Risk Of Exacerbations Research Articles

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.

Ohio Health Care Professionals' Pandemic-Related Help-Seeking Knowledge, Behaviors, and Concerns.

Health care professionals (HCPs) historically exhibit high rates of stress, burnout, and low rates of service utilization from Employee Assistance Programs (EAPs) and Professional Health Programs (PHPs). New and magnified stressors that accompanied COVID-19 exacerbated HCPs' risk of burnout. During the pandemic, this study examined Ohio HCP's utilization of EAPs and PHPs, knowledge of available services, barriers to accessing services, and likelihood of future service utilization. Conditions needing to change to increase likelihood of future utilization were also explored. A one-time survey was administered in July and August of 2021 to HCPs from 13 licensing boards in Ohio. This study used a subset of data to examine the extent of convergence between quantitative results-analyzed using frequency calculations-and results from thematic analysis of corresponding open-ended survey items. Qualitative results supported and elaborated the quantitative findings. Fewer than 25% of respondents (N = 12,807) utilized EAPs or PHPs to address mental health concerns. Obstacles impeding service utilization included issues around awareness, time commitment, and confidentiality-a concern encompassing issues of stigma and fear of employment repercussions. Noting multiple obstacles to accessing EAPs and PHPs, HCPs in Ohio reported low rates of support service utilization and low likeliness to use services in the future despite their experiences of extreme stress and burnout. Addressing the time commitment and confidentiality concerns could increase the likelihood of accessing services. Employers of HCPs should explore additional support mechanisms such as comprehensive wellness programs and innovative, brief intervention strategies to combat burnout, especially during viral outbreaks and other high-stress events.

Real-world biomarker variability and effects of biologics on severe asthma in Alberta

Rationale: Guidelines recommend biomarker testing to phenotype patients with severe asthma (SA), to guide treatment. However, biomarker levels fluctuate, and individual responses to biologics are not fully understood. Objectives: This study estimated the proportion of patients experiencing biomarker variability and the real-world effectiveness of biologics in SA. Methods: A population-based retrospective cohort study was conducted using administrative data from Alberta, Canada (April 1, 2010 to March 31, 2020) for patients with SA. Year-to-year variability in biomarker levels was assessed using clinical thresholds (blood eosinophil count [EOS] ≥ 300 cells/µL; immunoglobin E [IgE] ≥ 30 IU/mL) to explore category switching. Incidence rate ratios of exacerbations were estimated by biomarker level. Associations between follow-up time with biologics exposure (bio-experience), biomarker levels and exacerbation rates were modeled. Results: Up to 28% of SA patients displayed year-over-year biomarker threshold switching for EOS and up to 12% for IgE. Severe exacerbation rates were higher with blood EOS count ≥300cells/µL or IgE ≥30 IU/mL. Bio-experience was associated with lower blood EOS versus pre-bio-experience (relative mean EOS: 0.53 [0.42-0.68]), persisting >1 year following discontinuation. Bio-experience was associated with a nearly 50% reduction in exacerbation risk after initiating biologics (IRR = 0.54 [0.48, 0.62]), regardless of comorbid status. Conclusions: Higher biomarker levels were associated with higher exacerbation rates, but a proportion of patients demonstrated variability, crossing clinical thresholds. Treatments with upstream agents targeting multiple pathways of inflammation may circumvent this issue. Biologics had real-world effectiveness in reducing SA biomarkers. Their persistent temporal effect provides a groundwork for exploring cost-effective biologics use.

Exploring Symptom Overlaps: Post-COVID-19 Neurological Syndrome and Post-Concussion Syndrome in Athletes.

