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.

Impact of Asthma Inhalers on Global Climate: A Systematic Review of Their Carbon Footprint and Clinical Outcomes in Spain.

BACKGROUND: Pressurized metered-dose inhalers (pMDIs) exert an environmental impact resulting from CO2 emissions. Therapeutic alternatives with less environmental impact are widely used. Nevertheless, the choice of device and appropriate therapy should meet the clinical needs and the characteristics of the patient. OBJECTIVE: The primary objective was to estimate the impact of pMDIs prescribed for any indication on annual CO2 emissions in Spain.The secondary objective was to evaluate the potential impact of switching pMDIs to dry-powder inhalers (DPIs) in patients with asthma. METHODS: A systematic review of the evidence published during 2010-2021 was carried out. Average annual CO2 emissions of DPIs and pMDIs were calculated in 2 scenarios: the current situation and a hypothetical situation involving a switch from all pMDIs to DPIs. The impact of the switch on clinical outcomes was also evaluated. RESULTS: The total value of CO2-eq/year due to DPIs and pMDIs accounted for 0.0056% and 0.0909%, respectively, of total emissions in Spain. In the event of switching pMDIs to DPIs, except those used for rescue medication, the percentages were 0.0076% and 0.0579%. The evaluation of efficacy, handling, satisfaction, safety, and use of health care resources was not conclusive. CONCLUSIONS: Current CO2 emissions by pMDIs account for a small percentage of the total CO2 footprint in Spain. Nevertheless, there is a need for research into new and more sustainable devices. Suitability and patient clinical criteria such as age and inspiratory flow should be prioritized when prescribing an inhaler.

Molecular and immunomodulatory actions of new antiasthmatic agents: Exploring the diversity of biologics in Th2 endotype asthma.

Asthma is a major respiratory disorder characterised by chronic inflammation and airway remodelling. It affects about 1-8% of the global population and is responsible for over 461,000 deaths annually. Until recently, the pharmacotherapy of severe asthma involved high doses of inhaled corticosteroids in combination with ß-agonist for prolonged action, including theophylline, leukotriene antagonist or anticholinergic yielding limited benefit. Although the use of newer agents to target Th2 asthma endotypes has improved therapeutic outcomes in severe asthmatic conditions, there seems to be a paucity of understanding the diverse mechanisms through which these classes of drugs act. This article delineates the molecular and immunomodulatory mechanisms of action of new antiasthmatic agents currently being trialled in preclinical and clinical studies to remit asthmatic conditions. The ultimate goal in developing antiasthmatic agents is based on two types of approaches: either anti-inflammatory or bronchodilators. Biologic and most small molecules have been shown to modulate specific asthma endotypes, targeting thymic stromal lymphopoietin, tryptase, spleen tyrosine kinase (Syk), Janus kinase, PD-L1/PD-L2, GATA-3, and CD38 for the treatment and management of Th2 endotype asthma.

Asthma Exacerbations in Patients with Type 2 Diabetes and Asthma on Glucagon-like Peptide-1 Receptor Agonists.

Rationale: GLP-1R (glucagon-like peptide-1 receptor) agonists are approved to treat type 2 diabetes mellitus and obesity. GLP-1R agonists reduce airway inflammation and hyperresponsiveness in preclinical models.Objectives: To compare rates of asthma exacerbations and symptoms between adults with type 2 diabetes and asthma prescribed GLP-1R agonists and those prescribed SGLT-2 (sodium-glucose cotransporter-2) inhibitors, DPP-4 (dipeptidyl peptidase-4) inhibitors, sulfonylureas, or basal insulin for diabetes treatment intensification.Methods: This study was an electronic health records-based new-user, active-comparator, retrospective cohort study of patients with type 2 diabetes and asthma newly prescribed GLP-1R agonists or comparator drugs at an academic healthcare system from January 2000 to March 2018. The primary outcome was asthma exacerbations; the secondary outcome was encounters for asthma symptoms. Propensity scores were calculated for GLP-1R agonist and non-GLP-1R agonist use. Zero-inflated Poisson regression models included adjustment for multiple covariates.Measurements and Main Results: Patients initiating GLP-1R agonists (n = 448), SGLT-2 inhibitors (n = 112), DPP-4 inhibitors (n = 435), sulfonylureas (n = 2,253), or basal insulin (n = 2,692) were identified. At 6 months, asthma exacerbation counts were lower in persons initiating GLP-1R agonists (reference) compared with SGLT-2 inhibitors (incidence rate ratio [IRR], 2.98; 95% confidence interval [CI], 1.30-6.80), DPP-4 inhibitors (IRR, 2.45; 95% CI, 1.54-3.89), sulfonylureas (IRR, 1.83; 95% CI, 1.20-2.77), and basal insulin (IRR, 2.58; 95% CI, 1.72-3.88). Healthcare encounters for asthma symptoms were also lower among GLP-1R agonist users.Conclusions: Adult patients with asthma prescribed GLP-1R agonists for type 2 diabetes had lower counts of asthma exacerbations compared with other drugs initiated for treatment intensification. GLP-1R agonists may represent a novel treatment for asthma associated with metabolic dysfunction.

