Respiratory viral infections remain a major cause of hospitalization and death worldwide. Patients with respiratory infections often lose weight. While acute weight loss is speculated to be a tolerance mechanism to limit pathogen growth, severe weight loss following infection can cause quality of life deterioration. Despite the clinical relevance of respiratory infection-induced weight loss, its mechanism is not yet completely understood. We utilized a model of CD 8+ T cell-driven weight loss during respiratory syncytial virus (RSV) infection to dissect the immune regulation of post-infection weight loss. Supporting previous data, bulk RNA sequencing indicated significant enrichment of the interleukin (IL)-1 signaling pathway after RSV infection. Despite increased viral load, infection-associated weight loss was significantly reduced after IL-1 alpha (but not IL-1 beta) blockade. IL-1 alpha depletion resulted in a reversal of the gut microbiota changes observed following RSV infection. Direct nasal instillation of IL-1 alpha also caused weight loss. Of note, we detected IL-1 alpha in the brain after either infection or nasal delivery. This was associated with changes in genes controlling appetite after RSV infection and corresponding changes in signaling molecules such as leptin and growth/differentiation factor 15. Together, these findings indicate a lung-brain-gut signaling axis for IL-1 alpha in regulating weight loss after RSV infection.

Introduction The role of Xpert Ultra in bronchoalveolar lavage (BAL) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples for pulmonary and mediastinal lymph node tuberculosis (TB) remains unclear. Methods This was a retrospective observational service evaluation at a tertiary TB centre in a low-incidence setting. The diagnostic indices of Xpert Ultra, smear and culture (with cytology for EBUS-TBNA samples) were compared with culture positivity or a composite reference standard of clinical TB diagnosis. Trace readouts, a new category of results for Xpert Ultra indicating low bacillary load, were analysed in two ways as a true positive or true negative result. 282 BAL and 139 EBUS-TBNA samples were included in the analysis. Results BAL: sensitivity with 95% CI against culture-confirmed pulmonary TB from BAL samples for Xpert Ultra (trace as positive) was 0.91 (0.82 to 0.98), Xpert Ultra (trace as negative) was 0.76 (0.69 to 0.83), smear was 0.38 (p=0.0009) and culture was 1.00 (0.91 to 1.00). Specificities for all the tests were ≥0.99 (0.98 to 1.00). The addition of smear to Xpert Ultra did not improve the diagnostic accuracy. EBUS-TBNA: sensitivity against culture-confirmed TB from EBUS-TBNA samples for Xpert Ultra (trace as positive) was 0.71 (0.63 to 0.78), Xpert Ultra (trace as negative) was 0.59 (0.54 to 0.63), smear was 0.12 (p=0.002), culture was 1.00 (0.89 to 1.00), cytology was 0.87 (0.76 to 0.98) and rapid on-site evaluation of cytology (ROSE) was 0.92 (0.78 to 1.00). Specificities were 0.99 (0.97 to 1.00), 0.99 (0.97 to 1.00), 1.00 (0.98 to 1.00), 1.00 (0.98 to 1.00), 0.67 (0.67 to 0.68) and 0.42, respectively. Conclusion Xpert Ultra had a significantly higher sensitivity compared with smear in both BAL and EBUS-TBNA samples. Xpert Ultra had a lower sensitivity compared with culture but comparable specificity with results being available within <24 hours. Trace readings in our low-incidence setting were associated with culture positivity in all BAL samples.

Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause significant disease in both immunocompromised and immunocompetent individuals. The incidence of NTM pulmonary disease (NTM-PD) is rising globally. Diagnostic challenges persist and treatment efficacy is variable. This article provides an overview of NTM-PD for clinicians. We discuss how common it is, who is at risk, how it is diagnosed and the multidisciplinary approach to its clinical management.

