D. Stempel

Asthma in the elderly: Current understanding and future research needs—a report of a National Institute on Aging (NIA) workshop

n n Asthma in the elderly is underdiagnosed and undertreated, and there is a paucity of knowledge on the subject. The National Institute on Aging convened this workshop to identify what is known and what gaps in knowledge remain and suggest research directions needed to improve the understanding and care of asthma in the elderly. Asthma presenting at an advanced age often has similar clinical and physiologic consequences as seen with younger patients, but comorbid illnesses and the psychosocial effects of aging might affect the diagnosis, clinical presentation, and care of asthma in this population. At least 2 phenotypes exist among elderly patients with asthma; those with longstanding asthma have more severe airflow limitation and less complete reversibility than those with late-onset asthma. Many challenges exist in the recognition and treatment of asthma in the elderly. Furthermore, the pathophysiologic mechanisms of asthma in the elderly are likely to be different from those seen in young asthmatic patients, and these differences might influence the clinical course and outcomes of asthma in this population.n n

Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone.

BACKGROUNDnThe safe and appropriate use of long-acting beta-agonists (LABAs) for the treatment of asthma has been widely debated. In two large clinical trials, investigators found a potential risk of serious asthma-related events associated with LABAs. This study was designed to evaluate the risk of administering the LABA salmeterol in combination with an inhaled glucocorticoid, fluticasone propionate.nnnMETHODSnIn this multicenter, randomized, double-blind trial, adolescent and adult patients (age, ≥12 years) with persistent asthma were assigned to receive either fluticasone with salmeterol or fluticasone alone for 26 weeks. All the patients had a history of a severe asthma exacerbation in the year before randomization but not during the previous month. Patients were excluded from the trial if they had a history of life-threatening or unstable asthma. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization). Noninferiority of fluticasone-salmeterol to fluticasone alone was defined as an upper boundary of the 95% confidence interval for the risk of the primary safety end point of less than 2.0. The efficacy end point was the first severe asthma exacerbation.nnnRESULTSnOf 11,679 patients who were enrolled, 67 had 74 serious asthma-related events, with 36 events in 34 patients in the fluticasone-salmeterol group and 38 events in 33 patients in the fluticasone-only group. The hazard ratio for a serious asthma-related event in the fluticasone-salmeterol group was 1.03 (95% confidence interval [CI], 0.64 to 1.66), and noninferiority was achieved (P=0.003). There were no asthma-related deaths; 2 patients in the fluticasone-only group underwent asthma-related intubation. The risk of a severe asthma exacerbation was 21% lower in the fluticasone-salmeterol group than in the fluticasone-only group (hazard ratio, 0.79; 95% CI, 0.70 to 0.89), with at least one severe asthma exacerbation occurring in 480 of 5834 patients (8%) in the fluticasone-salmeterol group, as compared with 597 of 5845 patients (10%) in the fluticasone-only group (P<0.001).nnnCONCLUSIONSnPatients who received salmeterol in a fixed-dose combination with fluticasone did not have a significantly higher risk of serious asthma-related events than did those who received fluticasone alone. Patients receiving fluticasone-salmeterol had fewer severe asthma exacerbations than did those in the fluticasone-only group. (AUSTRI ClinicalTrials.gov number, NCT01475721.).

Pharmacoepidemiological Study of Long-Acting β-agonist/Inhaled Corticosteroid Therapy and Asthma Mortality: Clinical Implications

RationaleThe increased risk of asthma mortality in association with long-acting β2-agonist (LABA) monotherapy is well documented but the risk associated with LABA plus inhaled corticosteroid (ICS) therapy remains unclear.ObjectiveWe assessed the feasibility of a large pharmacoepidemiological study to compare the effect of combined LABAxa0+xa0ICS therapy with non-LABA maintenance therapy on the risk of asthma mortality.MethodsThis observational retrospective study used electronic data from ten US data partners to construct a cohort of patients with persistent asthma (defined as: four or more asthma maintenance medication dispensings in 12xa0months and a code diagnosis of asthma). Asthma deaths were determined by linking patient data with the National Death Index.ResultsFrom 5,881,438 asthma patients, a cohort of 994,627 met the criteria for persistent asthma and provided 2.4 million person-years of follow-up. The total number of deaths was 278 with only three of these occurring after incident exposure to an asthma maintenance medication. The overall pooled asthma mortality rate, standardized by age and data partner, was 1.16 [95xa0% confidence interval (CI) 0.98–1.34] per 10,000 person-years; crude mortality rates (per 10,000 person-years) increased with age and were higher in female individuals (1.34; 95xa0% CI 1.15–1.55) than in male individuals (0.92; 95xa0% CI 0.74–1.12).ConclusionsDespite a cohort size of almost 1 million asthma patients, the asthma mortality risk associated with combined LABAxa0+xa0ICS therapy could not be determined. This study showed that very few patients with persistent asthma have asthma-related deaths, and confirmed that those who die are more likely to be older and female.

