Practical Recommendations for Exercise Training in Patients with Long COVID with or without Post-exertional Malaise: A Best Practice Proposal.

People with long COVID may suffer from a wide range of ongoing symptoms including fatigue, exertional dyspnea, reduced exercise performance, and others. In particular, impaired exercise performance is a condition that can be recovered in many people through an individualized physical exercise training program. However, clinical experience has shown that the presence of post-exertional malaise (PEM) is a significant barrier to physical exercise training in people with long COVID. Currently, there is no guideline or consensus available on how to apply exercise training in this cohort. Therefore, we conducted a literature review in the PubMed library using the following search terms: "COVID", "post-COVID", "long COVID" and "exercise" searching for studies from January 2020 to January 2024. Data from 46 trials were included. Exercise training regimes were very heterogeneous and none of these studies reported on the management of PEM in the context of an exercise training program. Based on the feedback from an additional survey that was answered by 14 international experts in the field of exercise training in long COVID, combined with the authors´ own extensive practical experience, a best practice proposal for exercise training recommendations has been developed. This proposal differentiates exercise procedures according to the presence of no, mild/moderate or severe PEM in people with long COVID. These recommendations may guide allied healthcare professionals worldwide in initiating and adjusting exercise training programs for people with long COVID, stratified according to the presence and severity of PEM.

Impaired Sleep in Patients with Post-COVID-19 Syndrome Compared to Healthy Controls: A Cross-Sectional Trial.

INTRODUCTION: To objectify self-reported sleep disorders in individuals with post-COVID-syndrome (PCS), we aimed to investigate the prevalence and nature of sleep disturbances by polysomnography (PSG) in PCS compared to healthy individuals. METHODS: People with PCS (n = 21) and healthy controls (CON, n = 10) were included in this prospective trial. At baseline, clinical and social anamnesis, lung function, 1 min sit-to-stand test (STST) and Pittsburgh Sleep Quality Index (PSQI) were assessed. For a single-night, sleep health was evaluated by video-PSG. The apnoea/hypopnea index (AHI) was used as the primary outcome. RESULTS: Twenty patients with PCS (50 ± 11 y, BMI 27.1 m2/kg, SARS-CoV-2 infection 8.5 ± 4.5 months ago) and 10 CON participants (46 ± 10 y, BMI 23.0 m2/kg, no SARS-CoV-2 infection in the history) completed the study. Forced vital capacity (p = 0.018), STST repetitions (p < 0.001), and symptoms of dyspnoea (at rest: p = 0.002, exertion: p < 0.001) were worse in PCS compared to CON. PSQI score (PCS: 7.5 ± 4.7 points) was higher in PCS compared to CON (Δ = 3.7 points, 95% CI [0.4-7.1] p = 0.015), indicating poor sleep in 80% of patients with PCS. Although PSG showed comparable sleep stage distributions in both groups, AHI (Δ = 9.0 n/h, 95% CI [3.3-14.8], p = 0.002), PLM index (Δ = 5.1 n/h, 95% CI [0.4-9.8], p = 0.017), and the prevalence of sleep apnoea (60% vs. 10%, p = 0.028) was significantly higher in PCS compared to CON. CONCLUSION: Quantifiable subjective limitations of sleep have been revealed by PSG data in this PCS cohort. More than half of PCS patients had signs of sleep apnoea, highlighting the importance of sleep screening in PCS.

High-intensity non-invasive ventilation during exercise-training versus without in people with very severe COPD and chronic hypercapnic respiratory failure: a randomised controlled trial.

