypsin deficiency (AATD). We therefore aimed to investigate sex issues in the EARCO registry, a prospective, international, observational cohort study. METHODS: Baseline data from PiZZ individuals, enrolled in the registry with complete data on sex and smoking history were analysed by group comparisons and binary logistic regression analyses. RESULTS: 1283 patients with AATD, 49.3% women were analysed. Females reported less tobacco consumption (16.8±12.2 vs. 19.6±14.5 PY, p=0.006), occupational exposures towards gases, dusts or asbestos (p<0.005 each) and consumed less alcohol (5.5±7.6 vs. 8.4±10.3u/week, p<0.001). Females reported COPD (41% vs. 57%, p<0.001) and liver disease (11% vs. 20%, p<0.001) less often. However, they had a higher prevalence of bronchiectasis (24% vs. 13%, p<0.001). Despite better lung function (FEV1%pred. 73.6±29.9 vs. 62.7±29.5, p<0.001) females reported a similar symptom burden (CAT 13.4±9.5 vs. 12.5±8.9, p=ns) and exacerbation frequency (at least one in the previous year 30% vs. 26%, p=ns) compared to males. In multivariate analyses, female sex was an independent risk factor for exacerbations in the previous year OR 1.6 p=0.001 in addition to smoking history, COPD, asthma and bronchiectasis and was also identified as risk factors for symptom burden (CAT≥10) OR 1.4 p=0.014 besides age, BMI, COPD and smoking history. CONCLUSION: Men had higher rates of COPD and liver disease, women were more likely to have bronchiectasis. Women's higher symptom burden and exacerbation frequency suggest they may need tailored treatment approaches.

[Workplace-associated fever]. / Arbeitsplatzassoziiertes Fieber oder wenn es doch das Zebra ist .

INTRODUCTION: Febrile conditions often have an infectious etiology. However, there are also fevers associated with occupational exposures. A detailed occupational history can hold the key to the diagnosis. In the case of exposure to organic dusts, the development of hypersensitivity pneumonitis (HP) is possible. Thus, HP should be considered in the presence of interstitial lung disease of unclear etiology. Failure to recognize this can have dramatic consequences and, in extreme cases, lead to lung transplantation. Differentially, organic dust toxic syndrome (ODTS) must be considered. The syndrome of metal fume fever provoked by inhalation of inorganic substances is usually benign and self-limiting. The disease manifests with fever, cough, and flu-like sensations.

Low-load blood flow restriction strength training in patients with COPD: a randomised single-blind pilot study.

OBJECTIVE: The objective of this study is to compare the effectiveness of lower limb low-load blood flow restriction training (LL-BFRT) with high-load strength training (HL-ST) as part of an outpatient pulmonary rehabilitation programme on leg strength in patients with chronic obstructive pulmonary disease (COPD). METHODS: Participants were randomised to LL-BFRT or HL-ST (24 sessions). LL-BFRT was done at 30% 1-repetition maximum (1-RM) with 70% arterial occlusion pressure. HL-ST was done at 70% 1-RM. Primary outcome was isometric strength of knee extensors and flexors. Secondary outcomes were 1-RM, functional exercise capacity, physical activity, symptom burden and health-related quality of life. Perceptions of dyspnoea and leg fatigue were recorded after every exercise. We compared groups with t-tests. RESULTS: We included 30 participants (13 women, 17 men, 64 (9) years, forced expiratory volume in 1 s 47 (18)% pred.), 24 completed the study. Isometric knee extensor strength improved to a clinically relevant degree in both legs in both groups (LL-BFRT: right leg 9 (20) Nm, left leg 10 (18) Nm; HL-ST: right leg 15 (26) Nm, left leg 16 (30) Nm, data are mean (SD)), without statistically significant or clinically relevant between-group differences (right leg mean difference= -6.4, 95% CI= -13.20 to 25.92 Nm, left leg mean difference= -5.6, 95% CI= -15.44 to 26.55 Nm). 1 min sit-to-stand test performance improved to a clinically relevant degree only in the LL-BFRT group (4 (4) vs 1 (5) repetitions). Interestingly, physical activity improved to a clinically relevant degree only in the LL-BFRT group (1506 (2441) vs -182 (1971) steps/day). LL-BFRT lowered perceived in-exercise dyspnoea and increased leg fatigue compared with HL-ST in the initial 12 trainings. CONCLUSION: In patients with stable COPD undergoing outpatient pulmonary rehabilitation, LL-BFRT was not superior to HL-ST in improving leg strength. LL-BFRT led to similar strength gains as HL-ST while reducing perceptions of dyspnoea in the initial training phase. TRIAL REGISTRATION NUMBER: NCT04151771.

