Decreased Asthma Exacerbations Research Articles

Association of Novel Antihyperglycemic Drugs Versus Metformin With a Decrease in Asthma Exacerbations

BackgroundSimilar to metformin, dipeptidyl peptidase-4 inhibitors (DPP-4 Is), glucagon-like peptidase 1 receptor agonists (GLP-1 RAs), and sodium glucose co-transporter-2 inhibitors (SGLT-2 Is) may improve control of asthma owing to their multiple potential mechanisms, including differential improvements in glycemic control, direct anti-inflammatory effects, and systemic changes in metabolism. ObjectiveTo investigate whether these novel antihyperglycemic drugs were associated with fewer asthma exacerbations compared with metformin in patients with asthma comorbid with type 2 diabetes. MethodsUsing a Japanese national administrative database, we constructed three active comparators—new user cohorts of 137,173 patients with a history of asthma starting the novel antihyperglycemic drugs and metformin between 2014 and 2022. Patient characteristics were balanced using overlap propensity score weighting. The primary outcome was the first exacerbation requiring systemic corticosteroids, and the secondary outcomes included the number of exacerbations requiring systemic corticosteroids. ResultsDPP-4 Is and GLP-1 RAs were associated with a higher incidence of exacerbations requiring systemic corticosteroids compared with metformin (DPP-4 Is: 18.2 vs. 17.4 per 100 person-years; hazard ratio 1.09, 1.05 to 1.14; GLP-1 RAs: 24.9 vs. 19.0 per 100 person-years; 1.14, 1.01 to 1.28). In contrast, the incidence of exacerbations requiring systemic corticosteroids was similar between the SGLT-2 Is and metformin groups (17.3 vs. 18.1 per 100 person-years; hazard ratio 1.00, 0.97 to 1.03). While DPP-4 Is and GLP-1 RAs were associated with more exacerbations requiring systemic corticosteroids, SGLT-2 Is were associated with slightly fewer exacerbations requiring systemic corticosteroids (53.7 vs. 56.6 per 100 person-years; rate ratio 0.95, 0.91 to 0.99). ConclusionsWhile DPP-4 Is and GLP-1 RAs were associated with poorer control of asthma compared with metformin, SGLT-2 Is offered asthma control comparable to that of metformin.

The Use of Albuterol/Budesonide as Reliever Therapy to Reduce Asthma Exacerbations

Prevention of asthma exacerbations and reduction of systemic corticosteroid burden remain unmet needs in asthma. US asthma guidelines recommend concomitant short-acting β2-agonist (SABA) and inhaled corticosteroid (ICS) as alternative reliever at Step 2. The FDA approved a pressurized metered-dose inhaler containing albuterol and budesonide for as-needed treatment or prevention of bronchoconstriction and to reduce exacerbation risk in patients with asthma aged ≥18 years. This combination is approved for use as a reliever with or without maintenance therapy but it is not indicated for maintenance therapy (or for single maintenance and reliever therapy). Intervening with as-needed SABA–ICS during the window-of-opportunity to reduce inflammation during loss of asthma control can reduce exacerbation risk, by exerting both genomic and nongenomic anti-inflammatory effects. We propose that use of albuterol–budesonide rather than albuterol as reliever to manage episodic symptoms driven by acute bronchoconstriction and airway inflammation can improve outcomes. This combination approach, shown to decrease asthma exacerbations and oral corticosteroid burden in patients with moderate-to-severe asthma, represents a paradigm shift for asthma treatment in the US. Further safety and efficacy studies should provide evidence that this type of reliever should be standard of care.

A Retrospective Claims Database Study to Clarify Treatment Reality of Asthma Patients Before and After Referral to a Specialist.

