INTRODUCTION: Lung cancer screening (LCS) with low-dose CT offers a teachable moment for smoking cessation (SC), but the optimal way to implement SC within LCS is unclear. The Yorkshire Enhanced Stop Smoking (YESS) study...INTRODUCTION: Lung cancer screening (LCS) with low-dose CT offers a teachable moment for smoking cessation (SC), but the optimal way to implement SC within LCS is unclear. The Yorkshire Enhanced Stop Smoking (YESS) study assessed the efficacy of a personalised stop-smoking intervention delivered alongside LCS. METHODS: Opt-out, co-located SC support, comprising nicotine replacement therapy/e-cigarettes/pharmacotherapy and behavioural support, was offered to all individuals who currently smoked attending for LCS. Four weeks later, participants were offered recruitment to a randomised controlled trial of continued standard best practice (SBP) versus a personalised SC support package, including a booklet containing CT images of participants' own heart and lungs, annotated where appropriate to highlight emphysema or coronary artery calcification and scripted communication delivered by a smoking cessation practitioner. RESULTS: 1003 people were recruited; 52.5% were allocated to the intervention group. Validated 7-day point prevalent (PP) abstinence rates were 33.6% and 30.0% in the intervention versus SBP groups, respectively (OR 1.17, 95% CI 0.90 to 1.54) at 3 months and 29.2% versus 28.6% (OR 1.03, 95% CI 0.78 to 1.36) at 12 months post-screening. Subgroup analyses indicated a significant increase in 7-day PP abstinence at 3 months with the intervention in women (33.9% intervention, 23.1% SBP, OR 1.70, 95% CI 1.15 to 2.53) but not in men (33.3% intervention, 37.8% SBP, OR 0.82, 95% CI 0.57 to 1.19). CONCLUSION: Around one-third of study participants were abstinent from smoking at 3 months post-screening irrespective of study arm, but adding the personalised intervention did not increase quit rates. Further research is needed exploring possible sex differences in efficacy of personalised SC support. The high overall quit rate reinforces the value of SC support delivered alongside LCS. TRIAL REGISTRATION NUMBER: ISRCRN 63825779 and NCT03750110.
BACKGROUND: About half of patients with chronic obstructive pulmonary disease (COPD) have hypertension, which significantly worsens prognosis. Yet its critical environmental drivers and vulnerable phenotypes remain uncle...BACKGROUND: About half of patients with chronic obstructive pulmonary disease (COPD) have hypertension, which significantly worsens prognosis. Yet its critical environmental drivers and vulnerable phenotypes remain unclear. OBJECTIVES: To evaluate associations between size-fractionated particulate matter (PM) and blood pressure, assess differential effects by hypertension status and identify susceptible individuals by smoking and inflammatory phenotypes. METHODS: In this prospective panel study, 82 patients with COPD (42 with hypertension) completed 281 clinical visits. Personal exposure to ambient inhalable PM (PM), fine PM (PM) and ultrafine particles (UFPs) of 0-7 days was estimated using infiltration factors and time-activity patterns. Inflammatory phenotypes were defined by blood neutrophils and eosinophils. Linear mixed-effect models were applied to evaluate blood pressure changes associated with PM. RESULTS: UFPs and PM, rather than PM, were significantly associated with increased systolic blood pressure (SBP), whereas diastolic blood pressure (DBP) and pulse pressure showed non-significant changes. The effects appeared earlier after UFP exposure (lag 03d) than PM exposure (lag 06d), with central responses exceeding brachial responses. Notably, hypertensive individuals exhibited stronger responses to UFPs and PM exposure, in whom significant elevations were observed in both SBP and DBP. Stratification by smoking status revealed no evidence of effect modification. Comparatively, individuals with an eosinophilic, instead of neutrophilic, phenotype showed heightened susceptibility to PM-related and UFP-related blood pressure increases, particularly in those with hypertension. CONCLUSIONS: Small-sized PM is an important risk factor for blood pressure elevations in patients with COPD, especially among those with hypertension and an eosinophilic inflammatory phenotype. TRIAL REGISTRATION NUMBER: NCT05076630.
