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Background During exercise, dynamic hyperinflation (DH), measured by a reduction in inspiratory capacity (IC), increases exertional dyspnea and reduces functional capacity in many patients with severe COPD. Although noninvasive ventilation (NIV) during exercise can improve exercise duration, the effect on DH is unclear. Research Questions In people with COPD, resting hyperinflation, and evidence of DH during exercise, does bilevel NIV during exercise reduce DH and increase endurance time compared with exercise with no NIV, and does NIV with an individually titrated expiratory positive airway pressure (T-EPAP) reduce DH and increase exercise endurance time more than does NIV with standardized EPAP (S-EPAP) of 5 cm H2O? Study Design and Methods A randomized crossover trial in which investigators and participants were blinded between NIV interventions was performed. Participants (N = 19; FEV1 of 1.02 ± 0.24 L (39% ± 6% predicted) completed three constant work rate endurance cycle tests in random order—no NIV, NIV with S-EPAP, and NIV with T-EPAP—during exercise. Primary outcomes were isotime IC and exercise endurance time. Outcome measures from each intervention were compared at isotime and at end exercise by using a linear mixed-model analysis. Results Compared with those with no NIV, isotime IC and endurance time were greater with both NIV with S-EPAP (mean difference: 95% CI, 0.19 L [0.10-0.28]; 95% CI, 153 s [24-280], respectively) and T-EPAP (95% CI, 0.22 L [0.13-0.32]; 95% CI, 145 s [28-259], respectively). There was no difference between NIV with S-EPAP and NIV with T-EPAP. Interpretation In people with COPD and DH during exercise, NIV during exercise reduced DH and increased cycle endurance time. An S-EPAP of 5 cm H2O was adequate to obtain these benefits. Trial Registry Australian New Zealand Clinical Trials Registry; No.: ACTRN12613000804785; URL: http://www.anzctr.org.au

PURPOSE Pulmonary rehabilitation (PR) has been shown to be an effective intervention in patients with very severe chronic obstructive pulmonary disease (COPD) awaiting lung transplantation (LTx). The objective of this study was to characterize the prevalence of acute exacerbations (AEs) during PR and their impact on the outcomes of pre-LTx PR. METHODS In this retrospective analysis, 559 patients with COPD awaiting LTx who were referred to a 4-wk inpatient PR program were evaluated. A total of 114 patients (20%) acquired an AE during PR and continued in an adapted fashion. Pulmonary function testing, 6-min walk test (6MWT), and a health-related quality-of-life questionnaire (SF-36) were administered on admission and on discharge of PR. RESULTS Following PR, both groups, patients with and without AE, increased their 6MWT significantly (P < .001) to a clinically relevant amount (58 ± 72 and 52 ± 64 m, respectively). The sum scores of the SF-36 also improved significantly without any between-group differences. No observed changes were different between the two groups. No relevant predictors for PR outcomes could be detected by logistic regression. CONCLUSIONS Our data show that patients with end-stage COPD listed for LTx can achieve clinically relevant improvements in functional exercise capacity and quality of life even if they develop an AE during PR.

As of 10 March 2021, coronavirus disease 2019 (COVID-19) has resulted in more than 0.1 billion laboratory-confirmed cases and more than 2.5 million deaths globally [1]. Both the economic impact and disease burden of COVID-19 far exceeded those of severe acute respiratory syndrome and Middle East Respiratory Syndrome. The number of patients who have recovered from COVID-19 is increasing [2] despite an escalation of total number of cases worldwide., This editorial reviews the evidence supporting benefits of pulmonary rehabilitation in #COVID19 patients, as well as some unanswered research questions https://bit.ly/39JY3SU

IntroductionBioelectrical impedance analysis (BIA) can be used to estimate Fat-Free Mass Index (FFMI). However, the use of directly measured BIA variables, such as phase angle (PhA), has gained attention. The frequency of low FFMI and PhA and its associations with exercise capacity and health-related quality of life (HRQL) in patients with idiopathic pulmonary fibrosis (IPF) have been scarcely studied.ObjectivesTo investigate the frequency of low FFMI and PhA and their associations with exercise capacity and HRQL in patients with IPF.MethodsPatients underwent assessment of lung function, body composition, exercise capacity by the 6 min walk distance (6MWD), and HRQL by the Medical Outcomes Study Short-Form 36-item Questionnaire (SF-36). Patients were classified as presenting normal or low PhA or FFMI, accordingly to the 10th percentiles of age-sex-body mass index (BMI)-specific reference values.Results98 patients (84 males, age: 68±8 years, forced vital capacity: 64%±18%predicted) were included. 24 patients presented low PhA. They were characterised by worse lung function, exercise capacity and HRQL compared with patients with normal PhA. 10 patients presented low FFMI, but despite differences in body composition, no differences were found between these patients and patients with normal FFMI. In a single regression analysis, age, lung function and body composition variables (except FFMI) were related to 6MWD and SF-36 Physical Summary Score (R²=0.06–0.36, pConclusionOne-fourth of the patients with IPF with normal to obese BMI present abnormally low PhA. Patients classified as low PhA presented worse lung function, exercise capacity and HRQL.

Zusammenfassung Hintergrund Pulmonale Hypertonie (PH) ist definiert als ein Anstieg des mittleren pulmonal-arteriellen Drucks auf > 20 mmHg in Ruhe, der auf Dauer zu einer Rechtsherzinsuffizienz führen kann. Bis vor einigen Jahren wurde PH-Patienten wegen der Befürchtung einer möglichen Symptomverschlechterung und dem Auftreten unerwünschter, belastungsassoziierter klinischer Ereignisse von körperlichem Training abgeraten. Methoden Drei elektronische Datenbanken wurden mit folgenden Suchbegriffen nach randomisiert, kontrollierten Studien durchsucht, in denen eine Trainingsintervention bei PH-Patienten untersucht wurde: „pulmonary hypertension ODER „pulmonary arterial hypertension“ UND „exercise“ ODER „pulmonary rehabilitation“ UND „randomized“. Ergebnisse In dieser Metaanalyse konnten Daten von 5 Studien mit insgesamt 187 PH-Patienten eingeschlossen werden, welche 3- bis 12-wöchige Trainingsprogramme (z. B. 10 – 45 Minuten Ergometertraining; 60 – 80 % der maximalen Herzfrequenz) absolvierten. Patienten in den Trainingsgruppen wiesen im Vergleich zur Kontrollgruppe signifikante (p Schlussfolgerung Ein individuell angepasstes Trainingsprogramm bei stabilen PH-Patienten kann nach zuvor optimierter medikamentöser Therapie die körperliche Belastbarkeit und Lebensqualität ohne nachweisbare klinische Gefährdung verbessern. Diese Einschätzungen basieren bisher nur auf kleinen Fallzahlen und größere, randomisierte Studien mit unterschiedlichen PH-Schweregraden sind dringend notwendig.

