Background: Long-term outcome data of coronavirus disease 2019 (COVID-19) survivors are needed to understand their recovery trajectory and additional care needs.Methods: A prospective observational multicentre cohort study was carried out of adults hospitalised with COVID-19 from March through May 2020. Workup at 3 and 12 months following admission consisted of clinical review, pulmonary function testing, 6-min walk distance (6MWD), muscle strength, chest computed tomography (CT) and quality of life questionnaires. We evaluated factors correlating with recovery by linear mixed effects modelling.Results: Of 695 patients admitted, 299 and 226 returned at 3 and 12 months, respectively (median age 59 years, 69% male, 31% severe disease). About half and a third of the patients reported fatigue, dyspnoea and/or cognitive impairment at 3 and 12 months, respectively. Reduced 6MWD and quadriceps strength were present in 20% and 60% at 3 monthsversus7% and 30% at 12 months. A high anxiety score and body mass index correlated with poor functional recovery. At 3 months, diffusing capacity for carbon monoxide (D_LCO) and total lung capacity were below the lower limit of normal in 35% and 18%, decreasing to 21% and 16% at 12 months; predictors of poorD_LCOrecovery were female sex, pre-existing lung disease, smoking and disease severity. Chest CT improved over time; 10% presented non-progressive fibrotic changes at 1 year.Conclusion: Many COVID-19 survivors, especially those with severe disease, experienced limitations at 3 months. At 1 year, the majority showed improvement to almost complete recovery. To identify additional care or rehabilitation needs, we recommend a timely multidisciplinary follow-up visit following COVID-19 admission.

Telomere shortening has been associated with several lung diseases. However, telomere length is generally measured in peripheral blood leucocytes rather than in lung tissue, where disease occurs. Consequently, telomere dynamics have not been established for the normal human lung nor for diseased lung tissue. We hypothesized an age- and disease-dependent shortening of lung tissue telomeres. At time of (re-)transplantation or autopsy, 70 explant lungs were collected: from unused donors (normal, n = 13) and patients with cystic fibrosis (CF, n = 12), chronic obstructive pulmonary disease (COPD, n = 11), chronic hypersensitivity pneumonitis (cHP, n = 9), bronchiolitis obliterans syndrome (BOS) after prior transplantation (n = 11) and restrictive allograft syndrome (RAS) after prior transplantation (n = 14). Lungs were inflated, frozen and then scanned using CT. Four tissue cores from distinct lung regions were sampled for analysis. Disease severity was evaluated using CT and micro CT imaging. DNA was extracted from the samples and average relative telomere length (RTL) was determined using real-time qPCR. The normal lungs showed a decrease in RTL with age (p < 0.0001). Of the diseased lungs, only BOS and RAS showed significant RTL decrease with increasing lung age (p = 0.0220 and p = 0.0272 respectively). Furthermore, we found that RTL showed considerable variability between samples within both normal and diseased lungs. cHP, BOS and RAS lungs had significant shorter RTL in comparison with normal lungs, after adjustment for lung age, sex and BMI (p < 0.0001, p = 0.0051 and p = 0.0301 respectively). When investigating the relation between RTL and regional disease severity in CF, cHP and RAS, no association was found. These results show a progressive decline in telomere length with age in normal, BOS and RAS lungs. cHP, BOS and RAS lungs demonstrated shorter RTL compared to normal lungs. Lung tissue RTL does not associate with regional disease severity within the lung. Therefore, tissue RTL does not seem to fully reflect peripheral blood telomere length.

Many patients struggle with ongoing symptoms in different domains (physical, mental, cognitive) after hospitalisation for COVID-19, calling out for a multidisciplinary approach. An outpatient multidisciplinary rehabilitation programme, according to a respiratory rehabilitation strategy, was set up for adult patients who were able to attend group sessions during 12 weeks. Results of 22 adult patients with COVID-19, of which 15 had required intensive care, were analysed and some general impressions and challenges of rehabilitation in COVID-19 were reported. Impressive results on physical recovery were determined after 6 weeks and 3 months, with significant improvement of lung function, muscle force and exercise capacity variables. A positive evolution of mental and cognitive burden was present, although less pronounced than the physical recovery. These mental and cognitive consequences seem, next to musculoskeletal and medical complications, the most challenging aspect of rehabilitating patients with COVID-19. These real-world data show feasibility and efficiency of a multidisciplinary respiratory rehabilitation programme after moderate to severe COVID-19 disease.

