BACKGROUND: Antifibrotic (AF) therapy has been shown to potentially reduce the risk of lung cancer (LC) in patients with idiopathic pulmonary fibrosis (IPF). Our study further assesses the impact of AF use and LC inciden...BACKGROUND: Antifibrotic (AF) therapy has been shown to potentially reduce the risk of lung cancer (LC) in patients with idiopathic pulmonary fibrosis (IPF). Our study further assesses the impact of AF use and LC incidence in a real-world cohort with patient-level data. METHODS: A retrospective multisite cohort study involving patients with IPF followed at Mayo Clinic between 2005 and 2022 was conducted. We identified individuals with new diagnoses of LC in the pre-AF and post-AF eras and defined AF use as continuous treatment for 6 months or more before LC diagnosis. Given the inclusion of LC cases prior to the wide availability of AF therapy and potential differences in patients exposed and unexposed to treatment, propensity score analysis with inverse probability of treatment weighting (IPTW) was used to balance comparator groups. Fine and Gray modelling was used to explore risk factors for developing LC, reported as parameter subdistribution HRs (SHR). RESULTS: A total of 3313 patients with IPF were included (1161 treated and 2152 non-treated). LC incidence rates were lower for treated patients in the post-AF era (0.34 vs 1.25 per 100 person-years, p<0.001). After IPTW, 2148 treated were compared with 2167 non-treated individuals. AF treatment was independently associated with reduced LC risk (SHR 0.36 (0.16-0.82), p=0.02), while smoking history and higher forced vital capacity were associated with increased risk. CONCLUSION: AF use appears to be associated with a reduced incidence rate and risk of LC in patients with IPF.
Protein tyrosine phosphatase non-receptor type 2 () is a tyrosine phosphatase involved in T cell receptor signal transduction and cytokine response. Loss of function variants have previously been linked with immune media...Protein tyrosine phosphatase non-receptor type 2 () is a tyrosine phosphatase involved in T cell receptor signal transduction and cytokine response. Loss of function variants have previously been linked with immune mediated diseases such as inflammatory bowel disorders, rheumatoid arthritis and type 1 diabetes. We present a case of childhood interstitial lung disease with a newly identified pathogenic ) gene variant in a boy aged 4 years.
Labaki WW, Ram S, Namvar A
… +12 more, Bell AJ, Hoff BA, Kazerooni EA, Galban S, Martinez FJ, Hatt CR, Murray S, Mirkes EM, Gorban AN, Zinovyev A, Han MK, Galban CJ
BACKGROUND: Current quantitative chest CT techniques improve chronic obstructive pulmonary disease (COPD) phenotyping but do not capture spatial variability and potentially reversible disease in local lung parenchyma. ME...BACKGROUND: Current quantitative chest CT techniques improve chronic obstructive pulmonary disease (COPD) phenotyping but do not capture spatial variability and potentially reversible disease in local lung parenchyma. METHODS: Applying elastic principal graphing to CT scans from Genetic Epidemiology of COPD study participants (age 45-80 years; ≥10 pack-years), we developed elastic parametric response mapping (ePRM), a tiered scoring system (tiers 0-3 and tier Op, ie, lung opacities) that classifies lung subvolumes based on their relative composition of normal lung, emphysema, small airways disease and parenchymal disease. For 3631 participants with longitudinal data, we evaluated how relative tier assignment and mean tier position of subvolumes changed over 5 years and how they associated with forced expiratory volume in 1 s (FEV) change. We stratified analyses by baseline spirometry: no airflow obstruction, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1-2 and GOLD 3-4. RESULTS: The proportion of tier 0 subvolumes decreased with worsening airflow obstruction, while tier 2 and 3 proportions increased. Tier 1 proportions were similar in GOLD 1-2 (25.7%) and GOLD 3-4 (28.1%), with over half of subvolumes remaining in tier 1 or reverting to tier 0 at year 5. In contrast to tiers 0 and 2, baseline mean tier 1 position was strongly predictive of reassignment to more advanced tiers at year 5 in participants without airflow obstruction, GOLD 1-2 and GOLD 3-4 (area under the curves (95% CIs) 0.86 (0.85 to 0.87), 0.90 (0.89 to 0.91) and 0.92 (0.90 to 0.93), respectively). A higher per cent volume of lung retained in tier 1 was associated with less FEV decline in all groups. CONCLUSION: CT ePRM categorises local lung tissue into distinct and potentially reversible tiers of disease severity.
