Risk Of Exacerbations Research Articles

Translation speed slowdown and poleward migration of western North Pacific tropical cyclones

Detecting and interpreting long-term changes in typhoon translation speed in observations remains challenging, contrasting with increased confidence in the poleward migration of typhoons. Here, I show a significant relationship between the basin-wide translation speed and the latitudinal position of tropical cyclones in the western North Pacific over 1980–2023. First, because tropical cyclones move faster at higher latitudes, the significant poleward migration (80 km/decade) increases the yearly basin-wide translation speed by 5% over the period. This effect reduces the detectability of a slowing trend. Second, the basin-wide translation speed solely contributed by regional translation speed has slowed by 18%, mostly in the late stage of the cyclone lifecycle. The translation speed slowdown and the poleward migration are likely caused by the same climate drivers through the interconnected large-scale atmospheric circulation between the tropics and subtropics. My findings suggest exacerbated tropical cyclone-related risk in the subtropical regions in a changing climate.

DElaying disease Progression In COPD with early escalation to Triple therapy – A Modelling Study (DEPICT-2)

IntroductionIn patients with chronic obstructive pulmonary disease (COPD), dual bronchodilator (long-acting muscarinic antagonist (LAMA)/long-acting beta2-agonist (LABA)) and triple therapy (inhaled corticosteroid (ICS)/LAMA/LABA) reduce risk of exacerbations and lung function decline in short-mid-term, but their long-term impact is unknown. This modelling study explores long-term impact of these therapies on lung function decline, quality of life (QoL) and all-cause mortality.MethodsThis modelling approach used a longitudinal non-parametric superposition model using published data regarding exacerbations, QoL (assessed by St. George's Respiratory Questionnaire (SGRQ)), and mortality. The model simulated disease progression from 40 to 75 years of age and assessed the impact of initiating dual bronchodilator at age 45 years (“LAMA/LABA only” group) and escalation to triple therapy at age 50 years (“Escalation to triple” group) on forced expiratory volume in 1 s (FEV1) decline, QoL, and mortality.ResultsModel simulation predicted that by 75 years of age: “LAMA/LABA only” preserves 159.1 mL of FEV1versusno treatment, “Escalation to triple” preserves an additional 376.5 mL and 217.3 mL of FEV1versusno pharmacotherapy and “LAMA/LABA only”, respectively. In “LAMA/LABA only”, SGRQ score reduces (−3.2)versusno treatment, which further reduces to −7.5 therapy in “Escalation to triple”. In “LAMA/LABA only”, mortality reduces by 5.4% by 75 yearsversusno treatment, while the “Escalation to triple” shows further decrease in mortality by 12.0%.ConclusionEarly pharmacotherapy initiation and escalation from dual bronchodilator to triple therapy could slow disease progression by preserving lung function and improving QoL and survival in patients with COPD.

Multivariate time series approaches to extract predictive asthma biomarkers from prospectively patient-collected diary data: a systematic review

ObjectivesLongitudinal data are common in asthma studies, to assess asthma progression in patients and identify predictors of future outcomes, including asthma exacerbations and asthma control. Different methods can quantify temporal...

The clinical impacts of lung microbiome in bronchiectasis with fixed airflow obstruction: a prospective cohort study

