Severe Exacerbations Research Articles

Efficacy and safety of weekend cyclosporine treatment as maintenance therapy for preventing frequent disease exacerbations in moderate to severe chronic plaque psoriasis patients - A retrospective cohort study.

Background Psoriasis is a chronic, inflammatory, systemic disease with predominant manifestations in the skin and joints impairing patient's quality of life. A proportion of patients have frequent severe disease exacerbations requiring repeated systemic treatments. There is a scarcity of literature evaluating the role of systemic maintenance therapy in psoriasis patients in preventing such frequent disease flares. Objective To evaluate the efficacy and safety of weekend cyclosporine treatment (WCT) as maintenance therapy in moderate to severe chronic plaque psoriasis patients for the prevention of frequent disease exacerbations. Methods In this retrospective cohort study, 22 psoriasis patients with a history of frequent disease exacerbations (≥ 3 in the last 1 year) who were administered WCT (group A) were compared with the same number of matched patients (age and gender) not on WCT or any systemic maintenance therapy (group B). Results Four patients (18.2%) in group A had disease exacerbations which was significantly lower (p = 0.00, Fisher's exact test) as compared to 21 patients (95.5%) in group B during the study period. Also, patients in group A had significantly lower number of overall exacerbations [mean ± SD: 0.23 ± 0.53 vs 2.95 ± 1.43) p = 0.00, Mann-Whitney U test] as compared to group B. Four (9.1%) patients in group A encountered adverse effects (acneiform eruptions - two, mild gingival hyperplasia - one, myalgia - one) as compared to three (acneiform eruptions - two, headache - one) in group B (p = 1.00). Conclusion WCT significantly reduced the number of disease exacerbations and is a safe and effective mode of maintenance therapy in such subset of psoriasis patients.

Real-world characteristics of patients with asthma initiating fluticasone furoate/umeclidinium/vilanterol single-inhaler triple therapy in Japan

BackgroundReal-world data assessing characteristics of patients with asthma initiating inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β2-agonist (ICS/LAMA/LABA) triple therapy in Japan are limited. MethodsDescriptive, observational study of patients with asthma aged ≥15 years newly initiating single- or multiple-inhaler triple therapy (SITT: fluticasone furoate/umeclidinium/vilanterol [FF/UMEC/VI], SITT: indacaterol/glycopyrronium bromide/mometasone furoate [IND/GLY/MF] or MITT) or ICS/LABA using JMDC/Medical Data Vision (MDV) health insurance databases from February 2021–February 2022 (first prescription date: index date). Patients were assigned to three non-mutually exclusive cohorts: A) new FF/UMEC/VI initiators; B) new FF/UMEC/VI, IND/GLY/MF, or MITT initiators; C) new FF/UMEC/VI, IND/GLY/MF, MITT or ICS/LABA initiators as initial maintenance therapy (IMT). Patient characteristics were assessed descriptively for 12-months pre-treatment initiation (baseline period). ResultsCohort A: among new FF/UMEC/VI initiators, 12.8% and 0.1% (JMDC) and 21.7% and 0.9% (MDV) of patients had ≥1 moderate and severe exacerbation; 52.0% (JMDC) and 79.2% (MDV) had ICS/LABA use. Cohort B: most patients initiated FF/UMEC/VI and IND/GLY/MF over MITT (JMDC: 91.3% vs 8.7%; MDV: 67.8% vs 32.2%), with fewer exacerbations and lower rescue medication use. Cohort C: a greater proportion of FF/UMEC/VI initiators as IMT experienced a moderate exacerbation at index versus ICS/LABA initiators as IMT (JMDC: 17.8% vs 10.7%; MDV: 8.0% vs 5.1%). ConclusionsPatient characteristics were generally similar between treatment groups; SITT initiators had fewer exacerbations and lower rescue medication use than MITT initiators, represented by the greater proportion of IMT among SITT versus MITT initiators. Physicians may have prescribed triple over dual therapy as IMT in response to an exacerbation.