Background Supplemental oxygen is a recommended therapy option in stable hypoxemic COPD patients. Often, supplemental oxygen is provided by continuous flow (CF). However, demand oxygen delivery systems (DODS) that provide an oxygen bolus only during inspiration have gained increasing use as they prolong oxygen cylinder life (beside battery life). However, there is a lack of evidence if different DODS and CF devices are equivalent. Methods Seventy hypoxemic COPD patients (FEV1 32 ± 9% predicted, PaO2 56±7 mmHg) on long-term oxygen therapy were included in this prospective single-blinded, randomized cross-over trial. Following an initial incremental shuttle walk test, patients performed 3 endurance shuttle walk tests (ESWT) at 85% of their maximum walking speed in random order with: (A) CF (ESWT-CF), (B) a DODS based on liquid oxygen (ESWT-DL) and (C) an DODS oxygen concentrator (ESWT-DC). The primary outcome was oxygen saturation (SpO2) at ESWT isotime. Secondary outcomes were total ESWT duration, heart rate (HR) and breathing frequency (BF) at isotime and dyspnea at end-exercise. Results SpO2 at ESWT isotime was not clinically different between devices: 90 ± 4% (CF), 89 ± 5% (DL) and 90 ± 5% (DC). However, 20% of the patients showed a ≥4% lower oxygen desaturation while using a DODS device. Secondary outcomes were similar under the three conditions. Conclusion Oxygen supplementation via DODS (based on liquid oxygen or as a concentrator) yielded comparable physiological effects during standardized walking in stable hypoxemic COPD patients like CF. However, 20% of patients showed a clinically relevant lower oxygen saturation while using a DODS device. Therefore, we suggest individual testing of oxygen saturation of DODS suitability.

Background:\ud Cognitive impairment might interfere with the efficacy of Pulmonary Rehabilitation (PR) in Chronic Obstructive Pulmonary Disease (COPD). We aimed to identify differential responses to PR between cognitively impaired (CI) and cognitively normal (CN) COPD patients by assessing health status and exercise capacity.\ud \ud Methods:\ud Sixty patients (FEV1: 47 ± 15%) were classified as CI or CN according to the Montreal Cognitive Assessment (MoCA ≤25points) and completed a 3-week inpatient PR program. Cognitive function (neuropsychological battery), health-status (36-Item Short Form Survey [SF-36]), and exercise capacity (6-min walk test [6MWT], cycle-endurance test [CET]) were assessed before and after PR. Responsiveness to PR was estimated by mean change (delta-value [Δ]) and the d-Effect Size (ES).\ud \ud Results:\ud Twenty-five COPD patients (42%) presented evidence of mild CI prior to PR. Both, CI and CN patients significantly improved global cognitive function, health status (the majority of SF-36 components), and exercise capacity (6MWT and cycle endurance) in response to PR. Compared to CN, CI patients did not improve SF-36 subdomains of “role emotional” and “bodily pain”, and demonstrated a lower magnitude of improvement in 6MWT ([Δ]: 25 m; ES: 0.21) compared to CN ([Δ]: 46 m; ES: 0.54).\ud \ud Conclusions:\ud PR has favorable effects on global cognitive function, health status, and exercise capacity in both CI and CN COPD patients. There was no concrete evidence to indicate interference of cognitive impairment to PR effectiveness.

ERJ Open Research 7(3), 00454 (2021). doi:10.1183/23120541.00454-2021, Published by European Respiratory Society, [S.l.]

RationaleIn patients with COPD, oxygen (O2)-supplementation via a constant flow oxygen system (CFOS) can result in insufficient oxygen saturation (SpO22-system (ATOS) has been shown to be beneficial compared with an untitrated CFOS, however, it is unknown if ATOS is superior to CFOS, titrated during exercise as stipulated by guidelines. The aim was to investigate the effects of ATOS compared with titrated CFOS on walking capacity in people with hypoxaemic COPD.MethodsFifty participants completed this prospective randomised controlled, double-blind, crossover trial. Participants performed two endurance shuttle walk tests (ESWTs) with: (1) exercise titrated CFOS (ESWTCFOS) and (2) ATOS targeting an SpO2of 92% (ESWTATOS). Primary outcome measure was walking time. Secondary measures were SpO2, transcutaneous-PCO2(TcPCO2), respiratory rate (RR), heart rate (HR) at isotime (end of shortest ESWT) with blood gases and dyspnoea at rest and end exercise.ResultsParticipants (median (IQR): age 66 (59, 70) years, FEV128.8 (24.8, 35.1) % predicted, PO254.7 (51.0, 57.7) mm Hg, PCO244.2 (38.2, 47.8) mm Hg) walked significantly longer with ESWTATOSin comparison to ESWTCFOS(median effect (95% CI) +144.5 (54 to 241.5) s, p2was significantly higher (+3 (95% CI 1 to 4) %, p2, RR and HR were comparable. End exercise, PO2(+8.85 (95% CI 6.35 to 11.9) mm Hg) and dyspnoea (−0.5 (95% CI −1.0 to −0.5) points) differed significantly in favour of ATOS (each p2was comparable.ConclusionIn patients with hypoxaemia with severe COPD the use of ATOS leads to significant, clinically relevant improvements in walking endurance time, SpO2, PO2and dyspnoea with no impact on PCO2.Trial registration numberNCT03803384.

