Carolyn M. Kercsmar

Management of asthma based on exhaled nitric oxide in addition to guideline-based treatment for inner-city adolescents and young adults: a randomised controlled trial

BACKGROUND Preliminary evidence is equivocal about the role of exhaled nitric oxide (NO) in clinical asthma management. We aimed to assess whether measurement of exhaled NO, as a biomarker of airway inflammation, could increase the effectiveness of asthma treatment, when used as an adjunct to clinical care based on asthma guidelines for inner-city adolescents and young adults. METHODS We did a randomised, double-blind, parallel-group trial at ten centres in the USA. We screened 780 inner-city patients, aged 12-20 years, who had persistent asthma. All patients completed a run-in period of 3 weeks on a regimen based on standard treatment. 546 eligible participants who adhered to treatment during this run-in period were then randomly assigned to 46 weeks of either standard treatment, based on the guidelines of the National Asthma Education and Prevention Program (NAEPP), or standard treatment modified on the basis of measurements of fraction of exhaled NO. The primary outcome was the number of days with asthma symptoms. We analysed patients on an intention-to-treat basis. This trial is registered with clinicaltrials.gov, number NCT00114413. FINDINGS During the 46-week treatment period, the mean number of days with asthma symptoms did not differ between the treatment groups (1.93 [95% CI 1.74 to 2.11] in the NO monitoring group vs 1.89 [1.71 to 2.07] in the control group; difference 0.04 [-0.22 to 0.29], p=0.780). Other symptoms, pulmonary function, and asthma exacerbations did not differ between groups. Patients in the NO monitoring group received higher doses of inhaled corticosteroids (difference 119 mug per day, 95% CI 49 to 189, p=0.001) than controls. Adverse events did not differ between treatment groups (p>0.1 for all adverse events). INTERPRETATION Conventional asthma management resulted in good control of symptoms in most participants. The addition of fraction of exhaled NO as an indicator of control of asthma resulted in higher doses of inhaled corticosteroids, without clinically important improvements in symptomatic asthma control.

Characteristics of inner-city children with asthma: the National Cooperative Inner-City Asthma Study.

Asthma morbidity has increased dramatically in the past decade, especially among poor and minority children in the inner cities. The National Cooperative Inner‐City Asthma Study (NCICAS) is a multicenter study designed to determine factors that contribute to asthma morbidity in children in the inner cities. A total of 1,528 children with asthma, ages 4 to 9 years old, were enrolled in a broad‐based epidemiologic investigation of factors which were thought to be related to asthma morbidity. Baseline assessment included morbidity, allergy evaluation, adherence and access to care, home visits, and pulmonary function. Interval assessments were conducted at 3, 6, and 9 months after the baseline evaluations.

Reduction in asthma morbidity in children as a result of home remediation aimed at moisture sources.

Objective Home dampness and the presence of mold and allergens have been associated with asthma morbidity. We examined changes in asthma morbidity in children as a result of home remediation aimed at moisture sources. Design In this prospective, randomized controlled trial, symptomatic, asthmatic children (n = 62), 2–17 years of age, living in a home with indoor mold, received an asthma intervention including an action plan, education, and individualized problem solving. The remediation group also received household repairs, including reduction of water infiltration, removal of water-damaged building materials, and heating/ventilation/air-conditioning alterations. The control group received only home cleaning information. We measured children’s total and allergen-specific serum immuno-globulin E, peripheral blood eosinophil counts, and urinary cotinine. Environmental dust samples were analyzed for dust mite, cockroach, rodent urinary protein, endotoxin, and fungi. The follow-up period was 1 year. Results Children in both groups showed improvement in asthma symptomatic days during the preremediation portion of the study. The remediation group had a significant decrease in symptom days (p = 0.003, as randomized; p = 0.004, intent to treat) after remodeling, whereas these parameters in the control group did not significantly change. In the postremediation period, the remediation group had a lower rate of exacerbations compared with control asthmatics (as treated: 1 of 29 vs. 11 of 33, respectively, p = 0. 003; intent to treat: 28.1% and 10.0%, respectively, p = 0.11). Conclusion Construction remediation aimed at the root cause of moisture sources and combined with a medical/behavioral intervention significantly reduces symptom days and health care use for asthmatic children who live in homes with a documented mold problem.

Psychosocial characteristics of inner-city children with asthma: A description of the NCICAS psychosocial protocol

Previous research has demonstrated a significant reciprocal relationship between psychosocial factors and asthma morbidity in children. The National Cooperative Inner‐City Asthma Study investigated both asthma‐specific and non‐specific psychosocial variables, including asthma knowledge beliefs and management behavior, caregiver and child adjustment, life stress, and social support. This article presents these psychosocial characteristics in 1,528 4–9‐year‐old asthmatic urban children and their caretakers.

Asthma control, adiposity, and adipokines among inner-city adolescents.

