BMJ Open Respiratory Research最新文献

Background: Ferroptotic cell death is a highly regulated process characterised by the iron-dependent accumulation of lipid peroxides on cell membranes. However, the role of ferroptosis-related genes (FRGs) in severe influenza is not well characterised.

Methods: Influenza-related gene expression data and FRG lists were, respectively, downloaded from the gene expression omnibus and ferroptosis database. Differentially expressed FRGs (DE-FRGs) were then identified by comparing samples from patients with and without severe influenza, respectively, defined by patients who did and did not require mechanical ventilation. Enrichment analyses of these DE-FRGs were performed, and hub genes were subsequently identified, enabling the establishment of hub gene-drug interaction and competing endogenous RNA (ceRNA) networks.

Results: In total, these analyses revealed 171 DE-FRGs from patients with and without severe influenza. Least absolute shrinkage and selection operator and support vector machine-recursive feature elimination algorithms were used to identify eight hub genes from this dataset (ALOX12, MUC1, stearoyl-CoA desaturase, DECR1, EZH2, toll-like receptor 4 (TLR4), RICTOR and GSTM1), all of which exhibited good diagnostic utility for severe influenza. Functional enrichment analyses indicated that these genes may influence influenza pathogenesis through the regulation of immune and inflammatory responses. Single-sample gene set enrichment analysis approaches indicated that the expression levels for these hub DE-FRGs were negatively correlated with lymphocyte activity, whereas they were positively correlated with inflammatory cell activity. Predictive analyses additionally enabled the identification of 71 drugs targeting five of these genes, while ceRNA network diagrams highlighted the complex regulatory relationships among these genes.

Conclusion: The eight hub FRGs established in this study may play an important role in shaping the pathogenesis of severe influenza in individuals and may offer value as biomarkers that can guide the personalised prevention and treatment of this severe form of disease.

Background: Inhaled corticosteroids (ICS) are the foundation of asthma treatment, yet approximately 50% of patients are sub-optimally adherent to them. ICS non-adherence is associated with significant morbidity including uncontrolled symptoms, exacerbations, hospitalisation and, unfortunately, death. The factors influencing a patient's adherence to inhaled treatments vary, and healthcare professionals (HCPs) require multifactorial skills to address them. Effective tools must be available for HCPs to develop these skills.

Aim: To assess if a newly developed self-directed online module changed knowledge of and confidence in the management of ICS non-adherence in asthma.

Methods: This study employed a mixed-methods, pre-test and post-test quasi-experimental design. Before starting the module, participants rated their confidence to manage medicine non-adherence in asthma on a 5-item Likert scale (from 'not at all confident' to 'very confident') and answered five multiple choice questions that tested knowledge. The questions were answered again after completing the module. The change in individual knowledge score and confidence pre-module and post-module completion was analysed using a paired sample t-test. Volunteers undertook a semi-structured interview following module completion, and data were scrutinised by thematic analysis.

Results: 194 participants completed pre-module and post-module assessments. Compared with baseline, a significant increase in knowledge (t=-17.809, df=193, p<0.001) and confidence scores (t=-12.820, df=193, p<0.001) was noted. Nine participants were interviewed, revealing key themes including how the module changed their understanding of the patient perspective, practical advice gained to support the patient and barriers to making changes in practice.

Conclusion: Completion of the self-directed online module improved HCP knowledge of and confidence to manage non-adherence to ICS in asthma. Further research is required to determine if it has a measurable effect on patients' clinical outcomes.

Introduction: Subjective sleep disturbance is common in chronic obstructive pulmonary disease (COPD) and is related to hyperinflation when supine and tidal expiratory flow limitation (EFL). We hypothesised that abnormalities in supine lung mechanics disturb sleep and impair gas exchange in COPD. We aimed to assess relationships between supine lung derecruitment, EFL and hyperinflation, and polysomnographic measures of sleep disturbance and gas exchange in COPD.