The development of contractile muscle fatigue (CMF) affects training responses in patients with chronic obstructive pulmonary disease (COPD). Downhill walking induces CMF with lower dyspnoea and fatigue than level walking. This study compared the effect of pulmonary rehabilitation (PR) comprising downhill walking training (DT) to PR comprising level walking (conventional training (CT)) in patients with COPD.In this randomised controlled trial, 35 patients (62±8 years; forced expiratory volume in 1 s (FEV₁) 50±17% predicted) were randomised to DT or CT. Exercise tolerance (6-minute walk test distance (6MWD); primary outcome), muscle function, symptoms, quality-of-life and physical activity levels were assessed before and after PR. Absolute training changes and the proportion of patients exceeding the 30 m 6MWD minimally important difference (MID) were compared between groups. Quadriceps muscle biopsies were collected after PR in a subset of patients to examine physiological responses to long-term eccentric training.No between-group differences were observed in absolute 6MWD improvement (mean 6MWD change 77±46 m DTversus56±47 m CT; p=0.45), however 94% of patients in DT exceeded the 6MWD MID compared to 65% in CT (p=0.03). Patients in DT tended to have larger improvements than CT in other outcomes. Muscle biopsy analyses did not differ between groups.PR incorporating downhill walking confers similar magnitudes of effects to PR with conventional walking across clinical outcomes in patients with COPD, however, offers a more reliable stimulus to maximise the achievement of clinically relevant gains in functional exercise tolerance in people with COPD.

The role of Aspergillus fumigatus in the airways of chronic obstructive pulmonary disease (COPD) patients with bronchiectasis is currently unclear. We searched for a sensitive and noninvasive method for A. fumigatus detection in the sputum of COPD patients and addressed potential risk factors for its presence. Induced sputum samples of 18 COPD patients and 17 COPD patients with bronchiectasis were analyzed for the presence of A. fumigatus by culture, galactomannan detection, and PCR. Of the patients with COPD–bronchiectasis overlap, 23.5% had a positive culture for A. fumigatus versus 10.5% of COPD patients without bronchiectasis (p = 0.39). The median sputum galactomannan optical density index was significantly higher in patients with COPD and bronchiectasis compared with patients with COPD alone (p = 0.026) and ranged between the levels of healthy controls and A. fumigatus-colonized cystic fibrosis patients. Both the presence of bronchiectasis and the administration of systemic corticosteroids were associated with sputum galactomannan (p = 0.0028 and p = 0.0044, respectively) and showed significant interaction (p interaction = 0.022). PCR for Aspergillus was found to be a less sensitive method, but was critically dependent on the extraction technique. The higher sputum galactomannan levels suggest a more abundant presence of A. fumigatus in the airways of patients with COPD–bronchiectasis overlap compared with patients with COPD without bronchiectasis, particularly when systemic corticosteroids are administered.

Background: Bronchoscopic lung volume reduction using one-way endobronchial valves (EBVs) is a valid therapy for severe emphysema patients. However, alpha-1 antitrypsin (AAT)-deficient patients were excluded from the majority of clinical trials investigating this intervention. Objectives: The aim of this study was to investigate the feasibility, efficacy, and safety of EBV treatment in patients with AAT deficiency (AATD) or a reduced AAT level. Method: A retrospective analysis was performed of all patients treated with EBV with confirmed AATD or with a reduced AAT serum level at the University Medical Center Groningen between 2013 and 2021. Baseline and 6-month follow-up assessment included chest CT, pulmonary function measurement, 6-min walking distance (6MWD), and St. George’s Respiratory Questionnaire (SGRQ). Results: In total, 53 patients were included, 30 patients in the AATD group (AAT <0.6 g/L or confirmed ZZ phenotype) and 23 patients in the reduced AAT group (AAT 0.6–1 g/L). In both groups, all response variables improved significantly after treatment. There was a median increase in forced expiratory volume in 1 s of 105 mL (12% relative) and 280 mL (31% relative) in the AATD and reduced AAT groups, respectively. 6MWD increased by 62 min and 52 min, and SGRQ decreased by 12.5 patients and 18.7 patients, respectively. A pneumothorax occurred in 10% and 13% of patients, and no patients died. Conclusions: EBV treatment in patients with emphysema and AATD or a reduced AAT level is feasible and results in significant improvements in pulmonary function, exercise capacity, and quality of life and has an acceptable safety profile.