BackgroundAirflow obstruction is a hallmark of disease severity and prognosis in bronchiectasis. The relationship between lung microbiota, airway inflammation, and outcomes in bronchiectasis with fixed airflow obstruction (FAO) remains unclear. This study explores these interactions in bronchiectasis patients, with and without FAO, and compares them to those diagnosed with chronic obstructive pulmonary disease (COPD).MethodsThis prospective observational study in Taiwan enrolled patients with either bronchiectasis or COPD. To analyze the lung microbiome and assess inflammatory markers, bronchoalveolar lavage (BAL) samples were collected for 16S rRNA gene sequencing. The study cohort comprised 181 patients: 86 with COPD, 46 with bronchiectasis, and 49 with bronchiectasis and FAO, as confirmed by spirometry.ResultsPatients with bronchiectasis, with or without FAO, had similar microbiome profiles characterized by reduced alpha diversity and a predominance of Proteobacteria, distinctly different from COPD patients who exhibited more Firmicutes, greater diversity, and more commensal taxa. Furthermore, compared to COPD and bronchiectasis without FAO, bronchiectasis with FAO showed more severe disease and a higher risk of exacerbations. A significant correlation was found between the presence of Pseudomonas aeruginosa and increased airway neutrophilic inflammation such as Interleukin [IL]-1β, IL-8, and tumor necrosis factor-alpha [TNF]-α, as well as with higher bronchiectasis severity, which might contribute to an increased risk of exacerbations. Moreover, in bronchiectasis patients with FAO, the ROSE (Radiology, Obstruction, Symptoms, and Exposure) criteria were employed to classify individuals as either ROSE (+) or ROSE (−), based on smoking history. This classification highlighted differences in clinical features, inflammatory profiles, and slight microbiome variations between ROSE (−) and ROSE (+) patients, suggesting diverse endotypes within the bronchiectasis with FAO group.ConclusionBronchiectasis patients with FAO may exhibit two distinct endotypes, as defined by ROSE criteria, characterized by greater disease severity and a lung microbiome more similar to bronchiectasis without FAO than to COPD. The significant correlation between Pseudomonas aeruginosa colonization and increased airway neutrophilic inflammation, as well as disease severity, underscores the clinical relevance of microbial patterns. This finding reinforces the potential role of these patterns in the progression and exacerbations of bronchiectasis with FAO.

Breath and Sputum Analyses in Asthmatic Patients: An Overview.

Recent advancements in asthma management include non-invasive methodologies such as sputum analysis, exhaled breath condensate (EBC), and fractional exhaled nitric oxide (FeNO). These techniques offer a means to assess airway inflammation, a critical feature of asthma, without invasive procedures. Sputum analysis provides detailed insights into airway inflammation patterns and cellular composition, guiding personalized treatment strategies. EBC collection, reflecting bronchoalveolar lining fluid composition, provides a non-invasive window into airway physiology. FeNO emerges as a pivotal biomarker, offering insights into eosinophilic airway inflammation and aiding in asthma diagnosis, treatment monitoring, and the prediction of exacerbation risks. Despite inherent limitations, each method offers valuable tools for a more comprehensive assessment of asthma. Combining these techniques with traditional methods like spirometry may lead to more personalized treatment plans and improved patient outcomes. Future research is crucial to refine protocols, validate biomarkers, and establish comprehensive guidelines in order to enhance asthma management with tailored therapeutic strategies and improved patient outcomes.

Blood Transcriptomic and Inflammatory Protein Biomarkers Associated with Imminent Pulmonary Exacerbation Risk in Cystic Fibrosis.

The factors that lead to poor pulmonary exacerbation (PEx) outcomes in individuals with cystic fibrosis (CF) are still being investigated; however, delayed diagnosis and treatment are likely contributory. Identifying individuals at imminent risk of PEx could enable closer monitoring and/or earlier initiation of therapies to improve outcomes. The goal of this study was to develop blood-based biomarkers that associate with imminent PEx risk in CF individuals. We examined the whole blood transcriptome and 55 inflammatory proteins from plasma and serum on 72 blood samples from 53 CF individuals. Biomarker candidate genes and proteins were selected from 14 CF individuals with paired stable and PEx visits (Cohort 1). The biomarker candidates were then estimated and tested to classify CF individuals who would experience a PEx within 4-months of a stable clinic visit or not (Cohort 2). A 16-gene panel and 9-protein panel were identified that could distinguish paired stable and PEx visits (AUC = 0.83 ± SE 0.28 and AUC = 0.92 ± SE 0.18, respectively). These two panels also demonstrated strong performance in classifying CF individuals who would experience a PEx within 4 months of a clinically stable visit or not (16-gene panel: AUC = 0.88; 9-protein panel: AUC = 0.83). In comparison, serum calprotectin and clinical variables (i.e. sex, ppFEV1, and the number of IV antibiotics in the preceding year) had AUCs of 0.75 and 0.71, respectively. Blood-based mRNA and protein biomarkers demonstrated strong performance in classifying CF individuals at risk of imminent PEx. If the findings from this study can be validated, there is the potential to use blood biomarkers to enable more personalized disease activity monitoring in CF.

