BackgroundForced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) are two of the most common measurements in spirometry, which are used for the diagnosis and monitoring of respiratory disease. Within-individual variation in measured FEV1 and FVC may affect their clinical utility but estimates of this are based on limited and often poor-quality data.MethodsA retrospective cohort study was performed. Data on FEV1 and FVC results and sociodemographic, lifestyle and comorbidity covariates were extracted from the IQVIA Medical Research Database. A minimum of four measurements in the same individual within a 6-month time period from the first measurement was the only inclusion criterion. Within-individual measured variation was calculated as a coefficient of variation (CV) using a linear regression random effects model using within-subject variance to estimate CV for the whole population and various subgroups.Results4412 participants for FEV1 and 3567 participants for FVC were included in the main study. The mean number of measurements per individual in the 6-month period was 4.8 (SD 2.3) for FEV1 and 5.1 (SD 3.5) for FVC. The overall CV for FEV1 was 22.4% (95% CI 22.1% to 22.8%) and for FVC was 15.2% (95% CI 15.0% to 15.5%). This is much higher than seen in a previous systematic review of spirometry variation. CV increased as mean patient FEV1 and FVC decreased.ConclusionsEstimated within-individual variation in this analysis of real-world data is much higher than previously reported. Variation increases with more severe disease status. This has important implications for diagnosis, monitoring and clinical decision-making.

Community-acquired pneumonia (CAP) is one of the most common causes of hospital admission and is associated with significant morbidity and mortality. National and international guidelines are available to guide the management of CAP, including antibiotic prescribing. However, these guidelines are often not adhered to and there is significant overprescribing of broad-spectrum antibiotics, contributing to the growing pandemic of antimicrobial resistance. Clinical Decision Support Software (CDSS) are electronic tools that use individual patient data to generate patient specific assessments or recommendations, that can then be acted on by the patient or clinical decision maker. This article reviews the evidence surrounding the initial management of CAP in hospital and considers the potential of CDSS to support CAP management.

Massive haemoptysis is a life-threatening complication of pulmonary mucormycosis, often resulting from invasive destruction of pulmonary arteries. Early predictors and preventive strategies remain poorly defined. We retrospectively enrolled all hospitalised patients with pulmonary mucormycosis regardless of haemoptysis between 2019 and 2024. Patients were stratified into non-massive and massive haemoptysis groups. Clinical and radiological variables were compared between groups, and univariable and multivariable logistic regression analyses were performed. Given the limited number of events and separation, Firth's penalised logistic regression and reduced multivariable models were used to identify robust predictors of massive haemoptysis. Additionally, we explored the feasibility of prophylactic pulmonary artery embolisation (PPAE) in a subset of high-risk patients to evaluate its potential role in preventing fatal haemorrhage. Fifty-seven patients with pulmonary mucormycosis were enrolled, and 22 (38.6%) patients had massive haemoptysis, with a mortality rate of 72.7% (16/22). Cavity (68.2% vs 34.3%, p=0.026) and central necrosis (100% vs 74.3%, p=0.009) were significantly more common in the massive haemoptysis group. The pulmonary artery floating sign (PAFS) was observed in 81.8% (18/22) of the massive haemoptysis group versus 31.4% (11/35) of the non-massive haemoptysis group (p<0.001), and was the only independent predictor (adjusted OR 6.20, 95% CI 1.68 to 28.49). Five high-risk patients, including three with floating sign, underwent PPAE; only one subsequently died of bleeding. The PAFS is a novel and independent predictor of massive haemoptysis in pulmonary mucormycosis. Its early identification may support early risk stratification and inform consideration of PPAE in selected high-risk patients.

BackgroundThe frequency and determinants of persistent symptoms after microbiological cure remain incompletely defined in pulmonary tuberculosis. We aimed to determine the prevalence of persistent tuberculosis-related symptoms 6 months after treatment initiation and identify associated predisposing factors.MethodsWe analysed data from the prospective observational cohort study, enrolling adults treated for pulmonary tuberculosis at three tertiary hospitals in Korea between 2016 and 2018. Demographic, clinical and radiographic data, and symptoms were assessed using a standardised symptom checklist at baseline and at 2-month and 6-month follow-up visits. Symptom persistence was defined as the presence of any tuberculosis-related symptom at the 6-month visit. Multivariable logistic regression analysis was conducted to identify factors associated with persistent symptoms.ResultsAmong 354 participants (61% men, mean age of 58.5±19.4 years), symptom prevalence decreased from 80.2% at baseline to 25.1% at 6 months. Cough (14.4 %) and dyspnoea (7.6 %) were the most common persistent symptoms. Independent predictors of persistent symptoms included foreign nationality (adjusted OR (aOR) 5.586; 95% CI 1.618 to 19.28), chronic lung disease (aOR 5.034; 95% CI 1.995 to 13.26), presence of tuberculosis-related symptoms at 2 months (aOR 3.195; 95% CI 1.833 to 5.685) and bilateral infiltration on chest X-ray (aOR 1.933; 95% CI 1.018 to 3.650) in the multivariate analysis.ConclusionsA significant proportion of patients experience persistent tuberculosis-related symptoms even 6 months after treatment initiation. These findings highlight the need for ongoing clinical assessment and post-treatment care to address residual symptom burden following pulmonary tuberculosis.

