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Asthma medication ratio (AMR) ≥ 0.5 has been shown to predict asthma exacerbations. This study explores the impact of increasing or decreasing inhaled corticosteroid/long-acting beta-agonist (ICS/LABA) use over a 7-year period on achieving an AMR of ≥ 0.5.To (a) assess the impact of increasing use of ICS/LABAs on changes in a modified AMR (mAMR) and (b) examine asthma risk over time as measured by an mAMR over a 7-year period, adjusting for differences in baseline characteristics.This is a retrospective, observational study using pharmacy and medical claims from a medical group from January 1, 2003, to December 31, 2010. All patients with ≥ 1 asthma diagnosis (ICD-9-CM, 493.xx) with ≥ 1 inhaled asthma medication dispensed in each year of eligibility were included. The mAMR = total ICS controllers dispensed/(total ICS controllers dispensed + albuterol dispensed). The proportion of ICS/LABA use was determined as the number of ICS/LABA canisters dispensed/(total of ICS/LABA + ICS dispensed). Generalized linear mixed models were used to assess the effect of incremental change in ICS/LABA use on mAMR over 7 years, adjusting for differences in resource utilization, time, and asthma medication use. Nine hundred ninety patients (mean age [± SD] 34.7 years [± 18.2], 61.7% female) met all criteria. Overall, mean mAMR increased over time, while mean albuterol use decreased over time. Adjusting for covariates, we found that a 10% increase in ICS/LABA use was associated with a 9% increase (adjusted OR = 1.09, 95% CI = 1.06-1.12) in the likelihood of achieving an mAMR ≥ 0.5, while a 50% increase in ICS/LABA use was associated with a 53% increase (OR = 1.53, 95% CI = 1.31-1.80) in the likelihood of achieving an mAMR ≥ 0.5.Increase in ICS/LABA use over time in a population of asthma patients was significantly associated with a higher likelihood of achieving an mAMR ≥ 0.5.

The village that we know today as Juan Mata Ortiz came into existence under very different circumstances. The brilliant American electrical engineer and entrepreneur Fred Stark Pearson established the Mexico Transportation Company, Ltd., in Canada on February 17, 1909. Within a few months the company name was changed by a special act of parliament to the Mexico North Western Railway Co. (Ferrocarril Noroeste de Mexico). Four railroad systems were acquired to create the Mexico North Western. The largest was the Rio Grande, Sierra Madre and Pacific, which ran from Ciudad Juarez to Terrazas south of Nuevo Casas Grandes. The Chihuahua and Pacific ran from Chihuahua City to Minaca, while the Sierra Madre and Pacific ran from Temosachic to Madera. Also acquired was a subsidiary of the Rio Grande, Sierra Madre and Pacific, the El Paso Southern, which owned a bridge across the Rio Grande and track to its terminal in the United States, thus providing access to the entire railroad system of North America via El Paso. In addition to the railroad system the company acquired substantial timber rights to the forests of the Sierra Madre. Approximately 2.4 million acres, including a lumber mill in Madera, were obtained from the Sierra Madre Land and Lumber Company. An additional 200,000 hectares known as the Murphy Tract were acquired from the Development Corporation of America, bringing the total to approximately three million acres of timber. Pearson then renovated the Madera Mill, enhanced its capacity, and extended the rail line south to Madera. While work on the line was beginning in late 1909, construction of what was reputed to be the largest lumber mill in North America was started in a town that came to be named Pearson.

Monitoring indicators of subacute lack of asthma control (SALAC) may help to reduce asthma morbidity.To determine whether SALAC, independent of current asthma exacerbations, is associated with subsequent acute asthma exacerbations.Administrative claims data from PharMetrics/IMS Health were used to identify patients 12 years or older continuously enrolled in a participating U.S. health plan from 2001 to 2004 withor=1 asthma claim (International Classification of Diseases, Ninth Revision, Clinical Modification code 493.x), no chronic obstructive pulmonary disease or cystic fibrosis claims, andor=1 prescription for an asthma medication during 2001-2004. SALAC was defined as more than 4 asthma-related physician visits (oror=2/quarter) or more than 5 short-acting beta((2))-adrenergic agonist prescriptions during 2001. Effect of asthma control category (Exacerbation Only [EO], SALAC Only [SO], Both Exacerbation and SALAC [Both], Neither Exacerbation nor SALAC [Neither]) in 2001 on acute asthma exacerbations (hospitalization, emergency department visit, or short-term oral corticosteroid use) during 2002-2004 was assessed using logistic regression, adjusting for gender, age, health plan type, and region.Of 11,779 patients, 8% were assigned to the EO group, 26% to SO, 12% to Both, and 54% to Neither in 2001. The incidence of exacerbations in 2002-2004 was higher for Both (61.8%) versus EO (55.0%) and for SO (37.3%) versus Neither (31.9%). The risk of exacerbation in 2002-2004 was increased significantly (p.0001) for Both (3.394; 95% confidence interval [CI] = 3.009, 3.827), EO (2.503; 95% CI = 2.176, 2.879), and SO (1.277; 95% CI = 1.166, 1.399) versus Neither.In this study, the risk of subsequent exacerbation was greatest in patients with both SALAC and acute asthma exacerbations, followed by those with exacerbations only and those with SALAC only. SO identified an additional 26% of asthma patients at increased risk for subsequent exacerbation. The results from this study demonstrate that SALAC indicators and a history of acute asthma exacerbations are independent predictors of future acute asthma exacerbations and highlight the important role of subacute asthma worsening in predicting and preventing future asthma exacerbations.

