Compound heterozygous CORO1A mutations in siblings with a mucocutaneous-immunodeficiency syndrome of epidermodysplasia verruciformis-HPV, molluscum contagiosum and granulomatous tuberculoid leprosy.

PURPOSE: Coronin-1A deficiency is a recently recognized autosomal recessive primary immunodeficiency caused by mutations in CORO1A (OMIM 605000) that results in T-cell lymphopenia and is classified as T(-)B(+)NK(+)severe combined immunodeficiency (SCID). Only two other CORO1A-kindred are known to date, thus the defining characteristics are not well delineated. We identified a unique CORO1A-kindred. METHODS: We captured a 10-year analysis of the immune-clinical phenotypes in two affected siblings from disease debut of age 7 years. Target-specific genetic studies were pursued but unrevealing. Telomere lengths were also assessed. Whole exome sequencing (WES) uncovered the molecular diagnosis and Western blot validated findings. RESULTS: We found the compound heterozygous CORO1A variants: c.248_249delCT (p.P83RfsX10) and a novel mutation c.1077delC (p.Q360RfsX44) (NM_007074.3) in two affected non-consanguineous siblings that manifested as absent CD4CD45RA(+) (naïve) T and memory B cells, low NK cells and abnormally increased double-negative (DN) ϒδ T-cells. Distinguishing characteristics were late clinical debut with an unusual mucocutaneous syndrome of epidermodysplasia verruciformis-human papilloma virus (EV-HPV), molluscum contagiosum and oral-cutaneous herpetic ulcers; the older female sibling also had a disfiguring granulomatous tuberculoid leprosy. Both had bilateral bronchiectasis and the female died of EBV+ lymphomas at age 16 years. The younger surviving male, without malignancy, had reproducibly very short telomere lengths, not before appreciated in CORO1A mutations. CONCLUSION: We reveal the third CORO1A-mutated kindred, with the immune phenotype of abnormal naïve CD4 and DN T-cells and newfound characteristics of a late/hypomorphic-like SCID of an EV-HPV mucocutaneous syndrome with also B and NK defects and shortened telomeres. Our findings contribute to the elucidation of the CORO1A-SCID-CID spectrum.

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.

Assessing Available Adolescent Self-Reported Measures for Asthma Management: A Systematic Literature Review.

Objective: Asthma is a common chronic disease and a substantial public health problem for children, adolescents, and adults. Adolescence, a period of increased independence and striving for autonomy, is an opportune time for youth transitioning to adulthood to assume more responsibility for their own asthma self-management. However, accurate measures of adolescent asthma outcomes are limited. The purpose of this systematic review is to identify self-reported asthma measures currently available in the empirical literature focused on adolescent populations. Methods: Search terms were based on the National Library of Medical Subject Headings and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Databases searched included CINAHL, Nursing Allied Health Prevention, Medline, ProQuest, and PubMed. Included studies were peer reviewed and published in English between 2010 and 2022. All studies reported on asthma measures for adolescents between 10 and 19 years old. Results: Nineteen studies were included, comprising 15 experimental and 4 quasi-experimental. This review revealed the following asthma measure domains: asthma knowledge, self-efficacy, attitudes, self-care, self-regulation, symptom prevention and management, medication adherence, asthma disease control, symptoms, and quality of life (QOL) for evaluating psychosocial, behavioral, clinical, and QOL outcomes. Conclusion: This review revealed the necessity of developing a comprehensive measure to assess the asthma self-management behaviors of adolescents. A comprehensive tool related to adolescent asthma self-management behavior would enhance the assessment and evaluation of adolescent asthma self-management behaviors and extend the science and clinical practice around adolescent self-management. Present measures for asthma self-management behavior for adolescents are limited; therefore, developing a valid and reliable measure is necessary not only to assess adolescents' asthma self-management behavior outcomes but also to identify and evaluate the essential components to include in educational interventions for adolescent self-management.