The chronic obstructive pulmonary disease (COPD)-specific comorbidity test (COTE) aims to predict long-term mortality in patients with COPD, whereas the Charlson comorbidity index (CCI) score is used as a validated tool for predicting long-term mortality across medical conditions. Comparison of the two comorbidity scores' ability to predict mortality has only been studied scarcely. This study aimed to compare the predictive ability of the COTE and CCI scores including the updated CCI score with updated weights (CCI (Quan)) in patients with COPD following acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Using nationwide registry data, all Danish patients at first admission due to AECOPD during 2005-2018 were included in this retrospective cohort study. 1-year mortality was explored including age, sex and CCI or COTE comorbidity scores. Logistic regression was performed with fivefold cross-validation comparing area under the curve (AUC) and optimal threshold using Youden index. The logistic regression models were furthermore examined using 10 000 bootstrap analyses and comparing the distribution of accuracy using a T-test. Cox regression analysis was used to compare Brier scores over time for models including combinations of age, sex, COTE, CCI and CCI (Quan). A total of 87 271 individuals were identified with a first-time AECOPD during the study period. The median age was 74 IQR (66, 81) and 48.4% were males.The logistic regression revealed an AUC of the CCI and CCI (Quan) models of 0.714 and for the COTE model 0.707 (p<0.001).Comparison using T-test on 10 000 bootstrap samples revealed small differences with an accuracy of 0.7281 (95% CI 0.7241 to 0.7320) for the COTE model and 0.7275 (95% CI 0.7235 to 7314) for the CCI model (p<0.001).Brier scores were 0.1793 for CCI, 0.1789 for CCI (Quan) and 0.1802 for COTE, only slightly favouring the CCI model. In a cohort of patients with first-time AECOPD, we found similar predictive abilities of 1-year mortality comparing the CCI, CCI (Quan) and COTE score.

ObjectiveTo analyse the clinical features of AECOPD (acute exacerbation of chronic obstructive pulmonary disease) at different altitudes and GOLD (global initiative of chronic obstructive lung disease) stages in high-altitude regions.MethodThis was a retrospective cross-sectional study. Patients diagnosed with AECOPD through pulmonary function tests and hospitalised in People’s Hospital of the Tibet Autonomous Region from September 2018 to March 2024 were included. Patients were divided into three groups according to their native residential altitude prior to onset: low-altitude group (169 cases, 2700–3700 m), mid-altitude group (77 cases, 3700–4000 m) and high-altitude group (97 cases, 4000–4800 m). Patients were also classified into three groups according to their FEV1%pred in pulmonary function test on admission: mild (91 cases, FEV1%pred ≥80%), moderate (171 cases, 50%≤FEV1%pred <80%) and severe/very severe (81 cases, FEV1%pred <50%).Result(1) Altitude comparison: the mid-altitude group showed lower values for age (66.49±8.13 years), hospital length of stay (9.79±3.20 days) and time since diagnosis (1.89±1.73 years) compared with the low-altitude group. On the other hand, the mid-altitude group showed higher SPO2 (82.35±5.17%) and pulmonary fibrosis prevalence (40.26%) than the low-altitude group. The high-altitude group had higher rates of emphysema (56.70%) and pulmonary hypertension (51.55%) compared with the low-altitude group. The high-altitude group showed lower levels of B-type natriuretic peptide (BNP) (185.76±195.19 pg/mL), red blood cell count (RBC) (5.77±0.97×1012/L), D-dimer (D-D) (1.01±1.33 mg/L) and fibrinogen degradation product (FDP) (3.11±1.38 mg/L) than the low-altitude group. The high-altitude group had a longer time since diagnosis (2.63±3.39 years) than the mid-altitude group and lower SPO2 (80.01±7.60%), rate of pulmonary fibrosis (22.68%) and BNP level (185.76±195.19 pg/mL) compared with the mid-altitude group. These differences were statistically significant (p<0.05). No significant differences were found for other variables between altitude groups (p>0.05). (2) GOLD staging comparison: the moderate group had higher values for the time since diagnosis (2.61±2.95 years), prevalence of emphysema (50.29%), pulmonary fibrosis (28.07%), pulmonary hypertension (45.61%), cor pulmonale (40.94%), and levels of C-reactive protein (CRP) (23.89±34.01 mg/L) and procalcitonin (PCT) (0.32±0.71 ng/mL) than the mild group. The moderate and severe/very severe groups had lower SPO2 (80.77±6.71%, 78.38±8.31%) than the mild group. The severe/very severe group had higher rates of emphysema (54.31%), pulmonary bullae (28.40%), pulmonary hypertension (59.26%), cor pulmonale (56.79%), and levels of CRP (20.92±29.92 mg/L) and PCT (0.81±3.43 ng/mL) than the mild group. The severe/very severe group had a shorter time since diagnosis (2.27±1.97 years) than the moderate group. The severe/very severe group also had a higher percentage of males (72.84%), pulmonary hypertension (59.26%), cor pulmonale (56.79%), and levels of BNP (392.50±728.31 pg/mL) and PCT (0.81±3.43 ng/mL) compared with the moderate group. These differences were statistically significant (p<0.05). No significant differences were found for other variables between GOLD groups (p>0.05).ConclusionIn high-altitude regions, as the altitude increases, body mass index, the proportion of male patients, rate of emphysema and pulmonary hypertension become more prominent in AECOPD patients. Higher GOLD stages are associated with longer hospital stays, higher smoking indices and greater prevalence of emphysema, pulmonary fibrosis, pulmonary hypertension and cor pulmonale. Lower SPO2 is associated with higher levels of RBC, haemoglobin, haematocrit (HCT), CRP, PCT, white blood cell count and neutrophil%. However, as native residential altitude increases, BNP, RBC, HCT, D-D and FDP decrease.