Background: Frailty is prevalent in patients awaiting lung transplant (LTx) and is associated with delisting, death while on the waiting list and death after LTx. Decreasing frailty of LTx-candidates could therefore be important to improve pre- and post-LTx-status. Objective: Primary aim was to investigate the effects of a comprehensive PR-program on physical frailty in LTx-candidates. Methods: 32 participants from an inpatient PR-program with a confirmed diagnosis of COPD or interstitial lung disease who were listed or were in the process to be listed for a LTx were consecutively included in this trial. Primary outcome was the change in physical frailty measured by short physical performance battery test (SPPB; score 0-12) performed at PR-admission and discharge. SPPB results can be categorized into frail (SPPB≤7), pre-frail (SPPB=8-9) and not-frail (SPPB≥10). Participants with an SPPB score≤11 were considered for final analyses. Results: 28 participants (60±5years; FEV1 49±26%pred., SPPB-baseline: frail: n=5 [17.9%], pre-frail: n=10 [35.7%]; not-frail: n=13 [46.4%]) were analysed. Baseline SPPB-score (8.8±2.2) significantly (p Conclusion: Our findings show that a comprehensive PR-program can significantly and to a clinically meaningful extent, reduce frailty in LTx-candidates.

Background: Whole-body vibration training (WBVT) performed on a vibration platform can significantly improve physical performance in COPD patients. It has been suggested that an important mechanism of this improvement is based on an improvement in balance. Aim of this study was to investigate the effects of WBVT versus conventional balance training on exercise performance. Methods: 48 patients with severe COPD (FEV1: 37±7 %pred.) and low exercise performance (6-minute walk distance (6MWD): 55±10 %pred.) were included in a randomized controlled trial during a 3-week inpatient pulmonary rehabilitation. All patients completed a standardized endurance and strength training program. Additionally, patients performed 4 different balance exercises 3x/week for 2x1 minute each either on a vibration platform (Galileo) at varying frequencies (5 - 26 Hz) (WBVT) or on a conventional therapy tool inducing an instable surface (CON). Results: 6MWD improved significantly in both groups (WBVT: 48±46m, p Conclusion: WBVT can improve balance and muscular performance significantly more compared to conventional balance training.

Abstract Lymphangioleiomyomatosis (LAM) is a rare and progressive cystic lung disease with limited therapeutic options. We retrospectively analyzed the effects of a comprehensive 4-week inpatient pulmonary rehabilitation (PR) program in 58 patients with advanced LAM (FEV1: 45 ± 34%predicted, 6-min walk distance (6MWD): 338 ± 167 m). Exercise performance (6MWD: + 49 ± 50 m; p p = 0.049 and mental component: + 5.2 ± 12.1 points; p Trial registration Clinical-Trials registration number: NCT04184193; date of registration: December 3, 2019.

Patients with idiopathic pulmonary fibrosis (IPF) and concurrent hypoxaemia should be treated with oxygen therapy [1]. Oxygen therapy is commonly given by conventional nasal cannulas (CNC), but can also be delivered by other less conventional cannulas such as the Oxymizer. The Oxymizer is a nasal cannula with an internal pendant reservoir incorporated in the lumen at the patient end which has the potential to provide increased oxygenation while using the same oxygen setting as one would with CNC [2]., Something simple, like changing a nasal cannula for a technologically superior one, can improve exercise capacity and oxygenation in patients with IPF. There is a need to develop improved cannulas for comfort and patient acceptance. https://bit.ly/2NelacE

Insufficient cerebral blood flow regulation to meet increasing metabolic demand during physical exertion could be associated with cognitive impairment. We compared cerebral oxygen availability during exercise in cognitively impaired (CI) to cognitively normal (CN) COPD patients. Fifty-two patients (FEV1: 51 ± 16%) were classified as CN or CI according to the Montreal Cognitive Assessment. Patients performed cycle-ergometry at 75% peak capacity with continuous measurement of Near-Infrared Spectroscopy frontal-cortex Tissue oxygen Saturation Index (TSI), cerebral haemoglobin indices (oxy/deoxy/total- Hb), transcutaneous carbon-dioxide partial pressure (TcPCO2), and arterial oxygen saturation (SpO2). Twenty-one patients (40%) presented evidences of CI. During exercise, CN and CI patients exhibited mild to moderate SpO2decline (nadir[Δ]≥ −3 ± 2% and −5 ± 3%, respectively) but preserved baseline frontal-cortex TSI levels, whilst presenting small TcPCO2 perturbations and increased cerebral total-Hb (post [Δ]≥ 2.0 ± 3 μM sec−1). CI patients preserve the capacity to adequately maintain cerebral oxygen availability during submaximal exercise. Therefore, rehabilitative exercise training in CI patients with COPD exhibiting mild to moderate exercise-induced SpO2 decline does not appear to lead to reduced cerebral oxygen availability.

Background: Emphysematous destruction of lung parenchyma visible in computed tomography (CT) can be attributed to chronic obstructive pulmonary disease (COPD) or to α1-antitrypsin deficiency (AATD). Objectives: We evaluated if visual semiquantitative phenotyping of CT data helps identifying individuals with AATD in a group of smokers with severe emphysema and airflow limitation. Method: n = 14 patients with AATD and n = 15 with COPD and a minimum of 10 pack years underwent CT, clinical assessment, and full-body plethysmography. The extent and type of emphysema as well as large and small airway changes were rated semiquantitatively for each lobe using a standardized previously published scoring system. Lastly, a final diagnosis for each patient was proposed. Results: AATD had a significantly lower mean emphysema score than COPD, with 8.9 ± 3.4 versus 11.9 ± 3.2 (p < 0.001), respectively. Within both groups, there was significantly more emphysema in the lower lobes (p < 0.05–0.001). The COPD group showed an upper- and middle-lobe predominance of emphysema distribution when compared to the AATD group (p < 0.001). Centrilobular (CLE) and panlobular (PLE) emphysema patterns showed a uniform distribution within both groups, with a CLE predominance in the upper lung and a PLE predominance in the lower lung regions. AATD and COPD both showed significantly more airway changes in lower lobes compared to upper lobes (p = 0.05–0.001), without significant differences between both groups. Conclusion: The typical emphysema distribution patterns seen on CT traditionally assigned to AATD and COPD were of little use in discriminating both entities. Also, airway changes could not contribute to a more precise differentiation. We conclude that a concise standardized phenotyping-driven approach to chest CT in emphysema is not sufficient to identify patients with AATD in a cohort of smokers with advanced emphysema.