Assessment of patient-reported outcomes is important in evaluating the impact of asthma treatment. This study was conducted to compare effects of adjustable- and fixed-dose budesonide/formoterol pressurized metered-dose inhaler with fixed-dose fluticasone propionate/salmeterol dry powder inhaler regimens on patient-reported outcomes in patients agedor =18 years with moderate to severe asthma.In this phase III, randomized, open-label study, 1225 patients were randomized 2:1 to fixed-dose budesonide/formoterol 160/4.5 microg x 2 inhalations (320/9 mug) twice daily or fixed-dose fluticasone propionate/salmeterol 250/50 microg twice daily for 1 month. In the subsequent 6 months, patients receiving fixed-dose fluticasone propionate/salmeterol continued therapy, whereas those receiving fixed-dose budesonide/formoterol were randomized 1:1 to fixed-dose or adjustable-dose budesonide/formoterol (adjustable from 320/9 microg twice daily to 320/9 microg once daily or 640/18 microg twice daily).Mean improvements from baseline to end of treatment in the Asthma Quality of Life Questionnaire (standardized) overall and individual domain scores and the Asthma Control Questionnaire score were clinically important (or =0.5 points) for all treatments. Patients in both budesonide/formoterol groups reported greater treatment satisfaction on the Asthma Treatment Satisfaction Measure questionnaire than patients in the fluticasone propionate/salmeterol dry powder inhaler group for the attributes of timely relief of symptoms (por = .037) and feel medication working (por = .020). Onset of Effect Questionnaire scores showed a greater percentage of patients perceiving onset of effect with budesonide/formoterol regimens versus fixed-dose fluticasone propionate/salmeterol (por = .002).Treatment regimens did not differ regarding improvements in asthma-specific quality of life and asthma control. Questions related to perceived rate of onset and feeling medication working in the Asthma Treatment Satisfaction Measure and Onset of Effect Questionnaire generally elicited somewhat more favorable responses with budesonide/formoterol pressurized metered-dose inhaler regimens versus fixed-dose fluticasone propionate/salmeterol dry powder inhaler.

Asthma, the most common chronic disease in children, is characterized by chronic inflammation of the respiratory system. If left uncontrolled, persistent asthma can have serious negative clinical outcomes. Thus, the earliest possible diagnosis based on the recognition of specific clinical indicators, treatment with anti-inflammatory controller medications such as an inhaled corticosteroid (ICS) or a leukotriene receptor antagonist (LTRA), and patient-centered strategies for monitoring disease and improving patient adherence are essential to successful asthma care. Recent clinical studies support the efficacy of ICSs over LTRAs as daily treatment for pediatric asthma. Routine follow-up and patient education can facilitate adherence to daily controller therapy and successful asthma control in children.

The burden of asthma is substantial, and the overall cost of its management is growing.To compare asthma-related charges and resource utilization across disease severity levels in the year after initial asthma treatment with any inhaled corticosteroid (ICS) or leukotriene receptor antagonist (LTRA).This was a longitudinal, retrospective cohort study of claims data from managed care plans in the United States. All patients had a new prescription for an ICS or an LTRA between January 1999 and December 2000 and were enrolled in a managed care plan for at least 12 months before (preindex) and 12 months after (postindex) the initial claim. Asthma-related charges, hospitalizations, emergency department (ED) visits, physician visits, and asthma medication use were compared between the 2 cohorts. Propensity scores were calculated to control for baseline differences in patient characteristics and types of health care coverage.Claims from 31,860 patients were evaluated. Total postindex asthma-related charges were significantly lower in the ICS cohort than in the LTRA cohort (dollars 613 vs dollars 902, respectively; P.001), as were asthma-related pharmacy charges (dollars 305 vs dollars 564, respectively; P.001). Results were consistent for all propensity subclasses and all age groups.Results from this cohort study suggest that, across varying disease severities, treating asthma with an ICS as initial controller therapy leads to less health care resource utilization than does using an LTRA as initial therapy.