BACKGROUND: People with very severe chronic obstructive pulmonary disease (COPD) using nocturnal non-invasive ventilation (NIV) for chronic hypercapnic respiratory failure (CHRF) experience reduced exercise capacity and severe dyspnoea during exercise training (ET). The use of NIV during ET can personalise training during pulmonary rehabilitation (PR) but whether high-intensity NIV (HI-NIV) during exercise is accepted and improves outcomes in these extremely physically limited patients is unknown. The aim of this trial was to determine if ET with HI-NIV during PR was more effective than without at improving exercise capacity and reducing dyspnoea during exercise. METHODS: Patients with COPD, CHRF and nocturnal-NIV were randomised to supervised cycle-ET as part of PR with HI-NIV or without (control). Primary outcome was change in cycle endurance time (ΔCETtime), while secondary outcomes were dyspnoea at isotime during the cycle endurance test and during ET-sessions and for the HI-NIV group, post-trial preferred exercising method. RESULTS: Twenty-six participants (forced expiratory volume in 1 s 22±7%pred, PaCO251±7 mm Hg) completed the trial (HI-NIV: n=13, ET: IPAP 26±3/EPAP 6±1 cm H2O; control n=13). At completion of a 3 week ET-programme, no significant between-group differences in ΔCETtime were seen (HI-NIV-control: Δ105 s 95% CI (-92 to 302), p=0.608). Within-group ΔCETtime was significant (HI-NIV: +246 s 95% CI (61 to 432); control: +141 s 95% CI (60 to 222); all p<0.05). The number of responders (Δ>minimal important difference (MID)101 s: n=53.8%) was the same in both groups for absolute ΔCETtime and 69.2% of control and 76.9% of the HI-NIV group had a %change>MID33%.Compared with control, the HI-NIV group reported less isotime dyspnoea (Δ-2.0 pts. 95% CI (-3.2 to -0.8), p=0.005) and during ET (Δ-3.2 pts. 95% CI (-4.6 to -1.9), p<0.001). Most of the HI-NIV group (n=12/13) preferred exercising with NIV. CONCLUSION: In this small group of patients with very severe COPD requiring nocturnal NIV, participation in an ET-programme during PR significantly improved exercise capacity irrespective of HI-NIV use. Reported dyspnoea was in favour of HI-NIV. TRIAL REGISTRATION NUMBER: NCT03803358.

Rehabilitative interventions in patients with persistent post COVID-19 symptoms-a review of recent advances and future perspectives.

The SARS-CoV-2 pandemic has not only caused millions of deaths but left also millions of people with persistent symptoms behind. These long-term COVID-19 sequelae cause a considerable burden on individuals´ health, healthcare systems, and economies worldwide given the high rate of SARS-CoV-2 infections. Therefore, rehabilitative interventions and strategies are needed to counteract the post COVID-19 sequelae. The importance of rehabilitation for patients with persistent COVID-19 symptoms has been recently also highlighted in a Call for Action by the World Health Organisation. Based on previously published research, but also in line with clinical experience, COVID-19 is not one specific disease but rather presents in different phenotypes that vary in their pathophysiological mechanisms, symptomatic manifestations, and potential interventional approaches. This review provides a proposal for differentiating post COVID-19 patients in non-organ-specific phenotypes that may help clinicians to evaluate patients and to plan therapeutic options. Furthermore, we present current unmet needs and suggest a potential pathway for a specific rehabilitation approach in people with persistent post-COVID symptoms.

Automatic oxygen titration versus constant oxygen flow rates during walking in COPD: a randomised controlled, double-blind, crossover trial.

RATIONALE: In patients with COPD, oxygen (O2)-supplementation via a constant flow oxygen system (CFOS) can result in insufficient oxygen saturation (SpO2 <90%) during exercise. An automatically titrating O2-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. METHODS: Fifty 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 SpO2 of 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. RESULTS: Participants (median (IQR): age 66 (59, 70) years, FEV1 28.8 (24.8, 35.1) % predicted, PO2 54.7 (51.0, 57.7) mm Hg, PCO2 44.2 (38.2, 47.8) mm Hg) walked significantly longer with ESWTATOS in comparison to ESWTCFOS (median effect (95% CI) +144.5 (54 to 241.5) s, p<0.001). At isotime, SpO2 was significantly higher (+3 (95% CI 1 to 4) %, p<0.001) with ATOS while TcPCO2, 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 p<0.001) while PCO2 was comparable. CONCLUSION: In patients with hypoxaemia with severe COPD the use of ATOS leads to significant, clinically relevant improvements in walking endurance time, SpO2, PO2 and dyspnoea with no impact on PCO2. TRIAL REGISTRATION NUMBER: NCT03803384.

Using a smartphone application maintains physical activity following pulmonary rehabilitation in patients with COPD: a randomised controlled trial.

