BMJ Open Respiratory Research最新文献

Background and objective: Expression of programmed death-ligand 1 (PD-L1) in tumour cells (TCs) is predictive of immunotherapy efficacy in non-small cell lung cancer (NSCLC). Small biopsy samples collected by bronchoscopy are often used to diagnose peripheral lung cancer. It is questionable whether these small samples from radial endobronchial ultrasonography (r-EBUS) procedures are representative of PD-L1 expression in TCs.

Methods: We retrieved data of consecutive patients who had surgery for NSCLC and previous r-EBUS biopsy sampling, from 2017 to 2019 in our centre. PD-L1 expression in tumour cells was categorised as <1%, 1%-49% and ≥50%. PD-L1 expression was compared between r-EBUS samples and surgical specimens.

Results: Among 1026 patients who had r-EBUS, 521 had a diagnosis of lung cancer on r-EBUS sample. PD-L1 testing was indicated in 356 cases and results were considered contributive in 325 cases (91%). 82 patients with PD-L1 expression in r-EBUS samples had subsequent surgical resection of the nodule and were included in the study. PD-L1 expression was identical between r-EBUS samples and surgical specimens in 67% of cases, with kappa 0.44 (p<0.001). 82% of patients with PD-L1≥50% in surgical specimens were identified in r-EBUS samples. Nonetheless, 31% of patients with no PD-L1 expression in r-EBUS samples had some expression in surgical specimens.

Conclusion: Small samples obtained by r-EBUS are adequate for assessment of PD-L1 expression in tumour cells, with moderate concordance compared to surgical specimens. Reassessment of PD-L1 expression in larger samples may be useful to guide therapy in patients with no PD-L1 expression in r-EBUS samples.

Objectives: This study aimed to evaluate pulmonary diffusing capacity for nitric oxide (DLNO) and pulmonary diffusing capacity for carbon monoxide (DLCO) in Mexican Hispanics born and raised at 2240 m altitude (midlanders) compared with those born and raised at sea level (lowlanders). It also aimed to assess the effectiveness of race-specific reference equations for pulmonary diffusing capacity (white people vs Mexican Hispanics) in minimising root mean square errors (RMSE) compared with race-neutral equations.

Methods: DLNO, DLCO, alveolar volume (VA) and gas transfer coefficients (KNO and KCO) were measured in 392 Mexican Hispanics (5 to 78 years) and compared with 1056 white subjects (5 to 95 years). Reference equations were developed using segmented linear regression (DLNO, DLCO and VA) and multiple linear regression (KNO and KCO) and validated with Least Absolute Shrinkage and Selection Operator. RMSE comparisons between race-specific and race-neutral models were conducted using repeated k-fold cross-validation and random forests.

Results: Midlanders exhibited higher DLCO (mean difference: +4 mL/min/mm Hg), DLNO (mean difference: +7 mL/min/mm Hg) and VA (mean difference: +0.17 L) compared with lowlanders. The Bayesian information criterion favoured race-specific models and excluding race as a covariate increased RMSE by 61% (DLNO), 18% (DLCO) and 4% (KNO). RMSE values for VA and KCO were comparable between race-specific and race-neutral models. For DLCO and DLNO, race-neutral equations resulted in 3% to 6% false positive rates (FPRs) in Mexican Hispanics and 20% to 49% false negative rates (FNRs) in white subjects compared with race-specific equations.

Conclusions: Mexican Hispanics born and raised at 2240 m exhibit higher DLCO and DLNO compared with lowlanders. Including race as a covariate in reference equations lowers the RMSE for DLNO, DLCO and KNO and reduces FPR and FNR compared with race-neutral models. This study highlights the need for altitude-specific and race-specific reference equations to improve pulmonary function assessments across diverse populations.

Introduction: Treatment options for chronic obstructive pulmonary disease (COPD) are numerous but adherence remains a key challenge. We performed a discrete choice experiment (DCE) of patients' preferences in accessing care for the management of COPD. The aim of this study was to understand patients' preferences for modes of accessing care for the management of COPD. This piece of work was then used to inform resource allocation decisions in five integrated care systems (ICSs) in England.

Methods: People with diagnosed COPD in five ICSs were invited to complete an online survey from August to September 2022. An experimental design built on the principles of minimal overlap, level balance and orthogonality was used to create 20 sets of 11 scenarios for participants to assess. Participants were presented with three hypothetical options and asked to select their most preferred or state that none was preferred. Data were analysed using a hierarchal Bayes algorithm.