Methods: In this prospective, observational study, supine oscillometry was performed in stable COPD patients to assess lung derecruitment (reactance at 5 Hz (Xrs₅) z-score) and EFL (difference between mean inspiratory and expiratory reactance (∆Xrs₅)). Hyperinflation was assessed by supine inspiratory capacity (IC_supine) z-score. In-laboratory polysomnography was used to assess sleep disturbance, measured by Apnoea-Hypopnoea Index (AHI), Oxygen Desaturation Index (ODI) and AHI during rapid eye movement sleep (AHI REM). Monitoring of transcutaneous carbon dioxide (TcCO₂), and measurements of partial pressure of arterial carbon dioxide (PaCO₂) and HCO₃ ^- were performed in a subgroup.

Results: 28 COPD patients were enrolled (13 female, mean age (SD) 67.5 (8.71) years and mean forced expiratory volume in 1second (FEV1) z-scores (SD) -2.61 (1.06)). Worse Xrs_5(supine) correlated with greater respiratory arousals (AHI r_s =0.47, p=0.01; ODI r_s=-0.58, p=0.001), as did greater ∆Xrs_5(supine) (AHI REM r_s=0.53, p=0.005). Xrs_5(supine) correlated with peripheral oxygen saturation nadir (r_s=0.43, p=0.02). IC_supine correlated negatively with hypoventilation (PaCO₂ r_s=-0.77, p=0.001; HCO₃ ^- r_s=-0.78, p=0.001, n=15), as did Xrs_5(supine) (rise in TcCO₂ r_s=-0.65, p=0.009).

Conclusion: Lung derecruitment, EFL and supine hyperinflation likely contribute to sleep disturbance and sleep-related gas exchange impairment in COPD.

Objective: To investigate the interplay between the genetic predisposition to successful ageing and air pollution on lung disease in healthy aged German women under the hypothesis that ageing and lung diseases share mechanisms of oxidative stress and inflammation that can be regulated by genetic predisposition and environmental factors.

Design: German Study on the influence of Air pollution on Lung function, Inflammation and Aging prospective cohort between baseline (1985-1994) and follow-up (2007-2010).

Setting: Urban Ruhr area and the adjacent rural Münsterland in Germany.

Participants: At baseline, 4874 women aged 55 years living between 1985 and 1994 in the setting and at follow-up examination, 834 of them participated.

Main outcome measures: Chronic lung disease was defined as any of asthma, chronic bronchitis, cough (with sputum) or chronic obstructive pulmonary disease. Chronic individual exposures to nitrogen dioxide (NO₂), nitrogen oxides, particulate matter with median aerodynamic diameters <2.5 (PM_2.5), PM₁₀, PM_coarse and PM_{2.5 absorbance} based on European Study of Cohorts for Air Pollution Effects land-use regression models were used. Main and interaction effects between the genetic risk score (77 single-nucleotide polymorphisms (SNPs) related to successful ageing) and air pollutant exposures were investigated using adjusted logistic regression models.

Results: In 560 women (67-80 years), chronic lung disease was present in 156. Higher exposure to air pollution was associated with increased odds by up to 43% per IQR-increase in NO₂ (IQR=11.6 µg/m³, 95% CI 1.15 to 1.77). The genetic make-up reduced the negative impact of air pollution (gene-environment interaction with NO₂: OR=0.66, 95% CI 0.45 to 0.96), while a healthy lifestyle further strengthens this association.

Conclusions: In elderly women, genetic predisposition based on successful ageing SNPs likely reduces the negative impact of air pollution on chronic lung disease, while a healthy lifestyle further strengthens this association.

Background: Decision-making in non-small cell lung cancer (NSCLC) is complex and value-sensitive. A shared decision-making (SDM) approach is desirable to effectively weigh clinical considerations and patient preferences. However, implementing effective SDM remains challenging.

Objectives: This study explores the perspectives of patients with NSCLC and clinicians regarding SDM, identifying barriers and facilitators.

Methods: Two surveys were conducted: one with Dutch patients (n=116) and another with Dutch clinicians (n=143). The patient survey included demographics, treatment knowledge, information provision, decisional conflict scale and SDM. The clinician survey included demographics, patient information provision, treatment preferences (surgery vs radiation) using a 7-point Likert scale for five hypothetical cases, and SDM.

