Lower Exacerbation Rates Research Articles

Clinical characteristics and outcomes of psoriasis patients with COVID-19: A retrospective, multicenter cohort study in China.

Limited information exists regarding the impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on psoriasis patients. The objective of this study was to identify clinical factors associated with the prognosis of psoriasis following SARS-CoV-2 infection. A retrospective, multicenter study was conducted between March and May 2023. Univariable and multivariable logistic regression analyses were employed to identify factors associated with coronavirus disease 2019 (COVID-19)-related psoriasis outcomes. The study included 2371 psoriasis patients from 12 clinical centers, with 2049 of them having been infected with SARS-CoV-2. Among the infected groups, lower exacerbation rates were observed in individuals treated with biologics compared to those receiving traditional systemic or nonsystemic treatments (22.3% [236/1058] vs . 39.8% [92/231] vs . 37.5% [140/373], P <0.001). Psoriasis progression with lesions (adjusted odds ratio [OR]=8.197, 95% confidence interval [95% CI]=5.685-11.820, compared to no lesions), hypertension (adjusted OR=1.582, 95% CI=1.068-2.343), traditional systemic (adjusted OR=1.887, 95% CI=1.263-2.818), and nonsystemic treatment (adjusted OR=1.602, 95% CI=1.117-2.297) were found to be associated with exacerbation of psoriasis after SARS-CoV-2 infection, but not biologics (adjusted OR=0.931, 95% CI=0.680-1.274, compared to no treatment), according to multivariable logistic regression analysis. A reduced risk of psoriasis exacerbation after SARS-CoV-2 infection was observed with biologics compared to traditional systemic and nonsystemic treatments. Significant risk factors for exacerbation after infection were identified as existing psoriatic lesions and hypertension. ClinicalTrials.gov (No. NCT05961605).

Understanding the Clinical Implications of Individual Patient Characteristics and Treatment Choice on the Risk of Exacerbation in Asthma Patients with Moderate-Severe Symptoms.

The assessment of future risk has become an important feature in the management of patients with asthma. However, the contribution of patient-specific characteristics and treatment choices to the risk of exacerbation is poorly understood. Here we evaluated the effect of interindividual baseline differences on the risk of exacerbation and treatment performance in patients receiving regular maintenance doses of inhaled corticosteroids (ICS) or ICS/long-acting beta-agonists (LABA) combination therapy. Exacerbations and changes to asthma symptoms 5-item Asthma Control Questionnaire (ACQ-5) were simulated over a 12-month period using a time-to-event and a longitudinal model developed from phaseIII/IV studies in patients with moderate-severe asthma (N = 16,282). Simulations were implemented to explore treatment performance across different scenarios, including randomised designs and real-world settings. Treatment options included regular dosing with ICS monotherapy [fluticasone propionate (FP)] and combination therapy [fluticasone propionate/salmeterol (FP/SAL) or budesonide/formoterol (BUD/FOR)]. Exacerbation rate was analysed using the log-rank test. The cumulative incidence of events was summarised stratified by treatment. Being a woman, smoker, having higher baseline ACQ-5 and body mass index (BMI) and lower forced expiratory volume in the first second (FEV1) are associated with increased exacerbation risk (p < 0.01). This risk is bigger in winter because of the seasonal variation effect. Across the different scenarios, the use of FP/SAL resulted in a 10% lower annual incidence of exacerbations relative to FP or regular dosing BUD/FOR, independently of baseline characteristics. Similar differences in the annual incidence of exacerbations were also observed between treatments in obese patients (BMI ≥ 25-35kg/m2) (p < 0.01) and in patients who do not achieve symptom control on FP monotherapy. Individual baseline characteristics and treatment choices affect future risk. Achieving comparable levels of symptom control whilst on treatment does not imply comparable risk reduction, as shown by the lower exacerbation rates in FP/SAL vs. BUD/FOR-treated patients. These factors should be considered as a basis for personalised clinical management of patients with moderate-severe asthma.

Association of Sodium-Glucose Cotransporter 2 Inhibitor vs Dipeptidyl Peptidase-4 Inhibitor Use With Risk of Incident Obstructive Airway Disease and Exacerbation Events Among Patients With Type 2 Diabetes in Hong Kong

