Allan T. Luskin

Evidence for Chlamydia pneumoniae infection in steroid-dependent asthma

BACKGROUND Chlamydia pneumoniae is an obligate intracellular respiratory pathogen capable of persistent infection. Seroepidemiologic studies and the results of open-label antimicrobial treatment of patients with non-steroid-dependent asthma have suggested a potential role for C. pneumoniae in asthma. OBJECTIVE To evaluate the results of antimicrobial treatment in patients with uncontrolled steroid-dependent asthma and serologic evidence suggesting C. pneumoniae infection. METHODS Three nonsmoking asthmatic patients (aged 13 to 65 years) whose symptoms remained poorly controlled despite daily administration of inhaled and oral steroid (10 to 40 mg/d). All met serologic criteria for current or recent C. pneumoniae infection. RESULTS After prolonged treatment (6 to 16 weeks) with clarithromycin or azithromycin all three patients were able to discontinue oral steroids. All three patients have remained well controlled with inhaled antiasthma therapy only during 3 to 24 months of postantibiotic therapy observation. CONCLUSIONS In adolescent and adult asthmatic patients, Chlamydia pneumoniae infection may contribute to symptoms of asthma that are poorly controlled by steroids. Serologic evidence for C. pneumoniae infection should be sought in such patients. A trial of appropriate antibiotic therapy may be helpful in those patients with high titers of anti-C. pneumoniae IgG antibodies.

Particle size of inhaled corticosteroids: Does it matter?

A question with respect to asthma therapy revolves around the issue of whether better efficacy occurs with an ultrafine-particle inhaled corticosteroid because of better lung deposition into the distal airways. This article reviews particle size and delivery devices of different steroids, clinical outcomes of small- versus large-particle steroids, and the issue of pharmacoeconomics.

A comparison of asthma-related expenditures for patients started on montelukast versus fluticasone propionate as monotherapy

BACKGROUND The prevalence of asthma is increasing, and this chronic condition imposes a substantial economic burden worldwide. It is not known whether newer therapies, such as leukotriene receptor antagonists (LTRAs), can ease this burden. OBJECTIVE This analysis examined the association between choice of first-line asthma control therapy and health care resource utilization and expenditures in patients with mild asthma. METHODS A retrospective cohort analysis of claims data for patients who started therapy with fluticasone propionate or montelukast between January 1, 1997, and February 28, 1999, was performed, adjusting for baseline differences. RESULTS Data from 343 patients (229 fluticasone; 114 montelukast) were analyzed. Patients starting therapy with fluticasone were significantly older (33.3 vs 27.6 years; P = 0.015) and significantly less likely than patients starting therapy with montelukast to have been started on control therapy by an asthma specialist (52.0% vs 69.3%; P = 0.007). There were no significant differences in mean changes in total asthma-related health care expenditures, oral steroid and antibiotic prescriptions, hospitalizations, or emergent care visits. The mean increase in total asthma-related pharmacy expenses was significantly greater for patients who were prescribed montelukast than for those prescribed fluticasone (P < 0.001). Treatment adherence was better in patients prescribed montelukast versus fluticasone (5.1 vs 3.1 prescriptions filled per year, respectively; P < 0.001). Montelukast patients had a significantly lower increase in the number of beta-agonist prescriptions filled per year than fluticasone patients (0.19 vs 0.66; P = 0.03). In the subsequent year, 4% (10/229) of fluticasone patients added or switched to an LTRA. No montelukast patients added to or switched control therapy. CONCLUSION The mean change in total asthma-related health care expenditures was not significantly different in patients started on fluticasone propionate versus montelukast. Montelukast patients had better adherence to their treatment regimen and required fewer beta-agonist prescriptions, which is an indicator of asthma control and possibly therapeutic effectiveness.