INTRODUCTION: Physical exercise has been used to assist smoking cessation, but supervised programmes are bounded by limited scalability and generalisability. Mobile instant messaging (MIM) offers a scalable platform for...INTRODUCTION: Physical exercise has been used to assist smoking cessation, but supervised programmes are bounded by limited scalability and generalisability. Mobile instant messaging (MIM) offers a scalable platform for delivering exercise support with minimal supervision. We assessed the effectiveness of MIM-supported brief physical exercise intervention on smoking cessation. METHODS: In this two-arm, parallel, cluster randomised controlled trial, we recruited daily smokers aged 18 years or older from 70 community sites in Hong Kong from June to October 2022. Sites were randomised (1:1) to either the intervention group (n=492) or control group (n=539). Brief cessation advice, physical exercise instructions and MIM-based practice reminders were offered to the intervention group for 3 months. The primary outcome was biochemically validated 7-day point prevalence abstinence (PPA) at 6 months. RESULTS: Of the 1031 participants (80.9% male, mean age 44.2 years), 59.8% were followed up at 6 months. Biochemically validated abstinence rates at 6 months were non-significantly higher in the intervention than the control group (10.4% vs 9.1%; risk ratio (RR) 1.14, 95% CI 0.79 to 1.66, p=0.48). Self-reported 7-day PPA was 21.9% and 19.5%, respectively (RR 1.13, 95% CI 0.89 to 1.43, p=0.32). Weekly practice of handgrip and elastic band exercises in the intervention group declined significantly over 6 months (from 10.3 min to 2.5 min and from 9.4 min to 0.8 min; p<0.001). The proportion of participants with moderate to high physical activity levels was quite similar between groups at 6 months (41.1% vs 39.9%; RR 1.05, 95% CI 0.82 to 1.35, p=0.70). CONCLUSION: MIM-supported brief physical exercise intervention did not significantly increase smoking abstinence or physical activity compared with brief cessation advice alone. TRIAL REGISTRATION NUMBER: NCT05430451.
Minatsuki S, Hatano M, Funakoshi K
… +24 more, Taniguchi Y, Adachi S, Inami T, Hosokawa K, Yamashita J, Ogino H, Tsujino I, Yaoita N, Ikeda N, Tanabe N, Shimokawahara H, Kubota K, Shigeta A, Tatsumi K, Horimoto K, Ogihara Y, Dohi Y, Hiraide T, Kawakami T, Ikemiyagi H, Tamura Y, Fukumoto Y, Abe K, CTEPH AC Registry Study Group
Reduced diffusing capacity of the lungs for carbon monoxide (DLco) reflects microvasculopathy in chronic thromboembolic pulmonary hypertension, yet its clinical value is uncertain. In a Japanese nationwide registry (2018...Reduced diffusing capacity of the lungs for carbon monoxide (DLco) reflects microvasculopathy in chronic thromboembolic pulmonary hypertension, yet its clinical value is uncertain. In a Japanese nationwide registry (2018-2023) we studied 1270 patients: 486 formed an event cohort and 299 a treatment cohort who underwent pulmonary endarterectomy or balloon pulmonary angioplasty. Lower baseline DLco was indicative of smaller postprocedural improvements in mean pulmonary artery pressure, pulmonary vascular resistance and cardiac index (all p≤0.023) and a higher risk of clinical events (HR 0.971, p=0.005). Outcomes deteriorated below 59.6%, indicating DLco may help stratify prognosis and treatment benefit.
INTRODUCTION: Integrating smoking cessation supports into lung cancer screening can improve abstinence rates. However, healthcare decision-makers need evidence of cost-effectiveness to understand the cost/benefit of adop...INTRODUCTION: Integrating smoking cessation supports into lung cancer screening can improve abstinence rates. However, healthcare decision-makers need evidence of cost-effectiveness to understand the cost/benefit of adopting this approach. METHODS: To evaluate the cost-effectiveness of smoking cessation interventions, and service delivery, we used a cohort-based Markov model, adapted from previous National Institute for Health and Care Excellence (NICE) guidelines on smoking cessation. This uses long-term epidemiological data to capture the prevalence of the smoking-related illnesses, updated through targeted literature searches as required from the core NICE model, with costs extracted from publicly recognised UK sources. RESULTS: All smoking cessation interventions appeared cost-effective at a threshold of £20 000 per quality-adjusted life year, compared with no intervention or behavioural support alone. Offering immediate smoking cessation as part of lung cancer screening appointments, compared with usual care (onward referral to stop smoking services), was also estimated to be cost-effective with a net monetary benefit of £2198 per person, and a saving of between £34 and £79 per person in reduced workplace absenteeism among working age attendees. Estimated healthcare cost savings were more than four times greater in the most deprived quintile compared with the least deprived, alongside a fivefold increase in quality adjusted life years accrued. CONCLUSIONS: Smoking cessation interventions within lung cancer screening are cost-effective and should be integrated, so that treatment is initiated during screening visits. This is likely to reduce overall costs to the health service, and wider integrated care systems, improve quality and length of life, and may lessen health inequalities.
