Asthma control conundrum in clinical practice - Data from a two-stage Delphi survey and literature review.

Definitions and measures of asthma control used in clinical trials and practice often vary, as highlighted in the manuscript, "Is asthma control more than just an absence of symptoms? An expert consensus statement". Furthermore, the authors discussed differences between patients and healthcare professionals (HCPs) in terms of understanding and managing asthma. Given these disparities, there is a need for consensus regarding what constitutes well-controlled asthma and, especially, how best it can be measured and recorded. In the current work, we describe our data and provide more detail on the methodology from a two-stage Delphi survey and a structured literature review, which were designed to reach a consensus definition of asthma control and alleviate misalignments between patients and HCPs. Survey data were collected using a two-stage Delphi technique; a method used to collate expert opinions over a series of sequential questionnaires to reach a consensus. The collated Delphi survey data were compared with results from a comprehensive, structured literature review of 216 publications, to assess if there was a correlation between existing guidance and measures of asthma control used in clinical trials and standard clinical practice. In order to collate and interpret findings from the Delphi survey, responses from 82 panelists (73 HCPs and 9 authors) were qualitatively analyzed, quantitatively categorized, and presented as percentages or counts in Excel databases, which are detailed in the current work. Searches conducted using PubMed and Cochrane identified 664 manuscripts, and Embase was used to identify 89 congress abstracts. After applying a stringent screening method using predefined key words, the structured literature review consisted of 185 peer-reviewed manuscripts and 31 congress abstracts, and assessed existing guidance and measures of asthma control used in clinical trials. In this publication, we provide further insight into the predefined keywords, search strings, and strategy applied to identify manuscripts and congress abstracts for inclusion/exclusion, and detail methods for data extraction. Together, the data from the Delphi survey and structured literature review aimed to provide greater insights into challenges and approaches in achieving asthma control in clinical practice, with the potential for results to be used to guide a universally accepted definition and measure of asthma control that can be used and understood by patients, HCPs, and researchers. Qualitative and quantitative methodology and analysis from the Delphi survey and literature review search strategy can potentially be used to identify disparities and explore expert opinion and relevant literature in other therapeutic areas to guide a consensus where disparities exist.

Is asthma control more than just an absence of symptoms? An expert consensus statement.

PURPOSE: Definitions and measures of asthma control used in clinical trials and in clinical practice vary considerably. There is also misalignment between patients and healthcare professionals (HCPs) in terms of understanding and managing asthma control. This study aimed to progress towards a consensus definition of asthma control, and evaluate disparities between HCP and patient perspectives. BASIC PROCEDURES: A two-stage Delphi questionnaire involving asthma specialists sought to identify areas of consensus on aspects of asthma control in clinical practice. Results were compared with those of a structured literature review to assess if existing guidance and measures of asthma control used in studies correlated with practice. Eighty-two panelists took part in the Delphi questionnaire. The structured literature review included 185 manuscripts and 31 abstracts. MAIN FINDINGS: Panelists agreed that there was no standard definition of asthma control, confirmed by a total of 19 different composite consensus/guideline definitions and/or validated measures of control being identified across the Delphi study and literature review. Panelists agreed on the positive associations of well-controlled asthma with patient outcomes, but not on the components or thresholds of a working definition of control. PRINCIPAL CONCLUSIONS: A universally accepted definition and measure of asthma control that is utilized and understood by patients, HCPs, and researchers is required.

Inhaled indacaterol/glycopyrronium/mometasone furoate fixed-dose combination in moderate-to-severe asthma.

INTRODUCTION: Fixed-dose long-acting beta2-agonist (LABA)/inhaled corticosteroid (ICS) combinations and add-on therapies as needed are the mainstay for maintenance therapy in asthma. However, more than 40% of patients have an inadequately controlled disease. The development of triple fixed-dose combinations consisting of long-acting muscarinic antagonist (LAMA)/LABA/ICS has paved the way for a new approach to reach therapeutic goals of an optimal control of symptoms and an effective prevention of future exacerbations. AREAS COVERED: A search was conducted on PubMed (MEDLINE), using the MeSH terms [asthma] + [indacaterol] + [glycopyrronium] +[mometasone furoate] + [treatment], until October 2021. Original data from clinical trials, prospective and retrospective studies and reviews were selected. Clinical studies with IND/MF/GLY (Enerzair Breezhaler) are summarized, and its place in current asthma therapy is examined. EXPERT OPINION: Triple therapy has been shown to be an effective and safe therapeutic option for asthma patients who remain uncontrolled despite ICS/LABA combination. The recently approved single-inhaler indacaterol/glycopyrronium/mometasone fixed dose combination has demonstrated to significantly reduce exacerbations, improve FEV1, symptoms and quality of life compared to ICS/LABA, including, salmeterol/fluticasone combination. Moreover, once-daily dosing may improve adherence.

Long-term effectiveness of CPAP in patients with severe obesity-hypoventilation syndrome.