Patients with diabetes are at higher risk for obstructive airway disease (OAD). In recent meta-analyses of post hoc analyses of cardiorenal trials, sodium-glucose cotransporter 2 inhibitors (SGLT2Is) were suggested to reduce the risk of OAD adverse events. However, a clinical investigation of this association is warranted. This study aimed to investigate the association of SGLT2I use vs dipeptidyl peptidase-4 inhibitor (DPP4I) use with OAD incidence and exacerbation events in patients with type 2 diabetes. This retrospective population-based cohort study used electronic health data from a territory-wide electronic medical database in Hong Kong. Data were collected for patients with type 2 diabetes who were prescribed SGLT2Is or DPP4Is between January 1, 2015, and December 31, 2018. Patients were followed for a median of 2.2 years between January 1, 2015, and December 31, 2020. A prevalent new-user design was adopted to match patients based on previous exposure to the study drugs. Propensity score matching was used to balance baseline characteristics. Patients with type 2 diabetes using SGLT2Is (exposure of interest) or DPP4Is (active comparator). The main outcomes were the first incidence of OAD and the count of OAD exacerbations. The risk of incident OAD was estimated using a Cox proportional hazards regression model. The rate of exacerbations was estimated using zero-inflated Poisson regression. Statistical analysis was performed on November 13, 2022. This study included 30 385 patients. The propensity score-matched non-OAD cohort (incidence analysis) consisted of 5696 SGLT2I users and 22 784 DPP4I users, while the matched OAD cohort (exacerbations analysis) comprised 381 SGLT2I users and 1524 DPP4I users. At baseline, 56% of patients in the non-OAD cohort were men and the mean (SD) age was 61.2 (9.9) years; 51% of patients in the OAD cohort were men and the mean age was 62.2 (10.8) years. Compared with DPP4I use, SGLT2I use was associated with a lower risk of incident OAD (hazard ratio, 0.65 [95% CI, 0.54-0.79]; P < .001) and a lower rate of exacerbations (rate ratio, 0.54 [95% CI, 0.36-0.83]; P = .01). The associations were consistent in sex subgroup analysis. The findings of this retrospective cohort study of patients with type 2 diabetes in Hong Kong suggest that SGLT2I use was associated with a reduced risk of incident OAD and a lower rate of exacerbations in a clinical setting compared with DPP4I use. These findings further suggest that SGLT2Is may provide additional protective effects against OAD for patients with type 2 diabetes and that further investigation is warranted.

Clinical predictors of treatment response to tiotropium add-on therapy in adult asthmatic patients: From multicenter real-world cohort data in Korea

BackgroundTiotropium, a long-acting muscarinic antagonist, is recommended for add-on therapy to inhaled corticosteroids (ICS)-long-acting beta 2 agonists (LABA) for severe asthma. However, real-world studies on the predictors of response to tiotropium are limited. We investigated the real-world use of tiotropium in asthmatic adult patients in Korea and we identified predictors of positive response to tiotropium add-on. MethodsWe performed a multicenter, retrospective, cohort study using data from the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA). We enrolled asthmatic participants who took ICS-LABA with at least 2 consecutive lung function tests at 3-month intervals. We compared tiotropium users and non-users, as well as tiotropium responders and non-responders to predict positive responses to tiotropium, defined as 1) increase in forced expiratory volume in 1 s (FEV1) ≥ 10% or 100 mL; and 2) increase in asthma control test (ACT) score ≥3 after 3 months of treatment. ResultsThe study included 413 tiotropium users and 1756 tiotropium non-users. Tiotropium users had low baseline lung function and high exacerbation rate, suggesting more severe asthma. Clinical predictors for positive response to tiotropium add-on were 1) positive bronchodilator response (BDR) [odds ratio (OR) = 6.8, 95% confidence interval (CI): 1.6–47.4, P = 0.021] for FEV1 responders; 2) doctor-diagnosed asthma-chronic obstructive pulmonary disease overlap (ACO) [OR = 12.6, 95% CI: 1.8–161.5, P = 0.024], and 3) initial ACT score <20 [OR = 24.1, 95% CI: 5.45–158.8, P < 0.001] for ACT responders. FEV1 responders also showed a longer exacerbation-free period than those with no FEV1 increase (P = 0.014), yielding a hazard ratio for the first asthma exacerbation of 0.5 (95% CI: 0.3–0.9, P = 0.016). ConclusionsThe results of this study suggest that tiotropium add-on for uncontrolled asthma with ICS-LABA would be more effective in patients with positive BDR or ACO. Additionally, an increase in FEV1 following tiotropium may predict a lower risk of asthma exacerbation.

Managing chronic obstructive pulmonary disease in primary care: clinical characteristics of patients receiving inhaled corticosteroids

AbstractBackgroundInhaled corticosteroid (ICS) therapy in patients with chronic obstructive pulmonary disease (COPD) has been associated with a variety of unfavourable effects, including increased risk of pneumonia, and is only recommended if specific characteristics are present to ensure patients derive the most benefit.AimThe primary objective was to evaluate the clinical characteristics of patients prescribed ICS therapy for COPD management in two primary care clinics at an academic medical centre. The secondary objectives were to examine provider assessment and barriers to prescribing patterns concordant with guidelines in the ambulatory care setting.MethodA retrospective 24‐month study at two primary care clinics was undertaken at an academic medical centre in Arkansas, United States and focused on adult patients who were prescribed ICS maintenance therapy. Individuals within each clinic were identified by Classification of Diseases, Tenth Revision, Clinical Modification (ICD‐10‐CM) codes indicative of COPD from 1 January 2019 to 31 December 2020. Spirometry was also required to confirm diagnosis.ResultsOf the 189 unique patients identified, 100 were eligible for review of clinical characteristics. All patients received ICS therapy in combination with a long‐acting beta agonist (LABA) with 55% of patients also receiving a long‐acting muscarinic antagonist (LAMA). Furthermore, 32% of patients visited the emergency department or were hospitalised for a COPD exacerbation within the previous year. Approximately 47% and 36% of patients had a history of pneumonia and an eosinophil count &lt;100 cells/mcL respectively. Barriers to guideline adherence were identified through open discussion with providers within each clinic, which included a lack of readily available resources in the clinic setting, suboptimal recognition of clinical tools within the electronic medical record and alternative guideline preferences.ConclusionA small portion of patients evaluated in the study were discovered to have clinical characteristics suggestive of strong ICS benefit as these therapies either lacked efficacy due to low blood eosinophil count or exacerbation rate (80% and 68% respectively), or increased the risk for harm in this population secondary to previous pneumonia diagnosis (47%).