Use of Antiasthmatic Drugs and the Risk of Type 1 Diabetes in Children: A Nationwide Case-Cohort Study.

Asthma has been reported to be associated with an increased risk of type 1 diabetes mellitus in childhood, but the reasons are unclear. We examined whether the use of antiasthmatic drugs was associated with the development of type 1 diabetes in childhood in a nationwide, register-based case-cohort study. We identified all children who were born January 1, 1995, through December 31, 2008, in Finland and diagnosed with type 1 diabetes by 2010 (n = 3,342). A 10% random sample from each birth-year cohort was selected as a reference cohort (n = 80,909). Information on all dispensed antiasthmatic drugs (Anatomical Therapeutic Chemical classification system code R03) during 1995-2009 was obtained, and associations between the use of antiasthmatic drugs and the development of type 1 diabetes were investigated using time-dependent and time-sequential Cox regression models. Dispensed inhaled corticosteroids and inhaled ß-agonists were associated with an increased risk of type 1 diabetes after adjusting for other antiasthmatic drugs, asthma, sex, and birth decade (hazard ratio = 1.29, 95% confidence interval: 1.09, 1.52, and hazard ratio = 1.22, 95% confidence interval: 1.07, 1.41, respectively). These findings suggest that children using inhaled corticosteroids or inhaled ß-agonists might be at increased risk of type 1 diabetes.

Meta-analysis of asthma-related hospitalization in mepolizumab studies of severe eosinophilic asthma.

BACKGROUND: Studies show that mepolizumab can reduce the frequency of clinically significant exacerbations in patients with severe eosinophilic asthma, compared with placebo. However, important events such as hospitalizations and emergency room visits are rare and difficult to characterize in single studies. OBJECTIVE: We sought to compare hospitalization or hospitalization and/or emergency room visit rates in patients with severe eosinophilic asthma treated with mepolizumab or placebo in addition to standard of care for at least 24 weeks. METHODS: This study was conducted and reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. PubMed and the GSK Clinical Study Register were searched for suitable studies. The primary end points were the rate of exacerbations requiring hospitalization and the rate of exacerbations requiring hospitalization/emergency room visit. The proportion of patients with 1 or more event was also assessed. All mepolizumab doses were combined and individual patient-level data were analyzed. RESULTS: Four studies (n = 1388) were eligible for inclusion. Mepolizumab significantly reduced the rate of exacerbations requiring hospitalization (relative rate, 0.49; 95% CI, 0.30-0.80; P = .004) and hospitalization/emergency room visit (relative rate, 0.49; 95% CI, 0.33-0.73; P < .001) versus placebo. Significant reductions of 45% and 38% were also observed for the proportion of patients experiencing 1 or more hospitalization and hospitalization and/or emergency room visit, respectively. CONCLUSIONS: Mepolizumab approximately halved exacerbations requiring hospitalization and/or emergency room visits compared with placebo in patients with severe eosinophilic asthma. This treatment addresses a key outcome in a patient population with a high unmet need (GSK Study 204664).

Is higher population-level use of ICS/LABA combination associated with better asthma outcomes? Cross-sectional surveys of nationally representative populations in New Zealand and Australia.