Chinese expert consensus on treatment and management of chronic obstructive pulmonary disease combined with pneumoconiosis

Chronic obstructive pulmonary disease (COPD) often co-exists with other diseases (comorbidities), of which pneumoconiosis is an important one. The interaction between pneumoconiosis and COPD is manifested in the risk of disease, severity of disease, risk of acute exacerbation and the disease progression, and pharmaceutical and non-pharmaceutical treatment options. At present, there is a general lack of understanding of COPD complications in clinical practice, and there is a lack of clear clinical guidance for diagnosis and management of COPD patients with pneumoconiosis. Based on clinical evidence and experience, and the writing group puts forward five recommendations to improve the recognition and management of COPD patients with pneumoconiosis for medical professionals in hospitals at different levels, particularly in primary medical institutions.

A narrative review of factors affecting the welfare of dairy cows in larger Australasian pasture-based production systems

On the basis of current growth trajectories, pasture-based dairies of the future are likely to be bigger, have higher stocking rates and feed more concentrate to cows. This review uses the five-domains framework to consider risks to the welfare of dairy cows in these larger intensified pasture-based production systems. The factors considered in this review can be broadly categorised as (1) emerging welfare risks that can be managed, (2) emerging welfare risks that require research to be managed, or (3) persisting and/or exacerbated welfare risks. First, large herds could be subject to welfare risks associated with more stock per labour unit, longer milking times and longer distances walked to and from the dairy. To counter this, the time that cows in large herds spend off pasture can be reduced by splitting the herd into several more manageable groups, and animal-monitoring technologies can help identify health challenges with a reduced stockperson to animal ratio. Cow body condition and productivity can be maintained at high stocking rates by improving pasture production and feeding a higher proportion of concentrate. The risk of ruminal acidosis may then be reduced by appropriate transition feeding regimes and rumen buffers. Second, ensuring social stability and reducing competition may become difficult as herd sizes increase and feeding becomes more intensive. The resulting variability in feed intake, increased agonistic behaviour and social stress present emerging risks to cow welfare. Research is needed to better understand the social behaviour of cows in large intensive pasture-based herds, and how the design of the pre-milking area, the feeding pad and pasture feeding regimes (i.e. quantity and timing of pasture allocation) can improve accessibility for more vulnerable animals. Finally, intensive pasture-based dairies of the future will continue to face welfare challenges relating to lameness, mastitis and cull-cow management, whereas risks due to environmental exposure may be exacerbated by the removal of shelterbelts to facilitate irrigation. These require continued efforts in research (e.g. ways of incorporating shelter into intensive grazing systems), development (e.g. pathway to market for aged beef) and extension (e.g. improved record keeping and benchmarking of lameness and mastitis).

AM/PM dosing of LAMA for COPD: a randomized controlled trial protocol using digital recruitment and registries.

Long-acting muscarinic antagonists (LAMAs) reduce the risk of acute exacerbations of chronic obstructive pulmonary disease (AECOPD), usually taken once daily in the morning. However, the circadian activity of autonomic regulation suggests that the highest need for anticholinergic therapy may be in the late night/early morning. This is supported by evidence that AECOPD most often begins in the morning. Furthermore, the trough spirometry effect of LAMA is lower than the peak effect, which further argues that evening dosing may be more optimal than morning dosing. This trial aims to determine whether evening administration of LAMA reduces hospitalization-requiring AECOPD or death from all causes within 1 year as compared to morning administration of the same LAMA. Randomized controlled open-label trial. Persons aged 30 years or older with a once-daily LAMA prescription and a confirmed COPD diagnosis were recruited. Participants were randomized in a 1:1 ratio to either morning or evening LAMA administration. Complete follow-up for the primary outcome, hospitalization-requiring AECOPD, or death from all causes within 1 year was captured from the Danish National Health Register, as were patient-reported outcome assessments at 6 and 12 months. A total of 10,013 participants were randomized, and the recruitment process started on 9 March 2023. Secondary outcomes include (i) moderate COPD exacerbations; (ii) all-cause hospitalization; (iii) ICU admission; (iv) need for non-invasive ventilation; and (v) all-cause mortality, among others. All outcomes will be evaluated 12 months after recruitment.Clinical trial registration:ClinicalTrials.gov, NCT05563675.