The European Respiratory Society (ERS) and American Thoracic Society (ATS) guideline on management of chronic obstructive pulmonary disease (COPD) exacerbations was published in the March 2017 issue of the European Respiratory Journal [1]. Based on evidence syntheses, including meta-analyses, relevant evidence up to September 2015 was summarised and clinical recommendations for treatment of COPD exacerbations were formulated. These guidelines were endorsed by the ERS Executive Committee and approved by the ATS Board of Directors in December 2016.

ZusammenfassungDie vorliegende Leitlinie ist eine Neufassung und Aktualisierung der Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma, welche die bisher für den deutschen Sprachraum gültige Version aus dem Jahr 2006 ablöst. Die Fülle an neuen Erkenntnissen zur Pathophysiologie und zu den Phänotypen von Asthma und das erweiterte Spektrum an diagnostischen und therapeutischen Möglichkeiten bei dieser Erkrankung machte eine Neufassung und Aktualisierung notwendig. Es werden sowohl für Kinder und Jugendliche als auch für Erwachsene mit Asthma die aktuellen, Evidenz-basierten diagnostischen und therapeutischen Empfehlungen dargelegt.

ZusammenfassungDie Lebensqualität von COPD-Patienten ist häufig deutlich beeinträchtigt. Neben den körperlichen Limitationen der Betroffenen treten häufig psychische Komorbiditäten auf. Damit gehen häufig auch dysfunktionale Annahmen der Betroffenen in Bezug auf ihre Erkrankung und deren Behandlung einher. Diese können nicht nur die Lebensqualität der Betroffenen weiter beeinträchtigen, sondern auch Auswirkungen auf die Kommunikation zwischen Arzt und Patient sowie das Krankheitsverhalten haben. Aus diesem Grund ist es wichtig, dass Behandler sie im Dialog mit dem Patienten berücksichtigen. Der folgende Beitrag thematisiert, welches Gewicht dysfunktionalen Krankheitsannahmen und psychischen Komorbiditäten bei COPD zukommt, und geht auf die Möglichkeiten ein, diese im Arzt-Patient-Kontakt positiv zu berücksichtigen.

Background The acute effect of supplemental oxygen during exercise has been shown to differ largely among patients with COPD. It is unknown what factors influence oxygen response. Methods In a randomized, single-blind fashion, 124 patients with COPD underwent one 6-min walk test on supplemental oxygen (6MWTO2) and one 6-min walk test on room air after a practice 6-min walk test. Both gases were delivered via standard nasal prongs (2 L/min). For analyses, patients were stratified on the basis of PaO2 values and compared: (1) 34 patients with resting hypoxemia (HYX); (2) 43 patients with exercise-induced hypoxemia (EIH); and (3) 31 patients with normoxemia (NOX). Results Oxygen supplementation resulted in an increase in the 6-min walk distance in the total cohort (27 ± 42 meters; P Conclusions In contrast to patients with NOX, patients with HYX and EIH generally benefit from supplemental oxygen by increasing exercise capacity. However, less than one-half of patients reached the threshold of clinically relevant improvements. These oxygen responders were characterized by significantly lower exercise capacity levels. Trial Registry ClinicalTrials.gov; No.: NCT00886639; URL: www.clinicaltrials.gov.

Background: Numerous studies have reported positive effects of exercise training in patients with interstitial lung disease (ILD) on physical capacity and quality of life. However, evidence is rare on the effects of specific forms of training and further pathophysiological mechanisms in these patients. Objectives: In this multicenter study we aimed to explore the clinical effects of whole-body vibration training (WBVT) in patients with ILD on various outcome measures, including proinflammatory cytokines and myostatin. Methods: We randomly assigned 26 patients with different forms of multidisciplinary confirmed fibrotic ILDs either to the WBVT group (n = 11; 55% male, 61 ± 14 years old, forced vital capacity 83.2 ± 29.3% predicted, 6-min walking distance [6MWD] 478 ± 79 m) performing 3 months of a standardized training (3 times per week), or to a control training group (CTG, n = 15; 60% male, 63 ± 9 years old, FVC 74.6 ± 20.5% predicted, 6MWD 455 ± 85 m) performing sham WBV training. Training in the two groups was performed on a GalileoTM vibration plate (6–20 vs. 5 Hz). The functional assessments before and after the intervention period included pulmonary function, 6MWD test, chair rise test, ultrasonographic measurement of quadriceps muscle thickness (cross-sectional area), quality of life questionnaires, and serum samples. Results: We observed a significant increase in 6MWD (∆Training = 30 m [12–67], p = 0.024) and a decrease of myostatin (∆Training = –465 pg/mL [–713 to –166], p = 0.008) in the WBVT group. In contrast, no significant differences were observed in the CTG. Conclusions: The present study demonstrates that WBVT is able to significantly increase 6MWD and decrease myostatin in patients with fibrotic ILDs. Therefore, WBVT seems to be a beneficial and feasible training modality in ILD patients. Clinical Trial Registry: German Clinical Trials Registry (DRKS00012930).

The recommendation for pulmonary rehabilitation (PR) in idiopathic pulmonary fibrosis (IPF) is weak with low-quality evidence. Therefore, the aim of this study is to investigate short-term PR effects and their maintenance after a 3-month follow-up. Fifty-four IPF patients were randomized into a group receiving a 3-week comprehensive, inpatient PR (n = 34, FVC: 74 &plusmn, 19% pred.) or usual care (UC) (n = 17, FVC: 72 &plusmn, 20%pred.). Outcomes were measured at baseline (T1), after intervention (T2), and 3 months after T2 (T3). A 6-min walk distance (6MWD) was used as the primary outcome and chronic respiratory disease questionnaire (CRQ) scores as the secondary outcome. Change in 6MWD from T1 to T2 (&Delta, = 61 m, 95% CI (18.5&ndash, 102.4), p = 0.006) but not from T1 to T3 (∆ = 26 m, 95% CI (8.0&ndash, 61.5), p = 0.16) differed significantly between groups. Higher baseline FVC and higher anxiety symptoms were significant predictors of better short-term 6MWD improvements. For the change in CRQ total score, a significant between-group difference from T1 to T2 (∆ = 3.0 pts, 95% CI (0.7&ndash, 5.3), p = 0.01) and from T1 to T3 (∆ = 3.5 pts, 95% CI (1.5&ndash, 5.4), p = 0.001) was found in favour of the PR group. To conclude, in addition to the short-term benefits, inpatient PR is effective at inducing medium-term quality of life improvements in IPF. PR in the early stages of the disease seems to provoke the best benefits.

