Wheezing Characteristics and Predicting Reactivity to Inhaled ß2-Agonist in Children for Home Medical Care.

Background: Given that wheezing is treated with inhaled ß2-agonists, their effect should be reviewed before the condition becomes severe; however, few methods can currently predict reactivity to inhaled ß2-agonists. We investigated whether preinhalation wheezing characteristics identified by lung sound analysis can predict reactivity to inhaled ß2-agonists. Methods: In 202 children aged 10-153 months, wheezing was identified by auscultation. Lung sounds were recorded for 30 s in the chest region on the chest wall during tidal breathing. We analyzed the wheezing before and after ß2-agonist inhalation. Wheezing was displayed as horizontal bars of intensity defined as a wheeze power band, and the wheezing characteristics (number, frequency, and maximum intensity frequency) were evaluated by lung sound analysis. The participants were divided into two groups: non-disappears (wheezing did not disappear after inhalation) and disappears (wheezing disappeared after inhalation). Wheezing characteristics before ß2-agonist inhalation were compared between the two groups. The characteristics of wheezing were not affected by body size. The number of wheeze power bands of the non-responder group was significantly higher than those of the responder group (P < 0.001). The number of wheeze power bands was a predictor of reactivity to inhaled ß2-agonists, with a cutoff of 11.1. The 95% confidence intervals of sensitivity, specificity, and positive and negative predictive values were 88.8, 42, 44, and 81.1% (P < 0.001), respectively. Conclusions: The number of preinhalation wheeze power bands shown by lung sound analysis was a useful indicator before treatment. This indicator could be a beneficial index for managing wheezing in young children.

Wheeze Recognition Algorithm for Remote Medical Care Device in Children: Validation Study.

BACKGROUND: Since 2020, peoples' lifestyles have been largely changed due to the COVID-19 pandemic worldwide. In the medical field, although many patients prefer remote medical care, this prevents the physician from examining the patient directly; thus, it is important for patients to accurately convey their condition to the physician. Accordingly, remote medical care should be implemented and adaptable home medical devices are required. However, only a few highly accurate home medical devices are available for automatic wheeze detection as an exacerbation sign. OBJECTIVE: We developed a new handy home medical device with an automatic wheeze recognition algorithm, which is available for clinical use in noisy environments such as a pediatric consultation room or at home. Moreover, the examination time is only 30 seconds, since young children cannot endure a long examination time without crying or moving. The aim of this study was to validate the developed automatic wheeze recognition algorithm as a clinical medical device in children at different institutions. METHODS: A total of 374 children aged 4-107 months in pediatric consultation rooms of 10 institutions were enrolled in this study. All participants aged ≥6 years were diagnosed with bronchial asthma and patients ≤5 years had reported at least three episodes of wheezes. Wheezes were detected by auscultation with a stethoscope and recorded for 30 seconds using the wheeze recognition algorithm device (HWZ-1000T) developed based on wheeze characteristics following the Computerized Respiratory Sound Analysis guideline, where the dominant frequency and duration of a wheeze were >100 Hz and >100 ms, respectively. Files containing recorded lung sounds were assessed by each specialist physician and divided into two groups: 177 designated as "wheeze" files and 197 as "no-wheeze" files. Wheeze recognitions were compared between specialist physicians who recorded lung sounds and those recorded using the wheeze recognition algorithm. We calculated the sensitivity, specificity, positive predictive value, and negative predictive value for all recorded sound files, and evaluated the influence of age and sex on the wheeze detection sensitivity. RESULTS: Detection of wheezes was not influenced by age and sex. In all files, wheezes were differentiated from noise using the wheeze recognition algorithm. The sensitivity, specificity, positive predictive value, and negative predictive value of the wheeze recognition algorithm were 96.6%, 98.5%, 98.3%, and 97.0%, respectively. Wheezes were automatically detected, and heartbeat sounds, voices, and crying were automatically identified as no-wheeze sounds by the wheeze recognition algorithm. CONCLUSIONS: The wheeze recognition algorithm was verified to identify wheezing with high accuracy; therefore, it might be useful in the practical implementation of asthma management at home. Only a few home medical devices are available for automatic wheeze detection. The wheeze recognition algorithm was verified to identify wheezing with high accuracy and will be useful for wheezing management at home and in remote medical care.

Oral challenge tests for soybean allergies in Japan: A summary of 142 cases.

BACKGROUND: Soybeans are one of causative foods for infantile onset allergies in Japan. This study aimed to analyze the results of soybean challenge tests that were conducted over approximately 7 years at our institution. Using the test data, we sought to identify the responses and clinical profiles of patients with soybean allergies, and to investigate the relationship between the responses and soybean sensitization status. METHODS: Between July 2004 and May 2010, 142 cases (125 patients) underwent food challenge tests (100 g of silken tofu) for the diagnosis of soybean allergy or confirmation of their tolerance. The patients' characteristics, soybean sensitization status, and responses to the challenge tests were retrospectively evaluated. RESULTS: Among the subjects who underwent the soybean challenge test, the male/female ratio was 1.6 (87/55), and the mean age at the test was 2.8 ± 1.7 years. The positive rate for the challenge test was 38.7%. Induced symptoms were observed in the skin (81.8%), respiratory system (50.9%), and gastrointestinal system/mucosal membrane/anaphylaxis (12.7%). Intramuscular epinephrine was administered to all 7 patients who experienced an anaphylactic reaction. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic efficiency of soybean-specific IgE titers were low for predicting the responses to the challenge test. CONCLUSIONS: Soybean allergies were diagnosed in only 18% of the subjects with positive sensitization to soybeans. Therefore, soybean-specific IgE titers are not an effective predictor of a positive response to the challenge test.