OBJECTIVE: Anxiety affects up to one-third of adults with asthma and is linked to poorer disease outcomes and reduced quality of life. This study evaluated the efficacy of therapist-guided, internet-delivered cognitive b...OBJECTIVE: Anxiety affects up to one-third of adults with asthma and is linked to poorer disease outcomes and reduced quality of life. This study evaluated the efficacy of therapist-guided, internet-delivered cognitive behavioural therapy (ICBT) versus treatment as usual plus medical education for reducing asthma-related anxiety. METHODS: A randomised controlled trial was conducted including 90 adult participants with anxiety related to asthma. ICBT was therapist-guided and lasted 8 weeks. The primary outcome, the Catastrophising about Asthma Scale, was assessed from pretreatment to the primary endpoint at 16 weeks. Secondary outcomes included asthma control, avoidance behaviour and quality of life. Forced expiratory volume in 1 s (FEV) was collected using a digital spirometer. RESULTS: ICBT demonstrated a significantly larger reduction in catastrophising about asthma than the control group (mean difference -18.53, 95% CI -25.54 to -11.53, p<0.001). Asthma control, avoidance behaviour, quality of life and other key outcomes improved significantly more in the ICBT group compared with controls. No changes in FEV were observed. Improvements were sustained at 6 months follow-up. CONCLUSION: ICBT effectively and safely reduces catastrophising about asthma, improves asthma control, avoidance behaviour and quality of life and represents a promising adjunct to routine medical care for patients with asthma complicated by anxiety. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov (ID: NCT04230369).
BACKGROUND: The relationship of social determinants of health (SDOH), environmental exposures and medical history to lung function trajectories is underexplored. A better understanding of these relationships could inform...BACKGROUND: The relationship of social determinants of health (SDOH), environmental exposures and medical history to lung function trajectories is underexplored. A better understanding of these relationships could inform preventive strategies for lung health. METHODS: We analysed data from COPDGene, a US longitudinal, observational study. Participants were tobacco-exposed (≥10 pack-years of smoking) non-Hispanic Black and non-Hispanic White adults aged 45-80 years. We analysed 2990 males and 2945 females, using Bayesian trajectory modelling on post-bronchodilator forced expiratory volume in one second (FEV) and forced vital capacity (FVC). We applied multinomial logistic regression to assess the association of SDOH, environmental exposures and medical history with lung function trajectories. MEASUREMENTS AND MAIN RESULTS: Six trajectories were identified within each sex. Non-Hispanic Black race was more prevalent in trajectories characterised by lower FEV1 and FVC values (ie, lower lung function trajectories) compared with non-Hispanic White adults. In adjusted models, non-Hispanic Black race, residence in the Southeastern USA, lifetime asthma and a father with COPD were associated with significantly higher odds of the lowest trajectory (ie, trajectory six vs the reference trajectory) for both sexes. Higher income and private insurance showed inverse associations with lower lung function trajectories. The Social Vulnerability Index socioeconomic theme (based on census-level poverty, unemployment, income and educational attainment) was associated with the lowest trajectory in males. CONCLUSIONS: Significant disparities in lung function trajectories exist between non-Hispanic Black adults and non-Hispanic White adults. Individual- and community-level factors are associated with lower lung function trajectory in people exposed to tobacco.