Self-Reported Overall Adherence and Correct Inhalation Technique Discordance in Chronic Obstructive Pulmonary Disease Population.

Background: Adherence to inhaled medication constitutes a major problem in patients with chronic obstructive pulmonary disease (COPD) globally. However, large studies evaluating adherence in its entirety and capturing a large variety of potentially associated factors are still lacking. Objective: To study both elementary types of adherence to chronic inhaled COPD medication in “real-life” COPD patients and to assess relationships with a wide-ranging spectrum of clinical parameters. Methods: Data from the Czech Multicentre Research Database (CMRD) of COPD, an observational prospective study, were used. Overall adherence (OA) was evaluated with Morisky Medication Adherence Scale (©MMAS-4) and adherence to an application technique (A-ApplT) with the Five Steps Assessment. Mann–Whitney U test, Spearman’s correlation, and logistic regression were used to explore relationships between variables. Results: Data of 546 participants (69.6% of all patients from the CMRD) were analyzed. Two-thirds self-reported optimal OA, but only less than one-third demonstrated A-ApplT without any error. OA did not correlate with A-ApplT. Next, better OA was associated with higher education, a higher number of inhalers, a lower rate of exacerbations, poorer lung function, higher degree of upper respiratory tract symptoms (SNOT-22), absence of depressive symptoms, ex-smoking status, regular mouthwash after inhaled corticosteroids (ICS), and flu vaccination. By contrast, better A-ApplT was associated with a lower number of inhalers, better lung function, and regular mouthwash after ICS. Independent predictors of nonoptimal OA included lower degree of education, absence of flu vaccination, anemia, depression, and peptic ulcer history, whereas independent predictors of lower A-ApplT were lower education, absence of regular mouthwash after ICS, and higher COPD Assessment Test score. Conclusions: Parameters associated with OA and A-ApplT differ, and those associated with both adherence domains are sometimes associated inversely. Based on this finding, we understand these as two separate constructs with an overlap.

Comparative efficacy of mepolizumab, benralizumab, and dupilumab in eosinophilic asthma: A Bayesian network meta-analysis

The comparative safety and efficacy of the biologics currently approved for asthma are unclear. We compared the safety and efficacy of mepolizumab, benralizumab, and dupilumab in individuals with severe eosinophilic asthma. We performed a systematic review of peer-reviewed literature published 2000 to 2021. We studied Bayesian network meta-analyses of exacerbation rates, prebronchodilator FEV1, the Asthma Control Questionnaire, and serious adverse events in individuals with eosinophilic asthma. Eight randomized clinical trials (n= 6461) were identified. We found in individuals with eosinophils ≥300 cells/μL the following: in reducing exacerbation rates compared to placebo: dupilumab (risk ratio [RR], 0.32; 95% credible interval [CI], 0.23 to 0.45), mepolizumab (RR, 0.37; 95% CI, 0.30 to 0.45), and benralizumab (RR, 0.49; 95% CI, 0.43 to 0.55); in improving FEV1: dupilumab (mean difference in milliliters [MD] 230; 95% CI, 160 to 300), benralizumab (MD, 150; 95% CI, 100 to 200), and mepolizumab (MD, 150; 95% CI, 66 to 220); and in reducing Asthma Control Questionnaire scores: mepolizumab (MD, -0.63; 95% CI, -0.81 to -0.45), dupilumab (MD, -0.48; 95% CI, -0.83 to -0.14), and benralizumab (MD, -0.32; 95% CI, -0.43 to -0.21). In individuals with eosinophils 150-299 cells/μL, benralizumab (RR, 0.62; 95% CI, 0.52 to 0.73) and dupilumab (RR, 0.60; 95% CI, 0.38 to 0.95) were associated with lower exacerbation rates; and only benralizumab (MD, 81; 95% CI, 8 to 150) significantly improved FEV1. These differences were minimal compared to clinically important thresholds. For serious adverse events in the overall population, mepolizumab (odds ratio, 0.67; 95% CI, 0.48 to 0.92) and benralizumab (odds ratio, 0.74; 95% CI, 0.59 to 0.93) were associated with lower odds of a serious adverse event, while dupilumab was not different from placebo (odds ratio, 1.0; 95% CI, 0.74 to 1.4). There are minimal differences in the efficacy and safety of mepolizumab, benralizumab, and dupilumab in eosinophilic asthma.

