BACKGROUND: Multidrug-resistant tuberculosis is a type of tuberculosis that is resistant to at least the first-line antituberculosis drugs namely, rifampicin and isoniazid. However, most of these studies were limited only to a single hospital. Therefore, this study aimed to identify the determinants of multidrug-resistant tuberculosis among adults undergoing treatment for tuberculosis in the Tigray region of Ethiopia.
METHODS: Hospital-based unmatched case-control study was conducted from 1 April 2019 to 30 June 2019. A simple random sampling method was used to select the required sample size. Variables at a p value less than 0.25 in bivariate analysis were entered into a multivariable analysis to identify the determinant factors of multidrug-resistant tuberculosis. Finally, the level of significance was declared at p<0.05.
RESULTS: Rural residence (adjusted OR (AOR) 2.54; 95% CI 1.34 to 4.83), HIV (AOR 4.5; 95% CI 1.4 to 14.2), relapse (AOR 3.86; 95% CI 1.98 to 7.5), return after lost follow-up (AOR 6.29; 95% CI 1.64 to 24.2), treatment failure (AOR 5.87; 95% CI 1.39 to 24.8) were among the determinants of multidrug-resistant tuberculosis.
CONCLUSIONS: Rural residence, HIV, relapses, return after lost follow-up and treatment failure were the identified determinant factors of multidrug-resistance tuberculosis.

OBJECTIVE: Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease associated with the functional tumour suppressor genes TSC1 and TSC2 and causes structural destruction in the lungs, which could potentially increase the risk of lung cancer. However, this relationship remains unclear because of the rarity of the disease.
METHODS: We investigated the relative risk of developing lung cancer among patients diagnosed with LAM between 2001 and 2022 at a single high-volume centre in Japan, using data from the Japanese Cancer Registry as the reference population. Next-generation sequencing (NGS) was performed in cases where tumour samples were available.
RESULTS: Among 642 patients diagnosed with LAM (sporadic LAM, n = 557; tuberous sclerosis complex-LAM, n = 80; unclassified, n = 5), 13 (2.2%) were diagnosed with lung cancer during a median follow-up period of 5.13 years. All patients were female, 61.5% were never smokers, and the median age at lung cancer diagnosis was 53 years. Eight patients developed lung cancer after LAM diagnosis. The estimated incidence of lung cancer was 301.4 cases per 100,000 person-years, and the standardized incidence ratio was 13.6 (95% confidence interval, 6.2-21.0; p = 0.0008). Actionable genetic alterations were identified in 38.5% of the patients (EGFR: 3, ALK: 1 and ERBB2: 1). No findings suggested loss of TSC gene function in the two patients analysed by NGS.
CONCLUSIONS: Our study revealed that patients diagnosed with LAM had a significantly increased risk of lung cancer. Further research is warranted to clarify the carcinogenesis of lung cancer in patients with LAM.

OBJECTIVE: A post-hoc analysis of the INCREASE trial and its open-label extension (OLE) was performed to evaluate whether inhaled treprostinil has a long-term survival benefit in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD).
METHODS: Two different models of survival were employed; the inverse probability of censoring weighting (IPCW) and the rank-preserving structural failure time (RPSFT) models both allow construction of a pseudo-placebo group, thereby allowing for long-term survival evaluation of patients with PH-ILD receiving inhaled treprostinil. Time-varying stabilised weights were calculated by fitting Cox proportional hazards models based on the baseline and time-varying prognostic factors to generate weighted Cox regression models with associated adjusted HRs.
RESULTS: In the INCREASE trial, there were 10 and 12 deaths in the inhaled treprostinil and placebo arms, respectively, during the 16-week randomised trial. During the OLE, all patients received inhaled treprostinil and there were 29 and 33 deaths in the prior inhaled treprostinil arm and prior placebo arm, respectively. With a conventional analysis, the HR for death was 0.71 (95% CI 0.46 to 1.10; p=0.1227). Both models demonstrated significant reductions in death associated with inhaled treprostinil treatment with HRs of 0.62 (95% CI 0.39 to 0.99; p=0.0483) and 0.26 (95% CI 0.07 to 0.98; p=0.0473) for the IPCW and RPSFT methods, respectively.
CONCLUSIONS: Two independent modelling techniques that have been employed in the oncology literature both suggest a long-term survival benefit associated with inhaled treprostinil treatment in patients with PH-ILD.

