BMJ Open Respiratory Research最新文献

Introduction: Firefighting continues to be among the most hazardous yet least studied occupations in terms of the impact of exposure to occupational disease. In particular, firefighters are at increased risk of adverse health effects due to exposure to significant levels of potentially harmful substances, namely carbon monoxide, particulate matter and formaldehyde, during their professional duties.This paper reports an epidemiologic study aiming to reduce the gaps in assessing the long-term effects of air pollution exposure to forest fires' combat on firefighters, namely regarding chronic obstructive pulmonary Disease (COPD) and asthma.

Methods and analysis: Based on the implementation in an area with high forest fires (in Portugal), the study will analyse firefighters' exposure to fire emissions by measuring air pollutants with personal exposure monitors during forest fire combat through a retrospective cohort study (exposed vs non-exposed). Moreover, based on answers to validated questionnaires and medical examinations to be performed by medical doctors, the study will assess the prevalence, incidence and exacerbation of COPD and asthma in firefighters, thus considering both short-term and long-term effects. Based on the results above referred, the study aims to evaluate the impact of exposure and inhalation dose of air pollutants during forest fires' combat on the development of the above-referred chronic diseases. The approximate number of participants in the study will never be less than 186, guaranteeing 80% of study power (significant at a 5% level).

Ethics and dissemination: The study has been approved by the Ethical Committee of Centro Hospitalar Universitário São João. The results will be published in international and national journals and conferences, allowing the results obtained to be communicated to the scientific community. Moreover, up-to-date data will be disseminated to stakeholders and decision-makers to help them decide on triggering official control measures.

Objectives: This study aimed at identifying risk factors for the incidence of interstitial lung disease in patients with rheumatoid arthritis (RA-ILD) by a systematic review and meta-analysis.

Methods: Information sources: studies published by March 2021 were searched in PubMed, Web of Science, MEDLINE, EMBASE, Cochrane Library and Scopus databases. Eligibility criteria: cohort studies or nested case-control studies that reported OR or HR of risk factors for RA-ILD were included. Two researchers independently screened the studies and extracted data. Synthesis of results: the relative risks (RRs) were introduced to measure the association across studies. Risk bias: quality assessments of included studies were performed using the Newcastle-Ottawa Scale. Based on the result of heterogeneity, the random-effects model or fixed-effects model was chosen in the meta-analysis. Furthermore, a sensitivity analysis was conducted to identify the origins of heterogeneity, and publication bias was evaluated for the factors with no less than five included studies by funnel plots and Egger's test.

Results: Among 3075 identified articles, 12 studies met the inclusion criteria. 17 risk factors were included in the meta-analysis. Male (RR 1.94, 95% CI 1.33 to 2.85, p<0.001), elder age (>60 years, RR 1.42, 95% CI 1.05 to 1.94, p=0.02), older RA onset age (RR 1.05, 95% CI 1.01 to 1.10, p=0.02), smoking (RR 1.37, 95% CI 1.09 to 1.71, p=0.006), lung complications (RR 2.72, 95% CI 1.24 to 5.95, p=0.01), rheumatoid nodule (RR 1.85, 95% CI 1.36 to 2.51, p<0.001), leflunomide usage (RR 1.41, 95% CI 1.02 to 1.96, p=0.04) were identified as risk factors of RA-ILD.

Conclusion: Physicians should be aware that patients with RA with the above risk factors are likely to develop RA-ILD, and perform close ILD screening during follow-ups so that the patients can be early diagnosed and treated, and achieve improved prognosis.

Introduction: The characteristics and clinical relevance of pleural effusion (PLEF) in acute pulmonary embolism (APE) are not fully understood.

Methods: A single-centre, retrospective study was performed of patients admitted with APE classified according to the subsequent development or not of PLEF. A model was built to predict PLEF and its impact on 30-day all-cause mortality was investigated.

