Risk Of Severe Exacerbations Research Articles

Single inhaler with beclometasone, formoterol, and glycopyrronium versus triple therapies in adults with uncontrolled asthma: a systematic review and meta-analysis

Recent literature has shown that triple therapy is more effective than dual therapy for individuals with uncontrolled asthma. However, the comparative efficacy between different triple therapies remains unclear. The objective of this study was to determine the comparative efficacy of extra-fine single-inhaler medium-dose (MD) or high-dose (HD) of beclometasone/formoterol/glycopyrronium bromide (BDP/FOR/GLY) compared to other triple therapies in patients whose asthma remains uncontrolled with MD or HD inhaled corticosteroids and long-acting β2-agonists. A systematic literature review identified randomized control trials on adult patients with uncontrolled asthma. Two separate networks were constructed according to patients’ previous inhaled-corticosteroid dosage. Network meta-analyses evaluated severe and moderate-to-severe exacerbations, pre-dose forced expiratory volume, and asthma control questionnaire responses at 52 (± 3) weeks. Among single-inhaler triple therapies, MD BDP/FOR/GLY significantly reduced the risk of severe exacerbations (RR [95% CrI] compared to MD fluticasone/umeclidinium/vilanterol: 0.65 [0.49, 0.89]), while HD BDP/FOR/GLY demonstrated an improved trend in reducing severe and moderate-to-severe exacerbations versus HD indacaterol acetate/glycopyrronium bromide/mometasone, fluticasone/umeclidinium/vilanterol, and salmeterol/fluticasone + tiotropium. HD BDP/FOR/GLY and HD BDP/FOR + tiotropium did not differ significantly. Compared to relevant single-inhaler triple therapies, MD and HD BDP/FOR/GLY are associated with a significant benefit or trend for improvement in terms of reducing the rate of severe and moderate-to-severe exacerbations.

Regular versus as-needed treatments for mild asthma in children, adolescents, and adults: a systematic review and network meta-analysis

BackgroundInhaled corticosteroids (ICS) are recommended treatment for mild asthma. We aimed to update the evidence on the efficacy and safety of ICS-containing regimens, leukotriene receptor antagonists (LTRA), and tiotropium relative to as-needed (AN) short-acting β2-agonists (SABA) in children (aged 6–11 years) and adolescents/adults.MethodsA systematic review of randomized controlled trials (RCTs) of regular and AN treatment for mild asthma was conducted (CRD42022352384). PubMed, Scopus, and ClinicalTrials.gov were searched up to 31st March 2024. RCTs in children or adolescents/adults with mild asthma were eligible if they compared any of the following treatments: ICS alone or in combination with fast-acting bronchodilators (FABA, i.e., formoterol or SABA) or long-acting β2-agonists (LABA), LTRA, tiotropium, and SABA alone, for the following outcomes: exacerbations, asthma symptoms, forced expiratory volume in 1 s (FEV1), asthma-specific quality-of-life (QoL), or severe adverse events (SAEs). The two-stage network meta-analysis (NMA) was used to pool risk ratios (RR) or mean differences for treatment outcomes. The risk of bias was assessed using the Revised Cochrane risk-of-bias tool for randomized trials (RoB2). This review followed the PRISMA reporting guideline and the PRISMA checklist is presented in Additional file 2.ResultsThirteen RCTs in children and 29 in adolescents/adults were included. Regular ICS ranked best for preventing exacerbations and improving FEV1 in children. NMA of RCTs suggested regular ICS were better in preventing exacerbations than LTRA (RR [95% confidence intervals], (0.81 [0.69,0.96]) and AN-SABA (0.61 [0.48,0.78]), and not different from AN-ICS (0.83 [0.62,1.12]). In adolescents/adults, for preventing severe exacerbations, regular ICS outperformed AN-SABA (0.58 [0.46,0.73]), but AN-ICS/FABA (0.73 [0.54,0.97]), and regular ICS/LABA (0.68 [0.48,0.97]) surpassed regular ICS. Symptom relief and improved FEV1 were not different among the ICS-containing regimens. Regular ICS ranked best for improved QoL and least likely for SAEs.ConclusionsRegular ICS use may be the most effective treatment for preventing exacerbation and increasing FEV1 in children with mild asthma. In adolescents/adults, ICS-containing regimens outperformed AN-SABA for exacerbation prevention. With varying degrees of heterogeneity, severe exacerbation risk in adolescents/adults might be lower with regular ICS/LABA or AN-ICS/FABA than regular ICS, where AN-ICS/FABA may not be suitable for patients with low FEV1. Additionally, regular ICS use may enhance FEV1 and QoL more than AN-SABA and LTRA.

