[S1 guidelines for the management of postviral conditions using the example of post-COVID-19]. / Leitlinie S1 für das Management postviraler Zustände am Beispiel Post-COVID-19.

These S1 guidelines are an updated and expanded version of the S1 guidelines on long COVID differential diagnostic and management strategies. They summarize the state of knowledge on postviral conditions like long/post COVID at the time of writing. Due to the dynamic nature of knowledge development, they are intended to be "living guidelines". The focus is on practical applicability at the level of primary care, which is understood to be the appropriate place for initial access and for primary care and treatment. The guidelines provide recommendations on the course of treatment, differential diagnostics of the most common symptoms that can result from infections like with SARS-CoV-2, treatment options, patient management and care, reintegration and rehabilitation. The guidelines have been developed through an interdisciplinary and interprofessional process and provide recommendations on interfaces and possibilities for collaboration.

S2k-Guideline SARS-CoV-2, COVID-19 and (early) rehabilitation - a consensus-based guideline for Germany.

The consensus-based guideline "SARS-CoV-2, COVID-19 and (early) rehabilitation" for Germany has two sections: In the first part, the guideline addresses infection protection-related procedures during the COVID-19 pandemic. In the second part, it provides practice recommendations for rehabilitation after COVID-19. The specific recommendations for rehabilitation after COVID-19 as issued by 13 German medical societies and two patient-representative organizations are presented together with general background information for their development.

Volatile Phases Derived from Serum, DC, or MLC Culture Supernatants to Deduce a VOC-Based Diagnostic Profiling Strategy for Leukemic Diseases.

Volatile organic compounds (VOCs) reflect the metabolism in healthy and pathological conditions, and can be collected easily in a noninvasive manner. They are directly measured using electronical nose (eNose), and may qualify as a systemic tool to monitor biomarkers related to disease. Myeloid leukemic blasts can be transformed into leukemia-derived dendritic cells (DCleu) able to improve (anti-leukemic) immune responses. To profile immunological changes in healthy and acute myeloid leukemic (AML) patients' ex vivo cell cultures, we correlated the cell biological data with the profiles of cell culture supernatant-derived VOCs. DC/DCleu from leukemic or healthy whole blood (WB) were generated without (Control) or with immunomodulatory Kit M (Granulocyte macrophage-colony-stimulating-factor (GM-CSF) + prostaglandin E1 (PGE1)) in dendritic cell cultures (DC culture). Kit-pretreated/not pretreated WB was used to stimulate T cell-enriched immunoreactive cells in mixed lymphocyte cultures (MLC culture). Leukemia-specific adaptive and innate immune cells were detected with a degranulation assay (Deg) and an intracellular cytokine assay (InCyt). Anti-leukemic cytotoxicity was explored with a cytotoxicity fluorolysis assay (CTX). VOCs collected from serum or DC- and MLC culture supernatants (with vs. without Kit M pretreatment and before vs. after culture) were measured using eNose. Compared to the Control (without treatment), Kit M-pretreated leukemic and healthy WB gave rise to higher frequencies of mature (leukemia-derived) DC subtypes of activated and (memory) T cells after MLC. Moreover, antigen (leukemia)-specific cells of several lines (innate and adaptive immunity cells) were induced, giving rise to blast-lysing cells. The eNose could significantly distinguish between healthy and leukemic patients' serum, DC and MLC culture supernatant-derived volatile phases and could significantly separate several supernatant (with vs. without Kit M treatment, cultured vs. uncultured)-derived VOCs within subgroups (healthy DC or leukemic DC, or healthy MLC or leukemic MLC supernatants). Interestingly, the eNose could indicate a Kit M- and culture-associated effect. The eNose may be a prospective option for the deduction of a VOC-based profiling strategy using serum or cell culture supernatants and could be a useful diagnostic tool to recognize or qualify AML disease.

Surface proteome of plasma extracellular vesicles as mechanistic and clinical biomarkers for malaria.