Results: Patients lacked knowledge about the advantages and disadvantages of different treatment options, especially regarding radiotherapy for early-stage NSCLC. 85% of patients and 70% of clinicians believed the final treatment decision should be made collaboratively. However, 69% of patients reported not being offered a choice of treatment options. Preferences varied significantly among specialties (p<0.01) in three out of five hypothetical cases.

Discussion: This study underscores the importance of SDM in NSCLC treatment, revealing gaps in patient knowledge, clinician SDM skills and information provision.

Conclusions: Significant discrepancies between patient and clinician perspectives, along with variation in treatment approaches, highlight the need for more personalised, patient-centred care, such as information portals and decision aids, in clinical practice.

Background: Long covid has emerged as a complex health condition for millions of people worldwide following the COVID-19 pandemic. Previously, we have categorised healthcare pathways for patients after discharge from hospital with COVID-19 across 45 UK sites. The aim of this work was to estimate the clinical and cost-effectiveness of these pathways.

Methods: We examined prospectively collected data from 1013 patients at 12 months postdischarge on whether they felt fully recovered (self-report), number of newly diagnosed conditions (NDC), quality of life (EuroQoL-five dimension-five level (EQ-5D-5L) utility score compared with pre-COVID estimate) and healthcare resource costs (healthcare records). An analysis of the cost-effectiveness was performed by combining the healthcare resource cost and 1-year EQ-5D (giving a quality-adjusted life-year (QALY)) using statistical models that accounted for observed confounding.

Results: At 1 year, 29% of participants felt fully recovered, and 41% of patients had an NDC. The most comprehensive services, where all patients could potentially access assessment, rehabilitation and mental health services, were more clinically effective when compared with either no service or light touch services (mean (SE) QALY 0.789 (0.012) vs 0.725 (0.026)), with an estimated cost per QALY of £1700 (95% uncertainty interval: dominated to £24 800).

Conclusion: Our analysis supports the need for proactive, stratified, comprehensive follow-up, particularly assessment and rehabilitation for adults after hospitalisation with COVID-19, showing these services are likely to be both clinically and cost-effective according to commonly accepted thresholds.

Background: This systematic review and meta-analysis synthesises evidence from both randomised trials and observational studies to determine whether lobectomy or sublobar resection offers improved outcomes for patients with stage Ia non-small cell lung cancer (NSCLC).

Methods: Studies (up to June 2025) comparing lobectomy and sublobar resection (segmentectomy or wedge) for clinical stage Ia NSCLC (<2 cm) were included in the random-effects meta-analyses. Risk of bias was assessed using Risk of Bias 2 for randomised trials or Risk of Bias in Non-randomised Studies of Interventions-I for observational studies.

Results: 19 studies, including four randomised trials, were included. Overall survival at 5 years was comparable between lobectomy and sublobar resection (HR=1.00; 95% CI 0.84 to 1.19; I²=26%), as was disease-free survival (HR=1.05; 95% CI 0.90 to 1.23; I²=0%). Sublobar resection was associated with significantly higher local recurrence (OR=1.86; 95% CI 1.07 to 3.25; I²=73%). No differences were observed in 10-year survival (OR=0.99; 95% CI 0.27 to 3.59; I²=86%) or postoperative change in forced expiratory volume in 1 s (mean difference=-4.70; 95% CI -11.15 to 1.76; I²=99%). In 10 studies that mandated systematic hilar and mediastinal lymph node sampling, sublobar resection was associated with improved overall survival compared with lobectomy (HR=0.81; 95% CI 0.69 to 0.965; I²=0%).

Conclusion: Lobectomy and sublobar resection offer comparable long-term survival for patients with stage Ia NSCLC. While sublobar resection is associated with higher local recurrence rates, subgroup analysis suggests that when intraoperative systematic hilar and mediastinal lymph node sampling is performed, sublobar resection may offer a survival advantage.

