Inhaled Corticosteroids Group Research Articles

Retrospective, observational study of different medication regimens and outcome in children with cough variant asthma.

This retrospective longitudinal cohort study aimed to explore the best therapeutic regimen and treatment duration of cough variant asthma (CVA) in children. A total of 314 children with CVA were divided into receive inhaled corticosteroids (ICS) combined with long-acting beta2-agonist (LABA) group, ICS combined with leukotriene receptor antagonists (LTRA) group, ICS monotherapy group and LTRA monotherapy group. All clinical data were statistically analyzed. Logistic regression model was used to compare the advantages and disadvantages of different treatment schemes at each follow-up time point and the best treatment scheme. The Cox proportional hazard regression model based on inverse probability weighting was used to compare the effects of different medication regimens on adverse outcomes with asthma recurrence or progression as the end point. (1) After comprehensive analysis, ICS + LABA group was the preferred control regimen for CVA within 8 weeks. After 8 weeks of diagnosis, the efficacy of ICS group or LTRA group was comparable to that of ICS + LABA group and ICS + LTRA group. (2) The ICS + LABA group showed a significant improvement in cough at an early stage, particularly at 4 weeks; the symptoms of ICS + LTRA and ICS groups were significantly improved at 36 weeks. The LTRA group alone showed significant improvement at 20 weeks. ICS + LABA, ICS + LTRA, ICS alone and LTRA alone can effectively treat CVA. ICS + LABA could improve the symptoms most quickly within 8 weeks after CVA diagnosis, followed by ICS + LATR group. After 8 weeks, it can be reduced to ICS alone to control CVA for at least 36 weeks based on the remission of symptoms in children.

Clinical characteristics and effects of inhaled corticosteroid in patients with post-COVID-19 chronic cough during the Omicron variant outbreak

BackgroundChronic cough is a common symptom in patients post the coronavirus disease 2019 (COVID-19). In this study, we aimed to investigate the efficacy of inhaled corticosteroids (ICS) and the clinical characteristics of patients with post-COVID-19 chronic cough during the Omicron era.MethodsAn ambispective, longitudinal cohort study was conducted that included patients with post-COVID-19 who attended the respiratory clinic at our hospital between January 1, 2023, and March 31, 2023 with a complaint of persistent cough lasting more than 8 weeks. At 30 and 60 days after the first clinic visit for post-COVID-19 chronic cough, enrolled patients were prospectively followed up. We compared the changes in symptoms and pulmonary function between patients receiving ICS treatment (ICS group) and those not receiving ICS treatment (NICS group) at the two visits.ResultsA total of 104 patients with post-COVID-19 chronic cough were enrolled in this study (ICS group, n = 51; NICS group, n = 53). The most common symptoms accompanying post-COVID-19 chronic cough were sputum (58.7%, 61/104) and dyspnea (48.1%, 50/104). Seventy-one (82.6%, 71/86) patients had airway hyperresponsiveness, and 49 patients (47.1%, 49/104) were newly diagnosed with asthma. Most patients (95.2%, 99/104) exhibited improvement at 60 days after the first visit. The pulmonary function parameters of the patients in the ICS group were significantly improved compared to the baseline values (P < 0.05), and the improvement in the FEV1/FVC was significantly greater than that in the NICS group (P = 0.003) after 60 days.ConclusionsSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may contribute to the pathogenesis of asthma, which could be the underlying cause of persistent cough post-COVID-19 infection. Post-COVID-19 chronic cough during the Omicron era was often accompanied by sputum, dyspnea, and airway hyperresponsiveness. ICS treatment did not have a significant impact on symptom management of post-COVID-19 chronic cough; however, it can improve impaired lung function in in these individuals.

Inhaled corticosteroids to improve lung function in children (aged 6–12 years) who were born very preterm (PICSI): a randomised, double-blind, placebo-controlled trial