Serum immunoglobulin levels in group E of chronic obstructive pulmonary disease: insights for clinical management and immunoglobulin therapy strategies

ObjectiveThe study aimed to characterize serum immunoglobulin (Ig) concentrations and their relationship with clinical and paraclinical features in patients with COPD group E in the stable stage. Additionally, the study focused on evaluating the relationship between serum Ig levels and the risk of exacerbations over the next 12 months, thereby clarifying the role of serum Ig deficiency in affecting the future risk for these patients.MethodsA prospective observational study assessed IgG, IgA, IgM, and IgE levels in 67 COPD patients and 30 healthy controls at Military Hospital 103 from October 2017 to August 2020. Primary outcomes included Ig isotype levels in COPD patients, with secondary outcomes exploring differences compared to controls and associations with clinical variables.ResultsCOPD patients showed significantly lower IgG concentrations and higher IgA levels than controls. IgM and IgE levels did not differ significantly. Subgroup analysis revealed notable decreases in IgG1 and IgG3 concentrations, with 10.4% of patients exhibiting reduced IgG levels and 0.3% diagnosed with common variable immunodeficiency. No significant associations were found between Ig levels and exacerbation risk or clinical variables.ConclusionsSerum IgG and IgM concentrations were significantly reduced in COPD patients compared to normal individuals, with IgG1 and IgG3 concentrations notably low. Serum IgA levels were significantly higher in COPD patients compared with normal controls. However, no significant association was found between Ig concentrations, particularly serum IgG deficiency and its subclasses, with the frequency and risk of exacerbations during 12 months of longitudinal follow-up. Caution is warranted in the use of immunoglobulin therapy in the treatment of COPD patients.Trial registrationAn independent ethics committee approved the study (Ethics Committee of Military Hospital 103 (No. 57/2014/VMMU-IRB), which was performed in accordance with the Declaration of Helsinki, Guidelines for Good Clinical Practice.

Dual Phosphodiesterase 3 and 4 Inhibitor Ensifentrine Reduces Exacerbation Rate and Risk in Patients With Moderate to Severe COPD

IntroductionExacerbations in chronic obstructive pulmonary disease (COPD) can be life-threatening and lead to irreversible declines in lung function and quality of life. Medications that reduce exacerbation burden are an unmet need, as exacerbations put patients at risk for more exacerbations and decrease quality of life. Ensifentrine is a novel, first-in-class, selective, dual inhibitor of phosphodiesterase 3/4 with demonstrated nonsteroidal anti-inflammatory activity and bronchodilatory effects. Research QuestionDoes ensifentrine reduce the rate and/or risk of COPD exacerbations? Study Design and MethodsA prespecified, pooled analysis of the phase 3 clinical trials ENHANCE-1 (NCT04535986) and ENHANCE-2 (NCT04542057) was conducted to assess the effect of ensifentrine on exacerbation rate and risk (time to first exacerbation). The trials included symptomatic patients aged 40-80 years with moderate-to-severe COPD who received 3 mg twice-daily ensifentrine over 24 weeks or placebo. Subgroup analyses and frequent exacerbator transition risk were conducted post-hoc. ResultsIn total, 975 ensifentrine-treated and 574 placebo-treated patients were included in the pooled analysis, including 62% on concomitant LAMA or LABA therapy and 18% on concomitant inhaled corticosteroid therapy. Ensifentrine was associated with significant reductions in the rate (rate ratio, 0.59; 95% CI, 0.43-0.80; P < 0.001) and risk (hazard ratio, 0.59; 95% CI, 0.44-0.81; P < 0.001) of moderate/severe exacerbations compared with placebo. Reductions in the rate and risk of exacerbations were generally consistent across patient subgroups, including age, sex, race, background maintenance medication use, chronic bronchitis, eosinophil count, COPD severity, and exacerbation history. Ensifentrine was associated with a numerical delay in transitioning from an infrequent exacerbator (GOLD B) to a frequent exacerbator (GOLD E) compared with placebo. ConclusionEnsifentrine reduced the rate of exacerbations and increased the time to first exacerbation among patients with COPD across a broad range of clinically relevant subgroups.