BACKGROUND: Exacerbations are major causes of morbidity in individuals with chronic respiratory diseases such as chronic obstructive pulmonary disease, asthma and bronchiectasis. Increasing evidence implicates respirator...BACKGROUND: Exacerbations are major causes of morbidity in individuals with chronic respiratory diseases such as chronic obstructive pulmonary disease, asthma and bronchiectasis. Increasing evidence implicates respiratory viruses as predominant triggers, though the underlying immunopathogenic mechanisms remain poorly understood. NARRATIVE: This review synthesises current knowledge on the interplay between viral pathogens at the airway epithelial barrier, including structural and immunological mechanisms that may dysregulate antiviral immunity in chronic respiratory diseases. Furthermore, we discuss how perturbations in the respiratory microbiome, characterised by reduced microbial diversity, can modulate host antiviral immune defences. CONCLUSIONS: Collectively, these interconnected factors create a permissive environment predisposing to viral infection and exacerbations in chronic respiratory diseases. Understanding the complex interactions between airway structure, interferon-mediated antiviral responses, inflammation and microbiota is essential for developing targeted therapies to effectively manage virus-induced exacerbations and reduce disease burden.
BACKGROUND: The increasing number of patients treated by long-term non-invasive ventilation (NIV) challenges the capacity of specialised centres to perform in-hospital follow-up evaluations and requires, therefore, from...BACKGROUND: The increasing number of patients treated by long-term non-invasive ventilation (NIV) challenges the capacity of specialised centres to perform in-hospital follow-up evaluations and requires, therefore, from the clinician a thorough and critical appraisal of the information provided by ventilator software as an important component of follow-up assessment. A systematic approach of the information is required along with a knowledge of the limitations in the reliability of some parameters and the variability in modes of reporting, which may be confusing. METHODS: This review reports the summary of observations made by a multinational group of experts in this field (SomnoNIV) over several years, and the relevant items from the medical literature. RESULTS: We suggest a framework for a systematic approach of items provided by ventilator software, as well as a discussion of the different modes of reporting physiological variables according to manufacturers and pitfalls associated with some variables. An extensive iconography is included to illustrate and explicit the presentation of respiratory events occurring under NIV (impact of leaks, different patient-ventilator asynchronies, impact of inappropriate settings). CONCLUSION: The analysis of the detailed tracings provided by the ventilator, and, importantly, the knowledge that these signals are modified and processed by the ventilator software and are not raw data, is important for the understanding of patient-ventilator interaction.
Sadatsafavi M, Miravitlles M, Quint JK
… +5 more, Perugini V, Tavakoli H, Amegadzie JE, Alcazar Navarrete B, Respiratory Effectiveness Group (REG)-COPD working group
OBJECTIVES: In patients with chronic obstructive pulmonary disease (COPD), severe exacerbations (ECOPDs) impose significant morbidity and mortality. Current guidelines emphasise using ECOPD history to inform preventive t...OBJECTIVES: In patients with chronic obstructive pulmonary disease (COPD), severe exacerbations (ECOPDs) impose significant morbidity and mortality. Current guidelines emphasise using ECOPD history to inform preventive treatments but offer limited guidance for risk stratification for the first severe ECOPD. METHODS: We developed and validated PRECISE-X using a cohort of newly diagnosed COPD patients from the UK's Clinical Practice Research Datalink (2004-2022), to predict first severe ECOPD over 5 years (primary outcome) and 12 months (secondary outcome). Predictors were selected via clinical expertise and data-driven methods. Internal-external cross-validation was performed across practice regions to evaluate the model's out-of-sample performance in terms of discrimination (c-statistic), calibration and net benefit. RESULTS: The study included 2 19 015 patients (mean age 66.0; 42.4% female). Observed risk of first severe ECOPD was 29.5% at 5 years (4.2% at 1 year). The final model included four mandatory predictors (sex, age, Medical Research Council dyspnoea score and forced expiratory volume in 1 second) and 28 optional predictors. In internal-external cross-validation, the average out-of-sample c-statistic was 0.836 (95% CI 0.827 to 0.846) for 5-year prediction and 0.756 (95% CI 0.746 to 0.766) for 1-year prediction. Calibration across regions was robust, and the model showed positive NB across a wide range of risk thresholds. In a secondary validation assessment among those with available spirometry data with confirmed airflow obstruction, the model was well calibrated and had only a modest decline in discriminatory performance. CONCLUSIONS: PRECISE-X accurately predicts the first severe COPD exacerbation using routine clinical data, supporting earlier risk stratification and proactive disease management.
Expiratory airflow was measured by spirometry at ages 8 years, 18 years and 25 years in 297 survivors born extremely preterm (EP; <28 weeks' gestation) or extremely low birth weight (ELBW; <1000 g) and 260 normal birth w...Expiratory airflow was measured by spirometry at ages 8 years, 18 years and 25 years in 297 survivors born extremely preterm (EP; <28 weeks' gestation) or extremely low birth weight (ELBW; <1000 g) and 260 normal birth weight (>2499 g) controls. At 8 years, expiratory airflows were similar between males and females in both EP/ELBW and control groups. Worsening expiratory airflows with increasing age were noted in the EP/ELBW group but not controls. Specifically, males born EP/ELBW had z-scores for forced expired volume in 1 s which were lower by a mean of -0.17 SD per decade (95% CI -0.27 to -0.07), p=0.001.