Background: International guidelines recommend the use of supplemental oxygen (O2) in IPF patients who suffer from exercise-induced hypoxemia (EIH). As short-term effects of O2 during exercise are not known in IPF patients yet, the aim of our study was to investigate the effects of O2 on the endurance walking capacity in hypoxemic IPF patients. Methods: 53 IPF patients with EIH were investigated in a prospective double-blinded randomized-controlled cross-over trial. Following an initial incremental shuttle walk test (ISWT) which assess the individual maximum gait speed, each patient performed 3 endurance shuttle walk tests (ESWT) at 85%max under following conditions: (A) with medical air (compressed room air)(ESWTMA), (B) with 2 liters/min O2 (ESWT2L) and (C) with 4 liters/min O2 (ESWT4L). Walking endurance time during ESWT was the primary outcome. Data of secondary outcomes (oxygen saturation [SpO2], heart rate [HR], breathing frequency [BF]) were compared at the end of the shortest ESWT ("isotime"). Results: 50 patients (69 y, FVC 72%pred., DLCO 33%pred., ISWT: 389m) completed the study. Endurance walking time was longer during ESWT4L> ESWT2L >ESWTMA (585 sec vs. 462 sec vs. 404 sec, F=3.483, p=0.03). SpO2ISO was higher by breathing O2 and by using a higher flow rate (ESWT4L 88% vs. ESWT2L 85% vs. ESWTMA 80%, F=123.204, p Discussion: O2 showed significant and clinically relevant benefits on walking capacity and oxygen saturation compared to compressed room air in IPF patients with EIH. A dose-dependent effect has been found showing higher vs. lower oxygen flow rates to be more beneficial.

Background: In patients with IPF exercise intolerance is often associated with hypoxemia. Therefore, SOT may be offered. The Oxymizer® is a nasal cannula incorporating an internal reservoir with the potential to deliver higher oxygen (O2) doses to the patient on the same O2-flow compared to a conventional nasal cannula (CNC). Objectives: Primary aim was to investigate the effects of SOT delivered via Oxymizer compared to a CNC in hypoxemic IPF-patients on walking capacity. Secondary aim was to evaluate the effects on O2-saturation (SpO2), heart- and breathing rate at isotime (end of shortest endurance shuttle walk test; ESWT). Methods: 26 patients with a confirmed diagnosis of IPF and SOT-indication during exercise were consecutively included in this trial. After an initial incremental shuttle walk test, patients performed, in randomized order and with a 24h-resting period between tests, two ESWTs - one with Oxymizer and one with CNC. Results: 22 patients (70±7years; VC:54±15%/pred) completed all tests. Walking capacity was significantly greater while using the Oxymizer compared to CNC (523±369vs.419±332sec, p=0.027). 15 patients (68%) walked longer with the Oxymizer. At isotime, SpO2 (81.6±8.8 vs.78.5±8.1%, p=0.001) was significantly higher while heart- (112±16vs.118±13bpm) and breathing rate (38±8vs.41±8bpm) were significantly (p Conclusion: SOT when provided by the Oxymizer showed significant and clinically relevant benefits on walking capacity in IPF-patients by improving physiological parameters. However, only 8 (36%) patients would prefer the Oxymizer for their daily use.

Background: Dynamic hyperinflation (DH) can occur during exercise in people with stable COPD and is associated with increased dyspnoea and reduced exercise capacity. While NIV during exercise can improve endurance time, the effect of NIV on IC (a DH marker) is unclear. Objective: To determine the effect of NIV on IC and Tlim in patients with COPD during constant load cycle exercise. Method: 20 patients with severe COPD (FEV1:32±4%pred, RV/TLC:163±29%) and who showed DH during a peak cycle test, in one day, performed three cycle endurance tests at 75% peak work rate to exhaustion, in random order: no NIV, standard NIV (expiratory positive airway pressure (EPAP) 5cmH2O), titrated NIV (individualised EPAP to maximise IC at rest). Metabolic variables, breathing pattern, oxygen saturation (SpO2), transcutaneous carbon dioxide (TcCO2), heart rate and muscular oxygenation (SmO2) (via NIRS) were measured continuously. IC and dyspnoea were measured each minute. Results: Tlim and isotime change in IC (∆IC) were significantly increased (Table 1) with standard and titrated NIV during exercise vs no NIV. In both NIV tests, TcCO2, SpO2 and SmO2 were significantly improved. There were no differences between NIV tests. Conclusion: When using NIV compared to no NIV, stable patients with severe COPD had clinically improved exercise endurance time and significantly reduced DH at isotime

Background: Pulmonary rehabilitation (PR) has been shown to improve cognitive performance in COPD patients even after adjusting for sociodemographic factors. This favourable effect of PR, however, has not been evaluated in COPD lung-transplant (LTx) recipients where immunosuppressant toxicity and/or central nervous system events may be associated with cognitive decline. We investigated the effects of PR on cognitive function in LTx-recipients for COPD. Methods: Twenty-four COPD LTx-recipients (FEV1: 75±22%pred.) were assigned to a 3-week inpatient PR program. A comprehensive neuropsychological battery was used to assess memory, learning skills, attention/ flexibility, visuospatial abilities, psychomotor speed and behavioural activation before and after PR. The magnitude of changes was interpreted by d-Effect Size (ES). Results: In response to PR, LTx-recipients presented small to large improvements (ES range: 0.23 to 1.00, all p ≤0.34) in 50% of the administered cognitive tests. Learning skills and memory ability presented the greatest benefits (Composite scores ES: 0.31 and 0.62; Figure1) that remained similar after stratification by single or bilateral LTx, and sex. Conclusions: PR has a beneficial effect on cognitive function improving memory, learning skills and psychomotor speed in post-transplant phase. Improvements in cognitive function may facilitate recovery in COPD LTx-recipients.

