The latest medical research on Respiratory Medicine

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about respiratory medicine gathered by our medical AI research bot.

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Impact and timing of pulmonary rehabilitation in patients undergoing bronchoscopic lung volume reduction with endobronchial valves: A multicentre randomized controlled trial in patients with severe emphysema.

Respirology

Both bronchoscopic lung volume reduction with endobronchial valves (BLVR-EBV) and pulmonary rehabilitation (PR) are effective treatments for improving exercise capacity and patient-reported outcomes in patients with severe Chronic Obstructive Pulmonary Disease (COPD). According to current recommendations, all BLVR-EBV patients should have undergone PR first. Our aim was to study the effects of PR both before and after BLVR-EBV compared to BLVR-EBV alone.

We included patients with severe COPD who were eligible for BLVR-EBV and PR. Participants were randomized into three groups: PR before BLVR-EBV, PR after BLVR-EBV or BLVR-EBV without PR. The primary outcome was change in constant work rate cycle test (CWRT) endurance time at 6-month follow-up of the PR groups compared to BLVR-EBV alone. Secondary endpoints included changes in 6-minute walking test, daily step count, dyspnoea and health-related quality of life.

Ninety-seven participants were included. At 6-month follow-up, there was no difference in change in CWRT endurance time between the PR before BLVR-EBV and BLVR-EBV alone groups (median: 421 [IQR: 44; 1304] vs. 787 [123; 1024] seconds, p = 0.82) or in any of the secondary endpoints, but the PR after BLVR-EBV group exhibited a smaller improvement in CWRT endurance time (median: 107 [IQR: 2; 573], p = 0.04) and health-related quality of life compared to BLVR-EBV alone.

The addition of PR to BLVR-EBV did not result in increased exercise capacity, daily step count or improved patient-reported outcomes compared to BLVR-EBV alone, neither when PR was administered before BLVR-EBV nor when PR was administered after BLVR-EBV.

Predictors of lung function in early adulthood: A population-based cohort study.

Respirology

Lung function reaches a peak/plateau in early adulthood before declining with age. Lower early adult lung function may increase the risk for chronic obstructive pulmonary disease (COPD) in mid-late adult life. Understanding the effects of multiple childhood/adolescent exposures and their potential interactions on plateau lung function would provide insights into the natural history of COPD.

Longitudinal spirometry data from 688 participants with complete data from a population-based birth cohort (original n = 1037) were used to investigate associations between a wide range of childhood/adolescent exposures and repeated measures of FEV1, FVC and FEV1/FVC during the early-adult plateau phase. Generalized estimating equations were used to accommodate the multiple timepoints per participant.

FEV1 reached a peak/plateau between ages 18 and 26 and FVC from 21 to 32 years, whereas FEV1/FVC declined throughout early adulthood. Childhood asthma and airway hyperresponsiveness were associated with lower early adult FEV1 and FEV1/FVC. Smoking by age 18 was associated with lower FEV1/FVC. Higher BMI during early adulthood was associated with lower FEV1 and FVC and lower FEV1/FVC. Physical activity during adolescence was positively associated with FEV1 and FEV1/FVC but this was only statistically significant in men. There was no convincing evidence of interactions between exposures.

Childhood asthma and airway hyperresponsiveness are associated with lower lung function in early adulthood. Interventions targeting these may reduce the risk of COPD in mid-late adult life. Promotion of physical activity during adolescence, prevention of cigarette smoking and maintenance of a healthy body weight in early adulthood are also priorities.

Impact of age at ivacaftor initiation on pulmonary outcomes among people with cystic fibrosis.

Thorax

Ivacaftor (IVA) improves lung function and other extrapulmonary outcomes in people with cystic fibrosis (CF). However, the effect of initiating IVA at earlier versus later ages has not been studied.

We conducted an observational cohort study of people in the US CF Foundation Patient Registry aged ≥6 years with ≥1 CF transmembrane conductance regulator-gating mutation to compare the effects of initiating IVA at earlier ages on per cent predicted forced expiratory volume in 1 s (ppFEV1) and pulmonary exacerbation (PEx) outcomes. People with CF were grouped by age at IVA initiation (ages 6-10, 11-15, 16-20 and 21-25 years) to perform three analyses of younger versus older IVA initiation (6-10 vs 11-15, 11-15 vs 16-20 and 16-20 vs 21-25 years). For each analysis, baseline characteristics assessed over 1-year periods at the same age prior to IVA initiation were balanced by standardised mortality/morbidity ratio (SMR) weighting. For each analysis, outcomes were compared over a 5-year outcome assessment period when both groups were in the same age range and receiving IVA.

Baseline characteristics were well balanced between younger and older IVA initiator groups after SMR weighting. In the outcome assessment period, younger IVA initiators had significantly higher mean ppFEV1 than older initiators across all comparisons, and those initiating IVA between ages 6-10 and 11-15 years had significantly lower PEx rates.

