Inhaled Corticosteroid And Long-acting Beta-agonist Research Articles

Effect of fluticasone propionate/formoterol and fluticasone furoate/vilanterol on adolescents with chronic bronchial obstruction

BackgroundThe combination of inhaled corticosteroid and long-acting beta-agonist (ICS/LABA) has shown superiority in improving lung function (FEV1) compared with ICS. The clinical effect of ICS/LABA depends on the fine-particle fraction (FPF) and the pulmonary deposition. ObjectiveWe sought to compare the efficacy of two combinations of an inhaled corticosteroid (ICS) and a long-acting beta agonist (LABA), fluticasone propionate/formoterol and fluticasone furoate/vilanterol, in asthmatic adolescents with chronic bronchial obstruction. MethodsFluticasone propionate/formoterol (FP/FORM) (125/5 μg 2 doses twice daily via the k-haler®) and fluticasone furoate/vilanterol (FF/VI) (92/22 μg once daily via the Ellipta®) were administered to adolescents aged 12 to 17 years who required regular anti-asthmatic medication and had a forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio below -1.65 SD in a 2-sequence, 16-week crossover trial. The primary efficacy end point was change in FEV1 compared to baseline. Secondary end points were FEV1/FVC, maximal expiratory flow at 50% of the forced vital capacity (MEF50), impulse oscillometry indices respiratory resistance at 5 Hz (R5), difference of R5 and R20 (R5−20), area of reactance (AX), and Asthma Control Test. ResultsBoth ICS/LABA combinations resulted in a significant improvement in FEV1 and MEF50 Z-scores without any significant difference between FP/FORM and FF/VI. Forty percent of patients achieved a normal prebronchodilator FEV1/FVC Z-score with either treatment. AX or R5−20 did not improve significantly with either treatment. ConclusionBoth ICS/LABA combinations demonstrated significant improvements in FEV1 Z-score. Over one-third of the asthmatic adolescents with prolonged bronchial obstruction achieved a normal prebronchodilator FEV1/FVC level.

The Effect of Zingiber cassumunar (Phlai Capsule) on Bronchial Hyperresponsiveness in Asthmatic Patients: A Randomized Controlled Trial

Background: Bronchial hyperresponsiveness (BHR) is a key feature of asthma. Compound D, an active compound in Phlai, can bind cysteinyl leukotrienes receptors that play a role for asthma treatment. Objective: To determine the effect of Phlai capsules on BHR measured by the methacholine challenge test. Materials and Methods: A randomized, double-blind, placebo-controlled, crossover study was conducted in adult asthmatic patients with partly controlled symptoms. Each patient received four weeks of treatment with either Phlai or placebo separated by a 2-week washout period. The main outcome was provocative concentration of methacholine causing a 20% drop in FEV₁ (PC₂₀). Asthma control test (ACT) scores, and fractional exhaled nitric oxide (FeNO) levels were secondary end points. Results: Thirty patients were randomly allocated to either the Phlai or the placebo group. All patients had allergic rhinitis and received inhaled corticosteroid and long-acting beta2-agonist (ICS/LABA) or ICS alone. Four weeks after treatment, mean PC₂₀ in the Phlai group was higher than in the placebo group at 9.76±1.56 mg/mL versus 6.05±1.65 mg/mL (p=0.151). The improvement of ACT scores in the Phlai group was significantly higher than in the placebo group. FeNO levels decreased after treatment in the Phlai group. All patients tolerated the treatment well and had no side effects. Conclusion: In adult asthmatic patients with partly controlled symptoms, concomitant treatment with Phlai capsules tended to decrease BHR and significantly improve symptom scores. Keywords: Asthma; Asthma control test; Bronchial hyperresponsiveness; Zingiber cassumunar; Phlai

Are the Global Initiative for Asthma (GINA) Guidelines Being Correctly Used to Diagnose Severe Asthma in the UAE?

