ERJ Open Research最新文献

Early detection of potential severe disease progression facilitates implementation of relevant precise disease management strategies. MMP-7 is a reliable prognostic biomarker for long COVID persistent lung damage that should be considered for clinical use. https://bit.ly/3Ccxozg.

Background: Acute exacerbations of fibrosing interstitial lung diseases (ILDs) are associated with high mortality. We used prospective data from the INBUILD trial to investigate risk factors for acute exacerbations and the impact of these events in patients with progressive pulmonary fibrosis.

Methods: Patients with progressive fibrosing ILDs other than idiopathic pulmonary fibrosis (IPF) were randomised to receive nintedanib or placebo. Associations between baseline characteristics and time to first acute exacerbation were assessed using pooled data from both treatment groups using Cox proportional hazard models, firstly univariable models and then a multivariable model using forward stepwise selection. The risk of death was estimated based on the Kaplan-Meier method.

Results: Over a median follow-up of approximately 19 months, acute exacerbations were reported in 58 (8.7%) of 663 patients. In the risk factor analysis, the final model included diffusing capacity of the lung for carbon monoxide (D _LCO) % predicted, treatment and age. Lower D _LCO % predicted was associated with an increased risk of acute exacerbation with a hazard ratio (HR) of 1.56 (95% CI 1.21-2.02) per 10 units lower (p<0.001). Age ≥65 years was associated with a numerically increased risk (HR 1.55, 95% CI 0.87-2.77; p=0.14). Treatment with nintedanib conferred a numerically reduced risk versus placebo (HR 0.60, 95% CI 0.35-1.02; p=0.06). The estimated risks of death ≤30 days and ≤90 days after an acute exacerbation were 19.0% (95% CI 8.9-29.2) and 32.0% (95% CI 19.7-44.2).

Conclusions: Acute exacerbations of progressive pulmonary fibrosis may have similar risk factors and prognostic impact as acute exacerbations of IPF.

Introduction: Both combined endobronchial ultrasonography (EBUS) and transoesophageal bronchoscopic ultrasonography (EUS-B) and EBUS alone have been recommended for preoperative mediastinal staging of nonsmall cell lung cancer (NSCLC). However, no randomised study comparing these two methods has been published. The purpose of the present study was to compare the sensitivity of EBUS and that of combined EBUS and EUS-B (EBUS/EUS-B) in terms of detecting N2/N3 disease during staging of NSCLC.

Methods: Patients with known or suspected, potentially operable NSCLC were recruited and randomised to undergo EBUS or EBUS/EUS-B under conscious sedation. The primary end-point was a comparison of the sensitivity of EBUS alone and EBUS/EUS-B.

Results: A total of 240 patients were enrolled and randomised, among whom 219 (105 EBUS group; 114 EBUS/EUS-B group) were included in the analysis. The sensitivities of EBUS and EBUS/EUS-B in terms of detecting N2/N3 disease were 75.0% and 79.3% respectively (p=0.698). In the EBUS/EUS-B group, only EUS-B yielded diagnostic results in two patients; the sensitivity thus increased from 72.4% to 79.3% on addition of EUS-B to EBUS.

Conclusions: The difference in the sensitivities of EBUS alone and EBUS/EUS-B in terms of diagnosing N2/N3 disease was not statistically significant. Although the increase in sensitivity with the addition of EUS-B is modest, it is maximised when EUS-B is used to sample lymph nodes not accessible by EBUS alone.

Rationale: The measurement of cough frequency is widely used in clinical trials, typically expressed as the number of explosive cough sounds per hour. However, this measure does not capture the clustering of coughs into bouts. Coughing bouts contribute to perceived cough severity and the physical complications of coughing, but an agreed standard definition of cough bouts is lacking. The objectives of the present study were to explore the impact of different definitions of cough bouts on the parameters generated, their relationships with reported cough severity and influence of age and gender in refractory chronic cough (RCC).

