History Of Exacerbations Research Articles

IgE is associated with exacerbations and lung function decline in COPD

BackgroundBoth allergen-specific IgE and total IgE in serum play a major role in asthma. However, the role of IgE in chronic obstructive pulmonary disease (COPD) is poorly understood. It was the aim of this study to systematically analyze the relationship between serum IgE levels and disease characteristics in large COPD cohorts.MethodsCOSYCONET is a comprehensively characterized cohort of patients with COPD: total IgE and IgE specific to common aeroallergens were measured in serum of 2280 patients, and related to clinical characteristics of the patients. WISDOM is another large COPD population (2477 patients): this database contains the information whether total IgE in serum was elevated (≥ 100 IU/l) or normal in patients with COPD.ResultsBoth in COSYCONET and WISDOM, total IgE was elevated (≥ 100 IU/l) in > 30% of the patients, higher in men than in women, and higher in currently than in not currently smoking men. In COSYCONET, total IgE was elevated in patients with a history of asthma and/or allergies. Men with at least one exacerbation in the last 12 months (50.6% of all men in COSYCONET) had higher median total IgE (71.3 IU/l) than men without exacerbations (48.3 IU/l): this difference was also observed in the subgroups of not currently smoking men and of men without a history of asthma. Surprisingly, a history of exacerbations did not impact on total IgE in women with COPD. Patients in the highest tertiles of total IgE (> 91.5 IU/ml, adjusted OR: 1.62, 95% CI 1.12–2.34) or allergen-specific IgE (> 0.19 IU/ml, adjusted OR: 2.15, 95% CI 1.32–3.51) were at risk of lung function decline (adjusted by: age, gender, body mass index, initial lung function, smoking status, history of asthma, history of allergy).ConclusionThese data suggest that IgE may play a role in specific COPD subgroups. Clinical trials using antibodies targeting the IgE pathway (such as omalizumab), especially in men with recurrent exacerbations and elevated serum IgE, could elucidate potential therapeutic implications of our observations.

The long-term clinical impact of COPD exacerbations: a 3-year observational study (SHERLOCK).

Background and Aims:Exacerbations of chronic obstructive pulmonary disease (COPD) drive disease progression and can lead to an accelerated decline in lung function and a burden on healthcare systems. The retrospective, observational cohort Study on HEalthcare Resource utiLization related to exacerbatiOns in patients with COPD (SHERLOCK; D5980R00014) evaluated the associations between exacerbation history and rates of subsequent COPD exacerbations in primary care patients from the National Health Service in Greater Glasgow and Clyde, United Kingdom.Methods:Patients were stratified into four groups according to exacerbation history in the year before the index date: Group A (no exacerbations), Group B (1 moderate exacerbation only), Group C (1 severe exacerbation only), and Group D (⩾2 moderate or severe exacerbations). The frequencies of moderate and/or severe exacerbations were recorded over 36 months of follow-up and compared with reference Group A, using generalized linear models.Results:Over 36 months of follow-up, the adjusted rate ratios (RRs, 95% confidence interval) of moderate or severe exacerbations relative to Group A were 1.60 (1.53, 1.67), 1.75 (1.50, 2.04), 1.61 (1.54, 1.68), and 3.61 (3.48, 3.74) for Groups B, C, B + C, and D, respectively. Compared with Group A, patients in Group C exhibited an increased rate of moderate (RR, 1.58 (1.35, 1.85)) and severe exacerbations (RR, 3.13 (2.20, 4.46)).Conclusion:SHERLOCK highlights that even one moderate exacerbation increases the risk for subsequent exacerbations compared with having no recent prior exacerbations. Reviewing recent exacerbation history to ascertain future exacerbation risk and inform COPD management may reduce hospitalizations and improve patient outcomes.

POSA40 Cost-Effectiveness of Single-Inhaler Triple Therapy (FF/UMEC/VI) Versus Tiotropium Monotherapy in Patients with COPD in the UK

To evaluate the cost-effectiveness of once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 μg compared with once-daily tiotropium (TIO) 18 μg in patients with symptomatic chronic obstructive pulmonary disease (COPD) and a history of exacerbations from a United Kingdom (UK) National Healthcare System (NHS) perspective.