ObjectivesWe aimed to identify the percentage inaccuracy in classifying asthma severity as severe asthma based on the 2019 Global Initiative for Asthma (GINA) guidelines criteria, at Cleveland Clinic Abu Dhabi, and make recommendations to improve the assessment of asthma severity.MethodsAll asthma patients that attended the Pulmonology clinic or the Allergy clinic from May 2015 to December 2019 were retrospectively analyzed to identify which asthma patients classified as having severe asthma according to the 2019 GINA guidelines criteria. We then calculated the percentage inaccuracy associated with giving diagnoses of severe asthma.ResultsWe retrospectively analyzed a total of 902 patients, and out of those, we identified 334 as patients with severe asthma according to the 2019 GINA guidelines criteria. Of those 334 patients, 218 were given an incorrect asthma severity of either mild (N=14), moderate (N=203), or unspecified asthma severity (N=1) in the hospital’s electronic records. This represents a percentage inaccuracy of 65.3% in classifying asthma severity as severe asthma. Fluticasone propionate-salmeterol was the most used ICS-LABA (inhaled corticosteroid and long-acting beta-agonist) medication in the severe asthma group (58.1%). Fluticasone furoate-vilanterol was identified as the most incorrectly prescribed ICS-LABA medication (68.2%).ConclusionWe identified an inaccuracy of 65.3% in classifying asthma severity as severe at our hospital. This inaccuracy is associated with a lack of understanding of the GINA guidelines by clinicians, as well as a lack of acceptance of some of the criteria in the GINA guidelines by patients. We have made recommendations to help improve the accuracy of asthma severity assessment, in order to be fully adherent to the GINA guidelines criteria.

Asthma control factors in the Gulf Cooperation Council (GCC) countries and the effectiveness of ICS/LABA fixed dose combinations: a dual rapid literature review

BackgroundAsthma control is influenced by multiple factors. These factors must be considered when appraising asthma interventions and their effectiveness in the Gulf Cooperation Council (GCC) countries (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia and United Arab Emirates [UAE]). Based on published studies, the most prevalent asthma treatment in these countries are fixed dose combinations (FDC) of inhaled corticosteroid and long-acting beta-agonist (ICS/LABA). This study is a rapid review of the literature on: (a) factors associated with asthma control in the GCC countries and (b) generalisability of ICS/LABA FDC effectiveness studies.MethodsTo review local factors associated with asthma control and, generalisability of published ICS/LABA FDC studies, two rapid reviews were conducted. Review 1 targeted literature pertaining to asthma control factors in GCC countries. Eligible studies were appraised, and clustering methodology used to summarise factors. Review 2 assessed ICS/LABA FDC studies in conditions close to actual clinical practice (i.e. effectiveness studies). Eligibility was determined by reviewing study characteristics. Evaluation of studies focused on randomised controlled trials (RCTs). In both reviews, initial (January 2018) and updated (November 2019) searches were conducted in EMBASE and PubMed databases. Eligible studies were appraised using the Critical Appraisal Skills Program (CASP) checklists.ResultsWe identified 51 publications reporting factors associated with asthma control. These publications reported studies conducted in Saudi Arabia (35), Qatar (5), Kuwait (5), UAE (3), Oman (1) and multiple countries (2). The most common factors associated with asthma control were: asthma-related education (13 articles), demographics (11articles), comorbidities (11 articles) and environmental exposures (11 articles). Review 2 identified 61 articles reporting ICS/LABA FDC effectiveness studies from countries outside of the GCC. Of these, six RCTs were critically appraised. The adequacy of RCTs in informing clinical practice varied when appraised against previously published criteria.ConclusionsAsthma-related education was the most recurring factor associated with asthma control in the GCC countries. Moreover, the generalisability of ICS/LABA FDC studies to this region is variable. Hence, asthma patients in the region, particularly those on ICS/LABA FDC, will continue to require physician review and oversight. While our findings provide evidence for local treatment guidelines, further research is required in GCC countries to establish the causal pathways through which asthma-related education influence asthma control for patients on ICS/LABA FDC therapy.