Changing physician prescribing patterns through problem-based learning: an interactive, teleconference case-based education program and review of problem-based learning

BACKGROUND Although asthma guidelines have recommended the use of anti-inflammatory controller medications since 1991, studies have consistently shown widespread failure to follow the guidelines. Major barriers include lack of knowledge and the inability to operationalize knowledge. Improved continuing medical education methods should result in more effective learning by physicians and other health care professionals, leading to better adherence to guidelines, resulting in better outcomes. OBJECTIVE To evaluate the effectiveness of an interactive, case-based, educational intervention, also known as problem-based learning, using a series of interactive, case-based teleconferences. METHODS A series of interactive, case-based teleconferences was completed with 20 primary care physicians. Each case involved a child aged 16 months to 12 years with asthma. A 12-month analysis of physician prescribing patterns was conducted. RESULTS Program acceptance by the 20 physicians was uniformly positive. Significant improvement was noted, with an overall increase in controller use. Review of prescription data showed an increase in inhaled corticosteroid use from an average of 2.54 to 7.76 refills per month for the 6 months after the intervention (P < .001). CONCLUSIONS After participating in a unique educational intervention-problem-based learning using interactive, case-based teleconferences-the prescribing patterns of physicians were altered significantly toward better adherence to asthma guidelines, as demonstrated by an increased use of anti-inflammatory controller medications (inhaled corticosteroids and leukotriene antagonists).

A randomized multicenter study evaluating Xolair persistence of response after long-term therapy

Background Few data are available to assist clinicians with decisions regarding long‐term use of asthma therapies, including omalizumab. Objective We sought to evaluate the benefit and persistence of response in subjects continuing or withdrawing from long‐term omalizumab treatment. Methods Evaluating the Xolair Persistency Of Response After Long‐Term Therapy (XPORT) was a randomized, double‐blind, placebo‐controlled withdrawal study that included subjects with moderate‐to‐severe persistent asthma receiving long‐term omalizumab. Subjects were randomized by using a hierarchical dynamic randomization scheme to continue their same dose of omalizumab or withdraw to placebo and were then followed every 4 weeks for 1 year. The primary outcome was any protocol‐defined severe asthma exacerbation. The secondary outcome was time to first protocol‐defined severe asthma exacerbation. Exploratory outcomes included changes in Asthma Control Questionnaire and Asthma Control Test scores. Results Significantly more subjects in the omalizumab group (67%) had no protocol‐defined exacerbation than in the placebo group (47.7%); an absolute difference of 19.3% (95% CI, 5.0%, 33.6%) represents a 40.1% relative difference. Time to first protocol‐defined exacerbation analysis revealed a significantly different between‐group exacerbation pattern that was consistent with the primary analysis. Subjects continuing omalizumab had significantly better asthma control (mean [SD] change from baseline to week 52: Asthma Control Test score, −1.16 [4.14] vs placebo, −2.88 [5.38], P = .0188; Asthma Control Questionnaire score, 0.22 [0.66] vs placebo, 0.63 [1.13], P = .0039). Discontinuation of omalizumab was associated with an increase in free IgE levels and an increase in basophil expression of the high‐affinity IgE receptor. No safety concerns were noted. Conclusion Continuation of omalizumab after long‐term treatment results in continued benefit, as evidenced by improved symptom control and reduced exacerbation risk.

Impact of Asthma Exacerbations and Asthma Triggers on Asthma-related Quality of Life in Patients with Severe or Difficult-to-Treat Asthma