Clinical trials have demonstrated improved efficacy of fluticasone propionate/salmeterol (100/50 mcg) in a single device (FSC) compared with montelukast (10 mg) (MON). This study was designed to assess asthma control, asthma-related quality of life, asthma-related emergency department (ED) visit/hospitalization, treatment-related satisfaction, and productivity losses in patients newly started on FSC or MON.Patients who were newly prescribed FSC or MON during a regularly scheduled office visit were enrolled in a prospective observational study by nearly 500 physicians from eight managed care plans. Patient survey data were collected at baseline and at months 1, 3, 6, and 12, to measure study outcomes. ED visits/inpatient stays were reported from commercial claims data. Multivariate analyses assessed 12-month outcomes, controlling for several baseline patient characteristics.A total of 1414 patientsor= 15 years old were enrolled in the registry (FSC, n = 1061; MON, n = 353), 90% of which completed a 12-month survey. FSC patients had significantly greater improvement in both asthma control and quality of life, and reported significantly higher satisfaction with their medication (p = 0.003) and fewer days at work/school with asthma symptoms (p = 0.04) than MON. Other parameters of productivity losses such as missed work/school days due to asthma were not significantly different between the two groups. FSC use was also significantly associated with a lower risk of an asthma-related ED visit/hospitalization compared with MON (odds ratio = 0.35, 95% confidence interval: 0.15-0.92).In a 12-month office-based observational study, patients age 15 and older with persistent asthma, newly started on FSC, improved in symptom, quality of life, treatment, and utilization-related outcomes compared with patients newly started on MON. These results should be interpreted in light of the inherent limitations of non-randomized, uncontrolled studies.

Background Asthma control is the goal of therapeutic interventions. In observational studies, the use of short-acting β-agonists (SABAs) is a surrogate for symptoms and emergency department or hospital events for exacerbations. Objective To compare asthma exacerbations, medication switch, and use of SABAs among 3 treatment cohorts: fluticasone propionate and salmeterol as a single inhaler (FSC), fluticasone and salmeterol as separate inhalers (FP + SAL), and fluticasone propionate alone (FP). Methods Administrative claims data from approximately 10 million individuals from April 2000 to December 2002 were examined. Patients 15 years or older with claims for asthma, SABAs, and study medications were included in the study. Asthma-related medical and pharmacy claims were evaluated. Multivariate regression techniques were used to model the outcomes of interest, controlling for patient characteristics. Results The odds of a hospitalization or emergency department event were significantly lower for the patients receiving FSC (n = 1,013) compared with those receiving FP (n = 1,130) (odds ratio, 0.75; 95% confidence interval, 0.61-0.93) and those receiving FP + SAL (n = 271) (odds ratio, 0.69; 95% confidence interval, 0.51-0.95). Patients receiving FSC also had a significantly lower risk of switch or discontinuation of index medication and lower rates of postindex SABA use. Conclusion In this analysis, patients receiving FSC had lower rates of asthma-related symptoms and exacerbations as measured by SABA refills and hospitalization, respectively, when compared with patients receiving either FP or FP + SAL. This observational examination of medical and pharmacy claims data adds to the clinical reports that demonstrate the increased effectiveness of FSC when compared with FP or FP + SAL.