Background: Data on asthma with fixed airway obstruction (FAO) are heterogeneous due to different and misleading definitions. Describing the FAO phenotype has significant implications for severe asthma (SA) comprehension.

Objective: To characterise SA patients with FAO in the Severe Asthma Network in Italy (SANI) registry at baseline, and to compare with those with reversible airway obstruction (bronchodilator responsiveness, BDR). The potential for re-evaluating FAO or BDR in the follow-up was explored.

Methods: FAO was defined as a forced expiratory volume in the first second (FEV₁)/forced vital capacity ratio < Lower Limit of Normal (LNN) after a bronchodilator test with an increase in FEV₁ of <12% or 200 mL, compared with BDR and no airway obstruction (no-AO). Clinical reported outcomes, including asthma control (ACT), quality of life (AQLQ) and exacerbations (AEs) were collected. The effect of demographic, clinical and biohumoral variables on FAO, BDR and no-AO groups at baseline and during the follow-up was estimated.

Results: Among 354 patients, 190 (53.7%) reported AO with 116 (60.1%) resulting in FAO. The overall FAO rate at enrolment was 32.8%. Compared with BDR, FAO patients had better asthma control (34.5% vs 20.3%, p=0.004), a higher ACT (17.4 vs 15.2, p=0.005) and AQLQ (4.6 vs 3.8, p=0.001) score. FAO patients were less likely to visit the emergency room or be hospitalised than BDR (p=0.050), with no difference in AEs. The effect of airway calibre on fractional exhaled nitric oxide is more likely to cause its lower level within FAO compared with BDR (29.5 vs 46.0 ppb, p=0.04) than a lower T2 burden. A variation from FAO to BDR or no-AO was associated with the Global Initiative for Asthma classification (step 4 vs 5: HR 3.58 (95% CI 1.16 to 11.03)) and the age of asthma onset (30-39 vs <20 years: HR 3.94 (95% CI 1.09 to 14.30)) CONCLUSION: Stratifying SA patients from the SANI registry reveals an FAO phenotype that expresses different clinical outcomes and biological markers compared to BDR. Over time, FAO may be reversible in late-onset SA with less inhaled corticosteroid treatment.

Background: Asthma poses a great burden as one of the most common long-term non-communicable diseases. The April 2023 Sudanese war has severely disrupted the healthcare system, greatly affecting asthmatic patients by limiting access to medications and diagnostic services. Therefore, this research aims to investigate asthma control, self-management and healthcare access among asthma patients in Sudan during the ongoing war.

Methods: A cross-sectional study was conducted among Sudanese patients with asthma during the ongoing war using a convenience sampling. An online questionnaire was distributed from September 2024 to June 2025. It covered sociodemographic data, the validated Asthma Control Test (ACT), self-management and healthcare access. Data were analysed using SPSS software, employing descriptive statistics, χ² tests and linear regression, with significance set at p<0.05.

Results: Among the 229 asthmatic patients surveyed, 60.3% had poorly controlled asthma. Since the onset of the conflict, 43.2% had not attended any follow-up visits, while 48.5% required at least one emergency room visit during the war. Despite these challenges, 86.0% reported having quick access to healthcare during active attacks. However, 17.9% were unable to obtain their medications regularly, forcing many to adopt alternative coping strategies: 6.1% sought medical advice through online consultations, 15.7% increased their prescribed doses on their own and 39.3% used whatever medications were available without prescriptions, which was significantly associated with poor asthma control (χ²=29.29, p<0.01). Regression analysis revealed dose reduction was linked to worse control (β=-3.68, p=0.004), while refugee status and better adherence to medications predicted higher ACT scores (β=2.88, p<0.001; β=0.54, p=0.028).

Conclusions: This study highlights a considerable gap in asthma control during the ongoing war, despite the availability of healthcare services in times of urgent need. Many patients adopted coping strategies such as using whatever medications were available without prescriptions or independently increasing their prescribed doses. Enhancing patient education on proper asthma self-management and improving access to healthcare services, including telemedicine consultations, could play a crucial role in achieving better asthma control.