Despite the substantial burden of lung disease throughout childhood in children who were born very preterm, there are no evidence-based interventions to improve lung health beyond the neonatal period. We tested the hypothesis that inhaled corticosteroid improves lung function in this population. PICSI was a randomised, double-blind, placebo-controlled trial at Perth Children's Hospital (Perth, WA, Australia) to assess whether fluticasone propionate, an inhaled corticosteroid, improves lung function in children who had been born very preterm (<32 weeks of gestation). Eligible children were aged 6-12 years and did not have severe congenital abnormalities, cardiopulmonary defects, neurodevelopmental impairment, diabetes, or any glucocorticoid use within the preceding 3 months. Participants were randomly assigned (1:1) to receive 125 μg fluticasone propionate or placebo twice daily for 12 weeks. Participants were stratified for sex, age, bronchopulmonary dysplasia diagnosis, and recent respiratory symptoms using the biased-coin minimisation technique. The primary outcome was change in pre-bronchodilator forced expiratory volume in 1 s (FEV1) after 12 weeks of treatment. Data were analysed by intention-to-treat (ie, all participants who were randomly assigned and took at least the tolerance dose of the drug). All participants were included in the safety analyses. This trial is registered at the Australian and New Zealand Clinical Trials Registry, number 12618000781246. Between Oct 23, 2018, and Feb 4, 2022, 170 participants were randomly assigned and received at least the tolerance dose (83 received placebo and 87 received inhaled corticosteroid). 92 (54%) participants were male and 78 (46%) were female. 31 participants discontinued treatment before 12 weeks (14 in the placebo group and 17 in the inhaled corticosteroid group), mostly due to the impact of the COVID-19 pandemic. When analysed by intention-to-treat, the change in pre-bronchodilator FEV1 Z score over 12 weeks was -0·11 (95% CI -0·21 to 0·00) in the placebo group and 0·20 (0·11 to 0·30) in the inhaled corticosteroid group (imputed mean difference 0·30, 0·15-0·45). Three of 83 participants in the inhaled corticosteroid group had adverse events requiring treatment discontinuation (exacerbation of asthma-like symptoms). One of 87 participants in the placebo group had an adverse event requiring treatment discontinuation (inability to tolerate the treatment with dizziness, headaches, stomach pains, and worsening of a skin condition). As a group, children born very preterm have only modestly improved lung function when treated with inhaled corticosteroid for 12 weeks. Future studies should consider individual phenotypes of lung disease after preterm birth and other agents to improve management of prematurity-associated lung disease. Australian National Health and Medical Research Council, Telethon Kids Institute, and Curtin University.

Effects of Short-Acting Beta-Agonist (SABA) Alone and SABA with Inhaled Corticosteroids in the Management of Asthma among Children

Introduction: However, the comparative efficacy of SABA alone vs SABA in conjunction with ICS in the treatment of childhood asthma remains an important topic of research. Understanding the comparative efficacy of SABA alone versus SABA in conjunction with ICS in the treatment of childhood asthma is critical for evidence-based decision-making. Methodology: This randomized controlled study (RCT) included 80 children aged 6 to 12 years who were diagnosed with mild chronic asthma. The participants were separated into two groups: SABA alone and SABA plus ICS. For symptom alleviation, the SABA alone group got as-needed treatment with a short-acting beta-agonist (SABA). The SABA with ICS group got SABA therapy on a regular basis for symptom alleviation, as well as daily inhaled corticosteroid (ICS) therapy for maintenance. To compare the outcomes of the two groups, statistical analysis was done using an independent t-test. A statistically significant p-value of less than 0.05 was evaluated. Results: Spirometry measures were taken to quantify vital capacity (VC), forced expiratory volume at one second (FEV1), and the FEV1/VC ratio. Both groups had lower baseline values for these measures, indicating decreased lung function. However, both groups' lung function improved significantly following the intervention (p&lt;0.05). Practical Implication: The findings of this study can not only educate clinical practice, but also assist healthcare practitioners in making informed treatment decisions in order to enhance asthma management and outcomes for patients. Conclusion: According to the data, combining these drugs can enhance symptom management and lung function in children with moderate chronic asthma. Keywords: Asthma, Lung Function test, Forced expiratory volume, Short Acting Beta Agonist, Inhaled Corticosteroids, Children.

The effects of different inhalation therapies on less symptomatic chronic obstructive pulmonary disease patients in a Chinese population: a real-world study