Progressive pulmonary fibrosis (PPF) includes any diagnosis of progressive fibrotic interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis (IPF). However, disease progression appears comparable between PPF and IPF, suggesting a similar underlying pathology relating to pulmonary fibrosis. Following positive results in a phase II study in IPF, this phase III study will investigate the efficacy and safety of BI 1015550 in patients with PPF (FIBRONEER-ILD).
In this phase III, double-blind, placebo-controlled trial, patients are being randomised 1:1:1 to receive BI 1015550 (9 mg or 18 mg) or placebo twice daily over at least 52 weeks, stratified by background nintedanib use. Patients must be diagnosed with pulmonary fibrosis other than IPF that is progressive, based on predefined criteria. Patients must have forced vital capacity (FVC) ≥45% predicted and haemoglobin-corrected diffusing capacity of the lung for carbon monoxide ≥25% predicted. Patients must be receiving nintedanib for at least 12 weeks, or not receiving nintedanib for at least 8 weeks, prior to screening. Patients on stable treatment with permitted immunosuppressives (eg, methotrexate, azathioprine) may continue their treatment throughout the trial. Patients with clinically significant airway obstruction or other pulmonary abnormalities, and those using immunosuppressives that may confound FVC results (cyclophosphamide, tocilizumab, mycophenolate, rituximab) or high-dose steroids will be excluded. The primary endpoint is absolute change from baseline in FVC (mL) at week 52. The key secondary endpoint is time to the first occurrence of any acute ILD exacerbation, hospitalisation for respiratory cause or death, over the duration of the trial.
The trial is being carried out in accordance with the ethical principles of the Declaration of Helsinki, the International Council on Harmonisation Guideline for Good Clinical Practice and other local ethics committees. The study results will be disseminated at scientific congresses and in peer-reviewed publications.
NCT05321082.

BACKGROUND: Mycobacterium avium complex (MAC) causes chronic respiratory infectious diseases with diverse clinical features and prognoses. Pleuroparenchymal fibroelastosis (PPFE) is a rare disease characterised by pleural fibrosis with subjacent intra-alveolar fibrosis and alveolar septal elastosis, with unique chest high-resolution CT (HRCT) features (radiological PPFE). An association between recurrent respiratory infections and PPFE formation has been hypothesised; however, the clinical significance of PPFE in MAC lung disease remains unclear.
METHODS: This retrospective, multicentre study investigated the prevalence of radiological PPFE in patients with MAC lung disease and its association with clinical features and outcomes. Radiological PPFE was diagnosed on the basis of HRCT findings. Prognostic factors were identified using Cox proportional hazards and Fine-Gray models.
RESULTS: Of 850 consecutive patients with definite MAC lung disease, 101 (11.9%) exhibited radiological PPFE. Patients with radiological PPFE had unique characteristics, such as lower body mass index, lower survival rate (5-year cumulative survival rate, 63.1% vs 91.7%; p<0.001) and a higher incidence of respiratory-related death (5-year cumulative incidence, 31.1% vs 3.6%; p<0.001), than those without radiological PPFE. In the multivariable analysis, the presence of radiological PPFE was independently associated with all-cause mortality (adjusted HR, 4.78; 95% CI, 2.87 to 7.95; p<0.001) and respiratory-related death (adjusted HR, 3.88; 95% CI, 2.14 to 7.01; p<0.001).
CONCLUSIONS: This large-scale study demonstrated that in patients with MAC lung disease, radiological PPFE was common, a phenotype associated with unique clinical features and poor prognosis, particularly respiratory-related death. The specific management of this subgroup should be established.

