BackgroundIn the era of highly effective modulator therapies, pulmonary function, the number and severity of exacerbations and the quality of life of people with cystic fibrosis (CF) are improving significantly. The polymeric immunoglobulin receptor (pIgR)/IgA system, which is impaired in CF, protects the respiratory epithelium against harmful inhaled pathogens. The aims of this interventional prospective study were 1) to assess IgA mucosal immunity in bodily fluids from people with CF before and after elexacaftor/tezacaftor/ivacaftor (ETI) initiation, and 2) to investigate the mucosal IgA response in urine from people with CF compared with healthy controls.MethodsWe quantified by ELISA the different agents comprising the pIgR/IgA system (total IgA, IgA1, IgA2, secretory IgA (S-IgA), secretory component of pIgR, and specific IgA against Pseudomonas aeruginosa or against staphylococcal enterotoxin B in sputum, serum, and urine from 57 people with CF and 30 healthy controls.ResultsHyperactivation of the pIgR/IgA system was maintained under ETI, with no significant differences between total IgA, IgA1, IgA2, S-IgA nor secretory component levels in sputum, serum and urine from people with CF before and after ETI initiation, except for an increase in urine S-IgA after treatment. We demonstrate an activation of the mucosal immune system in the urinary tract of people with CF, with a higher level of total IgA (p=0.0141) compared with healthy controls.ConclusionEven with highly effective modulator therapy, the pIgR/IgA system remains hyperactivated after ≥3 months of treatment, suggesting that at this time the local IgA immunity is always impaired.

BackgroundAlthough the role of smoking as a risk factor for emphysema in α1-antitrypsin deficiency (AATD) is well known, never-smokers with severe AATD may also develop lung disease, ranging from mild asymptomatic disease to severe emphysema.MethodsWe performed a cross-sectional and observational study to analyse the characteristics of the population of never-smoker severe AATD (genotype) individuals of the international EARCO Registry.Results914 PI*ZZ individuals were analysed, of whom 472 (51.7%) were active or former smokers and 442 (48.3%) were never-smokers. Never-smokers were older (p<0.001), more frequently females (58.8% versus 43.9%; p<0.001) and had better forced expiratory volume in 1 s (FEV1) (81.3±26.5% versus 48.4±23% predicted; p<0.001). Lung disease was more frequent in smokers compared to never-smokers (98.5% versus 75%; p<0.001), but bronchiectasis was more frequent in never-smokers (28.6% versus 17.7%; p<0.001). A total of 319 (34.9%) patients were receiving augmentation therapy, of whom 235 (49.9%) were former smokers and 84 (19.2%) never-smokers. Among never-smokers, 320 (72.7%) were index cases, were older (61.8±11.2 versus 55.3±10.9 years; p<0.001) and had lower FEV1 (77.2±27.5% versus 92.7±19.3% predicted; p<0.001) compared to non-index cases, but there were no differences in sex distribution. Of the 84 never-smokers on augmentation, 11 (9.4%) were non-index cases.ConclusionsAmong PI*ZZ never-smokers lung disease remains prevalent, even if milder. Nonetheless, some never-smokers develop severe lung impairment requiring augmentation therapy. Non-index cases are healthier with a higher quality of life. Among never-smokers, lower body mass index, male sex, comorbidities and pulmonary exacerbations are associated with fixed airflow obstruction.

BackgroundThe incremental shuttle walk test (ISWT) may be a valuable tool for measuring exercise tolerance in patients after a hospital admission with COVID-19. However, the safety, physiological response and repeatability of the ISWT are unknown in this cohort. The present study aimed to explore the properties of this test using the Post-Hospital COVID-19 (PHOSP-COVID) study.MethodsParticipants performed two ISWTs, with a 30-min rest between tests, at 5 and 12 months post-hospital discharge for COVID-19. Heart rate and fingertip peripheral oxygen saturation were recorded pre- and post-test. Reasons for test termination were noted.Results1593 individuals (median (interquartile range) age 58 (50–66) years and body mass index 31.2 (27.6–35.8) kg·m−2; 967 (60.7%) males) performed an ISWT; two tests were performed by 1034 and 390 participants at the 5- and 12-month visit, respectively. At 5 months post-discharge, six patients (0.4%) had an adverse event and the most common reason contributing to test termination was breathlessness (826 (54.2%) participants). 336/1470 (22.9%) participants experienced exertional desaturation. Distance walked was greater in the second ISWT compared to the first ISWT at 5 and 12 months post-discharge (mean±sd difference: 5 months: 19±94 m; 12 months: 11±80 m; p<0.05), with an intraclass correlation coefficient estimate of 0.96 (95% CI 0.95–0.97) at 5 months and 0.97 (95% CI 0.96–0.97) at 12 months.ConclusionsThe ISWT appeared to be safe in this large cohort, supporting use of this field walking test for this population in clinical and research settings. A familiarisation test is recommended, with further study needed to determine the number of familiarisation tests required to achieve acceptable within-day repeatability.