Impact of a change of bronchodilator medications in a hospital drug formulary on intra- and out-of-hospital drug prescriptions: interrupted time series design with comparison group

BackgroundHospital drug formularies are reduced lists of drugs designed to optimise inpatient care. Adherence to the drugs included in such formularies is not always 100% but is generally very high. Little research has targeted the impact of a change in these formularies on outpatient drug prescriptions. This study therefore sought to evaluate the impact of a change affecting bronchodilator medications in a hospital drug formulary on intra- and out-of-hospital drug prescriptions in a region in north-western Spain. Two new drugs belonging to this same class were brought onto the out-of-hospital market, overlapping with the intervention.MethodsWe used a natural before-after quasi-experimental design with control group based on monthly data. The intervention evaluated was the modification of a hospital drug formulary, which involved withdrawing salmeterol/fluticasone in order to retain formoterol/budesonide as the sole inhaled corticosteroid and long-acting beta-agonist (ICS/LABA). Using official data sources, we extracted the following dependent variables: defined daily doses (DDD) per 1000 inhabitants per day, DDD per 100 bed-days, and cost per DDD.ResultsIntra-hospital use showed a 173.2% rise (95% CI 47.3–299.0%) in the medication retained in the formulary, formoterol/budesonide, and a 94.9% drop (95% CI 77.9–111.9%) in the medication withdrawn from the formulary, salmeterol/fluticasone. This intervention led to an immediate reduction of 75.9% (95% CI 82.8–68.9%) in the intra-hospital cost per DDD of ICS/LABA. No significant changes were observed in out-of-hospital use.ConclusionsAlthough this intervention was cost-effective in the intra-hospital setting, the out-of-hospital impact of a change in the drug formulary cannot be generalised to all types of medications and situations.

Factors associated with exhaled nitric oxide in children with asthma and allergic rhinitis.

Factors attributable to the level offraction of exhaled nitric oxide (FeNO) in different age groups of asthmatic children are still lack of report. To evaluate factors associated with FeNO and the response of FeNO to inhaled steroid in different age groups of asthmatic children with allergic rhinitis. Asthmatic children aged 5 to 12years were recruited. FeNO, lung function and bronchial hyperresponsiveness (BHR) to methacholine, skin prick testing to a panel of aeroallergens, total immunoglobulin E (T-IgE) in serum and eosinophils in blood were tested. Correlations between FeNO and the measured parameters were assessed. FeNO was measured again after the treatment of combined inhaled corticosteroid and long-acting beta-agonist (ICS/LABA) for 4weeks. Changes in FeNO between different age groups were compared. A total of 121 eligible subjects were enrolled in and completed this study. Asthmatic children aged 10 to 12years old had significantly higher FeNO than those between 8 and 9years and 5 to 7years of children (both P<0.01). Greater height/age (P<0.01) and higher level of total allergen IgE (P<0.01) are associated with a higher value of FeNO. After 4weeks of treatment with ICS/LABA, asthma control test scores were significantly increased in all age groups (P<0.01), while the level of FeNO significantly decreased in the elder age group only (P<0.01). Height and T-IgE are well correlated with FeNO in asthmatic children aged 5 to 12years. Measurement of FeNO is more suitable for evaluating the efficacy of ICS/LABA in elder asthmatic children.

Risk for pneumonia requiring hospitalization or emergency room visit according to delivery device for inhaled corticosteroid/long-acting beta-agonist in patients with chronic airway diseases as real-world evidence

A fixed-dose combination of inhaled corticosteroid and long-acting beta agonist (ICS/LABA) may increase the risk of pneumonia in patients with chronic airway diseases including chronic obstructive pulmonary disease and asthma. Although lung deposition of ICS/LABA is dependent on the inhaler device and inhalation technique, there have been few studies comparing the risk for pneumonia according to the type of device used to deliver ICS/LABA in real-world practice. A retrospective cohort study was performed using the National Health Insurance Database of the Korean Health Insurance Review & Assessment Service. New users who began ICS/LABA were selected and followed-up 180 days after ICS/LABA initiation. The risk for pneumonia requiring emergency room (ER) visit or admission was compared according to inhaler device used—pressurized metered-dose inhaler (pMDI) or dry powder inhaler (DPI)—after individual exact matching (1:5). Among the eligible cohort of 245,477 new ICS/LABA users, 7,942 patients who used pMDI only were matched with 39,690 patients who used DPI only. The incidence of pneumonia was higher in the pMDI group (1.6%) than the DPI group (1.1%); the adjusted hazard ratio (HR) for pneumonia was 1.6 (95% CI 1.3–2.0; p < 0.0001). In subgroup analyses, a significantly higher risk for pneumonia was found in the pMDI group compared with the DPI group regardless of the presence of history of pneumonia (HR 1.7 [95% CI 1.2–2.3]; p = 0.002), COPD (HR 1.6 [95% CI 1.2–2.0]; p = 0.0007), or asthma (HR 1.6 [95% CI 1.2–2.2]; p = 0.0008). In analyses of real-world data, pMDI users incurred a higher risk for pneumonia requiring hospitalization or ER visit compared with DPI users.