Asthma among adolescents (aged 12-<18 years) is a common condition with high disease burden. Many are undertreated, at risk of adverse outcomes and exhibit poor adherence to maintenance medication. As-needed albuterol-budesonide 180/160 µg reduced the risk of severe exacerbations by 27% compared with as-needed albuterol 180 µg in patients aged ≥12 years, with moderate-to-severe asthma receiving inhaled corticosteroid (ICS) maintenance therapy in the MANDALA trial. A small number of adolescents were included in MANDALA, but data were inconclusive. The randomised, double-blind, multicentre, phase IIIb ACADIA trial is evaluating as-needed albuterol-budesonide versus as-needed albuterol in adolescents with asthma. A planned 440 adolescents (aged 12-<18 years) with asthma using as-needed albuterol with low- to high-dose ICS-containing maintenance medications (with or without other controllers) and who had ≥1 severe exacerbation in the previous 12 months are randomised to as-needed albuterol-budesonide 180/160 µg or as-needed albuterol 180 µg for 52 weeks while continuing their own maintenance therapy. The primary endpoint is the annualised rate of severe asthma exacerbations. Secondary endpoints are the time to first severe asthma exacerbation and annualised total systemic corticosteroid exposure for asthma per participant. To minimise the number of adolescents exposed to study medications, the treatment effect will be estimated by partially extrapolating results from the patient population in the MANDALA trial using a Bayesian dynamic borrowing approach. Ethical approval was obtained from the investigators' institutional review boards. Enrolment began in May 2024. Results will be presented at respiratory congresses and published in peer-reviewed journals. NCT06307665.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition whose clinical severity may be influenced by social factors. We aimed to identify distinct COPD clinical phenotypes and assess variation by social determinants of health. In this retrospective cohort study, we identified adults aged 50-80 years with a diagnosis of COPD (n=59 797) at a tertiary academic medical centre in North-Central Florida using codes from International Classification of Diseases. Latent class analysis defined COPD clinical phenotypes using indicators of clinical severity, including frequency of acute care encounters (urgent care, emergency department visits and hospitalisations), presence of COPD as the principal diagnosis, comorbidity burden and use of Global Initiative for Chronic Obstructive Lung Disease Group D medications. Kaplan-Meier survival curves and Cox proportional hazards models assessed mortality across phenotypes. Multinomial logistic regression models estimated associations between phenotype membership and race/ethnicity, income, rurality and smoking status, using the minimal phenotype as reference. Five clinical phenotypes were identified: minimal (20.9%), mild (35.2%), moderate (22.5%), severe (12.2%) and very severe (9.3%). The very severe phenotype had the highest mortality (adjusted HR 2.94; 95% CI 2.72 to 3.18). Odds of very severe COPD were higher among non-Hispanic Black (adjusted OR (aOR) 1.29; 95% CI 1.21 to 1.36) and Hispanic individuals (aOR 1.75; 95% CI 1.63 to 1.87), those in the lowest income communities (aOR 1.25; 95% CI 1.18 to 1.32), rural residents (aOR 1.80; 95% CI 1.68 to 1.92) and individuals who currently smoke (aOR 1.30; 95% CI 1.20 to 1.42). Most patients with COPD had mild disease; however, the very severe phenotype, which was associated with higher mortality, was more common among Black and Hispanic individuals, those residing in lower-income and rural areas and those who currently smoke. These clinical phenotypes highlight sociodemographic differences in COPD severity as reflected in healthcare utilisation and outcomes.

