BMJ Open Respiratory Research最新文献

Introduction: The impact of breathing frequency on respiratory oscillometry measurements is unknown. We aimed to investigate the impact of different breathing frequencies in patients with asthma.

Method: We recruited patients from the severe asthma clinic at Cambridge University Hospitals. Using a randomised-crossover design, participants performed the forced oscillation technique at three different breathing frequencies (15, 30, 40 bpm) in a randomised order for each participant. A metronome was used to ensure the correct breathing frequency. Analysis of variance (ANOVA) and Friedman tests were utilised to assess the significance of any differences across the breathing frequencies. We then leveraged cross-sectional data from asthma patients who performed respiratory oscillometry and investigated the determinants of self-selected breathing frequency using multivariable linear regression.

Results: We recruited 59 patients. Mean age 54.1 years, 58% female, median forced expiratory volume in 1 s (FEV₁)/FVC z-score -2.56 (-3.26 to -1.96). As breathing frequency increased from 15 bpm to 40 bpm, there was a significant reduction (-8.6%, p<0.001) in total airway resistance (Rrs at 5 Hz), which was not mediated by changes in tidal volume or flow rate. There was also a significant reduction (-14.9%, p<0.001) in Delta R5-R19, and an increase (+10.9%, p=0.081) in reactance (Xrs at 5 Hz). At higher breathing frequencies, 5% of study participants were reclassified as having respiratory oscillometry measurements within normal limits. Data from 796 asthma patients were extracted for the cross-sectional analysis. The median (range) self-selected breathing frequency was 16.55 bpm (8.0, 42.0). Demographic data and lung function explained 23.5% of the variation in breathing frequency.

Conclusion: Higher breathing frequencies significantly reduce total Rrs . When performing respiratory oscillometry, breathing frequency should be controlled at approximately 15 bpm to reduce risk of misclassification.

Background and objective: Promoting physical activity is essential in chronic obstructive pulmonary disease (COPD) management, but the role of air quality in urban walking programmes remains unclear. This study assessed baseline factors and the impact of air quality on the success of a COPD walking programme.

Methods: In this prospective observational study, 72 patients with COPD and peripheral oxygen saturation (SpO_₂) ≥94%, were recruited from a university hospital. Baseline clinical data, functional tests, physical activity (steps/day) and sedentary status (Yale Physical Activity Survey (YPAS)) were collected. Patients participated in a 3-month walking programme, with self-documented physical activity tracked using pedometers and daily Air Quality Index (AQI) monitoring from a central site. Responders were defined as those with an increase of >600 steps/day. Baseline characteristics and AQI were compared between responders and non-responders, and multivariate logistic regression identified predictors of success.

Results: 42 patients (58%) achieved programme goals. The mean COPD Assessment Test score and forced expiratory volume in 1 second (FEV₁) were 11.5 and 54% predicted, respectively. Variables such as age, sex, Body Mass Index, comorbidities and exacerbation history showed no significant associations. Air quality (mean AQI: 71±10.7) did not influence outcomes (OR 1.018; 95% CI 0.949 to 1.092; p=0.622). Responders had higher baseline YPAS scores (OR 33.197; 95% CI 6.197 to 185.636; p<0.001) and greater FEV_₁ (OR 1.108; 95% CI 1.005 to 1.222; p=0.039).

Conclusions: AQI did not affect programme outcomes. Baseline sedentary status and FEV_₁ were key predictors of success. These findings support tailoring rehabilitation strategies to individual patient characteristics.

Background: Acute respiratory distress syndrome (ARDS) is a heterogeneous clinical syndrome with high morbidity and mortality. Despite advances in understanding its pathophysiology, definitive biomarkers for ARDS disease stratification and management remain lacking. This study evaluated the utility of circulating PRDX1 in predicting 28-day mortality in ARDS patients.