Application of the Lancet Commission COPD classification to COPD Cohort Population in South Korea

The Lancet Commissions on COPD recommended a new classification based on five main risk factors.Patients with COPD were prospectively enrolled in a Korean COPD subgroup study cohort between April 2012 and June 2022. Patients were classified according to the etiologies (Type 1: Genetically determined (COPD-G), Type 2: Abnormal lung development (COPD-D), Type 3: Infections (COPD-I), Type 4: Cigarette smoking (COPD-C), Type 5: Biomass and pollution (COPD-P)).The database enrolled 3476 patients. Among 3392 patients, 52 (2 %), 1339 (39 %), 2930 (86 %), and 2221 (65 %) were compatible with type 2 (COPD-D), 3 (COPD-I), 4 (COPD-C), and 5 (COPD-P), respectively. Most patients (71 %, 2405) had multiple risk factors contributing to their COPD. However, 93, 712, and 182 patients had only type 3 (COPD-I), 4 (COPD-C), and 5 (COPD-P), respectively. Type 3 (COPD-I) only patients were significantly younger, more often female, and had lower lung function. Both the rate and frequency of severe exacerbations were significantly higher in type 3 (COPD-I) only patients (p = 0.038 and p = 0.048, respectively). Compared with type 5 (COPD-P) only, type 3 (COPD-I) only was significantly associated with the risk of severe exacerbation (Odds ratio, 5.7 [95 % CI, 1.0–32.4]; P = 0.049, incident rate ratio, 8.7 [95 % CI, 1.7–44.0]; P = 0.009).Many patients were affected by multiple factors. Therefore, it is important to consider not only smoking history, but also other potential risk factors when evaluating patients with COPD. Further research is needed to explore the implications of this new COPD classification system for clinical practice and treatment strategies.

#2075 Impact of chronic obstructive pulmonary disease on the outcomes of hemodialysis patients

Abstract Background and Aims Chronic obstructive pulmonary disease, COPD, is a common cause of morbidity and mortality. Comorbidities are frequent among COPD patients, some of which are explained by shared risk factors of smoking and increased age. Chronic kidney disease, leading to end-stage renal disease requiring hemodialysis (HD) is not uncommon in patients with COPD, and vice-versa. The prevalence and the impact of coexistence of COPD among HD patients was not extensively described. We aimed to measure the prevalence of COPD among a cohort of HD patients, and study how it relates to significant outcomes of mortality, morbidity, including unplanned hospital admissions, and kidney transplantation (KT). Method A retrospective study of subjects who initiated HD during 2015-2018. Participants were categorized into one of two groups, with or without COPD. Clinical, laboratory and pulmonary function tests data were extracted from medical records, as were outcomes of mortality, morbidity, and KT (until December 31st, 2021, or until death). Results Forty-three of 234 were diagnosed with COPD (18.4%). Their average FEV1%pred was 60%. Thirty-eight subjects in the COPD group (88.4%) were hospitalized for severe COPD exacerbations during a mean follow-up of 36.1 months, averaging 3.6 severe exacerbations per patient. Despite this, maintenance inhaler therapy was underutilized. All-cause mortality rates were higher for HD patients with COPD (72.1% vs. 47.1%, p=0.003), as were rates of acute coronary syndrome (39.5% vs. 23.6%, p=0.026). Conclusion COPD is common among HD patients and is associated with significant morbidity and increased mortality.

The impact of exposure to tobacco smoke and e-cigarettes on asthma-related outcomes: Systematic review informing the EAACI guidelines on environmental science for allergic diseases and asthma.

To inform the clinical practice guidelines' recommendations developed by the European Academy of Allergy and Clinical Immunology systematic reviews (SR) assessed using GRADE on the impact of environmental tobacco smoke (ETS) and active smoking on the risk of new-onset asthma/recurrent wheezing (RW)/low lung function (LF), and on asthma-related outcomes. Only longitudinal studies were included, almost all on combustion cigarettes, only one assessing e-cigarettes and LF. According to the first SR (67 studies), prenatal ETS increases the risk of RW (moderate certainty evidence) and may increase the risk of new-onset asthma and of low LF (low certainty evidence). Postnatal ETS increases the risk of new-onset asthma and of RW (moderate certainty evidence) and may impact LF (low certainty evidence). Combined in utero and postnatal ETS may increase the risk of new-onset asthma (low certainty evidence) and increases the risk of RW (moderate certainty evidence). According to the second SR (24 studies), ETS increases the risk of severe asthma exacerbations and impairs asthma control and LF (moderate certainty evidence). According to the third SR (25 studies), active smoking increases the risk of severe asthma exacerbations and of suboptimal asthma control (moderate certainty evidence) and may impact asthma-related quality-of-life and LF (low certainty evidence).

