Patterns of rescue and maintenance therapy claims surrounding a clinical encounter for an asthma exacerbation.

BACKGROUND: A "window of opportunity" has been proposed where anti-inflammatory therapy administration in response to symptoms could prevent exacerbation. OBJECTIVE: To evaluate rescue and maintenance therapy claims surrounding a severe asthma exacerbation serious enough to require a face-to-face clinical encounter. METHODS: Merative MarketScan research databases (US administrative claims 2011 to 2017) were analyzed for patients aged ≥4 years, with an asthma diagnosis code, who filled short-acting ß2-agonist (SABA) and Global Initiative for Asthma Steps 3 to 5 maintenance therapies. Patients were indexed on a random SABA claim and had 12 months' continuous health plan eligibility pre- and post-index. Serious exacerbations were severe exacerbations requiring systemic corticosteroids prescribed from an outpatient clinic, urgent care or emergency department, or hospitalization for asthma. SABA and maintenance claims 30 days pre- and post-event were analyzed. RESULTS: Of 319,342 patients (30% children 4 to 11 years; 70% adults or adolescents ≥12 years), 27.2% of children and 16.8% of adolescents or adults experienced ≥ 1 serious exacerbation (unadjusted odds ratio [OR], 1.85 [95% confidence interval, 1.81-1.88]). In the 30 days pre-event, 42.6% filled ≥1 SABA (children: 44.3%; adolescents or adults: 41.5%; OR, 1.12 [1.09-1.16]) and 57.4% filled maintenance (children: 59.0%; adolescents or adults: 56.3%; OR, 1.12 [1.08-1.15]). In the 30 days post-event, 61.4% filled SABA (children: 69.7%; adolescents or adults: 55.6%; OR, 1.84 [1.78-1.90]) and 94.8% filled maintenance (children: 98.6%; adolescents or adults: 92.2%; OR, 6.09 [5.45-6.81]). CONCLUSION: Many patients treated as having moderate-to-severe asthma escalate SABA claims before a serious exacerbation, but approximately 40% have no anti-inflammatory maintenance fill, highlighting a "window of opportunity" to prevent exacerbations using inhaled corticosteroids concomitantly with SABA as rescue.

Can PPSV-23 Vaccine Impact Exacerbations of Chronic Cough Symptoms and Medication Use in Younger Adult Asthmatics? A Clinical Question That Needs Answering.

Symptoms of chronic cough (CC) from the airways are commonly treated with antibiotics, antitussives, bronchodilators, and steroids. There is a wide variability in treatment response, dependent on the exact cough etiology. Our case-series study was composed of 71 nonsmoking adults, 59 females, mean age 43 (±21) years, with a history of CC-asthma and history of ≥2 exacerbations/year requiring systemic steroids and/or antibiotics. All had decreased Streptococcus pneumoniae antibody titers, with a mean average of 3 of 23 normal serotypes and were subsequently vaccinated with PPSV-23. Pre- and post-12-month vaccination questionnaires were administered, and 35 (54%) reported both decreased CC symptoms and asthma medication use. Baseline comparisons to those with no change in CC symptoms or asthma medication use revealed significantly lower exhaled nitric oxide (FeNO) levels (17 ± 10; 62 + 40 ppb), serum eosinophils (192 ± 156; 280 ± 166/mcL), and total IgE (132 ± 167; 275 ± 290 IU/mL) in those with improvement post-vaccination. Higher baseline symptoms scores for upper respiratory infections as a trigger to their CC (* p > 0.05) were found in those responding to PPSV-23. These data reveal a subset of asthma in younger adults, <65 years, with significantly decreased S. pneumoniae antibody titers with less CC symptoms and asthma medication use for exacerbations after PPSV-23 vaccination.

Demographics, Treatment Patterns, and Morbidity in Patients with Exercise-Induced Bronchoconstriction: An Administrative Claims Data Analysis.