Background The Global Initiative for Chronic Obstructive Lung Disease (GOLD) document suggests that patients with chronic obstructive pulmonary disease (COPD) should be divided into a less symptomatic group. Moreover, single-inhaled drugs are recommended as initial inhalation therapy for them. However, many less symptomatic patients are provided double or triple-inhaled drugs as initial therapy in the real world. This study aimed to describe the inhalation prescriptions and compare the effects of different inhalation therapies on less symptomatic COPD patients. Patients and methods This was an observational study. Stable COPD patients were recruited and divided into a less symptomatic group including Groups A and C based on the GOLD 2019 document. We collected the data of inhalation therapies prescriptions. Then, the patients were classified into long-acting muscarinic antagonist (LAMA), long-acting β2-agonist (LABA) + inhaled corticosteroid (ICS), LABA + LAMA, and LABA + LAMA + ICS groups. All the patients were followed up for 1 year to collect exacerbation and mortality data. Results We found that only 45.4% of patients in Group A and 43.6% of patients in Group C received reasonable inhalation therapy in reference to the GOLD document. In addition, the LAMA group had a higher forced expiratory volume in one second (FEV1), FEV1%pred, FEV1/forced vital capacity and peak expiratory flow compared with LABA + ICS, LABA + LAMA and LABA + LAMA + ICS groups. However, we did not find any significant differences of exacerbation, hospitalization and mortality during the follow-up among different inhalation therapies groups on less symptomatic COPD patients. Conclusion Over half of the less symptomatic patients received inhalation therapy that were inconsistent with the GOLD document recommendations in a Chinese population in the real world. In fact, the single inhaled drug of LAMA should be recommended and pulmonary function is not a good indicator for the choice of initial inhalation therapy in less symptomatic COPD patients. KEY MESSAGES Over half of the less symptomatic COPD patients received inhalation therapy that were inconsistent with the GOLD document recommendations in a Chinese population in the real world. The clinicians should offer a single inhaled drug of LAMA to less symptomatic COPD patients and pulmonary function is not a good indicator for the choice of initial inhalation therapy.

890: THERAPEUTIC USE OF INHALED CORTICOSTEROIDS IN COVID-19: A SYSTEMATIC REVIEW AND META-ANALYSIS

Introduction: Previous randomized trials suggest the benefit of inhaled budesonide for COVID-19 patients in outpatient settings. We evaluated available studies on the effect of the therapeutic use of inhaled corticosteroids (ICS) on mortality and pertinent clinical outcomes. Methods: A comprehensive literature search was conducted across the WHO, LitCOVID, and EMBASE databases from inception until June 30th, 2022. The primary outcome was overall mortality and secondary outcomes included symptom-based clinical improvement rates at day 14, ER visits or hospitalization, and adverse events. Data analysis was performed using Review Manager Software, version 5.2, to evaluate the combined odds ratio (OR) with 95% confidence intervals (CI) using a random-effects model. Results: Nine studies (7 RCTs (3 budesonide, 3 ciclesonide, 1 fluticasone RCTs), & 2 observational studies) were included in the mortality meta-analysis. Of the 3,934 patients included, 103 patients died (44 out of 1925 in the ICS group and 59 out of 2009 in the non-ICS group). The odds of mortality in the therapeutic ICS use group were lower compared to the non-ICS therapy group (OR 0.78, 95% CI 0.48-1.28, p-value=0.33, I2=0%). The result was statistically insignificant, possibly due to the low mortality rate. But therapeutic ICS showed statistically significant clinical improvement rates at day 14 (5 RCTs; 3 Ciclesonide, 2 Budesonide) (OR 1.56, 95% CI 1.31-1.86, p < 0.0001, I2=0%). The number of ED visits/Hospitalization rate, and adverse events were not statistically significant between the groups (OR 0.73, 95% CI 0.32-1.70, p= 0.47 I2=75% and OR 1.10 95% CI 0.67-1.82, p=0.70, I2=28%). Conclusions: This meta-analysis shows that the therapeutic use of ICS in COVID-19 is associated with higher symptom-based clinical improvement rates. Although the reduction in mortality odds remained insignificant, as the overall mortality rates were low which increased the confidence interval overall. Early administration of ICS showed a trend towards the reduced likelihood of urgent care needs. Well-designed trials are needed to explore ICS efficacy in patients with a high risk of disease progression and in reducing the incidence of long-term COVID-19 symptoms or post-acute sequelae of SARS-CoV-2.

Dose-dependent association between inhaled corticosteroid use and risk of obesity and metabolic syndrome in asthma.

Background: Inhaled corticosteroids (ICS) are widely prescribed medications. Some studies have reported that ICS may suppress the hypothalamic-pituitary-adrenal axis and induce systemic effects. Objective: To explore the possibility of a dose-dependent association between the long-term use of ICS and the risk of obesity and other markers of metabolic syndrome. Methods: A 5-year retrospective two-arm cohort study explored patients on asthma and not on ICS relative to patients with asthma who were on varying doses of ICS (low, medium, and high) and attributes such as body mass index (BMI) trajectory and prescription of antihypertensive, antidiabetic, and cholesterol-lowering medications. Results: A total of 229 subjects with asthma were in the control cohort, and 215 subjects with asthma were in the ICS cohort. The ICS cohort was subdivided into individuals on low- (n = 88), medium- (n = 107), or high- (n = 20) dose ICS throughout the 5-year study period. For every 1-year increase in time, the BMI in the high-dose ICS group increased at a rate of 0.25 kg/m² when compared with the subjects in the control group after controlling for age and gender. Also, for every 1-year increase in time, the BMI of those on medium-dose ICS increased by 0.06 kg/m² compared with those in the control group after controlling for age and gender. The subjects on ICS also had a statistically increased risk of being prescribed antihypertensive, antidiabetic, and cholesterol-lowering medications. Conclusion: ICS use in the subjects with asthma was associated with a dose-dependent risk of increasing BMI trajectories over time and an increased requirement for antidiabetic and cholesterol-lowering medications. One possible conclusion from this study is that long-term medium- and high-dose ICS have the potential to induce systemic effects.

