Regulatory T cell and cytokine changes in children undergoing 3 days rush venom immunotherapy.

BACKGROUND: Rush venom immunotherapy (VIT) is the recommended treatment for patients with Hymenoptera anaphylaxis. Specific data regarding regulatory T cell and cytokine changes in children receiving rush VIT are sparse. OBJECTIVE: To study the changing of CD4+CD25+FOXP3+ regulatory T cells (Treg) and serum cytokines in children undergoing 3 days rush VIT. METHODS: Children younger than 15 years with systemic reaction to Hymenoptera who had evidence of IgE sensitization to Hymenoptera were enrolled for 3 days rush VIT. Peripheral blood CD4+CD25+FOXP3+ Treg and serum IL-4, IL5, IL-13, IFN-γ, and IL-10 were measured at baseline before rush VIT, achieving maintenance dose, 6 months, and 12 months after reaching maintenance dose. Specific IgE to Hymenoptera was measured at baseline and 12 months after VIT. RESULTS: A total of 15 children (11 boys and 4 girls) aged 6-15 years (mean age, 10 years) were enrolled. Four children were allergic to bee and 11 children were allergic to Vespid. The levels of CD4+CD25+FOXP3+ Treg were significantly increased at 6 months after maintenance dose compared with baseline (6.58% VS 4.01%, p = 0.001). Serum IL-13, IFN-γ, and IL-10 levels did not change significantly from baseline. However, there was a significant reduction of IL-4 in the serum at 12 months after MN when compared to the baseline levels. The systemic reaction requiring epinephrine intramuscular injection occurred only in 1 case who was on Vespid venoms rush VIT. CONCLUSIONS: Three days rush VIT provide acceptable systemic reaction and able to increase the number of CD4+CD25+FOXP3+ Treg in children.

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).

Safety and efficacy of ant rush immunotherapy in children.

BACKGROUND: The Rush Immunotherapy (RIT) protocol is a valid alternative in order to reach the maintenance phase early. However, there are scarce studies in the literature that have evaluated the safety and the efficacy of an ant RIT process in children. OBJECTIVE: To evaluate the safety and the efficacy of an ant RIT protocol and to identify the risk factors for systemic reactions (SRs) during an RIT procedure in children. METHOD: A retrospective review was conducted for those children who were receiving an ant RIT procedure. The 3-day RIT protocol consisted of hourly subcutaneous injections in order to achieve a 0.5 ml maintenance dose of a 1:100 weight/ volume (wt/vol) of the Solenopsis invicta whole body extract. The safety for an RIT procedure was monitored by using the World Allergy Organization Subcutaneous Immunology Systemic Reaction Grading System. The efficacy was assessed by the reactions after a field ant re-sting. RESULT: A total of 20 children who were receiving an ant RIT therapy were reviewed. The mean age was 9.5±3.07 years. There were 6 systemic reactions (SRs) from 324 injections during the RIT procedure (1.85%). All of the systemic reactions were Grade 1-2. There were no associations of SRs regarding age, gender, an atopic history, or the levels of immunoglobulin E (IgE) sensitization to the ants. Among the 14 patients who experienced a field ant re-sting, 4 (28.5%) patients developed Grade 3 SRs. These Grade 3 reactions were resolved after an increase of the maintenance dose to 0.5 ml of a 1:50 wt/vol. There was a significant difference in the mean age of those children who had ant re-sting systemic reactions and those who had no reactions (6.75±0.95 year vs. 10.8±3.29, p=0.036). CONCLUSION: Rush immunotherapy with ant in children is safe and it has a low occurrence of severe systemic reactions. It is an alternative treatment for those patients requiring a rapid protection.

Mosquito allergy in children: Clinical features and limitation of commercially-available diagnostic tests.

