Positive Asthma Predictive Index Research Articles

Clinical efficacy of antileukotriene therapy in children with acute bronchitis

Recurrent episodes of bronchial obstruction in preschool children are one of the important risk factors for the development of bronchial asthma.Purpose. The study aimed at investigating the clinical and immunological characteristics of children with acute bronchitis and to determine the clinical effectiveness of course anti-inflammatory therapy.Material and methods. The study was a single-center prospective cohort, including 1–5-year-old patients with acute bronchitis (main group, n = 109): a group with acute simple bronchitis (n = 34) and acute obstructive bronchitis (n = 75). Reference group: children of health group 2 (n = 29). Clinical and anamnestic and laboratory methods were used. Patients with a positive API (Asthma Predictive Index) were administered montelukast at a dose of 4 mg orally once a day for 3 months (control points at 1 and 3 months), reference patients received symptomatic therapy for respiratory infection. The end point of the study is the absence of bronchial obstruction. The effectiveness of the use of Montelukast was evaluated by calculating the clinical index, efficiency coefficient. Results. A statistically significant predominance of intoxication symptoms was found in patients with acute simple bronchitis (p = 0.02), signs of respiratory failure (p < 0.001), and peripheral eosinophilia — in children with acute obstructive bronchitis (p = 0.02). In etiology, rhinovirus significantly prevailed in patients with bronchial obstruction, and RS virus prevailed in patients with acute simple bronchitis (p = 0.02). The cytokine profile of patients with acute obstructive bronchitis is characterized by a decrease in the levels of macrophage inflammatory proteins (p = 0.01) and IL-8 (p = 0.048). A prolonged course of montelukast in children with a positive API significantly reduces the severity of subsequent acute respiratory infections, reduces the frequency of bronchial obstruction and the risk of bronchial asthma (p < 0.001).Conclusion. Evaluation of the results of montelukast therapy demonstrated clinical efficacy in patients with a positive API index.

Impact of Oral Corticosteroids on Respiratory Outcomes in Acute Preschool Wheeze: A Randomised Clinical Trial