Triple versus LAMA/LABA combination therapy for Japanese patients with COPD: A systematic review and meta-analysis.

In symptomatic COPD patients with a history of exacerbations, additional treatment with inhaled corticosteroid (ICS) to long-acting muscarinic antagonist (LAMA) and long-acting beta-agonist (LABA) combination therapy is recommended based on the evidence of low incidence of exacerbations but with a caution for pneumonia. However, ethnic differences may affect the response to drugs. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of this treatment in the Japanese population (PROSPERO: CRD42020191978). We searched relevant randomized control trials and analyzed the exacerbations, quality of life, lung function, and adverse events including pneumonia and mortality as the outcomes of interest. We identified a total of three RCTs (N=632). Treatment with ICS/LAMA/LABA triple therapy significantly decreased the exacerbations (rate ratio, 0.56; 95% CI, 0.38 to 0.85) and improved the trough FEV1 (mean difference, 0.04; 95% CI, 0.01 to 0.07) compared to LAMA/LABA therapy. However, triple therapy showed a significantly higher incidence of pneumonia compared to LAMA/LABA (odds ratio, 3.38; 95% CI, 1.58 to 7.22). Concerning other adverse events including mortality, there were no significant difference between these therapies. In the current meta-analysis of the Japanese population, we confirmed that triple therapy causes a higher incidence of pneumonia than LAMA/LABA treatment but is a more preferable treatment since it showed a lower incidence of exacerbations and higher trough FEV1 in patients with symptomatic moderate to severe COPD. However, since the sample sizes were not statistically large enough, further trials involving Japanese patients are needed.

Predictive modeling of COPD exacerbation rates using baseline risk factors.

Background:Demographic and disease characteristics have been associated with the risk of chronic obstructive pulmonary disease (COPD) exacerbations. Using previously collected multinational clinical trial data, we developed models that use baseline risk factors to predict an individual’s rate of moderate/severe exacerbations in the next year on various pharmacological treatments for COPD.Methods:Exacerbation data from 20,054 patients in the ETHOS, KRONOS, TELOS, SOPHOS, and PINNACLE-1, PINNACLE-2, and PINNACLE-4 studies were pooled. Machine learning was used to identify predictors of moderate/severe exacerbation rates. Important factors were selected for generalized linear modeling, further informed by backward variable selection. An independent test set was held back for validation.Results:Prior exacerbations, eosinophil count, forced expiratory volume in 1 s percent predicted, prior maintenance treatments, reliever medication use, sex, COPD Assessment Test score, smoking status, and region were significant predictors of exacerbation risk, with response to inhaled corticosteroids (ICSs) increasing with higher eosinophil counts, more prior exacerbations, or additional prior treatments. Model fit was similar in the training and test set. Prediction metrics were ~10% better in the full model than in a simplified model based only on eosinophil count, prior exacerbations, and ICS use.Conclusion:These models predicting rates of moderate/severe exacerbations can be applied to a broad range of patients with COPD in terms of airway obstruction, eosinophil counts, exacerbation history, symptoms, and treatment history. Understanding the relative and absolute risks related to these factors may be useful for clinicians in evaluating the benefit: risk ratio of various treatment decisions for individual patients.Clinical trials registered with www.clinicaltrials.gov (NCT02465567, NCT02497001, NCT02766608, NCT02727660, NCT01854645, NCT01854658, NCT02343458, NCT03262012, NCT02536508, and NCT01970878)

High Use of Antidepressant Medication in Both Mild-to-Modelate and Possible Severe Asthma – A Nationwide Cohort Study