PURPOSE: Exercise-induced bronchoconstriction (EIB) is generally treated with short-acting ß2-agonists (SABA) before exercising, to prevent symptoms. Real-world data on treatments and outcomes for patients with EIB alone (EIBalone), or with asthma (EIBasthma), in the USA are limited. This study compared demographics, treatment patterns, morbidity, and costs of treating EIB between these two groups of patients. PATIENTS AND METHODS: Administrative claims from US IBM® MarketScan® Research databases were analyzed retrospectively. Patients aged ≥4 years filling a SABA claim between 1/1/2011 and 12/31/2016 were evaluated. Patients were indexed on a random SABA claim and required to have 12 months' continuous eligibility pre- and post-index, ≥1 maintenance medication and/or SABA fill post-index, and were designated EIBalone or EIBasthma according to diagnostic codes (EIB only or EIB plus asthma, respectively). Descriptive statistics were used. RESULTS: In total, 13,480 patients had EIBalone and 14,862 had EIBasthma. Compared with EIBasthma, the EIBalone group was older (mean[SD] 20.4[13.6] vs 17.8[13.6] years), had more females (60.7% vs 54.7%), and filled fewer SABA claims (1.9[1.4] vs 2.5[2.2]) (all p<0.001). A smaller proportion of patients in the EIBalone than EIBasthma group had maintenance therapy claims (79.9% vs 90.6%, p<0.001). The EIBalone group also had a lower proportion of patients with oral or injectable corticosteroid claims (29.4% vs 32.0%) and asthma and/or EIB-related emergency department (1.0% vs 13.0%) or outpatient visits (65.1% vs 72.3%; all p<0.0001). Annual days' supply of oral corticosteroids was similar between groups (mean[SD] EIBalone: 20.7[30.8] vs EIBasthma: 19.8[28] days). CONCLUSION: Individuals with EIBalone or EIBasthma demonstrate considerable morbidity. New treatment paradigms may be needed to optimize outcomes for both patient groups.

Real-world patterns and implications of short-acting ß2-agonist use in patients with asthma in the United States.

BACKGROUND: Short-acting ß2-agonist (SABA) use is one measure reflecting asthma control. OBJECTIVE: To evaluate the associations between real-world SABA use and severe asthma exacerbations in the United States. METHODS: Patients with asthma 12 years of age or older receiving SABA in the IBM MarketScan research databases of US administrative claims from September 30, 2014, to September 30, 2016, were evaluated. Patients with 12 months' continuous eligibility before and after their first SABA claim (index SABA), an asthma diagnosis before through 60 days postindex, and either one additional SABA or at least 1 maintenance fill(s) were included. SABA claims postindex (including index fill) were grouped as follows: low: index only; medium: 2 to 3 canisters per year; and high: 4 or more canisters per year. Differences in SABA exposure with respect to disease severity groups and severe asthma exacerbations (hospitalizations, emergency visits, or outpatient systemic corticosteroids) were analyzed by analysis of variance and χ2 (significance, P ≤ .05). RESULTS: A total of 135,540 patients were included: 62.8% women; mean (SD) age, 40.9 (18.3) years; SABA fills per 12-months postindex: 3.0(2.7). Furthermore, 28% of patients filled 1 SABA, 47% 2 to 3, and 25% 4 or more canisters per year. Despite higher maintenance medication possession ratio with increasing SABA (low, 0.53 (0.37); medium, 0.59 (0.35); high, 0.66 (0.32)), annual exacerbation rate per person per year and percent of patients within each SABA group having at least 1 exacerbation rose as SABA fills increased (low, 1.00 (1.45), 45.8%; medium, 1.20 (1.62), 54.3%; high, 1.50 (1.94), 58.7%). Mean SABA fills differed between patients with 0 exacerbation, 2.8 (2.6); 1 exacerbation, 2.9 (2.5); and 2 or more exacerbations, 3.3 (2.9). CONCLUSION: Exacerbation risk increased with increasing SABA fills. Management strategies ensuring adequate anti-inflammatory therapy delivered to the airways when symptoms occur may be needed to mitigate asthma morbidity.

Impact of pneumococcal vaccine response on asthma exacerbation frequency in young children.