Preventable morbidity and mortality from chronic obstructive pulmonary disease (COPD) accrue from major adverse cardiovascular events (MACEs) and acute exacerbations of COPD (AECOPD). The study aims to summarise models for the prediction of these cardiopulmonary events in community-based settings. We searched for studies of multivariable models derived, validated or augmented for the prediction of cardiopulmonary events in COPD and used community-based data sources using MEDLINE and Embase from inception through 10 April 2025. Discrimination measures for the model with C-statistic data from ≥3 cohorts were pooled by Bayesian meta-analysis, and heterogeneity and risk of bias assessments were undertaken. No models were identified that predicted cardiopulmonary events in COPD using community-based data. Of the 71 models included, 5 predicted cardiovascular events, 32 predicted AECOPD and 30 predicted all-cause mortality. None were eligible for meta-analysis for the prediction of cardiovascular events or AECOPD. For all-cause mortality, age, dyspnoea and airflow obstruction-surprise question (ADO-SQ) (0.763, 95% CI 0.533 to 0.942) and body mass index, airflow obstruction, dyspnoea score and exercise capacity (BODE) (0.753, 95% CI 0.583 to 0.907) demonstrated good prediction performance, while ADO (0.638, 95% CI 0.443 to 0.827) demonstrated adequate prediction performance. The risk of bias was high for 57.9% of studies, and none had clinical utility evaluated. Despite the high burden of MACE and AECOPD, there is an absence of community-based models that predict this composite outcome. Models to identify individuals with COPD at high risk of cardiopulmonary events could enable targeted clinical intervention. CRD420251026275.

BackgroundThe metabolic score of visceral fat (METS-VF) is linked to chronic obstructive pulmonary disease (COPD) incidence, while its association with mortality and adverse outcomes in patients with COPD remains unclear.Materials and methodsWe analysed 7246 participants with COPD from the UK Biobank and 869 from US National Health and Nutrition Examination Survey (US NHANES) (1999–2018). METS-VF was categorised into quartiles. In UK Biobank, outcomes included all-cause, cardiovascular disease (CVD), COPD-specific mortality, pulmonary heart disease (PHD), pulmonary embolism (PE) and heart failure (HF); in NHANES, only all-cause and CVD mortality were evaluated. UK Biobank analyses used Cox models, restricted cubic splines, Kaplan-Meier curves, time-dependent receiver operating characteristic (ROC) curves and mediation analysis (C reactive protein (CRP), white blood cell count (WBC), platelet count (PLT)). NHANES served as an external validation cohort using survey-weighted Cox models, subgroup and sensitivity analyses and time-dependent ROC for the two mortality outcomes.ResultsIn UK Biobank, restricted cubic splines identified non-linear associations of METS-VF with all-cause and CVD mortality, with a common inflection point at 7.03, and linear associations with secondary outcomes. Compared with the lowest quartile, the highest METS-VF quartile showed significantly higher risks of all-cause mortality (HR 1.467), CVD mortality (HR 3.000), COPD-specific mortality (HR 1.952), PHD (HR 3.505), PE (HR 2.301) and HF (HR 2.567). Similar positive associations were observed in NHANES, where the highest METS-VF quartile remained significantly associated with all-cause mortality (HR 3.337) and CVD mortality (HR 3.011). Time-dependent ROC analyses demonstrated modest but stable discrimination across follow-up in both cohorts. Mediation analyses showed that CRP and WBC partially mediated the associations of METS-VF with mortality and cardiopulmonary outcomes, whereas PLT did not exhibit significant mediation effects.ConclusionsElevated METS-VF is consistently associated with increased long-term risks of mortality and cardiopulmonary complications in COPD across independent discovery and validation cohorts. METS-VF may serve as a practical prognostic biomarker for risk stratification in the clinical management of COPD.