PurposeIn asthma, increased severity has been linked to depression assessed as assessed by patient-reported outcomes. However, little is known about predictors of antidepressant use in asthma compared to the background population.MethodsThe study consists of 60,534 asthma patients aged 18–45 and a 1:1 age- and sex-matched control group. Using national registries and prescription data, the prevalence of and risk factors for antidepressant use were investigated by logistic regression adjusted for age, sex, workforce and civil status, income- and education-level and comorbidity. Results presented as odds ratio (OR) with 95% confidence intervals (CI).ResultsA total of 16% and 22%, respectively, among patients with mild-to-moderate and possible severe asthma redeemed antidepressant drugs, compared to 10% of controls. Antidepressant use was more prevalent amongst patients with high rescue medication use (>600 annual doses) and those with a history of moderate or severe exacerbation(s). Both mild-to-moderate and possible severe asthma were independent risk factors for antidepressant use (OR 1.40 (95% CI 1.35, 1.46) and OR 1.55 (95% CI 1.41, 1.70), respectively). Female sex, age, being divorced or never married, having only primary education or currently being under education, as well as being on welfare/transfer income increased odds of antidepressant use. Completing higher education and having high income were associated with lower odds.ConclusionIn asthma, antidepressant use is significantly higher than in the background population. Even after adjusting for known risk factors, asthma remains a predictor of antidepressant use, signalling a psychologic burden related to living with asthma.

Short-acting beta-2 agonist prescription patterns and clinical outcomes in Chinese patients with asthma: an observational study in mainland China for the SABINA programme.

Objectives:The SABINA CHINA study aimed to determine prescription data for asthma medication with a focus on SABA and ICS in a representative population of patients with asthma in China.Methods:SABINA China was a multicentre, observational, cross-sectional study with data collected retrospectively from a convenience sample of 25 tertiary centres across China. Patients (age ⩾ 12 years) with ⩾3 consultations/year were enrolled. Data were collected on clinical characteristics, asthma severity, and symptom control (as per GINA 2017), treatment and history of severe exacerbations over the past year. SABA over-prescription was defined as ⩾3 SABA canisters/year. Descriptive statistics are presented.Results:Between March and August 2020, 498 patients were included in the outcome analysis. Mean (SD) age was 48.7 (15.0) years, 57.9% were female and 91% had moderate-to-severe asthma (n = 453). Overall, 12.5% (n = 62) and 26.4% (n = 131) of patients had uncontrolled and partly controlled asthma, respectively. SABA add-on was prescribed to 20.3% (n = 101) of patients; one patient with moderate-to-severe asthma was prescribed SABA-alone. SABA over-prescription in the overall population was 4.0% (n = 20; all with moderate-to-severe asthma) and 19.8% (20/101) among those prescribed SABA add-on. In the mild asthma group, 50% (n = 22) were prescribed ICS/LABA and 43.2% (n = 19) were prescribed LTRA. Among those with moderate-to-severe asthma, 97.4% (n = 441) were prescribed ICS/LABA and 55.0% (n = 249) were prescribed LTRA. Approximately 30% of patients (n = 149) experienced ⩾1% and 6.6% (n = 33) ⩾3 severe exacerbations in the preceding year; mean annual number of severe exacerbation/patient was 0.6 (1.2). Among those prescribed SABA add-on, ICS/LABA and LTRA (non-mutually exclusive groups due to overlapping prescriptions), 54.5%, 29.9%, and 35.3% had ⩾1 severe exacerbations, respectively.Conclusion:Among patients with predominantly moderate-to-severe asthma managed in tertiary care and were prescribed SABA, 1 in 5 received ⩾3 canisters/year. Fewer patients who received ICS/LABA prescriptions experienced annual exacerbations than those prescribed SABA add-on.

Inhaled Corticosteroid Use Among COPD Patients in Primary Care in Spain.

PurposeInhaled corticosteroids (ICS) are frequently used to treat chronic obstructive pulmonary disease (COPD) outside the current recommendations. Our aim was to describe ICS use in COPD patients and to identify factors associated with ICS use among COPD patients treated within primary care in Spain.Patients and MethodsThis was a cross-sectional, non-interventional and multicenter study of patients with COPD treated in primary care. Patient characteristics and exacerbations were described in terms of ICS use among the overall cohort, and among those with spirometry confirmed COPD (post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC] ratio <70%). Multivariable logistic regression was used to identify factors associated with ICS use.ResultsA total of 901 patients were included, of which 47.9% (n = 432) were treated with ICS. A total of 240 patients (26.6%) experienced moderate/severe exacerbations in the prior year, while 309 (34.3%) during the previous two years. History of asthma totaled 11.6% (n = 105). The most frequent phenotype was non-exacerbator (51.6%), and the proportion of patient with moderate or severe exacerbations was significantly higher among ICS treated patients compared to non-treated: 37.5% versus 16.6% during the previous year (p < 0.001), and 46.8% versus 22.8% during the previous 2-years (p < 0.001), respectively. Patient characteristics were similar among spirometry confirmed patients and the overall population. Factors significantly associated with ICS use were a history of asthma (OR = 4.39, 95% CI: 2.67–7.26), the presence of moderate or severe exacerbations in the last year (OR = 2.52, 95% CI: 1.81–3.49), followed by higher mMRC and higher CAT score.ConclusionNearly half of patients in primary care in Spain are treated with ICS, despite most of them being non-exacerbators. History of asthma, exacerbations, and worse dyspnea and CAT scores are associated with ICS use.