Study findings showed the importance of early IVA initiation in people with CF.

Interstitial Lung Disease Associated with Systemic Sclerosis.

Seminars in Respiratory & Critical Care

Systemic sclerosis (SSc) is a rare autoimmune disease characterized by a tripod combining vasculopathy, fibrosis, and immune-mediated inflammatory ...

The fix is not yet in: recommendation for fixation of lungs within physiologic/pathophysiologic volume range in preclinical pulmonary structure-function studies.

Am J Physiol

Quantitative characterization of lung structures by morphometric or stereologic analysis of histologic sections is a powerful means of elucidating ...

Elastin-derived peptides favor type 2 innate lymphoid cells in COPD.

Am J Physiol

Chronic obstructive pulmonary disease (COPD) is a condition characterized by chronic airway inflammation and obstruction, primarily caused by tobac...

Review of Pulmonary Manifestations in Antisynthetase Syndrome.

Seminars in Respiratory & Critical Care

Antisynthetase syndrome (ASyS) is now a widely recognized entity within the spectrum of idiopathic inflammatory myopathies. Initially described in ...

Prevalence and burden of difficult-to-treat and severe asthma in Australia: A national population survey.

Respirology

Most evidence about difficult-to-treat and severe asthma (DTTA) comes from clinical trials and registries. We aimed to identify people with DTTA from a large nationally representative asthma population and describe their characteristics and healthcare utilization compared with people whose asthma was not 'difficult-to-treat'.

We conducted a cross-sectional survey of Australians aged ≥18 years with current asthma from large web-based survey panels. Enrolment was stratified by gender, age-group and state/territory based on national population data for people with asthma. Difficult-to-treat or severe asthma was defined by poor symptom control, exacerbations and/or oral corticosteroid/biologic use despite medium/high-dose inhaled therapy. Outcomes included exacerbations, healthcare utilization, multimorbidity, quality of life and coronavirus disease of 2019 (COVID-19)-related behaviour. Weighted data were analysed using SAS version 9.4.

The survey was conducted in February-March 2021. The weighted sample comprised 6048 adults with current asthma (average age 47.3 ± SD 18.1 years, 59.9% female), with 1313 (21.7%) satisfying ≥1 DTTA criteria. Of these, 50.4% had very poorly controlled symptoms (Asthma Control Test ≤15), 36.2% were current smokers, and 85.4% had ≥1 additional chronic condition, most commonly anxiety/depression. More than twice as many participants with DTTA versus non-DTTA had ≥1 urgent general practitioner (GP) visit (61.4% vs. 27.5%, OR 4.8 [4.2-5.5, p < 0.0001]), or ≥1 emergency room visit (41.9% vs. 17.9%, OR 3.8 [3.3-4.4, p < 0.0001]) in the previous 12 months.

Our findings emphasize the burden of uncontrolled symptoms, current smoking, multimorbidity and healthcare utilization in people with DTTA in the community, who may be under-represented in registries or clinical trials.

Epigenome-wide association study of lung cancer among never smokers in two prospective cohorts in Shanghai, China.

Thorax

The aetiology of lung cancer among individuals who never smoked remains elusive, despite 15% of lung cancer cases in men and 53% in women worldwide being unrelated to smoking. Epigenetic alterations, particularly DNA methylation (DNAm) changes, have emerged as potential drivers. Yet, few prospective epigenome-wide association studies (EWAS), primarily focusing on peripheral blood DNAm with limited representation of never smokers, have been conducted.

We conducted a nested case-control study of 80 never-smoking incident lung cancer cases and 83 never-smoking controls within the Shanghai Women's Health Study and Shanghai Men's Health Study. DNAm was measured in prediagnostic oral rinse samples using Illumina MethylationEPIC array. Initially, we conducted an EWAS to identify differentially methylated positions (DMPs) associated with lung cancer in the discovery sample of 101 subjects. The top 50 DMPs were further evaluated in a replication sample of 62 subjects, and results were pooled using fixed-effect meta-analysis.

Our study identified three DMPs significantly associated with lung cancer at the epigenome-wide significance level of p<8.22×10-8. These DMPs were identified as cg09198866 (MYH9; TXN2), cg01411366 (SLC9A10) and cg12787323. Furthermore, examination of the top 1000 DMPs indicated significant enrichment in epithelial regulatory regions and their involvement in small GTPase-mediated signal transduction pathways. Additionally, GrimAge acceleration was identified as a risk factor for lung cancer (OR=1.19 per year; 95% CI 1.06 to 1.34).

While replication in a larger sample size is necessary, our findings suggest that DNAm patterns in prediagnostic oral rinse samples could provide novel insights into the underlying mechanisms of lung cancer in never smokers.