Japanese guidelines recommend that patients with uncontrolled asthma be referred by non-specialists to specialists (allergists and/or pulmonologists). This study investigated the reality of clinical practice in asthma patients referred to specialists in Japan. This was a retrospective, observational cohort study of asthma patients in a health insurance claim database (Cross Fact) referred from facilities with non-specialists to those with specialists from January 2016 to December 2018. The referred asthma patients were defined as patients with ≥4 inhaled corticosteroid (ICS)-containing prescriptions during a 1-year baseline period, with an asthma diagnosis, and who had visited a facility with specialists. Asthma exacerbation, maintenance treatment, laboratory tests, and medical procedures before and after referral were analyzed. Data for 2135 patients were extracted, of which 420 with referral codes were analyzed. The proportion of patients with asthma exacerbations was 50.2% (95% confidence interval [CI]: 45.4-55.1%) before referral and 37.4% (95% CI: 32.7-42.2%) after, a significant decrease (P<0.001; McNemar test). The proportions of patients prescribed ICS alone, long-acting beta-agonists (LABA), and ICS/LABA were lower after referral than before, but the proportions of patients prescribed long-acting muscarinic antagonists (LAMA), ICS/LABA/LAMA, and biologics increased after referral. More asthma-related laboratory tests were performed after referral, and spirometry incidence increased from 16.4% before referral to 51.4% after referral. This study shows a decrease in asthma exacerbations, change in asthma treatments, and increase in laboratory tests after referral to a specialist, suggesting that referrals to specialists lead to better management of asthma.

Shared Decision-Making Aids for Pediatric Chronic Hematological and Non-Hematological Conditions: An in-Depth Literature Review

Background: Shared Decision Making (SDM) is a core component of facilitating patient-centered care. When implementing SDM, patients, parents and clinicians make health decisions together, ensuring that families are informed to make decisions based on their values and preferences. This is of particular importance among children and adolescents with chronic conditions, who are often presented with health-related decisions that can have social and psychological implications. Despite increasing recommendations for use of SDM tools, evidence-based recommendations regarding their use in clinical practice are limited. Studies suggest that barriers to SDM implementation include poor quality of information tailored to children and their families, the emotional state of the patients and their families (denial, anxious, overwhelmed, etc.), power imbalance with health care providers, and insufficient time from heavy physicians' workloads. Due to its limited implementation in clinical practice, little is known about proper approaches and outcomes of SDM tools among children and adolescents with chronic conditions. Objectives: To evaluate and summarize the literature related to how SDM tools are being studied and implemented children and adolescents with chronic medical conditions and how they influence decision making and health outcomes. Methods: A literature search was conducted for publications written in English from 2013-2023 using PubMed, MEDLINE, and Google Scholar. Search terms included “shared decision making”, “decision aid,” “pediatrics,” “infant,” “child,” “adolescents,” and “chronic conditions” to ensure adequate representation of the available literature. Relevant articles included those that covering SDM in hematological and non-hematological chronic conditions in pediatrics. Results: Out of 171 studies identified through literature search, 35 were included. Areas in which SDM has been most studied included hematologic and oncologic conditions (n=5), asthma (n=8), autism, other neurodevelopmental disorders (n=6), Obstructive Sleep Apnea (n=4), inflammatory bowel disease (n=1), chronic kidney disease (n=2), and diabetes (n=2), organ failure (n=3), and other conditions (n=4). Of those, 20 studies were descriptive and 15 had an experimental intervention design. Only 4 studies focused on the child's role in SDM while others focused on parent or caregiver role. Implementation of SDM toolkits and patient portals help decrease asthma exacerbations and emergency room visits. Similar toolkits and decision aids developed for decision making in hematologic and respiratory disease have shown reduced decisional conflict regarding treatment choice. In contrast, researched tools developed for diabetes patients did not show improved outcomes but did reduce decisional conflict. Results demonstrate that although patient with greatest functional neurodevelopmental impairment experience less SDM, its use leads to significant improvements in severity of their condition, behavioral, and psychoeducational levels. Research on hematological conditions such as sickle cell, thalassemia, and immune thrombocytopenia all show that their patients are not experiencing SDM, or it's limited to moderate amounts. Both children and parents desire to become more active members of the decision-making progress. Perspective of physicians show that they understand this desire but face barriers such as poor quality of available information, lack of time, or the family's emotional state. Effective training tools are being studied to help enhance SDM care and overcome these obstacles. Conclusions: There is limited evidence for the implementation of pediatric-focused SDM tools in hematological and non-hematological chronic conditions. Published studies in pediatrics have been mostly descriptive and have placed little emphasis on implementation and effectiveness of shared decision-making interventions. Barriers and facilitators to SDM have been explored, but a gap in knowledge still exists regarding the proven methods for SDM. In general, available studies showed benefit in patients' health outcomes, satisfaction with decision making, and treatment adherence. Future research should involve the implementation of patient-centered SDM aids in efforts to overcome known barriers and to establish evidence-based guidelines for their use.