Mortality risk prediction with ILD-GAP index in a fibrotic hypersensitivity pneumonitis cohort.

Fibrotic hypersensitivity pneumonitis (fHP) is associated with significant morbidity and mortality. Interstitial lung disease-gender-age-physiology (ILD-GAP) performance in fHP outside the initial cohort was never performed. To assess the ILD-GAP index's ability to predict mortality in a Portuguese cohort of patients with fHP and analyse whether other clinical variables add value. Retrospective analysis of fHP cohort in two Portuguese ILD centres. The baseline ILD-GAP index was calculated. Survival was analysed in months; mortality was the primary outcome. Univariate and multivariate analyses to identify mortality risk factors were performed. A total of 141 patients were included. Fifty-three patients (37.6%) died during the follow-up. The usual interstitial pneumonia (UIP) pattern was found in 49.6%, and their survival was inferior to non-UIP [32 months (interquartile range, IQR = 19, 60) versus 52 months (IQR = 28, 98), p = 0.048]. Patients with an ILD-GAP index higher than three double their risk of mortality [hazard ratio (HR) = 6.48, 95% confidence interval (CI) = (3.03-13.96)] when compared with the patients with an index between 2 and 3 [HR = 3.04, 95% CI = (1.62-5.71)] adjusting for acute exacerbation history. Even though UIP patients had worse survival, it did not reach statistical significance when UIP pattern was added to this model. Acute exacerbation history was an independent risk factor for mortality; however, ILD-GAP still predicted mortality after adjusting for this factor. PaO2 and 6-minute walk test desaturation were not significant risk factors. ILD-GAP index is a good predictor for mortality in fHP, even after adjusting for other mortality risk factors.

THE OVERLAPPING ELIGIBILITY FOR BIOLOGICS IN PATIENTS WITH SEVERE ASTHMA AND PHENOTYPES

Biologics are an important treatment option for patients with severe asthma. Four biologics are available in Japan, and an overlapping eligibility has been observed. The eligibility and availability of drugs depend on the local regulations of different countries. However, there is no precise information about the eligibility for biologics, including dupilumab, in Japan. The aim of the study was to investigate the overlapping eligibility and to analyze the phenotypes of patients with multiple eligibility. In this observational study, a retrospective chart review of patients was performed. The eligibility criteria for omalizumab were IgE 30-1500IU/mL and positive IgE for perennial aeroallergen. The eligibility criteria for IL-5-targeted biologics (mepolizumab and benralizumab) were eosinophil counts (Eos) > 150μL, while those for dupilumab were Eos > 150μL or fraction of exhaled nitric oxide (FeNO) > 150ppb or IgE > 167IU/mL. Severe asthma was defined by the severity criteria under treatment based on Japanese guidelines for adult asthma. One hundred patients with severe asthma were identified. The eligibility for omalizumab, IL-5-targeted therapies, and dupilumab was 43%, 69%, and 82%, respectively. Thirty percent of the patients were eligible for all the four biologics and showed the lowest FEV1, frequent exacerbation history, and the highest levels of Eos, FeNO, and serum periostin. Only 11% of the patients were not indicated for any biologics. A considerable portion of patients was eligible for all the biologics. Asthma control was poor, and type 2 inflammation was prominent in such patients.

Development of MDS-Based Predication Model for COPD Severity in Nursing Home Residents.