To determine if oral prednisolones given to acutely wheezing preschool-aged children alter respiratory outcomes.A total of 3247 children (aged 24–59 months) with acute wheezing episodes between August 2014 and September 2016 in 3 New Zealand emergency departments (EDs) were potentially eligible. A total of 493 were randomly assigned, and 477 patients were included in the intention-to-treat analysis (238 in the prednisolone group and 239 in the placebo group). Primary outcome data were available on 393 patients (82% overall; 195 (79%) in the prednisolone group and 198 (83%) in the placebo group). Children <24 months of age were purposely excluded, ensuring that those with bronchiolitis were not included.In this double-blind placebo-controlled trial, preschool-aged children with viral-induced wheeze who presented to the ED were randomly assigned to receive 3 days of prednisolone (2 mg/kg) or a placebo. The primary outcome measure was a change in the validated Preschool Respiratory Assessment Measure (PRAM) score 24 hours after the intervention. Secondary outcomes included PRAM score at 4 hours, admission rate, length of ED and inpatient stay, amount of albuterol given in 48 hours, additional treatment with open-label prednisolone, time to return to normal activity, and adverse events, including the need for intravenous (IV) medication, ICU admission, and representation to the ED or primary care provider within 7 days. Pediatric Respiratory Assessment Measure (PRAM) scores (ranging from 0–12) were calculated on the basis of suprasternal retractions, scalene retractions, wheezing, and oxygen saturation in room air. The study was designed as an equivalence trial and powered (power: 95%) to detect the minimal difference in PRAM scores that would disprove the null hypothesis that corticosteroids and placebo are equivalent treatments. In a pilot study (n = 137), researchers determined a SD of 2.3 for change in PRAM score at 24 hours was significant. Therefore, analysis was by intention to treat.Between groups, there was no difference in the primary outcome, the change in PRAM score at 24 hours (difference between means: −0.39; 95% confidence interval [CI]: −0.84 to 0.06, P = .09). The median PRAM score at 24 hours for both groups was 0, with only approximately one-third in either group showing mild disease (PRAM score 1–4) and few with PRAM scores >4 (2.0% and 3.6% in treatment and control groups, respectively). Change in PRAM score at 4 hours was significantly different in the treatment group (−0.67; 95% CI: −1.18 to −0.16; P = .01). No difference in length of ED stay was observed (−0.57; 95% CI: −1.15 to 0.02; P = .06), although admission to the hospital occurred more often in the placebo group (0.67; 95% CI: 0.45 to 1.01; P = .05) as well as additional corticosteroid (0.22; 95% CI: 0.06 to 0.79; P = .01) and IV medication use (0.27; 95% CI: 0.07 to 0.96; P = .03). No difference was observed in representation to the hospital or the primary care provider within 7 days (P = .33 and P = .22, respectively) or ICU admission (undefined P value because only 2 total children went to the ICU) as well as the amount of albuterol given in 48 hours (P = .27).Oral prednisolone does not alter respiratory outcomes at 24 hours or beyond in preschool-aged children presenting with acute wheezing to the ED because most children improved after 24 hours regardless of initial treatment. Subgroup analyses revealed no evidence that the 24-hour treatment effect differed for albuterol responsive children, those with a positive Asthma Predictive Index, or more severe disease at presentation (higher PRAM score). However, those who received prednisolone had less respiratory distress 4 hours after medication administration and a reduced requirement for hospital admission, additional corticosteroid, or IV treatment. These findings suggest that early in-hospital administration of oral prednisolone to preschoolers with wheeze may prevent further deterioration and requirement for escalation of therapy. Additionally, considering the lack of significant difference at 24 hours, oral prednisolone may improve short-term respiratory outcomes for preschoolers presenting with wheeze. However, subsequent doses of oral prednisolone may provide no additional therapeutic benefit.With this robustly designed randomized controlled trial, we are reminded that wheezing preschoolers are a heterogeneous group with numerous factors contributing to a wheezy phenotype. We should consider that they should not be treated the same as older asthmatics, with regards to corticosteroids. With this study, the authors question oral steroid dosing dogma and demonstrate that oral prednisolone may improve short-term respiratory outcomes for wheezing preschoolers but subsequent doses of oral prednisolone may provide no additional therapeutic benefit. Further studies are needed in this population to understand the timing and dosing of corticosteroids.

Characterization of severe asthma in the pediatric population.

Relationship between the causal mechanisms of pediatric severe asthma and severity of symptoms would be helpful for developing personalized strategies for treatment and prevention. For this study, 698 medical histories of asthmatics between 6 and 18 years of age were reviewed in a period of 2 years. Variables analyzed were: age, sex, ethnicity, perinatological history, allergy history, asthma predictive index (API), exposure to tobacco, heavy traffic or epithelium, lung function, age of onset of symptoms, hospitalization admissions/PICU, systemic corticosteroids, daily symptoms control, device prescribe for daily control, and adherence. A total of 86 children with severe asthma were included (12.3%). Mean age 13.3 +/- 1.86 years, sex ratio1:1, mean age of symptom onset 2.765 +/- 3.06 years, mean IgE 1076.18KU / L +/- 1136, mean eosinophils 604c / mcl +/- 511.9, mean of FEV1 93.15% +/- 16.3. Evidently, 70 children (81.4%) had positive API, 68 (79.1%) rhinitis, 34 (39.5%) atopic dermatitis. 73 (83.9%) sensitized to inhalants and 56 (65.1%) to dermatophagoides, 39 (45.3%) passive smokers, 19 (22.1%) exposure to heavy traffic; 55 (64%) showed symptoms with exercise, 35 (40.7%) had audible wheezing. The mean systemic corticosteroid cycles/year was 3.63 +/- 3.23, mean PICU admissions 0.36 +/- 0.83, mean hospital admissions 4.31 +/- 5.3, average emergency room visits/year 19.44 +/- 16.28. 38 (56.7%) had good adherence, 44 (51%) used an MDI device and 39 (45.3%) used dry powder. Children with severe asthma meet the following criteria: premature, positive API, rhinitis, atopic dermatitis, high IgE, eosinophilia, passive smokers, exposure to heavy traffic, decreased lung function, and low adherence to controller medication.