Asthma is a chronic disease, the two main components of which are inflammation and bronchoconstriction. Fluticasone propionate (FP) and salmeterol, a strategy that treats both main components of asthma, has been recently compared with FP plus montelukast in a randomised clinical trial. The present study reports economic evaluation of these two strategies.To determine the relative cost effectiveness when persistent asthma is treated with FP/salmeterol 100/50 microg twice daily administered via a single Diskus inhaler device versus treatment with FP 100 microg twice daily via a Diskus inhaler plus oral montelukast 10mg once daily.A cost-effectiveness analysis was performed by applying cost unit data to resource utilisation data collected prospectively during a US randomised, double-blind, 12-week trial of FP/salmeterol (n = 222) versus FP + montelukast (n = 225). Patients wereor =15 years of age and were symptomatic despite inhaled corticosteroid (ICS) therapy.Efficacy measurements in this analysis included improvement in forced expiratory volume in 1 second (FEV(1)) and symptom-free days. Direct costs included those related to study drugs, emergency room department visits, unscheduled physician visits, treatment of drug-related adverse events (oral candidiasis), and rescue medication (salbutamol [albuterol]). The study assumed a US third-party payer's perspective with costs in 2001 US dollars.Treatment with FP/salmeterol resulted in a significantly higher proportion (p0.001) of patients who achieved aor =12% increase in FEV(1) than treatment with FP + montelukast (54% [95% CI 47%, 61%] vs 32% [95% CI 26%, 38%]). Lower daily costs and greater efficacy of FP/salmeterol resulted in a cost-effectiveness ratio of US6.77 dollars (95% CI US5.99 dollars, US7.66 dollars) per successfully treated patient in the FP/salmeterol group compared with US14.59 dollars (95% CI US12.12 dollars, US17.77 dollars) for FP + montelukast. In addition, FP/salmeterol achieved similar efficacy in terms of symptom-free days compared with FP + montelukast (31% [95% CI 26%, 35%] vs 27% [95% CI 23%, 32%]), but at a significantly lower daily per-patient cost (US3.64 dollars [95% CI US3.60, US3.68 dollars] vs US4.64 dollars [95% CI US4.56 dollars, US4.73 dollars]). Sensitivity analyses demonstrated the stability of the results over a range of assumptions.From a US third-party payer's perspective, these findings suggest that treating the two main components of asthma (inflammation and bronchoconstriction) with FP/salmeterol may not only be a more cost-effective strategy but may actually lead to cost savings compared with the addition of montelukast to low-dose FP in patients with persistent asthma. The results were found to be robust over a range of assumptions.

Tumour necrosis factor (TNF) alpha affects immune response and airway inflammation, which are characteristics of asthma. Genetic factors may impact TNFalpha levels, and several polymorphisms in the TNF gene cluster on chromosome 6p21 have been associated with TNFalpha production and potential increased risk of asthma. The present paper evaluates the relation between two single nucleotide polymorphisms (SNPs) in the TNF gene cluster and asthma risk. The SNPs investigated here are guanine (G) to adenosine (A) substitutions in the TNFalpha and lymphotoxin alpha (LTalpha) genes. The TNFalpha SNP is at position -308 in the promoter region (TNFalpha-308), while the LTalpha SNP is in the first intron NcoI recognition sequence (LTalpha-NcoI). (For both SNPs the G allele is denoted as 1, and the A allele 2.) We determined TNFalpha-308 and LTalpha-NcoI genotypes in 511 individuals: 236 asthma cases and 275 non-asthmatic controls. Data were analysed by logistic regression of asthma status on the genotypes and potential confounders. TNFalpha-308*2 was positively associated with asthma, and this relation was strengthened when restricting cases to individuals reporting acute asthma: the adjusted odds ratio (OR) comparing carriers of one or two TNFalpha-308*2 alleles versus none was 1.86 (95% confidence interval (CI)=1.03-3.34, P=0.04). Further restricting the subjects to those with a family history of asthma, and those of European-American ancestry strengthened the association even more: adjusted OR=3.16 (95% CI=1.04-9.66; P=0.04). LTalpha-NcoI*1 was weakly associated with asthma, and analysis of both genes suggests that only the TNFalpha-308*2 allele increases risk of asthma.

This randomized clinical trial tested a behavioral medicine program designed to reduce asthmatic children's exposure to environmental tobacco smoke (ETS) in the home.Families were randomly assigned to an experimental preventive medicine counseling group, a monitoring control group, or a usual treatment control group. Families were measured six times over 1 year.Ninety-one families were recruited from four allergy clinics.The experimental group received a 6-month series of counseling sessions designed to decrease ETS exposure. This group also monitored smoking, exposure, and children's asthma symptoms. The monitoring group did not receive counseling and the usual treatment control group received outcome measures only.Parents reported the daily number of cigarettes children were exposed to during the week preceding interviews. A nicotine air monitor and construct validity analysis confirmed the validity of exposure reports. Exposure to the parent's cigarettes in the home decreased for all groups. The experimental group attained a 79 percent decrease in children's ETS exposure, compared with 42 percent for the monitoring control and 34 percent for the usual treatment control group. Repeated-measures analysis of variance resulted in a significant (F([10,350] = 1.92, p0.05) group by time effect. At the final 12-month visit, the experimental/counseling group sustained a 51% decrease in children's exposure to cigarettes in the home from all smokers, while the monitoring control group showed an 18% decrease and the usual treatment control group a 15% decrease from pre-intervention [corrected].A behavioral medicine program was successful in reducing exposure to ETS in the home for these asthmatic children.