One-year safety and tolerability of tezepelumab in Japanese patients with severe uncontrolled asthma: results of the NOZOMI study

Objective To assess the long-term safety of tezepelumab in Japanese patients with severe uncontrolled asthma. Methods This phase III, 52-week, open-label, single-arm study (NOZOMI, NCT04048343) evaluated the safety/tolerability of subcutaneous (SC) tezepelumab 210 mg every 4 weeks (Q4W) in Japanese patients aged 12–80 years with severe uncontrolled asthma using medium- to high-dose inhaled corticosteroids and at least one additional asthma controller medication, with/without oral corticosteroids. Exploratory outcomes included efficacy (asthma exacerbations, lung function, and asthma control), pharmacokinetic parameters, and immunogenicity. Results Among 65 patients (median age 52 years), 39 (60%) experienced 94 adverse events (AEs; predominantly nasopharyngitis [13/65]) of mild (49.2%), moderate (7.7%), or severe (3.1%) intensity. Two patients had transient injection site erythema related to tezepelumab. Four patients reported serious AEs unrelated to tezepelumab and one AE led to treatment discontinuation. AEs of special interest were infrequent and generally mild/moderate. Apart from a decrease in blood eosinophils (an expected pharmacodynamic effect), no notable trends/clinically relevant changes in hematology, clinical chemistry, or urinalysis parameters were observed. Among exploratory outcomes, tezepelumab was associated with a low annualized asthma exacerbation rate over the study period (0.11/patient-year), improved lung function (mean [standard deviation] change from baseline of 0.075 [0.226] L in pre-dose/pre-bronchodilator forced expiratory volume in 1 s), and better asthma control versus baseline (responder rate: 71.4% at Week 52). Conclusion Tezepelumab 210 mg SC Q4W in Japanese patients with severe uncontrolled asthma showed safety/tolerability profiles similar to international data, with low exacerbation rates and improvements in lung function and asthma control.

The effects of reducing the frequency of long-term physiotherapy on patients with severe COPD: a Dutch multicenter study

Purpose To investigate if a reduction in the frequency of long term physiotherapy leads to an increase of exacerbations, prescriptions of medication and hospital admissions in patients with chronic obstructive pulmonary disease (COPD). Intervention 296 adults with severe COPD (GOLD III & IV) followed a weekly physiotherapy program with a focus on endurance capacity, muscle function and education. In this study, participants were divided into two groups: a High-Frequency Group (HFG) and a Low Frequency Group (LFG). Results The HFG had consistent lower rates of exacerbations (LFG x̄ 4.14; HFG x̄ 2.71), prescriptions antibiotics LFG x̄ 28.63; HFG x̄ 12.64), number of hospital admissions (LFG x̄ 1.22; HFG x̄ 0.36) and days in hospital (LFG x̄ 8.85; HFG x̄ 1.36) compared to LFG. Differences between both groups (Independent samples T-test, p < 0.05) were significant for exacerbations (p = 0.001), antibiotic prescriptions (p = 0.009), hospital admissions (p = 0.000) and days in hospital (p = 0.000). Conclusion Reducing the frequency of long-term physiotherapy leads to significantly higher rates of exacerbations, medication use, hospital admissions and days in hospital in patients with severe COPD.

Treatment persistence and exacerbations in patients with asthma initiating treatment with inhaled corticosteroids and beta-adrenergic agonists: retrospective cohort study

ObjectiveTo determine treatment persistence and exacerbations in patients initiating inhaler treatment with fixed-dose combinations of inhaled corticosteroids/long-acting beta-2-adrenergic agonists (ICS/LABA) for the treatment of asthma.DesignRetrospective observational study conducted by review...

Dupilumab Reduces Oral Corticosteroid Use in Patients With Corticosteroid-Dependent Severe Asthma: An Analysis of the Phase 3, Open-Label Extension TRAVERSE Trial

