Bronchodilator Response in Post-COVID-19 Patients Undergoing Pulmonary Rehabilitation.

INTRODUCTION: SARS-CoV-2 infections can result in a broad spectrum of symptoms from mild to life-threatening. Long-term consequences on lung function are not well understood yet. METHODS: In our study, we have examined 134 post-COVID patients (aged 54.83 ± 14.4 years) with dyspnea on exertion as a leading symptom 6 weeks to 24 months after a SARS-CoV-2 infection for bronchodilator responsiveness during their stay in our pulmonary rehabilitation clinic. RESULTS: Prior to bronchial dilation, 6 out of 134 patients (4.47%) presented an FEV1/FVC ratio below lower limit of normal (Z-score = -1.645) indicative of an obstructive airway disease. Following inhalation of a ß2-adrenergic agonist we measured a mean FEV1 increase of 181.5 mL in our cohort, which was significantly elevated compared to a historical control group (ΔFEV1 = 118 mL). 28.7% of the patients showed an increase greater than 200 mL and 12% displayed a significant bronchodilation response (>200 mL ΔFEV1 and >12% FEV1 increase). Interestingly, no significant difference in bronchial dilation effect was observed when comparing patients hospitalized and those non-hospitalized during the course of their SARS-CoV-2 infection. CONCLUSION: Our data provide evidence for increased prevalence of obstructive ventilatory defects and increased bronchodilator responsiveness in patients with persisting symptoms after COVID-19. Depending on the extent of this complication, post-COVID patients may benefit from an adapted ß2-inhalation therapy including subsequent reevaluation.

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.

Perceptions of Noninvasive Ventilation During Exercise in Noninvasive Ventilation-Naïve Patients With COPD.

BACKGROUND: The perceptions of using noninvasive ventilation (NIV) during exercise in patients with COPD who are naïve to NIV is unknown. The present study aimed to examine the perceptions of using NIV during exercise in people with COPD and to determine the relationship between patient perceptions with both baseline patient characteristics and exercise outcomes. METHODS: During a trial examining the effect of NIV during exercise on dynamic hyperinflation in people with COPD who were naïve to NIV, participants completed a 5-point Likert scale questionnaire (scored strongly disagree -2 to strongly agree +2) before and after using NIV during exercise and a semi-structured interview after using NIV during exercise. RESULTS: Eighteen participants, mean age (SD) 69 (7) y, FEV1/FVC 0.44 (0.08), FEV1 39 (7)% predicted, completed the study. Prior to exercise with NIV, participants were neutral about NIV, (mean [SD]) (0.67[0.84]). After exercise with NIV, participants felt that NIV made breathing easier (1.00 [0.77]) and that it helped exercise (1.06 [0.64]). There were moderate correlations between feeling that NIV was comfortable or effective and a change in exercise endurance time (ρ = - 0.588, P = .02), isotime inspiratory capacity (ρ = 0.488, P = .03), and measures of resting hyperinflation (ρ = 0.603, \P = .02). Interviews revealed that despite feeling comfortable using NIV during exercise, NIV might be too complicated for patients to manage outside a supervised environment. CONCLUSIONS: Individuals with COPD, naïve to NIV, and using NIV during exercise for the first time reported a positive effect of NIV on breathlessness and exercise performance. Participants' perceived benefit of NIV correlated moderately with increased endurance time and resting hyperinflation and with a reduction in dynamic hyperinflation during exercise, suggesting that patient reports could also aid selection of those who will benefit from NIV during exercise.

[Overview on pulmonary rehabilitation]. / Übersicht zur pneumologischen Rehabilitation.

Pulmonary rehabilitation (PR) is an evidence-based multidisciplinary treatment for patients with chronic respiratory diseases. The indications for PR prescription are given if there is a rehabilitation capability, a need for rehabilitation and a beneficial rehabilitation prognosis. The aims of PR are to reduce symptoms and to improve the quality of life and the patients' physical capacity. The effectiveness of PR is well-proven for patients with chronic obstructive pulmonary disease (COPD) at the highest level of evidence 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 multimodal and multidisciplinary treatment team. To maintain the rehabilitation benefits of PR there is the possibility to participate in outpatient follow-up programs as well as to use digital technologies.

[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.

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.

Bilevel Noninvasive Ventilation During Exercise Reduces Dynamic Hyperinflation and Improves Cycle Endurance Time in Severe to Very Severe COPD.

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 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 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.

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.

[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.