Methods: We analysed 24-h acoustic recordings and concurrent cough severity visual analogue scales from 91 RCC patients (62% female, median (interquartile range) age 60.0 (54-67.0) years). A custom-built algorithm calculated cough bouts, defined by the intervals between explosive cough sounds. Bouts defined by inter-cough intervals from ≤0.5 to ≤10 s (0.5 s increments) were explored, and parameters including number of bouts, median/maximum bout length and total bout duration calculated.

Measurements and main results: Using inter-cough intervals of >3 s to define cough bouts made little difference to cough bout parameters. Correlations between cough severity and bout parameters were weak but most likely to be significant when single coughs were removed. Cough-free time/total time spent coughing tended to have more influence on cough severity than the average cough bout length, irrespective of the interval used.

Conclusion: These analyses favour definitions of cough bouts utilising inter-cough intervals of ≤3 s and the exclusion of single coughs from cough bout analysis.

Effective treatment of OSA reduces driving accident risk https://bit.ly/3zzQUEN.

Background: Community-acquired pneumonia (CAP) remains a leading cause of infectious disease mortality globally, necessitating intensive care unit (ICU) admission for ∼10% of hospitalised patients. Accurate prediction of disease severity facilitates timely therapeutic interventions.

Methods: Our study aimed to enhance the predictive capacity of the clinical CRB-65 score by evaluating eight candidate biomarkers: troponin T high-sensitive (TnT-hs), procalcitonin (PCT), N-terminal pro-brain natriuretic peptide, angiopoietin-2, copeptin, endothelin-1, lipocalin-2 and mid-regional pro-adrenomedullin. We utilised a machine-learning approach on 800 samples from the German CAPNETZ network (competence network for CAP) to refine risk prediction models combining these biomarkers with the CRB-65 score regarding our defined end-point: death or ICU admission during the current CAP episode within 28 days after study inclusion.

Results: Elevated levels of biomarkers were associated with the end-point. TnT-hs exhibited the highest predictive performance among individual features (area under the receiver operating characteristic curve, AUC=0.74), followed closely by PCT (AUC=0.73). Combining biomarkers with the CRB-65 score significantly improved prediction accuracy. The combined model of CRB-65, TnT-hs and PCT demonstrated the best balance between high predictive value and parsimony, with an AUC of 0.77 (95% CI: 0.72-0.82), while CRB-65 alone achieved an AUC of 0.67 (95% CI: 0.64-0.73).

Conclusion: Our findings suggest that augmenting the CRB-65 score with TnT-hs and PCT enhances the prediction of death or ICU admission in hospitalised CAP patients. Validation of this improved risk score in additional CAP cohorts and prospective clinical studies is warranted to assess its broad clinical utility.

Given the high mortality rate observed in our data, tocilizumab is not recommended as a salvage therapy for patients affected by acute exacerbation of pulmonary fibrosis who did not show clinical improvement after three steroids bolus https://bit.ly/3ClggYb.

Background: Obstructive sleep apnoea (OSA) is common in commercial drivers, and associated with increased risk of crashes if untreated, making diagnosis and effective treatment crucial in this population.

Study design and methods: This is a retrospective summary of a clinical programme based on telemedicine and remote treatment monitoring developed with a national trucking company to screen new hires in the USA for OSA and implement positive airway pressure (PAP) management. New hires were informed of the programme and consented as part of their employment. Drivers who did not comply with the evaluation or with PAP after diagnosis were removed from driving commercial vehicles by the company or did not pursue further employment.

Results: A total of 975 drivers were enrolled. Among screened drivers, 35.5% were cleared without a sleep study, 15.0% were cleared following a sleep study (apnoea-hypopnoea index (AHI) <5 events·h^-1), 22.1% had mild OSA (AHI 5-15) and 27.4% had moderate-severe OSA (AHI ≥15). Those with moderate-severe OSA were more obese (body mass index 36.2±6.3 kg·m^-2) and had more comorbidities. Of 269 drivers starting PAP, 160 (59.5%) maintained participation in a care management programme, 80 (29.7%) resigned or were terminated, 23 (8.6%) were cleared to discontinue PAP and six (2.2%) were complex cases requiring transfer of care. Illustrating effectiveness, those that maintained participation had excellent PAP adherence (5.27±1.61 h·night^-1; 88.5±12.9% days used; 79.7±17.7% days used ≥4 h).