Many patients with severe asthma require chronic corticosteroid treatment to maintain asthma control. Are the reduction in oral corticosteroid (OCS) use and the clinical efficacy observed with dupilumab treatment maintained long-term in patients with severe OCS-dependent asthma? The LIBERTY ASTHMA TRAVERSE study (ClinicalTrials.gov identifier: NCT02134028) was a multinational, multicenter, single-arm, open-label extension study in patients≥ 12 years of age with asthma who participated in previous dupilumab studies. Treatment consisted of dupilumab 300mg every 2weeks for up to 96weeks. In this analysis, we present the data from patients who initially enrolled in the LIBERTY ASTHMA VENTURE study (ClinicalTrials.gov identifier: NCT02528214), a 24-week placebo-controlled study of dupilumab in patients with OCS-dependent severe asthma, and continued in the TRAVERSE study. The subgroups analyzed were: those who received dupilumab in both (dupilumab/dupilumab group) and those who received placebo in the VENTURE study and dupilumab in the TRAVERSE study (placebo/dupilumab group). Outcomes included OCS use, exacerbation rates, and measures of lung function and asthma control. Ninety patients treated with dupilumab/dupilumab and 97 patients treated with placebo/dupilumab in the VENTURE study were enrolled and treated in the TRAVERSE study, with a mean OCS dosage of 11.0mg/d (dupilumab) and 11.6mg/d (placebo) at VENTURE study baseline. At TRAVERSE week 0, the mean daily OCS dosage was 3.1mg/d and 6.4mg/d (percentage decrease from the VENTURE study baseline, 68.8%and 41.3%) for the dupilumab/dupilumab group and placebo/dupilumab group, respectively, and decreased to 2.2mg/d and 4.9mg/d (78.3%and 53.4%) at week 48 and to 1.2mg/d and 3.0mg/d (89.3%and 74.4%) at week 96, respectively. Exacerbation rates were low during the TRAVERSE study. Further improvements from the VENTURE to TRAVERSE studies also were seen in FEV1 and 5-item Asthma Control Questionnaire scores. Safety findings were consistent with the known dupilumab safety profile. In the open-label TRAVERSE study, dupilumab demonstrated the ability to sustain the OCS dosage reduction from the parent OCS-sparing study, while maintaining a low exacerbation rate and improved lung function. ClinicalTrials.gov; Nos.: NCT02134028 (TRAVERSE) and NCT02528214 (VENTURE); URL: www. gov.

A systematic review of outcomes in COVID-19 patients treated with western medicine in combination with traditional Chinese medicine versus western medicine alone.

Since the outbreak of coronavirus disease 2019 (COVID-19) in late 2019, it has evolved into a global pandemic that has become a substantial public health concern. COVID-19 is still causing a large number of deaths in several countries around the world because of the lack of effective treatment. To systematically compare the outcomes of COVID-19 patients treated with integrated Chinese with western (ICW) medicine versus western medicine (WM) alone by pooling the data of published literature, and to determine if ICW treatment of COVID-19 patients has better clinical outcomes. We searched PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), China Clinical Trial Registry, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI) and Wanfang databases using keywords related to COVID-19, traditional Chinese medicine (TCM) and treatment effect. The search deadline was until 10 February 2021. All randomised controlled (RC) and non-randomised controlled (NRC) clinical trials of the ICW or WM treatment of COVID-19 patients were included. We analysed the effective rate, cure rate, exacerbation rate, turning negative rate of viral nucleic acid, remission rate and remission time of symptoms such as fever, cough, feebleness and chest computed tomography (CT) and the number of white blood cells (WBCs) and lymphocytes (LYM) of the COVID-19 patients. For qualitative and quantitative data, the ratio risk (RR) and weighted mean difference (WMD) were used as the indexes of the statistical analysis, respectively. RevMan 5.4 was used to perform meta-analyses and forest plots with the fixed-effects and random-effects models. Cochrane risk of bias tool (RoB 2.0) was used to assess the risk of bias in the included RC trials, whereas risk of bias in non-randomised studies of interventions was used to assess the risk of bias in NRC trials. This research includes 16 studies with 1645 valid confirmed COVID-19 patients, among which 895 patients of the experimental group received ICW treatment whereas 750 patients of the control group received WM treatment. The outcomes were assessed in three aspects, that is, overall indicator, symptoms indicator and blood indicator, respectively, and the results showed that the ICW group had better treatment outcomes compared with the WM. Among the overall indicators, the ICW group displayed a higher effective rate (RR = 1.24, 95% confidence interval (CI): 1.16-1.33), clinical cure rate (RR = 1.27, 95% CI: 1.03-1.56) and lower exacerbation rate (RR = 0.36, 95% CI: 0.25-0.52), but no statistical difference was observed in the turning negative rate of viral nucleic acid (RR = 1.20, 95% CI: 0.78-1.85). Among the symptom indicators, the ICW group had a higher fever remission rate (RR = 1.24, 95% CI: 1.09-1.42), less fever remission time (WMD = -1.49, 95% CI: -1.85 to -1.12), a higher cough remission rate (RR = 1.38, 95% CI: 1.10-1.73) and a feebleness remission rate (RR = 1.45, 95% CI: 1.18-1.77), less cough remission time (WMD = -1.61, 95% CI: -2.35 to -0.87) and feebleness remission time (WMD = -1.50, 95% CI: -2.38 to -0.61) and better improvement in chest CT (RR = 1.19, 95% CI: 1.11-1.28). For blood indicator, the number of WBCs in the blood of patients of ICW group rebounded significantly (WMD = 0.35, 95% CI: 0.16-0.54), and the recovery of LYM in the blood was more obvious (WMD = 0.23, 95% CI: 0.06-0.40). The results of this study show that the outcomes in COVID-19 patients treated by the ICW is better than those treated by the WM treatment alone, suggesting that WM and TCM can be complementary in the treatment of COVID-19.