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.

Evaluation of a pediatric asthma high-risk scoring algorithm.

OBJECTIVES: Identification of patients with asthma at increased risk for hospitalization and emergency department (ED) visits presents opportunity for intervention. STUDY DESIGN: Retrospective analysis of computerized health plan claims data. METHODS: Texas Children's Health Plan, a large Medicaid managed care program, developed an asthma risk scoring algorithm using the clinically relevant parameters of hospitalization for asthma, ED visits for asthma, short-acting ß agonist medication dispensing, inhaled corticosteroid medication dispensing, number of prescribing providers, loss to follow-up, and oral corticosteroid dispensing. The risk score performance was evaluated using 2016-2018 risk scores to predict 2017-2019 asthma hospitalizations and ED visits. RESULTS: We identified 107,811 unique members aged 1 to less than 18 years with an asthma diagnosis. For those aged 3 to less than 18 years, the area under the receiver operating characteristic curve (AUC) for risk score predicting hospitalization ranged from 0.72 to 0.79. For those aged 1 to less than 3 years, the AUC ranged from 0.65 to 0.69. Those with a risk score of 1 or greater accounted for 20% to 23% of pediatric members 3 to less than 18 years with asthma but 53% to 56% of asthma hospitalizations in the follow-up year. Sixteen to eighteen percent of those aged 3 to less than 18 years with a risk score of 9 or greater were hospitalized in the follow-up year. CONCLUSIONS: Texas Children's Health Plan asthma risk score stratifies risk of asthma hospitalization and ED visits for Medicaid-insured children. The risk score performs better for children aged 3 to less than 18 years than for those aged 1 to less than 3 years.

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.

Congenital Lung Malformations.

Congenital lung malformations (CLM) comprise a spectrum of anatomical anomalies of the lungs and respiratory tree. The prenatal growth pattern of CLMs is unpredictable with larger lesions causing life-threatening complications, such as hydrops fetalis, and smaller lesions remaining asymptomatic and potentially regressing. The most common CLMs are congenital pulmonary adenomatoid malformations, bronchopulmonary sequestrations, congenital lobar emphysema, and bronchogenic cysts. All these lesions have clinically similar presentations when symptomatic, but pathophysiologic differences that must be considered when evaluating and treating. This article reviews the most common CLMs, their pathophysiology, clinical presentation, diagnostic considerations, and current literature on the controversies surrounding CLM management. [Pediatr Ann. 2019;48(4):e169-e174.].

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.

Serum KL-6 and surfactant proteins A and D in pediatric interstitial lung disease.

OBJECTIVE: To determine if serum KL-6, surfactant protein A (SP-A), and surfactant protein D (SP-D) levels are elevated in pediatric interstitial lung disease (ILD) and associated with pulmonary function and disease severity score. METHODS: Serum KL-6, SP-A, and SP-D levels were measured by enzyme-linked immunosorbent assay in 10 children with ILD and in 10 healthy volunteers. In the ILD group, FEV1 percentage of predicted, FVC percentage of predicted, and ILD disease severity score were measured and correlated with serum KL-6, SP-A, and SP-D levels. RESULTS: For the ILD and control groups, respectively, mean serum KL-6 was 4,523 U/mL and 206 U/mL (p = 0.007), mean serum SP-A was 133 ng/mL and 21 ng/mL (p = 0.003), and mean serum SP-D was 304 ng/mL and 75 ng/mL (p = 0.004). There was an inverse relationship between SP-A and FVC (p = 0.05), and between SP-D and FEV1 (p = 0.05). There was a direct relationship between SP-D and ILD score (p = 0.05). CONCLUSIONS: Serum KL-6, SP-D and SP-D levels are elevated in children with ILD. SP-A and SP-D levels appear to correlate with some measures of disease severity.

Addressing tobacco smoke exposure: passive and active.

