ERJ Open Research最新文献

Background: Concavity of the maximal expiratory flow-volume curve is widely regarded as an early indicator of obstructive airways disease. However, its discriminatory accuracy for respiratory outcomes has remained poorly defined. We aimed to examine the discriminatory accuracy of concavity of the maximal expiratory flow-volume curve versus post-bronchodilator (BD) forced expiratory volume in 1 s/forced vital capacity (FEV₁/FVC) as predictors of incidence of COPD and respiratory symptoms.

Methods: Spirometry was performed on a subset of the Tasmanian Longitudinal Health Study cohort at age 45 years, and incidence of COPD and respiratory symptoms were prospectively monitored over the next 8 years (n=852). Central and peripheral concavity were assessed using a published algorithm based on post-BD forced expiratory flow at 50% of the FVC (FEF_50%) and FEF_75%, respectively. Optimal thresholds were determined using the unweighted Youden Index for COPD incidence.

Results: Among participants without COPD at age 45 years, central and peripheral concavity were greater in those who developed COPD by age 53 years than in those who did not (mean difference: +20%, 95% CI 12-28, and +15%, 95% CI 7-23, respectively). Central concavity above the optimal threshold (27%) had a sensitivity of 70% and specificity of 79% for COPD incidence, while peripheral concavity above the optimal threshold (47%) had a sensitivity of 79% and specificity of 50%. Excess central and peripheral concavity were associated with an increased odds of developing wheeze and exertional dyspnoea over the 8-year follow-up. Post-BD FEV₁/FVC was more sensitive and specific for COPD incidence than the concavity indices, but was not associated with incident respiratory symptoms.

Conclusion: Concavity indices were more useful for assessing future risk of respiratory symptoms but had lower discriminatory accuracy for COPD incidence compared to post-BD FEV₁/VC.

Induced sputum is a useful methodology to evaluate airway inflammation. Unfortunately, it is time consuming and not available in many asthma centres. New procedures could be useful to obtain airway inflammatory data. https://bit.ly/3Huyols.

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.

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