PURPOSE: Malaria is a life-threatening mosquito-borne disease caused by Plasmodium parasites, mainly in tropical and subtropical countries. Plasmodium falciparum (P. falciparum) is the most prevalent cause on the African continent and responsible for most malaria-related deaths globally. Important medical needs are biomarkers for disease severity or disease outcome. A potential source of easily accessible biomarkers are blood-borne small extracellular vesicles (sEVs). METHODS: We performed an EV Array to find proteins on plasma sEVs that are differentially expressed in malaria patients. Plasma samples from 21 healthy subjects and 15 malaria patients were analyzed. The EV array contained 40 antibodies to capture sEVs, which were then visualized with a cocktail of biotin-conjugated CD9, CD63, and CD81 antibodies. RESULTS: We detected significant differences in the protein decoration of sEVs between healthy subjects and malaria patients. We found CD106 to be the best discrimination marker based on receiver operating characteristic (ROC) analysis with an area under the curve of > 0.974. Additional ensemble feature selection revealed CD106, Osteopontin, CD81, major histocompatibility complex class II DR (HLA-DR), and heparin binding EGF like growth factor (HBEGF) together with thrombocytes to be a feature panel for discrimination between healthy and malaria. TNF-R-II correlated with HLA-A/B/C as well as CD9 with CD81, whereas Osteopontin negatively correlated with CD81 and CD9. Pathway analysis linked the herein identified proteins to IFN-γ signaling. CONCLUSION: sEV-associated proteins can discriminate between healthy individuals and malaria patients and are candidates for future predictive biomarkers. TRIAL REGISTRATION: The trial was registered in the Deutsches Register Klinischer Studien (DRKS-ID: DRKS00012518).

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.

[Guideline S1: Long COVID: Diagnostics and treatment strategies]. / Leitlinie S1: Long COVID: Differenzialdiagnostik und Behandlungsstrategien.

This guideline comprises the state of science at the time of the editorial deadline. In view of the high turnover of knowledge the guideline is designed as a living guideline. The main objective was to provide a tool for the use in primary care, being considered well suited as a first point of entry and for the provision of care. The guideline gives recommendations on the differential diagnosis of symptoms following SARS-CoV­2 infection, on their therapeutic options, as well as for guidance and care of the patients concerned. It also offers advice concerning return to daily life and rehabilitation. Long COVID being a very variable condition, we chose an interdisciplinary approach.

Health and functional status of tiotropium/olodaterol-treated patients with COPD: results from the AERIAL® non-interventional study.

Patients with COPD often have reduced physical activity, which can impair health status. Real-world data can provide valuable information on the health and functional status of patients with COPD treated with tiotropium/olodaterol. AERIAL® (ClinicalTrials.gov NCT03165045) was a German, non-interventional study of patients with COPD receiving treatment with tiotropium/olodaterol under real-world conditions for ∼6 weeks. The primary end-point was the proportion of patients achieving a decrease of ≥0.4 points in Clinical COPD Questionnaire (CCQ) score. The CCQ-4 subdomain was used to assess functional status, and the Physician's Global Evaluation (PGE) scale was used to assess the patients' general condition. Safety was assessed, as well as patient satisfaction and willingness to continue treatment. Out of 1351 screened patients, 1322 were treated and 1140 comprised the full analysis set. The primary end-point was met: 66.3% of patients achieved a ≥0.4-point decrease in overall CCQ score (mean±sd decrease 0.78±0.95). Mean±sd decreases in CCQ symptoms and functional state subdomains were 0.84±1.06 and 0.75±1.05 points, respectively. PGE scores improved. One fatality (not treatment-related) and 23 drug-related adverse events were recorded, most commonly nausea and vertigo. >85% of patients were satisfied/very satisfied with tiotropium/olodaterol overall and with the Respimat® device, both in terms of inhalation and handling. Most patients (95.2%) expressed willingness to continue treatment. Patients with COPD treated with tiotropium/olodaterol via Respimat® in routine clinical practice had clinically relevant improvements in health and functional status compared with baseline.

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.

Acute effects of supplemental oxygen therapy using different nasal cannulas on walking capacity in patients with idiopathic pulmonary fibrosis: a randomised crossover trial.

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.