Experience of using omalizumab in patients with severe bronchial asthma

Introduction. New insights into the complex pathophysiology of severe asthma (SA) have led to the development of personalized treatment strategies using genetically engineered drugs, which is based not only on disease severity, but also on specific patient characteristics and asthma endotypes.Aim. Evaluation of the effectiveness of omalizumab in patients with severe bronchial asthma (SBA).Materials and methods. A prospective observational study (12 months) with the participation of 39 patients with TB (20 women and 19 men, average age 47.7 ± 14.2 years) who were treated at the Ochapovsky Regional Clinic Hospital of Krasnodar Region. All patients included in the study were prescribed the drug omalizumab.Results. After 6 months of follow-up, there was an improvement in asthma control in the form of an increase in the average number of points according to the ACT questionnaire: 15.9 (1.19) vs 10.7 (3.19); a decrease in the proportion of patients with an ACT score of ≤ 19 points by 15.6% (from 32 patients to 27), a decrease in the proportion of patients with the result of the ACT is less than 15 points by 16%. Within 12 months from the start of treatment with omalizumab, there was a decrease in asthma exacerbations regardless of the initial level of IgE and eosinophils, a decrease in the number of days of disability by 68.9%, the number of emergency calls by 50%, outpatient visits to a pulmonologist by 65.2%, the number of hospitalizations by 63.6%, the number of days spent in hospital – by 49.2, there was a significant decrease in daily doses of IGCS, oral GCS, the total number of exacerbations, the average score on the ACT test in all patients (p = 0.01).Conclusions. Use of the drug omalizumab in patients with SBA, in combination with a different spectrum of sensitization, it was possible to bring the treatment of such patients to a qualitatively new level, providing a pronounced clinical effect by minimizing symptoms, stopping exacerbations, and improving the quality of life. It is important to have a good safety and portability profile, as well as a convenient application mode.

Metformin use is associated with decreased asthma exacerbations in adolescents and young adults.

Metformin is a commonly used antidiabetes medication with suggested anti-inflammatory and antioxidative effects. Metformin use has been associated with lower risk of asthma exacerbations and hospitalizations in adults. Here, we aimed to evaluate how asthma exacerbation rates changed after adolescents and young adults were prescribed metformin, and to learn if those changes were related to metformin prescription adherence. Using secondary data of patients between 12 and 20 years old with asthma diagnosis and a metformin prescription from the Arkansas All Payers Claim Database and Arkansas School body mass index (BMI) database, we estimated the change in annualized asthma exacerbation rates after metformin prescription. We also evaluated the association of prescription adherence to the changes in those rates using univariate and multivariate regression models. A total of 464 patients met inclusion criteria. Outpatient exacerbation rates decreased after metformin prescription (13.4% only before vs. 7.8% only after, p = .009), and the annualized rate decreased more after metformin prescription as adherence increased (rank r = -.165, p < .001). After adjusting for potential confounders-age, sex, BMI, and inhaled corticoid steroid use-the strength of the association was attenuated. Asthma exacerbation rates decreased after metformin prescription, but a larger sample of patients who have experienced exacerbations and including patients with asthma who have not been prescribed metformin is needed to better know whether these decreases are driven by metformin use.