Background: Various exercise training programs are used for patients with chronic obstructive pulmonary disease (COPD) of different severity. Objectives: To investigate the impact of individualized high-intensity training on exercise capacity with COPD. Methods: A total of 49 patients agreed to participate. Of these, 31 were assigned to the training group and 18 served as controls. The training group exercised twice a week for 90 min with consecutively increasing loads. At the time of enrollment (T0), as well as after 3 (T1) and 6 (T2) months, a 6-min walk test (6-MWT) was performed and data on health-related quality of life, femoral muscle thickness, and various serum markers were obtained. Results: The training group improved in their 6-MWT results (T0 = 407 ± 152 m vs. T1 = 459 ± 127 m, p = 0.002, vs. T2 = 483.2 ± 130.1 m, p = 0.004), in their cross-sectional area of the musculus rectus femoris (T0 = 6.2 ± 1.2 cm2 vs. T1 = 6.9 ± 1.2 cm2, p = 0.003, vs. 7.5 ± 1.6 cm2, p = 0.002), and in their St. George's Respiratory Questionnaire (SGRQ) score (T0 = 43.3 ± 18.0 vs. T1 = 36.0 ± 18.4, p = 0.001, vs. T2 = 34.7 ± 18. 0, p = 0.004). Serum levels of myostatin, irisin, resistin, and α-Klotho did not change significantly within the training period. Of note, the exercise group showed an inverse relationship between serum levels of resistin and those of α-Klotho after 6 months (r = -0.608, p = 0.021). Conclusions: COPD patients undergoing an individualized, structured, high-intensity training program improved their exercise capacity, gained muscle mass, and improved their quality of life.

Background Transcutaneous carbon-dioxide partial-pressure (TCPCO2) can be reliably measured and may be of clinical relevance in COPD. Changes in TCPCO2 and exercise-induced hypercapnia (EIH) during six-minute walk test (6MWT) need further investigation. We aimed (1) to define patterns of TCPCO2 trends during 6MWT and (2) to study determinants of CO2-retention and EIH. Methods Sixty-two COPD patients (age: 63 ± 8years, FEV1: 33 ± 10%pred.) were recruited and TCPCO2 was recorded by SenTec digital-monitoring-system during 6MWT. Results Half of patients (50%) exhibited CO2-retention (TCPCO2 [Δ] >4 mmHg); 26% preserved and 24% reduced TCPCO2. Nineteen (31%) patients presented EIH (TCPCO2 >45 mmHg). EIH was associated to higher baseline-PCCO2, worse FEV1, lower inspiratory-pressures, underweight/normal BMI, and pre-walk dyspnea. Stronger determinants of CO2-retention were FEV1 and pre-walk dyspnea, whereas baseline-PCCO2 and pre-walk dyspnea better predict EIH. Conclusions PCO2 response to 6MWT is highly heterogeneous; however, very low FEV1 and elevated baseline-PCCO2 together with pre-walk dyspnea increase the risk for CO2-retention and EIH. Overweight-BMI seems to carry a protective effect against EIH in very severe COPD.

Both loss of muscle mass (ie, sarcopenia) and obesity adversely impact clinically important outcomes in patients with chronic obstructive pulmonary disease (COPD). Currently, there are only a few studies in patients with COPD with sarcopenia and concurrent obesity, termed sarcopenic obesity (SO).To explore the effects of SO on exercise capacity, health status, and systemic inflammation in COPD.Baseline data collected from a total of 2548 participants (2000 patients with COPD, mean age (SD), 63.5 (7.1) years; and 548 controls, 54.8 (9.0) years) from ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) study, a multicenter longitudinal observational study, were used.All participants were divided into 4 body composition phenotypes using bioelectrical impedance analysis: (1) normal body composition, (2) obesity, (3) sarcopenia, and (4) SO. In patients with COPD, the 6-minute walking distance, disease-specific health status, and plasma inflammatory markers were compared among the respective body composition groups.Patients with COPD were 3 times more likely to present with SO compared with controls without COPD (odds ratio [OR] 3.3, 95% confidence interval [CI] 2.0-5.4, P.001). In patients with COPD, SO was related to reduced 6-minute walking distance (-28.0 m, 95% CI -45.6 to -10.4), P.01) and to higher systemic inflammatory burden (an elevation of at least 2 inflammatory markers, OR 1.6, 95% CI 1.1-2.5, P = .028) compared with the normal body composition group after adjustments for age, sex, smoking, body mass index, and airflow limitation.Our findings suggest that SO is associated with worse physical performance and higher systemic inflammatory burden compared with other body composition phenotypes in patients with COPD.ClinicalTrials.gov no. NCT00292552.

People with chronic obstructive pulmonary disease (COPD) are affected by somatic as well as psychological symptoms such as anxiety and depression and reduced quality of life. Protective psychological factors exist which enable people to adapt successfully to disease, but research about these factors in COPD is sparse. The aim of this study was to investigate whether sense of coherence (SOC), resilience and social support are potential protective factors and thus associated with reduced levels of symptoms of anxiety and depression and lower perceived disability in people with COPD. An online study was conducted in which n = 531 participants with COPD completed questionnaires assessing protective psychological factors, anxiety and depressive symptoms (Hospital Anxiety and Depression Scale) and disease-specific disability (COPD Disability Index). Regression analyses were conducted. SOC and resilience contributed significantly to reduced levels of symptoms of anxiety and depression and to lower disease-specific disability after controlling for confounding variables and disease severity. Symptoms of anxiety and depression were most strongly predicted by SOC. This study’s results indicated that SOC and resilience could represent helpful individual resources due to their protective potential helping people adjust to COPD. Limitations and implications of this study are discussed.