INTRODUCTION: Chronic asthma is a heterogeneous disease, and increased eosinophils have been shown to predict increased asthma exacerbations, especially in adults. Recent recommendations suggest the need for supplemental PPV-23 vaccination in older children with chronic asthma. METHODS: To investigate differences in preschool asthma, our case-cohort study comprised of 127 children, mean age 47 months (32-65), with a history of asthma exacerbations requiring more than three courses of systemic steroid bursts and more than six antibiotics courses in the previous year. RESULTS: At baseline, mean antibody titer response to Streptococcus pneumoniae was decreased at 2.6 ± 2 out of 14 serotypes, despite prior complete pneumococcal conjugate vaccine (PCV) vaccinations. All children were readministered pneumococcal vaccinations with PCV-13 booster and/or PPSV-23. Mean postvaccination pneumococcal vaccine (PV) titer response was 16 ± 5 out of 23 serotypes. After contacting 91 parents/caretakers, 75 responded with less frequency of corticosteroids and antibiotic use for asthma exacerbations after PV. This group had baseline eosinophil counts of 211 ± 36/µL, while those without improvement were significantly higher at 371 ± 123/µL,*P < .05. There were no significant differences (P > .05) between the two groups from other baseline measures including demography or atopic status. CONCLUSIONS: This subset of children with exacerbation-prone asthma had poor antibody titer response to Streptococcus pneumoniae, even with prior complete PCV-13 immunization. Identification of low antibody responses to PV serotypes may provide a targeted therapeutic approach to reduce wheezing exacerbations in a precise asthma phenotype in children.

Healthcare resource utilization, expenditures, and productivity in patients with asthma with and without allergies.

Objective: To compare healthcare resource utilization (HCRU), healthcare expenditures, and work productivity and activity impairment within a general asthma population with persistent asthma and evidence of allergy (PA-EA) and persistent asthma with no evidence of allergy (PA-NEA).Methods: We conducted a retrospective analysis of survey responses and claims from the Observational Study of Asthma Control and Outcomes (OSACO) study. Eligible patients with persistent asthma aged ≥12 years were sent four surveys over 15 months. Regression models were used to assess the association between: (1) PA-EA (defined as a positive response to a survey question about hay fever/seasonal allergies AND ≥1 diagnostic code for atopic conditions) and HCRU and expenditures; and (2) PA-EA and Work Productivity and Activity Impairment (WPAI)-Asthma questionnaire scores (vs. PA-NEA).Results: Adjusted data showed that, vs. PA-NEA (n = 312), patients with PA-EA (n = 971) incurred 1.34-times more all-cause prescriptions (95% confidence interval [CI], 1.20-1.48), $132.79 higher prescription costs (95% CI, $22.03-243.56), and $926.11 higher all-cause total healthcare costs (95% CI, $279.67-1572.54), per 4-month period. Patients with PA-EA were 4.1% less productive while working (95% CI, 3.75-4.48%) and experienced a 6.5% reduction in all activities (95% CI, 6.11-6.88%) vs. those with PA-NEA.Conclusions: Patients with PA-EA had greater HCRU, healthcare expenditures, and lower productivity compared with those patients with PA-NEA. These results highlight the burden of atopy in patients with persistent asthma and underscore the importance of allergic endotype identification for more vigilant disease management.

Impact of allergies on health-related quality of life in patients with asthma.

Objective: To estimate the health-related quality of life (HRQoL) and health utilities among asthma patients with and without comorbid allergies in a managed care population.Methods: This was a retrospective analysis of patient survey responses and pharmacy claims from the Observational Study of Asthma Control and Outcomes (OSACO). Patients ≥12 years-old with persistent asthma received four identical surveys between April-2011 and December-2012. The presence of allergy was identified by a positive response to a survey question about hay fever/seasonal allergies and ≥1 diagnosis-related ICD-9-CM code(s) for allergic conditions. HRQoL instruments included generic utility (EQ-5D-3L [including VAS]), asthma-specific utility (AQL-5D) and asthma-specific health status (Mini Asthma Quality of Life Questionnaire [MiniAQLQ]). Median regression was used for utility scores and Least Squares regression for MiniAQLQ, adjusting for sociodemographic characteristics and smoking.Results: Of the 2681 asthmatics who completed the first survey in the OSACO study, 971 had comorbid allergies. After adjusting for covariates, asthma patients with comorbid allergies had significantly lower MiniAQLQ scores than patients without allergies (-0.489 [95% CI -0.570, -0.409]; p < 0.01), with the greatest decrement/impairment observed for the environmental stimuli domain (-0.729 [95% CI -0.844, -0.613]; p < 0.01). Utility scores were also statistically significantly lower for asthma patients with comorbid allergies compared to those without allergies (EQ-5D, -0.031 [95% CI -0.047, -0.015]; AQL-5D, -0.036 [95% CI -0.042, -0.029]; p < 0.01 each).Conclusions: The presence of allergies with persistent asthma is associated with a significant deleterious impact on several different measures of HRQoL.