BACKGROUND AND OBJECTIVE: New Zealand (NZ) and Australia (AU) have similarly high asthma prevalence; both have universal public health systems, but different criteria for subsidized medicines. We explored differences in asthma management and asthma-related outcomes between these countries. METHODS: A web-based survey was administered in AU (2012) and NZ (2013) to individuals aged ≥16 years with current asthma, drawn randomly from web-based panels, stratified by national population proportions. Symptom control was assessed with the Asthma Control Test (ACT). Healthcare utilization was assessed from reported urgent doctor/hospital visits in the previous year. RESULTS: NZ (n = 537) and Australian (n = 2686) participants had similar age and gender distribution. More NZ than Australian participants used inhaled corticosteroid (ICS)-containing medication (68.8% vs 60.9%; P = 0.006) but ICS/long-acting ß2 -agonist (LABA) constituted 44.4% of NZ and 81.5% of Australian total ICS use (P < 0.0001). Adherence was higher with ICS/LABA than ICS-alone (P < 0.0001), and higher in NZ than in AU (P < 0.0001). ACT scores were similar (P = 0.41), with symptoms well controlled in 58.6% and 54.4% participants, respectively. More NZ participants reported non-urgent asthma reviews (56.6% vs 50.4%; P = 0.009). Similar proportions had urgent asthma visits (27.9% and 28.6%, respectively, P = 0.75). CONCLUSION: This comparison, which included the first nationally representative data for asthma control in NZ, showed that poorly controlled asthma is common in both NZ and AU, despite subsidized ICS-containing medications. The greater use of ICS-alone in NZ relative to ICS/LABA does not appear to have compromised population-level asthma outcomes, perhaps due to better adherence in NZ. Different ICS/LABA subsidy criteria and different patient copayments may also have contributed to these findings.

Inhaler reminders improve adherence with controller treatment in primary care patients with asthma.

BACKGROUND: Poor adherence contributes to uncontrolled asthma. Pragmatic adherence interventions for primary care settings are lacking. OBJECTIVE: To test the effectiveness of 2 brief general practitioner (GP)-delivered interventions for improving adherence and asthma control. METHODS: In a 6-month cluster randomized 2 × 2 factorial controlled trial, with GP as unit of cluster, we compared inhaler reminders and feedback (IRF) and/or personalized adherence discussions (PADs) with active usual care alone; all GPs received action plan and inhaler technique training. GPs enrolled patients prescribed combination controller inhalers, with suboptimal Asthma Control Test (ACT) scores (ACT score ≤19). Inhaler monitors recorded fluticasone propionate/salmeterol adherence (covertly for non-IRF groups) and, in IRF groups, provided twice-daily reminders for missed doses, and adherence feedback. PAD GPs received communication training regarding adherence. Outcomes collected every 2 months included ACT scores (primary outcome) and severe exacerbations. Intention-to-treat mixed-model analysis incorporated cluster effect and repeated measures. RESULTS: A total of 43 GPs enrolled 143 patients with moderate-severe asthma (mean age, 40.3 ± 15.2 years; ACT score, 14.6 ± 3.8; fluticasone propionate dose, 718 ± 470 µg). Over 6 months, adherence was significantly higher in the IRF group than in non-IRF groups (73% ± 26% vs 46% ± 28% of prescribed daily doses; P < .0001), but not between PAD and non-PAD groups. Asthma control improved overall (mean change in ACT score, 4.5 ± 4.9; P < .0001), with no significant difference among groups (P = .14). Severe exacerbations were experienced by 11% of the patients in IRF groups and 28% of the patients in non-IRF groups (P = .013; after adjustment for exacerbation history; P = .06). CONCLUSIONS: Inhaler reminders offer an effective strategy for improving adherence in primary care compared with a behavioral intervention or usual care, although this may not be reflected in differences in day-to-day asthma control.

Multivariate Cluster Analyses to Characterize Asthma Heterogeneity and Benralizumab Responsiveness.