Leptin in Cord Blood Associates with Asthma Risk at Age 3 in the Offspring of Women with Gestational Obesity.

Rationale: Maternal obesity is associated with asthma in the offspring. Whether cord blood leptin is associated with risk of asthma in offspring is unclear.Objectives: To assess whether cord blood leptin from women with pregestational obesity predict preschool asthma.Methods: In this birth cohort study, we divided pregnant women into three weight categories during the first obstetric visit: normal (NL), overweight (OW), and obese (OB).Results: We followed the offspring recording atopy, wheezing, and other respiratory illnesses through 30 months of age. Cord blood and peripheral blood at 30 months of age were taken to measure cytokines, adipokines, metabolic biomarkers, and specific immunoglobulin E. Adjusted regression models were used to evaluate the association between maternal obesity and offspring asthma risk, defined by a positive Asthma Predictive Index. Three hundred thirty-nine mothers were recruited; 140 offspring were born from NL, 80 from OW, and 119 from OB mothers. OB women were older and less educated and had higher parity and higher C-section frequency. Offspring from OB women had higher birthweight, head circumference, and placental weight compared with other groups. The proportion of Asthma Predictive Index positive at 30 months of age was 12.2% in the NL, 14.7% in the OW, and 16.8% in the OB group (P = 0.18). Offspring from OB women had higher leptin, leptin/adiponectin ratio, interleukin-10, and insulin than the OW group and higher leptin than the NL group. In the adjusted analysis, offspring from OB mothers with high cord blood leptin had increased risk of asthma (adjusted odds ratio, 1.30; 95% confidence interval, 1.1-1.55; P = 0.003).Conclusions: Offspring from obese mothers with high cord blood leptin have 30% higher asthma risk at age 3.Clinical trial registered with ClinicalTrials.gov (NCT02903134).

Predicting the outcome of respiratory disease in wheezing infants using tidal flow-volume loop shape

Introduction and objectivesWheezing (RW) infants with a positive asthma predictive index (API+) have a lower lung function as measured by forced expiratory techniques. Tidal flow-volume loops (TFVL) are easy to perform in infants, and sedation is not necessary. Materials and methodsA total of 216 wheezing infants were successfully measured, and 183 of them were followed for over a year. TFVL loops were classified into one of three categories depending of their geometric shape (symmetric, convex, and concave). Respiratory rate (Rr), presence of API+, and the number of exacerbations during the following year were also recorded. ResultsChildren with concave loops had more exacerbations in the following year (OR = 6.8 [IC95% 3.33;13.91]). Infants API + were also significantly more related to concave loops (OR = 10.02 [IC 95% 4.53; 22.15]). Rr was higher in infants with concave loops (44+/−15.5 vs. 36.6 +/−12.6; p < 0.01). ConclusionInfants with a concave TFVL have a higher probability of experiencing exacerbations in the following year, and are at a higher risk of suffering asthma.

Preschoolers with recurrent wheezing have a high prevalence of sleep disordered breathing

Objective: Sleep-disordered breathing (SDB) is highly prevalent in school children with poorly-controlled asthma. However, this association has not been assessed in preschoolers with recurrent wheeze, nor in those at risk for asthma. We hypothesized that preschoolers with asthma risk (positive asthma predictive index [API]) have a higher prevalence of SDB and higher inflammatory biomarkers (blood-hsCRP and urinary-LTE4) levels than those with negative API.Method: Children 2 to 5 years of age with recurrent wheezing were classified as positive or negative API. SDB was determined by the pediatric sleep questionnaire (PSQ) and its subscale (PSQSub6). Demographic characteristics, spirometry, blood hsCRP and urinary LTE4 were assessed.Results: We enrolled 101 preschoolers: 70 completed all measurements, 55.4% were males, mean age 4.07 ± 0.87 years, 45% overweight or obese, 70% had positive API, 87.5% had rhinitis. The prevalence of SDB measured by PSQ was 40.8% and by PSQSub6 was 29.6%. However, the proportion of SDB was similar between positive and negative API groups. The hsCRP (mean ± SD) was higher in the positive than in negative API (3.58 ± 0.58 and 1.32 ± 0.36 mg/L, p = 0.69, respectively); moreover, no differences in urinary LTE4 were found between groups. No correlation of PSQ (+) or PSQSub6 (+) with hsCRP and uLTE4 was found. However, preschoolers with positive API had significantly more post-bronchodilator percentage change in FEF25-75 than negative API (24.14 ± 28.1 vs. 4.13 ± 21.8, respectively, p = 0.01).Conclusions: In preschoolers with recurrent wheezing, we should be investigating for the coexistence of SDB, using early screening methods for detecting those conditions.

