ERJ Open Research最新文献

Introduction: Obstructive sleep apnoea (OSA) characterised by intermittent hypoxia promotes systemic inflammation. This study evaluated the association between OSA severity and circulating C-reactive protein (CRP) levels as marker of systemic inflammation in a pan-European patient cohort.

Methods: This cross-sectional analysis of the multicentre European Sleep Apnoea Database (ESADA) cohort used inverse probability weighted regression adjustment for multiple covariates within a linear mixed-effects model (LMEM) to test the independent association between OSA severity and CRP levels. Covariates included anthropometrics and comorbidities. Study centre and year of analysis accounted for methodological variability in CRP analysis.

Results: 18 445 subjects (71% male, median age 53 years (interquartile range 44-62), median apnoea-hypopnoea index (AHI) 22.1 events per h (9-44.9)) were included. CRP (median 3.0 mg·L^-1 (1.2-5.1)) increased in a dose-response fashion across OSA severity categories (2.0 (1.0-4.0) for AHI <5 events per h; 2.5 (1.0-5.0) for AHI 5-<15 events per h); 2.9 (1.2-5.0) for AHI 15-<30 events per h; and 3.7 mg·L^-1 (1.8-6.4) for AHI ≥30 events per h; p<0.001, respectively). In the final LMEM model, AHI remained an independent predictor of CRP concentration (p<0.001). Other significant predictors of CRP were age and female sex. Obesity (body mass index ≥35 kg·m^-2) had, among other comorbidities, the strongest independent effect on CRP levels with 2.7 mg·L^-1 (95% CI 2.45-2.90).

Conclusions: Our results showed a consistent and robust dose-response relationship between OSA severity and systemic inflammation independent of usual confounders. The combination of OSA and obesity amplified the association. Future studies should address whether elevated CRP could serve as a prognostic marker for subsequent cardiovascular events in OSA.

Background: Determination of reference values of respiratory impedance (Z) measured by oscillometry is of utmost importance for its clinical usefulness. The aim of our study was to develop reference values for within-breath and total oscillometry measurements in adults (18-90 years of age).

Methods: Healthy asymptomatic never-smoking adults of the Austrian LEAD study cohort were included in the analysis. Healthy never-smoking adults without any respiratory disease, with normal weight (body mass index (BMI) ≤35 kg·m^-2) and normal lung volumes (total lung capacity ≥ lower limit of normal) were included. Data were collected with the Resmon Pro FULL^® device using a multiple frequency mode of 5-11-19 Hz. Sex-specific reference equations were developed for within-breath and total resistance, reactance and the impedance modulus, as well as for the frequency dependence of resistance (R ₅-R ₁₉), the resonant frequency and the area under the reactance curve using the lambda, mu, sigma method.

Results: A total of 887 participants were included in the analysis. We developed sex-specific reference equations for 30 total and within-breath oscillometry parameters. Height, age and BMI were included in the modelling, and height showed the strongest association. Predicted values showed a narrower normality range compared with existing reference equations.

Conclusion: Our study provides highly accurate, adult reference equations derived from a large sample size with a wide age span. Development of reference equations supports further research on positioning of oscillometry in respiratory diagnostics.

Background: There is increasing concern about children with asthma developing progressive lung function impairment. The objective of the present study was to identify the best spirometric determinants of subsequent development of airflow obstruction (AO) in children with asthma in the clinic setting.

Methods: We assembled two retrospective cohort studies of children aged 6-17 years, managed in tertiary-care asthma clinics, with medical and drug coverage, and repeated spirometry testing. The primary outcome was AO, defined as pre-bronchodilation (pre-BD) forced expiratory volume in 1 s (FEV₁)/forced vital capacity (FVC) ratio below the lower limit of normal (LLN). Multiple lung function parameters, prior to index visit, were adjusted for potential covariates/confounders in multivariable logistic regression models, by cohort and clinical scenario (≥1 versus ≥2 prior visits with spirometry); cohort estimates were meta-analysed using inverse-variance-weighted average.

Results: Of 509 eligible children (mean age: 10 years), 17% subsequently developed AO. In patients with ≥1 prior visit, the likelihood of future AO independently increased by almost 4-fold (adjusted OR 3.91 (95% CI 2.54-6.01)) for every 1 z-score lower FEV₁/FVC ratio. In patients with ≥2 prior visits, the likelihood of future AO increased by 3.31 (1.98-5.54) for every 1 z-score lower FEV₁/FVC ratio at the last visit and by 1.50 (1.10-2.12) for every 1 z-score maximum between-visit variation in FEV₁.

Interpretation: Two spirometric parameters independently increased the likelihood of subsequently developing AO, namely FEV₁/FVC in the low range of normal and high between-visit FEV₁ variation, appearing as practical determinants of future impairment, before reaching the LLN.

Background: Sputum cytology utilising routine dithiothreitol (DTT) processing is a well-established method to assess airway eosinophilia. However, the multi-step nature of this protocol requires substantial resources, thereby limiting its broader clinical applicability. To address this, we evaluated formalin-fixed, paraffin-embedded (FFPE) sputum plugs as a simplified method for measuring airway eosinophilia.

