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1.  Sublingual Immunotherapy for Asthma: Affects T-Cells but Does not Impact Basophil Activation 
Objective: Allergen-specific immunotherapy (SIT) is the unique modifying treatment of atopic diseases. Dysregulation of T-cell apoptosis plays a crucial role in the in the development of asthma. Nevertheless, the effect of sublingual immunotherapy (SLIT) on T-cell apoptosis has not been elucidated. The aim of the study was to evaluate the influence of 1 year of SIT in atopic children on the frequency of Th1 and Th2 cells in peripheral blood, on T-cell apoptosis, and on the response of basophils to allergen challenge.
Methods: Children suffering from bronchial asthma were treated with SLIT for 12 months (Staloral 300). Basophil activation was evaluated by measurement of CD203c antigen expression. Th1 and Th2 cells frequencies and their associated frequencies of apoptosis by the expression of Bcl-2 were evaluated with flow cytometry.
Results: Basophil activation showed no difference in response before and after therapy. The frequency of Th1 cells increased (p=0.01, n=19), whereas the frequency of Th2 cells remained stable. Additionally, a significant increase of Bcl-2 positive Th1 cells was found (p=0.0465, n=19).
Conclusions: We conclude that the increase in frequency of Th1 cells secondary to SLIT might be associated with increased resistance to apoptotic signals. The basophil activation is not useful in evaluation of patient desensitization.
doi:10.1089/ped.2014.0328
PMCID: PMC3961768  PMID: 24669352
2.  Pulmonary Hypertension in Preterm Infants with Bronchopulmonary Dysplasia 
Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, is a significant contributor to perinatal morbidity and mortality. Premature birth disrupts pulmonary vascular growth and initiates a cascade of events that result in impaired gas exchange, abnormal vasoreactivity, and pulmonary vascular remodeling that may ultimately lead to pulmonary hypertension (PH). Even infants who appear to have mild BPD suffer from varying degrees of pulmonary vascular disease (PVD). Although recent studies have enhanced our understanding of the pathobiology of PVD and PH in BPD, much remains unknown with respect to how PH should be properly defined, as well as the most accurate methods for the diagnosis and treatment of PH in infants with BPD. This article will provide neonatologists and primary care providers, as well as pediatric cardiologists and pulmonologists, with a review of the pathophysiology of PH in preterm infants with BPD and a summary of current clinical recommendations for managing PH in this population.
doi:10.1089/ped.2013.0323
PMCID: PMC3961769  PMID: 24669351
3.  Gastroesophageal Reflux Disease Increases Infant Acute Respiratory Illness Severity, but not Childhood Asthma 
It is unknown whether gastroesophageal reflux disease (GERD) during infancy affects infant bronchiolitis severity or childhood asthma inception. Four hundred thirty-two infants presenting with acute respiratory illness due to bronchiolitis or upper respiratory infection were studied. The primary exposure was the parental report of a previous GERD diagnosis. Outcomes included bronchiolitis severity at initial presentation and childhood asthma diagnosis at age 4. Infants with parentally reported GERD had a higher bronchiolitis severity score (range=0–12, clinically significant difference=0.5), indicating more severe disease, than infants without reported GERD (median 5.5 [interquartile range 3.5–9.0] among those with reported GERD versus 4.0 [1.0–7.0] among those without, P=0.005). This association persisted after adjusting for infant age, race, gender, and secondhand smoke exposure by a propensity score (adjusted odds ratio [OR] 1.99, 95% confidence interval [CI] 1.14–3.46, P=0.02). The parental report of GERD during infancy was not associated with the parental report of asthma diagnosis at age 4. GERD during infancy may contribute to acute respiratory illness severity, but is not associated with asthma diagnosis at age 4. Future prospective studies are needed to confirm these findings.
doi:10.1089/ped.2013.0291
PMCID: PMC3961795  PMID: 24669353
4.  Small Airway Targeted Therapy in Pediatric Asthma: Are We There Yet? 
Asthma is characterized by inflammation of proximal and distal airways. As new formulations of extrafine aerosol particles have become available, targeting small airways for the management of asthma has been investigated. As new studies attempt to explore the correlation between small airway dysfunction and clinical outcomes in asthma, well-designed clinical trials are needed to compare targeted and standard therapy for asthma management especially in pediatric patients.
