Skin prick test and serum specific IgE in predicting dust mite-induced allergic rhinitis diagnosed from nasal provocation test in chronic rhinitis children.

BACKGROUND: Allergen skin prick test (SPT) and serum specific immunoglobulin E (sIgE) are effective diagnostic tests in allergic rhinitis (AR), however, positive results may not always correlate with clinical allergies. A nasal provocation test (NPT) can identify the causative allergen for immunotherapy, but it's not routinely performed. OBJECTIVE: To establish the cutoff value for the house dust mite (HDM) SPT mean wheal diameter (MWD) and HDM sIgE level for identifying children with HDM-induced AR diagnosed from NPT. METHODS: Children aged 5 to 18 years old with chronic rhinitis were evaluated by HDM SPT, sIgE, and NPT. Children with positive NPT results indicated HDM-induced AR. The cutoff values of the HDM SPT and sIgE level for predicting positive NPT were determined using a receiver operating characteristic curve. RESULTS: A total of 245 children with a mean age of 9.53 ± 3 years were enrolled. HDM SPT results were positive (≥ 3 mm) in 160 (65.3%) children. HDM NPT results were positive in 176 (71.8%) children. Among children with positive HDM SPT (n = 160), 153 children (95.6%) were confirmed as having AR on NPT findings. The cutoff values for positive NPT responses were 6.6 mm for HDM SPT (yielding 100% specificity and 100% positive predictive value) and 17.0 kUA/L for sIgE (98.6% specificity and 99.2% positive predictive value). CONCLUSIONS: This study proposes HDM SPT and sIgE cutoff values for use in the diagnosis of HDM-induced AR based on NPT. These cutoff values can be used to identify HDM-induced AR children who might benefit from immunotherapy.

Effect of dyslipidemia, obesity, and atopic status on exhaled and alveolar nitric oxide in asthmatic children.

BACKGROUND: Dyslipidemia and obesity contribute to a pro-inflammatory state. Eosinophilic airway inflammation can be indirectly measured by fractional exhaled nitric oxide (FeNO) produced in the airways of asthmatic subjects. OBJECTIVE: To compare exhaled nitric oxide (NO) and alveolar NO in asthmatic children with and without dyslipidemia. METHODS: Asthmatic children (5-18 years old) had fasting serum low-density lipoprotein cholesterol, triglyceride, and high-density lipoprotein cholesterol (HDL-C) concentrations, and C-reactive protein (CRP) concentrations measured. FeNO was measured at constant flow rates of 20, 50, 100, and 300 ml/s by the chemiluminescence method. NO concentrations in tissue of the upper airways (CawNO) and the total flux of NO in the conducting airways (JawNO) were determined through FeNO at 20, 100, and 300 ml/s using a mathematical model. The atopic status was assessed using the skin prick test for aero-allergens. RESULTS: One hundred forty-one asthmatic children were enrolled with a mean (standard deviation) age of 11.82 (3.38) years. Sixty-four (45.4%) children had dyslipidemia and 20 (14.2%) were obese. Children with low HDL-C concentrations had significantly higher CawNO and JawNO than those with normal HDL-C concentrations (both p = 0.03). Asthmatic children with obesity had higher CRP concentrations than those with a normal weight (p < 0.001). Atopic children had a significantly higher FeNO, CawNO, and JawNO than non-atopic children (all p < 0.05). CONCLUSIONS: This study suggests an effect of HDL-C on CawNO and JawNO in asthmatic children. An intervention that normalizes HDL-C concentrations may be beneficial for airway inflammation in asthmatic children.

Serum Periostin Predicts Wheezing Exacerbation: A Prospective Study in Preschool Children with Recurrent Wheezing.

INTRODUCTION: Wheezing is a common problem in preschool children. Currently, there are no reliable biomarkers that can predict subsequent wheezing in preschool children. This study aimed to compare serum periostin levels between preschool children with and without recurrent wheezing and investigate its utility for predicting acute wheezing exacerbation. METHODS: Children aged 2-5 years with recurrent wheezing and healthy control children were enrolled. They were evaluated for serum periostin level at enrollment and subsequently followed for wheezing episodes in a 1-year prospective study. RESULTS: A total of 122 children were enrolled. Children in the recurrent wheezing group (n = 80) had a greater median serum periostin level (1,122.32 pg/mL [<10-6,978.93]) than that of the healthy control group (n = 40) (<10 pg/mL [<10-2,116.69]), p value = 0.006. After 1-year follow-up, subjects who experienced subsequent wheezing exacerbation episodes had a greater median of periostin level (5,321 pg/mL) compared with those with no exacerbation (<10 pg/mL), p value = 0.014. ROC curve analysis revealed that the level of serum periostin >1,200 pg/mL, corresponding to 78.9% sensitivity and 64.6% specificity, with an AUC of 0.701, p value = 0.009, could be a predictor for acute wheezing exacerbation within 1 year. Besides, subjects with serum periostin >1,200 pg/mL had greater odds of subsequent wheezing episodes compared with those with lower levels of serum periostin (adjusted odds ratio 10.0, 95% confidence interval: 2.3-43.5). CONCLUSIONS: Preschool children with recurrent wheezing have a greater serum periostin level than healthy control. Serum periostin may be a valuable biomarker for predicting acute wheezing exacerbations in the following year.