BACKGROUND: Pulmonary fibrosis (PF) caused by interstitial lung diseases (ILDs) affects up to 0.1% of the global population. There is growing global interest in PF, evident from a nearly threefold increase in PF-related...BACKGROUND: Pulmonary fibrosis (PF) caused by interstitial lung diseases (ILDs) affects up to 0.1% of the global population. There is growing global interest in PF, evident from a nearly threefold increase in PF-related research publications over the last 15 years. Idiopathic PF, connective tissue disease-related ILD, sarcoidosis and hypersensitivity pneumonitis rank as the top four causes of ILD-related PF, in descending order of incidence. This article explores the variation in global incidence and prevalence, genetics, diagnostic pathways, treatment approach, care gaps and recent advances in PF management. FINDINGS: The global annual incidence of ILD-related PF has more than doubled between 1990 and 2019; conservative estimates suggest current incidence of about 15-20 cases per 100 000 population. The incidence, prevalence and spectrum of ILD-related PF vary greatly across regions based on genetics, environment, industries and diagnostic rigour. Diagnosis of PF hinges on chest imaging, lung histology and expert evaluation, which remain scarce in underserved regions. About 30-60% of patients with ILD-related PF develop progressive disease over 1-2 years. Annual PF care cost averages approximately US$30 000 in developed countries. Although significant gaps remain in PF care globally, recent progress is encouraging. Key steps to enhance PF care include ensuring universal health coverage via public systems or insurance, improving access to imaging and expert diagnostic teams, incorporating telehealth technologies, accelerating drug development and expanding the availability of pulmonary rehabilitation, palliative care and lung transplantation. Emerging techniques such as gene silencing, alveolar organoids, stem cells, lung-on-a-chip and nano-based drug delivery could transform PF care in the future. CONCLUSIONS: PF is an important global healthcare challenge, especially due to its clinical heterogeneity and geographic variation. Gaps in care need to be addressed by prioritising new drug development and ensuring wider dissemination of PF-related awareness and services.
INTRODUCTION: There is an unmet need for a validated qualitative and quantitative tool to assess environmental exposures in patients with interstitial lung disease (ILD). This study aimed to develop and validate a compre...INTRODUCTION: There is an unmet need for a validated qualitative and quantitative tool to assess environmental exposures in patients with interstitial lung disease (ILD). This study aimed to develop and validate a comprehensive tool to systematically identify exposures in patients with ILD. METHODS: A systematic literature search was completed to identify exposures associated with more than five documented hypersensitivity pneumonitis (HP) cases. These exposures were evaluated through a two-round Delphi survey involving 39 pulmonologists from India, Sri Lanka, Pakistan and Nepal. The questionnaire was prospectively derived at one centre and validated across five centres in India and Sri Lanka. The HP South Asian Questionnaire for Exposure (HP-SAQE) was validated against the gold standard multidisciplinary discussion diagnosis, distinguishing HP from non-HP ILD. RESULTS: The literature search screened 5170 records and included 407 studies, identifying 24 exposures. A 50-item Delphi survey achieved expert consensus (>70%) on 17 qualitative and 4 quantitative items (six questions) by 39 pulmonologists. HP-SAQE score ranged from 0 to 14. After pilot testing, the questionnaire was translated into Hindi, Tamil and Sinhala. In the derivation cohort (n=40), the HP-SAQE score was significantly higher in patients with HP versus non-HP (mean: 10.2±1.6 vs 6.7±4.2; p=0.001). This finding was validated in a separate cohort (n=163; mean: 9.4±2.2 vs 4.13±4.28; p<0.001). Receiver operating characteristic curve analysis showed good diagnostic performance (area under the receiver operating characteristic curve, AUC: 0.791 derivation; 0.858 validation, centre-wise AUCs 0.705-0.967). CONCLUSION: The HP-SAQE is the first qualitative and quantitative exposure assessment tool for patients with ILD that has a good diagnostic performance.