[Pulmonary Dyspnea]. / Pulmonale Dyspnoe.

INTRODUCTION: Dyspnea is one of the most common symptoms in patients with lung diseases. The term "dyspnea" refers to the subjective sensation of uncomfortable breathing, which is experienced and described very differently between individuals. Because of this, diagnosis can be very challenging and similar to pain, no true objective measurement parameters of dyspnea exist. A detailed symptom history and clinical examination are critical in establishing the diagnosis, but the severity of pulmonary functional impairment does not always correlate with the clinical picture. The diagnosis of lung diseases is led by pulmonary function tests and imaging techniques, which measure the response to therapy and assess the prognostic course of the disease. The purpose of this article is to review the causes of pulmonary dyspnea, present a guide to diagnostic work-up, and introduce common differential diagnoses.

[COPD : a still neglected condition]. / BPCO : une maladie encore négligée.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung disorder with a complex clinical picture. The diagnosis may be difficult at times, as COPD may develop insidiously and remain unnoticed for a long time. Therefore, general practitioners play a central role in early detection of disease. Suspected COPD may be confirmed by further investigations in collaboration with a pulmonologist. The most recent GOLD guideline defines three COPD risk groups (A-B-E) which should guide the personalized treatment concept. General practitioners are crucial for implementing non-pharmacological measures such as smoking cessation, regular exercise, vaccinations, and patient self-management education. However, this also underlines the challenges to implement the GOLD recommendations in daily practice.

La BPCO est une maladie hétérogène avec un tableau clinique complexe. Le diagnostic n'est pas toujours facile à évoquer, car elle peut se développer insidieusement et passer longtemps inaperçue. Les médecins de premier recours (MPR) jouent donc un rôle central dans le diagnostic précoce. La suspicion de BPCO peut être confirmée en collaboration avec un pneumologue par des examens fonctionnels respiratoires avant l'instauration d'un traitement médicamenteux. Les nouvelles recommandations GOLD, publiées en 2022 définissent trois groupes de risques pour la BPCO (A-B-E). Les MPR sont importants pour la mise en œuvre de mesures accompagnant le traitement (arrêt du tabac, activité physique régulière, vaccinations, éducation thérapeutique). Mais cela souligne également les exigences élevées de la mise en œuvre des recommandations GOLD dans la pratique quotidienne.*.

Characteristics of Severe Asthma Patients and Predictors of Asthma Control in the Swiss Severe Asthma Registry.

BACKGROUND: Asthma is a chronic airway disease, affecting over 300 million people worldwide. 5-10% of patients suffer from severe asthma and account for 50% of asthma-related financial burden. Availability of real-life data about the clinical course of severe asthma is insufficient. OBJECTIVES: The aims of this study were to characterize patients with severe asthma in Switzerland, enrolled in the Swiss Severe Asthma Registry (SSAR), and evaluate predictors for asthma control. METHOD: A descriptive characterisation of 278 patients was performed, who were prospectively enrolled in the registry until January 2022. Socio-demographic variables, comorbidities, diagnostic values, asthma treatment, and healthcare utilisation were evaluated. Groups of controlled and uncontrolled asthma according to the asthma control test were compared. RESULTS: Forty-eight percent of patients were female and the mean age was 55.8 years (range 13-87). The mean body mass index (BMI) was 27.4 kg/m2 (±6). 10.8% of patients were current smokers. Allergic comorbidities occurred in 54.3% of patients, followed by chronic rhinosinusitis (46.4%) and nasal polyps (34.1%). According to the ACT score, 54.7% had well controlled, 16.2% partly controlled and 25.9% uncontrolled asthma. The most common inhalation therapy was combined inhaled corticosteroids/long-acting ß2-agonists (78.8%). Biologics were administered to 81.7% of patients and 19.1% received oral steroids. The multivariable analysis indicated that treatment with biologics was positively associated with asthma control whereas higher BMI, oral steroids, exacerbations, and COPD were negative predictors for asthma control. CONCLUSION: Biologics are associated with improved control in severe asthma. Further studies are required to complete the picture of severe asthma in order to provide improved care for those patients.

Augmentation Therapy for Severe Alpha-1 Antitrypsin Deficiency Improves Survival and Is Decoupled from Spirometric Decline-A Multinational Registry Analysis.