DEFINING THE FREQUENT EXACERBATOR PHENOTYPE DURING A PANDEMIC IN COPD

TOPIC: Obstructive Lung Diseases TYPE: Original Investigations PURPOSE: Prior-year exacerbation history is the best predictor of future exacerbations and forms part of the global clinical guidelines for management of COPD patients. Frequent exacerbators (FEs) are patients who have >=2 moderate-to-severe exacerbations in a year. They have a high risk of poor outcomes and may benefit from close monitoring and therapeutic interventions. Clinical trials of novel COPD treatments that reduce exacerbations also select for patients who meet the FE definition. During the COVID-19 pandemic, the COPD exacerbation rate has declined dramatically, complicating the use of prior-year exacerbation frequency for identifying FEs. An alternate approach is to extend the observation period from one to two previous years; however, the impact of this change on the prognostic value of exacerbation history is not well understood. The aim of this study was to compare the prevalence of FEs in subsequent years when a two-year vs. one-year exacerbation history is used to identify FEs. METHODS: We used US national claims data (IQVIA Pharmetrics Plus) from 2015-2019 to identify COPD patients aged >=40 years on standard-of-care combination therapy and with 1-3 years of follow-up. Two patient groups were created; those with ≥2 exacerbations over a continuous 12-month period within two years preceding follow-up [group A] and those with ≥2 exacerbations in the year preceding follow-up [group B, a subset of group A]. Exacerbations were defined as COPD-related ER visits or hospital admissions and prescription fills for an antibiotic or an oral corticosteroid burst. We compared baseline characteristics and proportions of FEs in each follow-up year between groups A and B. RESULTS: Of the 41,998 COPD patients who met the inclusion criteria, 14,972 (35.6%) were in group A and 9,781 (23.3%) were in group B. Patients in groups A and B had comparable age and gender distributions. In years 1, 2 and 3 of follow-up, 41.7%, 38.6% and 38.0% of group A patients and 48.9%, 44.8% and 43.5% of group B patients had >=2 exacerbations. Overall, group A patients had a lower rate of exacerbations during follow-up (0.87 per patient-year (PY), 95% CI: 0.86-0.88) compared to group B patients (1.00 per PY, 95% CI: 0.99-1.01). Among patients with 3 years of follow-up, the proportions of FEs in group A vs. B were: 38.2% vs. 45.6% in year 1, 22.4% (58.6% of year 1 FEs) vs. 28.5% (62.6% of year 1 FEs) in year 2 and 15.7% (70.1% of year 2 FEs) vs. 20.5% (71.9% of year 2 FEs) in year 3. CONCLUSIONS: 41.7% of group A patients and 48.9% of group B patients were FEs in year 1 of follow-up. In both groups, the overall prevalence of FEs was consistent in each year of follow-up and the FE phenotype remained stable over the three years of follow-up. CLINICAL IMPLICATIONS: A two-year exacerbation history may be an acceptable alternative to the prior-year history to guide patient management while pandemic measures continue to impact typical patient behaviors and exacerbation rates. DISCLOSURES: Employee relationship with Genentech Inc. Please note: Current Added 04/01/2021 by Parul Dayal, source=Web Response, value=Salary Employee relationship with Genentech, Inc. Please note: 03/2021 to current Added 04/29/2021 by Colin Dimond, source=Web Response, value=Salary No relevant relationships by Matthew Kent, source=Web Response Employee relationship with Genentech Please note: June 2020 - ongoing Added 04/29/2021 by Divya Mohan, source=Web Response, value=Salary Employee relationship with GSK Please note: Aug 2015 - May 2020 Added 04/29/2021 by Divya Mohan, source=Web Response, value=Salary Employee relationship with Genentech Please note: 2019-present Added 04/27/2021 by Shemra Rizzo, source=Web Response, value=Salary Stockholder relationship with Roche Please note: 2019-present Added 04/27/2021 by Shemra Rizzo, source=Web Response, value=stocks Employee relationship with Genentech Please note: 4 years Added 04/27/2021 by Xiaoying Yang, source=Web Response, value=Salary

The Benefit of Benralizumab Monoclonal Antibody Treatment for Severe Eosinophilic Asthma in a Case Series (Pulmonology Clinic Târgu Mureș, Romania)