SARS-CoV-2 infection in two patients following recent lung transplantation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has become a global health problem with pandemic character. Lung transplant recipients may be particularly at risk due to the high degree of immunosuppression and the lung being the organ primarily affected by COVID-19. We describe a 16-year-old male and a 64-year-old female recently lung transplanted patients with COVID-19 during inpatient rehabilitation. Both patients were receiving triple immunosuppressive therapy and had no signs of allograft dysfunction. Both patients had close contact with a person who developed COVID-19 and were tested positive for SARS-CoV-2. Subsequently, both patients underwent systematic screening and SARS-CoV-2 was ultimately detected. Although the 16-year-old boy was completely asymptomatic, the 64-year-old woman developed only mild COVID-19. Immunosuppressive therapy was unchanged and no experimental treatment was initiated. No signs of graft involvement or dysfunction were noticed. In conclusion, our report of patients with asymptomatic SARS-CoV-2 infection and mild COVID-19, respectively, may indicate that lung transplant recipients are not per se at risk for severe COVID-19. Further observations and controlled trials are urgently needed to study SARS-CoV-2 infection in lung transplant recipients.

Surface Proteome of Plasma Extracellular Vesicles as Biomarkers for Pneumonia and Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

BACKGROUND: Community-acquired pneumonia (CAP) and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) represent a major burden of disease and death and their differential diagnosis is critical. A potential source of relevant accessible biomarkers are blood-borne small extracellular vesicles (sEVs). METHODS: We performed an extracellular vesicle array to find proteins on plasma sEVs that are differentially expressed and possibly allow the differential diagnosis between CAP and AECOPD. Plasma samples were analyzed from 21 healthy controls, 24 patients with CAP, and 10 with AECOPD . The array contained 40 antibodies to capture sEVs, which were then visualized with a cocktail of biotin-conjugated CD9, CD63, and CD81 antibodies. RESULTS: We detected significant differences in the protein decoration of sEVs between healthy controls and patients with CAP or AECOPD. We found CD45 and CD28 to be the best discrimination markers between CAP and AECOPD in receiver operating characteristic analyses, with an area under the curve >0.92. Additional ensemble feature selection revealed the possibility to distinguish between CAP and AECOPD even if the patient with CAP had COPD, with a panel of CD45, CD28, CTLA4 (cytotoxic T-lymphocyte-associated protein 4), tumor necrosis factor-R-II, and CD16. CONCLUSION: The discrimination of sEV-associated proteins is a minimally invasive method with potential to discriminate between CAP and AECOPD.

Sleep and rheumatic diseases.

This review article discusses various forms of sleep disorders associated with musculoskeletal diseases (MD). It presents the pathophysiology and interaction of sleep-related disorders and MD and summarizes clinical symptoms and therapies from a somnological perspective. BACKGROUND: A large number of patients suffering from MD report fragmented sleep with poor overall sleep quality. Sleep disorders often lead to increased symptoms such as daytime fatigue, depression, or increased pain intensity. In contrast, the perception of pain worsens the quality of sleep. Sleep is a complex regulation of hormonal and neuromodulatory influences to maintain regenerative processes and signal processing. Furthermore, interleukins (e.g., IL-6 and TNFα), messenger substances, or inflammatory markers (e.g., CRP) may have a regulatory influence on sleep. THERAPY: Sleep disorders in MD can often be treated with behavioral therapies or drug approaches. Another and very important influence is physical activity. In combination with training, regular physical activity can lead, for instance, to improved sleep quality, endurance performance, and reduced inflammation values. The change of lifestyle with regard to activity and nutrition is another key concept in the optimal therapy of patients with MD.

Improvements in functional and cognitive status following short-term pulmonary rehabilitation in COPD lung transplant recipients: a pilot study.

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<0.001), and had small to large improvements (ES range 0.23-1.00; all p≤0.34) in 50% of the administered cognitive tests. Learning skills and memory ability presented the greatest benefits (ES composite scores 0.62 and 0.31, respectively), which remained similar after stratification by single or bilateral LTx and sex. CONCLUSIONS: PR is an effective treatment for LTx recipients in the post-transplant phase, improving lung function, exercise responses, and domains of cognitive function of learning, memory and psychomotor speed. PR may facilitate the course of post-operative treatment and should be recommended in LTx.

Analysis of Human Breath by Millimeter-Wave/Terahertz Spectroscopy.