doi:10.1089/ped.2013.0304
PMCID: PMC3869414  PMID: 24380019
5.  Mobile Phones: Potential Sources of Nickel and Cobalt Exposure for Metal Allergic Patients 
The use of cellular phones has risen exponentially with over 300 million subscribers. Nickel has been detected in cell phones and reports of contact dermatitis attributable to metals are present in the literature. We determined nickel and cobalt content in popular cell phones in the United States. Adults (>18 years) who owned a flip phone, Blackberry®, or iPhone® were eligible. Seventy-two cell phones were tested using SmartPractice's® commercially available nickel and cobalt spot tests. Test areas included buttons, keypad, speakers, camera, and metal panels. Of the 72 cell phones tested, no iPhones or Droids® tested positive for nickel or cobalt. About 29.4% of Blackberrys [95% confidence interval (CI), 13%–53%] tested positive for nickel; none were positive for cobalt. About 90.5% of flip phones (95% CI, 70%–99%) tested positive for nickel and 52.4% of flip phones (95% CI, 32%–72%) tested positive for cobalt. Our study indicates that nickel and cobalt are present in popular cell phones. Patients with known nickel or cobalt allergy may consider their cellular phones as a potential source of exposure. Further studies are needed to examine whether there is a direct association with metal content in cell phones and the manifestation of metal allergy.
doi:10.1089/ped.2013.0280
PMCID: PMC3869443  PMID: 24380018
6.  Pediatric Mastocytosis: A Review of the Literature 
Mastocytosis has a bimodal distribution often presenting in children from birth to 2 years of age and in those over the age of 15. Pediatric mastocytosis is due to the effects of mast-cell degranulation enzymes such as histamine and tryptase causing the presentation of pruritis, flushing, vesicles, abdominal and bone pain, or headache. Three different forms of mastocytosis can occur: urticaria pigmentosa, diffuse cutaneous, and solitary mastocytoma. Systemic symptoms are typically a result of mast-cell mediator release but do not prove systemic mast-cell hyperplasia. In this review, we present several research studies related to pediatric mast-cell disorders, and discuss several cases of pediatric mastocytosis, acute myeloid leukemia, pathophysiology, genetic studies, and treatment.
doi:10.1089/ped.2013.0275
PMCID: PMC3869446  PMID: 24380017
7.  Chiral Switch Drugs for Asthma and Allergies: True Benefit or Marketing Hype 
Enantiomers are one of several possible molecular configurations present in a drug that has at least 1 chiral center. A drug containing 2 or more enatiomers is called a racemic mixture. Enatiomers are being developed from racemic mixtures as drugs in their own right often to extend patent protection of highly popular drugs. However, the therapeutic advantages of single enantiomer drugs developed for respiratory use such as levalbuterol, arformoterol, and levocetirizine over their racemate has been disappointing. In addition, single enantiomer drugs may be several fold more expensive than the racemic drug. New single enantiomer drugs, which are stable (no interconversion back to the racemate) and have fewer adverse effects and a more predictable pharmacodynamic or pharmacokinetic profile would confer a therapeutic advantage and thus would be beneficial for clinical use.