PURPOSE: The optimal mode of long-term positive airway pressure (PAP) treatment for obesity-hypoventilation syndrome (OHS) is not clear. The objectives of this study were to analyze whether or not patients with severe OHS treated with continuous positive airway pressure (CPAP) remained controlled with this therapy over the long term and to investigate which variables were associated with CPAP failure and the need to switch to non-invasive ventilation (NIV). METHODS: In a retrospective single-center study, patients admitted to the hospital because of severe OHS between 1996 and 2015 were analyzed. A multiple regression analysis was performed in order to determine which variables were associated with either CPAP success or failure to maintain long-term control. RESULTS: Of 126 consecutive patients, 115 accepted long-term PAP treatment. CPAP or NIV treatment was prescribed according to a protocol that included overnight polysomnographic PAP titration. Follow-up time was 8.0 ± 4.8 years. At the end of this period, 29% of CPAP-treated patients had been re-assigned to NIV because of recurrence of global respiratory failure. High levels of obesity, weight gain, lower FEV1/FVC values and the need for nocturnal supplementary oxygen independently predicted CPAP failure. CONCLUSION: CPAP therapy for severe OHS in patients who have these risk factors should be closely monitored in the long-term for possible treatment failure.

Eosinophilic COPD Patients Display a Distinctive Serum miRNA Profile From Asthma and Non-eosinophilic COPD.

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are common chronic airway diseases that may overlap in some individuals. Asthma COPD overlap (ACO) is a heterogeneous conditions that includes smoking-asthma (SA) and COPD with eosinophilia (COPDe). MicroRNAs (miRNA) are regulators of gene expression with a great potential as biomarkers. OBJECTIVES: The objective of this study was to identify distinctive miRNA signatures in patients from the whole spectrum of chronic obstructive bronchial disease (SA, COPDe, non-smoking asthmatics (NSA), and COPD) that could serve as diagnostic biomarkers or describe differential molecular mechanisms with potential therapeutic implications. METHODS: From a previously characterized cohort of ACO, COPD and asthma patients, we selected a discovery group of 40 patients for miRNA expression profiling by means of microarray technology. Differential expression of miRNAs were validated by quantitative PCR in the complete cohort (n=274). RESULTS: Thirty differentially expressed miRNAs (eBAYES p<0.05, fold change ≥2) were found among the different groups of patients regarding COPDe: 19 COPD-vs-COPDe, 13 NSA-vs-COPDe, 11 SA-vs-COPDe. A characteristic down-regulated miRNA expression pattern was identified in COPDe patients. Differential expression of miR-619-5p and miR-4486 in COPDe patients were validated in the complete cohort (n=274). CONCLUSIONS: We postulate that COPDe patients show a characteristic expression profile of miRNAs distinctive from asthma and COPD. Also that SA and COPDe patients, which have been typically clustered in the ACO group, display distinct molecular events.

Assessing adherence to inhaled medication in asthma: Impact of once-daily versus twice-daily dosing frequency. The ATAUD study.

INTRODUCTION: This study was aimed at evaluating whether once-daily regimens (od-r) show benefits in adherence when compared to twice-daily (td-r). METHODS: Prospective, multicenter, 6-month follow-up study with two visits. The main objective was to compare adherence assessed by the electronic prescription refill rate (EPRR) and by the 10-item Test of Adherence to Inhalers (TAI) in patients with od-r and td-r. Suboptimal adherence was defined as TAI < 50 or EPRR ≤ 80%. The effect of suboptimal adherence on meaningful clinical outcomes and the concordance between EPRR and TAI were also examined. RESULTS: One hundred and ninety-seven patients (47.3 ± 15.9 years, 65% women) were included and 180 completed the study. TAI score was <50 in 29.8% od-r patients and 46.9% in td-r (p = 0.01) and EPRR was ≤80% in 22.6% and 37.5% respectively (p = 0.02). The correlation between the two methods was moderate (rho = 0.548; p < 0.001). There were no significant differences in FEV1 (%), symptoms or exacerbations between patients with optimal and suboptimal adherence. During follow-up, five patients (6%) with o-dr and 17 patients (17.7%) with t-dr suffered an exacerbation (p = 0.013). At visit two, 13.1% of the patients with o-dr and 31.3% with t-dr had uncontrolled asthma (p = 0.003), although more patients with o-dr were receiving inhaled corticosteroids in the high-dose stratum (25.8% vs. 11.5%; p = 0.001). CONCLUSION: Mean adherence rates were greater with od-r than with td-r, but we did not observe an effect on clinical outcomes.

Mixed Th2 and non-Th2 inflammatory pattern in the asthma-COPD overlap: a network approach.