BACKGROUND: Obstructive sleep apnoea (OSA) pathogenesis during rapid-eye movement (REM) sleep has been linked to dips in ventilatory drive and downstream genioglossus hypotonia. The carbonic anhydrase inhibitor acetazola...BACKGROUND: Obstructive sleep apnoea (OSA) pathogenesis during rapid-eye movement (REM) sleep has been linked to dips in ventilatory drive and downstream genioglossus hypotonia. The carbonic anhydrase inhibitor acetazolamide is known to increase ventilatory drive and improve OSA severity. Therefore, we tested the effect of acetazolamide on REM-predominant OSA severity (apnoea hypopnoea index (AHI) and hypoxic burden, co-primary outcomes) and underlying physiological mechanisms (ventilatory drive, ventilation and pharyngeal muscle activity). METHODS: 11 participants with REM-predominant OSA per baseline polysomnography (REM AHI/non-REM AHI≥2) were allocated to receiving acetazolamide 500 mg for three nights (first night at half dose) or placebo according to a randomised, crossover, double-blind design. Detailed physiological polysomnography with recording of diaphragm and genioglossus electromyography was conducted after each intervention, with a 1-week washout in between. RESULTS: As hypothesised, acetazolamide reduced AHI by 35.5% (95% CI 23.1% to 46.3%) and hypoxic burden by 35.9% (95% CI 21.1% to 48.4%) vs placebo (p<0.001), meeting the primary endpoint. Mechanistic analysis in REM revealed that, unexpectedly, acetazolamide did not mitigate dips in ventilatory drive versus placebo (first decile (+0.1 (-1.0 to 1.3) L/min, p=0.8). Rather, acetazolamide reduced collapsibility (increased ventilation at eupneic drive: +1.4 (1.2 to 1.8) L/min) and raised muscle responsiveness (ventilation vs drive slope: +32 (25 to 41) %, p<0.001; genioglossus versus drive slope: +0.33 (0.13 to 0.54) %max/(L/min), p=0.001). CONCLUSIONS: Acetazolamide modestly improved REM OSA, with meaningful improvements in upper airway physiology, but failed to mitigate the dips in ventilatory drive responsible for REM OSA. TRIAL REGISTRATION NUMBER: NCT05589792.
INTRODUCTION: Smoked tobacco is a leading risk factor for cardiopulmonary disease. Pipe and cigar use remains common among US adults, yet its risks remain insufficiently understood. METHODS: We analysed data from five po...INTRODUCTION: Smoked tobacco is a leading risk factor for cardiopulmonary disease. Pipe and cigar use remains common among US adults, yet its risks remain insufficiently understood. METHODS: We analysed data from five pooled cohorts with adults enrolled from 1971 to 2011 with follow-up through 2018. Pipe/cigar use was defined by baseline self-report. Forced expiratory volume in 1 s (FEV), forced vital capacity (FVC) and FEV/FVC ratio were measured by spirometry. All-cause mortality, coronary heart disease mortality and hospitalisation, respiratory-related mortality, and chronic obstructive pulmonary disease (COPD) mortality and hospitalisation were classified via adjudication or validated algorithms. Associations were estimated with linear mixed models and Fine-Gray subdistribution hazards models adjusted for sociodemographic and clinical factors. RESULTS: Among 22 823 participants (mean (SD) age 48.0 (15.7) years; 44.9% male sex; 70.5% white, 25.4% black, 2.4% Hispanic/Latino), 2621 (11.5%) reported ever pipe/cigar use, including 518 (2.3%) exclusive users without cigarette history. Compared with never tobacco users (n=9931), exclusive pipe/cigar use was associated with faster decline in FEV (3.36 mL/year; 95% CI 1.99 to 4.72), FVC (3.73 mL/year; 95% CI 2.05 to 5.42) and FEV/FVC (0.031 per year; 95% CI 0.008 to 0.054). Exclusive users had higher all-cause mortality (adjusted HR (aHR) 1.24; 95% CI 1.08 to 1.41), COPD hospitalisation/mortality (aHR 2.02; 95% CI 1.41 to 2.90) and preserved ratio impaired spirometry (aHR 1.83; 95% CI 1.24 to 2.71). CONCLUSION: Pipe and cigar use was associated with accelerated lung function decline and increased mortality and cardiopulmonary events, including among never cigarette users. These findings underscore the need for prevention and cessation efforts targeting non-cigarette tobacco.