Assessing chronic obstructive pulmonary disease (COPD) severity is challenging in nursing home (NH) residents due to incomplete symptom assessments and exacerbation history. The objective of this study was to predict COPD severity in NH residents using the Minimum Data Set (MDS), a clinical assessment of functional capabilities and health needs. A cohort analysis of prospectively collected longitudinal data was conducted. Residents from geographically varied Medicare-certified NHs with age ≥60 years, COPD diagnosis, and ≥6 months NH residence at enrollment were included. Residents with severe cognitive impairment were excluded. Demographic characteristics, medical history, and MDS variables were extracted from medical records. The care provider-completed COPD Assessment Test (CAT) and COPD exacerbation history were used to categorize residents by Global Initiative for Chronic Lung Disease (GOLD) A to D groups. Multivariate multinomial logit models mapped the MDS to GOLD A to D groups with stepwise selection of variables. Nursing home residents (N = 175) were 64% women and had a mean age of 77.9 years. Among residents, GOLD B was most common (A = 13.1%; B = 44.0%; C = 5.7%; D = 37.1%). Any long-acting bronchodilator (LABD) use and any dyspnea were significant predictors of GOLD A to D groups. The predicted MDS-GOLD group (A = 6.9%; B = 52.6%; C = 4.6%; D = 36.0%) showed good model fit (correctly predicted = 60.6%). Nursing home residents may underuse group-recommended LABD treatment (no LABD: B = 53.2%; C = 80.0%; D = 40.0%). The MDS, completed routinely for US NH residents, could potentially be used to estimate COPD severity. Predicted COPD severity with additional validation could provide a map to evidence-based treatment guidelines and may help to individualize treatment pathways for NH residents.

Changes in the clinical course of psoriasis post-COVID-19: a clinical case series

During COVID-19 pandemic, researchers and clinicians worldwide have noted changes in the course of chronic disorders of various organs and systems, which are likely to be related to systemic effects of the pathogen. Specific heterogeneous skin lesions have been identified in SARS-CoV-2 infection, including those in the patients without any history of skin disorders and exacerbation of chronic dermatoses and/or changes in their clinical manifestation. Post-COVID-19 manifestation and exacerbation of psoriasis have been also described in the literature.&#x0D; We retrospectively analyzed medical files of 22 in-patients with exacerbation of psoriasis after mild or moderate SARS-CoV-2 infection in the Department of Dermatovenereology from April 2020 to April 2021. There were 7 male patients aged 42 to 74 (meanSD 57.714.1) years and 15 female patients aged 40 to 78 (59.210.3) years. The duration of psoriasis ranged from 1 to 15 (8.74.7) years. Their mean PASI before the coronavirus infection had been 10.25.2. In the majority of the patients the psoriasis exacerbation after COVID-19 was associated with a significant increase of PASI to 18.594.82 (n=12, p 0.05), 32.221.71 (n=5, p 0.01), and to 596 (n=2, p 0.01). In 3 patients, in addition to the increase of the rash area (PASI 10 to 17, mean 13.42.63), psoriatic arthritis was newly diagnosed after COVID-19.&#x0D; We present a clinical case of a 33-year old male patient with a 15-year history of psoriasis, dramatic worsening of his benign psoriasis vulgaris with its transformation to the Zumbusch type of generalized pustular psoriasis after SARS-CoV-2 infection and rapid clinical improvement after the initiation of treatment with an interleukin-17A inhibitor secukinumab.&#x0D; This clinical case series may contribute to the knowledge on the new coronavirus infection and its effects on the course of psoriasis.

