It has been noted that there is a missing word towards the end of page nine under ‘Drain size’. The correct sentence should be: The only RCT with adequate sample size found small-bore drains not to be non-inferior to large-bore drains in terms of pleurodesis efficacy.
]]>To address the substantial baseline heterogeneity inherent to this population, the investigators employed a non-parsimonious propensity score matching strategy. Early adjunctive corticosteroid therapy was defined as initiation of >1 mg/kg/day of equivalent prednisone within 5 days of anti-PcP treatment, with...]]>
Several mechanisms underlying this variability have been proposed, related both to individual biology and to environment or behaviour (
Against this background, personalised mask design offers an attractive potential solution. Advances in three-dimensional (3D) facial scanning and additive manufacturing have made it technically feasible to produce patient-specific PAP...]]>
In their Thorax paper, Muiser et al
Current guidelines for the evaluation of chronic obstructive pulmonary disease (COPD) do not recommend screening for pulmonary hypertension (PH), despite the high prevalence and impact on outcomes. A simple screening tool to identify patients with an elevated pulmonary vascular resistance (PVR) is urgently needed, as they may benefit from PH-specific therapy and more urgent referral for lung transplantation.
We sought to examine whether a ratio of forced expiratory volume in 1 s (FEV1) to diffusing capacity (DLCO) predicts haemodynamic patterns in COPD.
Individuals with COPD who underwent right heart catheterisation from two academic medical centres were included. Adjusted multinomial models tested associations between FEV1/DLCO and haemodynamic patterns. Receiver operating curves were generated to assess the discriminative performance of the FEV1/DLCO ratio in predicting PH with an elevated PVR.
Approximately 40% of the 411 individuals included had PH with an elevated PVR. For every 0.1 increase in the FEV1/DLCO ratio, there was a 12–14% increased rate of PH with an elevated PVR compared with No PH. FEV1/DLCO ratio had moderate discriminative performance (C-statistic 0.68–0.72), which was strengthened when combined in a model with elevated tricuspid regurgitant jet velocity on echocardiography (C-statistic 0.78–0.82). Above a threshold of 1.4, FEV1/DLCO demonstrated good specificity (75%) in predicting PH with an elevated PVR.
These findings suggest that disproportionate reductions in DLCO predict PH with an elevated PVR in a COPD population. The FEV1/DLCO ratio should be considered in the evaluation of PH in COPD.
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.
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.
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.
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.
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.
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.
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.
PRECISE-X accurately predicts the first severe COPD exacerbation using routine clinical data, supporting earlier risk stratification and proactive disease management.
CFTR modulators have transformed cystic fibrosis (CF) treatment, but individual responses vary even among patients with identical CFTR genotypes. This underscores the need for predictive biomarkers to optimise therapeutic selection.
We evaluated 24 paediatric patients homozygous for F508del-CFTR, assessing lung function (FEV1pp) and sweat chloride (SC) before and after CFTR modulator therapy. Whole-gene sequencing was utilised to identify CFTR and pharmacogene variants. Patient-derived human nasal epithelial cells (HNECs) were expanded and differentiated at the air-liquid interface to assess CFTR function via ion transport (Isc).
Clinical responses varied widely. Twelve participants changed modulators during the study. Sequencing identified 231 additional CFTR variants and pharmacogene polymorphisms, but none correlated with response variability. However, a significant linear relationship emerged between Isc and FEV1pp improvement in patients with baseline FEV1pp<90 (R² = 0.652, p =0.001) and SC reduction (R² = 0.535, p=0.004). Receiver operating characteristic analysis demonstrated high predictive accuracy for SC reduction (area under the curve (AUC)=0.88) and combined FEV1pp/SC response in patients with baseline FEV1pp<90 (AUC=1.00). Exploratory analysis confirmed that Isc predicts FEV1pp changes, modulated by baseline lung function and CFTR modulator type.