Уровень сывороточного периостина у детей с положительным и отрицатель¬ным предиктивным индексом астмы и у их здоровых сверстников

Уровень сывороточного периостина у детей с положительным и отрицатель¬ным предиктивным индексом астмы и у их здоровых сверстников

Association of a 4-Locus Gene Model Including IL13, IL4, FCER1B, and ADRB2 With the Asthma Predictive Index and Atopy in Chinese Han Children.

Asthma is a complex and heterogeneous disease. We found gene-gene interactions between IL13 rs20541, IL4 rs2243250, ADRB2 rs1042713, and FCER1B rs569108 in asthmatic Chinese Han children. This 4-locus set constituted an optimal statistical interaction model. We examined associations between the 4-gene model (IL13, IL4, FCER1B, and ADRB2) and the Asthma Predictive Index (API) and atopy in Chinese Han children. Four single-nucleotide polymorphisms in the 4 genes were genotyped in 385 preschool children with wheezing symptoms using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The t test and x2 tests were used for the analysis. Significant correlations were found between the 4-locus gene model and a stringent and loose API (both P<.0001). Additionally, a high-risk asthma genotype was a risk factor for a positive API (stringent API, OR=4.08; loose API, OR=2.36). We also found a statistically significant association between the 4-locus gene model and atopy (P<.01, OR=2.09). Our results indicated that the 4-locus gene model consisting of L13 rs20541, IL4 rs2243250, ADRB2 rs1042713, and FCER1B rs569108 was associated with the API and atopy. These findings provide evidence that this gene model can be used to determine a high risk of developing asthma and atopy in Chinese Han children.

Relation between serum CC16 levels and asthma predictive index in pre-schoolers with recurrent wheezing

BackgroundLow levels of serum CC16 were reported in asthmatic adults, but the studies on children were scarce and conflicting. The aim of this study was to compare serum CC16 levels in pre-school children with recurrent wheezing assessed using an asthma predictive index (API). MethodsWe performed a case-control study based on API, with all enrolled pre-school children who had recurrent wheezing episodes (>3 episodes/last year confirmed by a physician) and had presented at one paediatric clinic in Santiago, Chile. The population was divided according to stringent API criteria into positive or negative. ResultsIn a one-year period, 60 pre-schoolers were enrolled. After excluding 12, 48 pre-schoolers remained (27 males, age range from 24 to 71 months) and completed the study; 34 were API positive and 14 were API negative. There were no significant differences in demographics between groups. The level of serum CC16 levels for pre-schoolers with a positive API and negative API were (median 9.2 [7.1–11.5] and 9.4 [5.5–10], p=0.26, respectively). The area under the curve for the serum CC16 levels to predict a positive API was 0.6, 95% CI [0.43–0.77], p=0.3. A correlation between serum CC16 levels and age was found (r=0.36 [0.07–0.59], p=0.01], but not between serum CC16 levels and peripheral eosinophils blood. ConclusionThere was no evidence that serum CC16 levels played a role in recurrent wheezing and a positive API in pre-school children. More studies are needed to confirm this finding.

Short-term effect of a smart nebulizing device on adherence to inhaled corticosteroid therapy in Asthma Predictive Index-positive wheezing children.