OBJECTIVE: To review the consistency of scientific, clinical, and economic evidence related to dual-controller therapy with inhaled corticosteroids (ICS) and the inhaled long-acting beta2-agonist (LABA) salmeterol in treating patients whose asthma is not controlled with ICS alone. DATA SOURCES: This article is based on a presentation given by the author at a symposium entitled. Optimizing Clinical and Economic Outcomes in Asthma Management. at the Academy of Managed Care Pharmacy.s 2000 Educational Conference in San Diego, California, on October 5, 2000. CONCLUSIONS: Scientific research supports the complementary effect of ICSs and LABAs in preventing bronchoconstriction and inflammation. For patients using an ICS and still exhibiting symptoms, randomized clinical trials (RCTs) have shown that adding salmeterol resulted in greater clinical efficacy and fewer asthma exacerbations than either at least doubling the dose of ICS or adding a leukotriene modifier. Two studies comparing the clinical efficacy of adding either a LABA or leukotriene modifier to low-dose ICS therapy favored the former combination. The addition of a LABA has allowed a reduction of the steroid dose in patients with stable asthma without a decline in short-term asthma control. Whether the ICS dose reduction can be maintained long term without any deleterious effects remains unknown. While RCTs are useful for determining safety and clinical efficacy, their results may have limited applicability in general clinical practice. Retrospective cohort analysis using large administrative data sets from managed health plans is an alternative method for determining the economic outcomes of common dual-controller regimens. The economic benefits of ICS and salmeterol in 5 retrospective cohort analyses mirror the clinical results of the RCTs.

Inhaled corticosteroids are the most effective class of anti-inflammatory agents and are recommended for patients with persistent asthma.To compare the effectiveness of (1) fluticasone propionate, 100 microg, and salmeterol, 50 microg; (2) fluticasone propionate, 100 microg; and (3) montelukast, 10 mg, as first-line maintenance treatment for persistent asthma.Combined analysis of 4 clinical trials, 2 that compared fluticasone propionate-salmeterol with montelukast and 2 that compared fluticasone propionate with montelukast as initial asthma therapy.The 4 studies had a total of 1,910 patients 15 years or older with symptomatic asthma previously treated with inhaled short-acting beta2-agonists alone. At the end point, there were significantly greater increases in forced expiratory volume in 1 second with fluticasone propionate-salmeterol (0.57 L; Por = .004) vs fluticasone propionate (0.48 L) and montelukast (0.31 L) and significantly greater increases in morning peak expiratory flow rate (84.9 L/min; P.001) vs fluticasone propionate (56.0 L/min) and montelukast (36.1 L/min). Fluticasone propionate-salmeterol significantly increased the percentage of symptom- and rescue-free days and significantly reduced albuterol use vs fluticasone propionate and montelukast (Por = .04 for both). Patients treated with fluticasone propionate and montelukast had 2.6 and 3.6 greater risk, respectively, of having an asthma-related exacerbation vs fluticasone propionate-salmeterol users. In addition, mean daily exacerbation costs per treated patient were dollars 0.41 for fluticasone propionate-salmeterol, dollars 4.60 for fluticasone propionate, and dollars 7.57 for montelukast, whereas mean daily costs per patient exacerbation for fluticasone propionate-salmeterol, fluticasone propionate, and montelukast were dollars 29, dollars 128, and dollars 154, respectively.Patients with symptomatic asthma previously treated with short-acting beta2-agonists only who require maintenance therapy are likely to have greater clinical benefits, lower risk of an asthma exacerbation, and reduced exacerbation-related costs when initiating therapy with fluticasone propionate-salmeterol vs fluticasone propionate or montelukast.