Results: Of 82 639 patients with COPD in the study area, 520 completed the survey. The mean health-related quality of life score derived using EuroQol 5-Dimensions 5-Level was 0.57 (0.29). The attributes assigned greatest importance were treatment outcomes, treatment delivery and the type of staff who deliver treatment. Mean utility level scores were substantially higher for little relief (22.75 (SD 78.80)) or some relief from symptoms (20.67 (46.77)) than for complete relief (‒43.42 (83.03)). Of the treatment delivery options, in-person individual appointments were preferred (mean utility score 48.34 (SD 48.14)), and care being provided by healthcare professionals was viewed as very important (77.50 (64.39)).

Conclusions: The DCE approach can help resource allocation decisions by indicating attributes most important to patients and trade-offs they are willing to make in treatment access and delivery.

Backgrounds: The management of lung complications, especially fibrosis, after COVID-19 pneumonia, is an important issue in the COVID-19 post-pandemic era. We aimed to investigate risk factors for pulmonary fibrosis development in patients with severe COVID-19 pneumonia.

Methods: Clinical and radiological data were prospectively collected from 64 patients who required mechanical ventilation due to COVID-19 pneumonia and were enrolled from eight hospitals in South Korea. Fibrotic changes on chest CT were evaluated by visual assessment, and extent of fibrosis (mixed disease score) was measured using automatic quantification system.

Results: 64 patients were enrolled, and their mean age was 58.2 years (64.1% were males). On chest CT (median interval: 60 days [IQR; 41-78 days] from enrolment), 35 (54.7%) patients showed ≥3 fibrotic lesions. The most frequent fibrotic change was traction bronchiectasis (47 patients, 73.4 %). Median extent of fibrosis measured by automatic quantification was 10.6% (IQR, 3.8-40.7%). In a multivariable Cox proportional hazard model, which included nine variables with a p value of <0.10 in an unadjusted analysis as well as age, sex and Body Mass Index, male sex (HR, 3.01; 95% CI, 1.27 to 7.11) and higher initial Sequential Organ Failure Assessment (SOFA) score (HR, 1.18; 95% CI, 1.02 to 1.37) were independently associated with pulmonary fibrosis (≥3 fibrotic lesions).

Conclusion: Our data suggests that male gender and higher SOFA score at intensive care unit admission were associated with pulmonary fibrosis in patients with severe COVID-19 pneumonia requiring mechanical ventilation.

Rationale: In chronic obstructive pulmonary disease (COPD), accurately estimating lung function from electronic health record (EHR) data would be beneficial but requires addressing complexities in clinically obtained testing. This study compared analytic methods for estimating rate of forced expiratory volume in one second (FEV₁) change from EHR data.

Methods: We estimated rate of FEV₁ change in patients with COPD from a single centre who had ≥3 outpatient tests spanning at least 1 year. Estimates were calculated as both an absolute mL/year and a relative %/year using non-regressive (Total Change, Average Change) and regressive (Quantile, RANSAC, Huber) methods. We compared distributions of the estimates across methods focusing on extreme values. Univariate zero-inflated negative binomial regressions tested associations between estimates and all-cause or COPD hospitalisations. Results were validated in an external cohort.

Results: Among 1417 participants, median rate of change was approximately -30 mL/year or -2%/year. Non-regressive methods frequently generated erroneous estimates due to outlier first measurements or short intervals between tests. Average change yielded the most extreme estimates (minimum=-3761 mL/year), while regressive methods, and Huber specifically, minimised extreme estimates. Huber, Total Change and Quantile FEV₁ slope estimates were associated with all-cause hospitalisations (Huber incidence rate ratio 0.98, 95% CI 0.97 to 0.99, p<0.001). Huber estimates were also associated with smoking status, comorbidities and prior hospitalisations. Similar results were identified in an external validation cohort.

Conclusions: Using EHR data to estimate FEV₁ rate of change is clinically applicable but sensitive to challenges intrinsic to clinically obtained data. While no analytic method will fully overcome these complexities, we identified Huber regression as useful in defining an individual's lung function change using EHR data.

Background: An association between driving pressure (∆P) and the outcomes of invasive mechanical ventilation (IMV) may exist. However, the effect of a sustained limitation of ∆P on mortality in patients with acute respiratory distress syndrome (ARDS), including patients with COVID-19 (COVID-19-related acute respiratory distress syndrome (C-ARDS)) undergoing IMV, has not been rigorously evaluated. The use of emulations of a target trial in intensive care unit research remains in its infancy. To inform future, large ARDS target trials, we explored using a target trial emulation approach to analyse data from a cohort of IMV adults with C-ARDS to determine whether maintaining daily ∆p<15 cm H₂O (in addition to traditional low tidal volume ventilation (LTVV) (tidal volume 5-7 cc/PBW+plateau pressure (P_plat) ≤30 cm H₂O), compared with LTVV alone, affects the 28-day mortality.