Controller therapy attenuates asthma exacerbations associated with prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children

Controller therapy attenuates asthma exacerbations associated with prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children

Evaluation of the Clinical Features and Laboratory Data of Patients with Severe Eosinophilic Asthma Classified as Super-Responders, Partial Responders, or Nonresponders to Mepolizumab Treatment: A Real-Life Study

Introduction: Mepolizumab is a treatment option in patients with severe eosinophilic asthma, which inhibits interleukin-5. The aim of this study was to evaluate the clinical features and laboratory data of patients with severe eosinophilic asthma who were classified as super-responders, partial responders, or nonresponders to mepolizumab treatment. Methods: In this retrospective real-life study, the clinical features and laboratory data were compared between groups of patients with severe eosinophilic asthma who were classified as super-responders, partial responders, or nonresponders to mepolizumab treatment. Results: Evaluation was made of a total of 55 patients, comprising 17 (30.9%) males and 38 (69.1%) females with a mean age of 51.28 ± 14.32 years. All the patients were receiving mepolizumab treatment for severe eosinophilic asthma, with 17 (30.9%) patients evaluated as super-responders, 26 (47.3%) as partial responders, and 12 (21.8%) as nonresponders. After mepolizumab treatment, there was a statistically significant decrease in asthma exacerbations, the number of oral corticosteroids (OCSs) used, the rate of hospitalization due to asthma attacks, and the eosinophil count (cells/µL) (p < 0.001, p < 0.001, p < 0.001, and <0.001, respectively). A statistically significant increase was determined in the forced expiratory volume in 1 s (FEV1) value (p = 0.010) and asthma control test (ACT) score (p < 0.001) after mepolizumab treatment. The baseline eosinophil count, eosinophil/lymphocyte ratio and FEV1 (%) values were significantly higher in the super-responder and partial responder groups (p < 0.001, p = 0.002, and p = 0.002, respectively). The baseline ACT score and the rate of chronic sinusitis with nasal polyps were significantly higher in the partial responder group (p = 0.004, p = 0.015, respectively). The rate of regular OCS use before mepolizumab treatment was significantly higher in the nonresponder group (p = 0.049). As a result of the receiver operating characteristics curve analysis, the blood eosinophil count (area under the curve [AUC]: 0.967, p < 0.001), eosinophil/lymphocyte ratio (AUC: 0.921, p < 0.001), and FEV1 (%) (AUC: 0.828, p = 0.002) were found to have diagnostic value in predicting the response to mepolizumab treatment in patients with severe eosinophilic asthma. Conclusion: Baseline eosinophil count, eosinophil/lymphocyte ratio, and FEV1 (%) were found to be important predictors of response to mepolizumab treatment. Further studies are needed to define the characterization of mepolizumab responders in the real world.

The Presence of Non-pharmaceutical Interventions Correlates with Decreased Rates of Asthma Exacerbations and RSV infections in Arkansas

To reduce transmission of SARS-CoV-2, non-pharmaceutical interventions (NPIs), including school closures, hand hygiene, mask mandates, and social distancing, were enforced in Arkansas from 3/2020-2/2021. We hypothesized that the presence of NPIs would correlate with a decrease in asthma exacerbations and viral infections.

Severe allergic asthma: Does alexithymia interfere with omalizumab treatment outcome?