Interpretation: Remote assessment of OSA and PAP management in commercial drivers is feasible and effective. This approach has wide-ranging applications, particularly in populations and areas with a lack of sleep medicine providers.

Introduction: Despite shared features with pulmonary arterial hypertension, acute vasoreactivity in pulmonary hypertension with interstitial lung disease (PH-ILD) is not well characterised, including its potential ability to predict therapeutic outcomes. We sought to determine whether acute vasoreactivity in PH-ILD to oxygen (O₂) and inhaled nitric oxide (iNO) predicts inhaled treprostinil (iTre) outcomes.

Materials and methods: In this retrospective cohort analysis, we identified treatment-naive PH-ILD patients with vasoreactivity testing using O₂ and O₂+iNO. 6-month iTre outcome was assessed. "iTre improvement" required fulfilment of criteria on objective assessment without clinical worsening. "iTre failure" was defined by lack of objective improvement or a clinical worsening event.

Results: Among 75 PH-ILD patients, mean pulmonary arterial pressure (mPAP) decreased by -3 mmHg (-12.6%) and pulmonary vascular resistance (PVR) by -1.3 WU (-23.7%) with O₂+iNO. With O₂+iNO, mPAP decreased ≥10 mmHg to <40 mmHg in four patients (5.3%) and 23 (30.7%) had ≥20% reduction in mPAP and PVR. Among 33 iTre-treated patients, there were 13 improvements and 20 failures. The microvascular response, measured by distensibility, to O₂ alone versus O₂+iNO correlated with 6-month iTre outcome. Patients with 6-month iTre improvement had large relative distensibility increases with O₂+iNO (versus failure, 76.0% versus 15.3%, p=0.004). Conversely, iTre failure was associated with increased distensibility with O₂ alone (versus improvement, 26.8% versus -3.9%, p=0.045).

Conclusions: In PH-ILD, the microvascular response to O₂ versus O₂+iNO testing was associated with 6-month iTre outcome, likely reflecting the differential contributions of hypoxic vasoconstriction and remodelling. Acute vasoreactivity may inform therapeutic decision-making in PH-ILD.

Background: Severe asthma affects the working life of millions of people worldwide. Interleukin (IL)-5/anti-interleukin-5 receptor α (IL-5Rα) antibodies are highly effective in reducing symptoms in patients with severe eosinophilic asthma. We analysed effects of anti-IL-5/anti-IL-5Rα treatment on self-reported productivity and absenteeism at work in patients with severe eosinophilic asthma.

Methods: In this prospective single-centre study, patients with severe eosinophilic asthma received a questionnaire assessing their actual occupational status and the influence asthma has on their work life, productivity and missed days at work prior to initiation of antibody treatment and after 6 and 12 months of therapy. Among others, the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) was used.

Results: Out of 54 patients with a median age of 60 years, 27 (50%) were employed. In addition to an increase in asthma control and lung function, self-reported productivity increased significantly with a decrease on the WPAI:SHP from 30% (interquartile range (IQR) 20-50%) to 10% (IQR 0-27.5%) under treatment (p=0.001). Furthermore, self-reported missed days at work were reduced from 2 days·month^-1 (IQR 1.75-6 days·month^-1) to 0 days·month^-1 (IQR 0-2 days·month^-1; p=0.067). At baseline 22 employed patients (81%) stated they were affected at work by their asthma. After 12 months of treatment, this number decreased to eight patients (30%; p=0.038).

Conclusions: This prospective analysis could prove the substantial impact severe asthma has on patients' working life. Anti-IL-5/anti-IL-5Rα treatment in patients with severe eosinophilic asthma leads to a significant increase in self-reported productivity at work, and after 12 months of treatment patients state substantially fewer negative effects on their working situation.