Exacerbation history, severity of dyspnoea and maintenance treatment predicts risk of future exacerbations in patients with COPD in the general population

BackgroundWhether risk of exacerbations of chronic obstructive pulmonary disease (COPD) is influenced by severity of symptoms and maintenance treatment is unclear. ObjectiveWe hypothesized that in addition to history of exacerbations of COPD, the severity of dyspnoea and use of maintenance medications are associated with risk of future exacerbations. MethodsWe included 96,462 adults from the Copenhagen General Population Study and assessed risk of moderate and severe exacerbations from 2003 to 2013 according to exacerbation history, dyspnoea score (mMRC), and presence/absence of maintenance treatment with inhaled long-acting bronchodilators and/or inhaled corticosteroids. FindingsAmong 13,380 individuals with COPD, we observed 1543 moderate and 348 severe exacerbations. In treatment naïve individuals and in those on maintenance treatment, history of previous exacerbations and to a smaller degree also dyspnoea were associated with a higher risk of future exacerbations; 32% of the treatment naïve individuals with mMRC≥2 and a single moderate exacerbation in the previous year experienced a moderate exacerbation during the following year compared with only 3% in the individuals with similar severity of dyspnoea but no exacerbations in the previous year yielding an adjusted hazard ratio of 6.26 (95% confidence interval, 3.70–10.58). InterpretationThis observational study of the general population suggests that in addition to exacerbation history also the severity of dyspnoea predicts the risk of future COPD exacerbations. In subjects with severe dyspnoea, a history of a single moderate exacerbation is associated with a high risk of future exacerbations, suggesting that this subgroup needs special attention in order to prevent these events.

Is single-inhaler triple therapy for COPD cost-effective in the UK? The IMPACT trial.

BackgroundThe IMPACT trial demonstrated superior outcomes following 52 weeks of once-daily single-inhaler treatment with fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) (100/62.5/25 μg) compared with once-daily FF/VI (100/25 μg) or UMEC/VI (62.5/25 μg). This study evaluated the cost-effectiveness of FF/UMEC/VI compared with FF/VI or UMEC/VI for the treatment of chronic obstructive pulmonary disease (COPD) from a UK National Health Service perspective.MethodsPatient characteristics and treatment effects from IMPACT were populated into a hybrid decision tree/Markov economic model. Costs (GB£ inflated to 2018 equivalents) and health outcomes were modelled over a lifetime horizon, with a discount rate of 3.5% per annum applied to both. Sensitivity analyses were performed to test the robustness of key assumptions and input parameters.ResultsCompared with FF/VI and UMEC/VI, FF/UMEC/VI provided an additional 0.296 and 0.145 life years (LYs) (discounted) and 0.275 and 0.118 quality-adjusted life years (QALYs), at an additional cost of £1129 and £760, respectively. Incremental cost-effectiveness ratios (ICERs) for FF/UMEC/VI were £4104/QALY and £3809/LY gained versus FF/VI and £6418/QALY and £5225/LY gained versus UMEC/VI. At a willingness-to-pay threshold of £20 000/QALY, the probability that FF/UMEC/VI was cost-effective was 96% versus FF/VI and 74% versus UMEC/VI. Results were similar in a subgroup of patients recommended triple therapy in the 2019 National Institute for Health and Care Excellence COPD guideline.ConclusionsFF/UMEC/VI single-inhaler triple therapy improved health outcomes and was a cost-effective option compared with FF/VI or UMEC/VI for patients with symptomatic COPD and a history of exacerbations in the UK at recognised cost-effectiveness threshold levels.

A new, three-dimensional approach to the GOLD COPD assessment tool

Background: The 2-dimensional, 4-quadrant 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD A-D assessment tool (GOLD2017) does not include lung function variables to classify patients into different risk groups. The previous 2011 tool (GOLD2011) classified cases in the upper-quadrants (higher risk groups) regardless of whether they had a history of exacerbations or worse lung function. We hypothesized that a modified, three-dimensional classification (GOLD3D) that separately includes assessment of lung function and exacerbations history would improve the ability to predict adverse events. Methods: A total of 1303 COPD patients were included in a historical cohort study. The ability of GOLD3D to predict outcomes (all-cause death and hospitalizations due to severe exacerbation) was compared with GOLD2017 and GOLD2011. Results: Mean follow-up was 45.0 ± 28.0 months. Two hundred and twenty-eight patients (17.5%) died and 337 (25.9%) subjects suffered at least a severe exacerbation that required hospital admission. The area under the receiver-operating characteristics curve for mortality prediction was slightly but significantly higher for GOLD3D than for GOLD2011. The area under the curve for prediction of severe exacerbations was significantly higher for GOLD3D than for GOLD2011 and GOLD2017. A worse ventilatory obstruction was associated in most cases with a higher mortality risk and a higher exacerbation risk for the GOLD2017 A-D groups. Conclusions: The proposed GOLD3D classification system upgrades the previous ones, and is advantageous in predicting future adverse events.