Methods: A retrospective cohort study was conducted at Third Xiangya Hospital, enrolling 90 ARDS patients. Serum PRDX1 levels and clinical data were collected and compared with those from healthy volunteers and non-ARDS pneumonia patients to examine its alterations in ARDS patients; multivariate logistic regression and receiver operating characteristic (ROC) curve analyses were then employed to assess the prognostic value of circulating PRDX1 for 28-day mortality. An independent validation cohort of 20 ARDS patients was recruited from Xiangya Hospital intensive care units. Additionally, serum Prdx1 dynamics were assessed in LPS-induced acute lung injury (ALI) and sepsis-associated ALI murine models.

Results: Serum PRDX1 levels were significantly elevated in a cohort of 90 ARDS patients, particularly among those with multiorgan injury. Multivariate analysis identified PRDX1 and age as independent risk factors for 28-day mortality. ROC curves revealed PRDX1's prognostic utility (area under the curve, AUC=0.776, p<0.0001), which was comparable to the APACHE II score (AUC=0.778, p<0.0001). These findings were validated in the 20-patient cohort. Animal experiments confirmed that serum PRDX1 positively correlated with lung injury severity and exhibited earlier elevation and higher abundance in multiorgan injury contexts.

Conclusions: Serum PRDX1 was significantly elevated in ARDS patients, particularly in those with multiorgan injury, and demonstrated potential as a prognostic biomarker, showing correlation with 28-day mortality. Its integration into the ARDS management framework holds significant potential for improving clinical outcomes.

Introduction: Single-inhaler triple therapy (SITT) is known to be a cost-effective intervention for chronic obstructive pulmonary disease (COPD)in Western countries, but there is no such evidence for resource-limited countries. This study aimed to evaluate the cost-utility of SITT compared with multiple inhaler triple therapy (MITT) for COPD in Thailand.

Methods: A Markov model with a lifetime horizon from a societal perspective was conducted with seven health states, including moderate, severe and very severe, with and without acute exacerbation (AE) and death. Two SITTs, fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) and budesonide/glycopyrrolate/formoterol (BUD/GLY/FOR), were compared with MITT (salmeterol/fluticasone propionate with tiotropium (SAL/FP+TIO). A comprehensive literature review was performed to identify inputs. A quality-adjusted life year (QALY) and incremental cost-effectiveness ratio (ICER) were calculated. A series of sensitivity analyses was performed.

Results: FF/UMEC/VI could improve QALY by 0.014 with an increased lifetime cost of 25 649 Thai baht (THB) ($727) compared with SAL/FP+TIO. In contrast, BUD/GLY/FOR had a lower QALY of -0.007 with an increased total lifetime cost of 34,151 THB ($968). The ICER for FF/UMEC/VI was 1,899,408 THB/QALY ($53,823), while BUD/GLY/FOR was dominated by SAL/FP+TIO. Probabilistic sensitivity analysis indicated that FF/UMEC/VI had a 1.1% chance of being cost-effective at the threshold of 160,000 THB ($4,533). We found that a 30% reduction in FF/UMEC/VI price could lead to a cost-effective option.

Conclusion: Our study indicated that SITTs are not cost-effective at the current price compared with the current MITT for COPD treatment. However, FF/UMEC/VI could be a promising option, with an approximately 30% price reduction.

Background: Pulmonary fibrosis (PF) is a rare lung disease with diverse pathogenesis and biological mechanisms. Mosaic loss of chromosome Y (mLOY) has been reported to be associated with increased risk of fibrotic diseases. However, the exact role of mLOY in the development of PF remains to be elucidated.

Methods: Copy number on chromosome Y was used to estimate mLOY comparing patients in PROFILE and gnomAD cohorts and between cases and control patients from the GE100KGP cohort. Correlation of mLOY with demographic and clinical variables was tested using patients from the PROFILE cohort. Lung single-cell transcriptomic data were analysed to assess the cell types implicated in mLOY. Mendelian randomisation was performed to examine the causal relationship between mLOY, idiopathic pulmonary fibrosis (IPF) and telomere length.