Prevalence and Management of Chronic Obstructive Pulmonary Disease in the Gulf Countries with a Focus on Inhaled Pharmacotherapy.

Background: Chronic obstructive pulmonary disease (COPD) is a preventable, progressive disease and the third leading cause of death worldwide. The epidemiological data of COPD from Gulf countries are very limited, as it remains underdiagnosed and underestimated. Risk factors for COPD include tobacco cigarette smoking, water pipe smoking (Shisha), exposure to air pollutants, occupational dusts, fumes, and chemicals. Inadequate treatment of COPD leads to worsening of disease. The 2024 GOLD guidelines recommend use of inhaled bronchodilators, corticosteroids, and adjunct therapies for treatment and management of COPD patients based on an individual assessment of the severity of symptoms and risk of exacerbations. This article reviews COPD pharmacotherapy in the Gulf countries and explores the role of nebulization in the management of COPD in this region. Methods: To review the COPD pharmacotherapy in the Gulf Countries, literature search was conducted using PubMed, Medline, Cochrane Systematic Reviews, and Google Scholar databases (before December 2022), using search terms such as COPD, nebulization, inhalers/inhalation, aerosols, and Gulf countries. Relevant articles from the reference list of identified studies were reviewed. Consensus statements, expert opinion, and other published review articles were included. Results: In the Gulf countries, pressurized metered-dose inhalers (pMDIs), dry powder inhalers (DPIs), soft mist inhalers, and nebulizers are used for drug delivery to COPD patients. pMDIs and DPIs are most prone to errors in technique and other common device handling errors. Nebulization is another mode of inhalation drug delivery, which is beneficial in certain patient populations such as the elderly and patients with cognitive impairment, motor or neuromuscular disorders, and other comorbidities. Conclusion: There is no major difference between Gulf countries and rest of the world in the approach to management of COPD. Nebulizers should be considered for patients who have difficulties in accessing or using MDIs and DPIs, irrespective of geographical location.

Therapeutic relevance of eosinophilic inflammation and airway viral interactions in severe asthma.

The role of eosinophils in airway inflammation and asthma pathogenesis is well established, with raised eosinophil counts in blood and sputum associated with increased disease severity and risk of asthma exacerbation. Conversely, there is also preliminary evidence suggesting antiviral properties of eosinophils in the airways. These dual roles for eosinophils are particularly pertinent as respiratory virus infections contribute to asthma exacerbations. Biologic therapies targeting key molecules implicated in eosinophil-associated pathologies have been approved in patients with severe asthma and, therefore, the effects of depleting eosinophils in a clinical setting are of considerable interest. This review discusses the pathological and antiviral roles of eosinophils in asthma and exacerbations. We also highlight the significant reduction in asthma exacerbations seen with biologic therapies, even at the height of the respiratory virus season. Furthermore, we discuss the implications of these findings in relation to the role of eosinophils in inflammation and antiviral responses to respiratory virus infection in asthma.

