Thorax最新文献

Rationale/objectives: Despite plausible pathophysiological mechanisms, research is needed to confirm the relationship between sleep, circadian rhythm and delirium in patients admitted to the intensive care unit (ICU). The objective of this review is to summarise existing studies promoting, in whole or in part, the normalisation of sleep and circadian biology and their impact on the incidence, prevalence, duration and/or severity of delirium in ICU.

Methods: A sensitive search of electronic databases and conference proceedings was completed in March 2023. Inclusion criteria were English-language studies of any design that evaluated in-ICU non-pharmacological, pharmacological or mixed intervention strategies for promoting sleep or circadian biology and their association with delirium, as assessed at least daily. Data were extracted and independently verified.

Results: Of 7886 citations, we included 50 articles. Commonly evaluated interventions include care bundles (n=20), regulation or administration of light therapy (n=5), eye masks and/or earplugs (n=5), one nursing care-focused intervention and pharmacological intervention (eg, melatonin and ramelteon; n=19). The association between these interventions and incident delirium or severity of delirium was mixed. As multiple interventions were incorporated in included studies of care bundles and given that there was variable reporting of compliance with individual elements, identifying which components might have an impact on delirium is challenging.

Conclusions: This scoping review summarises the existing literature as it relates to ICU sleep and circadian disruption (SCD) and delirium in ICU. Further studies are needed to better understand the role of ICU SCD promotion interventions in delirium mitigation.

Background: Silicosis, a chronic respiratory disease caused by crystalline silica exposure, is a persistent global lung health issue. No systematic review of the relationship between cumulative respirable crystalline silica (RCS) exposure and silicosis exists. UK exposure limits are currently under review. We therefore performed a systematic review and dose-response meta-analysis of this relationship.

Methods: Web of Science, Medline and Embase were searched on 24 February 2023. Studies of radiographic, autopsy or death certificate silicosis, with an estimated average follow-up of over 20 years since first employment, were included. Cumulative silicosis risk methods were compared. The relative risks (RR) of silicosis at increasing cumulative exposures were calculated and used to estimate the absolute risk reduction (ARR).

Results: Eight eligible studies, including 10 cohorts, contributed 8792 cases of silicosis among 65 977 participants. Substantial differences in cumulative risk estimates between methodologies exist. Using the same method, we observed higher cumulative silicosis risks among mining compared with non-mining cohorts. A reduction from 4 to 2 mg/m³-years in cumulative RCS exposure corresponded to substantial risk reductions among miners (RR 0.23 (95% CI 0.18 to 0.29, I²=92.9%) with an ARR of 323 (95% CI 298 to 344) per 1000) and non-miners (RR 0.55 (95% CI 0.36 to 0.83, I²=77.0%) with an ARR of 23 (95% CI 9 to 33) per 1000).

Conclusion: Despite significant heterogeneity, our findings support a reduction in permissible exposure limits from 0.1 mg/m³ to 0.05 mg/m³, particularly among mining populations. Further research is needed among non-miners as only two studies were eligible.

Background: Antenatal factors and environmental exposures contribute to recurrent wheezing in early childhood.

Aim: To identify antenatal and environmental factors associated with recurrent wheezing in children from birth to 48 months in the mother and child in the environment cohort, using time-to-event analysis.

Method: Maternal interviews were administered during pregnancy and postnatally and children were followed up from birth to 48 months (May 2013-October 2019). Hybrid land-use regression and dispersion modelling described residential antenatal exposure to nitrogen dioxide (NO₂) and particulate matter of 2.5 µm diameter (PM_2.5). Wheezing status was assessed by a clinician. The Kaplan-Meier hazard function and Cox-proportional hazard models provided estimates of risk, adjusting for exposure to environmental tobacco smoke (ETS), maternal smoking, biomass fuel use and indoor environmental factors.