Alexithymia is among psychological factors reported to interfere with asthma management. Severe allergic asthma (SAA) is characterized by uncontrolled asthma despite maximal standard pharmacological treatment which can benefit from an add-on treatment with Omalizumab, an anti-IgE monoclonal antibody. To evaluate if alexithymia influences the efficacy of omalizumab in SAA. The total alexithymia score 20 (TAS 20) questionnaire allowed to detect alexithymia. SAA was monitored recording number of exacerbations, asthma control test (ACT) and asthma quality of life questionnaire (AQLQ) scores, as well as forced expiratory volumes in 1 second % (FEV1%) levels before starting omalizumab, 1 and 2 years after. The study was conducted on 18 patients; Group 1, TAS 20 ≥ 61, was of 2 males and 4 females with SAA and alexithymia, while Group 2 , TAS 20 ≤ 51, was of 8 males and 4 females, without alexithymia. Group 1 had a statistically significant decrease in asthma exacerbations "p = 0.004", while ACT "p = 0.008" and AQLQ scores statistically increased. FEV1 values increased but not statistically significantly. Group 2 had a highly statistically significant decrease in the number of exacerbations and a highly statistically significant increase of ACT "p < 0.0001", FEV1 "p = 0.008" and AQLQ scores. Regardless the presence or not of alexithymia, all patients with SAA obtained a marked improvement after starting treatment with omalizumab. Therefore alexithymia does not seem to influence the treatment outcome of omalizumab.

Beneficial Effects of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Asthma: A Literature Review.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are approved to treat type 2 diabetes mellitus. The anti-inflammatory and anti-obesity properties of GLP-1 RAs as well as their moderating effects on multiple pathobiological pathways in asthma pathogenesis may decrease asthma exacerbations, improve quality of life, and decrease premature death among patients with asthma and co-morbid diabetes or obesity. The aim of this literature review is to discuss evidence from basic science, human studies, and clinical trials to support the preferential use of GLP-1 RAs in asthma patients with co-occurring diabetes and obesity. The preliminary data on the effect of GLP-1 RAson asthma in patients with diabetes are promising and merit further trials and research studies.

COVID-19 Pandemic–Related Reductions in Pediatric Asthma Exacerbations Corresponded with an Overall Decrease in Respiratory Viral Infections

BackgroundRespiratory viruses, air pollutants, and aeroallergens are all implicated in worsening pediatric asthma symptoms, but their relative contributions to asthma exacerbations are poorly understood. A significant decrease in asthma exacerbations has been observed during the coronavirus disease 2019 pandemic, providing a unique opportunity to study how major asthma triggers correlate with asthma activity.ObjectiveTo determine whether changes in respiratory viruses, air pollutants, and/or aeroallergens during the coronavirus disease 2019 pandemic were concomitant with decreased asthma exacerbations.MethodsHealth care utilization and respiratory viral testing data between January 1, 2015, and December 31, 2020, were extracted from the Children’s Hospital of Philadelphia Care Network’s electronic health record. Air pollution and allergen data were extracted from US Environmental Protection Agency public databases and a National Allergy Bureau–certified station, respectively. Pandemic data (2020) were compared with historical data.ResultsRecovery of in-person asthma encounters during phased reopening (June 6 to November 15, 2020) was uneven: primary care well and specialty encounters reached 94% and 74% of prepandemic levels, respectively, whereas primary care sick and hospital encounters reached 21% and 40% of prepandemic levels, respectively. During the pandemic, influenza A and influenza B decreased to negligible frequency when compared with prepandemic cases, whereas respiratory syncytial virus and rhinovirus infections decreased to low (though nonnegligible) prepandemic levels, as well. No changes in air pollution or aeroallergen levels relative to historical observations were noted.ConclusionsOur results suggest that viral respiratory infections are a primary driver of pediatric asthma exacerbations. These findings have broad relevance to both clinical practice and the development of health policies aimed at reducing asthma morbidity.