Results: The genetic analysis suggests that mLOY is found in PF from both case cohorts but when compared with an age matched population the effect is minimal (p=0.00316, median: 0.288 vs 0.291). mLOY is related to age (p=0.000214) and shorter telomere length (p=0.00815) rather than PF severity or progression. Single-cell analysis indicates that mLOY appears to be found primarily in immune cells. Mendelian randomisation demonstrates that mLOY is not on the causal pathway for IPF, but partial evidence supports that telomere shortening is on the causal pathway for mLOY.

Conclusions: Our study confirms the existence of mLOY in PF patients, suggests that mLOY is not a major driver of IPF, and might support a triangulation model where telomere shortening leads to both IPF and mLOY.

Background: Benralizumab improves outcomes in severe eosinophilic asthma (SEA). We aimed to evaluate early effects of benralizumab on airway pathophysiology using functional respiratory imaging (FRI).

Methods: In this prospective, single-arm study, 20 adults with SEA underwent CT at baseline, 4 and 12 weeks. Coprimary endpoints were changes in specific airway volume (siVaw) and resistance (siRaw) at functional residual capacity (FRC) and total lung capacity (TLC) at 12 weeks. Imaging outcomes included mucus score/volume and air-trapping.

Results: At week 12, siVaw increased at FRC by 0.16 mL/L (27%; 95% CI 0.01% to 0.31%; p = 0.02) and at TLC by 0.14 mL/L (14%; 95% CI 0.03% to 0.25%; p = 0.02); siRaw at TLC decreased by -0.41 kPa·s/L (-24%; 95% CI -0.80% to -0.01%; p = 0.04). siRaw at FRC increased (2.99 kPa·s/L; 95% CI -4.57 to 10.54; p=0.42), with a significant relative change (293%; p=0.03) that lost significance after excluding outliers. siVaw at FRC increased early (week 4: 0.19 mL/L; 33%; 95% CI 0.03% to 0.34%; p = 0.01). At week 12, the mucus score decreased by 0.41 (95% CI -0.67 to -0.14; p<0.01), and air-trapping by 5.5% (95% CI -8.8 to -2.1; p < 0.01). Changes in siVaw and mucus correlated with improvements in forced expiratory volume in 1 s (r = 0.66 and -0.77; both p<0.01) and Saint George's Respiratory Questionnaire (mucus: r = 0.45; p = 0.05).

Conclusions: Benralizumab treatment in SEA was associated with early improvements in airway volume, resistance, mucus and air-trapping, correlating with better lung function and quality of life. These findings support FRI to monitor early treatment effects.

Trial registration number: NL-OMON26915.

Background: Sarcoidosis is a systemic granulomatous disease with an unpredictable course. While corticosteroids are the mainstay of treatment, recurrence is common and influenced by clinical, demographic and therapeutic factors. However, an integrated approach to patient stratification remains underdeveloped.

Research question: What are the key clinical, demographic and therapeutic factors influencing sarcoidosis recurrence, and how can an integrated risk stratification model improve disease management?

Methods: We conducted a clustering analysis on 160 sarcoidosis patients to identify recurrence risk subgroups. Key variables included age, sex, body mass index, smoking history, Scadding stage, corticosteroid and immunosuppressant use, therapy duration and recurrence. K-means clustering was employed, with the optimal number of clusters determined using silhouette and elbow methods.

Results: Three distinct clusters emerged: Cluster 1 (n=110): predominantly Scadding stage I-II, low recurrence, favourable steroid response, minimal long-term complications. Cluster 0 (n=30): more smokers, advanced disease (Scadding III-IV), high recurrence despite treatment (p=0.003). Cluster 2 (n=20): patients with obesity with systemic symptoms (fatigue, dyspnoea), high recurrence, particularly in women (p=0.02).Multivariate analysis confirmed smoking (OR 2.3, p=0.002), obesity (OR 1.9, p=0.01) and prolonged steroid use (>12 months, OR 2.5, p=0.004) as independent predictors of recurrence. Sex differences were observed, with women showing more extrapulmonary involvement and men a higher risk of pulmonary fibrosis, though sex alone was not a significant predictor (p=0.08).