Association of Dyslipidemia and Respiratory Resistance Assessed by the Forced Oscillation Technique in Asthmatic Children.

PURPOSE: This study aimed to evaluate the associations between dyslipidemia and pulmonary function parameters assessed by spirometry and the forced oscillation technique in asthmatic children. METHODS: Asthmatic children (5-18 years old) had fasting serum lipid profiles including low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) concentrations, and C-reactive protein (CRP) measured. Pulmonary function tests were assessed by spirometry and the forced oscillation technique (FOT). RESULTS: One hundred forty-one asthmatic children were enrolled with a mean (SD) age of 11.82 (3.38) years. Eighty-eight (62.4%) children were boys, 64 (45.4%) had dyslipidemia, and 20 (14.2%) were obese. Among the children with dyslipidemia, a high LDL-C concentration (65.6%) was the most common form of dyslipidemia, followed by high TC (57.8%), high TG (35.9%), and low HDL-C concentrations (15.6%). Multivariable analysis showed significant associations between HDL-C concentrations and respiratory resistance at 5 Hz (R5) and respiratory resistance at 20 Hz (R20), and TC concentrations were modestly associated with reactance at 5 Hz (X5), the frequency of resonance (Fres), and the area of reactance (ALX). Asthmatic children who had high LDL-C concentrations had a significantly higher expiratory phase R5, whole breath R20, and expiratory phase R20 than those in children with normal LDL-C concentrations. CONCLUSION: This study suggests an association of blood cholesterol, especially HDL-C and LDL-C, and respiratory resistance measured by the FOT, irrespective of the obesity status. An intervention for improving LDL-C and HDL-C concentrations may be beneficial on lung function parameters in asthmatic children. CLINICAL TRIAL REGISTRATION: TCTR20200305005; date of registration: 03-04-2020 (retrospectively registered).

Effect of vitamin D on lung function assessed by forced oscillation technique in asthmatic children with vitamin D deficiency: A randomized double-blind placebo-controlled trial.

BACKGROUND: The role of vitamin D and asthma in pulmonary function changes showed conflicting result. OBJECTIVE: To evaluate if vitamin D treatment would improve lung function assessed by forced oscillation technique (FOT) in vitamin D deficient asthmatic children. METHODS: A randomized double-blind placebo-controlled trial was performed in children, aged 3-18 years with well controlled asthma. Serum total 25(OH)D and FOT parameters including respiratory resistance at 5 Hz (R5), at 20 Hz (R20), respiratory reactance at 5 Hz (X5) and area of reactance (ALX), resonance frequency (Fres) were evaluated at baseline, 1 month and 3 months. Vitamin D deficient patients (serum total 25(OH)D < 20 ng/ml) were randomized to receive treatment with vitamin D2 (tVDD) or placebo (pVDD). Non-vitamin D deficient patients (nVDD) received placebo as a control group. RESULTS: A total of 84 children were recruited, 43 patients in nVDD group, 20 in tVDD group and 21 in pVDD group. There were no significant differences in age, sex, height and weight among groups. There were no significant differences of FOT parameters among groups at all visits. There was a trend toward decrease in R5/R20 from baseline to 1 month and 3 months visit in all groups, but the statistically significant improvement was observed only in nVDD group. Serum 25(OH)D showed no correlation with % predicted of FOT measures. CONCLUSIONS: Vitamin D treatment in asthmatic children who had vitamin D deficiency may have no short term beneficial effect on pulmonary function assessed by FOT. Vitamin D supplementation in all asthmatic patient needs further study.

Reference value of Forced Oscillation Technique for healthy preschool children.