Risk Factors and a Prediction Model for Frequent Acute Exacerbations of Chronic Obstructive Pulmonary Disease

Objective To identify the risk factors of patients with frequent acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and construct a prediction model based on the clinical data,providing a theoretical basis for the clinical prevention and treatment. Methods A total of 25 638 COPD patients admitted to the Department of Respiratory and Critical Care Medicine,the Third People's Hospital of Chengdu from January 1,2013 to May 1,2023 were selected.Among them,11 315 patients were included according to the inclusion and exclusion criteria,and their clinical characteristics were analyzed.Multivariate Logistic regression was carried out to identify the risk factors for frequent AECOPD.A nomogram model was utilized to quantify the risk of acute exacerbation,and the performance of the prediction model was assessed based on the area under the receiver operating characteristic (ROC) curve. Results In the patients with frequent AECOPD,male percentage (P<0.001),age (P<0.001),urban residence (P<0.001),smoking (P<0.001),length of stay (P<0.001),total cost (P<0.001),antibiotic cost (P<0.001),diabetes (P=0.003),respiratory failure (P<0.001),heart disease (P<0.001),application of systemic glucocorticoids (P<0.001),white blood cell count (P<0.001),neutrophil percentage (P<0.001),C-reactive protein (P<0.001),total cholesterol (P<0.001),and brain natriuretic peptide (BNP) (P<0.001) were all higher than those in the patients with infrequent AECOPD.Multivariate Logistic regression analysis revealed that age,urban residence,smoking,diabetes,heart disease,Pseudomonas aeruginosa infection,application of systemic glucocorticoids,antibiotics,respiratory failure,and elevated white blood cell count,total cholesterol,and BNP were independent risk factors for hospitalization due to frequent AECOPD.A nomogram model of hospitalization due to frequent AECOPD was constructed according to risk factors.The ROC curve was established to evaluate the performance of the model,which showed the area under the ROC curve of 0.899 (95%CI=0.892-0.905),the sensitivity of 85.30%,and the specificity of 79.80%. Conclusion Frequent AECOPD is associated with smoking,heart disease,application of systemic glucocorticoids,Pseudomonas aeruginosa infection,age,low body mass index,and elevated BNP.Predicting the risks of hospitalization due to frequent AECOPD by the established model can provide theoretical support for the treatment and risk factor management of the patients.

Distinguishing Childhood Asthma Exacerbations from Stable Asthma: The Utility of Inflammatory White Blood Cell Biomarkers.

Asthma is a chronic inflammatory condition characterized by episodes of acute asthma exacerbations (AAEs), in addition to chronic airway inflammation, which has a huge impact on both the affected patients and their parents. The main objective of this study was to explore the utility of available white-blood-cell-derived inflammatory markers in diagnosing AAEs and identifying children at risk for severe exacerbations requiring admission to the pediatric intensive care unit (PICU). This study was a retrospective cohort study. The medical records of 128 children diagnosed with asthma exacerbation and 131 children with stable asthma between the ages of 2 and 12 years were reviewed. A total of 259 participants were enrolled. Children with AAE demonstrated significantly higher white blood cell counts (WBC: 10.0 ± 4.2 × 103/μL vs. 7.1 ± 2.2 × 103/μL, p < 0.001), absolute neutrophil counts (ANC: 7398.5 ± 4600 cells/μL vs. 2634.8 ± 1448 cells/μL, p < 0.001), and neutrophil-to-lymphocyte ratios (NLR: 7.0 ± 6.8 vs. 0.9 ± 0.7, p < 0.001) but significantly lower absolute lymphocyte counts (ALC: 1794.1 ± 1536 × 103/μL vs. 3552.9 ± 1509 × 103/μL, p < 0.001). Interestingly, blood eosinophil count displayed an opposite trend: children with stable asthma had significantly more eosinophils compared to those experiencing an exacerbation (370.1 ± 342.7 cells/mm3 vs. 0.9 ± 1.9 cells/mm3, p < 0.001). Two criteria that are indicative of AAE were identified: NLR values greater than 1.2, with good discriminative ability (area under the curve [AUC] 0.90; 95% confidence interval [CI] 0.85-0.94; sensitivity 82.5%; specificity 79.5%), and ANC values exceeding 3866, with moderate discriminative ability (AUC 0.86; 95% CI 0.81-0.91; sensitivity 75.0%; specificity 82.3%). Moreover, a comparative analysis of these markers (NLR, ANC, PLR, WBC, AEC, and ALC) in patients with AAE did not demonstrate significant differences between those requiring PICU admission and those who did not require it. This study contributes two major findings. The first is that NLR, ANC, WBC, and PLR are significantly higher in AAE patients compared to those with stable asthma. The second is that children with stable asthma have higher AEC and ALC levels compared to those with AAE. Furthermore, this study has revealed that the studied markers (NLR, ANC, PLR, WBC, AEC, and ALC) did not differentiate between AAE patients requiring PICU admission and those managed in the general ward, suggesting a need for alternative predictive factors.