OBJECTIVE: To determine the clinical features of mosquito allergy in children and the ability of commercially available mosquito allergy tests to detect children with mosquito allergy in Thailand. METHODS: Patients with mosquito allergy aged 1 month to 18 years were recruited. Demographic data, history of mosquito allergy (onset of the reaction, reaction type) and clinical features were recorded. A skin prick test using a commercially available whole body allergen extract from Culex pipiens was performed, and serum was tested for specific IgE antibodies to Aedes communis whole body extract. RESULTS: A total of 50 patients with mosquito allergy were enrolled. The median age of enrolled children was 6.2 years with an average age of onset of 2 years [interquartile range (IQR) 1-6]. Half of the children were female. The most common skin lesion from mosquito allergy was erythematous papules (n = 45, 76.3%). The majority of children (58%) were in stage 3 (immediate and delayed type of reactions). One child (2%) was in the desensitization stage after 4.6 years of symptoms. The causative mosquito species could be identified only in 26 (52%) children: 16 (32%) children were positive for Aedes communis, 17 (34%) children were positive for Culex pipiens and 7 (14%) children were positive for both Aedes communis and Culex pipiens. Having positive IgE antibodies against Aedes communis was significantly more common in boys (n = 13, 48.1%) than girls (n = 3, 13%) (p < 0.01). CONCLUSIONS: Immediate and delayed skin reaction is the most common manifestation in mosquito allergy children. Commercially available tests for mosquito allergy can detect only 30-50% of children with mosquito allergy.

Skin testing with ß-lactam antibiotics for diagnosis of ß-lactam hypersensitivity in children.

OBJECTIVE: Skin testing with penicilloyl-polylysine (PPL) and a minor determinant mixture (MDM) were previously recommended for evaluating ß-lactam hypersensitivity. However, PPL and MDM have not been commercially available. This study was to determine the negative predictive value (NPV) of skin testing with ß-lactam antibiotics for the diagnosis of ß-lactam hypersensitivity. METHOD: Patients age 1-18 years old with a history of ß-lactam hypersensitivity were evaluated by skin tests (a skin prick test, an intradermal test) with penicillin G, ampicillin, amoxicillin-clavulanic acid, and the suspect ßlactam. The patients who had a negative skin test were performed with a drug provocation test (DPT) in a 3-dose-graded challenge. The hypersensitivity reactions were classified into immediate and non-immediate reactions. RESULTS: A total of 126 patients were evaluated for ß-lactam hypersensitivity. Twenty two patients (17.4%) were confirmed with a ?-lactam hypersensitivity. 12 (54.54 %) of them were confirmed by a skin test. There was no systemic reaction occurring after the skin tests. Ten patients (9.6%) from 104 patients with a negative skin test showed reactions after a DPT providing the NPV of the skin test with a 91.2% value. CONCLUSIONS: Among those children with a history of ß-lactam hypersensitivity, skin testing with penicillin G, ampicillin, amoxicillin-clavulanic acid, and the suspect ß-lactam was safe and provided a good NPV when PPL and MDM were unavailable. However, a skin test with ß-lactam antibiotics alone did not provide a high sensitivity, thus a DPT procedure was necessary in order to confirm the diagnosis of ß-lactam hypersensitivity.

Pediatric anaphylaxis: triggers, clinical features, and treatment in a tertiary-care hospital.

BACKGROUND: Anaphylaxis is a life-threatening condition. There are limited data about its etiology and clinical characteristics in Asian children with anaphylaxis. OBJECTIVE: To investigate triggers, presenting symptoms, treatment and clinical course of anaphylaxis in Thai children. METHOD: Medical record of children who were diagnosed with anaphylaxis between 2004 and 2013 at Ramathibodi Hospital, Bangkok, Thailand were reviewed. RESULTS: One hundred-seventy two episodes of anaphylaxis occurred in 160 children (91 boys, 69 girls) aged 3 months to 18 years. Anaphylaxis increased from 2.7 cases/1000 pediatric admission to 4.51 cases/1000 pediatric admission between 2004-2008 and 2009-2013. The main causes were food (34.92%), drug (33.1%), blood components (23.8%), insect sting (9%), and unidentified causes (2.8%). Allergy to the triggers was known prior to anaphylaxis in 42 episodes (24.6%). Treatment consisted of epinephrine intramuscularly (93.8%), corticosteroids (92.5%), H1antihistamines (96%), H2antihistamines (50%), and ß2agonists nebulization (35.1%). Biphasic anaphylaxis occurred in 8.7% of the documented episodes and severe anaphylaxis in 34.3% of the documented episodes. Biphasic anaphylaxis and severe anaphylaxis were associated with fewer administrations of intramuscular epinephrine (OR 0.08 [95% CI 0.014-0.43]; p =0.01 and OR 9.36 [95% CI 2.5-34.7]; p <0.001 respectively). There were no fatality cases. There were associations between triggers of anaphylaxis and atopic histories, patients with severe anaphylaxis and cardiovascular involvement (p <0.01). CONCLUSIONS: The incidence of anaphylaxis in Thai children is increasing. Anaphylaxis in children commonly occurred without the histories of prior reaction to the causative agent. Less frequent treatment with intramuscular epinephrine was associated with biphasic and severe anaphylaxis. A better knowledge of patterns and causes of anaphylaxis might contribute to a better management.