BACKGROUND: The reference values of Forced Oscillation Technique (FOT) parameters of the inspiratory and expiratory phase for preschool children have not yet been established. OBJECTIVE: To evaluate FOT measures in Thai healthy preschool children. METHODS: Preschool children, aged 3-6 years, were screened. Children who were positive for the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire for asthma, positive family history of allergic diseases, recent lower respiratory tract infections, and environmental tobacco smoke were excluded. FOT parameters, including resistance (Rrs), reactance (Xrs), frequency of resonance (Fres) and area of reactance (ALX), were measured. RESULTS: A total of 390 healthy children with the mean age of 5.1 ± 0.9 years were enrolled. FOT was successfully performed in 378 children (96.9%). The mean (SD) for the whole breath (WB) resistance at 5Hz (R5), 20 Hz (R20) and R5-20 were 11.49 (2.69) cmH2O/L/s, 9.46 (2.19) cmH2O/L/s and 2.02 (0.82) cmH2O/L/s, respectively. The median (IQR) for WB reactance at 5Hx (X5), Fres and ALX were -1.51 (-2.37 to -0.96) cmH2O/L/s, 11.17 (8.50-15.65) Hz, and 7.53 (3.72-14.32) cmH2O/L/s, respectively. Significantly difference in WB R5, R20, X5, Fres and ALX between male and female children were demonstrated. The expiratory phase R5, R20, R5-20 were significantly higher than those of the inspiratory phase (p < 0.001). There are significant correlations between the height and FOT parameters. Reference curve for the FOT parameters was generated based on height using the lambda-mu-sigma (LMS) method. CONCLUSIONS: Reference curve of FOT parameters measured in healthy preschool children were demonstrated. Majority of preschool children could perform FOT method.

Improvement of inattentive and hyperactive symptoms after real-life rhinitis treatment in school-aged children.

OBJECTIVES: Rhinitis treatment may improve attention-deficit/hyperactivity symptoms in children. The current study evaluated changes in inattentive and hyperactive symptoms after treatment in children with chronic rhinitis. METHODS: Children aged 5-18 years with chronic rhinitis were enrolled in a 3-month prospective study. The nasal provocation test for house dust mites (HDM) and evaluation of allergen sensitization, including the skin prick test and the Phadiatop test, were performed. The severity of rhinitis was assessed according to the ARIA guideline. The total nasal symptom score and the Vanderbilt ADHD Diagnostic Rating Scale (VADRS) score for assessing inattentive and hyperactive symptoms were recorded at baseline and at 1 and 3 months after rhinitis treatment. Children with rhinitis were classified into the following two groups: HDM-induced allergic rhinitis (AR group) and non-allergic rhinitis to HDM (NAR group) based on the NPT. RESULTS: Overall, 83 children completed the 3-month prospective study, and they had a mean age of 9.12 ± 2.89 years and 44.6% were boys. After rhinitis treatment, VADRS scores assessed by the parents and teachers were significantly decreased compared with those at baseline (p = 0.005). In subgroup analysis, 61 (73.49%) children had AR, and 22 (26.5%) children had NAR. No significant difference in the baseline VADRS score was found between the AR and NAR groups. After treatment, VADRS scores assessed by the parents and teachers were significantly decreased only in the AR group (p < 0.001). Forty-five (54.2%) children had moderate persistent rhinitis, 29 (34.9%) had mild persistent rhinitis, and 9 (10.8%) had mild intermittent symptoms. There were no differences in baseline VADRS scores assessed by the parents and teachers among children with mild intermittent, mild persistent, or moderate persistent symptoms. The total nasal symptom score and VADRS score were significantly decreased after treatment for all severities of rhinitis compared with those at baseline. A greater baseline VADRS score was associated with substantial improvement of inattentive and hyperactive symptoms after treatment. CONCLUSION: Early treatment for rhinitis may improve inattentive and hyperactive symptoms in school-aged children.

Airway Nitric Oxide in Children with HDM-Induced Allergic Rhinitis.

BACKGROUND: Rhinitis is a common problem in children. Airway nitric oxide (NO) was proposed to represent eosinophilic inflammation. OBJECTIVES: To evaluate airway NO level in children with house dust mite (HDM)-induced allergic rhinitis. METHODS: Children aged 5 to 18 years old with moderate-severe persistent rhinitis and positive result for the HDM nasal provocation test (NPT) was enrolled. The nasal symptoms evaluated by total nasal symptom score (TNSS) and visual analog scale (VAS) were recorded. Skin prick test (SPT) to common aeroallergens, fractional exhaled nitric oxide (FeNO), nasal nitric oxide (nNO), and blood test for specific IgE (sIgE) to HDM was measured. Rhinitis severity was categorized as severe if the VAS score > 7. RESULTS: Forty-eight children with HDM-induced allergic rhinitis with the mean age of 9.3 ± 2.4 years were enrolled. nNO levels and VAS score were significantly correlated (R = 0.398, P = .005). Children with severe rhinitis had significantly higher nNO levels than moderate rhinitis (1652.05 vs 941.30 parts per billion [ppb], P = .002), while there was no difference in FeNO level. ROC curve analysis demonstrated the cut-off value of nNO at 1350 ppb (AUC 0.764, 95% CI: 0.616-0.911, P = .002) for detecting severe HDM-induced allergic rhinitis with the sensitivity of 78% and the specificity of 71%. The level of FeNO in children who had HDM mean wheal diameter (MWD) > 8 mm was significantly higher than those with HDM MWD of 3 to 8 mm and those with a negative test (39.7 vs 14.3 vs 14.4 ppb; P = .006, respectively). Children who had sIgE to HDM < 0.35 KUA/L had significantly lower FeNO than those with sIgE to HDM 0.35 to 50 KUA/L and >50 KUA/L (9.5 vs 19.7 vs 40.4 ppb; P = .029, respectively). CONCLUSIONS: Cut-off value for the diagnosis of severe HDM-induced chronic rhinitis was proposed. Rhinitis children who had a higher degree of HDM sensitization had a higher level of FeNO.