ObjectiveTo explore the effect of a smart nebulizing device on the rate of adherence to inhaled corticosteroid (ICS) in children with positive Asthma Predictive Index.MethodsIn total, 65 children with positive Asthma Predictive Index and under the age of 5 years who visited our hospital from October 2015 through October 2016, were randomly assigned to receive conventional nebulization or smart nebulization. The smart nebulizer was connected to smart phones via an App. The following information was collected: rate of adherence to ICS, frequency of emergency visits or hospitalizations, application of antibiotics or oral steroids, and wheezing progression or improvement.ResultsThe rate of adherence to ICS was 86.67% (26/30), 76.67% (23/30), and 67.33% (20/30) in the smart nebulization group, and 62.86% (22/35), 51.42% (18/35), and 40.00% (14/35) in the conventional nebulization group after 4-, 8-, and 12-week therapy, respectively. There were significant differences between the 2 groups at all of the time points (P<0.05). Both day- and night-time wheezing scores were significantly lower in the smart nebulization group than those of the conventional nebulization group after 4-, 8-, and 12-week therapy (P<0.05). The frequency of emergency visits, comorbidity of respiratory infection, antibiotics or systemic steroid usage, and therapeutic cost for additional treatment during the 12-week study period, was significantly lower in the smart nebulization group than that in the conventional nebulization group (P<0.05).ConclusionA smart electronic nebulization device could significantly improve the rate of adherence to ICS in children under the age of 5 years, and thus could significantly reduce the frequency of emergency visits and respiratory infections as well as the usage of antibiotics or systemic steroids.

Serum periostin is not related to asthma predictive index

BackgroundIn contrast to adult asthmatic patients, studies on the role of serum periostin levels in schoolchildren with asthma are still conflictive, and very few studies have been performed in pre-schoolers. The aim of this study was to compare serum periostin levels in recurrent wheezer pre-schoolers according to their asthma predictive index (API) condition. MethodsWe performed a case–control study enrolling pre-schoolers with recurrent wheezing episodes (>3 episodes confirmed by physician) presented at one paediatric clinic in Santiago, Chile. The population was divided according to stringent API criteria into positive or negative. ResultsIn a one-year period, 60 pre-schoolers were enrolled. After excluding 12 (due to not fulfilment of inclusion criteria or refusal of blood sample extraction), 48 remaining pre-schoolers (27 males, age range from 24 to 71 months) completed the study; 34 were API positive and 14 were API negative. There were no significant differences in demographics between groups. The level of serum periostin levels for pre-schoolers with positive API and negative API were (median 46.7 [25.5–83.1] and 67.5 [20.5–131.8], p=0.9, respectively). The area under the curve for the serum periostin levels for predict positive API was 0.5, 95% CI [0.29–0.70], p=0.9. No significant correlation between serum periostin levels and peripheral blood eosinophils was found. ConclusionSerum periostin levels were no significantly different between wheezer pre-schoolers with positive and negative API. More studies are needed to confirm this finding.

Differences between preschoolers with asthma and allergies in urban and rural environments

ABSTRACTObjective: Previous studies have provided conflicting results about how living in a rural or urban environment influences schoolchildren with asthma and allergic diseases in different ways. The aim of the present study was to evaluate if recurrent wheezing preschoolers from rural or urban areas differ in asthma, allergic diseases, and atopy.Methods: A cross-sectional-study in Rafaela, Argentina, on 143 preschoolers with recurrent wheezing from rural and urban settings was performed (2010–2012). Diagnosis of asthma (by positive asthma predictive index [API]), allergic diseases (rhinitis, dermatitis), and atopy (by skin prick test [SPT], peripheral blood eosinophils, and serum total IgE) were assessed.Results: Preschoolers from rural settings had significantly higher prevalence of vaginal delivery, longer breastfeeding, earlier onset of wheezing, more parental smoking, siblings, shared a bedroom, and more exposure to chemicals used in plant fumigation or farm animals, and unpasteurized milk consumption, in comparison to preschoolers living in urban setting. In contrast, preschoolers from urban areas had significantly higher prevalence of parental history of allergy, positive skin prick test, and positive API. After multivariate analysis adjusting for covariates, maternal smoking [odds ratio (OR) = 3.44] and positive SPT (OR = 5.57) significantly increase the risk of asthma diagnosis (positive API); in contrast, living in rural setting (OR = 0.04), and having more siblings (OR = 0.51) decrease their risk.Conclusions: Recurrent wheezing preschoolers from rural areas had a significant inverse odds of being diagnosed with asthma (type-2 inflammation) when compared to those from urban areas. Exposure to farm animals and consumption of unpasteurized milk might have a role.