Exacerbation and Mortality Risk in Individuals with Bronchiectasis Post-COVID-19 Recovery

BackgroundIndividuals with bronchiectasis have an increased risk of exacerbation by coronavirus 2019 (COVID-19), even after recovery from COVID-19. However, the impact of COVID-19 severity on severe exacerbation and mortality remains uncertain.MethodsWe enrolled 48 342 individuals diagnosed with bronchiectasis between January 1, 2015 and October 7, 2020 from Korea National Health Insurance Service. Of these individuals, 2711 with bronchiectasis were identified as also having recovered from COVID-19. A COVID-19 and matched cohort (n=2711 for both) were established after 1:1 propensity matching. The exposure was COVID-19 (non-severe and severe), and outcomes were severe exacerbation of bronchiectasis and death following the COVID-19 recovery date.ResultsDuring a median follow-up of 70 days (interquartile range [IQR], 31–216 days) for severe exacerbation and a median of 71 days (IQR, 32–129 days) for death, including 14 days of recovery time, the incidence of severe exacerbation and death were 402.2/10 000 person-years and 342.9/10 000 person-years in the COVID-19 cohort. Although the COVID-19 cohort did not show higher risk of severe exacerbation, the cohort exhibited a significantly higher risk of mortality (adjusted hazard ratio [aHR] 1.46, 95% confidence interval [CI] 1.06–2.01) compared with the matched cohort. In a stratified analysis, the severe COVID-19 cohort showed a significantly higher risk of severe exacerbation (aHR 2.38, 95% CI 1.25–4.51) and mortality (aHR 2.99, 95% CI 2.08–4.28) compared with the matched cohort.ConclusionThe risk of severe exacerbation and mortality in individuals with bronchiectasis was increased after recovery from COVID-19, particularly in those who experienced severe COVID-19.

Dysregulation of lipid mediators in patients with frequent exacerbations of chronic obstructive pulmonary disease

Specialised pro-resolving mediators (SPMs) are endogenously produced lipid mediators that regulate the propagation of inflammation and promote tissue repair. We hypothesised that SPM production is dysregulated in COPD; and associated with disease severity, defined by patients with stable COPD (no exacerbations)versuspatients with frequent exacerbations.MethodsLipid mediators were measured in plasma samples from patients with COPD (stable and frequent exacerbators) and age, sex, BMI-matched healthy controls using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Lipid mediator (LM) profiles were compared between controls and stable COPD patients, and stable COPD patients compared with frequent exacerbators. Exploratory association with ever occurrence of severe exacerbation over 4.1 years of follow up was examined. Data are presented as mean±semin pg·mL−1for LMs, or mean±sd.ResultsForty-nine stable COPD patients had increased levels of pro-inflammatory mediators and some SPMs compared with 28 controls (prostaglandin (PG)D2: 13.97±2.44versus0.53±0.13, p<0.001, lipoxins: 226.83±23.84versus59.84±20.25, p<0.01, respectively). Fifty-two frequent exacerbators had lower PGD2(3.07±0.97versus13.97±2.44, p<0.01) and SPMs (D-resolvins: 8.73±1.25versus34.53±8.95, p<0.01, lipoxins: 53.93±9.23versus226.83±23.84, p<0.01, respectively) compared with stable COPD patients, despite a higher neutrophil count (5.28±2.16versus4.28±1.60×109/L, p=0.004).In exacerbators, D-resolvins levels were independently, inversely associated with occurrence of severe exacerbation (OR:0.88 (95%CI: 0.79,0.97), p=0.03, over follow-up.ConclusionThese findings demonstrate distinct LM profiles of stable COPD and frequent exacerbator patients. In exacerbators, D-resolvins were downregulated compared with stable COPD patients and associated with future risk of severe exacerbations over follow up. Further work is needed to understand these findings.

The Role of Severe Vitamin D Deficiency in Predicting the Risk of Severe Exacerbation in Patients With Chronic Obstructive Pulmonary Disease.