The nationwide retrospective cohort study by Health Insurance Review and Assessment Service proves that asthma management decreases the exacerbation risk of asthma

Medical costs have recently increased in South Korea due to the rising rate of asthma. Primary clinics serve an important role in asthma management, as they are the first stop for patients presenting with symptoms. The Health Insurance Review and Assessment Service (HIRA) in South Korea has assessed asthma-management quality since 2013, but studies are lacking on whether these assessments have been performed properly and contribute toward reducing asthma exacerbations. Therefore, we investigated whether the HIRA’s quality assessments have decreased asthma exacerbations using national health insurance claims data from 2013 to 2017 of 83,375 primary-clinic and 15,931 tertiary-hospital patients with asthma. These patients were classified into four groups based on disease severity according to the monthly prescribed amount of asthma medication using K-means clustering. The associations between HIRA assessments and asthma exacerbation were analyzed using a generalized estimating equation. Our results showed that exacerbation odds gradually decreased as the HIRA assessments progressed, especially in the mild-severity group, and that exacerbation risk among patients with asthma decreased in the order of assessment grades: “Unsatisfactory,” “Satisfactory,” and “Tertiary.” Therefore, we may conclude that asthma exacerbations may decrease with high quality asthma management; appropriate quality assessment could be helpful in reducing asthma exacerbations.

Clinical and histopathologic predictors of therapeutic response to bronchial thermoplasty in severe refractory asthma

Phenotypes and endotypes predicting optimal response to bronchial thermoplasty (BT) in patients with severe asthma remain elusive. Our aim was to compare the clinical characteristics and hallmarks of airway inflammation and remodeling before and after BT in responder and partial responder patients with severe asthma refractory to oral steroids and to omalizumab. In all, 23 patients with severe refractory asthma were divided into BT responders (n= 15) and BT partial responders (n= 8), according to the decrease in asthma exacerbations at 12 months after BT. Clinical parameters were compared at baseline and 12 months after BT, and hallmarks of airway inflammation and remodeling were analyzed by immunohistochemistry in bronchial biopsy specimens before and 3 months after BT. At baseline, the BT responders were around 8 years younger than the BT partial responders (P= .02) and they had a greater incidence of atopy, higher numbers of blood eosinophils (both P= .03) and IgE levels, higher epithelial IFN-α expression, and higher numbers of mucosal eosinophils and IL-33-positive cells (P≤ .05). Areduction in blood eosinophil count, serum IgE level, type 2 airway inflammation, and numbers of mucosal IL-33-positive cells and mast cells associated with augmented epithelial MUC5AC and IFN-α/β immunostaining was noted after BT in responders, whereas the numbers of mucosal IL-33-positive cells were augmented in BT partial responders. Most of these changes were correlated with clinical parameters. Subepithelial membrane thickening and airway smooth muscle area were similar in the 2 patient groups at baseline and after BT. By reducing allergic type 2 inflammation and increasing epithelial MUC5AC and anti-viral IFN-α/β expression, BT may enhance host immune responses and thus attenuate exacerbations and symptoms in BT responders. Instead, targeting IL-33 may provide a clinical benefit inBTpartial responders.

The Current State of Biologic Therapies for Treatment of Refractory Asthma

Asthma is a heterogeneous disease, with the immune processes behind the chronic inflammation underlying this disorder differing between the various identified asthma endotypes. In addition to heterogeneity in underlying disease pathophysiology, asthmatics fall across a broad spectrum of disease severity and can vary greatly in their response to convention asthma therapies. A small percentage of patients with severe persistent asthma will remain uncontrolled despite treatment with high-dose inhaled corticosteroids and a long-acting beta-agonist. Less than two decades ago, there were few options for these treatment-refractory asthmatics beyond chronic systemic steroids, with their myriad of treatment-limiting side effects. However, in recent years, there have been a growing number of Food and Drug Administration (FDA)-approved biologic medications with targets that include immunoglobulin E (IgE), interleukin-5 (IL-5), the IL-5 receptor and the IL-4/IL-13 receptor-alpha subunit. The current FDA-approved biologics for severe persistent asthma are omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab. These monoclonal antibodies have been shown to improve asthma control, decrease asthma exacerbations and decrease glucocorticoid dependence in certain subsets of patients with asthma. The optimal biologic for treatment of severe asthma varies from patient to patient, depending on the underlying pathophysiology of the patient's disease. For each of these medications, there are certain biomarkers that can help predict whether a patient is likely to respond favorably to the medication. This review will discuss the currently approved biologics for severe persistent asthma, including their indications, efficacy and side effects.