Airway tone dysfunction among pre-schoolers with positive asthma predictive index: A case–control study

ObjectiveTo measure lung function by impulse oscillometry (IOS) and spirometry in recurrent wheezer pre-schoolers according to their asthma predictive index (API) condition. MethodsWe performed a case–control study enrolling all pre-schoolers with recurrent wheezing episodes (>3 episodes confirmed by physician) who presented at a paediatric pulmonology clinic. The population was divided according to stringent API criteria into positive or negative. ResultsIn the nine-month period, 109 pre-schoolers were enrolled. After excluding one patient (due to lung function technique problems) 108 pre-schoolers (56 males, age range from 24 to 72 months) completed the study; 50 belong to positive API and 58 to negative API group. There were no differences in demographics between groups. More use of ICS was found in those with positive API than with negative API (62% vs. 12%, respectively, p=0.001). No differences in basal lung function and post-bronchodilator response to salbutamol (by IOS or spirometry) were found between positive and negative API pre-schoolers. However, those positive API pre-schoolers with ICS had significantly higher central basal airway resistance (RA at 20Hz) and higher post-BD response (% change in FEF25–75 and in FEV0.5) than those positive API without ICS. ConclusionRecurrent wheezer pre-schoolers with positive API and ICS used may have airway dysfunction. More studies are needed to confirm this finding.

Risk factors for recurrent wheezing in infants: a case-control study.

ABSTRACTOBJECTIVE To evaluate the association between recurrent wheezing and atopy, the Asthma Predictive Index, exposure to risk factors, and total serum IgE levels as potential factors to predict recurrent wheezing.METHODS A case-control study with infants aged 6-24 months treated at a specialized outpatient clinic from November 2011 to March 2013. Evaluations included sensitivity to inhalant and food antigens, positive Asthma Predictive Index, and other risk factors for recurrent wheezing (smoking during pregnancy, presence of indoor smoke, viral infections, and total serum IgE levels).RESULTS We evaluated 113 children: 65 infants with recurrent wheezing (63.0% male) with a mean age of 14.8 (SD = 5.2) months and 48 healthy infants (44.0% male) with a mean age of 15.2 (SD = 5.1) months. In the multiple analysis model, antigen sensitivity (OR = 12.45; 95%CI 1.28–19.11), positive Asthma Predictive Index (OR = 5.57; 95%CI 2.23–7.96), and exposure to environmental smoke (OR = 2.63; 95%CI 1.09–6.30) remained as risk factors for wheezing. Eosinophilia ≥ 4.0% e total IgE ≥ 100 UI/mL were more prevalent in the wheezing group, but failed to remain in the model. Smoking during pregnancy was identified in a small number of mothers, and secondhand smoke at home was higher in the control group.CONCLUSIONS Presence of atopy, positive Asthma Predictive Index and exposure to environmental smoke are associated to recurrent wheezing. Identifying these factors enables the adoption of preventive measures, especially for children susceptible to persistent wheezing and future asthma onset.

Asociación del índice predictivo de asma y presencia de la enfermedad en niños de la comuna de Valdivia

There are predictive indexes to identify asthmatic patients from the rest of the recurrent wheezing phenotypes. The aim of this work was to evaluate the association between the positive Asthma Predictive Index (API) and the presence of asthma between the age of six and seven years old, in children from Valdivia, Chile. Methods: API was applied to 101 asthmatic children (cases) and 100 non-asthmatic children (controls). Data were analyzed using STATA v. 11 (2009). Fisher Exact Test was used to determine the relationship between variables. Results: 72.3% of asthmatic patients and 3% of non- asthmatic patients had a positive index. Significant differences (p < 0.001) were shown in all the variables included in the API. In our group of patients, the probability for a child to develop asthma was at least 24 times higher if he/she had a positive API (OR = 84.3 CI95% 24.1-436.5). Conclusion: API is a good tool to predict asthma and allows to take right decisions in recurrent wheezing children younger than 36 months old.