Role of Vitamin D in Reducing the Frequency of Asthma Attacks in Patients with Frequent Exacerbation of Asthma

Introduction: Vitamin D deficiency is common among asthmatics with literature suggesting that its low levels in the body may trigger exacerbations and decrease the response to corticosteroid treatment. It has also shown to inhibit the production of cytokines, which in turn enhances the body’s response to corticosteroid treatment during an exacerbation. Therefore, maintenance of adequate levels of vitamin D in patients with asthma may reduce the risk of exacerbation and improve their general health. This study aims to explore the role of vitamin D supplementation in preventing asthma exacerbations.&#x0D; Methods: This single blind parallel arm interventional study was conducted in the pulmonology ward in a tertiary care hospital from June 2018 to April 2020. Two hundred (n= 200) participants with a history of frequent acute exacerbation of asthma were enrolled in the study via consecutive convenient non-probability technique. Participants were divided into two groups; the placebo and the interventional group that received 200,000 IU of vitamin D capsule.&#x0D; Results: Compared to day 0, mean episodes of exacerbation in the interventional group were significantly lower after 180 days (1.1 ± 0.4 vs. 0.61 ± 0.3; p-value &lt;0.0001). Similarly, number of asthma attacks in past 7 days was significantly lower in intervention group after 180 days (4.4&#x0D; ± 2.7 vs. 3.1 ± 1.5; p-value 0.0001)&#x0D; Conclusion: Vitamin D supplementation is a safe and cost-friendly approach to reducing asthma exacerbations. It may also help to improve the condition in severe asthmatics with low vitamin D levels.

Integrated Disease Management for Chronic Obstructive Pulmonary Disease in Primary Care, from the Controlled Trial to Clinical Program: A Cohort Study.

PurposeIntegrated disease management (IDM) for COPD in primary care has been primarily investigated under clinical trial conditions. We previously published a randomized controlled trial (RCT) where the IDM intervention improved quality of life (QoL) and exacerbation-related outcomes. In this study, we assess the same IDM intervention in a real-world evaluation and identify patient characteristics associated with improved outcomes.MethodsThis historical cohort study included patients enrolled for 12 (±3 months) in the Best Care COPD IDM program. The main outcome was a ≥3 point improvement in COPD assessment test (CAT). Secondary outcomes were COPD exacerbations requiring antibiotics and/or prednisone, unscheduled physician visits, emergency department visits and hospitalizations.ResultsData for 571 patients (all patients) were included, 158 met the reference RCT eligibility (RCT matched). Improved QoL was observed in 43% (95% CI:38.9,47.2) of all patients, 47% (95% CI:39.5,55.6) of RCT matched vs 92% (95% CI:79.2,95.1) in the reference RCT intervention arm (n=72). Reductions (12 months IDM vs prior year) were observed in the proportion of patients experiencing exacerbation-related events (all patients): antibiotics/prednisone (−9.0%,95% CI:-13.9,-3.9); unscheduled physician (−33.1%,95% CI:-38.2,-27.9); emergency department (−9.6%,95% CI:-13.5,-5); and hospitalizations (−6.8%,95% CI:-10.0,-3.7). For the RCT matched group all reductions were comparable to the reference RCT intervention arm. The strongest predictors of improved QoL were baseline CAT, CAT≥20 vs CAT<10 (OR 15.6,95% CI:7.91,30.83), GOLD group B (OR 6.4,95% CI:3.42,11.85) and D (OR 5.64,95% CI:2.80,11.37) vs GOLD group A. Patients with prior antibiotic/prednisone use, FEV1 <30% predicted and GOLD group D were less likely to have no urgent health service utilization (OR 0.5,95% CI:0.30,0.68), (OR 0.2,95% CI:0.07,0.78) and (OR 0.3,95% CI:0.14,0.51), respectively.ConclusionBest Care COPD improved QoL and reduced exacerbation-related outcomes in a manner directionally similar to the RCT from which it emanated. Baseline QoL, exacerbation history, and GOLD category were identified as possible predictors of IDM impact and will inform future program development and resource allocation.