Results: A total of 1602 patients with APE were included (median age, 74 (61, 82) years; 674 men (42.1%); 382 (23.8%) with PLEF). PLEF was associated with a higher number of comorbidities (p=0.015); more peripheral APE (0.001); a higher frequency of pulmonary infarctions (p<0.001) and higher 30-day all-cause mortality (p=0.004) compared with those without PLEF. Bilateral PLEFs, as compared with unilateral, were associated with a higher number of comorbidities (p=0.009); more severe (simplified Pulmonary Embolism Severity Index ≥1; p<0.001) and higher 30-day all-cause mortality (p<0.001).On multivariate analysis, the presence of PLEF was associated with atrial fibrillation (OR 2.00; 95% CI 1.32 to 3.02), congestive heart failure (OR 3.00; 95% CI 1.81 to 5.00), pulmonary infarction (OR 3.19; 95% CI 2.38 to 4.29) and a Charlson index ≥3 (OR 1.59; 95% CI 1.03 to 2.45). The predictive model for PLEF had a moderate power of discrimination (area under the curve, AUC 0.76; 95% CI 0.73 to 0.79), whereas the predictive model for mortality showed a good predictive power (AUC 0.89; 95% CI 0.86 to 0.93). The presence of PLEF doubles the probability of death (OR 2.02; 95% CI 1.11 to 3.68). When PLEF is bilateral, the probability of death is four times higher, as compared with unilateral PLEF (OR 4.07; 95% CI 1.53 to 10.85; AUC 0.90; 95% CI 0.84 to 0.95).

Conclusions: A significant number of APE patients develop PLEF. The model showed a good power of discrimination for the prediction of mortality. The probability of death from APE doubles in the presence of PLEF. Patients with APE and concomitant bilateral PLEF have a fourfold higher risk of mortality, as compared with patients with concomitant unilateral PLEF.

Purpose: Our research aimed to evaluate whether proto-oncogene serine/threonine-protein kinase Pim-1 (Pim1) inactivation could attenuate asthma by promoting runt-related transcription factor 3 (Runx3) expression and explore the underlying molecular mechanism.

Method: Phorbol 12-myristate 13-acetate (PMA, 50 nM) was used to induce inflammation in BEAS-2B human airway epithelial cells. ELISA and immunofluorescence double staining confirmed inflammation modelling and differential expression of Pim1 and Runx3. Pim1 inhibitor (SGI-1776) and Runx3 siRNA (siRunx3) were used in this study. Apoptosis, inflammation, MUC5AC protein expression, Pim1 kinase and Runx3 protein expression, and PI3K/AKT/nuclear factor-κB (NF-κB) pathway-associated protein expression were also assessed by flow cytometry, immunofluorescence and western blot. The effects of Pim1 inactivation on airway inflammation, pathological injury and mucus secretion in wild-type and Runx3 knockout mice were observed by in vivo experiments.

Results: The results of the in vitro experiments showed that PMA stimulation causes BEAS-2B cell apoptosis and promotes the MUC5AC expression. In addition, PMA stimulation activated the PI3K/AKT/NF-κB pathway. SGI-1776 treatment partially reversed these effects, whereas siRunx3 attenuated the effects of SGI-1776 on PMA-stimulated BEAS-2B cells. In vivo experiments showed that in Runx3-KO asthmatic mice, inhibition of Pim1 kinase had less effect on airway inflammation, pathological injury and mucus secretion. Meanwhile, Pim1 kinase expression was higher in Runx3-KO asthmatic mice than in wild-type asthmatic mice. Furthermore, inhibition of Pim1 kinase inhibited activation of the PI3K/AKT/NF-κB pathway, whereas these effects were attenuated in Runx3-KO mice.

Conclusion: Our results suggest that Pim1 inactivation can ameliorate airway inflammation and mucus hypersecretion through upregulation of Runx3 and the effect could be mediated through modulation of the PI3K/AKT/NF-κB pathway.

Objective: Five definitions of clinical instability have been published to assess the appropriateness and safety of discharging patients hospitalised for pneumonia. This study aimed to quantify the level of agreement between these definitions and estimate their discriminatory accuracy in predicting post-discharge adverse events.

Study design and setting: We conducted a retrospective cohort study involving 1038 adult patients discharged alive following hospitalisation for pneumonia.