BACKGROUND There is an association between adiposity and asthma prevalence, but the relationship to asthma control is unclear. OBJECTIVES We sought to understand the relationships among adiposity, sex, and asthma control in inner-city adolescents with asthma. METHODS We prospectively followed 368 adolescents with moderate-to-severe asthma (ages 12-20 years) living in 10 urban areas for 1 year. Asthma symptoms and exacerbations were recorded, and pulmonary function and exhaled nitric oxide levels were measured every 6 weeks. Adiposity measures (body mass index [BMI] and dual-energy X-ray absorptiometric scans) were made, and blood was collected for measurement of allergy markers, adiponectin, leptin, TNF-alpha, IL-6, and C-reactive protein levels. RESULTS More than 60% of female subjects and 50% of male subjects were above the 85th percentile of BMI for age. Higher BMI was associated with more symptom days (R = 0.18, P = .02) and exacerbations (R = 0.18, P = .06) among female subjects only. Adiponectin was inversely related to asthma symptoms (R = -0.18, P < .05) and exacerbations (R = -0.20, P < .05) and positively with FEV(1)/forced vital capacity ratio (R = 0.15, P < .05) in male subjects only independent of body size. There was no relationship between adiposity or adipokines and total IgE levels, blood eosinophil counts, and exhaled nitric oxide levels. Dual-energy X-ray absorptiometry provided little additional value in relating adiposity to asthma outcome in this population of adolescents. CONCLUSION Adiposity is associated with poorer asthma control in female subjects. Adiponectin is associated with improved asthma control in male subjects.

Design and Methods of the National Cooperative Inner-City Asthma Study

The National Cooperative Inner‐City Asthma Study (NCICAS) was established to identify and then intervene on those factors which are related to asthma morbidity among children in the inner‐city. This paper describes the design and methods of the broad‐based initial Phase I epidemiologic investigation. Eight research centers enrolled 1,528 children, 4 to 9 years of age, from English‐ or Spanish‐speaking families, all of whom resided in major metropolitan inner‐city areas. The protocol included an eligibility assessment and an extensive baseline visit, during which symptom data, such as wheezing, lost sleep, changes in activities of daily living, inpatient admissions, and emergency department and clinic visits were collected. A comprehensive medical history for each child was taken and adherence to the medical regimen was assessed. Access, as well as barriers, to the medical system were addressed by a series of questions including the location, availability, and consistency of treatment for asthma attacks, follow‐up care, and primary care. The psychological health of the caretaker and of the child was also measured. Asthma knowledge of the child and caretaker was determined. Sensitization to allergens was assessed by skin‐prick allergen testing and exposure to cigarette smoke and the home environment were assessed by questionnaire. For more than a third of the families, in‐home visits were conducted with dust sample allergen collection and documentation of the home environment, such as the presence of pets and evidence of smoking, mildew, and roaches. Urine specimens were collected to measure passive smoke exposure by cotinine assays, blood samples were drawn for banking, and children age 6 to 9 years were given spirometric lung function assessment. At 3, 6 and 9 months following the baseline assessment, telephone interviews were conducted to ask about the childs symptoms, unscheduled emergency department or clinic visits, and hospitalizations. At this time, peak flow measurements with 2‐week diary symptom records were collected. Pediatr. Pulmonol. 1997;24:237–252.

Preseasonal treatment with either omalizumab or an inhaled corticosteroid boost to prevent fall asthma exacerbations

BACKGROUND Short-term targeted treatment can potentially prevent fall asthma exacerbations while limiting therapy exposure. OBJECTIVE We sought to compare (1) omalizumab with placebo and (2) omalizumab with an inhaled corticosteroid (ICS) boost with regard to fall exacerbation rates when initiated 4 to 6 weeks before return to school. METHODS A 3-arm, randomized, double-blind, double placebo-controlled, multicenter clinical trial was conducted among inner-city asthmatic children aged 6 to 17 years with 1 or more recent exacerbations (clincaltrials.gov #NCT01430403). Guidelines-based therapy was continued over a 4- to 9-month run-in phase and a 4-month intervention phase. In a subset the effects of omalizumab on IFN-α responses to rhinovirus in PBMCs were examined. RESULTS Before the falls of 2012 and 2013, 727 children were enrolled, 513 were randomized, and 478 were analyzed. The fall exacerbation rate was significantly lower in the omalizumab versus placebo arms (11.3% vs 21.0%; odds ratio [OR], 0.48; 95% CI, 0.25-0.92), but there was no significant difference between omalizumab and ICS boost (8.4% vs 11.1%; OR, 0.73; 95% CI, 0.33-1.64). In a prespecified subgroup analysis, among participants with an exacerbation during the run-in phase, omalizumab was significantly more efficacious than both placebo (6.4% vs 36.3%; OR, 0.12; 95% CI, 0.02-0.64) and ICS boost (2.0% vs 27.8%; OR, 0.05; 95% CI, 0.002-0.98). Omalizumab improved IFN-α responses to rhinovirus, and within the omalizumab group, greater IFN-α increases were associated with fewer exacerbations (OR, 0.14; 95% CI, 0.01-0.88). Adverse events were rare and similar among arms. CONCLUSIONS Adding omalizumab before return to school to ongoing guidelines-based care among inner-city youth reduces fall asthma exacerbations, particularly among those with a recent exacerbation.