BACKGROUND: An improved understanding of how severe asthma heterogeneity affects response could inform treatment decisions. OBJECTIVES: Characterize heterogeneity and benralizumab responsiveness in patients grouped by predefined Severe Asthma Research Program clusters using a multivariate approach. METHODS: In post-hoc analyses of the randomized, double-blind, placebo-controlled phase III SIROCCO (NCT01928771) and CALIMA (NCT01914757) studies, patients with severe asthma who received benralizumab or placebo were assigned to clusters using an established discriminant function to analyze 11 clinical characteristics simultaneously. The annualized asthma exacerbation rate, exacerbation incidence, and lung function were analyzed across clusters. RESULTS: Patients (n = 2,281) met criteria for four of five clusters: cluster 2 (early-onset moderate asthma, n = 393), cluster 4 (early-onset severe asthma, n = 386), cluster 3 (late-onset severe asthma, n = 641), and cluster 5 (late-onset severe, obstructed asthma, n = 861); no patients met cluster 1 criteria. Exacerbation rate reductions were significant in late-onset severe asthma (-48% [95% CI, -61% to -31%]; P < .0001) and late-onset severe, obstructed asthma (-50% [95% CI, -59% to -38%]; P < .0001), with nonsignificant reductions in early-onset clusters. These differences could not be fully explained by blood eosinophil count differences. Values for improvements in FEV1 were significant in late-onset severe asthma (+133 mL [95% CI, 66-200]; P = .0001) and late-onset severe, obstructed asthma (+160 mL [95% CI, 85-235]; P < .0001) while maintaining acute bronchodilator responsiveness. CONCLUSIONS: Benralizumab reduced exacerbations and improved lung function, primarily in late-onset asthma clusters. This multivariate approach to identify subphenotypes, potentially reflecting pathobiological mechanisms, can guide therapy beyond univariate approaches.

Factors Associated With Asthma Biologic Prescribing and Primary Adherence Among Adults in a Large Health System.

BACKGROUND: The availability of asthma biologics may not benefit all patients equally. OBJECTIVE: We sought to identify patient characteristics associated with asthma biologic prescribing, primary adherence, and effectiveness. METHODS: A retrospective, observational cohort study of 9,147 adults with asthma who established care with a Penn Medicine asthma subspecialist was conducted using Electronic Health Record data from January 1, 2016, to October 18, 2021. Multivariable regression models were used to identify factors associated with (1) receipt of a new biologic prescription; (2) primary adherence, defined as receiving a dose in the year after receiving the prescription, and (3) oral corticosteroid (OCS) bursts in the year after the prescription. RESULTS: Factors associated with a new prescription, which was received by 335 patients, included being a woman (odds ratio [OR] 0.66; P = .002), smoking currently (OR 0.50; P = .04), having an asthma hospitalization in the prior year (OR 2.91; P < .001), and having 4+ OCS bursts in the prior year (OR 3.01; P < .001). Reduced primary adherence was associated with Black race (incidence rate ratio 0.85; P < .001) and Medicaid insurance (incidence rate ratio 0.86; P < .001), although most in these groups, 77.6% and 74.3%, respectively, still received a dose. Nonadherence was associated with patient-level barriers in 72.2% of cases and health insurance denial in 22.2%. Having more OCS bursts after receiving a biologic prescription was associated with Medicaid insurance (OR 2.69; P = .047) and biologic days covered (OR 0.32 for 300-364 d vs 14-56 d; P = .03). CONCLUSIONS: In a large health system, primary adherence to asthma biologics varied by race and insurance type, whereas nonadherence was primarily explained by patient-level barriers.

Chemistry and Biology of Selected Mexican Medicinal Plants.

Herbal medicines are an integral element of alternative medical care in Mexico, and the best testimony to their efficacy and cultural value is their persistence in contemporary Mexican marketplaces where the highest percentages of medicinal and aromatic plants are sold. This chapter summarizes current trends in research on medicinal plants in Mexico, with emphasis on work carried out at the authors' laboratories. The most relevant phytochemical and pharmacological profiles of a selected group of plants used widely for treating major national health problems are described.From this contribution, it is evident that in the last five decades a significant amount of research on medicinal plants has been performed by Mexican scientists. Such efforts have led to the publication of many research papers in noted peer-reviewed journals and technical books. The isolation and structural characterization of hundreds of bioactive secondary metabolites have been accomplished, and most importantly, these studies have tended to support the ethnomedical uses of many different species. A multidisciplinary approach for investigating these plants has led to an increased emphasis on areas such as phytopharmacology, phytotoxicology, quality control, regulation, and conservation issues for these valuable resources. The medicinal plants analyzed so far have shown a very broad chemical diversity of their constituents, which have a high potential for exhibiting novel mechanistic effects biologically. The chapter shows also that there is need to conduct additional clinical studies on herbal drugs, in particular because the longstanding traditional evidence for their safety is not always sufficient to assure their rational use. There is also need to move to "omics" approaches for investigating the holistic effect and the influence of groups of phytochemicals on the whole organism. Mexican scientists may be expected to have bright prospects in this regard, which will imbue medicinal plant research with a new dynamism in the future.