Introduction: The asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is a clinical condition that combines features of those two diseases, and that is difficult to define due to the lack of understanding of the underlying mechanisms. Determining systemic mediators may help clarify the nature of inflammation in patients with ACO. Objectives: We aimed at investigating the role and interaction of common markers of systemic inflammation (IL-6, IL-8, and tumor necrosis factor-α), Th2-related markers (periostin, IL-5, and IL-13), and IL-17 in asthma, COPD, and ACO. Methods: This is a cross-sectional study of patients aged ≥40 years with a post-bronchodilator forced expiratory volume in the first second/forced vital capacity <0.70 recruited from outpatient clinics in tertiary hospitals with a clinical diagnosis of asthma, COPD, or ACO. ACO was defined by a history of smoking >10 pack-years in a patient with a previous diagnosis of asthma or by the presence of eosinophilia in a patient with a previous diagnosis of COPD. Clinical, functional, and inflammatory parameters were compared between categories using discriminant and network analysis. Results: In total, 109 ACO, 89 COPD, and 94 asthma patients were included. Serum levels (median [interquartile range]) of IL-5 were higher in asthma patients than in COPD patients (2.09 [0.61-3.57] vs 1.11 [0.12-2.42] pg/mL, respectively; p=0.03), and IL-8 levels (median [interquartile range]) were higher in COPD patients than in asthma patients (9.45 [6.61-13.12] vs 7.03 [4.69-10.44] pg/mL, respectively; p<0.001). Their values in ACO were intermediate between those in asthma and in COPD. Principal component and network analysis showed a mixed inflammatory pattern in ACO in between asthma and COPD. IL-13 was the most connected node in the network, with different weights among the three conditions. Conclusion: Asthma and COPD are two different inflammatory conditions that may overlap in some patients, leading to a mixed inflammatory pattern. IL-13 could be central to the regulation of inflammation in these conditions.

Validation of the 'Test of the Adherence to Inhalers' (TAI) for Asthma and COPD Patients.

BACKGROUND: To validate the 'Test of Adherence to Inhalers' (TAI), a 12-item questionnaire designed to assess the adherence to inhalers in patients with COPD or asthma. METHODS: A total of 1009 patients with asthma or COPD participated in a cross-sectional multicenter study. Patients with electronic adherence ≥80% were defined as adherents. Construct validity, internal validity, and criterion validity were evaluated. Self-reported adherence was compared with the Morisky-Green questionnaire. RESULTS: Factor analysis study demonstrated two factors, factor 1 was coincident with TAI patient domain (items 1 to 10) and factor 2 with TAI health-care professional domain (items 11 and 12). The Cronbach's alpha was 0.860 and the test-retest reliability 0.883. TAI scores correlated with electronic adherence (ρ=0.293, p=0.01). According to the best cut-off for 10 items (score 50, area under the ROC curve 0.7), 569 (62.5%) patients were classified as non-adherents. The non-adherence behavior pattern was: erratic 527 (57.9%), deliberate 375 (41.2%), and unwitting 242 (26.6%) patients. As compared to Morisky-Green test, TAI showed better psychometric properties. CONCLUSIONS: The TAI is a reliable and homogeneous questionnaire to identify easily non-adherence and to classify from a clinical perspective the barriers related to the use of inhalers in asthma and COPD.

Effects of omalizumab in non-atopic asthma: results from a Spanish multicenter registry.

Aim. To evaluate the effectiveness of omalizumab in non-atopic asthma. Methods. Using data from a multicenter registry of severe asthma, we evaluated and compared the clinical outcome of 29 omalizumab-treated severe non-atopic asthmatics with 266 omalizumab-treated severe allergic asthmatics. Effectiveness was assessed by considering severe exacerbations, pulmonary function, the Global Evaluation of Treatment Effectiveness (GETE) scale, and Asthma Control Test (ACT). Results. Omalizumab demonstrated significant improvement in the clinical status of non-atopic asthmatics as measured by GETE, which rose from 1.6 ± 1.1 to 2.8 ± 0.9 [corrected] at 4 months (p = .0215) to 2.9 ± 0.9 at 1 year (p = .0093) and to 3.4 ± 0.6 at 2 years (p = .0078), and by the ACT, which increased from 13.3 ± 5.5 [corrected] to 17.5 ± 5.4 at 4 months (p = .0236) to 17.9 ± 4.8 at 1 year (p = .0136) and to 20.6 ± 3.9 at 2 years (p = .0024). Forced expiratory volume in 1 second (FEV1) improved from 61.0 ± 19.4% to 65.1 ± 17.2 at 4 months to 64.1 ± 24.7 at 1 year and to 67.3 ± 23.0% [corrected] at 2 years, but without significant differences between initial and follow-up measurements (p = .52, .91, and .45, respectively) and exacerbations decreased from 3.1 ± 3.5 to 1.9 ± 2.8 at 1 year (p = .1709) to 1.8 ± 4.4 at 2 years (p = .2344). The results were not significantly different from those obtained in atopic asthmatics. Conclusion. Anti-IgE therapy can be effective in non-atopic severe asthma.