Skin Prick Test Versus Phadiatop as a Tool for Diagnosis of Allergic Rhinitis in Children.

BACKGROUND: Skin prick test (SPT) or Phadiatop, a multi-allergen IgE screening test, was used as a tool for detecting aeroallergen sensitization. OBJECTIVE: To compare SPT and Phadiatop as a tool for diagnosis allergic rhinitis (AR) using the nasal provocation test (NPT) as a comparative standard. METHODS: Children aged 5-18 years with rhinitis symptoms more than 6 times in the past year were enrolled. SPT to 13 common aeroallergens, serum for Phadiatop, and NPT to Dermatophagoides pteronyssinus (Der p) were performed. NPT to mixed cockroach (CR) were performed in children who had CR sensitization and negative NPT to Der p. Children who had a disagreement between the result of SPT and Phadiatop or having negative results were evaluated for specific IgE (sIgE) to common aeroallergens. RESULTS: One hundred-forty children were enrolled with the mean age of 9.8 ± 3 years, 56% were male. Of 92 children (65.7%) with positive SPT to any aeroallergens, 88 children (95.6%) were sensitized to house dust mite (HDM). NPT showed positive results in 97 children (69.3%). Of 48 children who showed negative SPT, 4 children (8.3%) had sIgE to aeroallergens but NPT was positive in 1 child. Eighty-eight children (62.9%) had positive tests for Phadiatop and 4 (4.5%) of them had negative results for NPT to Der p. Among 52 children who had negative results for Phadiatop, 4 children (7.6%) had sIgE to aeroallergens but NPT was positive in 2 children (3.8%). SPT and Phadiatop showed 94.2% agreement: with Kappa 0.876, p < 0.001. Using NPT as a comparative standard for diagnosis for AR, SPT showed a sensitivity of 89.6% and specificity of 88.3% and Phadiatop provided the sensitivity of 88.6% and specificity of 95.3%. CONCLUSIONS: SPT to aeroallergen and Phadiatop have good and comparable sensitivity and specificity for the diagnosis of AR in children.

Forced oscillation technique as a predictor for loss of control in asthmatic children.

BACKGROUND: A reliable objective tool using as a predictor of asthma control status could assist asthma management. OBJECTIVE: To find the parameters of forced oscillation technique (FOT) as predictors for the future loss of asthma symptom control. METHODS: Children with well-controlled asthma symptom, aged 6-12 years, were recruited for a 12-week prospective study. FOT and spirometer measures and their bronchodilator response were evaluated at baseline. The level of asthma symptom control was evaluated according to Global Initiative for Asthma. RESULTS: Among 68 recruited children, 41 children (60.3%) maintain their asthma control between 2 visits (group C-C), and 27 children (39.7%) lost their asthma control on the follow-up visit (group C-LC). Baseline FOT parameters, including the values of respiratory resistance at 5 Hz (R5), respiratory resistance at 20 Hz (R20), respiratory reactance at 5 Hz, area of reactance, %predicted of R5 and percentage of bronchodilator response (%∆) of R5 and R20 were significantly different between C-C and C-LC groups. In contrast, only %∆ of forced vital capacity, forced expiratory volume in 1 second (FEV1), and FEF25%-75% (forced expiratory flow 25%-75%) were significantly different between groups. Multiple logistic regression analysis revealed that %predicted of R5, %∆R5, %predicted of FEV1 and %∆FEV1 were the predictive factors for predicting the future loss of asthma control. The following cutoff values demonstrated the best sensitivity and specificity for predicting loss of asthma control: %predicted of R5=91.28, %∆R5=21.2, %predicted of FEV1=89.5, and %∆FEV1=7.8. The combination of these parameters predicted the risk of loss of asthma control with area under the curve of 0.924, accuracy of 83.8%. CONCLUSION: Resistance FOT measures have an additive role to spirometric parameter in predicting future loss of asthma control.