Mepolizumab for the treatment of severe eosinophilic asthma.

PURPOSE: Published data on the pharmacology, pharmacokinetics and pharmacodynamics, and clinical efficacy and safety of the interleukin-5 antagonist mepolizumab are reviewed. SUMMARY: Asthma of the eosinophilic phenotype is characterized by persistent eosinophilic airway inflammation promoted primarily by T-helper type 2 cytokines, the key regulator of eosinophils. Patients with severe eosinophilic asthma are burdened by the need to administer high doses of corticosteroids to help manage their symptoms. In November 2015, mepolizumab (Nucala, GlaxoSmithKline) gained U.S. marketing approval for use as an add-on maintenance treatment for severe eosinophilic asthma in patients 12 years of age or older, making it the first personalized targeted therapy for this population. Efficacy results from clinical trials provided evidence of the corticosteroid-sparing effects of mepolizumab and its ability to reduce both blood and sputum eosinophil counts. Safety data from several Phase II or III studies involving a total of more than 1,300 patients indicated that mepolizumab was generally well tolerated, and types and rates of adverse events in mepolizumab recipients were comparable to those reported with placebo use; the only mepolizumab-associated serious adverse drug events were asthma exacerbations in 2 patients. The recommended dosage of mepolizumab is 100 mg administrated via subcutaneous injection every 4 weeks. CONCLUSION: Mepolizumab is a safe and efficacious novel add-on therapy for a small subgroup of patients with severe eosinophilic asthma whose asthma is not adequately controlled by standard regimens for asthma treatment.

A Randomized Pragmatic Trial of Changing to and Stepping Down Fluticasone/Formoterol in Asthma.

BACKGROUND: Guidelines recommend reducing treatment in patients with well-controlled asthma after 3 months of stability. However, there is inadequate real-life data to guide physicians on therapy change in daily practice. OBJECTIVE: To assess asthma control after change to and step-down of fluticasone propionate/formoterol fumarate dihydrate (FP/FOR) in real-life patients. METHODS: In a randomized controlled, pragmatic, open-label trial, 225 well-controlled patients with asthma were randomized (1:2) to maintain high-dose fluticasone propionate/salmeterol xinafoate (FP/SAL, 1000/100 µg) or switch to FP/FOR (1000/40 µg) daily for 12 weeks (phase 1). One hundred sixteen patients stable on FP/FOR at week 12 were subsequently randomized (1:1) to maintain this therapy, or stepped down to FP/FOR (500/20 µg) daily for 12 weeks (phase 2). The primary end point was the 7-question Asthma Control Questionnaire (ACQ7) score. RESULTS: In phase 1, FP/FOR (1000/40 µg) (n = 126) was noninferior to FP/SAL (1000/100 µg) (n = 73) for ACQ7 (difference in means, -0.12; 95% CI, -0.32 to 0.09). In phase 2, FP/FOR (500/20 µg) (n = 52) was noninferior to FP/FOR (1000/40 µg) (n = 52) for ACQ7 (difference in means, 0.01; 95% CI, -0.20 to 0.22). There was no significant difference in exacerbation rate between the groups in either phase. However, 1 to 2 exacerbations in 12 months before phase 1 were associated with the occurrence of an exacerbation after step-down (P = .007). CONCLUSIONS: In patients with well-controlled asthma, a change from FP/SAL to FP/FOR did not compromise asthma control. Step-down of FP/FOR was well tolerated; however, in contrast to current guidelines, our data suggest caution in stepping down patients uncontrolled in the last 12 months. Larger step-down studies are required to confirm these findings.

Asthma Controller Medications for Children in Japan: Analysis of an Administrative Claims Database.

Background. Treatment and management strategies for asthma in children are generally consistent internationally, but prescription of antiasthma drugs differs among countries. The objective of this study was to examine the prescribing patterns of antiasthma drugs, particularly controller medications, in children. Methods. A retrospective cohort study was performed in children with asthma using an administrative claims database in Japan. Results. A total of 1149 preschool-age and 3226 school-age children were identified. Leukotriene receptor antagonists were prescribed for about 80% of the children. Long-acting ß-agonists were prescribed for 87.6% and 59.6% of preschool-age and school-age children, respectively, whereas prescriptions of inhaled corticosteroids had lower rates of 8.2% and 16.5%, respectively. In an examination of prescriptions at 1-month intervals, a relatively high number of children were prescribed bronchodilators without anti-inflammatory agents. Conclusion. Our findings suggest that asthma care for children in Japan can be improved through changes in drug prescriptions.