Introduction and Objectives Fungal lung infections may complicate the clinical trajectories of individuals with nontuberculous mycobacterial pulmonary disease (NTM-PD). It remains unclear whether NTM infection or therapies predispose to fungal disease. We hypothesised that there are differences in pulmonary fungal burden in NTM-PD according to NTM species, NTM treatment use and underlying structural lung diseases. We aimed to quantify this longitudinally in people with NTM-PD. Methods Sputum samples were acquired at baseline, weekly for 4 weeks and monthly up to 3 months from 37 participants who: had NTM-PD requiring treatment; had NTM-PD not requiring treatment; or did not have NTM-PD. Additional samples were collected monthly from those on NTM treatment until 12 months; then 3-monthly until 18 months. Sputum DNA was extracted using hexadecyl-trimethyl-ammonium bromide phenol chloroform. Total fungal burden was quantified using 18S rRNA gene quantitative polymerase chain reaction. Results There was no difference in pulmonary fungal burden at baseline or 3 months between: individuals with or without NTM-PD; those with Mycobacterium avium complex pulmonary disease (MAC-PD) or Mycobacterium abscessus pulmonary disease (MAB-PD); those on or off NTM treatment; or those with bronchiectasis, cystic fibrosis or chronic obstructive pulmonary disease. Fungal burden was higher in MAB-PD than MAC-PD (P<0.05) following 6 months of NTM treatment; no difference was observed at 12 or 18 months. Among those on NTM treatment, there was no difference in the change in fungal burden that occurred between baseline and 6, 12 or 18 months according to NTM species or underlying lung disease. Conclusion No difference in pulmonary fungal burden between individuals with or without NTM-PD was found. In NTM-PD, no difference was observed in fungal burden according to underlying lung disease, NTM species (except at 6 months if on NTM treatment) or NTM therapy. NTM treatment was not associated with changes in fungal burden at 6, 12 or 18 months relative to baseline. Fungal burden alone is therefore unlikely to explain the clinical associations between NTM-PD and fungal sequelae. Using internal transcribed spacer 2 sequencing to evaluate the relationship between fungal diversity and NTM species, therapies and outcomes is therefore warranted. Please refer to page A288 for declarations of interest related to this abstract.

BACKGROUND:Non-tuberculous mycobacteria (NTM) are environmental microorganisms and opportunistic pathogens in individuals with pre-existing lung conditions such as cystic fibrosis (CF) and non-CF bronchiectasis. While recent studies of Mycobacterium abscessus have identified transmission within single CF centres as well as nationally and globally, transmission of other NTM species is less well studied. METHODS:To investigate the potential for transmission of the Mycobacterium avium complex (MAC) we sequenced 996 isolates from 354 CF and non-CF patients at the Royal Brompton Hospital (London, UK; collected 2013-2016) and analysed them in a global context. Epidemiological links were identified from patient records. Previously published genomes were used to characterise global population structures. RESULTS:We identified putative transmission clusters in three MAC species, although few epidemiological links could be identified. For M. avium, lineages were largely limited to single countries, while for Mycobacterium chimaera, global transmission clusters previously associated with heater-cooler units (HCUs) were found. However, the immediate ancestor of the lineage causing the major HCU-associated outbreak was a lineage already circulating in patients. CONCLUSIONS:CF and non-CF patients shared transmission chains, although the lack of epidemiological links suggested that most transmission is indirect and may involve environmental intermediates or asymptomatic carriage in the wider population.

Non-tuberculous mycobacteria (NTM) and Aspergillus are ubiquitous organisms that have the potential to cause significant pulmonary disease in certain clinical contexts. An association is known to exist between NTM and Aspergillus lung infections. However, it is unclear if NTM infection predisposes to Aspergillus infection or vice versa. It is also unclear whether treatment for one results in a favourable ecological niche that facilitates the growth of the other and promotes subsequent clinical disease. An improved understanding of the link between these two pulmonary pathogens is critical to guide improvements in clinical practice, and ultimately, enhance outcomes among patients who are at risk of experiencing these infections, either concomitantly or sequentially. Here, we discuss the association between pulmonary NTM and Aspergillus infections. We address the frequency with which coinfection or sequential infections are reported to occur, predisposing risk factors that have been identified and the impact on clinical outcomes. Current data on the mechanistic links between NTM and Aspergillus lung infections are also considered. The potential implications for routine clinical practice are explored.

Long-term pulmonary sequelae of Coronavirus 2019 (COVID-19) remain unclear. Thus, we aimed to establish post-COVID-19 temporal changes in chest computed tomography (CT) features of pulmonary fibrosis and to investigate associations with respiratory symptoms and physiological parameters at 3 and 12 months' follow-up. Adult patients who attended our initial COVID-19 follow-up service and developed chest CT features of interstitial lung disease, in addition to cases identified using British Society of Thoracic Imaging codes, were evaluated retrospectively. Clinical data were gathered on respiratory symptoms and physiological parameters at baseline, 3 months, and 12 months. Corresponding chest CT scans were reviewed by two thoracic radiologists. Associations between CT features and functional correlates were estimated using random effects logistic or linear regression adjusted for age, sex and body mass index. In total, 58 patients were assessed. No changes in reticular pattern, honeycombing, traction bronchiectasis/bronchiolectasis index or pulmonary distortion were observed. Subpleural curvilinear lines were associated with lower odds of breathlessness over time. Parenchymal bands were not associated with breathlessness or impaired lung function overall. Based on our results, we conclude that post-COVID-19 chest CT features of irreversible pulmonary fibrosis remain static over time; other features either resolve or remain unchanged. Subpleural curvilinear lines do not correlate with breathlessness. Parenchymal bands are not functionally significant. An awareness of the different potential functional implications of post-COVID-19 chest CT changes is important in the assessment of patients who present with multi-systemic sequelae of COVID-19 infection.