This study aims to investigate the association between vitamin D levels and the risk of severe acute exacerbations of chronic obstructive pulmonary disease (AECOPD). We conducted a prospective observational study with 636 COPD patients admitted for exacerbations between January 2021 and December 2022. Patients were categorized based on serum 25-hydroxyvitamin D levels: severe deficiency (<10 ng/mL), deficiency (10-20 ng/mL), insufficiency (20-30 ng/mL), or sufficiency (>30 ng/mL). Severe exacerbation was defined when the patient visits an emergency room or is hospitalized due to COPD exacerbation. Multivariate Cox regression was used to evaluate the risk associated with vitamin D deficiency. Over an 18-month follow-up, 178 (28.0%) patients experienced at least one severe exacerbation. The severe deficiency group had the highest exacerbation rate (40.6%), followed by deficiency (27.8%), insufficiency (22.5%), and sufficiency (18.1%) groups (P<0.01). Multivariate Cox regression analysis showed that severe vitamin D deficiency was significantly associated with an increased risk of severe exacerbations (HR=2.74, 95% CI: 1.55-4.84; P<0.01) compared to vitamin D sufficiency. Severe vitamin D deficiency is a significant predictor of severe COPD exacerbations, highlighting the importance of routine vitamin D assessment and supplementation in COPD management.

Combination Inhaled Corticosteroid and Short-acting Beta2 Agonist (ICS-SABA) Use for Older Adults With Asthma

The first combination inhaled corticosteroid and short-acting beta2 agonist (ICS-SABA) was approved by the Food and Drug Administration (FDA) in 2023 for as-needed treatment or prevention of bronchoconstriction and to reduce the risk of asthma exacerbations in patients 18 years of age and older. The recently approved product contains an ICS-albuterol combination. The 2024 Global Initiative for Asthma (GINA) guidelines recommend as-needed ICS-formoterol as the preferred asthma reliever therapy; however, a GINA alternative recommendation is the use of ICS whenever an as-needed (SABA) is used. There is no difference in as-needed asthma treatment recommended by the GINA guidelines in older adults, and there has been minimal study in older adults. Because of limited guidance on the use of the ICS-SABA reliever inhaler in older adults, the purpose of this review is to evaluate the DENALI and MANDALA studies and the potential role of ICS-SABA in older adults. The mean ages in both studies were 50 years. The MANDALA primary outcome result was a statistically significant lower risk of severe exacerbations in the ICS-SABA reliever group compared with the as-needed albuterol (ALB) group at 24 weeks. In the MANDALA older adults subgroup analysis, there was not a statistically significant difference in the ICS-SABA reliever group compared with the as-needed ALB-alone group but the results favored ICS-SABA. The DENALI primary outcome results were a greater change from baseline in forced expiratory volume in the first second (FEV1) area under the curve averaged over 12 weeks with albuterol/budesonide (ALB-BUD) 180/160 ug compared with budesonide alone and placebo and a greater change from baseline in trough FEV1 with ALB-BUD 180/160 ug and 180/80 ug than ALB-alone and placebo. Because of minimal adverse effects in both trials and the benefits in preventing asthma exacerbations reported in the MANDALA trial, it is important to assess and recommend that older adults with asthma receive inhaled corticosteroid with their reliever asthma inhaler.