doi:10.1089/ped.2013.0285
PMCID: PMC3777548  PMID: 24066264
8.  Caregiver Asthma Knowledge, Aptitude, and Practice in High Healthcare Utilizing Children: Effect of an Educational Intervention 
Factors underlying high healthcare utilization among Hispanic and African American (AA) children with asthma are not well known. We hypothesized that low parental knowledge and suboptimal practices are associated with high healthcare utlization and sought to elucidate these factors and identify ethnicity-specific differences. We also hypothesized that a targeted educational intervention will decrease emergency department (ED) visits and hospitalizations. A 57-item questionnaire investigating asthma knowledge, aptitude, and practice was administered during a hospitalization to 268 caregivers (158 Hispanic and 110 AA) of high healthcare utilizer children. Responses were compared between ethnicities. Participants were randomized into an education group and a control group to investigate the impact of an in-hospital educational intervention on future ED visits and hospitalizations. More than 80% of caregivers knew that asthma is associated with muscle constriction and mucus production. Overall, 66.7%–86.9% of caregivers found preventive steps including allergen avoidance, regular primary care physician (PCP) follow–up, and medication adherence helpful, but only 45.2% reported adherence to controller medications. Similarly, caregivers found management steps, including albuterol use, avoidance of ineffective medications, and need to contact PCP helpful but 33% Hispanic caregivers contacted their child's PCP at the time of the exacerbation leading the current hospitalization, compared with 17% AA caregivers (P=0.006). Moreover, 40% and 30% Hispanic and 27% and 18% AA caregivers felt stressed and helpless, respectively, about their child's asthma. Despite high baseline levels of knowledge, there were fewer ED visits in the education group (1.56±1.94) compared with the control group (2.05±2.32) (P=0.02) 2 years after the intervention. Although Hispanic and AA caregivers of children with high healthcare utilization were knowledgeable of asthma pathophysiology, and preventive and management steps, they reported being stressed and helpless and were unable to implement the steps at the time of an exacerbation, seeking care at the ED rather than contacting their PCP. The high health utilizers who underwent a targeted educational intervention had fewer ED visits 2 years following the intervention.
doi:10.1089/ped.2013.0226
PMCID: PMC3777550  PMID: 24066262
9.  Racial, Ethnic, and Language Disparities in Children's Exposure to Secondhand Smoke 
Race and ethnicity affect children's risk of secondhand smoke exposure. However, little is known about how race and language preference impact parents' self-reported smoking and stopping smoking rates. We analyzed data for 16,523 children aged 0–11 years from a pediatric computer decision support system (Child Health Improvement through Computer Automation [CHICA]). CHICA asks families in the waiting room about household smokers. We examined associations between race, insurance, language preference, and household smoking and reported stopping smoking rates using logistic regression. Almost a quarter (23%) of the children's families reported a smoker at home. Hispanic children are least likely (odds ratio [OR]: 0.17, confidence interval [CI]: 0.12–0.24) to have secondhand smoke exposure when compared to African American and white children, as were those with private insurance (OR: 0.52, CI: 0.43–0.64) or no insurance (OR: 0.79, CI: 0.71–0.88) compared to publicly insured. Children from English speaking families were more likely (OR: 1.55, CI: 1.24–1.95) to have secondhand smoke exposure compared to Spanish speaking families. Among smoking families, 30% reported stopping smoking subsequently. Stopping rates were higher in Hispanic (OR: 3.25, CI: 2.06–5.13) and African American (OR: 1.39, CI: 1.01–1.91) families compared to white children's families. Uninsured families were less likely than publicly insured families to report stopping smoking (OR: 0.76, CI: 0.63–0.92). English speaking families were less likely (OR: 0.56, CI: 0.41–0.75) to report stopping smoking compared to Spanish speaking even in a subgroup analyses of Hispanic families (OR: 0.55, CI: 0.39–0.76). In our safety net practices serving children predominantly on public insurance, Spanish speaking families reported the lowest risk of secondhand smoke exposure in children and the highest rate of stopping smoking in the household. Hispanic families may have increasing secondhand exposure and decreasing rates of stopping smoking as they acculturate.
doi:10.1089/ped.2013.0257
PMCID: PMC3777551  PMID: 24066263
10.  Does Use of Inhaled Corticosteroid for Management of Asthma in Children Make Them Shorter Adults? 
The purpose of this review is to discuss the effect of daily inhaled corticosteroids (ICSs) on the height of children with asthma. The effect of ICSs on growth and height is dependent on the dose and the therapeutic index of the ICS; however, the effect on final adult height was not clear until recently. New data suggest that if growth suppression occurs with the use of ICSs in children, it is sustained, but not cumulative over the years. The observed reduction in the final adult height is small and does not outweigh the benefits of ICSs, and the growth effect may be minimized by use of newer ICSs and other approaches for management of asthma in children with mild to moderate asthma.