Inflammatory bowel diseases and modern methods of their treatment

Chronic inflammatory bowel diseases are a group of diseases that still do not have a specific cause of their occurrence, are characterized by a particularly complex pathogenesis, a variety of clinical manifestations and a significant impact on the patient’s quality of life. Crohn’s disease and non-specific ulcerative colitis are diseases that run with the risk of severe exacerbations and can also lead to the patient’s disability. The main task in the treatment of inflammatory bowel diseases is the initiation of the remission stage and its long-term maintenance. For this, several groups of drugs are used, among which the drug of the first line of therapy is Mesalazine (Mesacol®), its effect on the intestinal wall consists in preventing the development of the inflammatory process by reducing the synthesis of pro-inflammatory prostaglandins and leukotrienes, slowing down the migration, degranulation and phagocytosis of neutrophils. In addition, mesalazine neutralizes free radicals, which increases the protective effect on the intestinal wall.

Symptom Exacerbation and Adverse Events during a Randomized Trial of Early-stage Concussion Rehabilitation.

Few studies utilize randomized clinical trials (RCT) to quantify clinical intervention safety of rehabilitation after sport-related concussion across sport levels. Describe symptom exacerbation and adverse events (AEs) associated with two concussion rehabilitation interventions. Cluster Randomized Controlled Trial (XXX). Sports medicine clinic and field settings. The RCT enrolled 251 concussed athletes (median age=20 years; female n=48) across 28 sites from New Zealand professional rugby (n=31), Canadian professional football (n=52), United States (U.S.)/Canadian colleges (n=128) and U.S. high schools (n=40). Two medically supervised interventions: 1) Enhanced Graded Exertion (EGE): international return to sport strategy and sport specific activities only (EGE-only n=119) and 2) Multidimensional Rehabilitation (MDR) followed by EGE: early symptom-directed exercises once symptoms were stable, followed by EGE after symptoms resolved (MDR+EGE n=132). Primary outcomes were intrasession total symptom severity score exacerbation and significant intersession (increase 10+ severity points) sustained total symptom severity exacerbation, each measured with a Postconcussion Symptom Scale (132 total severity points on scale). Reported AEs were also described. Activity-based rehabilitation sessions (n=1437) were the primary analysis unit. Frequencies, proportions, medians, and Interquartile Ranges (IQRs) were calculated for outcomes by treatment group. The 251 post-injury participants completed 1437 (MDR+EGE=819, EGE-only=618) activity-based intervention sessions. A total of 110 and 105 participants contributed data (those missing had no documented session data) to at least 1 activity-based session in the MDR+EGE and EGE-only arms respectively. Intrasession symptom exacerbations were equivilantly low in MDR+EGE and EGE-only arms (MDR+EGE: 16.7%, 95% CI:14.1%,19.1%; EGE-only: 15.7%, 95% CI: 12.8%,18.6%). In total, 9/819 MDR+EGE sessions (0.9%) and 1/618 EGE-only sessions (0.2%) resulted in a pre- to post-session symptom exacerbation beyond a 10+ severity point increase; 8/9 resolved to <10 points by the next session. Two study-related AEs (1 in each arm) were reported. Participants in MDR+EGE and EGE-only activities reported equivalently low rates of symptom exacerbation.

Low T3 syndrome is associated with the severity of myelin oligodendrocyte glycoprotein antibody-associated disease exacerbation.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare autoimmune inflammatory disease of the central nervous system, (CNS) different from multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). While numerous studies have delved into the involvement of thyroid antibodies (ATAbs) and thyroid function in NMOSD and MS. The objective of this study is to explore the clinical significance of thyroid dysfunction and ATAbs abnormalities in adult patients with MOGAD. 36 adult inpatients diagnosed with MOGAD and 47 sex- and age-matched healthy controls were enrolled. Patients were divided into two groups based on the presence or absence of low T3 syndrome. Demographics, clinical characteristics, and results of auxiliary examinations were compared across the subgroups. Moreover, an analysis was conducted to explore the correlations between thyroid hormone levels and Expanded Disability Status Scale (EDSS) scores. Thyroid dysfunction was notably more frequent in MOGAD patients than healthy controls (p < 0.0001), particularly low T3 syndrome (p=0.03). Furthermore, subgroup analyses revealed that the low T3 syndrome group exhibited higher EDSS scores and a higher proportion of individuals with EDSS scores > 3, in comparison to the non-low T3 syndrome group (p = 0.014, p = 0.046). However, no significant differences were observed in demographic characteristics, annual relapse rates, clinical phenotypes, laboratory and MRI results, and EEG abnormalities between the two groups. Additional Spearman's analysis showed significantly negative correlations between the TT3 and FT3 levels with EDSS scores (r = -0.367, p = 0.028; r = -0.377, p = 0.024). Typical brain lesions and paralateral ventricle lesions were significantly rare in patients with positive ATAbs compared to those with negative ATAbs (p = 0.0001, p = 0.03), although the incidence of ATAbs abnormalities did not differ significantly between MOGAD patients and healthy controls. Overall, this study confirmed thyroid dysfunction, especially low T3 syndrome, is frequent in adult MOGAD patients. Patients with low T3 syndrome exhibited elevated EDSS scores and a significantly higher incidence of unfavorable condition. additionally, the correlation analysis model manifests that FT3 and TT3 levels were negatively correlated with EDSS scores. These evidences indicate that low T3 syndrome is associated with the severity of MOGAD exacerbation.