Breath gas analysis is a promising tool for medical research and diagnosis. A particularly powerful technological approach is millimeter-wave/terahertz (mmW/THz) spectroscopy, because it is a very sensitive and highly selective technique. In addition, it offers the potential for compact and affordable sensing systems for wide use. In this work, we demonstrate the capability of a mmW/THz spectrometer for breath analysis. Samples from three volunteers and a sample from ambient air were analyzed with respect to 31 different molecular species. High-resolution absorption spectra were measured by scanning two absorption lines from each species. Out of the 31, a total of 21 species were detected. The results demonstrate the potential of mmW/THz spectroscopy for breath analysis.

Liver Fibrosis and Metabolic Alterations in Adults With alpha-1-antitrypsin Deficiency Caused by the Pi*ZZ Mutation.

BACKGROUND & AIMS: Alpha-1 antitrypsin deficiency (AATD) is among the most common genetic disorders. Severe AATD is caused by a homozygous mutation in the SERPINA1 gene that encodes the Glu342Lys substitution (called the Pi*Z mutation, Pi*ZZ genotype). Pi*ZZ carriers may develop lung and liver diseases. Mutation-associated lung disorders have been well studied, but less is known about the effects in liver. We assessed the liver disease burden and associated features in adults with this form of AATD. METHODS: We collected data from 554 Pi*ZZ adults (403 in an exploratory cohort, 151 in a confirmatory cohort), in 9 European countries, with AATD who were homozygous for the Pi*Z mutation, and 234 adults without the Pi*Z mutation (controls), all without pre-existing liver disease. We collected data on demographic parameters, comorbidities, lung- and liver-related health, and blood samples for laboratory analysis. Liver fibrosis was assessed non-invasively via the serum tests Aspartate Aminotransferase to Platelet Ratio Index and HepaScore and via transient elastography. Liver steatosis was determined via transient elastography-based controlled attenuation parameter. We performed histologic analyses of livers from transgenic mice that overexpress the AATD-associated Pi*Z variant. RESULTS: Serum levels of liver enzymes were significantly higher in Pi*ZZ carriers vs controls. Based on non-invasive tests for liver fibrosis, significant fibrosis was suspected in 20%-36% of Pi*ZZ carriers, whereas signs of advanced fibrosis were 9- to 20-fold more common in Pi*ZZ carriers compared to non-carriers. Male sex; age older than 50 years; increased levels of alanine aminotransferase, aspartate aminotransferase, or γ-glutamyl transferase; and low numbers of platelets were associated with higher liver fibrosis burden. We did not find evidence for a relationship between lung function and liver fibrosis. Controlled attenuation parameter ≥280 dB/m, suggesting severe steatosis, was detected in 39% of Pi*ZZ carriers vs 31% of controls. Carriers of Pi*ZZ had lower serum concentrations of triglyceride and low- and very-low-density lipoprotein cholesterol than controls, suggesting impaired hepatic secretion of lipid. Livers from Pi*Z-overexpressing mice had steatosis and down-regulation of genes involved in lipid secretion. CONCLUSIONS: In studies of AATD adults with the Pi*ZZ mutation, and of Pi*Z-overexpressing mice, we found evidence of liver steatosis and impaired lipid secretion. We identified factors associated with significant liver fibrosis in patients, which could facilitate hepatologic assessment and counseling of individuals who carry the Pi*ZZ mutation. ClinicalTrials.gov Number NCT02929940.

[Digital Health in Respiratory Medicine - Current Status]. / Stand der digitalen Medizin in der Pneumologie.

Everyday life is increasingly influenced by digitization. Digitization creates large, often unstructured amounts of data ("big data"), which have been used in consumer industry for years, but yet not widely in medicine. For pulmonology, digitization offers opportunities and risks in different areas like obstructive lung diseases, thoracic oncology, pulmonary rehabilitation, sleep medicine, home mechanical ventilation, and in intensive care medicine. One of the opportunities is that the use of new technologies such as telemedicine and medical apps and the analysis of this new support make it possible to better understand and manage diseases. One of the key advantages is the use of "big data" for displaying dynamic behavior ("trajectories" = movement paths), to better understand disease processes, and to optimize patient management by using analytic techniques such as machine learning. Risks to be considered are data privacy and security as well as the use of artificial intelligence. The vision is to enable precision medicine in pulmonology.