Abstract Background: Monoclonal antibody therapy is currently an additional treatment option to reduce exacerbations and improve symptom control in patients with severe eosinophilic asthma (SEA) that is uncontrolled despite treatment with high-dose inhaled corticosteroids and long-acting beta-2 agonists. Benralizumab, a monoclonal antibody that binds to the interleukin-5 receptor (IL-5), significantly reduces symptoms and annual exacerbations, as well as the use of systemic corticosteroids in patients with SEA. However, few studies are available on the effectiveness of this biological treatment in real life. The aim of this case series was to evaluate the efficacy of benralizumab by analyzing changes in clinical parameters and blood eosinophils in patients with SEA. Methods: We analyzed four patients with SEA who started treatment with benralizumab. The history of symptoms and exacerbations, eosinophil counts, data regarding the oral corticosteroid dose, need for rescue treatment, spirometry measurements and asthma control questionnaires (ACT) regarding the level of asthma control were recorded. A positive response to treatment was defined by a significant reduction in eosinophil counts, increased ACT scores, and lower rates of exacerbations. Results and conclusions: Benralizumab monoclonal antibody was effective in all four patients. This was shown by a reduction in exacerbation rates, symptom severity, and lower dose of oral corticosteroids and rescue medication. This novel treatment was well tolerated by the analyzed patients, thus indicating that benralizumab is an attractive choice for patients due to eosinophilic count reduction as well as the less frequent dosing schedule. However, further studies are required, on larger populations.

Comparative Effectiveness and Safety of Different Types of Inhaled Long-Acting β2-Agonist Plus Inhaled Long-Acting Muscarinic Antagonist vs Inhaled Long-Acting β2-Agonist Plus Inhaled Corticosteroid Fixed-Dose Combinations in COPD A Propensity Score-Inverse Probability of Treatment Weighting Cohort Study

Despite multiple available fixed-dose combinations (FDCs) of inhaled long-acting β2-agonists (LABAs) plus long-acting muscarinic antagonists (LAMAs) and LABAs plus inhaled corticosteroids (ICS) for COPD, uncertainty remains regarding their comparative effects. Can comparative effectiveness and safety of LABA plus LAMA (LABA/LAMA) and LABA plus ICS (LABA/ICS) FDCs vary by different individual components of the dual combinations in COPD? We conducted a new user, propensity score-inverse probability of treatment weighting cohort study to compare the effectiveness and safety of two frequently used LABA/LAMA FDCs (indacaterol plus glycopyrronium [IND/GLY] and vilanterol plus umeclidinium [VI/UMEC]) vsthree commonly prescribed LABA/ICS FDCs (salmeterol plus fluticasone propionate [SAL/FP], formoterol fumarate plus budesonide [FF/BUD], and formoterol fumarate plus beclomethasone dipropionate [FF/BDP]) using the Taiwanese nationwide health care claims from 2014 through 2017. The primary effectiveness outcome was the annual moderate to severe exacerbation rate, and safety outcomes included risks of severe pneumonia and cardiovascular disease requiring hospitalization. Weighted generalized linear mixed models and Cox proportional hazard models were used to assess the effectiveness and safety outcomes, respectively. Patients with COPD initiating IND/GLY and VI/UMEC showed an 11%(incidence rate ratio [IRR], 0.89; 95%CI, 0.80-0.98) and 20%(IRR, 0.80; 95%CI, 0.71-0.90) reduced annual rate of moderate to severe exacerbations, respectively, than those initiating SAL/FP, but showed a similar rate as those initiating FF/BUD or FF/BDP. Both LABA/LAMA FDCs, compared with SAL/FP and VI/UMEC vsFF/BDP, were associated with a 27%(hazard ratio [HR], 0.73; 95%CI, 0.59-0.90) to 42%(HR, 0.58; 95%CI, 0.48-0.70) reduced pneumonia risk. Cardiovascular risk was comparable in five groups. An intraclass difference existed in rates of moderate to severe COPD exacerbation and risks of pneumonia among LABA/ICS FDCs, but not between LABA/LAMA FDCs. Both LABA/LAMAs vsSAL/FP are associated with a lower exacerbation rate and pneumonia risk, but exhibit similar effectiveness and safety outcomes compared with FF/BDP or FF/BUD, suggesting that comparative effects may differ by individual components of the dual therapies in COPD.

The Impact of Tobacco Smoking on Adult Asthma Outcomes.

Background: Tobacco smoking is associated with more severe asthma symptoms, an accelerated decline in lung function, and reduced responses to corticosteroids. Our objective was to compare asthma outcomes in terms of disease control, exacerbation rates, and lung function in a population of asthmatic patients according to their smoking status. Methods: We compared patients’ demographics, disease characteristics, and lung-function parameters in current-smokers (CS, n = 48), former-smokers (FS, n = 38), and never-smokers (NS, n = 90), and identified predictive factors for asthma control. Results: CS had a higher prevalence of family asthma/atopy, a lower rate of controlled asthma, impaired perception of dyspnea, an increased number of exacerbations, and poorer lung function compared to NS. The mean asthma control questionnaire’s (ACQ) score was higher in CS vs. NS and FS (1.9 vs. 1.2, p = 0.02). Compared to CS, FS had a lower rate of exacerbations, a better ACQ score (similar to NS), a higher prevalence of dyspnea, and greater lung-diffusion capacity. Non-smoking status, the absence of dyspnea and exacerbations, and a forced expiratory volume in one second ≥80% of predicted were associated with controlled asthma. Conclusions: CS with asthma exhibit worse clinical and functional respiratory outcomes compared to NS and FS, supporting the importance of smoking cessation in this population.