Inhaled Reliever Therapies for Asthma

The optimal inhaled reliever therapy for asthma remains unclear. To compare short-acting β agonists (SABA) alone with SABA combined with inhaled corticosteroids (ICS) and with the fast-onset, long-acting β agonist formoterol combined with ICS for asthma. The MEDLINE, Embase, and CENTRAL databases were searched from January 1, 2020, to September 27, 2024, without language restrictions. Pairs of reviewers independently selected randomized clinical trials evaluating (1) SABA alone, (2) ICS with formoterol, and (3) ICS with SABA (combined or separate inhalers). Two reviewers independently extracted data and assessed risk of bias. Random-effects meta-analyses synthesized outcomes. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used to evaluate the certainty of evidence. Asthma symptom control (5-item Asthma Control Questionnaire; range, 0-6, lower scores indicate better asthma control; minimum important difference [MID], 0.5 points), asthma-related quality of life (Asthma Quality of Life Questionnaire; range, 1-7, higher scores indicate better quality of life; MID, 0.5 points), risk of severe exacerbations, and risk of serious adverse events. A total of 27 randomized clinical trials (N = 50 496 adult and pediatric patients; mean age, 41.0 years; 20 288 male [40%]) were included. Compared with SABA alone, both ICS-containing relievers were associated with fewer severe exacerbations (ICS-formoterol risk ratio [RR], 0.65 [95% CI, 0.60-0.72]; risk difference [RD], -10.3% [95% CI, -11.8% to -8.3%]; ICS-SABA RR, 0.84 [95% CI, 0.73-0.95]; RD, -4.7% [95% CI, -8.0% to -1.5%]) with high certainty. Compared with SABA alone, both ICS-containing relievers were associated with improved asthma control (ICS-formoterol RR improvement [MID] in total score, 1.07 [95% CI, 1.04-1.10]; RD, 4.1% [95% CI, 2.3%-5.9%]; ICS-SABA RR, 1.09 [95% CI, 1.03-1.15]; RD, 5.4% [95% CI, 1.8%-8.5%]) with high certainty. In an indirect comparison with ICS-SABA, ICS-formoterol was associated with fewer severe exacerbations (RR, 0.78 [95% CI, 0.66-0.92]; RD, -5.5% [95% CI, -8.4% to -2.0%]) with moderate certainty. Compared with SABA alone, ICS-formoterol (RD, -0.6% [95% CI, -1.3% to 0%]) was not associated with increased risk of serious adverse events (high certainty) and ICS-SABA (RD, 0% [95% CI, -1.1% to 1.2%]) was not associated with increased risk of serious adverse events (moderate certainty). In this network meta-analysis of patients with asthma, ICS combined with formoterol and ICS combined with SABA were each associated with reduced asthma exacerbations and improved asthma control compared with SABA alone.

Serum Immunoglobulin G Levels Are Associated with Risk for Exacerbations: An Analysis of SPIROMICS.

Rationale: Serum IgG deficiency is associated with morbidity in chronic obstructive pulmonary disease (COPD), but it is unclear whether concentrations in the lower end of the normal range still confer risk. Objectives: To determine if levels above traditional cutoffs for serum IgG deficiency are associated with exacerbations among current and former smokers with or at risk for COPD. Methods: Former and current smokers in SPIROMICS (the Subpopulations and Intermediate Outcome Measures of COPD study) (n = 1,497) were studied: 1,026 with COPD and 471 at risk for COPD. In a subset (n = 1,031), IgG subclasses were measured. Associations between total IgG or subclasses and prospective exacerbations were evaluated with multivariable models adjusting for demographic characteristics, current smoking, smoking history, FEV1 percent predicted, inhaled corticosteroids, and serum IgA. Measurements and Main Results: The 35th percentile (1,225 mg/dl in this cohort) of IgG was the best cutoff by Akaike information criterion. Below this, there was increased exacerbation risk (incidence rate ratio [IRR], 1.28; 95% confidence interval [CI], 1.08-1.51). Among subclasses, IgG1 and IgG2 below the 35th percentile (354 and 105 mg/dl, respectively) were associated with increased risks of severe exacerbation (IgG1, IRR, 1.39; 95% CI, 1.06-1.84; IgG2, IRR, 1.50; 95% CI, 1.14-1.1.97). These associations remained significant when additionally adjusting for a history of exacerbations. Conclusions: Lower serum IgG is prospectively associated with exacerbations in individuals with or at risk for COPD. Among subclasses, lower IgG1 and IgG2 are prospectively associated with severe exacerbations. The optimal IgG cutoff was substantially higher than traditional cutoffs for deficiency, suggesting that subtle impairment of humoral immunity may be associated with exacerbations.

Treatment With Bilevel PAP Is Associated With a Reduction in Severe Exacerbations in COPD-OSA Overlap: A Retrospective Claims Analysis

Treatment With Bilevel PAP Is Associated With a Reduction in Severe Exacerbations in COPD-OSA Overlap: A Retrospective Claims Analysis

Low smoking exposure and development and prognosis of COPD over four decades: a population-based cohort study.