Increased Dose of Inhaled Corticosteroid versus Add-On Long-acting ß-Agonist for Step-Up Therapy in Asthma.

RATIONALE: Guidelines advocate adding long-acting ß-agonist (LABA) to inhaled corticosteroid as the preferred step-up therapy to increasing inhaled corticosteroid dose for patients with uncontrolled asthma on inhaled corticosteroid monotherapy. However, less than 5% of patients with asthma qualify for the randomized controlled trials on which guidelines are based. Thus, real-world data are needed to complement the results of randomized trials with narrow entry criteria. OBJECTIVES: To compare the effectiveness of stepping up asthma therapy with an increased dose of various types of inhaled corticosteroid as compared with add-on LABA. METHODS: We performed a historical matched cohort study using large primary care databases to compare asthma step-up therapy with small- and standard size-particle inhaled corticosteroid versus added LABA for patients 12-80 years old. As outcomes, we examined a composite of asthma control and rates of severe exacerbations. MEASUREMENTS AND MAIN RESULTS: The odds of asthma control and rates of severe exacerbations over one outcome year were comparable with increased inhaled corticosteroid dose versus added LABA. The adjusted odds ratios (95% confidence interval) for achieving asthma control with increased inhaled corticosteroid dose versus inhaled corticosteroid/LABA were 0.99 (0.88-1.12) for small-particle inhaled corticosteroid (n = 3,036 per cohort) and 0.85 (0.67-1.07) for standard size-particle inhaled corticosteroid (n = 809 per cohort). The adjusted rate ratios (95% confidence interval) for severe exacerbations, compared with inhaled corticosteroid/LABA combination inhaler, were 1.04 (0.91-1.20) and 1.18 (0.92-1.54), respectively. The results were not affected by smoking status. CONCLUSIONS: When applied to a broad primary care population, antiinflammatory therapy using increased doses of small- or standard size-particle inhaled corticosteroid is as effective as adding LABA, as measured by outcomes important to both patients and providers. Real-world populations and outcomes need to be taken into consideration when formulating treatment recommendations.

High blood eosinophil count is a risk factor for future asthma exacerbations in adult persistent asthma.

BACKGROUND: Exacerbation-associated uncontrolled asthma represents a major public health problem. The relationship of elevated blood eosinophils to this process needs study. OBJECTIVE: To determine whether a high blood eosinophil count is a risk factor for future asthma exacerbations in adult persistent asthma. METHODS: By using electronic pharmacy and health care data from Kaiser Permanente Southern California, 2392 patients, ages 18 to 64 years, were identified who met the Health Effectiveness Data and Information Set 2-year criteria for persistent asthma, did not manifest chronic obstructive pulmonary disease and other major illnesses, and had a blood eosinophil determination in 2010. Exacerbations (primary outcome) were defined as asthma outpatient visits that required systemic corticosteroid dispensing within ±7 days or asthma emergency department visits or hospitalizations. A period of ≥8 days defined a new exacerbation. Multivariate modelling used negative binomial and Poisson regression to examine the association between a blood eosinophil count determined in 2010 and risk of exacerbations, and ≥7 short-acting ß2-agonist (SABA) canisters dispensed (secondary outcome) in 2011 by adjusting for demographics, comorbidities, and asthma burden. RESULTS: The rate of asthma exacerbations in 2011 was 0.41 events per person year (95% CI, 0.37-0.45). Eosinophil count ≥400/mm(3) in 2010 was a risk factor for asthma exacerbations in 2011 (adjusted rate ratio 1.31 [95% CI, 1.07-1.60]; P = .009) and ≥7 SABA dispensed (adjusted risk ratio 1.17 [95% CI, 1.03-1.1.33]; P = .015). CONCLUSION: A high blood eosinophil count is a risk factor for increased future asthma exacerbations and excessive short-acting ß2-agonist use after adjustment of potential confounders in adults with persistent asthma, which suggests a higher disease burden in patients with asthma and with high blood eosinophil counts.