Results: The prevalence of unstable criteria within 24 hours before discharge was 4.5% for temperature >37.8°C, 13.8% for heart rate >100/min, 1.0% for respiratory rate >24/min, 2.6% for systolic blood pressure <90 mm Hg, 3.3% for oxygen saturation <90%, 5.4% for inability to maintain oral intake and 6.4% for altered mental status. The percentage of patients classified as unstable at discharge ranged 12.8%-41.0% across different definitions (Fleiss Kappa coefficient, 0.47; 95% CI 0.44 to 0.50). Overall, 140 (13.5 %) patients experienced adverse events within 30 days of discharge, including 108 unplanned readmissions (10.4%) and 32 deaths (3.1%). Clinical instability was associated with a 1.3-fold to 2.0-fold increase in the odds of postdischarge adverse events, depending on the definition, with c-statistics ranging 0.54-0.59 (p=0.31).

Conclusion: Clinical instability was associated with higher odds of 30-day postdischarge adverse events according to all but one of the published definitions. This study supports the validity of definitions that combine vital signs, mental status and the ability to maintain oral intake within 24 hours prior to discharge to identify patients at a higher risk of postdischarge adverse events.

Introduction: Uzbekistan is one of the 30 countries with the highest tuberculosis (TB) morbidity, accounting for 87% of all cases globally. The incidence of TB in the Republic of Karakalpakstan (RK) remains consistently high in comparison with other regions of Uzbekistan. The incidence rates of TB strongly differ even among the regions within RK. In 2019, the highest rates were registered in the northern and north-western regions, and the lowest in the southern regions. An important issue is the extent to which specific residencies impact individual health. The ethnic composition of the population of RK can be one of the possible causes for such geographical heterogeneity in TB morbidity.

Methods and analysis: The case-control design of this study primarily aims to evaluate the role of ethnicity and residency on the development of active TB in the community living in RK. Additionally, the study aims to measure the association between factors of TB morbidity and ethnicity/residency in the community of RK. It was decided to include one matched control for every included case, to control potential confounders. Cases with clinically diagnosed or bacteriologically confirmed TB will be randomly sampled from the patient registry. Controls will comprise individuals without TB, living in RK at the same time as the cases. They will be randomly sampled from a general roster of the residents.

Ethics and dissemination: This study was approved by the Bioethics Committee of the Medical Association of Uzbekistan (approval report of meeting #1 on 18 January 2024). The results of this study will be widely disseminated at scientific meetings and conferences, and published in a peer-reviewed journal.

Introduction: Chronic obstructive pulmonary disease (COPD)/obstructive sleep apnoea (OSA) overlap syndrome (OVS) is associated with higher mortality compared with COPD alone in stable outpatients. However, the prognosis of patients hospitalised with acute hypercapnic respiratory failure (ARF) is unclear.

Methods: In this retrospective cohort study, 124 patients with COPD and 44 patients with OVS were treated with positive airway pressure (PAP) for ARF and followed up for a median of 20.6 months (IQR 3.80-53.4). Patients treated in the emergency or intensive care units and did not continue PAP on the wards were excluded. We compared patient characteristics and overall survival.

Results: Mean (SD) age of participants was 71 (9.7) years and 51% were males. Patients with OVS had a higher prevalence of hypertension (75% vs 50.0%, p=0.004) and type 2 diabetes mellitus (45.5% vs 19.4%, p<0.001). There was no difference in arterial pH or carbon dioxide levels at presentation. On univariate analysis, mortality was lower in OVS compared with patients with COPD alone (HR 0.57, 95% CI 0.37 to 0.87). Median survival was 51.0 (95% CI 38.1 to 93.7) months in OVS and 27.7 (95% CI 16.9 to 35.1) months in COPD alone. Median survival in OVS prescribed home PAP therapy was significantly higher (59.0 months) compared with OVS not discharged on therapy (36.1 months), and to patients with COPD, irrespective of home therapy prescription (p=0.022). After adjusting for multiple known confounders, patients with OVS still appeared to have lower mortality; however, this was no longer statistically significant (HR 0.75, 95% CI 0.45 to 1.24).

Discussion: We found that patients with COPD and ARF requiring non-invasive ventilation may have higher mortality rates compared with patients with OVS. Patients with OVS treated with home PAP had lower mortality compared with patients not prescribed PAP on discharge. These findings suggest that patients with COPD who present with ARF may benefit from early diagnosis of OSA and initiation of long-term PAP therapy.