Medication use and indicators of poor asthma control in patients with and without allergies.

Background: Approximately two-thirds of people with asthma have some evidence of allergy; their condition differs from nonallergic asthma in terms of predominant symptoms and clinical outcomes. Objective: To compare asthma control and medication use among patients with persistent asthma with evidence of allergy (PA-EA) and patients with persistent asthma with no evidence of allergy (PA-NEA). Methods: A retrospective analysis of survey responses and medication claims data from the Observational Study of Asthma Control and Outcomes study, a prospective survey linked to retrospective claims-based analysis of patients ages ≥ 12 years with persistent asthma in a U.S. health maintenance organization. Evidence of allergy was defined as both a positive response to a survey question about hay fever and/or seasonal allergies and one or more medical diagnostic codes for atopic conditions. Regression models were used to compare asthma control (Asthma Control Questionnaire [ACQ] scores) and asthma medication use between PA-EA and PA-NEA. Results: Adjusted data showed that, versus the patients with PA-NEA (n = 312), patients with PA-EA (n = 971) had higher (worse) 5-item and 6-item ACQ (ACQ-5 and ACQ-6) scores (by 0.34 [95% confidence interval {CI}, 0.24-0.44]; and 0.31 [95% CI, 0.21-0.40], respectively), were more likely to have poorly controlled asthma (ACQ-5 score ≥ 1.5: odds ratio 3.37 [95% CI, 2.07-5.50]; ACQ-6 score ≥ 1.5: odds ratio 3.46 [95% CI, 2.13-5.62]) and less likely to have well-controlled asthma (ACQ-5 score ≤ 0.75: odds ratio 0.21 [95% CI, 0.13-0.34]; ACQ-6 score ≤ 0.75: odds ratio 0.21 [95% CI, 0.13-0.35]). Patients with PA-EA also had greater asthma medication use, most notably 2.5 times more prescriptions of high-dose inhaled corticosteroid in a 4-month period (95% CI, 1.21-5.16) and 16.15 times higher odds of chronic oral corticosteroid use (95% CI, 1.50-174.09) versus PA-NEA. Conclusion: The patients with PA-EA versus PA-NEA had worse asthma control and greater medication use. These patients may need more vigilant clinical oversight and treatment management to ensure adequate asthma control.

Can early intervention in pediatric asthma improve long-term outcomes? A question that needs an answer.

OBJECTIVE: Although many children with asthma do not experience persistence into adulthood, recent studies have suggested that poorly controlled asthma in childhood may be associated with significant airflow obstruction in adulthood. However, data regarding disease progression are lacking, and clinicians are not yet able to predict the course of a child's asthma. The goal of this article was to assess the current understanding of childhood asthma treatment and progression and to highlight gaps in information that remain. DATA SOURCES: Nonsystematic PubMed literature search and authors' expertise. STUDY SELECTION: Articles were selected at the authors' discretion based on areas of interest in childhood asthma treatment and progression into adulthood. RESULTS: Uncontrolled asthma in early childhood can potentially have lasting effects on lung development, but it is unclear whether traditional interventions in very young children preserve lung function. Although not all children respond to standard interventions, certain asthma phenotypes have been identified that can help to understand which children may respond to a particular treatment. CONCLUSION: Clinicians should monitor children's asthma control and pulmonary function over time to assess the long-term impact of an intervention and to minimize the effect of uncontrolled asthma, especially exacerbations, on lung development. New biologic therapies have shown promise in treating adults with severe, uncontrolled asthma, and some of these therapies are approved in the United States for children as young as age 6. However, knowledge gaps regarding the efficacy and safety of these treatments in younger children hamper our understanding of their effect on long-term outcomes.

Efficacy and safety of budesonide/formoterol pMDI vs budesonide pMDI in asthmatic children (6-<12 years).