Rationale: Intravenous plasma-purified alpha-1 antitrypsin (IV-AAT) has been used as therapy for alpha-1 antitrypsin deficiency (AATD) since 1987. Previous trials (RAPID and RAPID-OLE) demonstrated efficacy in preserving computed tomography of lung density but no effect on FEV1. This observational study evaluated 615 people with severe AATD from three countries with socialized health care (Ireland, Switzerland, and Austria), where access to standard medical care was equal but access to IV-AAT was not. Objectives: To assess the real-world longitudinal effects of IV-AAT. Methods: Pulmonary function and mortality data were utilized to perform longitudinal analyses on registry participants with severe AATD. Measurements and Main Results: IV-AAT confers a survival benefit in severe AATD (P < 0.001). We uncovered two distinct AATD phenotypes based on an initial respiratory diagnosis: lung index and non-lung index. Lung indexes demonstrated a more rapid FEV1 decline between the ages of 20 and 50 and subsequently entered a plateau phase of minimal decline from 50 onward. Consequentially, IV-AAT had no effect on FEV1 decline, except in patients with a Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2 lung index. Conclusions: This real-world study demonstrates a survival advantage from IV-AAT. This improved survival is largely decoupled from FEV1 decline. The observation that patients with severe AATD fall into two major phenotypes has implications for clinical trial design where FEV1 is a primary endpoint. Recruits into trials are typically older lung indexes entering the plateau phase and, therefore, unlikely to show spirometric benefits. IV-AAT attenuates spirometric decline in lung indexes in GOLD stage 2, a spirometric group commonly outside current IV-AAT commencement recommendations.

Acceptability, Appropriateness and Feasibility of a Nurse-Led Integrated Care Intervention for Patients with Severe Exacerbation of COPD from the Healthcare Professional's Perspective - A Mixed Method Study.

Purpose: To improve inpatient care and self-management in patients with severe acute exacerbations of COPD, we implemented a nurse-led behavioral intervention. This study aimed to assess implementation outcomes from the perspective of the healthcare professionals (HCP) who delivered it. Methods: Using an explanatory sequential mixed method approach, we conducted an online questionnaire and two small group interviews. We applied descriptive statistics for quantitative data, a framework analysis for qualitative data, and a mixed methods matrix to integrate the results. Results: A total of 19 of 27 invited participants answered the online questionnaire; 9 of 19 participated in the group interviews. The intervention's overall acceptability, appropriateness, and feasibility was rated high to very high (median 5/5; 4/5 and 4/5). Enablers to implementation included general recognition of the need for specialized care, sufficient knowledge of the intervention by HCP, and strong interprofessional collaboration. Main barriers included the lack of resident physician's resources and difficulties in adaptability. Conclusion: While the acceptance of the intervention was very high, the perceived appropriateness and feasibility were affected by its complexity. The availability of a knowledgeable interprofessional core team is a strategy that supports the implementation of complex interventions.

Physical Health-Related Quality of Life Improves over Time in Post-COVID-19 Patients: An Exploratory Prospective Study.

(1) Background: Ongoing symptoms after mild or moderate acute coronavirus disease 19 (COVID-19) substantially affect health-related quality of life (HRQoL). However, follow-up data on HRQoL are scarce. We characterized the change in HRQoL over time in post-COVID-19 patients who initially suffered from mild or moderate acute COVID-19 without hospitalization. (2) Methods: Outpatients who visited an interdisciplinary post-COVID-19 consultation at the University Hospital Zurich and suffered from ongoing symptoms after acute COVID-19 were included in this observational study. HRQoL was assessed using established questionnaires. Six months after baseline, the same questionnaires and a self-constructed questionnaire about the COVID-19 vaccination were distributed. (3) Results: In total, 69 patients completed the follow-up, of whom 55 (80%) were female. The mean (SD) age was 44 (12) years and the median (IQR) time from symptom onset to completing the follow-up was 326 (300, 391) days. The majority of patients significantly improved in EQ-5D-5L health dimensions of mobility, usual activities, pain and anxiety. Furthermore, according to the SF-36, patients showed clinically relevant improvements in physical health, whereas no significant change was found regarding mental health. (4) Conclusions: Physical aspects of HRQoL in post-COVID-19 patients relevantly improved over 6 months. Future studies are needed to focus on potential predictors that allow for establishing individual care and early interventions.

[COPD - An Underestimated Disease]. / COPD ­ eine unterschätzte Erkrankung.

