Dataset Information

Symptom-driven inhaled corticosteroid/long-acting beta-agonist therapy for adult patients with asthma who are non-adherent to daily maintenance inhalers: a study protocol for a pragmatic randomized controlled trial.

ABSTRACT:

Background

While inhaled corticosteroids (ICS) are considered the essential foundation of most asthma therapy, ICS inhaler nonadherence is a notoriously common problem and a significant cause of asthma-related morbidity. Partially acknowledging the problem of nonadherence, international organizations recently made paradigm-shifting recommendations that all patients with mild-to-moderate persistent asthma be considered for symptom-driven ICS-containing inhalers rather than relying on adherence to traditional maintenance ICS inhalers and symptom-driven short-acting beta-agonists (SABA). With this new approach, asthma patients are at least exposed to the important anti-inflammatory effects of ICS-containing inhalers when their symptom reliever inhaler is deployed due to acute symptoms.

Methods

This study will (Part 1) complete a pragmatic randomized controlled trial to evaluate if an inhaler strategy that utilizes symptom-driven ICS inhalers is particularly beneficial in maintenance ICS inhaler non-adherent asthma patients, and (Part 2) use a dissemination and implementation (D&I) science conceptual framework to better understand patients' and providers' views of inhaler nonadherence. This study, which will have an option of taking place entirely remotely, will use a Food and Drug Administration (FDA)-approved electronic sensor (Hailie® sensor) to monitor inhaler adherence and includes semi-structured interviews guided by the Consolidated Framework for Implementation Research (CFIR).

Discussion

This study is assessing the problem of nonadherence using a D&I implementation science research lens while testing a new inhaler approach to potentially ameliorate the detrimental consequences of maintenance inhaler nonadherence. We hypothesize that the use of a symptom-driven ICS/LABA management strategy, as compared to traditional maintenance ICS treatment and symptom-driven SABA, will lead to improved adherence to an asthma treatment strategy, decreased asthma-related morbidity, less cumulative ICS exposure, and greater patient satisfaction with an inhaler approach.

Trial registration

ClinicalTrials.gov NCT05111262. Registered on November 8, 2021.

SUBMITTER: Krings JG

PROVIDER: S-EPMC9720948 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

Symptom-driven inhaled corticosteroid/long-acting beta-agonist therapy for adult patients with asthma who are non-adherent to daily maintenance inhalers: a study protocol for a pragmatic randomized controlled trial.

Krings James G JG Wojcik Kaitlyn M KM Chen Vanessa V Sekhar Tejas C TC Harris Kelly K Zulich Abigail A Sumino Kaharu K Brownson Ross R Lenze Eric E Castro Mario M

Trials 20221205 1

<h4>Background</h4>While inhaled corticosteroids (ICS) are considered the essential foundation of most asthma therapy, ICS inhaler nonadherence is a notoriously common problem and a significant cause of asthma-related morbidity. Partially acknowledging the problem of nonadherence, international organizations recently made paradigm-shifting recommendations that all patients with mild-to-moderate persistent asthma be considered for symptom-driven ICS-containing inhalers rather than relying on adhe ...[more]

PMID: 36471430

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Project description:Background: Peripheral deposition of inhaled medication is important as small airway disease has a key role in asthma. In this study, we compared the lung deposition at different mean flow rates of three inhaled corticosteroid (ICS)/long-acting beta2-agonist (LABA) combinations delivered by dry powder inhaler (DPI), that is, Foster NEXThaler® (extrafine formulation of beclomethasone/formoterol), Relvar Ellipta® (fluticasone furoate/vilanterol trifenatate), and Symbicort Turbohaler® (budesonide/formoterol). Materials and Methods: In vitro drug delivery parameters were applied to lung computerized tomography (CT) scans of 20 asthma patients by functional respiratory imaging (FRI). Aerosol airway deposition patterns were calculated as percentage (standard deviation) intrathoracic versus extrathoracic deposition, percentage peripheral deposition, and central-to-peripheral (C/P) ratio at different inspiratory mean flow rates. Results: At 60 and 40 L/min, intrathoracic deposition of ICS/LABA was significantly higher with NEXThaler versus Ellipta. Peripheral deposition (60 L/min) with NEXThaler was higher than Ellipta for ICS (24.7% [3.5%] vs. 5.0% [2.0%]; p < 0.001) and LABA (25.3% [3.5%] vs. 13.0% [3.0%]; p < 0.001). C/P ratio with NEXThaler was lower (indicating higher peripheral deposition) than Ellipta (ICS: 0.63 vs. 1.63; LABA: 0.63 vs. 0.99). Inspiratory flow rate did not impact lung deposition with NEXThaler or Ellipta. In contrast, Turbohaler performance was negatively impacted by decreasing inspiratory flow rate. In fact, although lung deposition with Turbohaler was similar to that of NEXThaler at 60 L/min, lung deposition with Turbohaler was significantly lower than NEXThaler at both 40 L/min (∼30%) and 30 L/min (∼50%). Conclusions: Using FRI, we demonstrated better peripheral deposition and C/P ratios of ICS/LABA with NEXThaler versus Ellipta. NEXThaler demonstrated inspiratory flow rate independency of lung deposition versus Turbohaler. These findings suggest that the extrafine formulation is superior to large particle formulations in delivering ICS/LABA consistently both to the large and small airways.

Project description:BackgroundEvidence suggests that variation in the length of the poly-C repeat in the 3' untranslated region (3'UTR) of the β2-adrenergic receptor gene (ADRB2) may contribute to interindividual variation in β-agonist response. However, methodology in previous studies limited the assessment of the effect of sequence variation in the context of poly-C repeat length. The objectives of this study were to design a novel genotyping method to fully characterize sequence variation in the ADRB2 3'UTR poly-C repeat in asthma patients treated with inhaled corticosteroid and long-acting β2-adrenergic agonist (ICS/LABA) combination therapy, and to analyze the effect of the poly-C repeat polymorphism on clinical response.MethodsIn 2,250 asthma patients randomized to treatment with budesonide/formoterol or fluticasone/salmeterol in a six-month study (AstraZeneca study code: SD-039-0735), sequence diversity in the ADRB2 poly-C repeat region was determined using a novel sequencing-based genotyping method. The relationship between the poly-C repeat polymorphism and the incidence of severe asthma exacerbations, and changes in pulmonary function and asthma symptoms from baseline to the average during the treatment period, were analyzed.ResultsPoly-C repeat genotypes were assigned in 97% (2,192/2,250) of patients. Of the 13 different poly-C repeat alleles identified, six alleles occurred at a frequency of >5% in one or more population in this study. The repeat length of these six common alleles ranged from 10 to 14 nucleotides. Twelve poly-C repeat genotypes were observed at a frequency of >1%. No evidence of an association between poly-C repeat genotype and the incidence of severe asthma exacerbations was observed. Patients' pulmonary function measurements improved and asthma symptoms declined when treated with ICS/LABA combination therapy regardless of poly-C repeat genotype.ConclusionsThe extensive sequence diversity present in the poly-C repeat region of the ADRB2 3'UTR did not predict therapeutic response to ICS/LABA therapy.

Dataset Information

Symptom-driven inhaled corticosteroid/long-acting beta-agonist therapy for adult patients with asthma who are non-adherent to daily maintenance inhalers: a study protocol for a pragmatic randomized controlled trial.

Background

Methods

Discussion

Trial registration

Publications

Symptom-driven inhaled corticosteroid/long-acting beta-agonist therapy for adult patients with asthma who are non-adherent to daily maintenance inhalers: a study protocol for a pragmatic randomized controlled trial.

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