doi:10.1089/ped.2013.0244
PMCID: PMC3678560  PMID: 23781396
11.  Provider Perceptions of Parent Health Literacy and Effect on Asthma Treatment Recommendations and Instructions 
Little is known about how pediatric providers assess parental health literacy, how concordant they are with validated measures of health literacy, and how these perceptions may influence treatment recommendations, how instructions are given or how reliable they perceive parents to be in carrying out instructions. Two hundred and eighty-one parents of 6–12-year-old asthma patients attending a pediatric clinic visit were recruited to a cross-sectional study of health literacy and asthma outcomes. Fourteen pediatric healthcare providers participated. Parents completed surveys that included 2 measures of health literacy: the Test of Function Health Literacy in Adults (TOFHLA) and the Rapid Estimate of Adult Literacy in Medicine (REALM). Immediately postvisit, pediatric providers completed a brief survey asking their assessment of the parent's health literacy and how it impacted treatment instructions and recommendations. Kappa statistics tested concordance; chi square and logistic regression tested associations among provider ratings, rating concordance, and demographic factors. Six providers were interviewed regarding the bases for their ratings. Providers' perceptions influenced asthma treatment recommendations (p=0.001) and how treatment instructions were given (p=0.001). Providers indicated that their perceptions were shaped by parent's verbal communication skills and patterns of past behavior related to children's asthma management. Data from 277 parents indicated that most had adequate health literacy with a lower percentage scored as adequate by the REALM versus the TOFHLA. Pediatric provider estimates of parental health literacy had low concordance with the validated measures. Providers were more likely to designate whites as adequately health literate. Pediatric asthma providers' perceptions of parents' health literacy can influence treatment recommendations and instructional practices.
doi:10.1089/ped.2013.0237
PMCID: PMC3678582  PMID: 23781393
12.  Analysis of CFTR Gene Variants in Idiopathic Bronchiectasis in Serbian Children 
This study has investigated a potential role of common Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene variants in the etiology of noncystic fibrosis bronchiectasis in Serbian children. The study has encompassed 48 patients (19 male and 29 female, aged between 5 and 18 years, median age 10.6±3.3), diagnosed with idiopathic bronchiectasis based on high-resolution computed tomography of thorax and pathologic examination of lobectomy materials. The CFTR gene analysis was performed on genomic DNA extracted from peripheral blood samples of patients by polymerase chain reaction (PCR)-Mediated Site-Directed Mutagenesis method, Denaturing Gradient Gel Electrophoresis method, and DNA sequencing. Mutation c.1521_1523delCTT (F508del) was detected with an allelic frequency of 1.0%, and c.224G>A (R75Q) variant. Carriers of c.1210-12T[5] (IVS8-5T) allele were significantly more common than in the general population (10.4% vs. 5.0%, P=0.0302). The frequency of homozygotes for Met 470 allele was higher in patients than in the general population (33% vs. 20%), while heterozygotes for p.Met470Val were less frequent (31% vs. 50%), and this difference was statistically significant (P=0.0222). The results obtained in this study indicate involvement of 2 common CFTR variants, c.1210-12T[5] and c.1408A, in idiopathic bronchiectasis in children, but this observation should be further confirmed by more extensive analysis of the CFTR gene in a larger group of patients.
doi:10.1089/ped.2013.0238
PMCID: PMC3678584  PMID: 23781395
13.  Determining the Relative Burden of Childhood Asthma at the Local Level by Surveying School Nurses 
Schools are effective venues for providing pediatric asthma education programs. Resources are limited, however, so ideally, these programs should be provided to schools with the highest prevalence. National and state asthma surveillance data cannot be extrapolated to local geographic areas. The objective of this study was to survey local schools on Long Island to obtain this information. Survey forms were mailed to the school nurses at every school in Nassau and Suffolk Counties, New York, in 2004, 2006, 2008, and 2010 asking for the number of children with asthma and the number who had permission to access rescue medication in the school. School nurses completed and returned the forms. We analyzed data from elementary and high schools separately, as high-school students often carry their medications with them without obtaining permission. Of the 3,327 surveys sent, 2,060 (61.9%) were returned and 1,807 (54.3%) could be included in the analyses. Overall, asthma prevalence increased from 7.6% in 2004 to 8.7% in 2010. This mirrored the New York State and national trends, although the rates we found were generally lower. The rate of asthmatic children with permission to access rescue medication in school was about the same throughout the study period (39.7% in 2004 and only 42.3% in 2010). Both rates were lower in elementary schools in low socioeconomic areas. These methods allowed us to compare the burden of childhood asthma in individual responder schools in a relatively large geographic area.