Background: Chronic respiratory diseases (CRDs) affect at least 545 million people globally, leading to symptoms such as dyspnoea, fatigue and limited physical activity. Pulmonary rehabilitation (PR) programmes aim to improve the exercise capacity and quality of life of patients with CRD through exercise training. High-flow nasal cannula (HFNC) therapy shows potential as an adjunct treatment during exercise, but its effects on CRD populations are unclear. The purpose of this systematic review was to evaluate the effects of HFNC during exercise in people with CRD.

Methods: A systematic review was conducted and eight databases and other resources were searched from inception (28 June 2022) to 4 April 2023. Studies that used adult patients with CRD and randomised controlled trial that compared the effect of HFNC versus standard care (conventional oxygen therapy or room air) during exercise were included. Two authors independently selected trials, extracted the data, assessed risks of bias and employed the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach to judging the certainty of evidence. We pooled trials using random-effect models and inverse variance estimation.

Results: Seventeen studies (n=8406) were included in the review (570 patients). The evidence suggests that HFNC increases exercise time after multiple training sessions (weighted mean difference (WMD)=160.58 s; 95% 95% CI=67.32-253.83, 2 studies) and increase after a single session (WMD=72.10 s; 95% CI=28.95-115.24, 11 studies). HFNC may result in little improvements in secondary outcomes (quality of life, dyspnoea, comfort, complications and adherence).

Discussion: The evidence suggests that HFNC may increase functional exercise capacity and positively enhance secondary outcomes. Continued research is justified to elucidate the role of HFNC in PR during exercise training.

Prospero registration number: CRD42022336263.

Introduction: A wide range of recent ventilators, dedicated or not, is available for non-invasive ventilation (NIV) in respiratory or intensive care units (ICU). We conducted a bench study to compare their technical performances.

Methods: Ventilators, including five ICU ventilators with NIV mode on, two dedicated NIV ventilators and one transport ventilator, were evaluated on a test bench for NIV, consisting of a 3D manikin head connected to an ASL 5000 lung model via a non-vented mask. Ventilators were tested according to three simulated lung profiles (normal, obstructive, restrictive), three levels of simulated air leakage (0, 15, 30 L/min), two levels of pressure support (8, 14 cmH₂O) and two respiratory rates (15, 25 cycles/min).

Results: The global median Asynchrony Index (AI) was higher with ICU ventilators than with dedicated NIV ventilators (4% (0; 76) vs 0% (0; 15), respectively; p<0.05) and different between all ventilators (p<0.001). The AI was higher with ICU ventilators for the normal and restrictive profiles (p<0.01) and not different between ventilators for the obstructive profile. Auto-triggering represented 43% of all patient-ventilator asynchrony. Triggering delay, cycling delay, inspiratory pressure-time product, pressure rise time and pressure at mask were different between all ventilators (p<0.01). Dedicated NIV ventilators induced a lower pressure-time product than ICU and transport ventilators (p<0.01). There was no difference between ventilators for minute ventilation and peak flow.

Conclusion: Despite the integration of NIV algorithms, most recent ICU ventilators appear to be less efficient than dedicated NIV ventilators. Technical performances could change, however, according to the underlying respiratory disease and the level of air leakage.

Objectives: Responding to prior research findings that lack of knowledge about their disease impacted patients' quality of life, the objective of this study was to identify and prioritise information gaps about hypersensitivity pneumonitis (HP) from the perspective of patients living with the disease.

Design: This study used the nominal group technique, a semiquantitative and qualitative method to identify stakeholder priorities.

Setting: Virtual group sessions were conducted in an academic medical centre in the USA.

Participants: 21 patients diagnosed with HP participated in this study. Participants were eligible if they spoke English and had access to the internet and were excluded if they had cognitive impairment.

Results: The patient statements were grouped into seven themes that were prioritised by participants in the following order: (1) natural history and prognosis; (2) current treatment options and therapeutic research; (3) epidemiology and aetiology of HP; (4) living well with HP; (5) origin and management of symptoms; (6) identifying and mitigating exposures and (7) methods of educating patients, clinicians and others about HP.

Conclusions: This study provides an understanding of patients' prioritisation of knowledge gaps in HP to inform targeted educational interventions and provide avenues for future research.