The COVID-19 pandemic has introduced new challenges in managing neurological conditions, particularly among athletes. This paper explores the intersection of post-COVID-19 neurological syndrome (PCNS/PASC) and post-concussion syndrome (PCS), focusing on their implications in sports medicine. Our analysis covers the symptomatology, pathophysiology, and management strategies for PCNS/PASC and PPCS, with special attention paid to the unique challenges faced by athletes recovering from these conditions, including the risk of symptom exacerbation and prolonged recovery. Key findings reveal that both PCNS/PASC and PPCS present with overlapping symptoms such as cognitive difficulties, exercise intolerance, and mental health issues, but differ in specific manifestations like anosmia and ageusia, unique to COVID-19. Pathophysiological analysis reveals similarities in blood-brain barrier disruption (BBB) but differences in the extent of immune activation. Management strategies emphasize a gradual increase in physical activity, close symptom monitoring, and psychological support, with a tailored approach for athletes. Specific interventions include progressive aerobic exercises, resistance training, and cognitive rehabilitation. Furthermore, our study highlights the importance of integrating neurology, psychiatry, physical therapy, and sports medicine to develop comprehensive care strategies. Our findings underscore the dual challenge of COVID-19 and concussion in athletes, necessitating a nuanced, interdisciplinary approach to effective management. Future research should focus on the long-term neurological effects of both conditions and optimizing treatment protocols to improve patient outcomes. This comprehensive understanding is crucial for advancing the management of athletes affected by these overlapping conditions and ensuring their safe return to sports.

The Impact of Malnutrition on Chronic Obstructive Pulmonary Disease (COPD) Outcomes: The Predictive Value of the Mini Nutritional Assessment (MNA) versus Acute Exacerbations in Patients with Highly Complex COPD and Its Clinical and Prognostic Implications.

Current management of COPD is predominantly focused on respiratory aspects. A multidimensional assessment including nutritional assessment, quality of life and disability provides a more reliable perspective of the true complexity of COPD patients. This was a prospective observational study of 120 elderly COPD patients at high risk of acute exacerbations. The Mini Nutritional Assessment (MNA) was administered in addition to the usual respiratory assessment. The primary outcome was a composite of moderate or severe acute exacerbations during 52 weeks of follow-up. The median MNA Short Form (SF) score was 11 (8-12), 39 participants (32.50%) had a normal nutritional status, 57 (47.5%) were at risk of malnutrition and 24 (20%) were malnourished. Our multivariate linear regression models showed that the MNA score was associated with dyspnea and respiratory symptom severity, assessed by the Modified British Medical Research Council (mMRC) scale and the COPD Assessment Test (CAT) score, with spirometric variables, in particular with the severity of airflow limitation based on the value of FEV1, and with poorer QoL, as assessed by the EQ-5D-3 questionnaire. Competing risk analysis according to nutritional status based on the MNA Total Score showed that COPD participants "at risk of malnutrition" and "malnourished" had a higher risk of moderate to severe acute exacerbations with sub-hazard ratios of 3.08 (1.40-6.80), p = 0.015, and 4.64 (1.71-12.55), p = 0.0002, respectively. Our study confirms the importance of assessing nutritional status in elderly COPD patients and its prognostic value.

Linkage of serum ITIH4 with Th2 signature cytokine, inflammation, exacerbation risk and severity in childhood asthma.

Aim: ITIH4has anti-inflammatory properties toward eosinophilic/neutrophilic inflammation. This study aimed to explore clinical value of ITIH4 in childhood asthma.Materials & methods: Serum ITIH4 and inflammatory cytokines were determined in 120 childhood asthma patients by enzyme-linked immunosorbent assay.Results: In the entire and acute exacerbation patients, ITIH4 positively associated with IFN-γ, but negatively related to proinflammatory cytokines. ITIH4 was lowest in patients with acute exacerbation, followed by chronic persistent, and highest in clinical remission. By receiver-operating characteristic analysis, ITIH4 potentially estimated acute exacerbation asthma risk. Moreover, ITIH4 negatively related to exacerbation severity in acute exacerbation patients.Conclusion: Serum ITIH4 negatively links with Th2 cell signature cytokine, proinflammatory cytokines, exacerbation risk and severity in childhood asthma.