BACKGROUND: In real-world chronic obstructive pulmonary disease (COPD) care, poor adherence often leads to treatment discontinuations. Discontinuing inhaled corticosteroids (ICS) can trigger withdrawal effects transientl...BACKGROUND: In real-world chronic obstructive pulmonary disease (COPD) care, poor adherence often leads to treatment discontinuations. Discontinuing inhaled corticosteroids (ICS) can trigger withdrawal effects transiently increasing exacerbation risk; but evidence for long-acting muscarinic antagonists (LAMA) withdrawal remains limited. METHODS: We performed a post hoc analysis of the 52-week, double-blind, Effect of Indacaterol Glycopyrronium versus Fluticasone Salmeterol on COPD Exacerbations trial that compared long-acting beta-2 agonist (LABA)+LAMA with LABA+ICS in 3362 patients with moderate-to-severe COPD and exacerbation history. Potential withdrawal effects after discontinuing LAMA or ICS were suggested by monthly exacerbation incidence plots during the first quarter of follow-up. Participants were stratified by their baseline use of these therapies, and outcomes were compared between the first and subsequent quarters among those who continued versus discontinued each treatment. Multivariable mixed-effects models assessed differences in exacerbation rates, with temporal variation in treatment effects interpreted as indicative of withdrawal effects. RESULTS: Discontinuing LAMA was associated with a marked, transient increase in moderate-to-severe exacerbations during the first versus subsequent quarters (p=0.001; rate ratio up to 2.2 (95% CI 1.2 to 4.1) in the subgroup least influenced by concomitant ICS use). This observation was not confirmed for severe exacerbations, likely due to low event count. In contrast, discontinuing ICS was associated with a significant early rise in severe exacerbations (p=0.023), though the difference for moderate-to-severe events did not reach statistical significance. Importantly, ICS withdrawal effects appeared consistent regardless of baseline blood eosinophil count. CONCLUSION: Our findings suggest potent LAMA and ICS treatment withdrawal effects on exacerbations, highlighting the importance of treatment adherence and accounting for withdrawal effects in clinical trials. TRIAL REGISTRATION NUMBER: NCT01782326.
INTRODUCTION: Our aim was to evaluate the diagnostic and safety performance of shape-sensing robotic-assisted bronchoscopy (ssRAB) with cone beam CT (CBCT) for the biopsy of pulmonary nodules. Additional analysis was per...INTRODUCTION: Our aim was to evaluate the diagnostic and safety performance of shape-sensing robotic-assisted bronchoscopy (ssRAB) with cone beam CT (CBCT) for the biopsy of pulmonary nodules. Additional analysis was performed to assess outcomes for small nodules and those close to the fissure, pleura or mediastinum. METHODS: This single arm, multicentre prospective study enrolled 200 subjects with suspicious pulmonary nodules. Each subject underwent a ssRAB procedure with CBCT and was subsequently followed up. The primary outcome was tool-in-lesion (TIL) confirmed with CBCT. Further endpoints included diagnostic outcomes and rate of adverse events. RESULTS: Of 200 subjects recruited, 198 subjects had a successful biopsy (whereby lesion was reached and sample was taken) and 97% completed the required follow-up. The median size of the nodules was 13 mm; 26.8% (60/224) have a positive bronchus sign and 181 (80.8%) were located in the outer two-thirds of the lung. TIL was obtained in 99.0% (198/200). The strict diagnostic yield was 85% (170/200) with diagnostic accuracy of 92.0% (184/200) and sensitivity for malignancy of 95.5% (147/154). Diagnostic accuracy for nodules under 20 mm size, within 5 mm from a critical structure (eg, heart, aorta or main pulmonary artery) or from the pleura was 88.2% (172/195), 100% (11/11) and 93.3% (56/60), respectively. There were four (2%) serious procedure-related adverse events, with one patient (0.5%) suffering a pneumothorax. CONCLUSION: ssRAB with CBCT can effectively reach and biopsy small pulmonary nodules, including perifissural, peripleural and paramediastinal lesions with a strong safety profile. TRIAL REGISTRATION NUMBER: NCT05867953.