BACKGROUND: Evidence suggests that patients with COPD struggle to maintain improved physical activity (PA) after completing pulmonary rehabilitation (PR). Smartphone applications (apps) providing a comprehensive training programme have conferred healthy benefits. This study was conducted to determine whether regular usage of an app maintains PA following PR. METHODS: Patients with stage II-IV COPD were enrolled in a 6-month trial following PR. After the screening period, participants were randomised into the Kaia COPD app group (intervention group (IG)) or the control group (CG). The primary outcome was PA (daily steps), measured using an activity tracker. Secondary outcomes included the COPD Assessment Test (CAT), the Chronic Respiratory Disease Questionnaire (CRQ) and the 1 min Sit-to-Stand Test (STST). RESULTS: Sixty participants completed the study. The median steps from baseline to 6 months were significantly different between the groups, in favour of the IG (-105.3, IQR -1970.1 to 2105.8, vs CG -1173.0, IQR -3813.1 to -93.8; p=0.007). CAT was significantly decreased in the IG (15.1±8.6 vs 19.7±6.4, p=0.02), whereas the CRQ subdomains for dyspnoea (4.5±1.7 vs 3.7±1.3, p=0.033) and fatigue (4.5±1.4 vs 3.5±1.3, p=0.028) improved significantly in the IG. The STST at 6 months was not significant. Sleep duration and sleep efficiency showed no significant differences between the two groups at any time. CONCLUSIONS: A comprehensive program by using the Kaia app following PR maintained PA and improved symptoms in patients with COPD at 6 months. The app might be an important accessory tool for enhanced COPD care. TRIAL REGISTRATION NUMBER: DRKS00017275.

Millimeter-wave gas spectroscopy for breath analysis of COPD patients in comparison to GC-MS.

The analysis of human breath is a very active area of research, driven by the vision of a fast, easy, and non-invasive tool for medical diagnoses at the point of care. Millimeter-wave gas spectroscopy (MMWGS) is a novel, well-suited technique for this application as it provides high sensitivity, specificity and selectivity. Most of all, it offers the perspective of compact low-cost systems to be used in doctors' offices or hospitals. In this work, we demonstrate the analysis of breath samples acquired in a medical environment using MMWGS and evaluate validity, reliability, as well as limitations and perspectives of the method. To this end, we investigated 28 duplicate samples from chronic obstructive lung disease patients and compared the results to gas chromatography-mass spectrometry (GC-MS). The quantification of the data was conducted using a calibration-free fit model, which describes the data precisely and delivers absolute quantities. For ethanol, acetone, and acetonitrile, the results agree well with the GC-MS measurements and are as reliable as GC-MS. The duplicate samples deviate from the mean values by only 6% to 18%. Detection limits of MMWGS depend strongly on the molecular species. For example, acetonitrile can be traced down to 1.8 × 10-12mol by the MMWGS system, which is comparable to the GC-MS system. We observed correlations of abundances between formaldehyde and acetaldehyde as well as between acetonitrile and acetaldehyde, which demonstrates the potential of MMWGS for breath research.

Survival after inpatient or outpatient pulmonary rehabilitation in patients with fibrotic interstitial lung disease: a multicentre retrospective cohort study.

BACKGROUND: The impact of pulmonary rehabilitation (PR) on survival in patients with fibrotic interstitial lung disease (ILD) is unknown. Given the challenges conducting a large randomised controlled trial, we aimed to determine whether improvement in 6-minute walk distance (6MWD) was associated with better survival. METHODS: This retrospective, international cohort study included patients with fibrotic ILD participating in either inpatient or outpatient PR at 12 sites in 5 countries. Multivariable models were used to estimate the association between change in 6MWD and time to death or lung transplantation accounting for clustering by centre and other confounders. RESULTS: 701 participants (445 men and 256 women) with fibrotic ILD were included. The mean±SD ages of the 196 inpatients and 505 outpatients were 70±11 and 69±12 years, respectively. Baseline/changes in 6MWD were 262±128/55±83 m for inpatients and 358±125/34±65 m for outpatients. Improvement in 6MWD during PR was associated with lower hazard rates for death or lung transplant on adjusted analysis for both inpatient (HR per 10 m 0.94, 95% CI 0.91 to 0.97, p<0.001) and outpatient PR (HR 0.97, 95% CI 0.95 to 1.00, p=0.042). Participation in ≥80% of planned outpatient PR sessions was associated with a 33% lower risk of death (95% CI 0.49% to 0.92%). CONCLUSIONS: Patients with fibrotic ILD who improved physical performance during PR had better survival compared with those who did not improve performance. Confirmation of these hypothesis-generating findings in a randomised controlled trial would be required to definitely change clinical practice, and would further support efforts to improve availability of PR for patients with fibrotic ILD.