Outcomes of patients with COPD switching from multiple-inhaler to once-daily single-inhaler triple therapy in a real-world primary care setting in England: a retrospective pre-post cohort study

BackgroundCompared with multiple-inhaler triple therapy (MITT), single-inhaler triple therapy (SITT) with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) demonstrated improved lung function and meaningful improvements in chronic obstructive pulmonary disease (COPD) Assessment Test score....

Dupilumab for COPD with Blood Eosinophil Evidence of Type 2 Inflammation

BackgroundDupilumab, a fully human monoclonal antibody that blocks the shared receptor component for interleukin-4 and interleukin-13, key and central drivers of type 2 inflammation, has shown efficacy and safety in a phase 3 trial involving patients with chronic obstructive pulmonary disease (COPD) and type 2 inflammation and an elevated risk of exacerbation. Whether the findings would be confirmed in a second phase 3 trial was unclear.MethodsIn a phase 3, double-blind, randomized trial, we assigned patients with COPD who had a blood eosinophil count of 300 cells per microliter or higher to receive subcutaneous dupilumab (300 mg) or placebo every 2 weeks. The primary end point was the annualized rate of moderate or severe exacerbations. Key secondary end points, analyzed in a hierarchical manner to adjust for multiplicity, included the changes from baseline in the prebronchodilator forced expiratory volume in 1 second (FEV1) at weeks 12 and 52 and in the St. George’s Respiratory Questionnaire (SGRQ; scores range from 0 to 100, with lower scores indicating better quality of life) total score at week 52.ResultsA total of 935 patients underwent randomization: 470 were assigned to the dupilumab group and 465 to the placebo group. As prespecified, the primary analysis was performed after a positive interim analysis and included all available data for the 935 participants, 721 of whom were included in the analysis at week 52. The annualized rate of moderate or severe exacerbations was 0.86 (95% confidence interval [CI], 0.70 to 1.06) with dupilumab and 1.30 (95% CI, 1.05 to 1.60) with placebo; the rate ratio as compared with placebo was 0.66 (95% CI, 0.54 to 0.82; P<0.001). The prebronchodilator FEV1 increased from baseline to week 12 with dupilumab (least-squares mean change, 139 ml [95% CI, 105 to 173]) as compared with placebo (least-squares mean change, 57 ml [95% CI, 23 to 91]), with a significant least-squares mean difference at week 12 of 82 ml (P<0.001) and at week 52 of 62 ml (P=0.02). No significant between-group difference was observed in the change in SGRQ scores from baseline to 52 weeks. The incidence of adverse events was similar in the two groups and consistent with the established profile of dupilumab.ConclusionsIn patients with COPD and type 2 inflammation as indicated by elevated blood eosinophil counts, dupilumab was associated with fewer exacerbations and better lung function than placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; NOTUS ClinicalTrials.gov number, NCT04456673.)

Frailty and in-hospital mortality in older patients with acute exacerbation of COPD: A real-world prospective cohort study

BackgroundFew evidence exists for the effect of frailty on the patients admitted with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). ObjectiveWe explored the link between frailty and in-hospital death in AECOPD, and whether laboratory indicators mediate this association. MethodsThis was a real-world prospective cohort study including older patients with AECOPD, consisting of two cohorts: a training set (n = 1356) and a validation set (n = 478). The independent prognostic factors, including frail status, were determined by multivariate logistic regression analysis. The relationship between frailty and in-hospital mortality was estimated by multivariable Cox regression. A nomogram was developed to provide clinicians with a quantitative tool to predict the risk of in-hospital death. Mediation analyses for frailty and in-hospital death were conducted. ResultsThe training set included 1356 patients (aged 86.7 ± 6.6 years), and 25.0 % of them were frail. A nomogram model was created, including ten independent variables: age, sex, frailty, COPD grades, severity of exacerbation, mean arterial pressure (MAP), Charlson Comorbidity Index (CCI), Interleukin-6 (IL-6), albumin, and troponin T (TPN-T). The area under the receiver operating characteristic curve (ROCs) was 0.862 and 0.845 for the training set and validation set, respectively. Patients with frailty had a higher risk of in-hospital death than those without frailty (HR,1.83, 95%CI: 1.14, 2.94; p = 0.013). Furthermore, CRP and albumin mediated the associations between frailty and in-hospital death. ConclusionsFrailty may be an adverse prognostic factor for older patients admitted with AECOPD. CRP and albumin may be part of the immunoinflammatory mechanism between frailty and in-hospital death.