Methods: To emulate a target trial, adults with C-ARDS requiring >24 hours of IMV were considered to be assigned to limited ∆P or LTVV. Lung mechanics were measured twice daily after ventilator setting adjustments were made. To evaluate the effect of each lung-protective ventilation (LPV) strategy on the 28-day mortality, we fit a stabilised inverse probability weighted marginal structural model that adjusted for baseline and time-varying confounders known to affect protection strategy use/adherence or survival.

Results: Among the 92 patients included, 27 (29.3%) followed limited ∆P ventilation, 23 (25.0%) the LTVV strategy and 42 (45.7%) received no LPV strategy. The adjusted estimated 28-day survival was 47.0% (95% CI 23%, 76%) in the limited ∆P group, 70.3% in the LTVV group (95% CI 37.6%, 100%) and 37.6% (95% CI 20.8%, 58.0%) in the no LPV strategy group.

Interpretation: Limiting ∆P may not provide additional survival benefits for patients with C-ARDS over LTVV. Our results help inform the development of future target trial emulations focused on evaluating LPV strategies, including reduced ∆P, in adults with ARDS.

Introduction: Work-related asthma accounts for ≥25% of asthma in working-age populations, though the relationship between work exposures and symptoms is frequently missed, leading to poor health and employment outcomes. We hypothesised that inhalable exposures at work are associated with poor asthma control in severe asthma (SA).

Methods: We searched the Birmingham (UK) Regional NHS SA Service clinical database (n=1453 records; 1 March 2004 to 1 March 2021) and undertook a cross-sectional study using baseline data collected at diagnosis. We included all employed patients aged 16-64 with documented current occupation (n=504), and collected socio-demographic, general health and asthma-specific data, including Asthma Control Questionnaire 7 (ACQ7) score. The Occupational Asthma Specific Job-Exposure Matrix (OAsJEM) was employed to determine the likelihood of exposure to respiratory sensitisers, irritants, cleaning agents and detergents; associations between exposures and ACQ7 were investigated using binary and multinomial regression.

Results: Frequently reported occupations were care assistants (7%) and nurses (6%); 197/504 (39%) patients were exposed to an asthmagen, including respiratory sensitisers (30%), airway irritants (38%) and cleaning products/disinfectants (29%). ACQ7 score was available for 372/504 (74%) patients, of whom 14% had adequate control (ACQ7=0-1.5). After adjustment for major confounders there were no significant associations between inhaled asthmagens and ACQ7 score (either as binary or multinomial outcomes).

Conclusion: JEM-determined workplace exposures to inhaled asthmagens are not associated with asthma control in SA; 29-39% of patients may have current exposure to workplace asthmagens. Routine collection of lifetime occupational data including current job role and level of exposure, in the national asthma registry, would give further insights into this relationship.

Background: The optimal number of lymph nodes to be dissected during lung cancer surgery to minimise the postoperative recurrence risk remains undetermined. This study aimed to elucidate the impact of the number of dissected lymph nodes on the risk of postoperative recurrence of non-small cell lung cancer (NSCLC) using machine learning algorithms and statistical analyses.

Methods: We retrospectively analysed 650 patients with NSCLC who underwent complete resection. Five machine learning models were trained using clinicopathological variables to predict postoperative recurrence. The relationship between the number of dissected lymph nodes and postoperative recurrence was investigated in the best-performing model using Shapley additive explanations values and partial dependence plots. Multivariable Cox proportional hazard analysis was performed to estimate the HR for postoperative recurrence based on the number of dissected nodes.

Results: The random forest model demonstrated superior predictive performance (area under the receiver operating characteristic curve: 0.92, accuracy: 0.83, F1 score: 0.64). The partial dependence plot of this model revealed a non-linear dependence of the number of dissected lymph nodes on recurrence prediction within the range of 0-20 nodes, with the weakest dependence at 10 nodes. A linear increase in the dependence was observed for ≥20 dissected nodes. A multivariable analysis revealed a significantly elevated risk of recurrence in the group with ≥20 dissected nodes in comparison to those with <20 nodes (adjusted HR, 1.45; 95% CI 1.003 to 2.087).

Conclusions: The number of dissected lymph nodes was significantly associated with the risk of postoperative recurrence of NSCLC. The risk of recurrence is minimised when approximately 10 nodes are dissected but may increase when >20 nodes are removed. Limiting lymph node dissection to approximately 20 nodes may help to preserve a favourable antitumour immune environment. These findings provide novel insights into the optimisation of lymph node dissection during lung cancer surgery.