Patient-derived differentiated HNEC cultures serve as a robust predictive tool for CFTR modulator response in paediatric CF patients. Their integration into clinical practice can enhance personalised treatment strategies, minimising ineffective therapy use and improving CF patient outcomes with precision medicine.
Personalised management of cystic fibrosis (CF) lung disease in the era of CF transmembrane conductance regulator (CFTR) modulator therapy will require novel approaches to assess treatment response and monitor longitudinal progression.
We evaluated the heterogeneity of short-term response to elexacaftor-tezacaftor-ivacaftor (ETI) using 129Xe MRI, multiple breath washout (MBW) and spirometry. For CFTR modulator-naïve people ≥6 years old starting commercial ETI, we measured same-day 129XeMRI ventilation defect per cent (VDP), lung clearance index (LCI), forced expiratory volume in 1 s (FEV1) and CF Questionnaire-Revised respiratory-domain (CFQ-R(R)) at pre-ETI baseline and up to 4 months post-ETI. Baseline versus follow-up measures were compared using Wilcoxon-signed-rank tests with r effect size coefficients. Abnormal follow-up measures determined using z-scores and upper/lower limits of normal; correlations evaluated using Spearman coefficients.
VDP, FEV1, LCI and CFQ-R(R) significantly improved in the total group (n=40; all p<0.001, r=0.69, r=0.79, r=0.70, r=0.77) and both ≥12-year-old subgroups (n=15 FEV1<80%, p=0.005/r=0.69, p<0.001/r=0.87, p=0.004/r=0.70, p<0.001/r=0.88; n=17 FEV1≥80%, p=0.003/r=0.54, p=0.003/r=0.74, p=0.01/r=0.56, p=0.006/r=0.73). VDP (p=0.008/r=0.89), LCI (p=0.03/r=0.83) and percent-predicted FEV1 (p=0.03/r=0.83) significantly improved in the 6–11-year-old subgroup, with VDP having the greatest effect size in children. VDP remained abnormal at follow-up in 21 participants with normal FEV1, whereas LCI was abnormal in 12. Baseline VDP (=0.39/p=0.01) and LCI (=0.43/p=0.008) were significantly correlated with the change in CFQ-R(R).
Though all outcome measures showed a positive response, response to ETI was heterogeneous between individuals and between 129XeMRI, MBW and spirometry. Leveraging the rich information provided by multimodal tools will be critical to understanding the nature of CF lung disease and measuring response to future therapies in the era of CFTR modulators.
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.
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.
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.
ssRAB with CBCT can effectively reach and biopsy small pulmonary nodules, including perifissural, peripleural and paramediastinal lesions with a strong safety profile.
The sit-to-stand (STS) test can assess physical function in people with chronic obstructive pulmonary disease (COPD); however, there are multiple versions. No study has used current guidelines to assess the measurement properties of the STS tests in people with COPD.
We conducted a systematic review using current COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines. Full text peer-reviewed publications were included if they assessed the measurement properties (validity, reliability and/or responsiveness) of at least one STS test among community-dwelling people with COPD. We searched six databases and imported results into Covidence where title/abstract screening and full text selection was completed independently and in duplicate. Extraction was conducted independently and in duplicate using the COSMIN extraction file. We assessed study risk of bias (very good, adequate, doubtful or inadequate), measurement property quality (sufficient, indeterminate or insufficient) and overall certainty of evidence (high, moderate, low or very low) using the COSMIN recommended tools.
We assessed 2577 titles/abstracts and 102 full texts for inclusion; 30 publications met eligibility. Seven unique STS tests were located with the most common being the 1 min STS test (n=14, 39%), 5-repetition STS test (n=10, 28%) and the 30 s STS test (n=8, 22%). Where assessed, reliability was sufficient for the 1 min, the 5-repetition and the 30 s STS tests. Only the 1 min STS test had high-quality evidence of sufficient construct validity, while the 30 s STS test was the sole test with at least moderate quality evidence of sufficient responsiveness.
The 1 min STS test has the most robust measurement properties for cross-sectional assessments while the 30 s STS test is more robust to assess change.