doi:10.1089/ped.2013.0231
PMCID: PMC3678585  PMID: 23781394
14.  Dietary Patterns and Wheezing in the Midst of Nutritional Transition: A Study in Brazil 
To assess the influence of dietary patterns on the prevalence of wheezing in the child and adolescent population in Northeastern Brazil. This is a cross-sectional study of male and female students, 6–12 years old, from the public elementary schools of São Francisco do Conde, Bahia, Northeastern Brazil. The report of wheezing in the past 12 months was collected using a questionnaire from the International Study of Asthma and Allergies in Childhood Program phase III, adapted to Portuguese. Consumption patterns were derived from principal component analysis based on the frequency of consumption of 97 food items by the food frequency questionnaire. We also obtained the anthropometric status, level of physical activity, pubertal development, and socioeconomic information, for each participant. Multivariate logistic regression analyses were used to assess the associations of interest. Of the children surveyed, 10.6% reported having wheezing. We identified 2 dietary patterns named Western and Prudent. We found a positive statistically significant association of the Western pattern with wheeze (odds ratio=1.77, 95% confidence interval: 1.10–2.84) after adjustment for total energy intake and controlling for potential confounders. The results showed that the Western dietary pattern was associated with wheezing. Our result is according with previous findings reported in several other studies.
doi:10.1089/ped.2012.0182
PMCID: PMC3609612  PMID: 23555072
15.  Adolescent Asthma Self-Management: A Concept Analysis and Operational Definition 
Background
Adolescents with asthma have a higher risk of morbidity and mortality than other age groups. Asthma self-management has been shown to improve outcomes; however, the concept of asthma self-management is not explicitly defined.
Methods
We use the Norris method of concept clarification to delineate what constitutes the concept of asthma self-management in adolescents. Five databases were searched to identify components of the concept of adolescent asthma self-management, and lists of relevant subconcepts were compiled and categorized.
Results
Analysis revealed 4 specific domains of self-management behaviors: (1) symptom prevention; (2) symptom monitoring; (3) acute symptom management; and (4) communication with important others. These domains of self-management were mediated by intrapersonal/cognitive and interpersonal/contextual factors.
Conclusions
Based on the analysis, we offer a research-based operational definition for adolescent asthma self-management and a preliminary model that can serve as a conceptual base for further research.
doi:10.1089/ped.2012.0150
PMCID: PMC3522127  PMID: 23285426
16.  Asthma Research for All of the United States 
Asthma disproportionally affects different ethnic/racial groups, with Puerto Ricans and African Americans suffering the highest asthma prevalence and morbidity, Mexicans the lowest, and non-Hispanic whites in between. Genome-wide association studies of asthma have found both shared and race/ethnic-specific genetic risks factors for asthma. However, the majority of genetic asthma research is performed in populations of European descent, which limits the benefits of genetic research to European populations. It is important to biomedical and clinical research to include more diverse and underrepresented populations. The rich genetic diversity of all populations can be leveraged to scientific advantage. For example, admixture mapping provides a more powerful approach than traditional genome-wide allelic association studies in discovering genetic associations for complex diseases. By being more inclusive we can achieve a better understanding of the genetics of asthma, address health disparities, and ensure that scientific advances will benefit populations worldwide.