GLP-1 Receptor Agonists Among Patients With Overweight or Obesity, Diabetes, and HFpEF on SGLT2 Inhibitors

BackgroundAlthough the use of glucagon-like peptide-1 receptor agonist (GLP-1 RA) in patients with obesity and heart failure with preserved ejection fraction (HFpEF) has demonstrated improvement in cardiovascular outcomes, the incremental benefits of GLP-1 RA for patients already on sodium-glucose cotransporter 2 inhibitors (SGLT2is) remain underexplored. ObjectivesThis study aimed to assess the incremental benefits of GLP-1 RA in patients with type 2 diabetes mellitus, overweight/obesity, and HFpEF receiving SGLT2i therapy. MethodsThe authors conducted a retrospective cohort study using the TriNetX research database including patients ≥18 years with type 2 diabetes mellitus, body mass index ≥27 kg/m2, and HFpEF on SGLT2i. Two cohorts were created based on GLP-1 RA prescription. The outcomes were heart failure exacerbation, all-cause emergency department visits/hospitalizations among others over a 12-month period. ResultsA total of 7,044 patients remained in each cohort after propensity score matching. There was a significantly lower risk of heart failure exacerbations, all-cause emergency department visits/hospitalizations, new-onset atrial arrhythmias, new-onset acute kidney injury, and pulmonary hypertension in the GLP-1 RA plus SGLT2i cohort compared with the SGLT2i-only cohort. The associated benefits persisted across different body mass indexes and ejection fractions as well as in patients with elevated natriuretic peptide. The risk of diabetic retinopathy was higher in the combination therapy group than with SGLT2i-only use. ConclusionsGLP-1 RA, in addition to SGLT2i, was associated with a significantly lower risk of heart failure hospitalizations in this patient population, suggesting a potential incremental benefit. This highlights the need for prospective studies to confirm the clinical benefits.

Perceived indoor environment and exacerbations of COPD and asthma – a cohort study between 2000–2018

Background. Ambient air pollution has been associated with exacerbations of chronic obstructive pulmonary disease (COPD) and asthma; however, little is known about indoor environmental factors. Our aim was to study the association between perceived indoor environment and the long-term risk of exacerbations of COPD or asthma. Methods. We followed 2,317 individuals aged ≥16 years with COPD or asthma from the Danish Health and Morbidity Survey from 2000 to 2018. Individuals developing COPD or asthma during the study period were included at the time of incident diagnosis. Individuals were grouped according to their patterns of perceived indoor environment and followed up for exacerbations defined based on information from the Danish National Health Registers. The association between perceived indoor environment and exacerbations was examined using a generalized mixed model with the Poisson distribution of the number of exacerbations and logarithmic transformation of follow-up time as offset. Analyses were adjusted for age, sex, education, household income, smoking, calendar year, construction year, urbanization, home ownership, and resident density. Results. A total of 5,352 exacerbations were recorded in 2,317 individuals during a median of 13.9 years (interquartile range, 7.9–18.2 years). The adjusted incidence rate ratio (IRR) of exacerbations were 1.40 (95% CI 0.85–2.29 and 0.82 (95% CI 0.49–1.38) among individuals with medium and high levels om annoyances, respectively. For annoyances related to temperature and traffic the IRR was 0.88 (95% CI 0.61–1.27) and 1.39 (95% CI 0.88–2.19), respectively. Conclusion. We found no association between indoor environment assessed as annoyances at a single time-point and exacerbations of COPD and asthma.