There were respiratory consultant post vacancies in 82% of surveyed UK hospitals in 2021. Understanding respiratory trainees' career intentions is vital to plan and train a future respiratory workforce. In 2020, the British Thoracic Society surveyed trainee members (n=144) to assess career plans and perceived barriers and facilitators when applying for consultant posts. Most trainees (79, 55.6%) report intending to pursue UK-based posts with general internal medicine responsibilities. Consultant applications are influenced by location, hospital type, previous local experience and availability of subspecialty posts. Insufficient guidance is available regarding consultant applications.

Nontuberculous mycobacterial pulmonary disease (NTM-PD) remains a challenging condition to diagnose and treat effectively. Treatment of NTM-PD is prolonged, frequently associated with adverse effects and has variable success. In this review, we consider the factors influencing clinicians when treating NTM-PD and discuss outcomes from key studies on the pharmacological management of Mycobacterium avium complex pulmonary disease and M. abscessus pulmonary disease. We highlight issues relating to treatment-related toxicity and provide an overview of repurposed and emerging therapies for NTM-PD.

ABSTRACT Wirelessly observed therapy (WOT) offers a novel way of monitoring treatment adherence. In this article, we provide an overview of how this technology works and discuss the evidence for its clinical effectiveness in tuberculosis, hepatitis C virus infection, mental health and cardiovascular disease. We consider the acceptability of WOT to patients as well as potential issues relating to patient autonomy and data protection. We highlight the current limited data on its economic impact and reflect on its future role in patient care.

Introduction and Objectives Nontuberculous mycobacterial pulmonary disease (NTM-PD) incidence is rising. 16S rRNA gene sequencing has demonstrated that the lung microbiome has a role in the pathogenesis of pulmonary diseases. Data on the relationship between the lung microbiome and NTM-PD are limited. We aimed to quantify the total pulmonary bacterial burden in NTM-PD patients and characterise changes in their lung microbiome over time. Methods Sputum samples were acquired longitudinally at baseline, weekly for 4 weeks and then monthly up to 3 months from 37 patients who either had NTM-PD and were starting NTM treatment; had NTM-PD but did not require treatment; or did not have NTM-PD. Sputum DNA was extracted using a hexadecyl-trimethyl-ammonium bromide phenol chloroform protocol. Total bacterial burden was quantified using 16S rRNA gene SYBR green quantitative polymerase chain reaction. 16S rRNA gene sequencing was performed on an Illumina MiSeq™ Next Generation Sequencer. Statistical analysis was performed in R version 4.1.3. Results At baseline, sputum biomass was higher in Mycobacterium avium complex (MAC) pulmonary disease (MAC-PD) patients than M. abscessus (MAB) pulmonary disease (MAB-PD) patients (P<0.05); there was no significant difference at 3 months. Alpha diversity measures (richness, Shannon index, Simpson index, Pielou's evenness index) were higher among MAC-PD than MAB-PD patients at baseline and at 3 months (P<0.05 for all measures). Beta diversity measured using the Bray-Curtis dissimilarity index significantly differed between the MAC-PD, MAB-PD and non-NTM groups at baseline (P<0.05) and at 3 months (P<0.01). Richness was lower in the MAC-PD treatment group compared to the non-treatment group at 3 months (P<0.05); there were no other differences between these groups in diversity or sputum biomass at baseline or 3 months. There was a higher mean abundance of Pseudomonas in the MAB-PD non-treatment group compared to the MAB-PD treatment group and the MAC-PD non-treatment or treatment groups across all timepoints (figure 1). Conclusion Our study demonstrates that the lung microbiome is influenced by the presence of MAC and MAB. This may impact progression and prognosis in NTM-PD. Further investigation will evaluate how lung microbiome perturbations correlate with clinical parameters and identify biomarkers of NTM pathogenicity and treatment response. Please refer to page A210 for declarations of interest related to this abstract.

Nontuberculous mycobacterial pulmonary disease (NTM-PD) continues to impose a significant clinical burden of disease on susceptible patients. The incidence of NTM-PD is rising globally, but it remains a condition that is challenging to diagnose and treat effectively. This review provides an update on the global epidemiologic features, risk factors, and diagnostic considerations associated with the management of NTM-PD.