Therapeutic Potential of Vitamin D in Asthma Control

In 2019, according to WHO estimates, 262 million people were affected by asta, resulting in 455,000 deaths. Asthma, is a chronic inflammatory disease of the airways that causes reversible bronchoconstriction, making it difficult for patients to breathe. Exacerbations of the disease can be caused by a variety of factors but share similar symptoms such as wheezing, coughing, shortness of breath and chest tightness. Severe asthma exacerbations are defined as symptoms that do not respond to inhaled medications and improve only after oral or intravenous steroid administration. Asthma-related deaths often occur during exacerbations. Vitamin D, which is produced naturally in the body and found in some foods, is a steroid-derived vitamin. Adequate doses of this vitamin, administered through medication or supplements, can be used to maintain its proper levels in the organism. Vitamin D is essential for regulating calcium levels in the body and for bone remodeling. It also has immunomodulatory effects, affecting both innate and adaptive immunity. This partly explains its association with changes in the airway epithelium that occur as a result of inflammation in asthma. The study aims to summarize the current knowledge on the relationship of vitamin D with asthma symptom control. The present study is based on literature available in scientific databases from 2013-2016, such as PubMed, Corchane Library and Google Scholar, using the following keywords: "vitamin D" and "asthma." Vitamin D deficiency is prevalent in children and adults worldwide. A critical analysis of the literature reveals that the therapeutic administration of vitamin D has no apparent advantage in treating asthma, especially in children. Nevertheless, for adults with mild asthma, vitamin D supplementation shows promise for improved outcomes. However, there is a pressing need for large-scale clinical trials to determine the efficacy and safety of this therapeutic approach for both age groups.

Differences in the effectiveness of single, dual, and triple inhaled corticosteroid therapy for reducing future risk of severe asthma exacerbation: A systematic review and network meta-analysis

ImportanceThe effectiveness of different combinations of inhaled corticosteroid (ICS) therapies in reducing severe exacerbations of adult asthma remains unclear. ObjectiveThis network meta-analysis (NMA) extensively evaluated the treatment effects of single ICS; dual ICS i.e., ICS/long-acting β2-adrenergic agonists (LABA); ICS/LABA as single maintenance and reliever therapy (SMART); and triple ICS, i.e., ICS/LABA/long-acting muscarinic antagonists (LAMA) in preventing severe asthma exacerbations. Data sourcesA systematic search of English databases, including PubMed and Web of Science, was conducted until December 31, 2022, using PRISMA-NMA. Study selectionUsing the PICOS criteria, the questions for this study were carefully selected so that the correct keywords could be identified. Data extraction and synthesisA pairwise meta-analysis was used to select trials based on the criteria for minimizing heterogeneity (I2). Subsequently, the “BUGSnet” package of R software was used to perform a Bayesian network meta-analysis. Main outcome measuresThe main outcome measures were risk rate and annualized rate ratio of severe asthma exacerbations. ResultsThis review included 56 randomized control trials (RCTs; n = 78,171 patients). As the pairwise meta-analysis demonstrated that the annualized rate ratio of severe asthma exacerbation had moderate heterogeneity, we analyzed the risk rate of severe asthma exacerbation using a network meta-analysis. In terms of direct/indirect comparisons with non-ICS, single ICS, dual ICS, SMART, and triple ICS reduced severe asthma exacerbations by 34 %, 47 %, 58 %, and 57 %, respectively. SMART and triple ICS showed high effectiveness in reducing severe exacerbations. ConclusionAND RELEVANCE: SMART and triple ICS were ranked higher in effectiveness in reducing severe asthma exacerbations in comparison with other therapies, indicating that these are the most effective treatments for reducing the future risk of severe asthma exacerbations.