Interpretation: Distinct sarcoidosis phenotypes influence recurrence risk, underscoring the need for personalised management. While Cluster 1 may achieve remission with minimal therapy, Clusters 0 and 2 highlight smoking, obesity and advanced disease as recurrence drivers. Targeted interventions, including smoking cessation, weight management and early steroid-sparing therapy, could improve long-term outcomes and reduce disease burden.

Introduction: Preschool wheeze and asthma are associated with substantial morbidity and impaired future lung function. Yet, wheeze is unreliably reported with high disagreement (>50%) between parental and physician observations. Objectively defining wheeze and its reversibility could enable an earlier asthma diagnosis and improve preschool wheeze management.Our primary aim is to determine in preschool children (aged 0.5-6 years) suspected of asthma whether adding WheezeScan to routine clinical assessment (vs assessment without WheezeScan) improves the diagnosis of asthma. Our primary hypothesis is that using WheezeScan in preschool children suspected of asthma is associated with increased definitive asthma diagnoses in this age group. Our secondary aims are to (a) examine the effect of using WheezeScan on patient-reported outcomes (PROs) and (b) healthcare costs. Our secondary hypothesis is that using WheezeScan in preschool children suspected of asthma is associated with improved quality of life without incurring additional healthcare costs.

Methods and analysis: Our multicentre prospective cohort study involves recruiting 102 preschool children suspected of asthma. WheezeScan, a user-friendly digital device, incorporates artificial intelligence to objectively define wheeze and its response to bronchodilators. Over 6 weeks, parents/caregivers use the WheezeScan two times per day and whenever wheezing is suspected. If wheeze is detected, an inhaled short-acting β₂-agonist is administered and WheezeScan determines if wheeze resolves thereafter.Our primary endpoint is the proportion of children with a definitive asthma diagnosis, compared with baseline, based on the treating clinician's assessment using WheezeScan data. Our secondary outcomes are PROs, reflecting generic health-related quality-of-life and cough-specific (if chronic cough present) outcomes and health costs.

Ethics and dissemination: The Children's Health Queensland Human Research Ethics Committee (HREC/23/QCHQ/100691) and the Queensland University of Technology Office of Research Ethics and Integrity approved the study. We will publish and share results with the academic and healthcare communities and relevant patient organisations.

Trial registration number: Australian New Zealand Clinical Trials Registry ACTRN12623000904673.

Background: Pulmonary non-tuberculous mycobacterial (NTM) disease is a respiratory infection with an increasing incidence worldwide, including Japan. Host factors may also be involved in the establishment of pulmonary NTM disease. Cystic fibrosis transmembrane conductance regulator (CFTR) variants are associated with pulmonary NTM disease and bronchiectasis. However, data on CFTR variants in the Japanese population remain limited.

Objectives: We aimed to determine the frequency of CFTR variants and the impact on the clinical features of pulmonary NTM disease and bronchiectasis in the Japanese population.

Methods: We analysed 458 patients with either pulmonary NTM disease, non-cystic fibrosis bronchiectasis or both at Keio University Hospital from February 2016 to March 2019. CFTR variants were identified using exome sequencing, Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). These variants were determined to be deleterious using CFTR2 and in silico tools. Clinical characteristics of patients with and without CFTR variants were compared in a 1:8 age-matched and sex-matched ratio. Additionally, exome sequencing was performed for the family of a patient with a family history of pulmonary NTM disease.

Results: Deleterious CFTR variants were identified in 16 patients (3.5%). One variant was identified by MLPA, and 15 by Sanger sequencing. All patients harboured a CFTR variant in one allele. Compared with matched controls, these patients had lower sputum culture conversion rates and higher rates of macrolide resistance. In one family cluster, members with pulmonary NTM disease were found to carry the same CFTR variant.

Conclusions: We defined the frequency and clinical characteristics of CFTR variants among the Japanese population with either pulmonary NTM disease, non-cystic fibrosis bronchiectasis or both and found that patients with CFTR variants may be refractory to pulmonary Mycobacterium avium complex disease. Further comprehensive research is needed to assess the impact of CFTR variants on pulmonary NTM disease and bronchiectasis in non-European populations.