Lung function trajectories from school age to adulthood and their relationship with markers of cardiovascular disease risk.

Thorax

Lung function in early adulthood is associated with subsequent adverse health outcomes.

To ascertain whether stable and reproducible lung function trajectories can be derived in different populations and investigate their association with objective measures of cardiovascular structure and function.

Using latent profile modelling, we studied three population-based birth cohorts with repeat spirometry data from childhood into early adulthood to identify trajectories of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC). We used multinomial logistic regression models to investigate early-life predictors of the derived trajectories. We then ascertained the extent of the association between the derived FEV1/FVC trajectories and blood pressure and echocardiographic markers of increased cardiovascular risk and stroke in ~3200 participants at age 24 years in one of our cohorts.

We identified four FEV1/FVC trajectories with strikingly similar latent profiles across cohorts (pooled N=6377): above average (49.5%); average (38.3%); below average (10.6%); and persistently low (1.7%). Male sex, wheeze, asthma diagnosis/medication and allergic sensitisation were associated with trajectories with diminished lung function in all cohorts. We found evidence of an increase in cardiovascular risk markers ascertained by echocardiography (including left ventricular mass indexed to height and carotid intima-media thickness) with decreasing FEV1/FVC (with p values for the mean crude effects per-trajectory ranging from 0.10 to p<0.001). In this analysis, we considered trajectories as a pseudo-continuous variable; we confirmed the assumption of linearity in all the regression models.

Childhood lung function trajectories may serve as predictors in the development of not only future lung disease, but also the cardiovascular disease and multimorbidity in adulthood.

Incidence, prevalence and mortality of idiopathic pulmonary fibrosis in England from 2008 to 2018: a cohort study.

Thorax

Owing to discrepancies in methodologies and how idiopathic pulmonary fibrosis (IPF) is diagnosed it is challenging to establish a consistent understanding of the disease burden In the UK, over 10 years ago, the incidence and prevalence of IPF were reported as 2.8-8.7 per 100 000 person-years (from 2000 to 2012) and 39 per 100 000 persons (in 2012), respectively. Here, we estimated the incidence and prevalence of IPF in England from 2008 to 2018 and investigated IPF mortality.

Using Clinical Practice Research Datalink Aurum and Hospital Episode Statistics (HES) linked datasets, we estimated incidence and prevalence using four validated diagnostic-code-based algorithms. Using the registered number of deaths (from Office of National Statistics) with the underlying cause being recorded as IPF, we estimated IPF mortality for the same period.

Using Aurum-based definitions, incidence increased over time by 100% for Aurum narrow (3-6.1 per 100 000 person-years) and by 25% for Aurum broad (22.4-28.6 per 100 000 person-years). However, using HES-based definitions showed a decrease in incidence over the same period and lay between the two extremes derived for Aurum-based definition. IPF mortality in 2018 was 7.9 per 100 000 person-years and increased by 53% between 2008 and 2018.

When using best-case definitions, incidence rose throughout the study period. Scaling this to England's population (2018), our best estimate would be in the range of 8000-9000 new cases per year which is higher than previously reported estimates (5000-6000). This increased burden in the new cases of IPF each year impacts future health service planning and resource allocation.

Treatment with inhaled aerosolised ethanol reduces viral load and potentiates macrophage responses in an established influenza mouse model.

Exp Lung Res

Treatment options for viral lung infections are currently limited. We aimed to explore the safety and efficacy of inhaled ethanol in an influenza-infection mouse model.

In a safety and tolerability experiment, 80 healthy female BALB/c mice (20 per group) were exposed to nebulized saline (control) or three concentrations of ethanol (40/60/80% ethanol v/v in water) for 3x30-minute periods, with a two-hour break between exposures. In a separate subsequent experiment, 40 Female BALB/c mice were nasally inoculated with 104.5 plaque-forming units of immediate virulence "Mem71" influenza. Infection was established for 48-h before commencing treatment in 4 groups of 10 mice with either nebulized saline (control) or one of 3 different concentrations of ethanol (40/60/80% ethanol v/v in water) for 3x30-minute periods daily over three consecutive days. In both experiments, mouse behavior, clinical scores, weight change, bronchoalveolar lavage cell viability, cellular composition, and cytokine levels, were assessed 24-h following the final exposure, with viral load also assessed after the second experiment.

In uninfected BALB/c mice, 3x30-minute exposures to nebulized 40%, 60%, and 80% ethanol resulted in no significant differences in mouse weights, cell counts/viability, cytokines, or morphometry measures. In Mem71-influenza infected mice, we observed a dose-dependent reduction in viral load in the 80%-treated group and potentiation of macrophage numbers in the 60%- and 80%-treated groups, with no safety concerns.

Our data provides support for inhaled ethanol as a candidate treatment for respiratory infections.