Methods: Excess sputum plugs from 113 patients with complex airway disease and 16 asthma patients on corticosteroid or monoclonal antibodies were fixed in 10% formalin and embedded in paraffin (Sputum-Minimising Processing, Maximising Clinical Outcomes (SSIMPLE) method). FFPE blocks were sectioned, stained with haematoxylin and eosin, and assessed by four blinded observers, who performed a differential cell count on 400 total nonsquamous cells. Eosinophil proportions were then compared between matched FFPE and DTT-processed sputum slides. Airway eosinophilia was defined as ≥2.2% sputum eosinophils in DTT-processed samples.

Results: Of the 113 FFPE slides, 96% were adequate for cellular analysis, with 90% having matched DTT-processed sputum slides. The SSIMPLE method demonstrated excellent interobserver reproducibility (consistency: 0.975; agreement: 0.976). Eosinophil proportions obtained from SSIMPLE and DTT processing were significantly correlated (ρ=0.9, p<0.0001) and showed agreement (Bland-Altman, -0.38±9.51). A cut-off of 2.6% detected airway eosinophilia with high sensitivity (85.4%) and specificity (93.0%) using the SSIMPLE method, showing strong agreement with the routine DTT method, as indicated by an area under the curve of 0.957. Additionally, the method effectively assessed treatment responsiveness to monoclonal antibody therapy.

Conclusion: The SSIMPLE method is a reliable, noninferior approach to DTT processing for detecting airway eosinophilia in complex airway diseases, with high reproducibility and strong concordance in monitoring treatment responsiveness.

Background: Culture-independent molecular techniques could potentially be used to measure microbiological efficacy in response to antibiotic treatment and improve understanding of the role of the airway microbiota in determining response in patients with chronic respiratory disease.

Methods: Using molecular methods, we analysed changes in the sputum microbiota in samples from 107 participants with bronchiectasis recruited to the iBEST-1 study, and defined community endotypes based on response to tobramycin inhalation powder (TIP) treatment. The relationship between microbiota metrics in these endotypes and clinical and inflammatory biomarkers were also determined.

Results: There was a significant reduction in Pseudomonas aeruginosa density, measured by quantitative polymerase chain reaction (qPCR), between Days 1 and 29 for participants in the TIP treatment (n=63; p<0.0001) but not placebo (n=20; p>0.05) group. Based on decrease in P. aeruginosa density (oprL copies·mL^-1) over 28 days, two clusters of participants receiving TIP were observed and stratified as either responders (≥2Log₁₀; n=26) or non-responders (<2Log₁₀; n=37). In responders, a shift to a microbial community structure less dominated (p=0.018) by a pathogen was apparent and associated with a greater improvement in inflammatory and fewer participant exacerbations in the following 6 months (27% versus 49%; p=0.117) when compared to non-responders. Lung function was higher at Day 1 in responders (_median=64.6% predicted) than non-responders (μ̃_median=50.3% predicted) and independently predicted response to treatment with TIP (p=0.013).

Conclusions: qPCR may be a useful, culture-independent microbiological efficacy end-point in clinical trials. Using qPCR, participants with bronchiectasis were stratified into endotpyes which predicted response to antimicrobial treatment, potentially allowing for a more personalised approach to therapy.

Introduction: In mild to moderate obstructive sleep apnoea (OSA), positive airway pressure (PAP) and mandibular advancement devices (MADs) are recommended treatments according to guidelines. This cross-sectional study aimed to determine the clinical and organisational predictors for treatment recommendations in mild to moderate OSA.

Methods: In the European Sleep Apnea Database, factors predicting the choice of MAD or PAP treatment were determined in patients with newly diagnosed mild to moderate OSA. Accessibility and reimbursement of MADs study sites was obtained via questionnaire. The regression model included anthropometrics, Epworth Sleepiness Scale score, OSA severity, MAD accessibility and reimbursement, and a comorbidity index variable.

Results: 6618 (65.5%) patients received PAP and 3491 (34.5%) were recommended MADs. MAD recommendations varied between centres (0% to 76%). Significant factors favouring MADs include mild versus moderate OSA (odds ratio 6.0, 95% CI 5.3-6.8), negligible versus moderate intermittent hypoxia (OR 2.0, 95% CI 1.7-2.4), no versus excess daytime sleepiness (OR 2.6, 95% CI 2.1-3.1), a comorbidity index score of 0 compared to 3 or more (OR 3.8, 95% CI 3.1-4.6) and no insomnia diagnosis versus diagnosed insomnia (OR 2.0, 95% CI 1.7-2.4). MAD accessibility and reimbursement predicted MAD treatment recommendations (OR 2.3, 95% CI 1.8-2.9 and OR 1.5, 95% CI 1.4-1.7, respectively).

Conclusion: In mild to moderate OSA, MADs are less frequently recommended than PAP, particularly amongst patients with a higher disease burden. MADs were more frequently used when they were more accessible and reimbursed. Thus, MADs are likely an underused treatment in mild to moderate OSA.