To review the consistency of scientific, clinical, and economic evidence related to dual-controller therapy with inhaled corticosteroids (ICS) and the inhaled long-acting beta2-agonist (LABA) salmeterol in treating patients whose asthma is not controlled with ICS alone.This article is based on a presentation given by the author at a symposium entitled. Optimizing Clinical and Economic Outcomes in Asthma Management. at the Academy of Managed Care Pharmacy.s 2000 Educational Conference in San Diego, California, on October 5, 2000.Scientific research supports the complementary effect of ICSs and LABAs in preventing bronchoconstriction and inflammation. For patients using an ICS and still exhibiting symptoms, randomized clinical trials (RCTs) have shown that adding salmeterol resulted in greater clinical efficacy and fewer asthma exacerbations than either at least doubling the dose of ICS or adding a leukotriene modifier. Two studies comparing the clinical efficacy of adding either a LABA or leukotriene modifier to low-dose ICS therapy favored the former combination. The addition of a LABA has allowed a reduction of the steroid dose in patients with stable asthma without a decline in short-term asthma control. Whether the ICS dose reduction can be maintained long term without any deleterious effects remains unknown. While RCTs are useful for determining safety and clinical efficacy, their results may have limited applicability in general clinical practice. Retrospective cohort analysis using large administrative data sets from managed health plans is an alternative method for determining the economic outcomes of common dual-controller regimens. The economic benefits of ICS and salmeterol in 5 retrospective cohort analyses mirror the clinical results of the RCTs.

Objective To compare asthma-related health-care utilization and expenditures for patients prescribed one of three dual-controller therapies: fluticasone plus salmeterol, inhaled corticosteroids (ICS) [excluding fluticasone] plus salmeterol, and ICS plus a leukotriene modifier (LTM). Materials and methods: Asthma-related medical claims from two major health plans were obtained for the 12 months before and after the initiation of dual therapy. A total of 1,325 patients ≥ 12 years old with no claims for COPD or respiratory tract cancer were selected from the approximately 3.5 million lives covered. Multivariable regression was used to assess differences in asthma-related expenditures. To compensate for positive skew, all cost variables were log-transformed. Results: Risk-adjusted total asthma-related costs for the fluticasone-plus-salmeterol cohort (n = 121), the ICS-plus-salmeterol cohort (n = 844), and the ICS-plus-LTM cohort (n = 30) were $975, $1,089, and $1,268, respectively. Risk-adjusted pharmacy costs were $813, $841, and $996, respectively. Generalized linear modeling, controlling for baseline covariates, indicated that compared to ICS-plus-LTM therapy, fluticasone-plus-salmeterol therapy was associated with a significant reduction in asthma-related total (p = 0.0014) and pharmacy (p = 0.001) costs. Similar results were found when the ICS-plus-salmeterol group and the ICS-plus-LTM group were compared (p = 0.0001). The number of inpatient, outpatient, and emergency department visits and their corresponding costs were lower for the fluticasone-plus-salmeterol cohort, but were not statistically significant (p > 0.05). Conclusion Results from managed-care practice suggest that treatment with fluticasone plus salmeterol, and more broadly ICS plus salmeterol, yield important cost savings when compared to treatment with ICS plus LTM.

Background To improve asthma disease management, the National Asthma Education Program (NAEP) Expert Panel published Guidelines for the Diagnosis and Management of Asthma in 1991. Objectives To compare the current status of asthma disease management among patients in a large health maintenance organization with the NAEP guidelines and to identify the factors that may be associated with medical care (eg, emergency department visits and hospital admissions) and adherence to the guidelines. Methods Analyses of 1996 survey data from 5580 members with asthma (age range, 14 to 65 years) covered by a major health maintenance organization in California (Health Net). Results In general, adherence to NAEP guidelines was poor. Seventy-two percent of respondents with severe asthma reported having a steroid inhaler, and of those, only 54% used it daily. Only 26% of respondents reported having a peak flowmeter, and of those, only 16% used it daily. Age (older), duration of asthma (longer), increasing current severity of disease, and treatment by an asthma specialist correlated with daily use of inhaled steroids. Ethnicity (African American and Hispanic) correlated negatively with inhaled steroid use but positively with emergency department visits and hospital admissions for asthma. Increasing age and treatment by an asthma specialist were also identified as common factors significantly related to the daily use of a peak flowmeter and, interestingly, to overuse of β 2 -agonist metered-dose inhalers. Conclusions Although the NAEP guidelines were published 7 years ago, compliance with the guidelines was low. It was especially poor for use of preventive medication and routine peak-flow measurement. Furthermore, the results showed that asthma specialists provided more thorough care than did primary care physicians in treating patients with asthma. Combining the results of the regression analyses revealed that some of the variation in rates of emergency department visits and hospitalizations among some subpopulations can be explained by the underuse of preventive medication. This study serves the goal of documenting the quality of care and services currently provided to patients with asthma through a large health maintenance organization and provides baseline information that can be used to design and assess effective population-based asthma disease management intervention programs.