Effects of Inhaled Corticosteroids on Lung Function in Children With Post-infectious Bronchiolitis Obliterans in Remission.

BackgroundPost-infectious bronchiolitis obliterans (PIBO) is a rare and irreversible chronic obstructive pulmonary disease with no specific treatment, especially for patients with PIBO in remission. In this study, we evaluated the effects of continuous inhaled corticosteroids (ICSs) and intermittent ICSs on lung function in the remission of PIBO.MethodsThis was a retrospective study, and all the subjects we included were divided into continuous ICS group and intermittent ICS group according to treatment regimens. Patients in continuous ICS group received continuous ICSs (2 times a day), and patients in intermittent ICS group received intermittent ICSs (inhaled corticosteroids after acute respiratory tract infection or wheezing). Different lung function tests were performed at different ages. Tidal breathing lung function tests were performed in patients with PIBO aged ≤ 5 years, and the lung ventilation function test and the bronchial dilation test were performed in patients with PIBO aged more than 5 years. Lung function was assessed at the beginning of follow-up and at the end of follow-up (1 year of ICSs).ResultsAfter 1 year of ICSs, patients aged more than 5 years, forced vital capacity (FVC), and forced expiratory volume in 1 s (FEV1) were significantly higher than at the beginning of follow-up. After 1 year of ICSs, the difference in VT/Kg, TPTEF/TE, and VPEF/VE between the end and the beginning of follow-up in continuous ICS group shows an upward trend. But those showed a downward trend in intermittent ICS group. FVC, FEV1, and maximal mid-expiratory flow velocity 25–75% (MMEF25–75%) of continuous ICS group were significantly higher than at the beginning of follow-up. The difference in FEV1 and MMEF25–75% between the end of follow-up and the beginning of follow-up in continuous ICS group was significantly higher than that in intermittent ICS group. A total of 52.94% of patients with PIBO aged more than 5 years were positive for bronchial dilation tests.ConclusionInhaled corticosteroids can effectively improve lung function and relieve airway obstruction in patients aged more than 5 years in PIBO remission, especially continuous ICSs. Patients with PIBO may have reversible airflow limitations.

An assessment of asthma exacerbations in pediatric patients using a long-acting B2-agonist plus inhaled corticosteroid versus an inhaled corticosteroid alone

BackgroundAn asthma exacerbation is an anticipated sudden worsening of the disease severity, which usually does not respond to conservative therapy. The management of asthma depends on the severity of the disease symptoms, which includes an inhaled corticosteroid (ICS) and a bronchodilator. This study aimed to assess the efficacy of combining a long-acting B2-agonist (LABA) with ICS, compared to ICS alone, to reduce the incidence of asthma exacerbations in pediatric patients, diagnosed with severe persistent asthma. MethodsA retrospective analysis of the medical records was conducted for 586 children, admitted to the Emergency Department (ED) at King Abdullah Specialized Children Hospital in Riyadh, Saudi Arabia, for the management of severe persistent asthma symptoms, from January 2016 to September 2019. ResultsThe majority (n = 480, 81.9%) of the patients received fluticasone (Flovent)® as the standard of care ICS treatment for controlling asthma, and a small proportion (n = 106, 18.1%) were treated with a combination of LABA and ICS. A significant increase in the frequency of recurrent asthma exacerbation episodes occurred in the group receiving ICS alone (98.5%), compared to 67.0% in the combination group (p < 0.0001). Moderate to severe exacerbations were significantly higher in the ICS group compared to the combination group (95.6% versus 84.5%, respectively, p = 0.0005). ConclusionsThe current results confirm the substantial efficacy of the LABA/ICS combination therapy in reducing the incidence and severity of asthma exacerbations in pediatric patients, compared to ICS alone.