BACKGROUND Few data are available that evaluate the relationship among asthma exacerbations, asthma triggers, and asthma-related quality of life (QoL). OBJECTIVE To evaluate the impact of asthma exacerbations and asthma triggers on QoL. METHODS Patients with severe or difficult-to-treat asthma, ages ≥ 13 years (n = 2679) from the TENOR (The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens) 3-year observational study were included. Exacerbations were defined hierarchically in descending order of severity (hospitalization, emergency department [ED] visit, steroid burst, no exacerbation) by using data from months 6 and 12. The total number (frequency) of exacerbations was assessed. Asthma-related QoL was measured at month 12 by using the Mini-Asthma QoL Questionnaire (Mini-AQLQ); self-reported asthma triggers were collected at baseline and annually. We used 1-way ANOVA to test for differences in Mini-AQLQ domain scores across asthma exacerbation severity, the total number of asthma exacerbations, and the number of asthma triggers. RESULTS A significant decrease (P < .001) in Mini-AQLQ domain scores was seen with increasing severity of asthma exacerbation (no exacerbation, steroid burst, ED visit, and hospitalization); symptom (5.5, 4.8, 4.3, and 4.2), activity (5.8, 5.2, 4.6, and 4.4), emotional (5.6, 5.0, 4.4, and 4.2), exposure (5.0, 4.5, 4.0, and 3.9); and overall (5.5, 4.9, 4.3, and 4.1). Increasing exacerbation frequency and the number of baseline asthma triggers also were associated with significant decreases in Mini-AQLQ domain scores. An increasing number of asthma triggers were associated with an increase in severity and frequency of exacerbations. CONCLUSION Avoidance of asthma triggers may reduce exacerbation rates and improve asthma-related QoL in patients with severe or difficult-to-treat asthma. Interventional studies are warranted to further explore these outcomes.

An overview of the recommendations of the Working Group on Asthma and Pregnancy

Asthma is the most common potentially serious medical disease complicating pregnancy, and uncontrolled asthma during pregnancy may produce both maternal and fetal complications. The Working Group on Asthma and Pregnancy was established by the National Asthma Education and Prevention Program (NAEPP) to address the issues surrounding asthma management during pregnancy, working within the background of the NAEPPs published asthma guidelines. The Working Groups report, published in 1993, presents recommendations and information for diagnosing and managing asthma during pregnancy. Some key points are: (1) asthma should be treated as aggressively in pregnant women as in nonpregnant women; (2) asthma care and obstetric care should be carefully integrated and should include monitoring of fetal growth and development, maternal symptoms, and maternal lung function; (3) as for nonpregnant women with asthma, medications used to treat asthma during pregnancy should include a short-acting symptom reliever medication (usually an inhaled short-acting beta2 -agonist) and long-term daily medication to address the underlying inflammation for all patients with more than mild, intermittent disease.

Asthma rescue and allergy medication use among asthmatic children with prior allergy prescriptions who initiated asthma controller therapy.

BACKGROUND Asthma and allergic rhinitis are frequently comorbid conditions. Montelukast is effective in treating both diseases and may reduce total medication use among children with asthma and allergic rhinitis. OBJECTIVE To determine the differences in respiratory and allergy medication use and costs, as proxies for control, in pediatric patients with asthma and allergy who initiated asthma controller therapy. METHODS A 24-month, retrospective, pre-post cohort study using a pharmacy claims database of children (age < 16 years) with 2 or more consecutive asthma controller prescriptions and 1 or more allergy prescription (within 12 months before initial controller prescription). Children taking inhaled corticosteroids (ICSs) and montelukast were matched one to one based on age, days of prior allergic rhinitis therapy supply, duration of controller therapy, and propensity score. Differences in costs of rescue or acute asthma medications, prescription allergy medications, other respiratory medications, and the number of days of rescue or acute asthma medication use and allergy medication use were calculated. RESULTS A total of 1,236 children were matched into ICS and montelukast groups (n = 618 each). Montelukast patients had a smaller cost increase overall compared with ICS patients (combined cost for rescue or acute asthma medications, allergy medications, and other respiratory medications:

Symptom Control and Improved Functioning: The Effect of Omalizumab on Asthma-Related Quality of Life (ARQL)

5.55 vs

Exhaled nitric oxide as a tool in managing and monitoring difficult-to-treat asthma.

12.08, P < .001). Cost increase for rescue or acute asthma medications was significantly lower in the montelukast group (