The burden of severe exacerbations, their relationship to clinical outcomes and the use of health resources in the Russian population of patients with chronic obstructive pulmonary disease: a subanalysis of the Russian population of EXACOS International Study

According to the literature, the risk of death in patients with chronic obstructive pulmonary disease (COPD) increases with both frequency and severity of the disease exacerbations. However, the clinical burden and healthcare resource utilization associated with severe COPD exacerbations in the Russian population have not been adequately studied.The aim of this study was to assess the clinical burden of severe COPD in Russia by examining the relationship between frequency of severe exacerbations, clinical outcomes, and healthcare utilization among the Russian patients.Methods. The EXACOS International Study on Exacerbations and Outcomes was an observational, cross-sectional study that collected retrospective data from medical records over a five-year period. The study population included a broad range of COPD patients monitored by pulmonologists. The purpose of the study was to assess the frequency of severe exacerbations that were defined as hospitalizations (with or without admission to an intensive care unit) or emergency department visits due to worsening of COPD symptoms.Results. A total of 326 patients with COPD were included (mean age: 64.8 years, 87.1% male). Most participants had moderate (137 (42.0%)) or severe COPD (135 (41.4%)), as well as comorbidities (275 (84.4%)). The most common comorbidities included hypertension, heart failure, and diabetes. During the study period, 120 (40.0%), 158 (48.5%), and 247 (75.8%) patients received courses of oral corticosteroids, injectable corticosteroids and antibiotics, respectively. 250 (76.7%) patients experienced at least one severe COPD exacerbation, with a total of 1,026 events; and 102 (31.3%) had more than 3 exacerbations. The annual number of exacerbations increased from 128 in 2019 to 294 in 2021 (p &lt; 0.0001), and the proportion of patients with severe exacerbations also increased from 23.6% in 2009 to 54.7% in 2021.Conclusion. The high clinical burden of severe COPD exacerbations among the Russian population indicates a significant need for further research into factors leading to these events, modification of these factors and optimization of therapy to prevent the exacerbations.

Statins did not reduce the frequency of exacerbations in individuals with COPD and cardiovascular comorbidities in the COSYCONET cohort

BackgroundThe evidence regarding effects of statins on exacerbation risk in COPD remains controversial. Previous studies often excluded patients with cardiovascular comorbidities despite their high prevalence in COPD and role for exacerbations. Based on the cardioprotective properties of statins, we hypothesised that statins may reduce the risk of exacerbations especially in patients with cardiovascular comorbidities.MethodsOne thousand eight hundred eighty seven patients of the German COPD cohort COSYCONET (COPD and Systemic Consequences Comorbidities Network) of GOLD grades 1–4 (37.8% female, mean age 64.78 ± 8.3) were examined at baseline and over a period of 4.5 years for the occurrence of at least one exacerbation or severe exacerbation per year in cross-sectional and longitudinal analyses adjusted for age, gender, BMI, GOLD grade and pack-years. Due to their collinearity, various cardiovascular diseases were tested in separate analyses, whereby the potential effect of statins in the presence of a specific comorbidity was tested as interaction between statins and comorbidity. We also identified patients who never took statins, always took statins, or initiated statin intake during the follow-up.ResultsOne thousand three hundred six patients never took statins, 31.6% were statin user, and 12.9% initiated statins during the follow-up. Most cardiovascular diseases were significantly (p < 0.05)may associated with an increased risk of COPD exacerbations, but in none of them the intake of statins was a significant attenuating factor, neither overall nor in modulating the increased risk linked to the specific comorbidities. The results of the cross-sectional and longitudinal analyses were consistent with each other, also those regarding at least 1 exacerbation or at least 1 severe exacerbation per year.ConclusionThese findings complement the existing literature and may suggest that even in patients with COPD, cardiovascular comorbidities and a statin therapy that targets these comorbidities, the effects of statins on exacerbation risk are either negligible or more subtle than a reduction in exacerbation frequency.Trial registrationTrial registration ClinicalTrials.gov, Identifier: NCT01245933.Other Study ID (BMBF grant): 01GI0881, registered 18 November 2010, study start 2010–11, primary completion 2013–12, study completion 2023–09.https://clinicaltrials.gov/study/NCT01245933?cond=COPD&term=COSYCONET&rank=3

The role of 14-3-3β in acute asthma in children and analysis of the risk factors for asthma exacerbation