Inhaled Corticosteroids Alone and in Combination With Long-Acting β2 Receptor Agonists to Treat Reduced Lung Function in Preterm-Born Children

Decreases in future lung function are a hallmark of preterm birth, but studies for management of decreased lung function are limited. To determine whether 12 weeks of treatment with inhaled corticosteroids (ICS) alone or in combination with long-acting β2 agonists (LABA) improves spirometry and exercise capacity in school-aged preterm-born children who had percent predicted forced expiratory volume in 1 second (%FEV1) less than or equal to 85% compared with inhaled placebo treatment. A double-blind, randomized, placebo-controlled trial was conducted to evaluate ICS and ICS/LABA against placebo. Preterm-born children (age, 7-12 years; gestation ≤34 weeks at birth) who did not have clinically significant congenital, cardiopulmonary, or neurodevelopmental abnormalities underwent spirometry, exercise testing, and measurement of fractional exhaled nitric oxide before and after treatment. A total of 144 preterm-born children at the Children's Hospital for Wales in Cardiff, UK, were identified and enrolled between July 1, 2017, and August 31, 2019. Each child was randomized to 1 of 3 cohorts: fluticasone propionate, 50 μg, with placebo; fluticasone propionate, 50 μg, with salmeterol, 25 μg; or placebo inhalers, all given as 2 puffs twice daily for 12 weeks. Children receiving preexisting ICS treatment underwent washout prior to randomization to ICS or ICS/LABA. The primary outcome was between-group differences assessed by adjusted pretreatment and posttreatment differences of %FEV1 using analysis of covariance. Intention-to-treat analysis was conducted. Of 144 preterm-born children who were identified with %FEV1 less than or equal to 85%, 53 were randomized. Treatment allocation was 20 children receiving ICS (including 5 with prerandomization ICS), 19 children receiving ICS/LABA (including 4 with prerandomization ICS), and 14 children receiving placebo. The mean (SD) age of children was 10.8 (1.2) years, and 29 of the randomized children (55%) were female. The posttreatment %FEV1 was adjusted for sex, gestation, bronchopulmonary dysplasia, intrauterine growth restriction, pretreatment corticosteroid status, treatment group, and pretreatment values. Posttreatment adjusted means for %FEV1, using analysis of covariance, were 7.7% (95% CI, -0.27% to 15.72%; P = .16) higher in the ICS group and 14.1% (95% CI, 7.3% to 21.0%; P = .002) higher in the ICS/LABA group compared with the placebo group. Active treatment decreased the fractional exhaled nitric oxide and improved postexercise bronchodilator response but did not improve exercise capacity. One child developed cough when starting inhaler treatment; no other adverse events reported during the trial could be attributed to the inhaler treatment. The results of this randomized clinical trial suggest that combined ICS/LABA treatment is beneficial for prematurity-associated lung disease in children. EudraCT number: 2015-003712-20.

Blood eosinophils to guide inhaled maintenance therapy in a primary care COPD population.

Blood eosinophils are a potentially useful biomarker for guiding inhaled corticosteroid (ICS) treatment decisions in COPD. We investigated whether existing blood eosinophil counts predict benefit from initiation of ICS compared to bronchodilator therapy.We used routinely collected data from UK primary care in the Clinical Practice Research Datalink. Participants were aged ≥40 years with COPD, were ICS-naïve and starting a new inhaled maintenance medication (intervention group: ICS; comparator group: long-acting bronchodilator, non-ICS). Primary outcome was time to first exacerbation, compared between ICS and non-ICS groups, stratified by blood eosinophils (“high” ≥150 cells·µL−1 and “low” <150 cells·µL−1).Out of 9475 eligible patients, 53.9% initiated ICS and 46.1% non-ICS treatment with no difference in eosinophils between treatment groups (p=0.71). Exacerbation risk was higher in patients prescribed ICS than those prescribed non-ICS treatment, but with a lower risk in those with high eosinophils (hazard ratio (HR) 1.04, 95% CI 0.98–1.10) than low eosinophils (HR 1.19, 95% CI 1.09–1.31) (p-value for interaction 0.01). Risk of pneumonia hospitalisation with ICS was greatest in those with low eosinophils (HR 1.26, 95% CI 1.05–1.50; p-value for interaction 0.04). Results were similar whether the most recent blood eosinophil count or the mean of blood eosinophil counts was used.In a primary care population, the most recent blood eosinophil count could be used to guide initiation of ICS in COPD patients. We suggest that ICS should be considered in those with higher eosinophils and avoided in those with lower eosinophils (<150 cells·µL−1).

Combination fixed-dose β agonist and steroid inhaler as required for adults or children with mild asthma: a Cochrane systematic review

BackgroundIn people with mild asthma poor adherence to regular therapy is common and increases the risk of exacerbations, morbidity and mortality. The use of fixed-dose combination inhalers containing an inhaled...

Combination fixed-dose beta agonist and steroid inhaler as required for adults or children with mild asthma.