Pneumocystis jirovecii pneumonia (PcP) in HIV-negative patients is associated with high mortality rates. While early adjunctive corticosteroid (AC) therapy benefits HIV-positive patients with severe PcP, its efficacy and safety in HIV-negative patients remain poorly investigated.
This multicentre retrospective observational study included consecutive patients diagnosed with proven or probable PcP, from January 2011 to January 2021. This study assessed the prognostic impact and safety of early AC in HIV-negative patients with PcP. To address baseline characteristic imbalances between patients, a non-parsimonious propensity matching analysis was performed with a 1/1 ratio. Survival analysis, day-90 mortality rate and healthcare-associated infections (HCAI) were compared using Cox and logistic regressions.
350 consecutive HIV-negative patients with proven or probable PcP were included. Of these, 116 (33.1%) received early AC within 5 days of anti-PcP therapy initiation. The median arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) ratio was 224 (114–229). The 90-day mortality rate was 29.4% (103/350). There was no significant difference in 90-day mortality according to AC, both in overall and matched populations (OR 1.27 (0.78–2.05); p=0.336 and 0.92 (0.52–1.62); p=0.772, respectively). HCAI incidences appeared similar between groups. In the matched population, a higher proportion of AC patients required high-flow oxygen therapy (OR 2.15 (1.17–4.05); p=0.015) and mechanical ventilation duration was higher in corticosteroid recipients (OR 1.04 (1.01–1.09); p=0.048).
Early AC therapy was not associated with reduced 90-day mortality in HIV-negative PcP patients. Although recommended in hypoxemic HIV-positive PcP patients, the benefit of this strategy in HIV-negative patients remains to be proven.
Positive airway pressure (PAP) therapy is the recognised treatment for sleep disordered breathing (SDB), delivered via a tight-fitting face mask (interface). Conventional interfaces do not consider facial geometries, often resulting in poor fit and ineffective therapy. Three-dimensional (3D) printing of customised interfaces may improve comfort and outcomes.
To evaluate the clinical impact of customised versus conventional oronasal interfaces in adults with obstrcutive sleep apnoea (OSA). The primary outcome was residual Apnoea Hypopnea Index (AHI) at 6 months; secondary outcomes included interface leak, therapy concordance and patient reported symptoms.
A randomised controlled trial with 160 adults naïve to PAP therapy and diagnosed with SDB (AHI ≥15 events/hour). Randomisation was minimised by age and ethnicity. Structured light facial scans (POP2, Revopoint, China) were used to produce 3D printed moulds (Fuse 30+, Formlabs, Massachusetts, USA) for silicone injected oronasal customised interface cushions.
AHI was compared using quantile regression to account for the skewed distribution of the AHI data. Secondary outcomes were compared using logistic, quantile and linear regressions.
160 participants were recruited (intervention: 82, control: 78). Customised interfaces were associated with a 1.5 (events/hour) increase in AHI (p=0.059), higher interface leak (difference in medians 30.0 L/min, 95% CI 7.36 to 40.14, p<0.0001) and lower compliance (difference in compliance 0.78, 95% CI 0.05 to 1.54, p=0.04) at 6 months.
This trial did not demonstrate customised oronasal interfaces were superior to conventional interfaces. Future research should focus on addressing design and manufacturing limitations before any potential advantages can be evaluated.
Burr hole aspiration grew Aggregatibacter aphrophilus and he was treated with 6 weeks of intravenous antibiotics. CT performed to exclude malignancy demonstrated a 2.4 cm pulmonary arteriovenous malformation (PAVM) in the left upper lobe, unusually containing thrombus within the nidus (
This review explores the current methods employed to help mitigate problems encountered by survivors of critical illnesses and current barriers that limit their implementation. We will explore the effect of these issues on under-represented communities and the feasibility of delivering these strategies globally, as well as recent advances in mechanistic research and methodological innovation as promising areas for further work. In doing so, it summarises the potential avenues for future research with a view to advancing clinical care and outcomes in survivors of critical illness.
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