Many smoking parents are receptive to receiving smoking counseling messages and pediatric health care providers need to increase their efforts to address ETS exposure. Efforts to prevent smoking acquisition should continue by parents, doctors, schools, and the community. Start early in childhood to promote positive family communication and role modeling. Screen for tobacco use or intention and provide counseling to teen without the parent in room. Brief tobacco-dependence interventions are effective. Every patient/parent that uses tobacco should be identified, urged to quit, and offered treatment. Those willing to quit should be provided effective treatments using the "5 A's". Those unwilling to quit should be motivated using "5 R's". Quitting smoking is a major challenge but it is one that many people successfully achieve every day. Even a small increase in smoking cessation can be significant impact from a public health perspective and pediatric providers can play a significant role.

Environmental allergens and irritants in schools: a focus on asthma.

As part of the Partners in School Asthma Management Program, environmental data were collected from 385 rooms in 60 elementary schools in southeast Texas, using an Environmental Observation Checklist and a Q-TRAK Indoor Air Quality Monitor. Dust samples for allergen analysis were collected from floors, carpets, and area rugs in 80 classrooms in a subset of 20 schools. CO2 levels > 1,000 ppm were found in 86% of rooms; 69% had indoor humidity above recommended levels. Der p I dust mite allergen levels > 2,000 ng/g were present in 20% of rooms, but only 2.5% of rooms had Der f I mite allergen levels exceeding recommended tolerances. Detectable levels of cockroach allergen (Bla g II) were found in all schools (median 5.5 ng/g), with 10% of rooms over the recommended threshold. Almost two-thirds of classrooms had mold spore counts > 10,000 col/g (median, 14,400 col/g; range, 2,000-52,000 col/g).

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.

Respiratory symptoms and acute painful episodes in sickle cell disease.

The authors examined the prevalence of respiratory symptoms and determined whether respiratory symptoms were associated with prevalence of chest pain and number of acute painful episodes in children and adolescents with sickle cell disease. Participants (N = 93; 44 females, 49 males; mean age 9.8 +/- 4.3 years) reported coughing in the morning (21.5%), at night (31.2%), and during exercise (30.1%). Wheezing occurred both when they had a cold or infection (29.0%) and when they did not have (23.7%) a cold or infection. Sleep was disturbed by wheezing in 20.4%. Among the 76 patients who were school-age (>5 years), 19.7% of patients missed more than 4 days of school because of respiratory symptoms. The majority of patients reported having acute painful episodes (82.8%), and most (66.7%) reported having chest pain during acute painful episodes in the previous 12 months. Participants with acute pain episodes greater than 3 during the previous 12 months had significantly higher reports of breathing difficulties (P = .01) and chest pain (P = .002). The high number of respiratory symptoms (cough and wheeze) among patients with sickle cell disease may trigger acute painful episodes. Early screening and recognition, ongoing monitoring, and proactive management of respiratory symptoms may minimize the number of acute painful episodes.

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-management skills. This study tests a tailored self-management 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.

Asthma management simulation for children: translating theory, methods, and strategies to effect behavior change.

Translating behavioral theories, models, and strategies to guide the development and structure of computer-based health applications is well recognized, although a continued challenge for program developers. A stepped approach to translate behavioral theory in the design of simulations to teach chronic disease management to children is described. This includes the translation steps to: 1) define target behaviors and their determinants, 2) identify theoretical methods to optimize behavioral change, and 3) choose educational strategies to effectively apply these methods and combine these into a cohesive computer-based simulation for health education. Asthma is used to exemplify a chronic health management problem and a computer-based asthma management simulation (Watch, Discover, Think and Act) that has been evaluated and shown to effect asthma self-management in children is used to exemplify the application of theory to practice. Impact and outcome evaluation studies have indicated the effectiveness of these steps in providing increased rigor and accountability, suggesting their utility for educators and developers seeking to apply simulations to enhance self-management behaviors in patients.