Combination fixed-dose beta agonist and steroid inhaler as required for adults or children with mild asthma.

Discontinuation of inhaled corticosteroids in patients with controlled asthma: The DISCO (Discontinuation of Inhaled Steroid in Controlled asthmatics Over 6 months) study

BackgroundAlthough inhaled corticosteroids (ICSs) are the recommended first-line therapy for asthma, determining whether to continue or discontinue ICS treatment in patients with mild asthma remains challenging for clinicians. Several studies have revealed that patients with mild-persistent asthma maintained a well-controlled state after ICS withdrawal. However, the long-term outcomes of ICS withdrawal have not yet been determined. ObjectiveTo determine the possible clinical outcomes of the discontinuation of ICS in patients with well-controlled mild asthma. MethodsWe investigated the clinical outcomes of discontinuing ICSs in patients with well-controlled mild asthma and compared the time to loss of control (LOC) between patients who stopped ICS treatment (ICS withdrawal group, IWG) and those who continued treatment for 3 years (continuous ICS group, CIG). ResultsA significant difference in the time to LOC was observed between the IWG and CIG (hazard ratio, 2.56; 95% confidence interval, 1.52-4.33; P < .001). Increasing fractional exhaled nitric oxide levels (P = 0.008) and sputum eosinophil counts (%) (P = 0.015) revealed a weak but significant association with LOC risk in the CIG. The sputum eosinophil counts (P = 0.039) and serum total immunoglobulin E levels (P = 0.014) were significantly higher in the LOC group than in the non-LOC group of the CIG. ConclusionOur results suggest that the maintenance of ICS treatment may help keep patients’ asthma under control. Furthermore, patients with LOC had significantly higher sputum eosinophil counts in the CIG than those in the non-LOC group. Therefore, continuous ICS use by patients with mild, well-controlled asthma could be associated with good clinical outcomes. Trial RegistrationClinicalTrials.gov Identifier: KCT0002234.

Treatment of COPD Groups GOLD A and B with Inhaled Corticosteroids in the COSYCONET Cohort - Determinants and Consequences.

BackgroundIn COPD patients of GOLD groups A and B, a high degree of treatment with inhaled corticosteroids (ICS) has been reported, which is regarded as overtreatment according to GOLD recommendations. We investigated which factors predict ICS use and which relationship it has to clinical and functional outcomes, or healthcare costs.MethodsWe used pooled data from visits 1 and 3 of the COSYCONET cohort (n=2741, n=2053, interval 1.5 years) including patients categorized as GOLD grades 1–4 and GOLD group A or B at both visits (n=1080). Comparisons were performed using ANOVA, and regression analyses using propensity matching and inverse probability weighting to adjust for differences between ICS groups. These were defined as having ICS at both visits (always) vs no ICS at both visits (never). Measures were divided into predictors of ICS treatment and outcomes.ResultsAmong 1080 patients, 608 patients were eligible for ICS groups (n=297 never, n=311 always). Prior to matching, patients with ICS showed significantly (p<0.05 each) impaired lung function, symptoms and exacerbation history. After matching, the outcomes generic quality of life and CO diffusing capacity were increased in ICS patients (p<0.05 each). Moreover, costs for respiratory medication, but not total health care costs, were significantly elevated in the ICS group by 780€ per year.ConclusionICS therapy in COPD GOLD A/B patients can have small positive and negative effects on clinical outcomes and health care costs, indicating that the clinical evaluation of ICS over-therapy in COPD requires a multi-dimensional approach.

Normal growth variance by Z scores should be considered when interpreting the growth inhibitory effect of inhaled corticosteroids.

Randomized clinical trials suggest that long-term inhaled corticosteroid (ICS) treatment significantly inhibits growth velocity (GV) assessed by centimeters/year (cm/year) in primarily prepubescent, mild asthmatics. However, several observational studies measuring normal growth variance by Z score suggest the absence of the ICS inhibitory effect. To demonstrate the generalizability of ICS growth inhibition in cm/year by establishing whether this measure exceeds the expected normal changes in GV by Z score for similar age and sex. This was a retrospective, observational study comparing height and GV across a 2 year period in asthmatics aged 2-10 years, receiving ICS therapy (Group 3) with non-asthmatics, and non-ICS asthmatics (Groups 1 and 2), respectively. Generalized linear model procedure compared GV measures after adjustment for age, gender, and dependence of group differences on the age of the child. Before initiation of ICS therapy at baseline, Group 3 patients (n = 22) were shorter than Groups 1 (n = 67) and 2 (n = 44) by mean height in cm, and height for age Z score in the adjusted model (p < .05). GV was also significantly reduced in Group 3 after initiation of ICS therapy versus Groups 1 and 2 by 1.0-1.5 cm/year, respectively, p < .05, but not significantly in comparison to expected normal GV variance determined by Z score, p ≥ .05. Our findings suggest the need to consider normal growth variance by Z scores in addition to absolute changes (cm/year) when interpreting the inhibitory effect of ICS on GV. Larger sample size studies will be necessary to confirm our findings.

