Anosmia, the loss of smell, is a common and often the sole symptom of COVID-19. The onset of the sequence of pathobiological events leading to olfactory dysfunction remains obscure. Here, we have developed a postmortem bedside surgical procedure to harvest endoscopically samples of respiratory and olfactory mucosae and whole olfactory bulbs. Our cohort of 85 cases included COVID-19 patients who died a few days after infection with SARS-CoV-2, enabling us to catch the virus while it was still replicating. We found that sustentacular cells are the major target cell type in the olfactory mucosa. We failed to find evidence for infection of olfactory sensory neurons, and the parenchyma of the olfactory bulb is spared as well. Thus, SARS-CoV-2 does not appear to be a neurotropic virus. We postulate that transient insufficient support from sustentacular cells triggers transient olfactory dysfunction in COVID-19. Olfactory sensory neurons would become affected without getting infected.

Background: Bronchiectasis is a common lung condition associated with wide range of infectious, immunological, autoimmune, allergic and genetic conditions. Exacerbations and daily symptoms have the largest impact on patients and healthcare systems, and they are the key focus of treatments. Current practice is heterogeneous globally, and bronchiectasis has historically been a neglected disease. Here, we present evidence-based international guidelines for the management of adults with bronchiectasis. Methods: A European Respiratory Society (ERS) Task Force, comprising global experts, a methodologist and patient representatives, developed clinical practice guidelines in accordance with ERS methodology and the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach. Systematic literature searches, data extraction and meta-analysis were performed to generate evidence tables, and recommendations were formulated using the evidence-to-decision framework. A total of eight PICO (Patients, Intervention, Comparator, Outcomes) questions and three narrative questions were developed. Recommendations: The Task Force recommendations include strong recommendations in favour of airway clearance techniques for most patients with bronchiectasis, and pulmonary rehabilitation for those with impaired exercise capacity. We issue a strong recommendation for the use of long-term macrolide treatment for patients at high risk of exacerbations and a strong recommendation in favour of long-term inhaled antibiotics in patients with chronic Pseudomonas aeruginosa infection at high risk of exacerbation. Conditional recommendations support the use of eradication treatment or mucoactive drugs in specific circumstances. We suggest not to routinely use long-term oral, non-macrolide antibiotic treatment or inhaled corticosteroids. Additional guidance is also provided on testing for underlying causes, managing exacerbations and managing the deteriorating patient. Conclusion: The ERS bronchiectasis guidelines provide an evidence-based framework for optimal management of adults with bronchiectasis and serve as a benchmark for evaluating the quality of care.

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.

Background: Primary ciliary dyskinesia (PCD) represents a group of rare hereditary disorders characterised by deficient ciliary airway clearance that can be associated with laterality defects. We aimed to describe the underlying gene defects, geographical differences in genotypes and their relationship to diagnostic findings and clinical phenotypes.Methods: Genetic variants and clinical findings (age, sex, body mass index, laterality defects, forced expiratory volume in 1 s (FEV₁)) were collected from 19 countries using the European Reference Network's ERN-LUNG international PCD Registry. Genetic data were evaluated according to American College of Medical Genetics and Genomics guidelines. We assessed regional distribution of implicated genes and genetic variants as well as genotype correlations with laterality defects and FEV₁.Results: The study included 1236 individuals carrying 908 distinct pathogenic DNA variants in 46 PCD genes. We found considerable variation in the distribution of PCD genotypes across countries due to the presence of distinct founder variants. The prevalence of PCD genotypes associated with pathognomonic ultrastructural defects (mean 72%, range 47–100%) and laterality defects (mean 42%, range 28–69%) varied widely among countries. The prevalence of laterality defects was significantly lower in PCD individuals without pathognomonic ciliary ultrastructure defects (18%). The PCD cohort had a reduced median FEV₁z-score (−1.66). Median FEV₁z-scores were significantly lower inCCNO(−3.26),CCDC39(−2.49) andCCDC40(−2.96) variant groups, while the FEV₁z-score reductions were significantly milder inDNAH11(−0.83) andODAD1(−0.85) variant groups compared to the whole PCD cohort.Conclusion: This unprecedented multinational dataset of DNA variants and information on their distribution across countries facilitates interpretation of the genetic epidemiology of PCD and indicates that the genetic variant can predict diagnostic and phenotypic features such as the course of lung function.

Background: International guidelines recommend airway clearance management as one of the important pillars of bronchiectasis treatment. However, the extent to which airway clearance is used for people with bronchiectasis in Europe is unclear. The aim of the study was to identify the use of airway clearance management in patients with bronchiectasis across different countries and factors influencing airway clearance use.Methods: This was a prospective observational study using data from the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) Registry between January 2015 and April 2022. Prespecified options for airway clearance management were recorded, including airway clearance techniques, devices and use of mucoactive drugs.Results: 16 723 people with bronchiectasis from 28 countries were included in the study. The mean age was 67 years (interquartile range 57–74 years, range 18–100 years) and 61% were female. 72% of the participants reported daily sputum expectoration and 52% (95% CI 51–53%) of all participants reported using regular airway clearance management. Active cycle of breathing technique was used by 28% of the participants and airway clearance devices by 16% of participants. The frequency of airway clearance management and techniques used varied significantly between different countries. Participants who used airway clearance management had greater disease severity and worse symptoms, including a higher daily sputum volume, compared to those who did not use it regularly. Mucoactive drugs were also more likely to be used in participants with more severe disease. Access to specialist respiratory physiotherapy was low throughout Europe, but particularly low in Eastern Europe.Conclusions: Only a half of people with bronchiectasis in Europe use airway clearance management. Use of and access to devices, mucoactive drugs and specialist chest physiotherapy appears to be limited in many European countries.