doi:10.1089/ped.2012.0173
PMCID: PMC3429272  PMID: 22970422
17.  The Relationship between Asthma and Obesity in Urban Early Adolescents 
Asthma and obesity, which have reached epidemic proportions, impact urban youth to a great extent. Findings are inconsistent regarding their relationship; no studies have considered asthma management. We explored the association of obesity and asthma-related morbidity, asthma-related health care utilization, and asthma management in urban adolescents with uncontrolled asthma. We classified 373 early adolescents (mean age=12.8 years; 82% Hispanic or Black) from New York City public middle schools into 4 weight categories: normal (body mass index [BMI]<85th percentile); overweight (85th percentile≤BMI<95th percentile); obese (95th percentile≤BMI<97th percentile); and very obese (BMI≥97th percentile). We compared sample obesity prevalence to national estimates, and tested whether weight categories predicted caregiver reported asthma outcomes, adjusting for age and race/ethnicity. Obesity prevalence was 37%, with 28% of the sample being very obese; both rates were significantly higher than national estimates. We found no significant differences in asthma-related health care utilization or asthma management between weight categories, and a few differences in asthma-related morbidity. Relative to normal weight and obese youth, overweight youth had higher odds of never having any days with asthma-related activity limitations. They also had higher odds of never having asthma-related school absences compared with obese youth. Overweight youth with asthma-related activity limitations had more days with limitations compared with normal weight youth. Overweight, but not obese youth, missed more school due to asthma than normal weight youth. Overweight and obesity prevalence was very high in urban, Hispanic, and Black adolescents with uncontrolled asthma, but not strongly associated with asthma-related morbidity, asthma-related health care utilization, or asthma management practices.
doi:10.1089/ped.2012.0145
PMCID: PMC3429276  PMID: 22970423
18.  Obesity, Nutrition, and Asthma in Children 
Obesity rates have increased dramatically among children in many parts of the world, especially in North America and several other English-speaking countries. The impact of obesity on pediatric health has become a major prevention initiative by the Obama administration and several public health organizations. Children with obesity are at increased risk for developing asthma, which is already one of the most common chronic diseases among children. The cause underlying obesity's impact on asthma risk is unknown. Commonly cited potential etiologies include airway smooth muscle dysfunction from thoracic restriction, obesity-related circulating inflammation priming the lung, and obesity-related comorbidities mediating asthma symptom development. Each of these theories does not fit precisely with all of the data that have accumulated over the last decade. In this review, I will explore other possible causes including: (1) dietary characteristics common in Westernized countries that might lead to both obesity and asthma; (2) reductions in physical activity; and (3) genetic alterations that increase the propensity to both obesity and asthma together. Next, I will review the current data on how obesity affects common characteristics of asthma such as airway inflammation, lung function, risk of exacerbation, atopy, and response to treatment. Obesity in children with asthma appears to be associated with greater airflow obstruction and a mildly diminished response to inhaled corticosteroids. Little objective evidence in children suggests that obesity significantly heightens the risk of exacerbation or worsens disease stability in children. Lastly, I will discuss the current literature that suggests that obese children with asthma generally should receive the same guidelines-based management as lean children. However, interventions that encourage daily physical activity, weight-loss, normalization of nutrient levels, and monitoring of common obesity-related sequelae should be considered by healthcare providers managing obese children with difficult-to-control asthma.
doi:10.1089/ped.2011.0137
PMCID: PMC3377949  PMID: 22768385
19.  The Greater Cincinnati Pediatric Clinic Repository: A Novel Framework for Childhood Asthma and Allergy Research 
Background
Allergic disorders, including asthma, allergic rhinitis, atopic dermatitis, eosinophilic esophagitis, and food allergy, are a major global health burden. The study and management of allergic disorders is complicated by the considerable heterogeneity in both the presentation and natural history of these disorders. Biorepositories serve as an excellent source of data and biospecimens for delineating subphenotypes of allergic disorders, but such resources are lacking.
Methods
In order to define subphenotypes of allergic disease accurately, we established an infrastructure to link and efficiently utilize clinical and epidemiologic data with biospecimens into a single biorepository called the Greater Cincinnati Pediatric Clinic Repository (GCPCR). Children with allergic disorders as well as healthy controls are followed longitudinally at hospital clinic, emergency department, and inpatient visits. Subjects' asthma, allergy, and skin symptoms; past medical, family, social, diet, and environmental histories; physical activity; medication adherence; perceived quality of life; and demographics are ascertained. DNA is collected from all participants, and other biospecimens such as blood, hair, and nasal epithelial cells are collected on a subset.
Results
To date, the GCPCR has 6,317 predominantly Caucasian and African American participants, and 93% have banked DNA. This large sample size supports adequately powered genetic, epidemiologic, environmental, and health disparities studies of childhood allergic diseases.