Compare the Effect of Inhaled Corticosteroids and Systemic Corticosteroids on Sputum Microbiome of AECOPD.

Background: To observe the effects of inhaled corticosteroids (ICS) and systemic corticosteroids (SCS) on the sputum microbiology of patients with AECOPD.Methods: The 16S rRNA sequencing results for sputum samples from 36 admitted AECOPD patients were analyzed using ICS or SCS on the basis of standard treatment; sputum samples were collected before and after treatment for 1 day, 7, and 14 days.Results: After 7 days of SCS treatment, the bacterial abundance of Sorangium, Acidibacter, and Fretibacterium decreased at the genus level. After 14 days of SCS treatment, the bacterial abundance of Prevotella_2, Bergeyella, Corynebacterium_1, and Ruminococcaceae_UCG-014 was decreased at the genus level, and an increase in the bacterial abundance of the Clostridiales_vadinBB60_group was observed at the family level. The linear discriminant analysis effect size (LEfSe) algorithm showed that after treatment for 14 days, Sphingobacterium increased in the SCS group, and Corynebacterium_1 (genus level), Bacillales (order level), and Lactobacillales (order level) decreased in the ICS group. However, the abundance of the above bacteria in each group of samples was <1%, suggesting that the two treatments may have similar effects on bacterial abundance. Alpha diversity analysis results showed that there was no significant difference in the ACE index, Chao1 index, Shannon index, or Simpson index between the ICS group and the SCS group. Beta diversity analysis showed that there was little difference in bacterial diversity among each group. BugBase predicted that although bacteria containing mobile elements in the SCS group decreased significantly compared with those in patients using ICS after treatment for 14 days, these two treatments had similar effects on other phenotype categories assigned to the bacterial contents.Conclusions: Our results show that ICS and SCS have remarkably similar effects on the sputum microbiome of AECOPD patients.

A randomized prospective study to compare the efficacy and safety of budesonide plus formoterol and tiotropium plus formoterol in patients having mild to moderate chronic obstructive pulmonary disease

Background: Chronic obstructive pulmonary disease (COPD) is a leading respiratory illness affecting the quality of lives around the world. The present study aims to compare the efficacy and safety of combination of inhaled corticosteroid (ICS) and long acting β2 agonist (LABA) with long acting β2 agonist and long acting muscarinic antagonist (LAMA) in treatment of mild to moderate COPD in a tertiary care hospital.Methods: Total 132 patients with COPD were recruited on the basis of inclusion and exclusion criteria for 8 weeks study from outpatient clinic. A complete pulmonary examination including spirometry examination was done to rule out severe and very severe forms of COPD. Spirometry was performed at the time of recruitment for evaluation of forced expiratory volume in one second (FEV1) and measurement of SpO2 at the time of recruitment at 2 weeks and 8 weeks. Appropriate statistical methods were used to compare the qualitative and quantitative primary and secondary efficacy end points, p value &lt;0.05 was considered significant.Results: On analysis, there was a significant difference (p&lt;0.05) was observed in FEV1 and SpO2 from baseline in ICS plus LABA group (n=66). A similarly significant difference (p&lt;0.05) was observed in LABA and LAMA group (n=66). On comparison between ICS plus LABA and LABA plus LAMA no significant difference in FEV1 and SpO2 was observed between the two groups. More adverse drug reactions were observed in ICS plus LABA group than LAMA plus LABA group.Conclusions: Combination of ICS and LABA combination is as effective as combination of LABA and LAMA in patients having mild to moderate COPD. However, LABA and LAMA combination is preferable because it is associated with fewer side effects.