Toxic oil syndrome-associated PAH can develop decades after exposure, highlighting the need for lifelong monitoring of exposed individuals, better understanding of delayed pathophysiological mechanisms and vigilance for future large-scale toxic exposures https://bit.ly/423Gbhh.

Aims: Toxic oil syndrome (TOS) was one of the first described forms of drug-induced pulmonary arterial hypertension (PAH). Its long-term clinical evolution remains poorly understood. The objectives of the present study were to provide new clinical, pathological and genetic insights into TOS-associated PAH (TOS-PAH), and to evaluate its long-term outcomes.

Methods: Patients diagnosed with TOS-PAH and included in the Spanish Registry of PAH (REHAP) were prospectively analysed.

Results: 59 new cases were diagnosed between 1997 and 2025 (63% female; median age 47 years), including several in the past two decades. The median interval between TOS exposure and PAH diagnosis was 270.8 months (interquartile range (IQR) 204.9-398.0). Patients diagnosed in earlier periods were younger, with more advanced functional impairment and more severe haemodynamics. In contrast, recent cohorts showed a higher prevalence of cardiovascular and respiratory comorbidities. No significant differences were observed in overall or transplant-free survival across decades (p=0.677). Median transplantation-free survival was 97.2 months (IQR 64.2-199.4). Three patients achieved complete haemodynamic resolution. Genetic testing was negative in all evaluated patients. Pathological findings were comparable with those observed in other PAH forms, with some cases with significant venous remodelling.

Conclusions: TOS-PAH remains a distinct clinical entity, with new cases diagnosed decades after toxic exposure. Despite differences in presentation over time, its long-term clinical course appears similar to that of other PAH types.

Background: Plethysmographic airway resistance (R _aw) and specific airway resistance (sR _aw) are widely used to assess baseline lung function and bronchodilator reversibility in children unable to perform spirometry. However, no consensus exists on cut-offs for significant reversibility.

Methods: We conducted a retrospective study on a large cohort of asthmatic children tested during panting without electronic thermal compensation, to determine optimal R _aw and sR _aw cut-offs for detecting significant forced expiratory volume in 1 s (FEV₁) reversibility. A smaller cohort undergoing tidal breathing plethysmography with electronic thermal compensation was also analysed.

Results: From 2436 tests without thermal compensation, receiver operating characteristic curve analysis identified cut-offs of -34.4% (R _awtot) and -36.0% (sR _awtot) from baseline to detect significant FEV₁ reversibility, with sensitivities of 70% (95% CI 65-74%) and 72% (95% CI 67-76%) and specificities of 70% (95% CI 68-72%) and 73% (95% CI 71-75%), respectively. Expressing reversibility as a percentage of predicted did not improve accuracy, but required larger cut-offs (-42.6% for R _awtot, -56.1% for sR _awtot) and increased the influence of baseline value. In the 106 tests performed using electronic thermal compensation, R _awtot/eff and sR _awtot/eff cut-offs were lower than that without electronic thermal compensation (-25% of baseline) with sensitivities and specificities ranging from 63% to 70%.

Conclusion: R _awtot and sR _awtot reversibility effectively identify FEV₁ reversibility with cut-offs around -35% of the baseline value, showing no added benefit when using larger cut-offs expressed as a percentage of the predicted value. When electronic thermal compensation is applied, it may necessitate lower cut-offs of -25% of the baseline, compared to those determined without it.

Background: Refractory chronic cough (RCC) is a burdensome condition with few effective treatments. While behavioural cough-suppression therapy (BCST) has demonstrated high efficacy, access is limited by geographical and provider constraints. This pilot study evaluated the efficacy of BCST delivered in a group telehealth format.

Methods: BCST was delivered to small groups (2-5 participants) via telehealth using a rolling enrolment model. Participants attended 4-6 sessions (60-90 min each), led by a trained speech-language pathologist and a graduate student. Each session followed a structured format with emphasis on understanding cough hypersensitivity, training in cough-suppression techniques, adherence monitoring and discussion of participant challenges related to cough suppression. Outcome measures included the Leicester Cough Questionnaire (LCQ) and Patient Global Impression of Severity (PGI-S), with optional cough frequency monitoring using the CoughPro smartphone app.

Results: 47 participants (mean age 56.8 years; 42 women) from four countries completed the study. Six participants provided sufficient cough monitoring data. After treatment, 98% (46 of 47) exceeded the LCQ's minimal clinically important difference of 1.3 points. Mean LCQ improvement was 7.04 at both 1 week and 1 month after treatment assessments (both p<0.001; d=2.54 and 2.35, respectively). PGI-S scores showed a median reduction of 2 points. Among those with cough monitoring, the mean hourly cough rate dropped by 68% and cough bouts decreased by 78%.

Discussion: Group telehealth BCST focused primarily on consistent cough suppression is an extremely efficacious intervention and can increase availability and access to treatment for patients with RCC.