The effect of maternal and infant avoidance of allergenic foods on food allergy was examined in a prenatally randomized, controlled trial of infants of atopic parents. The diet of the prophylactic-treated group (N = 103) included (1) maternal avoidance of cow's milk, egg, and peanut during the third trimester of pregnancy and lactation and (2) infant use of casein hydrolysate (Nutramigen) for supplementation or weaning, and avoidance of solid foods for 6 months; cow's milk, corn, soy, citrus, and wheat, for 12 months; and egg, peanut, and fish, for 24 months. In the control group (N = 185), mothers had unrestricted diets, and infants followed American Academy of Pediatrics feeding guidelines. The cumulative prevalence of atopy was lower at 12 months in the prophylactic-treated (16.2%) compared to the control (27.1%) group ( p = 0.039), resulting from reduced food-associated atopic dermatitis, urticaria and/or gastrointestinal disease by 12 months (5.1% versus 16.4%; p = 0.007), and any positive food skin test by 24 months (16.5% versus 29.4%; p = 0.019), caused primarily by fewer positive milk skin tests (1% versus 12.4%; p = 0.001). The prevalences of allergic rhinitis, asthma, and inhalant skin tests were unaffected. Serum IgE levels in the prophylactictreated group were marginally lower only at 4 months. Thus, reduced exposure of infants to allergenic foods appeared to reduce food sensitization and allergy primarily during the first year of life.

Peripheral blood leukocytes from patients with severe atopic dermatitis (serum IgE levels between 1,560 and 28,000 U/ml) showed a significantly weaker increase in intracellular cAMP after stimulation with epinephrine (10––5–10––3M) than leukocytes from normals. At the same time stimulation with methylcholine (10––10–10––4M) induced a significantly higher increase in intracellular levels of cGMP in the atopic group compared to normals. The immunomodulating agent levamisole induced a slight increase in cAMP and cGMP response both in leukocytes from atopic patients and in normals. Platelet cAMP concentrations were lowered by epinephrine stimulation both in atopies and controls. There was no effect of methylcholine upon platelet cyclic nucleotide levels in the dose range examined. The data support the concept that abnormal cyclic nucleotide responsiveness – not only as β-adrenergic blockade but also as cholinergic hyperreactivity – may play a role in the pathogenesis of atopic dermatitis.

The ultrastructural distribution of PHA receptors on lymphocytes from two patients with ataxia-telangiectasia was visualized using transmission electron microscopy and ferritin covalently linked to PHA. Lymphocytes from these two patients failed to undergo PHA-induced blastogenesis. The initial time course and ultrastructure of membrane adherence, endocytosis of PHA-Fe-receptor complexes, and formation of multivesicular bodies were the same as for control lymphocytes. The subsequent development of blastogenesis did not occur. At 48–72 hr, when blastogenesis was maximal in control cells, the lymphocytes from these patients failed to exhibit nuclear enlargement, remained heterochromatic and did not develop prominent nucleoli. There was also a marked delay in exocytosis of the multivesicular bodies as compared to control cells. It is concluded that receptor attachment to PHA occurs normally and that an intracellular rather than membrane defect is responsible for absent blastogenesis in these patients. Ferritin-labeled PHA and electron microscopy will be useful in examining lymphocyte activation in other immunodeficiency diseases.

Ecto-5′-nucleotidase activity was measured in lymphocyte subpopulations isolated from normal subjects and patients with congenital X-linked agammaglobulinemia. B lymphocytes from normal subjects have at least three times more ecto-5′-nucleotidase activity than T lymphocytes. Patients with X-linked agammaglobulinemia have 56% of normal activity in their T cells, and lack a lymphocyte subpopulation high in nucleotidase activity. High activity of ecto-5′-nucleotidase may be a biochemical marker for mature surface immunoglobulin-bearing B cells.

A deficiency of lymphocyte ecto-5′-nucleotidase (ecto-5′-NT) 1 activity in patients with common variable immunodeficiency (CVI), congenital X-linked agammaglobulinemia (CAG), severe combined immunodeficiency (SCID), and a variety of other immunodeficiency diseases is well described (1-6). Adult peripheral B cells have three- to five-fold higher ecto-5′-NT activity than peripheral T cells (3). Thus, any disease which causes a loss of surface immunoglobulin-positive (slg+) B cells from the peripheral blood, such as CAG, will cause a decrease in total lymphocyte ecto-5′-NT activity (3). Ecto-5′-NT deficiency may also be caused by decreased enzyme activity in T cells, B cells, or both (1,3,4). We have previously shown that decreased ecto-5′-NT activity in T cells of patients with CVI and CAG is due to decreased numbers of ecto-5′-NT+ cells from both the helper (0KT4-) and suppressor (0KT8+) subpopulations (4). Furthermore, increased percentages of ecto-5′-NT- T cells in these patients appears to be correlated with an increased capacity for the suppression of pokeweed mitogen (PWM) driven immunoglobulin synthesis in vitro. Ecto-5′-NT- maternally engrafted T cells in a patient with SCID and maternal graft versus host disease also suppressed PWM-driven immunoglobulin synthesis (6). Thus, T cell ecto-5′-NT deficiency does not necessarily indicate T cell immaturity.

