Marianna M. Sockrider

Lansoprazole for children with poorly controlled asthma: a randomized controlled trial.

CONTEXT Asymptomatic gastroesophageal reflux (GER) is prevalent in children with asthma. Untreated GER has been postulated to be a cause of inadequate asthma control in children despite inhaled corticosteroid treatment, but it is not known whether treatment with proton pump inhibitors improves asthma control. OBJECTIVE To determine whether lansoprazole is effective in reducing asthma symptoms in children without overt GER. DESIGN, SETTING, AND PARTICIPANTS The Study of Acid Reflux in Children With Asthma, a randomized, masked, placebo-controlled, parallel clinical trial that compared lansoprazole with placebo in children with poor asthma control who were receiving inhaled corticosteroid treatment. Three hundred six participants enrolled from April 2007 to September 2010 at 19 US academic clinical centers were followed up for 24 weeks. A subgroup had an esophageal pH study before randomization. INTERVENTION Participating children were randomly assigned to receive either lansoprazole, 15 mg/d if weighing less than 30 kg or 30 mg/d if weighing 30 kg or more (n = 149), or placebo (n = 157). MAIN OUTCOME MEASURES The primary outcome measure was change in Asthma Control Questionnaire (ACQ) score (range, 0-6; a 0.5-unit change is considered clinically meaningful). Secondary outcome measures included lung function measures, asthma-related quality of life, and episodes of poor asthma control. RESULTS The mean age was 11 years (SD, 3 years). The mean difference in change (lansoprazole minus placebo) in the ACQ score was 0.2 units (95% CI, 0.0-0.3 units). There were no statistically significant differences in the mean difference in change for the secondary outcomes of forced expiratory volume in the first second (0.0 L; 95% CI, -0.1 to 0.1 L), asthma-related quality of life (-0.1; 95% CI, -0.3 to 0.1), or rate of episodes of poor asthma control (relative risk, 1.2; 95% CI, 0.9-1.5). Among the 115 children with esophageal pH studies, the prevalence of GER was 43%. In the subgroup with a positive pH study, no treatment effect for lansoprazole vs placebo was observed for any asthma outcome. Children treated with lansoprazole reported more respiratory infections (relative risk, 1.3 [95% CI, 1.1-1.6]). CONCLUSION In this trial of children with poorly controlled asthma without symptoms of GER who were using inhaled corticosteroids, the addition of lansoprazole, compared with placebo, improved neither symptoms nor lung function but was associated with increased adverse events. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00442013.

Clinical, radiological and pathological features of ABCA3 mutations in children

Background: Mutations in the ABCA3 gene can result in fatal surfactant deficiency in term newborn infants and chronic interstitial lung disease in older children. Previous studies on ABCA3 mutations have focused primarily on the genetic abnormalities and reported limited clinical information about the resultant disease. A study was undertaken to analyse systematically the clinical presentation, pulmonary function, diagnostic imaging, pathological features and outcomes of children with ABCA3 mutations. Methods: The records of nine children with ABCA3 mutations evaluated at Texas Children’s Hospital between 1992 and 2005 were reviewed and their current clinical status updated. Previous diagnostic imaging studies and lung biopsy specimens were re-examined. The results of DNA analyses were confirmed. Results: Age at symptom onset ranged from birth to 4 years. Cough, crackles, failure to thrive and clubbing were frequent findings. Mean lung function was low but tended to remain static. CT scans commonly revealed ground-glass opacification, septal thickening, parenchymal cysts and pectus excavatum. Histopathological patterns included pulmonary alveolar proteinosis, desquamative interstitial pneumonitis and non-specific interstitial pneumonitis, and varied with age. Dense abnormalities of lamellar bodies, characteristic of ABCA3 mutations, were seen by electron microscopy in all adequate specimens. Outcomes varied with the age at which the severity of lung disease warranted open lung biopsy, and some patients have had prolonged survival without lung transplantation. Conclusions: The presentation and course of interstitial lung disease due to ABCA3 mutations are variable, and open lung biopsy and genetic testing are warranted early in the evaluation of children with a consistent clinical picture.