Results: Among 520 mother-child pairs, 85 (16%) children, had a single wheeze episode and 57 (11%) had recurrent wheeze. Time to recurrent wheeze (42.9 months) and single wheeze (37.8 months) among children exposed to biomass cooking fuels was significantly shorter compared with children with mothers using electricity (45.9 and 38.9 months, respectively (p=0.03)). Children with mothers exposed to antenatal ETS were 3.8 times more likely to have had recurrent wheeze compared with those not exposed (adjusted HR 3.8, 95% CI 1.3 to 10.7). Mean birth month NO₂ was significantly higher among the recurrent wheeze category compared with those without wheeze. NO₂ and PM_2.5 were associated with a 2%-4% adjusted increased wheezing risk.

Conclusion: Control of exposure to ETS and biomass fuels in the antenatal period is likely to delay the onset of recurrent wheeze in children from birth to 48 months.

Introduction: Asthma is an inflammatory airways disease encompassing multiple phenotypes and endotypes. Several studies suggested gene expression in nasal epithelium to serve as a proxy for bronchial epithelium, being a non-invasive approach to investigate lung diseases. We hypothesised that molecular differences in upper airway epithelium reflect asthma-associated differences in the lower airways and are associated with clinical expression of asthma.

Methods: We analysed nasal epithelial gene expression data from 369 patients with asthma and 58 non-asthmatic controls from the Assessment of Small Airways Involvement in Asthma study. Unsupervised hierarchical clustering was performed on asthma-associated genes. Asthma-associated gene signatures were replicated in independent cohorts with nasal and bronchial brushes data by comparing Gene Set Variation Analysis scores between asthma patients and non-asthmatic controls.

Results: We identified 67 higher expressed and 59 lower expressed genes in nasal epithelium from asthma patients compared with controls (false discovery rate<0.05), including CLCA1, CST1 and POSTN, genes well known to reflect asthma in bronchial airway epithelium. Hierarchical clustering revealed several molecular asthma endotypes with distinct clinical characteristics, including an endotype with higher blood and sputum eosinophils, high fractional exhaled nitric oxide, and more severe small airway dysfunction, as reflected by lower forced expiratory flow at 50%. In an independent cohort, we demonstrated that genes higher expressed in the nasal epithelium reflect asthma-associated changes in the lower airways.

Conclusion: Our results show that the nasal epithelial gene expression profile reflects asthma-related processes in the lower airways. We suggest that nasal epithelium may be a useful non-invasive tool to identify asthma endotypes and may advance personalised management of the disease.

Rationale: Early natural menopause (early-M; <45 years of age) increases the risk of lung morbidities and mortalities in smokers. However, it is largely unknown whether early-M due to surgery demonstrates similar effects and whether menopausal hormone therapy (MHT) is protective against lung diseases.

Objectives: To assess the associations of early-M and MHT with lung morbidities and mortalities using the prospective Prostate, Lung, Colorectal and Ovarian (PLCO) trial.

Methods: We estimated the risk among 69 706 postmenopausal women in the PLCO trial, stratified by menopausal types and smoking status.

Results: Early-M was associated with an increased risk of most lung disease and mortality outcomes in ever smokers with the highest risk seen for respiratory mortality (HR 1.98, 95% CI 1.34 to 2.92) in those with bilateral oophorectomy (BO). Early-M was positively associated with chronic bronchitis, and all-cause, non-cancer and respiratory mortality in never smokers with natural menopause or BO, with the highest risk seen for BO- respiratory mortality (HR 1.91, 95% CI 1.16 to 3.12). Ever MHT was associated with reduced all-cause, non-cancer and cardiovascular mortality across menopause types regardless of smoking status and was additionally associated with reduced risk of non-ovarian cancer, lung cancer (LC) and respiratory mortality in ever smokers. Among smokers, ever MHT use was associated with a reduction in HR for all-cause, non-cancer and cardiovascular mortality in a duration-dependent manner.

Conclusions: Smokers with early-M should be targeted for smoking cessation and LC screening regardless of menopause types. MHT users had a lower likelihood of dying from LC and respiratory diseases in ever smokers.