BACKGROUND: The efficacy and safety of budesonide/formoterol pressurized metered-dose inhaler (pMDI) have been demonstrated in patients with asthma at least 12 years old. OBJECTIVE: To evaluate the efficacy of 2 formoterol doses added to budesonide as fixed combinations vs budesonide alone in children 6 to younger than 12 years with asthma. METHODS: This randomized, double-blinded, parallel-group, multicenter study (NCT02091986; CHASE 3) included children 6 to younger than 12 years with asthma previously receiving a medium-dose inhaled corticosteroid (ICS) or an ICS plus a long-acting ß2-agonist. Children symptomatic during a 7-28-day run-in on low-dose ICS, 1 inhalation of budesonide dry powder inhaler 90 µg twice daily (BID), were randomized to receive 2 inhalations of budesonide/formoterol pMDI 80/4.5 µg (160/9 µg) BID (n = 92), budesonide/formoterol pMDI 80/2.25 µg (160/4.5 µg) BID (n = 95), or budesonide pMDI 80 µg (160 µg) BID (n = 92) for 12 weeks. RESULTS: Change in forced expiratory volume in 1 second from baseline to 1 hour after dosing (primary end point), change in forced expiratory volume in 1 second 15 minutes after dosing, and peak expiratory flow 1 hour after dosing at week 12 were statistically significantly greater for budesonide/formoterol 160/9 µg vs budesonide (P ≤ .015 for all comparisons), but not for budesonide/formoterol 160/4.5 µg vs budesonide. Bronchodilator effects, evident 15 minutes after the dose on day 1, were maintained at week 12. Incidence of protocol-defined asthma exacerbations and improvements in asthma symptom-related and quality-of-life outcomes were similar across treatments. There were no notable safety differences among treatments. CONCLUSION: Budesonide/formoterol pMDI 160/9 µg showed statistically significant and clinically meaningful lung function improvements vs budesonide pMDI 160 µg, demonstrating appropriateness as a therapeutic option for children 6 to younger than 12 years with asthma symptomatic on ICS alone. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02091986.

Nasal nitric oxide and nasal eosinophils decrease with levocetirizine in subjects with perennial allergic rhinitis.

BACKGROUND: Allergic rhinitis is commonly treated with antihistamines. Monitoring improvement of airway inflammation noninvasively using nasal nitric oxide (nNO) would be clinically useful. To determine the anti-inflammatory effect of oral levocetirizine dihydrochloride (LC), we measured nNO and nasal eosinophils (nEos) in perennial allergic rhinitis (PAR) subjects. METHODS: A randomized double-blind placebo-controlled crossover design was used. Inclusion criteria consisted of subjects having a PAR history, exam and diary scores consistent with active symptoms, and positive skin testing. Subjects taking allergy medications 1 month before the study were not enrolled. After consenting, 31 subjects (24 female subjects; mean age, 29 years) were randomized to either oral LC (5 mg) or matching placebo for 2 weeks. After 2 week washout, subjects started the other 2-week treatment. At each visit, nNO was measured by aspiration at each nare using a nasal kit from NIOX (Aerocrine, Sweden) in parts per billion; nEos was collected from nasal smears and measured by microscopy using the scoring system (0-4+) and symptoms were self-reported using the allergic Rhinitis Quality of Life Questionnaire (RQLQ). Daily allergy symptom scores (total symptom score [TSS] 4) were collected at each visit. RESULTS: During LC, mean baseline nNO was 807 ± 317 parts per billion (ppb; left) and 831 ± 332 ppb (right) and decreased significantly to 688 ± 266 ppb and 702 ± 286 ppb, respectively (p < 0.05). No significance was found during placebo treatment (778 ± 270 ppb, 808 ± 299 ppb to 802 ± 271 ppb, 813 ± 273 ppb). The mean nNO change was also significant compared with placebo (-125 ppb versus +14 ppb; p < 0.05). There was a significant decrease in nEos with LC compared with placebo (3.1-2.5 versus 2.9-2.6; p < 0.05). RQLQ scores were significantly improved with LC only. In TSS-4 scoring, a trend toward improvement during LC and significant worsening during placebo was found. Baseline nNO predicted changes in nasal eosinophils (nEos) and RQLQ. CONCLUSION: We showed that oral LC therapy decreased objective markers of rhinitis inflammation, nNO and nEos, in patients with PAR. Improvement in symptom scoring was also found with LC treatment.