Conclusions
The GCPCR is a unique biorepository that is continuously evaluated and refined to achieve and maintain rigorous clinical phenotype and biological data. Development of similar disease-specific repositories using common data elements is necessary to enable studies across multiple populations of comprehensively phenotyped patients.
doi:10.1089/ped.2011.0116
PMCID: PMC3377950  PMID: 22768387
20.  Exhaled Nitric Oxide in Acute Phase of Bronchiolitis and Its Relation with Episodes of Subsequent Wheezing in Children of Preschool Age 
Background
Fractional exhaled nitric oxide (FENO) levels are increased in children with asthma and in infants with recurrent wheezing, but the role of FENO in the acute phase of bronchiolitis is still not defined.
Objective
The aim of this study is to evaluate FENO values in the acute phase of bronchiolitis, compare them with healthy infants, and relate those values with the appearance of other wheezing episodes.
Methods
FENO values were determined in infants between 2 months and 2 years affected with RVS bronchiolitis by offline method. The FENO values collected in the acute phase were related with the respiratory clinical symptoms presented in the 2 years following the episode.
Results
A total of 30 patients were recruited: 15 in the bronchiolitis group and 15 in the control group. The average of the FENO values in the acute phase was 18.74 ppb (range 2–88) in the bronchiolitis group, and 8.75 ppb (range 2–24) in the control group. However, these results showed no significant statistical differences (p=0.176). Nevertheless, we found a positive correlation between the FENO values and the clinical score (Downes) of the bronchiolitis episode (p=0.023). In infants that presented other wheezing episodes in the 2 years after, the average of FENO in the acute phase of the first episode was 23.1 ppb (average of 10.25 ppb) versus 8.4 ppb (average 5.4 ppb) in the group of patients with no other episodes. The comparison of averages has no statistical significance.
Conclusion
We found no differences in FENO between infants with bronchiolitis and healthy ones. The FENO values in the acute phase seems to be related to the severity of the disease but do not predict the appearance of wheezing episodes in the following 2 years.
doi:10.1089/ped.2011.0127
PMCID: PMC3377953  PMID: 22768386
21.  Availability of Asthma Quick Relief Medication in Five Alabama School Systems 
Objectives
This paper documents individual asthma action plan presence and quick relief medication (albuterol) availability for elementary students enrolled in five Alabama school systems.
Patients and Methods
Data were obtained during baseline data collection (fall 2005) of a school-based supervised asthma medication trial. All students attended 1 of 36 participating elementary schools across five school systems in Jefferson County, Alabama. In addition, they had to have physician-diagnosed asthma requiring daily controller medication. Each school system had its own superintendent and elected school board. Asthma action plan presence and albuterol availability was confirmed by study personnel. Asthma action plans had to contain daily and acute asthma management instructions. Predictors of asthma action plan presence and albuterol availability were also investigated. Associations between albuterol availability and self-reported characteristics including health care utilization prior to study enrollment and outcomes during the study baseline period were also investigated.
Results
Enrolled students had a mean (SD) age of 11.0 (2.1) years, 91% were African American, and 79% had moderate persistent asthma. No student had a complete asthma action plan on file and only 14% had albuterol physically available at school. Albuterol availability was not predicted by gender, race, insurance status, second-hand smoke exposure, need for pre-exercise albuterol, asthma severity, or self-reported health care utilization prior to study enrollment. Albuterol availability did not predict school absences, red/yellow peak flow recordings, or medication adherence during the study's baseline period.
Conclusion
Despite policies permitting students to possess albuterol, few elementary students across five independent school systems in Alabama actually had it readily available at school.
doi:10.1089/ped.2011.0118
PMCID: PMC3306583  PMID: 22454787
22.  How Do Perceptions of Asthma Control and Severity Relate to Indicators of Asthma Status and Treatment Recommendations by Pediatricians? 
Background
According to National Institutes of Health (NIH) guidelines, asthma control and severity are unique constructs. Little is known about how asthma control and severity are distinguished by pediatricians and if they influence treatment recommendations.
Methods
We conducted a random-sample survey of 500 pediatricians using patient vignettes with different asthma status indicators (recent hospitalization, parental report of bother from asthma, frequent symptoms, parental report of worsening asthma, and wheeze during physical exam) and a visual analog scale (VAS) to rate control and severity. Regression models assessed the independent effects of these indicators on asthma control and severity ratings, and the effects of these ratings on treatment recommendations.