P239 Effect Of Inhaled Corticosteroid (ics) Particle Size On Asthma Efficacy And Safety Outcomes: A Systematic Literature Review

Introduction and objectives ICS of differing particle size, due both to the formulation and propellant, may impact patient outcomes. This systematic review of randomised controlled trials compared asthma efficacy and safety outcomes from the use of fluticasone propionate (FP)-containing medications and alternative smaller particle ICS. Methods English language published peer-reviewed literature (Jan 1, 1998-Feb 13, 2014) with FP-containing medications, yielded 1,655 potentially-relevant articles: 1,575 were excluded, 80 full-text articles were reviewed, and 25 were extracted for data with treatment comparisons (FP- vs. small particle ICS-containing medicines). Efficacy measures included lung function, asthma exacerbations, and rescue medication use. Safety endpoints included adverse events, growth and bone measures, and cortisol. Benefit-risk interval plots of risk differences with 95% confidence intervals were produced for FP vs. comparators. Results Ten controlled trials compared the efficacy of FP with beclomethasone diproprionate (BDP-HFA). Six studies found no appreciable differences in efficacy while four trials identified improvement in lung function with FP vs. BDP-HFA. In ten randomised trials comparing the efficacy of ciclesonide (CIC) with FP, CIC was found to be non-inferior or not statistically different from FP on numerous efficacy endpoints in the majority of the studies. Most safety assessments across nine trials did not differ between treatments. Results were similar for fixed dose combination therapies that contained FP and BDP-HFA (n = 3 trials). Conclusions This systematic review suggests no differences in efficacy or safety between FP-containing medications and small particle size ICS medications for the treatment of asthma. (GSK-funded, LS2270)

Building Bridges for Asthma Care Program: A School-Centered Program Connecting Schools, Families, and Community Health-Care Providers

Asthma imposes tremendous burden on children, families, and society. Successful management requires coordinated care among children, families, health providers, and schools. Building Bridges for Asthma Care Program, a school-centered program to coordinate care for successful asthma management, was developed, implemented, and evaluated. The program consists of five steps: (1) identify students with asthma; (2) assess asthma risk/control; (3) engage the family and student at risk; (4) provide case management and care coordination, including engagement of health-care providers; and (5) prepare for next school year. Implementation occurred in 28 schools from two large urban school districts in Colorado and Connecticut. Significant improvements were noted in the proportions of students with completed School Asthma Care Plans, a quick-relief inhaler at school, Home Asthma Action/Treatment Plans and inhaler technique (p < .01 for all variables). Building Bridges for Asthma Care was successfully implemented extending asthma care to at-risk children with asthma through engagement of schools, health providers, and families.

Safety Study of Salmeterol in Asthma in Adults.

n engl j med 375;11 nejm.org September 15, 2016 1096 danazol. Findings in the endocrinology literature provide some support for these explanations.2-4 The mechanism of sex steroids is complex, and there are probably multiple mechanisms of action in patients with telomeropathy. We agree with Grossmann that the effects of danazol have not been fully elucidated, but a clinical study of these effects is under way. Jouneau et al. ask whether changes in FVC were observed in patients who received danazol and why this measure of lung function was not included in our article. We agree that FVC has been used in clinical trials as a primary measurement, but there are no validated surrogate end points in idiopathic pulmonary fibrosis, and selection of a primary end point is not standardized.5 Indeed, various other primary end points have been used in clinical trials involving patients with idiopathic pulmonary fibrosis, including DLCO, 6-minute walk distance, and death. In our cohort of patients with telomere diseases, the most prevalent abnormality at enrollment was decreased DLCO; thus, this abnormality was the most indicative measure of subclinical pulmonary fibrosis at initial evaluation. Similar to the rate of decline in the DLCO, there was an accelerated decline in the percentage of predicted FVC among patients who were not receiving danazol (before enrollment and 12 months after discontinuation of the drug) (Fig. 1), as compared with the predicted FVC during the 24 months of treatment with danazol. However, these results should be interpreted cautiously, since the study was not designed primarily to test this hypothesis. Changes in pulmonary function were a secondary end point, and statistical power is limited for this analysis. Danielle M. Townsley, M.D. Bogdan Dumitriu, M.D. Neal S. Young, M.D.