They just don't take their medicines: Reframing medication adherence in asthma from frustration to opportunity.

Assessing and addressing suboptimal adherence to asthma medications is a key component in the treatment of all children with asthma, particularly those with difficult-to-treat asthma. However, parents often overreport adherence to asthma medications. Increased medication adherence could lead to improved outcomes in the form of better asthma control and decreased asthma exacerbations, as well as decreased healthcare utilization costs. Yet there are many complex factors that affect medication adherence, and barriers are often different in each family. Social determinants of health, complex healthcare relationships, and patient-related factors may all affect medication adherence. Multicomponent patient-centered strategies, as well as strategies that utilize technology and habit formation strategies may be helpful in improving medication adherence. Further study is needed to reliably and sustainably improve medication adherence in children with asthma across the broader population; in some populations, alternate diagnoses, adjusting therapy, and other intervention may be required to improve asthma control and health.

Effect of Anti-IL5, Anti-IL5R, Anti-IL13 Therapy on Asthma Exacerbations: A Network Meta-analysis

Several new treatments for severe asthma have become available in the last decade; yet, little data exist to guide their use in specific patient populations. A network meta-analysis was conducted comparing the efficacy of FDA-approved monoclonal antibody therapies in preventing exacerbations in patients with severe eosinophilic asthma. PubMed and Ovid were searched from inception until July 2019 for randomized controlled trials that studied the efficacy of benralizumab, dupilumab, mepolizumab, and reslizumab, in preventing acute exacerbations of asthma. Studies were included if they reported data for patients with severe eosinophilic asthma (defined in this meta-analysis as absolute eosinophil count ≥ 250 cells/μL). Annualized rate ratios for asthma exacerbations (during treatment) were calculated and converted to log rate ratios. Direct and indirect treatment estimates (for inter-drug differences) were analyzed using frequentist network meta-analysis methodology in R and treatments were ranked based on P-scores. In total, nine studies were included in the final analysis. Network meta-analysis revealed that all drugs were superior to placebo in preventing rates of asthma exacerbation in the study population and no inter-drug differences existed. Dupilumab was found to have the greatest magnitudes of effect on decreasing log rate ratio of asthma exacerbation based on P-score (0.83). Benralizumab, dupilumab, mepolizumab, and reslizumab are all associated with decreased asthma exacerbations in patients with eosinophilic asthma, with no significant inter-drug differences.

A behavioral intervention can decrease asthma exacerbations in older adults

BackgroundOlder adults have higher rates of asthma morbidity and mortality compared with younger age groups. Few interventions are tailored to this population. ObjectiveTo evaluate a self-management asthma intervention in older adults. MethodsAdults age 55 and older with persistent asthma were enrolled into blinded, randomized controlled trial of a 6-session asthma self-management intervention. This educational intervention was conducted in group sessions and through individual telephone calls. Outcomes including asthma exacerbations (defined as unscheduled office visits, emergency department visits, or hospitalizations for asthma), spirometric values, FeNO, asthma control, asthma quality of life, and asthma self-management were assessed at 3, 6, and 12 months. ResultsOne hundred eighty-nine subjects were enrolled, 172 were randomized and received at least 1 treatment dose, and 145 (84%) were analyzed at 12 months. On a modified intent-to-treat analysis, those in the intervention group were less likely to have an asthma exacerbation (26.9% vs 47.1%, P = .01), had a lower asthma exacerbation rate (0.8 vs 1.9, P = .02), had better asthma control (19.9 vs 18.6, P = .08), and had a higher asthma self-management score (8.9 vs 8.4, P = .03). After a mixed-model analysis to control for confounding factors, a decrease in asthma exacerbations (P = .02), as well as a decreased asthma exacerbation rate (P = .04), remained statistically significant, whereas asthma control and self-management did not. No other significant outcome differences were found. ConclusionA 6-session asthma self-management intervention can successfully decrease asthma exacerbations among older adults.