Objective To investigate the role of 14-3-3β in acute asthma exacerbations in children and analyze the risk factors for asthma exacerbations. Methods This study recruited 101 children with acute asthma exacerbations, 101 children with stable asthma, and 65 healthy children. Serum 14-3-3β was compared among the three groups. Factors such as asthma family history, skin prick test, serum-specific IgE test, coinfections, and clinical indicators (FeNO, FEV1, white blood cells, eosinophils, and serum IgE level) were compared between the asthma groups. Risk factors associated with acute asthma exacerbations were identified using multivariate logistic regression models. ROC curve was drawn to determine the diagnostic sensitivity and specificity of 14-3-3β. Results Serum 14-3-3β was significantly greater in the acute asthma group than in the stable asthma and control groups. Serum 14-3-3β was higher in severe acute asthma group than in mild-moderate asthma group. There were no significant differences in serum 14-3-3β levels between stable asthma and control groups (p > .05). Multivariate logistic regression analysis revealed that serum 14-3-3β level, FeNO, coinfection, and FEV1 z-score significantly increased the odds of acute asthma exacerbations in children. The optimal 14-3-3β cutoff value (39.79 ng/mL), had a sensitivity of 69.3% and specificity of 94.1% for predicting acute asthma exacerbations. Conclusions 14-3-3β is elevated in children with acute exacerbations of asthma, and increases with exacerbation severity. 14-3-3β, FeNO, FEV1, and coinfection could be independent risk factors for predicting asthma exacerbations. The optimal 14-3-3β cutoff value for predicting asthma exacerbations was 39.79 ng/mL.

Blood eosinophils levels in a Colombian cohort of biomass-and tobacco-related COPD patients.

Chronic obstructive pulmonary disease (COPD) is a major cause of illness and death among adults. In 2019, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy incorporated blood eosinophils as a biomarker to identify patients at increased risk of exacerbations which, with the history of exacerbations during the previous year, allows identification of patients who would benefit from anti-inflammatory treatment to reduce the risk of future exacerbations. The aim of this study was to describe demographic and clinical characteristics, eosinophil counts, and exacerbations in a cohort of COPD patients stratified by clinical phenotypes (non-exacerbator, frequent exacerbator, asthma-COPD overlap) in a Colombian cohort at 2600 meters above sea level. A descriptive analysis of a historical cohort of patients with a confirmed diagnosis of moderate to severe COPD (FEV1/FVC < 0.7 and at least one risk factor for COPD) from two specialized centers with comprehensive disease management programs was performed from January 2015 to March 2019. Data were extracted from medical records 1 year before and after the index date. 200 patients were included (GOLD B: 156, GOLD E: 44; 2023 GOLD classification); mean age was 77.9 (SD 7.9) years; 48% were women, and 52% had biomass exposure as a COPD risk factor. The mean FEV1/FVC was 53.4% (SD 9.8), with an FEV1 of 52.7% (20.7). No differences were observed between clinical phenotypes in terms of airflow limitation. The geometric mean of absolute blood eosinophils was 197.58 (SD 2.09) cells/μL (range 0 to 3,020). Mean blood eosinophil count was higher in patients with smoking history and frequent exacerbators. At least one moderate and one severe exacerbation occurred in the previous year in 44 and 8% of patients, respectively; during the follow-up year 152 exacerbations were registered, 122 (80%) moderate and 30 (20%) severe. The highest rate of exacerbations in the follow-up year occurred in the subgroup of patients with the frequent exacerbator phenotype and eosinophils ≥300 cells/μL. In this cohort, the frequency of biomass exposure as a risk factor is considerable. High blood eosinophil count was related to smoking, and to the frequent exacerbator phenotype.

AERIFY-1/2: two phase 3, randomised, controlled trials of itepekimab in former smokers with moderate-to-severe COPD

BackgroundAccumulating data implicate interleukin (IL)-33, a proinflammatory cytokine released locally upon epithelial cell damage, in the pathogenesis of COPD. In a phase 2 study, itepekimab, a human monoclonal antibody against IL-33, reduced exacerbations and improved lung function in a subgroup analysis of former smokers with COPD with an acceptable safety profile.MethodsThe study designs of AERIFY-1 and AERIFY-2 are described in this article.DiscussionThe primary objective of AERIFY-1/2 (NCT04701983/NCT04751487), two phase 3 randomised, double-blind, placebo-controlled trials, is to assess the efficacy and safety of itepekimabversusplacebo in a population of former smokers with moderate-to-severe COPD over up to 52 weeks. An additional secondary population of current smokers are being enrolled in AERIFY-2. These two studies will enrol patients (aged 40–85 years) with COPD and chronic bronchitis who had ≥2 moderate or ≥ 1 severe exacerbations within the previous year despite standard-of-care triple or double background therapy. All participants are required to have ≥10-pack-year smoking history, and ≥6 months since smoking cessation for former smokers. The primary end-point is the annualised rate of moderate or severe acute exacerbation of COPD. Secondary end-points include change from baseline in pre- and post-bronchodilator forced expiratory volume in 1 s, and annualised frequency of severe exacerbations. Symptomatic end-points include Evaluating Respiratory Symptoms in COPD and St. George's Respiratory Questionnaire, safety and anti-drug antibody responses.