Short-term compliance with peak flow monitoring: Results from a study of inner city children with asthma

The objective of the study was to assess the feasibility of initiating daily peak flow monitoring in a research study of asthma in inner city children. We performed a descriptive study of patterns of peak flow monitoring in children randomized to receive a simple mini‐Wright (SM) or an electronic recording meter (ERM). The ERM served as a “covert” meter, providing objective documentation of actual peak flow use. Sixty‐five Hispanic or African‐American children, ages 5–9 years, with a history of physician‐diagnosed asthma participated in the study. All children resided in census tracts with 40% or more of the population living at or below the poverty level. Subjects were instructed to use a peak flow meter (the SM or ERM) at least twice daily over a 3 week period, and to record peak flow values in a paper diary. Subjects who received the ERM were not made aware that measurements were also recorded electronically. Differences in patterns of use of the SM and ERM were assessed with the Wilcoxon signed rank test and Wilcoxon sum rank test. Adherence to peak flow monitoring was evaluated by comparing the percent days with missing values in the manually completed diary with those obtained by computer record. The Friedman statistic was used to compare changes in compliance (percent of days with missing peak flow entries) over time. Accuracy of peak flow readings was assessed by comparing the manual and electronic recordings with paired and unpaired t‐tests and with Pearson product moment correlations.

Comparison of racemic albuterol and levalbuterol for treatment of acute asthma

OBJECTIVE To determine whether levalbuterol resulted in fewer hospital admissions than racemic albuterol when used for treatment of acute asthma. Study design A randomized, double-blind, controlled trial was conducted in the emergency department (ED) and inpatient asthma care unit of an urban tertiary childrens hospital. Children age 1 to 18 years (n=482) provided a total of 547 enrollments. Patients received a nebulized solution of either 2.5 mg racemic albuterol or 1.25 mg levalbuterol every 20 minutes (maximum six doses). Patients admitted to the asthma care unit were treated in a standardized fashion by using the same blinded drug assigned in the ED. Hospitalization rate was the primary outcome. RESULTS Hospitalization rate was significantly lower in the levalbuterol group (36%) than in the racemic albuterol group (45 %, P=.02). The adjusted relative risk of admission in the racemic group compared with the levalbuterol group was 1.25 (95% confidence interval, 1.01-1.57). Hospital length of stay was not significantly shorter in the levalbuterol group (levalbuterol, 44.9 hours; racemic albuterol, 50.3 hours; P=.63). No significant adverse events occurred in either group. CONCLUSIONS Substituting levalbuterol for racemic albuterol in the ED management of acute asthma significantly reduced the number of hospitalizations.

Hospital treatment of asthma: lack of benefit from theophylline given in addition to nebulized albuterol and intravenously administered corticosteroid**

STUDY OBJECTIVE To determine the efficacy of theophylline when given in addition to nebulized albuterol and intravenously administered corticosteroid to children hospitalized with mild to moderate asthma. DESIGN Randomized, prospective, placebo-controlled, double-blind trial. SETTING Tertiary-care childrens hospital. PATIENTS Twenty-nine patients with asthma between the ages of 2 and 16 years completed the study. The treatment and placebo groups were similar in age, gender, race, illness severity, and emergency department treatment. INTERVENTIONS All patients received intravenously administered methylprednisolone and nebulized albuterol. The treatment group received intravenous theophylline therapy and the placebo group dextrose in water. When intravenously administered medications were discontinued, therapy continued with oral administration of theophylline (or placebo) and of prednisone. MEASUREMENTS AND MAIN RESULTS Twice-daily assessments of clinical asthma symptoms were made by using a scoring system consisting of respiratory rate, inspiratory/expiratory ratio, wheeze, and accessory muscle use. Time required to reach study discharge criteria (asthma score < or = 2) (30.4 +/- 16.8 vs 27.0 +/- 10.3 hours; p = 0.51) and the rate of improvement of the clinical asthma score (-0.10 +/- 0.05 unit/hr vs -0.11 +/- 0.09 unit/hr; p = 0.88) were not significantly different between the theophylline and placebo groups. The number of albuterol aerosol treatments required and the adverse effects experienced were not significantly different between groups. CONCLUSION When the combination of systemically administered corticosteroid and inhaled albuterol is used in the treatment of children hospitalized with mild to moderate asthma, addition of theophylline may not be justified.