MEASUREMENT OF QUALITY OF WELL BEING IN A CHILD AND ADOLESCENT CYSTIC FIBROSIS POPULATION

Substantial interest in the Quality of WellBeing Scale (QWB) has been shown recently, especially in chronic illness populations.1,2 Designed as a single metric to apply to general populations, the QWB combines physical symptoms and functionality in the areas of mobility, physical activity, and social activity. Although the QWB has been used for policy analysis, its application in clinical populations has been more limited.3

An Official American Thoracic Society Workshop Report: Optimal Lung Function Tests for Monitoring Cystic Fibrosis, Bronchopulmonary Dysplasia, and Recurrent Wheezing in Children Less Than 6 Years of Age

Although pulmonary function testing plays a key role in the diagnosis and management of chronic pulmonary conditions in children under 6 years of age, objective physiologic assessment is limited in the clinical care of infants and children less than 6 years old, due to the challenges of measuring lung function in this age range. Ongoing research in lung function testing in infants, toddlers, and preschoolers has resulted in techniques that show promise as safe, feasible, and potentially clinically useful tests. Official American Thoracic Society workshops were convened in 2009 and 2010 to review six lung function tests based on a comprehensive review of the literature (infant raised-volume rapid thoracic compression and plethysmography, preschool spirometry, specific airway resistance, forced oscillation, the interrupter technique, and multiple-breath washout). In these proceedings, the current state of the art for each of these tests is reviewed as it applies to the clinical management of infants and children under 6 years of age with cystic fibrosis, bronchopulmonary dysplasia, and recurrent wheeze, using a standardized format that allows easy comparison between the measures. Although insufficient evidence exists to recommend incorporation of these tests into the routine diagnostic evaluation and clinical monitoring of infants and young children with cystic fibrosis, bronchopulmonary dysplasia, or recurrent wheeze, they may be valuable tools with which to address specific concerns, such as ongoing symptoms or monitoring response to treatment, and as outcome measures in clinical research studies.

Randomized trial of the effect of drug presentation on asthma outcomes: The American Lung Association Asthma Clinical Research Centers

BACKGROUND Information that enhances expectations about drug effectiveness improves the response to placebos for pain. Although asthma symptoms often improve with placebo, it is not known whether the response to placebo or active treatment can be augmented by increasing expectation of benefit. OBJECTIVE The study objective was to determine whether response to placebo or a leukotriene antagonist (montelukast) can be augmented by messages that increase expectation of benefit. METHODS A randomized 20-center controlled trial enrolled 601 asthmatic patients with poor symptom control who were assigned to one of 5 study groups. Participants were randomly assigned to one of 4 treatment groups in a factorial design (ie, placebo with enhanced messages, placebo with neutral messages, montelukast with enhanced messages, or montelukast with neutral messages) or to usual care. Assignment to study drug was double masked, assignment to message content was single masked, and usual care was not masked. The enhanced message aimed to increase expectation of benefit from the drug. The primary outcome was mean change in daily peak flow over 4 weeks. Secondary outcomes included lung function and asthma symptom control. RESULTS Peak flow and other lung function measures were not improved in participants assigned to the enhanced message groups versus the neutral messages groups for either montelukast or placebo; no differences were noted between the neutral placebo and usual care groups. Placebo-treated participants had improved asthma control with the enhanced message but not montelukast-treated participants; the neutral placebo group did have improved asthma control compared with the usual care group after adjusting for baseline difference. Headaches were more common in participants provided messages that mentioned headache as a montelukast side effect. CONCLUSIONS Optimistic drug presentation augments the placebo effect for patient-reported outcomes (asthma control) but not lung function. However, the effect of montelukast was not enhanced by optimistic messages regarding treatment effectiveness.

Delivering Tailored Asthma Family Education in a Pediatric Emergency Department Setting: A Pilot Study

OBJECTIVE. Many children are brought to the pediatric emergency department (ED) with acute asthma symptoms. Emergency asthma care is costly, and many ED visits may be preventable. Families often do not have written asthma action plans and lack asthma self-managment skills. This study tests a tailored self-managment intervention delivered in the ED for families of children with asthma. The primary hypotheses were that the intervention group would have greater confidence to manage asthma 14 days postintervention and more well-asthma visits and fewer urgent care/ED visits at 9 and 12 months. METHODS. This randomized intervention/usual-care study was part of a larger ED asthma surveillance project in 4 urban pediatric ED sites. Asthma educators used a computer-based resource to tailor the intervention messages and provide a customized asthma action plan and educational summary. Children with acute asthma were enrolled during an ED visit, and follow-up telephone interviews were conducted during the next 9 months. The ED clinician classified the child’s acute and chronic severity. RESULTS. To date, 464 subjects aged 1 to 18 years have been enrolled. The ED clinicians reported that 46% had intermittent and 54% had persistent chronic severity with 51% having mild acute severity episodes. The confidence level to prevent asthma episodes and keep them from getting worse was significantly higher in the intervention group at 14 days postintervention. More subjects in the intervention group reported well-asthma visits by 9 months. Return ED visits were significantly lower in the intervention group in those with intermittent asthma. Twelve-month follow-up is in process. CONCLUSIONS. The tailored ED self-management intervention demonstrates significant effects on caregiver self-confidence and well-visit follow-up. Additional evaluation is needed to determine what impact this intervention has long-term.