A diagnosis of COPD is mainly considered in individuals with >10 pack-years of smoking. We tested the hypothesis that low smoking exposure, below the critical threshold of 10 pack-years, increases risk of COPD and leads to poor prognosis. We followed non-obstructed adult smokers from the Copenhagen City Heart Study for COPD, defined as a forced expiratory volume in 1 s (FEV1)/forced vital capacity <0.70 and FEV1 <80% predicted, and for related clinical outcomes. First, we followed individuals for 5 years according to baseline smoking for risk of developing COPD, and thereafter for up to four decades for severe exacerbations and death. In 6098 non-obstructed smokers, 1781 (29%) developed COPD after 5 years of follow-up: 23% of individuals with <10 pack-years of smoking at baseline, 26% of those with 10-19.9 pack-years, 30% of those with 20-39.9 pack-years and 39% of those with ≥40 pack-years. During four decades of follow-up, we recorded 620 exacerbations and 5573 deaths. Compared to individuals without COPD with <10 pack‑years of smoking, multivariable adjusted hazard ratios (HRs) for exacerbations were 1.94 (95% CI 1.36-2.76) in those without COPD and ≥10 pack-years, 2.83 (95% CI 1.72-4.66) in those with COPD and <10 pack-years, 4.34 (95% CI 2.93-6.43) in those with COPD and 10-19.9 pack-years, 4.39 (95% CI 2.98-6.46) in those with COPD and 20-39.9 pack-years and 4.98 (95% CI 3.11-7.97) in those with COPD and ≥40 pack-years. Corresponding HRs for all-cause mortality were 1.20 (95% CI 1.10-1.32), 1.31 (95% CI 1.13-1.53), 1.59 (95% CI 1.40-1.79), 1.81 (95% CI 1.62-2.03) and 1.81 (95% CI 1.55-2.10). Low smoking exposure below the critical threshold of 10 pack-years increases risk of COPD in middle-aged adults within 5 years, and these individuals have increased risk of severe exacerbation and early death over four decades.

Stakeholder-informed positivity thresholds for disease markers and risk scores: a methodological framework and an application in obstructive lung disease

A positivity threshold is often applied to markers or predicted risks to guide disease management. These thresholds are often decided exclusively by clinical experts despite being sensitive to the preferences of patients and general public as ultimate stakeholders. We propose an analytical framework for quantifying the net benefit (NB) of an evidence-based positivity threshold based on combining preference-sensitive (eg, how individuals weight benefits and harms of treatment) and preference-agnostic (eg, the magnitude of benefit and the risk of harm) parameters. We propose parsimonious choice experiments to elicit preference-sensitive parameters from stakeholders, and targeted evidence synthesis to quantify the value of preference-agnostic parameters. We apply this framework to maintenance of azithromycin therapy for chronic obstructive pulmonary disease using a discrete choice experiment to estimate preference weights for attribute level associated with treatment. We identify the positivity threshold on 12-month moderate or severe exacerbation risk that would maximize the NB of treatment in terms of severe exacerbations avoided. In the case study, the prevention of moderate and severe exacerbations (benefits) and the risk of hearing loss and gastrointestinal symptoms (harms) emerged as important attributes. Four hundred seventy seven respondents completed the discrete choice experiment survey. Relative to each percent risk of severe exacerbation, preference weights for each percent risk of moderate exacerbation, hearing loss, and gastrointestinal symptoms were 0.395 (95% confidence interval [CI] 0.338-0.456), 1.180 (95% CI 1.071-1.201), and 0.253 (95% CI 0.207-0.299), respectively. The optimal threshold that maximized NB was to treat patients with a 12-month risk of moderate or severe exacerbations ≥12%. The proposed methodology can be applied to many contexts where the objective is to devise positivity thresholds that need to incorporate stakeholder preferences. Applying this framework to chronic obstructive pulmonary disease pharmacotherapy resulted in a stakeholder-informed treatment threshold that was substantially lower than the implicit thresholds in contemporary guidelines.

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.

Type 2 Inflammation and Asthma in Children: A Narrative Review

Increased understanding of the underlying pathophysiology has highlighted the heterogeneity of asthma and identified that most children with asthma have type 2 inflammation with elevated biomarkers, such as blood eosinophils and/or fractional exhaled nitric oxide. Although in the past most of these children may have been categorized as having allergic asthma, identifying the type 2 inflammatory phenotype provides a mechanism to explain both allergic and non-allergic triggers in pediatric patients with asthma. Most children achieve control with low to medium doses of inhaled corticosteroids. However, in a small but significant proportion of children, asthma remains uncontrolled despite maximum conventional treatment, with an increased risk of severe exacerbations. In this review, we focus on the role of type 2 inflammation and allergic processes in children with asthma, together with evidence of the efficacy of available treatment options for those who experience severe symptoms.