EOSINOPHIL LEVELS, EXACERBATIONS, RESOURCE UTILIZATION AND COSTS AMONG MODERATE-TO-SEVERE ASTHMA PATIENTS

Introduction In the US, ∼900,000 patients (≥12 years) have uncontrolled moderate-to-severe asthma despite using available treatments. Elevated eosinophils (EOS) are a marker of Type-2 asthma; however, their association with asthma exacerbations, healthcare resource utilization (HCRU) and costs has not been well described in a real-world setting. Methods Patients with diagnosis codes for asthma (ICD-9 493, 493.9, 493.92, or ICD-10 J45.40, J45.41, J45.50, J45.51, J45.998) were identified from the Geisinger Health System electronic health records (EHR). Patients with ≥1 EOS measurement within 90 days of an inhaled corticosteroid and long-acting beta-2 agonist (ICS/LABA) prescription from 01/01/2010–11/01/2016 were identified. Date of EOS result was the index date (ID); patients had continuous EHR enrollment for 12 months before and after ID. Patients were stratified by baseline EOS. Baseline demographics, comorbidities, HCRU and costs during 12 months before ID were compared across baseline EOS levels using ANOVA or chi-square tests. Results 491 patients were categorized into four EOS levels: –299 (n=168), 300–499 (n=87), and ≥500 (n=64) cells/uL. Overall, top three diagnosed Type-2 comorbidities were allergic rhinitis, chronic sinusitis, and eczema. Over 75% of patients experienced ≥1 exacerbation in the past year across all baseline EOS levels. HCRU, cost, and asthma exacerbations were not significantly different across baseline EOS levels (Table 1). Conclusions A large proportion of moderate-to-severe asthma patients experienced exacerbations, while HCRU and costs were high irrespective of baseline EOS level. The results demonstrate a high unmet need among patients across all EOS levels. Table 1. Baseline characteristics (during 12 months prior to index date). *P-values represent results of chi-square tests or ANOVA. †Asthma exacerbations were defined as either an asthma-related hospital admission or emergency department visit, or a prescription order for an oral or injectable corticosteroid.

Bronchoprotective tolerance with indacaterol is not modified by concomitant tiotropium in persistent asthma.

Tiotropium is a long acting muscarinic antagonist (LAMA), licensed as triple therapy with inhaled corticosteroid and long-acting beta-agonist (ICS/LABA). There may be a synergistic benefit between LAMA and LABA as a consequence of receptor cross-talk, which in turn could modify beta-2 receptor downregulation and associated tolerance induced by LABA. We hypothesize this mechanism may result in a reduction of airway hyperresponsiveness (AHR) when using triple therapy. We evaluated 14 non-smoking asthmatics using an open-label, randomized crossover design. ICS with Indacaterol and Tiotropium (IND/TIO) vs ICS with Indacaterol (IND) over 4weeks with challenge performed after first and last doses at trough. We found no significant difference in mannitol sensitivity, expressed as the provocative dose of mannitol required to reach a 15% drop in FEV1 , or mannitol reactivity, expressed as the response dose ratio (RDR: max % fall in FEV1 /cumulative dose), when comparing ICS/IND/TIO to ICS/IND. Geometric mean fold differences for RDR comparing single and chronic dosing were 3.26-fold (95% CI 1.46-7.29) and 2.51-fold (95% CI 1.32-4.79) for IND and IND/TIO, respectively. Furthermore, salbutamol recovery post-challenge was significantly blunted after chronic compared to single dosing with either ICS/IND (P<.005) or ICS/IND/TIO (P<.05). Our data suggest that concomitant tiotropium does not modify the bronchoprotective tolerance induced by Indacaterol, in turn suggesting that cross-talk may not be clinically relevant when using triple therapy. This study was registered on clinicaltrials.gov as NCT02039011.

