European Respiratory Journal最新文献

Background: Tuberculosis (TB) remains a major cause of infectious disease mortality globally, with significant underdiagnosis perpetuating transmission. Tongue swab analysis has emerged as a promising non-invasive method for pulmonary TB diagnosis. This study evaluates the diagnostic accuracy of the TB-EASY quantitative PCR (qPCR) assay using tongue swab specimens.

Methods: In this prospective multicentre study, conducted across seven designated TB hospitals in China, 729 participants were included in the analysis. Tongue swabs were tested using the new TB-EASY assay from Hugobiotech, while sputum samples were analysed by Xpert MTB/RIF (Xpert), smear and culture tests. Diagnostic performance was compared to a composite microbiological reference standard (MRS).

Results: The TB-EASY assay demonstrated high diagnostic accuracy, with sensitivity and specificity of 89.6% and 96.2% compared to sputum Xpert, and 87.4% and 98.0% compared to the MRS. Sensitivity varied by bacterial load, ranging from 100% in high-load cases to 70.4% in very-low-load cases. The assay demonstrated robust performance in diverse epidemiological settings.

Conclusions: The TB-EASY qPCR assay using tongue swabs offers a reliable, non-invasive diagnostic alternative for pulmonary TB, especially where sputum collection is challenging. Its potential for wider use in high TB burden settings warrants further validation in community-based studies. Limitations include potential overestimation of sensitivity due to the selection of symptomatic patients and the use of sputum Xpert rather than Xpert Ultra. Additionally, the performance in non-sputum-producing patients remains untested, and the cost-effectiveness should be further evaluated to assess the feasibility of its implementation.

Background: This multicentre, international, retrospective study aimed to investigate whether respiratory system reactance (X _rs) assessed by respiratory oscillometry on day 7 of life is associated with respiratory outcomes in preterm infants below 32 weeks gestational age (GA).

Methods: Sinusoidal pressure oscillations (2-5 cmH₂O peak-to-peak, 10 Hz) were superimposed on the positive end-expiratory pressure. We assessed the association of X _rs z-score with the duration of respiratory support using linear regression and with bronchopulmonary dysplasia (BPD) using logistic regression. We used the likelihood ratio test to evaluate whether X _rs z-score adds significantly to clinical predictors, including GA, birthweight (BW) and the National Institute of Child Health and Human Development (NICHD) BPD prediction model.

Results: 137 infants (median (interquartile range) 28.43 (26.11-30.29) weeks GA) were included; 44 (32%) developed BPD. X _rs z-score was significantly associated with the duration of respiratory support (R²=0.35). X _rs z-score was significantly higher in infants who developed BPD (p<0.001); the optimal cut-off value was 2.6, associated with 77% sensitivity and 80% specificity. In univariable analysis, per z-score increase in X _rs, the odds ratio for BPD increased by 60% and the respiratory support by 8 days. In multivariable analysis, X _rs z-score added significantly to the NICHD model and to GA and BW z-score to predict respiratory support duration (p=0.016 and p=0.014, respectively) and BPD development (p=0.003 and p<0.001, respectively).

Conclusion: X _rs z-score on the 7th day after birth improves the prediction of respiratory outcome in preterm infants.

Background: Few studies have investigated the influence of body mass index (BMI) trajectories on lung function covering the entire growth period.

Methods: We conducted a prospective study using data from the Swedish BAMSE birth cohort. Latent class mixture modelling was employed to examine the diversity in BMI z-scores from birth to 24 years of age. Participants with four or more BMI z-scores were included (n=3204, 78.4%). Pre-bronchodilator spirometry was tested at 8, 16 and 24 years, while post-bronchodilator spirometry, multiple-breath nitrogen washout (for lung clearance index) and urinary metabolomics data were assessed at 24 years.

Results: Six distinct BMI development groups were identified. Compared to the stable normal BMI group, the accelerated increasing BMI group exhibited reduced pre- and post-bronchodilator forced expiratory volume in 1 s (FEV₁)/forced vital capacity (FVC) ratio z-scores (pre: β= -0.26, 95% CI -0.44- -0.08; post: β= -0.22, 95% CI -0.39- -0.05), along with elevated lung clearance index (0.30, 95% CI 0.22-0.42) at 24 years. The persistent high BMI group demonstrated lower FEV₁ (-0.24, 95% CI -0.42- -0.05) and FVC (-0.27, 95% CI -0.45- -0.01) z-score growth between 16 and 24 years, and elevated lung clearance index (0.20, 95% CI 0.03-0.39) at 24 years. However, those impairments were not observed in the accelerated resolving BMI group. Conversely, the persistent low BMI group displayed persistently decreased FEV₁ and FVC from 8 to 24 years, as well as decreased lung function growth. Additionally, histidine-related metabolites were associated with pre- and post-bronchodilator FEV₁ (hypergeometric false discovery rate=0.008 and <0.001, respectively).

Conclusions: Early interventions aiming for normal BMI during childhood may contribute to improved lung health later in life.

Persistent neutrophilic inflammation is a central feature in both the pathogenesis and progression of bronchiectasis. Neutrophils release neutrophil serine proteases (NSPs), such as neutrophil elastase (NE), cathepsin G and proteinase 3. When chronically high levels of free NSP activity exceed those of protective antiproteases, structural lung destruction, mucosal-related defects, further susceptibility to infection and worsening of clinical outcomes can occur. Despite the defined role of prolonged, high levels of NSPs in bronchiectasis, no drug that controls neutrophilic inflammation is licensed for the treatment of bronchiectasis. Previous methods of suppressing neutrophilic inflammation (such as direct inhibition of NE) have not been successful; however, an emerging therapy designed to address neutrophil-mediated pathology, inhibition of the cysteine protease cathepsin C (CatC, also known as dipeptidyl peptidase 1), is a promising approach to ameliorate neutrophilic inflammation, since this may reduce the activity of all NSPs implicated in bronchiectasis pathogenesis, and not just NE. Current data suggest that CatC inhibition may effectively restore the protease-antiprotease balance in bronchiectasis and improve disease outcomes as a result. Clinical trials for CatC inhibitors in bronchiectasis have reported positive phase III results. In this narrative review, we discuss the role of high NSP activity in bronchiectasis, and how this feature drives the associated morbidity and mortality seen in bronchiectasis. This review discusses therapeutic approaches aimed at treating neutrophilic inflammation in the bronchiectasis lung, summarising clinical trial outcomes and highlighting the need for more treatment strategies that effectively address chronic neutrophilic inflammation in bronchiectasis.