Mucus Plugs as Precursors to Exacerbation and Lung Function Decline in COPD Patients

BackgroundMucus plugs identified through chest computed tomography (CT) scans have emerged as potential prognostic factors in chronic obstructive pulmonary disease (COPD). This 5-year longitudinal study investigated their impact on exacerbations and FEV1 decline. MethodsCOPD patients with baseline chest CT and spirometric assessments were categorized based on mucus plug presence. Propensity-score matching yielded balanced groups. Exacerbation rates, time to exacerbation events, hazard ratio (HR) for exacerbations, and annual rates of FEV1 decline were evaluated. Sensitivity analysis was performed with stratification according to mucus plug scores of 0, 1–2, and ≥3. ResultsAmong 623 eligible patients, the mucus plug group was 44.3%. Through 1:1 propensity-score matching, each group was comprised of 187 individuals with balanced covariates. The mucus plug group showed higher rates of moderate-to-severe (0.51/year vs. 0.58/year, P=0.035), severe exacerbations (0.21/year vs. 0.24/year, P=0.032), and non-eosinophilic exacerbations (0.45/year vs. 0.52/year, P=0.008). Mucus plugs were associated with increased hazard of moderate-to-severe (adjusted HR=1.502 [95% CI 1.116–2.020]), severe (adjusted HR=2.106 [95% CI, 1.429–3.103]), and non-eosinophilic exacerbations (adjusted HR=1.551 [95% CI, 1.132–2.125]). Annual FEV1 decline was accelerated in the mucus plug group (β-coefficient=−62 [95% CI, −120 to −5], P=0.035). Sensitivity analysis showed higher risk of exacerbations and accelerated FEV1 decline in mucus plug score ≥3 compared to score 0. ConclusionsMucus plugs are associated with increased risks of exacerbations, particularly non-eosinophilic, and accelerated FEV1 declines over 5 years. Our study identified the potential prognostic value of mucus plugs on future exacerbation risks and lung function decline trajectories.

Clinical Research Progress of Peripheral Blood Eosinophils in Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) accounts for one of the major health and economic burdens worldwide. As a heterogeneous disease, the underlying inflammatory pattern of COPD differs from the previously thought neutrophil-dominated inflammation, with eosinophilic inflammation occupying approximately one third of stable COPD. Although the eosinophil (EOS) threshold associated with clinical relevance in patients with COPD is currently debated, eosinophil count can be used as a biomarker to guide treatment and to assess the risk of acute exacerbations of COPD, the efficacy of inhaled corticosteroids, and clinical outcomes. The purpose of this review is to describe the biological characteristics of eosinophils and the related research progress as clinical biomarkers.

Immunological Effects of Diesel Particles in a Murine Model of Healthy Mice.

Introduction: Exposure to environmental pollutants such as diesel exhaust particles (DEP) increases the risk of respiratory disease exacerbation. However, the possible effects of these particles on the general population remain poorly understood. The present study aimed to assess the immunomodulatory and inflammatory effects of the inhalation of DEP in a model of healthy mice undergoing short-, mid- and long-term exposure. Materials and Methods: BALB/c ByJ mice were randomly divided into five experimental groups. The control group received three intranasal instillations of saline over 8 days while the other four groups received intranasal instillations of 150 µg of DEP 3 days per week for 8, 17, 26, and 53 days. Lung function assessment and flow cytometry were performed. Results: In lung tissue, intranasal exposure to DEP decreased total monocytes (p < 0.015 in all groups). At 26 days, a reduction in inflammatory monocytes and an increase in resident monocytes were observed, p = 0.001 and 0.0001, respectively. Eosinophils and neutrophils decreased at 26 days (p = 0.017 and p = 0.041, respectively). The intranasal challenges of DEP increased the total population of dendritic cells (DC) at 26 and 53 days (p = 0.017 and p = 0.022, respectively) and decreased the total and alveolar populations of macrophages (p < 0.003 for all groups compared to control), while interstitial macrophage populations increased over the time period (p = 0.0001 for all groups compared to control). Conclusions: Continuous DEP exposure triggers immune mechanisms that predispose healthy individuals to a pro-inflammatory and hyper-reactive microenvironment. This mouse model provides evidence of the capacity of DEP to increase DC, interstitial macrophages, and resident monocytes.