Diffuse pulmonary ossification is a specific lung condition that is accompanied by underlying diseases. However, idiopathic dendriform pulmonary ossification (IDPO) is extremely rare, and the clinical features remain unclear. In this study, we aimed to report the clinical characteristics of IDPO.
We conducted a nationwide survey of patients with IDPO from 2017 to 2019 in Japan and evaluated the clinical, radiological, and histopathological findings of patients diagnosed with IDPO.
Twenty-two cases of IDPO were identified. Most subjects (82%) were male, aged 22-56 years (mean (SD), 37.9 (9.1)) at diagnosis. Nearly 80% of the subjects were asymptomatic, and the condition was discovered during a medical check-up. However, 36% of the subjects showed a decline in forced vital capacity (%FVC) predicted <80% at diagnosis. The typical radiological features of high-resolution CT (HRCT) are calcified branching structures that are predominantly distributed in the lower lung fields without any other conspicuous finding. Histopathological analysis also showed dendriform ossified lesions from the intraluminal areas to interstitial areas. Notably, during the follow-up period of 20 years, disease progression was found in 88% on HRCT and more than 50% on pulmonary function tests (FVC and/or forced expiratory volume in 1 s). Two cases with rapid decline of 10% /year in %FVC predicted were observed.)) at diagnosis. Nearly 80% of the subjects were asymptomatic, and the condition was discovered during a medical check-up. However, 36% of the subjects showed a decline in forced vital capacity (%FVC) predicted <80% at diagnosis. The typical radiological features of high-resolution CT (HRCT) are calcified branching structures that are predominantly distributed in the lower lung fields without any other conspicuous finding. Histopathological analysis also showed dendriform ossified lesions from the intraluminal areas to interstitial areas. Notably, during the follow-up period of 20 years, disease progression was found in 88% on HRCT and more than 50% on pulmonary function tests (FVC and/or forced expiratory volume in 1 s). Two cases with rapid decline of 10% /year in %FVC predicted were observed.
IDPO develops at a young age with gradually progressive phenotype. Further research and long-term (>20 years) follow-up are required to clarify the pathogenesis and clinical findings in IDPO.

Malignant pleural mesothelioma is a rare, incurable cancer arising from previous asbestos exposure; patients have a poor prognosis, with a median survival rate of 8-14 months. Variation in mesothelioma clinical decision-making remains common with a lack of multidisciplinary knowledge sharing, leading to inconsistencies in treatment decisions. The study aimed to explore which factors impacted on clinicians\' decision-making in mesothelioma care, with a view to optimising the mesothelioma care pathway.
This mixed methods study consisted of documentary analysis of local and national guidelines, policies or documents pertaining to mesothelioma care pathways, secondary analysis of mesothelioma patient data, and interviews with clinicians attending lung cancer and/or mesothelioma-specific multidisciplinary team meetings. The study took place at three National Health Service trusts in England. Documentations relating to patients\' treatment pathways were collated and reviewed qualitatively. Records of patients with mesothelioma were extracted from hospital patient records and data collected on diagnosis date, treatment, mortality rates, survival postdiagnosis, age and clinical care team. Data were statistically analysed. Interviews with clinicians explored influences on clinical decision-making, including challenges or barriers involved. Data were thematically analysed. The Strengthening the Reporting of Observational Studies in Epidemiology reporting checklist was used.
There were differences in the structure and delivery of mesothelioma treatment and care between trusts. Four main themes were identified: \'collaboration and communication\', \'evidence base and knowledge\', \'role of the clinician\' and \'role of the patient\'. Two cross-cutting themes relating to the role of the mesothelioma nurse specialist and the impact of COVID-19 were identified.
There is a need to review the structure of mesothelioma multidisciplinary team meetings to ensure patients are reviewed by clinicians with appropriate knowledge, expertise and understanding of how, why and when decisions should be made. There is a need for expert clinicians in mesothelioma care to promote an up-to-date evidence and knowledge base within the wider multidisciplinary team.