COPD - An Underestimated Disease Abstract: Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung condition with a complex clinical picture. The diagnosis is not easy to make because COPD can develop insidiously and remain unnoticed for a long time. Therefore, general practitioners play a central role in the early detection of the disease. Suspected COPD can be confirmed by special examinations in collaboration with pulmonologists. The new GOLD guideline defines three COPD risk groups (A-B-E) which should guide the personalized treatment concept. A short- or long-acting bronchodilator (SAMA/SABA or LAMA/LABA) is recommended for group A, and a dual long-acting bronchodilator therapy (LABA+LAMA) is recommended for group B and E. In case of blood eosinophilia (≥300 cells/µl) and/or recent hospitalization for COPD exacerbation, triple therapy (LABA+LAMA+ICS) is recommended. General practitioners are important in implementing non-pharmacological measures (smoking cessation, regular exercise, vaccinations, patient selfmanagement education). However, this also underlines the high demands of the implementation of the GOLD guideline in daily practice.

Impaired health-related quality of life in long-COVID syndrome after mild to moderate COVID-19.

A growing number of patients with SARS-CoV-2 infections experience long-lasting symptoms. Even patients who suffered from a mild acute infection show a variety of persisting and debilitating neurocognitive, respiratory, or cardiac symptoms (Long-Covid syndrome), consequently leading to limitations in everyday life. Because data on health-related quality of life (HRQoL) is scarce, we aimed to characterize the impact of Long-Covid symptoms after a mild or moderate acute infection on HRQoL. In this observational study, outpatients seeking counseling in the interdisciplinary Post-Covid consultation of the University Hospital Zurich with symptoms persisting for more than 4 weeks were included. Patients who received an alternative diagnosis or suffered from a severe acute Covid-19 infection were excluded. St. George's Respiratory Questionnaire (SGRQ), Euroquol-5D-5L (EQ-5D-5L), and the Short form 36 (SF-36) were distributed to assess HRQoL. 112 patients were included, 86 (76.8%) were female, median (IQR) age was 43 (32.0, 52.5) years with 126 (91, 180) days of symptoms. Patients suffered frequently from fatigue (81%), concentration difficulties (60%), and dyspnea (60%). Patients mostly stated impairment in performing usual activities and having pain/discomfort or anxiety out of the EQ-5D-5L. EQ index value and SGRQ activity score component were significantly lower in females. SF-36 scores showed remarkably lower scores in the physical health domain compared to the Swiss general population before and during the COVID-19 pandemic. Long-Covid syndrome has a substantial impact on HRQoL. Long-term surveillance of patients must provide clarity on the duration of impairments in physical and mental health.Trial registration: The study is registered on www.ClinicalTrials.gov , NCT04793269.

Chest CT Findings after Mild COVID-19 Do Not Explain Persisting Respiratory Symptoms: An Explanatory Study.

(1) Background: Lung tissue involvement is frequently observed in acute COVID-19. However, it is unclear whether CT findings at follow-up are associated with persisting respiratory symptoms after initial mild or moderate infection. (2) Methods: Chest CTs of patients with persisting respiratory symptoms referred to the post-COVID-19 outpatient clinic were reassessed for parenchymal changes, and their potential association was evaluated. (3) Results: A total of 53 patients (31 female) with a mean (SD) age of 46 (13) years were included, of whom 89% had mild COVID-19. Median (quartiles) time from infection to CT was 139 (86, 189) days. Respiratory symptoms were dyspnea (79%), cough (42%), and thoracic pain (64%). Furthermore, 30 of 53 CTs showed very discrete and two CTs showed medium parenchymal abnormalities. No severe findings were observed. Mosaic attenuation (40%), ground glass opacity (2%), and fibrotic-like changes (25%) were recorded. No evidence for an association between persisting respiratory symptoms and chest CT findings was found. (4) Conclusions: More than half of the patients with initially mild or moderate infection showed findings on chest CT at follow-up. Respiratory symptoms, however, were not related to any chest CT finding. We, therefore, do not suggest routine chest CT follow-up in this patient group if no other indications are given.

Azithromycin alters spatial and temporal dynamics of airway microbiota in idiopathic pulmonary fibrosis.

Background: High bacterial burden in the lung microbiota predicts progression of idiopathic pulmonary fibrosis (IPF). Azithromycin (AZT) is a macrolide antibiotic known to alter the lung microbiota in several chronic pulmonary diseases, and observational studies have shown a positive effect of AZT on mortality and hospitalisation rate in IPF. However, the effect of AZT on the lung microbiota in IPF remains unknown. Methods: We sought to determine the impact of a 3-month course of AZT on the lung microbiota in IPF. We assessed sputum and oropharyngeal swab specimens from 24 adults with IPF included in a randomised controlled crossover trial of oral AZT 500 mg 3 times per week. 16S rRNA gene amplicon sequencing and quantitative PCR (qPCR) were performed to assess bacterial communities. Antibiotic resistance genes (ARGs) were assessed using real-time qPCR. Results: AZT significantly decreased community diversity with a stronger and more persistent effect in the lower airways (sputum). AZT treatment altered the temporal kinetics of the upper (oropharyngeal swab) and lower airway microbiota, increasing community similarity between the two sites for 1 month after macrolide cessation. Patients with an increase in ARG carriage had lower bacterial density and enrichment of the genus Streptococcus. In contrast, patients with more stable ARG carriage had higher bacterial density and enrichment in Prevotella. Conclusions: AZT caused sustained changes in the diversity and composition of the upper and lower airway microbiota in IPF, with effects on the temporal and spatial dynamics between the two sites.