Background Pulmonary rehabilitation (PR) following lung transplantation (LTx) is considered part of the optimal treatment in chronic obstructive pulmonary disease (COPD) for favourable post-operative outcomes. We investigated the effects of a PR intervention in the post-transplant phase with regard to lung function, exercise responses and cognitive function in COPD LTx recipients. Methods 24 COPD LTx recipients (mean±sd forced expiratory volume in 1 s 75±22% predicted) were assigned to a comprehensive 3-week inpatient PR programme. Changes from PR admission to discharge in lung function variables, 6-min walk test-derived outcomes and cognitive function were assessed and examined for several factors. The magnitude of changes was interpreted by effect size (ES). Results In response to the PR intervention, LTx recipients had improved lung function with regard to diffusing capacity of the lung for carbon monoxide (+4.3%; p=0.012) and static hyperinflation (residual volume/total lung capacity −2.3%; p=0.017), increased exercise capacity (6-min walk test +86 m; p, Pulmonary rehabilitation (PR) demonstrates beneficial effects on functional and cognitive status in COPD LTx recipients. Even a short PR programme of 3 weeks may improve memory ability, learning skills and psychomotor speed in the post-transplant phase. http://bit.ly/2xbRViD

Background More than 60,000 people have health problems due to chemical weapons exposure during the Iran–Iraq war. Respiratory consequences of mustard gas exposure are common and disabling; medical interventions have limited effect. Patients complain of cough, sputum, breathlessness and exercise limitation. We hypothesized that patients with this condition would benefit from pulmonary rehabilitation. Methods We outline the protocol for an assessor-blind, two-armed, parallel-design randomized controlled clinical trial (IRCT2016051127848N1). Sixty patients with respiratory disease due to documented sulfur mustard gas exposure will be randomized to either take part in a 6-week pulmonary rehabilitation programme or receive usual care. Inclusion criteria include forced expiratory volume in 1 second < 80% predicted and Medical Research Council dyspnoea score ≥ 3. The primary endpoint will be the change in cycle endurance time at 70% baseline exercise capacity at 6 weeks. Lung function, physical activity, the strength and endurance of the quadriceps muscle, and quality of life will also be compared. Outcomes will be assessed at 6 weeks and 12 months. Health care utilization will also be assessed. Discussion If the study confirms that rehabilitation is effective for patients with mustard gas lung disease this should prompt provision of the intervention to this patient group. Trial registration Iranian Registry of Clinical Trials, IRCT2016051127848N1. Registered on 24 May 2016. Electronic supplementary material The online version of this article (10.1186/s13063-019-3180-3) contains supplementary material, which is available to authorized users.

BackgroundIn patients with interstitial lung disease (ILD) a cardinal feature is exercise intolerance, often associated with significant dyspnea and severe hypoxemia. Supplemental oxygen therapy may be offered during exercise. The Oxymizer is a nasal cannula with an incorporated reservoir with the potential to deliver higher oxygen doses to the patient.ObjectiveThe primary aim was to investigate the effect of supplemental oxygen delivered via Oxymizer compared to a conventional nasal cannula (CNC) in patients with ILD during constant work rate tests (CWRT). Secondary aim was to evaluate effects on oxygen saturation (SpO(2)), dyspnea and heart rate at isotime.MethodsIn this randomized crossover study 24 ILD patients established on long-term oxygen treatment were included. Patients performed four cycling CWRT at 70% of their peak work rate; twice with the Oxymizer and twice with the CNC.ResultsTwenty-one patients finished all CWRTs (age 60 +/- 10.9 years, VC 55.4 +/- 23.0% predicted). Cycle endurance time was significantly higher while using the Oxymizer compared to CNC (718 +/- 485 vs. 680 +/- 579 seconds, p = 0.02), and SpO(2) at isotime was significantly higher while using the Oxymizer (85.5 +/- 6.7 vs. 82.8 +/- 7.2, p = 0.01). Fifteen of the 21 (71%) patients cycled longer with the Oxymizer. There were no significant differences for dyspnea and heart rate.ConclusionsSupplemental oxygen provided by the Oxymizer significantly, but modestly, improved cycle endurance time and SpO(2) at isotime in ILD patients compared to CNC.

BACKGROUND Long-term oxygen therapy (LTOT) is an established treatment for patients with chronic hypoxemia. Its scientific basis is derived mainly from two trials from the early 1980s that showed a survival advantage for patients with chronic obstructive pulmonary disease (COPD) treated with LTOT. Robust data are not available for other diseases associated with hypoxemia. METHODS This review is based on pertinent publications retrieved by a selective search in PubMed. RESULTS The use of LTOT for 15 to 16 hours per day (or, better, 24 hours per day) is recommended in current guidelines for patients with chronic hypoxemia (PaO2 ≤ 55 mm Hg) because this treatment was found to be associated with a lower mortality rate compared to no LTOT (33% vs. 55%, p

Background: Previous research has calculated the minimal important difference (MID) for the 1-minute sit-to-stand test (1-STST) in patients with COPD to be three repetitions and stated that the 1-STST could be an alternative to the traditional 6-minute walk test (6MWT) to measure exercise performance. Objective: The aim of our study was to prospectively estimate the MID for the 1-STST in response to a 3-week inpatient pulmonary rehabilitation program (PR) in patients with advanced COPD. Methods: 95 patients with COPD (66±8years; FEV1: 37±12%/pred.;1-STST: 19.3±6.9reps) were included in this observational study (NCT02708719). At PR-start and PR-end patients performed a 1-STST on a force platform. Patients also performed two 6MWTs and filled out the chronic respiratory questionnaire (CRQ) for performing an anchor based method. Additionally, difference distribution based methods were used to estimate the MID. Results: An anchor based method could not be used due to the lack of properly associated anchors. Neither the change in 6MWD, nor the changes in the CRQ scores correlated well with the change in 1-STST (all r Conclusion: Results from this study estimated the MID for the 1-STST after PR to be between 2.03 and 3.45 repetitions in this specific population. However, since the change in 1-STST only correlated weakly with the change in 6MWD (r=0.21) it can be assumed that the 1-STST and the 6MWT may measure different qualities of exercise performance.

Background: Demand oxygen delivery systems (DODS) prolong oxygen cylinder life compared to continuous flow (CONT) use, however evidence regarding their effects during use is lacking. Methods: Four databases were searched from 1980 - Jan 2018. Outcomes were oxyhaemoglobin saturation (SpO2%) at rest and during exercise and exercise performance. Risk of bias was evaluated using the Cochrane tool. Data were analyzed via meta-analysis where possible using the generic inverse variance method in Revman 5.3 and narrative synthesis. Results: 10 randomized crossover trials involving 152 COPD patients (FEV1 range 27-42% pred) were included. There was a large degree of uncertainty regarding potential bias related to allocation concealment and blinding for all studies. Data from 3 studies (n=44) showed no significant differences between DODS and CONT in terms of SpO2% at rest or during exercise (Figure). The pooled mean difference in 6-minute walk distance was 3.7m (95%CI -3.0 to 10.3; 2 studies; n=56). Findings were consistent between the meta-analysis and narrative synthesis. Conclusion: DODS and CONT appear to confer similar effects in terms of SpO2% or exercise performance for people with COPD. SpO2% testing may still be indicated for those considering DODS due to intra-individual differences that may arise from different DODS specifications.