Transforming Growth Factor-β1 Decreases β2-Agonist-induced Relaxation in Human Airway Smooth Muscle.

Helper T effector cytokines implicated in asthma modulate the contractility of human airway smooth muscle (HASM) cells. We have reported recently that a profibrotic cytokine, transforming growth factor (TGF)-β1, induces HASM cell shortening and airway hyperresponsiveness. Here, we assessed whether TGF-β1 affects the ability of HASM cells to relax in response to β2-agonists, a mainstay treatment for airway hyperresponsiveness in asthma. Overnight TGF-β1 treatment significantly impaired isoproterenol (ISO)-induced relaxation of carbachol-stimulated, isolated HASM cells. This single-cell mechanical hyporesponsiveness to ISO was corroborated by sustained increases in myosin light chain phosphorylation. In TGF-β1-treated HASM cells, ISO evoked markedly lower levels of intracellular cAMP. These attenuated cAMP levels were, in turn, restored with pharmacological and siRNA inhibition of phosphodiesterase 4 and Smad3, respectively. Most strikingly, TGF-β1 selectively induced phosphodiesterase 4D gene expression in HASM cells in a Smad2/3-dependent manner. Together, these data suggest that TGF-β1 decreases HASM cell β2-agonist relaxation responses by modulating intracellular cAMP levels via a Smad2/3-dependent mechanism. Our findings further define the mechanisms underlying β2-agonist hyporesponsiveness in asthma, and suggest TGF-β1 as a potential therapeutic target to decrease asthma exacerbations in severe and treatment-resistant asthma.

Real-life effectiveness of inhaler device switch from dry powder inhalers to pressurized metred-dose inhalers in patients with asthma treated with ICS/LABA.

Mixed inhaler device use for asthma is associated with worse inhaler technique and outcomes. Given that relievers are commonly prescribed as pressurized metred-dose inhalers (pMDI), changing preventers from dry powder inhalers (DPI) to pMDI may improve asthma outcomes. This study aimed to assess the persistence and effectiveness of switching from DPI to pMDI for inhaled corticosteroid and long-acting β2 -agonist combination therapy (ICS/LABA). This was a historical cohort study using Ajou University Hospital (Korea) patient records. Persistence of switch was defined as receiving ≥1 pMDI and no DPI after the switch. Effectiveness of switch was assessed as the proportion without severe asthma exacerbation and the proportion achieving risk domain asthma control (RDAC; no asthma-related hospitalization, antibiotics without upper respiratory diagnosis or acute course of oral corticosteroids) and overall asthma control (OAC; RDAC and ≤ 200 μg salbutamol/≤500 μg terbutaline average daily dose) comparing 1 year after and before the switch. Within 85 patients who switched from DPI to pMDI and persisted for a year, higher proportion were free from asthma exacerbation after the switch (mean difference in proportion = 0.129, 95% CI: 0.038-0.220). Switching to pMDI was also associated with better RDAC (75.3% vs 57.7%, P = 0.001) and OAC (57.7% vs 45.9%, P = 0.021). From the entire 117 patients who switched to fixed-dose combination (FDC)/ICS LABA pMDI, 76.1% (95% CI: 69.0-100.0%) patients persisted in the following 6 months. Switching to and persisting with pMDI was associated with decreased asthma exacerbations and improved asthma control. The majority of patients persisted with the switch to pMDI for ICS/LABA treatment.