Role of the asthma predictive index (API) in assessing the development of asthma among Brazilian children

Methods Sixty one of 76 children who participated in a previous study (Camara et al JACI 2004;113;551-7) aimed at identifying risk factors for acute wheezing in infancy were re-evaluated at the ages of 2-4 and 8-12 years. They had been seen at the Emergency Room (ER) for an episode of wheezing at the age of 6-24 months. At the age of 8-12 years, parents completed a questionnaire on respiratory symptoms; 52 children underwent skin prick testing with a panel of inhalant and food allergens and 48 performed methacholine challenge tests. Children were considered asthmatic at the age of 8-12 years if they presented previous physician-diagnosed asthma, or at least one of the following symptoms in the past 12 months: wheezing, cough or chest tightness with exercise, or dry cough without colds, accompanied by bronchial hyperresponsiveness, defined by a PC20 <4mg/ml methacholine challenge test. A positive API (at least one major criteria: physician-diagnosed eczema or parental asthma; or 2 of 3 minor criteria: physician-diagnosed allergic rhinitis, wheezing without colds or peripheral eosinophilia ≥4%) was established based on information collected when the children were 2-4 years-old. Sensitivity, specificity, predictive values, likelihood ratios and confidence intervals (CI) of the API for the diagnosis of asthma at 8-12 years-old were calculated. Results Among the 48 children evaluated at school age, 20 (41.7%) were diagnosed with asthma; 13 of them (65%) had a positive API at 2-4 years. Of the 28 children who did not develop asthma, only 9 (32.1%) had a positive API. Sensitivity and specificity of the API were 65% (CI=40.8-84.6) and 67.9% (CI=47.7-84.1), respectively. Positive and negative predictive values were 59.1 (CI=38.7-79.7) and 73.1 (IC=53.9-86.3); and positive and negative likelihood ratios were 2.02 (CI=1.5-2.73) and 0.51 (CI=0.37-0.72), respectively.

Serum level of vitamin D and trace elements in children with recurrent wheezing: a cross-sectional study.

BackgroundWe aimed to show the relationship between recurrence of wheezing and serum levels of vitamin D, zinc, and copper in wheezy children compared with a healthy group.MethodsIn this cross sectional study, seventy-three children with wheezing and seventy-five controls were included without a follow-up period. The clinical characteristics of the children were assessed, the asthma predictive index and temporal pattern of wheeze were determined. The serum levels of vitamin D, zinc, and copper were measured. Pearson correlation analysis was used to evaluate the relationship between homogeneously distributed variables.ResultsThirty-two of the seventy-three children (43.8%) had more than three wheezing attacks (recurrent wheezing). The Asthma Predictive Index index was positive in 26 patients (35.6%). When classified to temporal pattern of wheeze, fifty-three of the study group (72.6%) had episodic wheezing and the remainder (27.4%) was classified as multiple-trigger wheezing. We found no overall significant difference between the study and control group in terms of vitamin D and trace elements . The vitamin D and zinc levels were significantly lower and serum copper and copper/zinc ratio was significantly higher in patients with recurrent wheezing (p =0.03, p <0.01, p =0.013, p <0.01, respectively) positive Asthma Predictive Index and multiple-trigger temporal pattern of wheeze compared with patients with non- recurrent wheezing, negative Asthma Predictive Index and episodic temporal pattern of wheeze.ConclusionIt may be postulated that for the determination of asthma risk in patients with recurrent wheezing, the serum level of vitamin D, copper and zinc can be used as a routine biomarker alongside the Asthma Predictive Index and temporal pattern of wheeze.