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.

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.

Frequency and economic burden of exacerbations in inhaled corticosteroid/long-acting beta-agonist-treated patients with asthma: a retrospective US claims study

Despite adherence to inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) therapy, many patients with asthma experience moderate exacerbations. Data on the impact of moderate exacerbations on the healthcare system are limited. This study assessed the frequency and economic burden of moderate exacerbations in patients receiving ICS/LABA. Retrospective, longitudinal study analyzed data from Optum's de-identified Clinformatics® Data Mart Database recorded between October 1, 2015, and December 31, 2019. Eligibility criteria included patients ≥18 years of age with ≥1 ICS/LABA claim and ≥1 medical claim for asthma in the 12 months pre-index (first ICS/LABA claim). Primary objectives included describing moderate exacerbation frequency, and associated healthcare resource utilization (HRU) and costs. A secondary objective was assessing the relationship between moderate exacerbations and subsequent risk of severe exacerbations. Patients were stratified by moderate exacerbation frequency in the 12 months post index. Moderate exacerbations were identified using a newly developed algorithm. In the first 12 months post index 61.6% of patients experienced ≥1 moderate exacerbation. Mean number of asthma-related visits was 4.1 per person/year and median total asthma-related costs was $3544. HRU and costs increased with increasing exacerbation frequency. Outpatient and inpatient visits accounted for a similar proportion of these costs. Moderate exacerbations were associated with an increased rate and risk of future severe exacerbations (incidence rate ratio, 1.56; hazard ratio, 1.51 [both p<0.001]). This study highlighted that a high proportion of patients continue to experience moderate exacerbations despite ICS/LABA therapy and subsequently experience increased economic burden and risk of future severe exacerbations.

Longitudinal BMI change and outcomes in Chronic Obstructive Pulmonary Disease: a nationwide population-based cohort study

BackgroundThe association between longitudinal body mass index (BMI) change and clinical outcomes in patients with chronic obstructive pulmonary disease (COPD) has not fully investigated.MethodsThis retrospective cohort study included 116,463 COPD patients aged ≥ 40, with at least two health examinations, one within 2 years before and another within 3 years after COPD diagnosis (January 1, 2014, to December 31, 2019). Associations between BMI percentage change with all-cause mortality, primary endpoint, and initial severe exacerbation were assessed.ResultsBMI decreased > 5% in 14,728 (12.6%), while maintained in 80,689 (69.2%), and increased > 5% in 21,046 (18.1%) after COPD diagnosis. Compared to maintenance group, adjusted hazard ratio (aHR) for all-cause mortality was 1.70 in BMI decrease group (95% CI:1.61, 1.79) and 1.13 in BMI increase group (95% CI:1.07, 1.20). In subgroup analysis, decrease in BMI showed a stronger effect on mortality as baseline BMI was lower, while an increase in BMI was related to an increase in mortality only in obese COPD patients with aHRs of 1.18 (95% CI: 1.03, 1.36). The aHRs for the risk of severe exacerbation (BMI decrease group and increase group vs. maintenance group) were 1.30 (95% CI:1.24, 1.35) and 1.12 (95% CI:1.07, 1.16), respectively.ConclusionsA decrease in BMI was associated with an increased risk of all-cause mortality in a dose-dependent manner in patients with COPD. This was most significant in underweight patients. Regular monitoring for weight loss might be an important component for COPD management.

Long-Term Impacts of COVID-19 on Severe Exacerbation and Mortality in Adult Asthma: A Nationwide Population-Based Cohort Study

In adults with asthma, the long-term impact of previous coronavirus disease 2019 (COVID-19) on severe exacerbations and mortality is unclear. We evaluated the long-term risk of severe exacerbation and mortality in adults with asthma who recovered from COVID-19. Using the Korean National Health Insurance claim-based database, we compared the risk of severe exacerbations (emergency room visits or hospitalization) and mortality in adults with asthma aged greater than 20 years who had recovered from COVID-19 between October 8, 2020, and December 16, 2021 (COVID-19 cohort, n= 10,739) with 1:1 propensity score-matched controls (n= 10,739). During a median follow-up of 87 days (range, 15-448 days), the incidence rate of severe exacerbations in the COVID-19 cohort and the matched cohort was 187.3 and 119.3 per 10,000 person-years, respectively. The COVID-19 cohort had a higher risk of severe exacerbation compared with the matched cohort (hazard ratio= 1.57; 95% CI, 1.06-2.32). During a median follow-up of 360 days (range, 15-721 days), the incidence rate of death in the COVID-19 and matched cohorts was 128.3 and 73.5 per 10,000 person-years, respectively. The COVID-19 cohort had a higher risk of death (hazard ratio= 1.76; 95% CI, 1.33-2.30) compared with the matched cohort. When further analyzed by COVID-19 severity, severe COVID-19 was associated with a 5.12-fold (95% CI, 3.27-8.01) and 7.31-fold (95% CI, 5.41-9.88) increased risk of severe exacerbation and death, respectively, but non-severe COVID-19 was not. Our study shows that severe COVID-19 is associated with an increased long-term risk of severe exacerbation and mortality among individuals with asthma.