Self-management of cystic fibrosis : a structural model for educational and behavioral variables

One hundred and ninety-nine patients and their primary caregivers at two metropolitan cystic fibrosis centers participated in a clinical trial to evaluate the effectiveness of a health education program designed to help improve self-management skills for the care of CF. The baseline data from the study was used to test a structural model that hypothesized the relationship between educational, behavioral, and health status variables. Controlling for the effects of all other variables, including demographic, self-efficacy (confidence in being able to perform a behavior) was the most important educational factor predicting self-management behavior for monitoring and treating respiratory problems. Knowledge about the management of CF was only related to the ability of caretakers to apply coping skills to problems associated with CF. The more caretakers reported performing monitoring behaviors the more likely they were to report performing self-management treatment behaviors. The findings suggest that educational interventions that focus on increased knowledge alone are not likely to be effective in improving self-management behavior for CF. Based on the structural model analyses, it is recommended that educational programs for CF patients and families address increased self-efficacy and improved monitoring skills to influence the improvement of self-management treatment for CF.

Computer-based decision support for pediatric asthma management: description and feasibility of the Stop Asthma Clinical System.

Clinical guidelines can assist in the management of asthma. Decision support systems (DSSs) can enhance adherence to clinical guidelines but tend not to provide clinicians with cues for behavioral change strategies to promote patient self-management. The Stop Asthma Clinical System (SACS) is a DSS designed for this purpose. To assess feasibility, seven clinicians used SACS to guide well visits with 26 predominantly persistent pediatric asthma patients. Data were collected via survey and in-depth semi-structured interviews. SACS improved assessment of asthma severity and control, classification of and intervention in medicine and environmental trigger management problems, and development of an action plan (all p < 0.05). Clinician-patient communication was enhanced. The primary challenge was that SACS increased clinic visit time. SACS can enhance clinician behavior to improve patient asthma self-management, but more studies are indicated to mitigate temporal constraints and evaluate impact on clinician and patient communication and behavior as well as clinical outcomes.

Asthma Symptom Utility Index: Reliability, validity, responsiveness, and the minimal important difference in adult asthmatic patients

BACKGROUND The evaluation of asthma symptoms is a core outcome measure in asthma clinical research. The Asthma Symptom Utility Index (ASUI) was developed to assess the frequency and severity of asthma symptoms. The psychometric properties of the ASUI are not well characterized, and a minimal important difference (MID) is not established. OBJECTIVES We assessed the reliability, validity, and responsiveness to change of the ASUI in a population of adult asthmatic patients. We also sought to determine the MID for the ASUI. METHODS Adult asthmatic patients (n = 1648) from 2 previously completed multicenter randomized trials were included. Demographic information, spirometric results, ASUI scores, and other asthma questionnaire scores were obtained at baseline and during follow-up visits. Participants also kept a daily asthma diary. RESULTS The internal consistency reliability of the ASUI was 0.74 (Cronbach α). Test-retest reliability was 0.76 (intraclass correlation). Construct validity was demonstrated by significant correlations between ASUI scores and Asthma Control Questionnaire scores (Spearman correlation r = -0.79; 95% CI, -0.85 to -0.75; P < .001) and Mini Asthma Quality of Life Questionnaire scores (r = 0.59; 95% CI, 0.51-0.61; P < .001). Responsiveness to change was demonstrated, with significant differences between mean changes in ASUI scores across groups of participants differing by 10% in percent predicted FEV(1) (P < .001) and by 0.5 points in Asthma Control Questionnaire scores (P < .001). Anchor-based and statistical methods support an MID for the ASUI of 0.09 points. CONCLUSIONS The ASUI is reliable, valid, and responsive to changes in asthma control over time. The MID of the ASUI (range of scores, 0-1) is 0.09.

Severe necrotizing pneumonitis in a child with Mycoplasma pneumoniae infection

Lower respiratory tract illness due to Mycoplasma pneumoniae is typically mild and self‐limited. There are, however, numerous reports of serious and life‐threatening cases of mycoplasma pneumonia in adults. We present a case involving a 4‐year‐old girl with severe mycoplasma infection and necrotizing pneumonitis requiring lobectomy. A detailed pathological report is provided. Pediatr. Pulmonol. 1997;24:61–65.