Asociación entre el índice de predicción de asma y el óxido nítrico exhalado en niños pequeños con sibilancias recurrentes

It is difficult to make an early identification of which children with recurrent wheezing will develop asthma in the following years. The Asthma Predictive Index (API) is a questionnaire based on clinical and laboratory parameters used for this end. The measurement of fractional exhaled nitric oxide (FE NO) has been used as a marker of eosinophilic airway infammation in asthma patients. Objective. To determine the association between the Asthma Predictive Index and FE NO levels in children younger than 3 years old with recurrent wheezing. Materials and methods. Observational, cross sectional study. Children younger than 36 months old with 3 or more episodes of bronchial obstruction in the past year who were inhaled corticosteroid-naive or leukotriene receptor antagonist-naive were included. After recording clinical data, FE NO was measured by a chemiluminescence analyzer during tidal breathing (online method). Results. A total of 52 children aged 5-36 months old were included. Patients with a positive API accounted for 60% of the population and had higher levels of FE NO than those with a negative API, with a median (range) of 13.5 ppb (0.7-31) versus 5.6 ppb (0.1-20.8), respectively (p <0.01). A high FE NO (>8 ppb) was observed in 74% of children with a positive API and in 26% of those with a negative API (p <0.01). Conclusions. This study found an association between high levels of exhaled nitric oxide and a positive Asthma Predictive Index in children younger than 3 years old with recurrent wheezing.

Young Infants with Recurrent Wheezing and Positive Asthma Predictive Index Have Higher Levels of Exhaled Nitric Oxide

Objective. The aim of this post hoc analysis was to establish the relationship between FENO levels and the asthma predictive index (API) among infants with recurrent wheezing. Methods. Infants with recurrent wheezing (three or more episodes) were recruited consecutively and online FENO tests at tidal breathing with multiple breaths were performed. Results. Twenty-seven (84%) out of 32 infants (median age of 12 months) who met the inclusion criteria for this post hoc analysis, successfully performed the FENO determinations. Eighteen (66%) infants were classified with positive stringent API. FENO levels were significantly higher among patients with positive API than those with negative (median [IQR] of 12.3 [14.8] ppb vs. 4.1 [7.9] ppb, respectively, p = .016). Furthermore, FENO and positive API had a significant correlation (Spearman’s rho, ρ = 0.4741, p = .0125). After logistic regression analysis including FENO levels, gender, age, and use of controller therapy, FENO was the only variable that was marginally related to API (OR = 1.12, 95% CI: 0.99–1.27, p = .07). Conclusion. Infants with recurrent wheezing who had a positive stringent API already had higher FENO levels than those with a negative API. This finding needs to be corroborated in a larger prospective study.

Ciclesonide in wheezy preschool children with a positive asthma predictive index or atopy

Few large-scale studies have examined inhaled corticosteroid treatment in preschool children with recurrent wheeze. We assessed the effects of ciclesonide in preschool children with recurrent wheeze. We included children 2-6 yrs with recurrent wheeze and a positive asthma predictive index or aeroallergen sensitization to, excluding patients with episodic viral wheezing. After a 2-4-week baseline period, patients with ongoing symptoms or rescue medication use were randomised to once-daily ciclesonide 40, 80, 160 μg or placebo for 24 weeks. The number of wheeze exacerbations requiring systemic corticosteroids was unexpectedly low in all groups: 25 (10.2%) in placebo group, as compared to 11 (4.4%), 18 (7.3%), and 17 (6.7%) in ciclesonide 40, 80, and 160 μg, respectively. The difference in time to first exacerbation was not significantly different between groups (p = 0.786), but the difference in exacerbation rates between placebo and the pooled ciclesonide groups was (p = 0.03). Large and significant (p < 0.0001) improvements in symptom scores and rescue medication use occurred in all groups, including placebo. Improvements in FEV(1) and FEF(25-75) (measured in 284 4-6 yr olds) were larger in the ciclesonide than in the placebo group. No differences in safety parameters (adverse events, height growth, serum and urinary cortisol levels) between ciclesonide and placebo were observed. In preschool children with recurrent wheeze and a positive asthma predictive index, ciclesonide modestly reduces wheeze exacerbation rates and improves lung function. A large placebo response and unexpected selection of patients with mild disease may have affected outcomes, highlighting the heterogeneity of preschool wheezing disorders.