Опыт применения генно-инженерных биологических препаратов при тяжелой бронхиальной астме в Республике Саха (Якутия)

In the Republic of Sakha (Yakutia), from 2001 to 2020, the incidence of asthma is increasing from 4.1 per 1000 population to 12.5 per 1000 population. Considering that currently one of the most effective modern methods of treating severe asthma is genetic engineering biological therapy, research on biologically active medications, as well as the lack of research on this problem in the Yakut population, our work seems relevant. The purpose of this study was to evaluate the effectiveness of treatment with genetic engineering biological drugs (GEBD) in patients with severe asthma in the Yakut population. The study included 17 patients suffering from severe asthma. In 5 patients with severe asthma, the effectiveness of the following GEBD was assessed: anti IL-4, IL-13 drug, in 6 patients – anti IL-5 drug, in 6 patients – anti IgE drug. The effectiveness of treatment was assessed using the ACQ-5 symptom control test, the number of exacerbations over the previous 12 months of asthma therapy, IgE levels, the absolute number of eosinophils, indicators of external respiratory function, and the need of patients for additional asthma therapy. Before initiation, 8 (47.10%) patients had exacerbations and sought medical help; 2 patients were hospitalized in the pulmonology department; after 6 and 12 months, no exacerbations or hospitalizations in specialized hospitals were registered. When using a GEBD for 12 months, the need for inhaled corticosteroids decreased in micrograms/day. Thus, treatment of severe asthma in the Yakut population with GEBD makes it possible to achieve control over its symptoms, reduce the risk of severe exacerbations and the number of hospitalizations, and prevent side effects from high doses of standard therapy.

Gabapentinoids and Risk for Severe Exacerbation in Chronic Obstructive Pulmonary Disease : A Population-Based Cohort Study.

North American and European health agencies recently warned of severe breathing problems associated with gabapentinoids, including in patients with chronic obstructive pulmonary disease (COPD), although supporting evidence is limited. To assess whether gabapentinoid use is associated with severe exacerbation in patients with COPD. Time-conditional propensity score-matched, new-user cohort study. Health insurance databases from the Régie de l'assurance maladie du Québec in Canada. Within a base cohort of patients with COPD between 1994 and 2015, patients initiating gabapentinoid therapy with an indication (epilepsy, neuropathic pain, or other chronic pain) were matched 1:1 with nonusers on COPD duration, indication for gabapentinoids, age, sex, calendar year, and time-conditional propensity score. The primary outcome was severe COPD exacerbation requiring hospitalization. Hazard ratios (HRs) associated with gabapentinoid use were estimated in subcohorts according to gabapentinoid indication and in the overall cohort. The cohort included 356 gabapentinoid users with epilepsy, 9411 with neuropathic pain, and 3737 with other chronic pain, matched 1:1 to nonusers. Compared with nonuse, gabapentinoid use was associated with increased risk for severe COPD exacerbation across the indications of epilepsy (HR, 1.58 [95% CI, 1.08 to 2.30]), neuropathic pain (HR, 1.35 [CI, 1.24 to 1.48]), and other chronic pain (HR, 1.49 [CI, 1.27 to 1.73]) and overall (HR, 1.39 [CI, 1.29 to 1.50]). Residual confounding, including from lack of smoking information. In patients with COPD, gabapentinoid use was associated with increased risk for severe exacerbation. This study supports the warnings from regulatory agencies and highlights the importance of considering this potential risk when prescribing gabapentin and pregabalin to patients with COPD. Canadian Institutes of Health Research and Canadian Lung Association.