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.

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.

Immunologic changes after house dust mite modified rush subcutaneous immunotherapy in allergic rhinitis children.

BACKGROUND: House dust mites (HDM) are the major causative allergen for allergic rhinitis. The sole disease-modifying therapy for allergic rhinitis is allergen immunotherapy (AIT). Rush immunotherapy is the accelerated build-up schedules to reach the target maintenance dose. OBJECTIVE: To evaluate the kinetic changes of peripheral blood CD4+CD25+FOXP3+ regulatory T cells (Treg) and serum cytokines in children undergoing 2-day modified rush HDM AIT. METHODS: Children aged 5-15 years with allergic rhinitis were enrolled for a 2-day modified rush HDM AIT. Peripheral blood CD4+CD25+FOXP3+ Treg, serum interleukin (IL)-4, IL-13, interferon-γ, and IL-10 were measured at baseline, finishing rush, achieving maintenance dose, 6 months, and 12 months after reaching maintenance dose. Specific IgE (sIgE) to HDM was evaluated at baseline and 12 months after getting the maintenance dose. Rhinitis symptoms were assessed daily using a daily card. RESULTS: A total of 12 children with a mean age of 13 years were enrolled. Rhinitis symptom-free days per month increased significantly after reaching the maintenance dose compared to baseline (from 9.5 days to 19.5 days, p = 0.002), and the maximum improvement was seen at 1 year. The levels of Treg were significantly increased at 6 months after maintenance dose compared to baseline level (6.27%±1.63% vs. 3.83%±1.80%, p < 0.001). After treatment, there were significantly decreased serum IL-13 at 1 year after maintenance but no significant changes in sIgE to HDM. The systemic reaction during AIT occurred 7 episodes from 119 shots (5.9%). CONCLUSION: Two-day modified rush HDM AIT provides acceptable systemic reactions and increases the number of CD4+CD25+FOXP3+ Treg in children.

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.

Novel salivary gland allergens from tropical mosquito species and IgE reactivity in allergic patients.

BACKGROUND: Mosquito allergy is common in tropical countries but remains under-diagnosed. This may be due to the lack of knowledge and diagnostic tools for tropical mosquito allergens. OBJECTIVE: We aimed to characterize allergens from tropical mosquito species and investigate IgE reactivity in mosquito-allergic patients to the salivary gland proteins from these mosquitoes. METHODS: Salivary gland extract (SGE) from 4 mosquito species, highly distributed in the tropics, including Aedes aegypti, Aedes albopictus, Culex quinquefasciatus, and Anopheles dirus b, were studied. SGE-specific IgE and IgG ELISA were developed, and serum from 64 mosquito-allergic and 22 non-allergic healthy control subjects was assayed. Further investigations using IgE-immunoblots followed by mass spectrometry analysis were performed to identify and characterize allergens from each species. RESULTS: Mosquito-allergic subjects have detectable serum IgE to SGE derived from local mosquito species, while the IgE levels to Aedes communis using commercially available ELISA were mostly minimal. IgE-immunoblot analysis and mass spectrometry identified 5 novel mosquito allergens from A. albopictus (Aed al 2, Aed al 3), C. quinquefasciatus (Cul q 2.01, Cul q 3), and A. dirus b (Ano d 2). Interestingly, 4 of the 5 new allergens belong to the D7 protein family. CONCLUSIONS & CLINICAL RELEVANCE: Five novel allergens from 3 tropical mosquito species were characterized. The majority of mosquito-allergic subjects who live in the tropics have IgE reactivity to these allergens. Our study paves the way for the development of diagnostic tests, component-resolved diagnostics, and future immunotherapy for mosquito allergy in tropical countries.