[The pulmonary view on post-/Long-COVID]. / Post-COVID aus pneumologischer Sicht.

A majority of COVID patients suffers from hetereogenous symptoms after acute infection which are limiting patients participation in social life, activities of daily living and the return to work. In March 2021, the German Society of Pneumology initiated the AWMF S1 guideline Post-COVID/Long-COVID in order to show an individual practice-oriented, diagnostic and therapeutic clinical algorithm according to the individual symptoms. This article is based on the S1 guideline and highlights some trials of interest with a focus on pulmonary symptoms. The guideline and, accordingly, this article have an explicitly practical and clinical purpose. The guideline will be further developed by the author team based on the current increase in knowledge this is reflected in the clinical summary article.

Relationship between body composition, exercise capacity and health-related quality of life in idiopathic pulmonary fibrosis.

INTRODUCTION: Bioelectrical 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. OBJECTIVES: To investigate the frequency of low FFMI and PhA and their associations with exercise capacity and HRQL in patients with IPF. METHODS: Patients 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. RESULTS: 98 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, p<0.05). None of the variables were related to SF-36 Mental Summary Score. CONCLUSION: One-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.

Pulmonary rehabilitation in long COVID: more than just natural recovery!?

In the light of missing randomised controlled trials, some arguments suggest that pulmonary rehabilitation has beneficial effects beyond natural recovery https://bit.ly/3ze2xvw.

Influence of an Acute Exacerbation During Pulmonary Rehabilitation in Patients With Chronic Obstructive Pulmonary Disease Awaiting Lung Transplantation.

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.

Benefits of pulmonary rehabilitation in COVID-19: a prospective observational cohort study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can result in a large variety of chronic health issues such as impaired lung function, reduced exercise performance and diminished quality of life. Our study aimed to investigate the efficacy, feasibility and safety of pulmonary rehabilitation in COVID-19 patients and to compare outcomes between patients with a mild/moderate and a severe/critical course of the disease. METHODS: Patients in the post-acute phase of a mild to critical course of COVID-19 admitted to a comprehensive 3-week inpatient pulmonary rehabilitation programme were included in this prospective, observational cohort study. Several measures of exercise performance (6-min walk distance (6MWD)), lung function (forced vital capacity (FVC)) and quality of life (36-question short-form health survey (SF-36)) were assessed before and after pulmonary rehabilitation. RESULTS: 50 patients were included in the study (24 with mild/moderate and 26 with severe/critical COVID-19). On admission, patients had a reduced 6MWD (mild: median 509 m, interquartile range (IQR) 426-539 m; severe: 344 m, 244-392 m), an impaired FVC (mild: 80%, 59-91%; severe: 75%, 60-91%) and a low SF-36 mental health score (mild: 49 points, 37-54 points; severe: 39 points, 30-53 points). Patients attended a median (IQR) 100% (94-100%) of all provided pulmonary rehabilitation sessions. At discharge, patients in both subgroups improved in 6MWD (mild/moderate: +48 m, 35-113 m; severe/critical: +124 m, 75-145 m; both p<0.001), FVC (mild/moderate: +7.7%, 1.0-17.8%, p=0.002; severe/critical: +11.3%, 1.0-16.9%, p<0.001) and SF-36 mental component (mild/moderate: +5.6 points, 1.4-9.2 points, p=0.071; severe/critical: +14.4 points, -0.6-24.5, p<0.001). No adverse event was observed. CONCLUSION: Our study shows that pulmonary rehabilitation is a feasible, safe and effective therapeutic option in COVID-19 patients independent of disease severity.

Benefits of pulmonary rehabilitation in COPD patients with mild cognitive impairment - A pilot study.

BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

[Rehabilitation in pneumology]. / Rehabilitation in der Pneumologie.