T lymphocytes from control subjects were separated into subsets using monoclonal antibodies of the OKT series and complement lysis and analyzed for ecto-5'-nucleotidase activity both by quantitative radiochemical assay and a histochemical stain. T cells from 15 control subjects contained 54+/-4% OKT4(+) (helper/inducer) cells and 32+/-3% OKT8(+) (cytotoxic/suppressor) cells. Total T cell ecto-5'-nucleotidase activity was 10.9+/-2.1 nmol/h per 10(6) cells with 25+/-7% positive by histochemical stain. Ecto-5'-nucleotidase activity in OKT4-enriched populations was 5.43+/-1.8 nmol/h per 10(6) cells with 14+/-2% positive by histochemical stain; that in OKT8-enriched populations was 17.1+/-5.9 nmol/h per 10(6) cells with 35+/-8% positive by histochemical stain. Two of four patients with congenital agammaglobulinemia and four of seven patients with common variable immunodeficiency had decreased proportions of OKT4(+) T cells with corresponding increases in the proportions of OKT8(+) T cells (OKT4/OKT8 = 0.60 to 1.0 as compared with 1.7+/-0.2 for control subjects). All four patients with congenital agammaglobulinemia, and three of seven patients with common variable immunodeficiency also had low T cell ecto-5'-nucleotidase activity (

The in vitro effect of levamisole (LMS) on lymphocyte, neutrophil, basophil and platelet function was investigated in patients with severe atopic dermatitis and hyperimmunoglobulinaemia E. Lymphocyte stimulation by several concentrations of PHA, con A and PWM, polymorphonuclear leukocyte chemotaxis and basophil histamine release were unaffected by LMS (10 micrograms/ml). Platelet serotonin release induced by iodipamide was decreased in patient and control groups by LMS but release induced by methacholine, epinephrine and thrombin was not.

The histamine content of commercial preparations of pokeweed mitogen was measured by amino acid analysis technique, automated fluorometry, and bioassay employing the guinea pig ileum. Ten samples from 5 companies were examined and found to contain between 0.026 micrograms and 167.5 micrograms of histamine per ml of solution. The protein content of 9 of these putative 5 mg samples measured by folin assay and by amino acid analysis varied from 0.56 to 4.4 mg. Their amino acid compositions were similar, except for notable variations in 3 of the 16 residues quantitated.

A patient with severe combined immunodeficiency due to adenosine deaminase deficiency was also found to be deficient in lymphocyte ecto-5′-nucleotidase activity. The ecto-5′-nucleotidase deficiency was probably secondary to the presence of predominantly immature lymphocytes. Three of eight lymphoblastoid cell lines derived from other patients with adenosine deaminase deficiency were also found to be deficient in ecto-5′-nucleotidase activity. None of these three adenosine deaminase and ecto-5′-nucleotidase-deficient lymphoblastoid cell lines exhibited increased sensitivity to growth inhibition by deoxyadenosine. Therefore, in contrast to previous reports, deoxyadenosine-mediated growth inhibition does not appear to be controlled by the activity of ecto-5′-nucleotidase.

The importance of allergy in the pathogenesis of serous otitis media continues to be controversial. Our aim is to clarify the role of atopy in the development of serous otitis and to describe a technique for the further study of this relationship. Nasal challenges were performed with both diluent and rye grass pollen extract in 43 children with allergic rhinitis. Nasal airway resistance was measured by anterior rhinomanometry and nearly simultaneous tympanometry was utilized to detect changes in middle ear pressure. Fifteen of the patients had significant changes in middle ear pressure of minus 35 mm H2O or greater in one or both ears (mean=minus 60 mm). The control diluent challenges in the same group resulted in a mean change of plus 20 mm H2O (p

RESULTS OF DOUBLE-BLIND RANDOMLY SELECTED PLACEBO CONTROLLED THERAPEUTIC TRIALS OF HUMAN IgE PENTAPEPTIDE (HEPP)