BackgroundRespiratory oscillometry measures the physiological effort and mechanics of moving air in and out of the lungs during normal breathing. It provides complementary information to spirometry. Uncertainty regarding the interpretation of oscillometry is a barrier to routine use. The aim of this study was to aid in oscillometry interpretation among adults with asthma or COPD by generating expert consensus statements.MethodsA Delphi method was used to develop consensus statements regarding the clinical use of oscillometry in adults to identify abnormal lung function, bronchodilator response and minimal clinically important differences. Initial statements were refined in the brainstorming round. Statements were assessed by 60 pulmonologists over three rounds, with consensus defined as ≥70% agreement.ResultsPulmonologists agreed that oscillometry is clinically useful to assess abnormal lung function and its severity, and to measure bronchodilator response. High consensus was reached for resistance at 5 Hz (R5, 85%), reactance at 5 Hz (X5, 79%) and area under the reactance curve (AX, 77%) based on z-scores, where >1.64 was considered abnormal for R5 and AX and < −1.64 was considered abnormal for X5. For measuring bronchodilator response, good agreement was based on using percentage change for R5, X5 and AX.DiscussionThis international Delphi study combined evidence-based and expert opinion to inform clinicians in the interpretation of respiratory oscillometry. Focusing on a few key parameters of oscillometry will allow clinicians to become confident in its everyday use to assess abnormal lung function, grade severity of impairment, monitor progression over time and assess bronchodilator response.

BackgroundNeuroendocrine hyperplasia of infancy (NEHI), also called persistent tachypnoea of infancy (PTI), is one of the most prevalent forms of childhood interstitial lung disease (chILD) and one of the few with an overall favourable prognosis. Nevertheless, there is still much to be understood about the pathophysiology of NEHI and much to be done to harmonise diagnostic work-up and management.MethodsA systematic search was conducted in PubMed, Embase, Cochrane Library, Scopus and Web of Science to identify eligible studies.ResultsThe results are presented in a narrative format, providing an overview of the current understanding of NEHI epidemiology, clinical presentation, investigations and outcomes. In-depth discussions include the roles of clinical assessment, chest computed tomography scan and lung biopsy, along with prospects for new diagnostic tools. Additionally, the discussion covers the pathophysiology of NEHI, focusing on the possible roles of genetic predisposition and infectious triggers.ConclusionsThe morbidity of NEHI is particularly significant in the first months of life, underscoring the need for clinical and basic research to develop new targeted treatments. Some of these are discussed in this review. Finally, the improved diagnosis of this rare lung disease is facilitating the formation of new parent groups, which are becoming a crucial asset for progress.

BackgroundThis study investigated the effect of population ageing on the epidemiology of tuberculosis (TB) in South Korea.MethodsWe conducted a retrospective cohort study using an integrated database from three national databases. We analysed trends in age-specific TB incidence, mortality, case fatality rates and risk factors for all-cause mortality among 328 637 patients with drug-susceptible TB from 2011 to 2020.ResultsFrom 2011 to 2020, the proportion of patients aged ≥65 years increased from 30.5% to 50.7% of TB cases and from 74.3% to 86.8% of deaths. The TB incidence rate decreased from 90.3 to 39.5 per 100 000 (average annual per cent change (AAPC) −8.5%; 95% confidence interval (CI) −9.2 to −7.7). The crude mortality rate remained largely unchanged, shifting from 4.6 to 5.4 per 100 000 (AAPC 1.6%; 95% CI −0.1 to 3.1). The case fatality rate increased from 5.1% to 13.5% (AAPC 11.3%; 95% CI 10.5 to 12.1). Although incidence and mortality declined across all age groups, the rate of decline slowed with increasing age. Patients aged ≥80 years showed the slowest decline in incidence (AAPC −4.3%; 95% CI −5.4 to −3.5) and stagnation in mortality (AAPC 0.5%; 95% CI −1.4 to 2.2).ConclusionsThis study highlights the challenges of population ageing on TB control, including increasing case fatality rates and slower declines in TB incidence and mortality. These findings call for a reassessment of current strategies to address the needs of the elderly.

Shareable abstractIs autoimmune screening impactful in bronchiectasis? Not really.https://bit.ly/3HGVXY6

Shareable abstractDIPNECH is a rare entity, often associated with carcinoids. Sporadic cases of DIPNECH and adenocarcinoma have been published in literature, all showing a more favourable prognosis than adenocarcinoma alone. This large series seems to confirm this hypothesis.https://bit.ly/3G3wWWF

A case of ulcerative colitis-associated bronchiectasis relapse after lung transplantation, with new bronchiectasis and inflammatory airway infiltrates of recipient origin, confirmed by chimaerism analysis and immune repertoire studies https://bit.ly/42z1BDh.

BackgroundMonitoring lung function course in patients with pulmonary fibrosis is crucial to guide treatment decisions. Online home spirometry holds great potential for close monitoring and improving care access in times of pressured healthcare systems. However, little data is available on its large-scale use in daily practice. We evaluated the clinical applicability of online home spirometry in pulmonary fibrosis care.MethodsWe analysed data of a nationwide Dutch cohort of patients with idiopathic pulmonary fibrosis (IPF) and other forms of pulmonary fibrosis (PF) that used a home monitoring programme with home spirometry (forced vital capacity (FVC)) as part of daily practice. Changes in FVC were evaluated with a joint model. Within-patient variability was measured using coefficient of variation. Home spirometry use over time and patient experiences were assessed.ResultsOnline home spirometry data of 334 patients (IPF 73.1%) were analysed. Patients with IPF had a mean baseline FVC of 3.02 L (95% CI: 2.27–3.79), with a mean annualised decline of 170 mL (4.0%). Patients with PF had a mean baseline FVC of 2.81 L (95% CI: 2.07–3.55) with a mean annualised decline of 88 mL (1.2%). Mean±sd within-patient variability was 5.6±4.6%. Overall patient satisfaction was high, and after 1 year 63.4% still performed online home spirometry.ConclusionOnline home spirometry is feasible on a large scale in daily clinical practice to monitor disease trajectories in patients with IPF and PF. Online home spirometry could guide management decisions and improve care access for a majority of patients with pulmonary fibrosis.