Introduction: Dynamic hyperinflation (DHI), an increase in end-expiratory lung volume, can occur during exercise among people with COPD and can be measured by a reduction in inspiratory capacity (IC). No studies have evaluated the use of metronome paced tachypnoea (MPT) as a measurement of DHI against both an incremental peak cycle test (INC) and a constant work rate cycle test (CWR), which is more representative of daily physical activity. Aim: To compare DHI during MPT to DHI in an INC and a CWR. Methods: People with COPD and resting hyperinflation (RV/TLC > 110%) were recruited. Participants performed an MPT, INC and CWR with breath-by-breath measures. In the MPT test, participants performed an IC manoeuvre at rest and after 30 seconds of MPT at twice the resting respiratory rate (RR) with a 1:1 ratio. CWR was performed at 75% peak INC work rate. Both cycle tests were terminated at volitional fatigue. An IC manoeuver was performed before and at end exercise for the INC and CWR tests. Results: Nine participants completed the study. MPT resulted in a significantly smaller IC and higher RR when compared with INC and CWR (Table). There was a non-significant correlation between IC during MPT and INC (r=-0.21 p>0.05) and MPT and CWR (r=0.52 p>0.05). Conclusion: MPT resulted in a smaller IC (i.e greater DHI) and a higher RR than INC or CWR. There was no relationship between the degree of DHI during MPT and that during either INC or CWR and thus MPT may not be able to predict the extent of DHI in exercise.

Background The benefits of pulmonary rehabilitation (PR) on fatigue-resistant skeletal muscle fibre type I have been found to be smaller in COPD patients with alpha-1 antitrypsin deficiency (AATD) than in those without AATD. Alpha-1 antitrypsin (AAT) augmentation therapy was suggested as a potential factor of influence. Whether this finding mirrors different improvements in 6-min walk distance (6MWD) between both groups remains unknown. Methods 140 patients with AATD-related COPD (phenotype PiZZ, FEV 1 : 31 ± 8%pred.) and 280 COPD patients without AATD (FEV 1 : 31 ± 8%pred.) were matched for baseline 6MWD and included in a retrospective analysis. AATD patients were divided into those “on” (AATD AUG+ ) or “off” (AATD AUG- ) augmentation therapy. 6MWD was assessed pre and post an inpatient 4-week PR program. Plasma level of creatinine was analysed at baseline. Results In AATD and COPD patients with comparable initial 6MWD (331 ± 106 m and 326 ± 101 m, p = n.s.), improvements in 6MWD following PR were similar (+49 ± 49 m and +53 ± 52 m, intra-group change: p AUG+ : +51 ± 55 m, AATD AUG- : +47 ± 40 m, p = n.s.). Only in AATD group, higher baseline creatinine levels and lower 6MWD were positive predictors for the PR-related increase in 6MWD. Conclusions Independently of the genetic variant of AAT, COPD patients achieved the same training-related benefit in 6MWD. Augmentation therapy showed no effect on 6MWD adaptation during PR.

Introduction: Non-invasive ventilation (NIV) can increase exercise endurance time and reduce respiratory muscle work in patients with COPD. Previous studies measuring oxygen consumption (VO2) in exercise with NIV did not correct for the effect of NIV pressure on the oxygen sensor of the metabolic measuring device. We have previously published a VO2 correction factor for use with NIV. Aims: To determine the effect of NIV on VO2 (using VO2 correction) at rest and during constant work rate cycle tests (CWR) among patients with COPD. Methods: People with COPD were recruited. Two CWR were performed in random order with and without NIV. In the NIV arm, whilst participants were seated on the cycle ergometer, 10 min of resting data was collected, the last 5 min with NIV applied. Participants then cycled at 75% of their previous peak work rate until fatigue. Breath-by-breath measures of VO2 were recorded continuously. VO2 at rest with and without NIV was of the last 30 seconds of the first 5 minutes rest and the 5 minutes of rest with NIV. Exercise VO2 was calculated from a 30-second average at isotime of the trial with the shortest exercise duration. Results: Nine participants with COPD (mean ± SD) FEV1 43 ± 8 %pred, RV/TLC ratio 0.51 ± 0.10, PCO2 37 ± 4 completed the study. NIV (inspiratory pressure 16.4 ±1.9 cmH2O, expiratory 5 cmH2O) reduced VO2 at rest by a mean difference (MD) of 1.05 mL/Kg/min (95% CI: 0.38 to 1.73; p Conclusion: NIV reduced VO2 at rest and during exercise in people with normocapnic COPD compared to exercise without NIV, most likely due to a lower oxygen cost of breathing.

Aim: To compare the effect of Pulmonary Rehabilitation (PR) on cognitive function, health status, and exercise outcomes in cognitive normal (CN) and cognitive impaired (CI) patients with COPD. Methods: 60 COPD patients (FEV1: 47±15%; 42%women) referred to 3-week in-patient PR and classified as “CN” or “CI” according to the Montreal Cognitive Assessment (MoCA) cutoff-score (≤25points). Domain-specific cognitive function (MoCA, SMMSE, ACER, TICS), health status (CAT), health-related quality of life (SF-36), the 6MWT and cerebral oxygen availability during cycle endurance test (CET) at 75%WR, were assessed on admission and discharge. Results: 25 patients (42%) presented evidences of CI and low performance in cognitive tests. Compared to CN, CI patients improved visuospatial skills and fluency (effect size; ES: 0.44; 0.48), whilst similar improvements in memory (ES: 0.75), physical and social function (ES: 0.45; 0.47), vitality (ES: 0.56), general and mental health (ES: 0.47; 0.67) were observed, respectively. CI patients did not improve body pain and limitations from emotional problems as assessed by SF-36 but increased 6MWD (from 378 to 403m, p=0.052), CET (from 10.0 to 12.3min, p Conclusion: CI patients gain significant benefits in cognitive function from PR but are not responsive to improvements in body pain and emotional limitations compared to CN. Persistent body pain may have limited the effectiveness of PR and improvements in the 6MWT in CI patients with COPD.