Results
A total of 270 respondents provided usable data. Compared to patients with well-controlled asthma: (1) medication intensity influenced only severity ratings; (2) frequent symptoms and recent hospitalization influenced control and severity ratings; (3) wheeze and bother influenced control ratings only (p<0.001 for all comparisons); (4) a report of worse asthma did not significantly affect any ratings (p>0.2). Poorer VAS control ratings were associated with recommendations to step-up treatment (odds ratio [OR] 2.61, 95% confidence interval [CI], 2.2–3.1, p<0.001), but more severe VAS ratings were not (OR 1.02, 95% CI, 0.9–1.2, p=0.8). Recommendations to step-down treatment were associated with poorer VAS control ratings (OR 0.70, 95% CI, 0.6–0.8, p<0.001) and more severe VAS ratings (OR 0.82, 95% CI, 0.7–0.9, p<0.001).
Conclusions
Pediatricians who step-up asthma treatment base their assessments on asthma control, while assessments of both control and severity factor into their decision to step-down asthma therapy.
doi:10.1089/ped.2011.0107
PMCID: PMC3306591  PMID: 22454788
23.  Primary Ciliary Dyskinesia in Children: A Review for Pediatricians, Allergists, and Pediatric Pulmonologists 
Primary ciliary dyskinesia (PCD) is a rare genetic condition that causes impaired mucociliary clearance due to poorly functioning cilia. PCD is one disease manifestation of the many recently recognized associations with ciliary malfunction, referred to as “ciliopathies.” Manifestations of PCD commonly begin in the neonatal period with cough, pneumonia, and chronic ear infections or effusions. Approximately half of the affected individuals have situs inversus totalis. The diagnosis is often made in later childhood or early adulthood, because symptoms mimic more common childhood illnesses and because the definitive diagnosis of PCD can be challenging. Treatment recommendations are largely based on therapies used for other conditions with impaired mucociliary clearance in the absence of evidence-based research specific for PCD. Early recognition and initiation of both otolaryngologic and pulmonary management might reduce potential long-term morbidities. The purpose of this article is to update primary care providers, allergists, and pediatric pulmonologists on recent advances in this interesting condition.
doi:10.1089/ped.2011.0099
PMCID: PMC3255511  PMID: 22276227
24.  Polymorphism in Osteopontin Gene (SPP1) Is Associated with Asthma and Related Phenotypes in a Puerto Rican Population 
Recent studies have shown that osteopontin, a cytokine with suggested immunoregulatory functions, may contribute to pathogenesis of asthma. To determine whether single-nucleotide polymorphisms (SNPs) in SPP1, the gene encoding osteopontin, are associated with risk of asthma, we genotyped 6 known SNPs in SPP1 in the well-characterized Genetics of Asthma in Latino Americans population of 294 Mexican and 365 Puerto Rican parent–child asthma trios. The associations between SNPs and asthma or asthma-related phenotypes were examined by transmission disequilibrium tests as implemented in the family-based association test program. Three polymorphisms, 1 in exon 7 (rs1126616C) and 2 in the 3′-untranslated region (rs1126772A and rs9138A) of SPP1, were associated with diagnosis of asthma, severity of asthma, asthma in subjects with elevated immunoglobulin E (IgE) (IgE >100 IU/mL), and postbronchodilator FEV1 in Puerto Ricans (P values=0.00007–0.04). The CC genotype of rs1126616 conferred an odds ratio of 1.7 (95% CI=[1.3, 2.3], P value adjusted for multiple comparisons=0.001) for asthma compared with the CT and TT genotypes. Furthermore, haplotype analysis identified rs1126616C-rs1126772A-rs9138A to be associated with an increased risk for asthma, severity of asthma, and asthma in subjects with elevated IgE (P=0.03). There was no association between the SPP1 SNPs and asthma outcomes in Mexicans. Our findings suggest that the SPP1 gene is a risk factor for asthma and asthma-related phenotypes in Puerto Ricans, and are consistent with previous animal and human studies on the role of osteopontin in pathogenesis of asthma.
doi:10.1089/ped.2011.0095
PMCID: PMC3255512  PMID: 22276228

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