Efficacy of Nasal Cellulose Powder in the Symptomatic Treatment of Allergic Rhinitis: A Randomized, Double-Blind, Placebo-Controlled Trial.

PURPOSE: Nasal Cellulose Powder (NCP), which can prevent from binding an allergen to nasal mucosa, may reduce allergic rhinitis (AR) symptoms in dust mite-sensitized children. This study was conducted to assess the efficacy of NCP in improving clinical symptoms of a nasal airflow limitation and the response of nasal inflammatory cells. METHODS: Children with dust mite-sensitized AR aged 6-18 years were recruited. After a 4-week run-in period, NCP or a placebo was administered, 1 puff per nostril 3 times daily for 4 weeks. The nasal provocation test (NPT) with Dermatophagoides pteronyssinus (Der p) was performed before and after treatment. The daily symptom scores (DSS), daily medication scores (DMS), the peak nasal inspiratory flows (PNIF), nasal airway resistance (NAR), as well as the maximum tolerated dose of NPT and eosinophil counts in nasal scraping, were evaluated. RESULTS: Sixty children (30 NCP and 30 placebos) were enrolled. Before treatment, there were no significant differences in age, dust mite control measures, DSS, DMS, PNIF, NAR, the maximum tolerated dose of NPT, or nasal eosinophil scores between children receiving NCP and placebos. After treatment, there were no significant differences between the NCP and placebo groups in the median (range) of the outcomes-DSS: 2.06 (0.18-3.77) vs 1.79 (0.08-7.79), P=0.756; DMS: 1.60 (0-5.13) vs 0.56 (0-4.84), P=0.239; PNIF (L/min): 110 (60-160) vs 100 (50-180), P=0.870; NAR (Pa/cm³/s): 0.40 (0.20-0.97) vs 0.39 (0.24-1.32), P=0.690; the maximum tolerated dose of NPT and the nasal eosinophil scores: 1 (0-4) vs 1 (0-4), P=0.861. CONCLUSIONS: NCP treatment may not be more effective than placebo treatment in dust mite-sensitized AR children.

Detection of ß-lactoglobulin in human breast-milk 7 days after cow milk ingestion.

BACKGROUND: ß-lactoglobulin (BLG), a major allergen in cow milk (CM) can be detected in human breast-milk (BM) and is associated with exacerbation of symptoms in breastfed infants with cow milk protein allergy (CMPA). Currently, it is not known how long lactating mothers who consume dairy products need to withhold breastfeeding. OBJECTIVE: To elucidate the kinetics of BLG in BM after maternal ingestion of a single dose of CM. METHODS: Nineteen lactating mothers, four of whom had infants with CMPA, were instructed to avoid CM for 7 days before ingesting a single dose of CM and to continue to withhold CM thereafter throughout the study period. BLG was measured by ELISA in BM from 15 mothers of healthy infants before and at 3, 6 and 24 h, and 3 and 7 days after CM ingestion. Four pairs of mothers and CMPA infants were enrolled for BM challenge after the mothers had ingested CM. RESULTS: After CM ingestion, the level of BLG in BM increased significantly from 0.58 ng/ml (0.58 g/L) (IQR 0.38-0.88) to a peak level of 1.23 ng/ml (IQR 1.03-2.29), p < 0.001. The BLG level on day 3 (1.15 ng/ml, IQR 0.89-1.45) and day 7 (1.08 ng/ml (IQR 0.86-1.25) after CM ingestion was significantly higher than baseline (p = 0.01 and p = 0.001, respectively). BLG was detected in all BM samples from the four mothers of CMPA infants after CM ingestion, and the level was not different from that in the mothers of the 15 healthy infants. Three of the four CMPA infants developed symptoms such as maculopapular rash and hypersecretion in the airways after BM challenge. CONCLUSIONS: BLG can be detected in BM up to 7 days after CM ingestion. Lactating mothers should suspend breastfeeding to CMPA infants more than 7 days after CM ingestion.