A qualitative study of the sources of chronic obstructive pulmonary disease-related emotional distress.

OBJECTIVE: The aim of this study is to identify the sources of illness-related emotional distress from the perspective of individuals living with mild to severe chronic obstructive pulmonary disease (COPD). METHODS: A qualitative study design with purposive sampling was applied at a Swiss University Hospital. Eleven interviews were conducted with individuals who suffered from COPD. To analyze data, framework analysis was used, guided by the recently presented model of illness-related emotional distress. RESULTS: Six main sources for COPD-related emotional distress were identified: physical symptoms, treatment, restricted mobility, restricted social participation, unpredictability of disease course and COPD as stigmatizing disease. Additionally, life events, multimorbidity and living situation were found to be sources of non-COPD-related distress. Negative emotions ranged from anger, sadness, and frustration to desperation giving rise to the desire to die. Although most patients experience emotional distress regardless of the severity of COPD, the sources of distress appear to have an individual manifestation. DISCUSSION: There is a need for a careful assessment of emotional distress among patients with COPD at all stages of the disease to provide patient-tailored interventions.

The effects of standardised versus individualised seat height on 1-minute sit-to-stand test performance in healthy individuals: a randomised crossover trial.

PURPOSE: We aimed to (i) investigate differences in 1-minute sit-to-stand test (1MSTST) performance (i.e., the number of repetitions) between a standardised modality (i.e., starting from a conventional chair with 46 cm seat height) and an individualised modality (i.e., starting with a knee joint flexion angle of 90°), and to (ii) quantify the influence of tibia and femur length on 1MSTST performance. METHODS: Healthy participants were recruited for this randomised crossover study, performing each 1MSTST modality twice in a randomised order. The primary outcome was the number of repetitions in the 1MSTST. Secondary endpoints were the acute responses in peripheral oxygen saturation, heart rate, and leg fatigue and dyspnoea. Additionally, we investigated correlations of performance with knee extensor strength in both modalities. RESULTS: Thirty participants were recruited and completed the study. They achieved significantly less repetitions in the standardised 1MSTST compared to the individualised 1MSTST (B = - 12.1, 95% confidence interval [95% CI] = - 14.8/- 9.4, p < 0.001). We found a significant effect of femur length on 1MSTST performance (B = - 1.6, 95% CI = - 2.6/- 0.7, p = 0.01), tibia length showed significant interaction with the 1MSTST modality (B = 1.2, 95% CI = 0.2/2.2, p = 0.03). CONCLUSION: An individualisation of the 1MSTST starting position to 90° knee flexion angle leads to more repetitions compared to the traditional starting position. The higher repetition count is explained by controlling for differences in tibia length. We recommend individualisation of the 1MSTST, enabling more valid comparisons across populations and study samples. TRIAL REGISTRATION NUMBER: http://www. CLINICALTRIALS: gov , NCT04772417. TRIAL REGISTRATION DATE: February 26, 2021.

Are Predictors for Overall Mortality in COPD Patients Robust over Time?

(1) Background: Mortality is a major outcome in research on chronic obstructive pulmonary disease (COPD) with various predictors described. However, the dynamic courses of important predictors over time are disregarded. This study evaluates if longitudinal assessment of predictors provides additional information on the mortality risk in COPD when compared with a cross-sectional analysis.; (2) In a longitudinal, prospective, non-interventional cohort study including mild to very severe COPD patients, mortality and its various possible predictors were annually assessed up to seven years.; (3) Results: 297 patients were analysed. Mean (SD) age was 62.5 (7.6) years and 66% males. Mean (SD) FEV1 was 48.8 (21.4)%. A total of 105 events (35.4%) happened with a median (95% CI) survival time of 8.2 (7.2/NA) years. No evidence for a difference between the raw variable and the variable history on the predictive value for all tested variables over each visit was found. There was no evidence for changing effect estimates (coefficients) across the study visits due to the longitudinal assessment; (4) Conclusions: We found no evidence that predictors of mortality in COPD are time dependent. This implies that cross-sectional measured predictors show robust effect estimates over time and multiple assessments seem not to change the predictive value of the measure.