Clinical and Economic Consequences of Inhaled Corticosteroid Doses and Particle Size in Triple Inhalation Therapy for COPD: Real-Life Study.

ObjectiveTo determine the clinical and economic consequences of inhaled corticosteroid doses and particle size in patients on triple-inhalation therapy for COPD.MethodsPatients aged ≥40 years who initiated treatment with multi-inhaler triple-inhaled therapy between 1 January 2015 and 31 March were included and followed for 1 year. Patients were grouped according to inhaled corticosteroid (ICS) dose (low/medium/high) and particle size device (extrafine/non-extrafine particles). Outcome variables were moderate and severe exacerbations, pneumonia and healthcare resource use (HCRU) costs. A multivariate analysis was performed for model correction (p<0.05).ResultsA total of 2185 patients (mean age 72.3 years, 82.9% male) were analysed. Of these, 849 (38.9%) patients received low-dose ICS, 612 medium-dose ICS (28.0%) and 724 (33.1%) high-dose ICS. Exacerbations occurred more frequently with increasing IC dose (low: 26.4%, medium: 28.7% and high: 30.4%; p=0.047), as did the proportion of pneumonia (3.4%, 4.2% and 6.9%, respectively (p=0.041)). The annual mean cost/unit was € 2383 for low dose, € 2401 for medium dose and € 2625 for high dose (p=0.024). Four hundred and sixty-two (31.6%) patients used an extrafine particle device and 999 (68.4%) a non-extrafine particle device: the proportion of exacerbations was 24.0% vs 30.4% (p=0.012), and the annual mean cost/unit was € 2090 vs € 2513, respectively (p<0.001). The number of exacerbations was directly correlated with FEV1 (β= −0.157), age (β=0.071), Charlson index (β=0.050) and device type (extrafine: β=0.049) (p<0.02).ConclusionIn patients with COPD receiving multi-inhaler triple therapy, higher ICS doses were not associated with a further reduction in exacerbations, whereas we found an increased risk of pneumonia. The use of inhaler devices delivering extrafine ICS particle was associated with a lower rate of exacerbations, resulting in lower overall HCRU costs.

Is Quarantine for COVID-19 Pandemic Associated with Psychological Burden in Primary Ciliary Dyskinesia?

Background: Information on psychological impact of COVID-19 quarantine in primary ciliary dyskinesia (PCD), a chronic disorder with recurrent pulmonary exacerbations, is lacking. Psychological well-being was prospectively assessed during COVID-19 lockdown in Italy in a PCD population. Methods: we recruited 27 PCD patients and 27 healthy controls. To assess psychological well-being, psychological general well-being index and parenting stress index-short questionnaires were administered to participants ≥15 years-old and to mothers of participants <15 years-old, respectively. The PCD exacerbations since outbreak onset and frequency of quarantine weekly chest physiotherapy were compared to the same period of 2019. Outcomes: 70% of PCD mothers and 90% of PCD patients did not show parental stress levels or distress levels, respectively, and these groups showed no significant difference in stress compared to controls. The PCD pulmonary exacerbations occurred less frequently and weekly chest physiotherapy sessions significantly increased compared to the same period during 2019 (p < 0.05). Interpretation: During COVID-19 quarantine, a PCD population showed psychological well-being. Low exacerbation rate, explained by lower infectious exposure or improved compliance to chest physiotherapy, likely contributed to psychological well-being. Evaluating psychological burden and parental stress is a valuable tool for measuring the emotional impact of PCD and improving PCD medical care.

Maintenance inhaler therapy preferences of patients with asthma or chronic obstructive pulmonary disease: a discrete choice experiment

BackgroundA variety of maintenance inhaler therapies are available to treat asthma and COPD. Patient-centric treatment choices require understanding patient preferences for the alternative therapies.MethodsA self-completed web-based discrete choice experiment was...

Effectiveness of chest physiotherapy and pulmonary rehabilitation in patients with non-cystic fibrosis bronchiectasis: a narrative review.

Respiratory physiotherapy and rehabilitation are important therapeutic options in non-cystic fibrosis bronchiectasis (NCFB). The aims of this review of clinical trials were to evaluate the safety and the effects on physiologic and clinical outcomes of airway clearance techniques (ACTs) and rehabilitation in NCFB patients, in comparison to usual care. The search was performed on March 2018 by using PubMed and PeDro databases. 33 studies were selected. The use of ACTs for NCFB were effective in increasing sputum volume although no benefit in quality of life (QoL) or pulmonary exacerbations were observed. There were no differences in effectiveness between the several techniques used. Humidification and saline inhalation were able to aid airway clearance. Hypertonic solution (HS) was more effective than isotonic solutions (IS) in improving expectoration and sputum viscosity. Pulmonary rehabilitation (PR) was found to be associated with short term benefits in exercise capacity, dyspnea and fatigue. Exercise training seems to improve quality of life and lower exacerbation rate, but long-term data are not available. Further studies are necessary to identify the most feasible long-term outcomes such as QoL and exacerbation rate.