THE EFFECT OF TEZEPELUMAB ON EXACERBATIONS IN PATIENTS WITH SEVERE, UNCONTROLLED ASTHMA ACCORDING TO BASELINE INHALED CORTICOSTEROID DOSE: RESULTS FROM THE PHASE 2B PATHWAY STUDY

SESSION TITLE: Updates in the Management of Severe Asthma SESSION TYPE: Original Investigations PRESENTED ON: October 18-21, 2020 PURPOSE: Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin, an epithelial cytokine implicated in asthma pathogenesis. In the phase 2b PATHWAY study (NCT02054130), tezepelumab significantly reduced annualized asthma exacerbation rates (AAER) by up to 71% versus placebo in adults with severe, uncontrolled asthma. This post hoc analysis evaluated the effect of tezepelumab on AAER and forced expiratory volume in 1 second (FEV1) in patients from PATHWAY taking medium-dose (MD) or high-dose (HD) inhaled corticosteroids (ICS) at baseline. METHODS: Adults (18–75 years) with severe, uncontrolled asthma were randomized to receive subcutaneous tezepelumab (70mg every 4 weeks [Q4W], 210mg Q4W, 280mg every 2 weeks) or placebo for 52 weeks. AAER and FEV1 were determined in patients taking MD (250–500μg/day of fluticasone propionate [FP] or equivalent) or HD (>500μg/day FP or equivalent) ICS at baseline. Data are reported for tezepelumab 210mg and pooled tezepelumab doses. RESULTS: Overall, 550 patients were randomized to placebo (n=138) or tezepelumab 70mg (n=138), 210mg (n=137) or 280mg (n=137). Patients taking HD ICS (n=269) had more exacerbations in the prior year (mean: 2.6 vs 2.2), higher fractional exhaled nitric oxide levels (median: 24.3 vs 20.5 ppb) and lower post-bronchodilator FEV1 reversibility (median: 287.0 vs 340.0 mL) at baseline than those taking MD ICS (n=281), and higher occurrence of nasal polyps (18.6% vs 11.4%) and maintenance oral corticosteroid (OCS) use (18.6% vs 0.4%). Over 52 weeks, AAER in placebo-treated patients was higher in the HD ICS group than in the MD ICS group (1.12 [95% confidence interval (CI): 0.76–1.66] vs 0.38 [95% CI: 0.24–0.61], respectively). For tezepelumab 210mg, AAER was reduced by 77% (95% CI: 54–89) and 60% (95% CI: 8–83) versus placebo in the HD and MD ICS groups, respectively. Results were similar for pooled tezepelumab doses versus placebo (HD ICS, 74% [95% CI: 57–84]; MD ICS, 52% [95% CI: 12–73]). Compared with placebo, the least squares mean change from baseline in FEV1 at week 52 was 160mL (95% CI: 10–300) and 140mL (95% CI: 0–280) in patients taking HD and MD ICS, respectively, in the tezepelumab 210mg group, and 190mL (95% CI: 70–310) and 120mL (95% CI: 10–230), respectively, in the pooled tezepelumab dose group. CONCLUSIONS: Patients with severe, uncontrolled asthma taking HD ICS had more exacerbations in the prior year and higher baseline maintenance OCS use than those taking MD ICS, which is consistent with patients taking HD ICS having more severe disease. Treatment with tezepelumab reduced exacerbations and improved FEV1 versus placebo in both ICS dose groups, with a trend of greater effects in patients taking HD ICS. CLINICAL IMPLICATIONS: This study further supports the potential benefits of tezepelumab treatment in patients with severe, uncontrolled asthma, irrespective of pre-treatment maintenance ICS dose. 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Comparison of Two Therapies on Asthma Control in Children.

Background: Childhood asthma carries significant morbidity. Aim/Objectives: Aim of the study was to compare efficacy of 2 commonly used therapies for asthma control in children with asthma. Methods: This was a 1-year, prospective cohort study at a tertiary care children's hospital. Patients were referred by their primary care physicians (PCPs) for asthma control. All patients were on low-dose inhaled corticosteroids (ICSs) at baseline. They were either switched to medium-dose ICS (ICS group) or medium-dose ICS and long-acting beta agonist (ICS+LABA group). Results were compared over time and between both groups. Results: Our cohort included 163 children (ages 2-18 years) with mean age of 5.62 ± 3.61 years. Mean Asthma Control Test (ACT) score at baseline was 15.9 ± 5.4. Mean ACT and percent predicted forced expiratory volume in one second improved (P < 0.0001 for both) in both groups. Median emergency department visits, short courses of oral steroids, and unscheduled PCP visits for acute asthma significantly decreased (P < 0.001 for all) in both groups. Similarly, days/month with wheezing, nighttime cough, and missed school days significantly decreased in both groups (P < 0.001 for all). Patients in ICS group were more likely to fail to achieve asthma control compared to patients in ICS+LABA group. Conclusion: Our study suggests that in children with uncontrolled asthma on low-dose ICS, switching to either medium-dose ICS or medium-dose ICS+LABA resulted in better symptom control, ACT improvement, and less asthma exacerbations over time. ICS+LABA had the additional benefit of less risk of treatment failure when compared to medium-dose ICS.