Cerebral oxygen availability during exercise in COPD patients with cognitive impairment.

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 ±â€¯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 ±â€¯2% and -5 ±â€¯3%, respectively) but preserved baseline frontal-cortex TSI levels, whilst presenting small TcPCO2 perturbations and increased cerebral total-Hb (post [Δ]≥ 2.0 ±â€¯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.

Effect of Pulmonary Rehabilitation on Inspiratory Capacity During 6-min Walk Test in Patients With COPD: A PROSPECTIVE CONTROLLED STUDY.

PURPOSE: Purpose of this study was to analyze the impact of a pulmonary rehabilitation (PR) program on the measured inspiratory capacity (IC) in patients with chronic obstructive pulmonary disease (COPD) while performing a 6-min walk test (6MWT). METHODS: Before and after PR, IC was measured by spirometry both at the beginning and at the end of the 6MWT for 15 patients with COPD in the PR group (PRG) and compared with a similar calisthenics training group (CTG; n = 15). In addition, the COPD Assessment Test (CAT), St George's Respiratory Questionnaire (SGRQ), and other lung function tests were recorded and compared. RESULTS: Both groups were not significantly different at baseline. Compared with the CTG, the PRG achieved a significant increase in the delta of IC measured during the 6MWT (0.5 ± 0.2 L [PRG] vs -0.2 + 0.2 L [CTG], P = .001). Significant differences were found for the 6MWT walking distance (PRG: 99 ± 36 m vs CTG: 5 ± 25 m, P = .001). No significant increase in dyspnea while performing the 6MWT was found in either group. The differences in the CAT score and the SGRQ Global score were significant only for the PRG in intragroup comparisons, whereas the intergroup comparison showed no significant differences. Except for residual volume, no significant changes in all parameters of the static lung function tests were observed in either group. CONCLUSION: Participation in a PR may lead to a significant and clinically relevant increase in IC and the walking distance. Additional research is necessary to define the effects of this increase in IC on exercise capacity.

Different Training-Induced Skeletal Muscle Adaptations in COPD Patients with and without Alpha-1 Antitrypsin Deficiency.

BACKGROUND: Pulmonary rehabilitation (PR) improves oxidative capacity of peripheral muscles in patients with chronic obstructive pulmonary disease (COPD). The exercise-induced oxidative skeletal muscle adaptation in COPD patients with inherited alpha-1 antitrypsin deficiency (A1ATD) has not been studied. OBJECTIVES: To compare PR effects on skeletal muscle adaptation in COPD patients with and without A1ATD. METHODS: Nine COPD patients with A1ATD (genotype PiZZ, 6 receiving A1AT augmentation therapy), and 10 'usual' COPD patients (genotype PiMM) performed an incremental cycling test and underwent musculus vastus lateralis biopsies before and after a 3-week PR program including exercise training. RESULTS: PiZZ and PiMM patients improved peak work rate following PR (+9 ± 11 W, p < 0.05, and +18 ± 9 W, p < 0.001, between-group difference p < 0.05). PiMM patients increased fibre type I (+8.1%), reduced fibre type IIA (-2.1%) and hybrid fibre type IIA/IIX proportion (-3.9%). Following PR, PiMM patients also raised mitochondrial signalling proteins PGC-1α (4.5-fold), and TFAM (6.4-fold). PiZZ patients had no change in fibre type I but showed a shift of type IIA/IIX (-8.8%) towards fibre type IIA distribution (+8.9%). The capillary to fibre ratio increased by 28% (p < 0.05) in PiZZ, whereas no change was observed in PiMM patients. Linear regression analysis revealed that diffusion capacity and A1AT therapy are predictor variables for myofibre type I response to PR (r2 = 0.684, p < 0.01). CONCLUSIONS: Following a 3-week PR with comparable training modalities, PiMM but not PiZZ patients increased the oxidative myofibre type I proportion. This skeletal muscle adaptation pattern suggests better improvement of exercise capacity in PiMM than in PiZZ patients with COPD.