Idiopathic pulmonary fibrosis (IPF) greatly impacts quality of life and eventually leads to premature death from respiratory failure. Inhaled treprostinil was associated with improvements in forced vital capacity (FVC) and reduced exacerbations of underlying lung disease in post hoc analyses from a phase 3 study in patients with precapillary pulmonary hypertension due to interstitial lung disease. These results, combined with preclinical evidence of treprostinil\'s antifibrotic activity, support its investigation in the treatment of IPF.
The TETON programme consists of two replicate, 52-week, randomised, double-blind placebo-controlled, phase 3 studies, each enrolling 396 subjects (NCT04708782, NCT05255991). Eligible subjects must have a diagnosis of IPF confirmed by central imaging review, along with an FVC ≥45%. Stable background use of pirfenidone or nintedanib is allowed. The primary endpoint is change in absolute FVC at week 52. Secondary endpoints include time to clinical worsening (first event of death, respiratory hospitalisation or ≥10% decline in % predicted FVC), time to first acute exacerbation of IPF, overall survival, change in % predicted FVC and change in the King\'s Brief Interstitial Lung Disease Questionnaire at week 52. Safety parameters include adverse events, hospitalisations, oxygenation and laboratory parameters. Patients who complete week 52 will be eligible to enter an open-label extension study.
Studies will be conducted in accordance with the International Conference on Harmonisation Guideline for Good Clinical Practice, Declaration of Helsinki principles, and local regulatory, ethical and legal requirements. Results will be published in a peer-reviewed publication.

Therapeutic advances have markedly increased life expectancy for those with cystic fibrosis (CF), resulting in a median predicted survival over 50 years. Consequently, people with CF (pwCF) are living through their reproductive years and the rate of pregnancy is rapidly rising. Despite the increased relevance of this topic, multicentre studies investigating the association between maternal health and choices made during pregnancy on maternal and fetal outcomes do not exist. Furthermore, there are very limited data on the outcomes following CF transmembrane conductance regulator (CFTR) modulator use during pregnancy and lactation.
Maternal and Fetal Outcomes in the Era of Modulators (MAYFLOWERS) is a prospective, multicentre observational clinical trial which will enrol approximately 285 pregnant pwCF including those who are modulator ineligible and those who choose to continue or discontinue CFTR modulator therapy during pregnancy and lactation. The primary aim of this 35-month study is to assess whether lung function changes during pregnancy differ based on the continued use of modulators or other factors such as pre-existing comorbid conditions. Secondary objectives include evaluation of pregnancy related and obstetrical complications and changes in mental health.
The design of this study required special consideration of study burden on pregnant and lactating people with chronic illness in the setting of a substantial number of unanswered questions under these conditions. MAYFLOWERS is the first prospective clinical trial examining pregnancy in CF; the outcomes will guide providers on pregnancy management in pwCF and others with chronic respiratory disease.

Inorganic antigens may contribute to paediatric sarcoidosis. Thirty-six patients matched with 36 healthy controls as well as a group of 21 sickle-cell disease (SCD) controls answered an environmental questionnaire. Patients\' indirect exposure to inorganic particles, through coresidents\' occupations, was higher than in healthy and SCD controls (median score: 2.5 (0.5-7) vs 0.5 (0-2), p=0.003 and 1 (0-2), p=0.012, respectively), especially for construction, exposures to metal dust, talc, abrasive reagents and scouring products. Wood or fossil energies heating were also linked to paediatric sarcoidosis. This study supports a link between mineral environmental exposure due to adult coresident occupations and paediatric sarcoidosis.