Pulmonary rehabilitation (PR) is an evidence-based multidisciplinary treatment for patients with chronic respiratory diseases. The indications for applying for PR are given if there is an appropriate rehabilitation capability, need for rehabilitation and favorable rehabilitation prognosis. The aims of PR are the reduction of symptoms and improvement of the quality of life and physical resilience. The efficiency of PR is well proven for patients with chronic obstructive pulmonary disease (COPD) with the highest evidence grade and for non-COPD patients with an increasing level of evidence based on randomized controlled trials and meta-analyses. The treatment content of PR is individually adapted to the patients' needs by a multidisciplinary treatment team. In order to sustainably maintain the success of PR there is the possibility to participate in outpatient aftercare programs (e.g. breathing exercises) and to utilize digital technologies as supporting measures.

Whole-body vibration training versus conventional balance training in patients with severe COPD-a randomized, controlled trial.

BACKGROUND: Whole-body vibration training (WBV) performed on a vibration platform can significantly improve physical performance in patients with chronic obstructive pulmonary disease. It has been suggested that an important mechanism of this improvement is based on an improvement in balance. Therefore, the aim of this study was to investigate the effects of WBV compared to conventional balance training. METHODS: 48 patients with severe COPD (FEV1: 37 ± 7%predicted) and low exercise performance (6 min walk distance (6MWD): 55 ± 10%predicted) were included in this 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 2 sets of 1 min each, either on a vibration platform (Galileo) at varying frequencies (5-26 Hz) (WBV) or on a conventional balance board (BAL). The primary outcome parameter was the change in balance performance during a semi tandem stance with closed eyes assessed on a force measurement platform. Muscular power during a countermovement jump, the 6MWD, and 4 m gait speed test (4MGST) were secondary outcomes. Non-parametric tests were used for statistical analyses. RESULTS: Static balance performance improved significantly more (p = 0.032) in favor of WBV (path length during semi-tandem stand: - 168 ± 231 mm vs. + 1 ± 234 mm). Muscular power also increased significantly more (p = 0.001) in the WBV group (+ 2.3 ± 2.5 W/kg vs. - 0.1 ± 2.0 W/kg). 6MWD improved to a similar extent in both groups (WBV: 48 ± 46 m, p < 0.001 vs. BAL: 38 ± 32 m; p < 0.001) whereas the 4MGST increased significantly only in the WBV-group (0.08 ± 0.14 m/s2, p = 0.018 vs. 0.01 ± 0.11 m/s2, p = 0.71). CONCLUSIONS: WBV can improve balance performance and muscular power significantly more compared to conventional balance training. TRIAL REGISTRATION: Clinical-Trials registration number: NCT03157986; date of registration: May 17, 2017. https://clinicaltrials.gov/ct2/results?cond=&term=NCT03157986&cntry=&state=&city=&dist = .

Protocol for an observational study to identify potential predictors of an acute exacerbation in patients with chronic obstructive pulmonary disease (the PACE Study).

INTRODUCTION: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are the most critical events for patients with COPD that have a negative impact on patients' quality of life, accelerate disease progression, and can result in hospital admissions and death. Although there is no distinct definition or detailed knowledge about AECOPD, it is commonly used as primary outcome in clinical studies. Furthermore, it may be difficult in clinical practice to differentiate the worsening of symptoms due to an AECOPD or to the development of heart failure. Therefore, it is of major clinical importance to investigate the underlying pathophysiology, and if possible, predictors of an AECOPD and thus to identify patients who are at high risk for developing an acute exacerbation. METHODS AND ANALYSIS: In total, 355 patients with COPD will be included prospectively to this study during a 3-week inpatient pulmonary rehabilitation programme at the Schoen Klinik Berchtesgadener Land, Schoenau am Koenigssee (Germany). All patients will be closely monitored from admission to discharge. Lung function, exercise tests, clinical parameters, quality of life, physical activity and symptoms will be recorded, and blood samples and exhaled air will be collected. If a patient develops an AECOPD, there will be additional comprehensive diagnostic assessments to differentiate between cardiac, pulmonary or cardiopulmonary causes of worsening. Follow-up measures will be performed at 6, 12 and 24 months.Exploratory data analyses methods will be used for the primary research question (screening and identification of possible factors to predict an AECOPD). Regression analyses and a generalised linear model with a binomial outcome (AECOPD) will be applied to test if predictors are significant. ETHICS AND DISSEMINATION: This study has been approved by the Ethical Committee of the Philipps University Marburg, Germany (No. 61/19). The results will be presented in conferences and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04140097.