Monocyte distribution width (MDW) and DECAF: two simple tools to determine the prognosis of severe COPD exacerbation

Monocyte distribution width (MDW) has been associated with inflammation and poor prognosis in various acute diseases. Chronic obstructive pulmonary disease (COPD) exacerbations (ECOPD) are associated with mortality. The objective of this study was to evaluate the utility of the MDW as a predictor of ECOPD prognosis. This retrospective study included patient admissions for ECOPD. Demographic, clinical and biochemical information; intensive care unit (ICU) admissions; and mortality during admission were recorded. A total of 474 admissions were included. MDW was positively correlated with the DECAF score (r = 0.184, p < 0.001) and C-reactive protein (mg/dL) (r = 0.571, p < 0.001), and positively associated with C-RP (OR 1.115 95% CI 1.076–1.155, p < 0.001), death (OR 9.831 95% CI 2.981– 32.417, p < 0.001) and ICU admission (OR 11.204 95% CI 3.173–39.562, p < 0.001). High MDW values were independent risk factors for mortality (HR 3.647, CI 95% 1.313–10.136, p = 0.013), ICU admission (HR 2.550, CI 95% 1.131–5.753, p = 0.024), or either mortality or ICU admission (HR 3.084, CI 95% 1.624–5.858, p = 0.001). In ROC analysis, a combined MDW–DECAF score had better diagnostic power (AUC 0.777 95% IC 0.708–0.845, p < 0.001) than DECAF (p = 0.023), MDW (p = 0.026) or C-RP (p = 0.002) alone. MDW is associated with ECOPD severity and predicts mortality and ICU admission with a diagnostic accuracy similar to that of DECAF and C-RP. The MDW– DECAF score has better diagnostic accuracy than MDW or DECAF alone in identifying mortality or ICU admission.

Factors associated with non-fatal heart failure and atrial fibrillation or flutter within the first 30 days post COPD exacerbation: a nested case-control study

BackgroundAn immediate, temporal risk of heart failure and arrhythmias after a Chronic Obstructive Pulmonary Disease (COPD) exacerbation has been demonstrated, particularly in the first month post-exacerbation. However, the clinical profile of patients who develop heart failure (HF) or atrial fibrillation/flutter (AF) following exacerbation is unclear. Therefore we examined factors associated with people being hospitalized for HF or AF, respectively, following a COPD exacerbation.MethodsWe conducted two nested case-control studies, using primary care electronic healthcare records from the Clinical Practice Research Datalink Aurum linked to Hospital Episode Statistics, Office for National Statistics for mortality, and socioeconomic data (2014-2020). Cases had hospitalization for HF or AF within 30 days of a COPD exacerbation, with controls matched by GP practice (HF 2:1;AF 3:1). We used conditional logistic regression to explore demographic and clinical factors associated with HF and AF hospitalization.ResultsOdds of HF hospitalization (1,569 cases, 3,138 controls) increased with age, type II diabetes, obesity, HF and arrhythmia history, exacerbation severity (hospitalization), most cardiovascular medications, GOLD airflow obstruction, MRC dyspnea score, and chronic kidney disease. Strongest associations were for severe exacerbations (adjusted odds ratio (aOR)=6.25, 95%CI 5.10-7.66), prior HF (aOR=2.57, 95%CI 1.73-3.83), age≥80 years (aOR=2.41, 95%CI 1.88-3.09), and prior diuretics prescription (aOR=2.81, 95%CI 2.29-3.45).Odds of AF hospitalization (841 cases, 2,523 controls) increased with age, male sex, severe exacerbation, arrhythmia and pulmonary hypertension history and most cardiovascular medications. Strongest associations were for severe exacerbations (aOR=5.78, 95%CI 4.45-7.50), age≥80 years (aOR=3.15, 95%CI 2.26-4.40), arrhythmia (aOR=3.55, 95%CI 2.53-4.98), pulmonary hypertension (aOR=3.05, 95%CI 1.21-7.68), and prescription of anticoagulants (aOR=3.81, 95%CI 2.57-5.64), positive inotropes (aOR=2.29, 95%CI 1.41-3.74) and anti-arrhythmic drugs (aOR=2.14, 95%CI 1.10-4.15).ConclusionsCardiopulmonary factors were associated with hospitalization for HF in the 30 days following a COPD exacerbation, while only cardiovascular-related factors and exacerbation severity were associated with AF hospitalization. Understanding factors will help target people for prevention.