Terms and Definitions Used to Describe Recurrence, Treatment Failure and Recovery of Acute Exacerbations of COPD: A Systematic Review of Observational Studies.

IntroductionAcute exacerbations of chronic obstructive pulmonary disease (AECOPDs) are important clinical events, with many patients experiencing multiple AECOPDs annually. The terms used in the literature to define recurring AECOPD events are inconsistent and may impact the ability to describe the true burden of these events. We undertook a systematic review to identify and summarize terms and definitions used in observational studies to describe AECOPD-related events occurring after an initial AECOPD (hereafter “subsequent AECOPD”).MethodsPubMed was searched (2000–2019) for observational studies on subsequent AECOPD events using broad search strings for “COPD”, “exacerbation”, and “subsequent exacerbation events”. Only English-language studies were included. Small studies (n<50) and studies focusing on hospital re-admission only were excluded. Extracted data were analyzed descriptively to generate a narrative summary, using a thematic approach to group studies utilizing similar terms for subsequent AECOPD.ResultsForty-seven studies were included. No single, distinct terms or definitions were used to define and identify multiple occurrences of AECOPDs, though most (46) studies used one or more of four clustered terms and definitions: reapse (n = 13), recurrence/re-exacerbation (n = 11), treatment failure (n = 12) and non-recovery/time to recovery (n = 16). Heterogeneity was observed within and between the four clusters with respect to study setting, starting point for observing subsequent AECOPDs, time frame to identify a subsequent AECOPD (except for studies using “time to recovery”), and basis for identifying a subsequent exacerbation.ConclusionOur review demonstrates that subsequent AECOPDs (including events such as relapse, recurrence/re-exacerbation, treatment failure, non-recovery/time to recovery) are ill-defined in the observational study literature, emphasizing the need to reach consensus on precise and objective definitions (for example, when one AECOPD ends and another begins). Use of standardized terminology and definitions may aid comparability between, and synthesis of, studies, thus improving the understanding of the natural history and burden of exacerbations in COPD patients.

Benefit–harm analysis of azithromycin for the prevention of acute exacerbations of chronic obstructive pulmonary disease

BackgroundLow-dose oral azithromycin therapy is recommended as a preventive treatment for acute exacerbations of COPD. However, the overall benefit–harm balance of this treatment has not been well studied.MethodsA probabilistic Markov...

Evaluation of selected IL6/STAT3 pathway molecules and miRNA expression in chronic obstructive pulmonary disease

COPD has been regarded as a global epidemic due to an increase in pollution and tobacco exposure. Therefore, the study of molecular mechanism as the basis for modern therapy is important. The aim of the study was the assessment of gene expression levels, IL-6, IL-6ST, PIAS3, STAT3, and miRNAs, miRNA-1, miRNA-106b, miRNA-155, in patients with COPD. Induced sputum as well as PBMC were collected from 40 patients clinically verified according to the GOLD 2021 (A–D) classification and from the control group (n = 20). The levels of gene and miRNA expression were analysed by qPCR. In induced sputum IL6 was significantly down-regulated in COPD group compared with control (p = 0.0008), while IL6ST were up-regulated (p = 0.05). The results were also statistically significant for STAT3 (p = 0.04) and miRNA-155 (p = 0.03) with higher expression in the current smokers compared to ex-smokers. Higher expression levels for IL6ST (p = 0.03) in COPD patients with the exacerbation history compared to COPD patients without the exacerbation history were noted. Compared induced sputum and PB lymphocytes we observed higher expression of IL6 (p = 0.0003), STAT3 (p = 0.000001) miRNA-106b (p = 0.000069 and miRNA-155 (p = 0.000016) in induced sputum with lower expression of PIAS3 (p = 0.006), IL6ST (p = 0.002) and miRNA-1 (p = 0.001). Differences in gene expression levels of the IL-6/IL6ST/STAT3 pathway and miRNA depending on the smoking status and classification of patients according to GOLD suggest the importance of these genes in the pathogenesis of COPD and may indicate their potential utility in monitoring the course of the disease.