Predictors of ICS/LABA prescribing in COPD patients: a study from general practice.

BackgroundA combination of inhaled corticosteroid and long-acting beta2 agonist (ICS/LABA) is used frequently to treat chronic obstructive pulmonary disease (COPD) patients. The aim of the study was to determine whether prescribing ICS/LABA to COPD patients in primary care in 2009/10 was within the GOLD guidelines and whether and to what degree patient characteristics were associated with prescription of these drugs by GPs.MethodsThis was a cross-sectional study in seven Norwegian GP practices. Patients registered with a diagnosis of asthma or COPD in the previous five years were included.ResultsAmong the 376 patients included in the analysis, 149 patients had COPD, defined as a post-bronchodilator FEV1/FVC <0.7 and 55.6% of these patients were treated with ICS/LABA. The rate of prescribing was significantly higher in the COPD patients also diagnosed with asthma than in those with COPD as the only diagnosis, 66.7%, and 39.0%, respectively (P = 0.001). The prescribing rate in the latter subgroup would have been 18.6% if the 2007 GOLD guidelines had been followed. One or more exacerbations in the previous year was the strongest predictor of ICS/LABA prescribing in the COPD patients who were not registered with a concomitant diagnosis of asthma (OR 3.2, 95% CI 1.0–10.0) but this association was limited to the patients with severe disease (FEV1% predicted <50) (OR 13.5, 95% CI 1.8–101.1). Cardiovascular disease was associated with decreased ICS/LABA prescribing (OR 0.4, 95% CI 0.2–0.8) in the COPD group. A Kappa coefficient of 0.32 was found between the actual prescribing rate and that recommended in the 2007 GOLD guidelines.ConclusionsOverprescribing of ICS/LABA for the COPD patients was shown. Previous exacerbation was a strong predictor of ICS/LABA prescribing only in patients with severe COPD. Because of the low emphasis on previous exacerbation when prescribing for COPD patients with mild to moderate disease, the actual prescribing rate agreed more closely with the GOLD guidelines from 2007 than with those published in 2011. Cardiovascular disease was associated with decreased prescribing, indicating that GPs adjust the treatment in cases with multimorbidity.

Quantifying asthma patient preferences for onset of effect of combination inhaled corticosteroids and long-acting beta2-agonist maintenance medications

The Onset-of-Effect Questionnaire (OEQ) is a self-administered instrument used to assess patient perception of how quickly asthma maintenance medications begin to work. This study was designed to quantify the relative importance that patients using combination inhaled corticosteroid and long-acting beta(2)-agonist (ICS/LABA) maintenance medication place on the onset-of-effect outcomes. Patients aged >or=18 years with a self-reported diagnosis of asthma, currently using combination ICS/LABA maintenance medication, completed an Internet-based SC conjoint survey instrument that included 10 choice trade-off tasks. In four choice tasks, patients were asked to choose between two hypothetical medications. In six choice tasks, patients were asked to choose among two hypothetical medications and their current medication. Each choice alternative was defined by response levels of the five OEQ statements and out-of-pocket cost. We used random-parameters logit methods to estimate the relative importance of outcomes assessed by the OEQ. Five hundred nine patients completed the study. Satisfied was the most important OEQ outcome and physical sensations were the least important. When offered a choice, 80% (95% CI, 75-85%) of patients preferred a maintenance medication for which they are satisfied with how quickly they feel it begins to work and 62% (95% CI: 57-67%) of patients preferred a maintenance medication that they feel begins to work right away. Combination maintenance medications with rapid onset of effect, especially those that impact a patients' ability to feel the medication work right away and patient satisfaction with how quickly the medication works, may increase the use of and adherence to maintenance medications.