Budesonide inhalation suspension versus methylprednisolone for treatment of moderate bronchial asthma attacks.

BACKGROUND: Owing to their side effects, administration of steroids for bronchial asthma attacks should be minimized. We investigated whether budesonide inhalation suspension (BIS) could replace intravenous steroid administration for the treatment of moderate bronchial asthma attacks. SUBJECTS AND METHODS: The subjects were children aged 5 years and younger hospitalized for moderate bronchial asthma attacks. Patients were randomly assigned to one of two groups: 20 patients received methylprednisolone (mPSL) and 20 were treated with BIS. The mPSL group began treatment with inhalation of procaterol hydrochloride (0.3 mL) and disodium cromoglycate (2 mL) three times a day and systemic administration of mPSL (1 mg/kg) three times a day. The BIS group began treatment with inhalation of procaterol hydrochloride (0.3 mL) and BIS (0.5 mg) three times a day. The frequency of inhalations and steroid administration was adjusted according to the severity of symptoms. The cortisol level at discharge was measured. RESULTS: There were no significant differences between the two groups in terms of the severity of attacks and duration of management, or in terms of therapeutic efficacy, duration of wheezing, or period of hospitalization. The frequency of inhalations on days 3 to 6 of hospitalization was lower in the BIS group than in the mPSL group, and the cortisol level at discharge was significantly higher in the BIS group (13.9 ± 6.1 µg/dL) than in the mPSL group (8.0 ± 2.1 µg/dL) (p = 0.008). CONCLUSION: In patients with recurrent wheezing or bronchial asthma of <5 years, the efficacy of BIS is equivalent or better than mPSL for moderate bronchial asthma attacks, and in contrast to steroid treatment, BIS treatment do not suppress adrenocortical function.

The skin prick test is not useful in the diagnosis of the immediate type food allergy tolerance acquisition.

BACKGROUND: Some studies have been reported about positioning of SPT in the diagnosis of food allergy. On the other hand, it is not yet clear about the positioning of SPT in the diagnosis of tolerance acquisition of the immediate type food allergy. METHODS: The retrospective study had been conducted for 236 egg allergic children (51.3 months in mean), 127 milk allergic children (53.4 months), and 96 wheat allergic children (42.6 months). The retrospective analysis of serum nonspecific and antigen-specific IgE levels, SPT, and OFC had been conducted for each allergic patient. All OFC had been conducted to verify the acquisition of tolerance against eliminated food. RESULTS: The OFC was positive in 61 (25.8%) hen's egg allergies, 34 (26.8%) milk allergies and 33 (34.4%) wheat allergies. The greatest AUC for each allergen is as following; hen's egg for egg white specific IgE at 0.745, milk/histamine (wheal) index at 0.718, and wheat for wheal size at 0.597. For the predictive decision points, the highest accuracy rate was at 25.8% for an egg white wheal of 9.5mm, at 26.8% for a milk wheal of 9.5mm, and at 34.4% for a wheal of 6.5mm. CONCLUSIONS: As a result of this analysis, the diagnostic accuracy of SPT had not been satisfactory to judge the acquisition of tolerance in allergic children for eggs, milk and wheat. Therefore, this is not a strong evidence to testify the tolerance of the immediate type food allergy.

Utility of the peripheral blood basophil histamine release test in the diagnosis of hen's egg, cow's milk, and wheat allergy in children.

BACKGROUND: The diagnosis of food allergy (FA) is made by oral food challenge tests (OFCs) that occasionally produce serious symptoms in patients; therefore, whether to perform OFCs should be carefully considered. The utility of the histamine release test (HRT) in the diagnosis of childhood FA has not been fully examined. METHODS: Sixty-four subjects with suspected hen's egg allergy, cow's milk allergy (CMA), and wheat allergy (WA) were enrolled. The diagnosis of FA was made based on the outcomes of OFCs or a convincing history of symptoms after food ingestion within 6 months before or after sample collection. HRT was performed using an HRT Shionogi kit. The threshold of histamine release (HRT threshold), which was defined as the minimum concentration of food antigen to induce a 10% net histamine release, was analyzed in association with FA diagnosis. RESULTS: Receiver operating characteristic analysis showed that the HRT threshold was useful in the diagnosis of heated egg allergy (HEA), raw egg allergy (REA), CMA, and WA. We were able to determine the cutoff value for the HRT threshold in relation to outcomes of OFCs. The cutoff value was 6 ng/ml of egg white antigen in HEA and REA (p < 0.01), 40 ng/ml of milk antigen in CMA (p < 0.01), and 500 ng/ml of wheat antigen in WA (p < 0.05). The efficiency was 70.3% for HEA, 78.0% for REA, 77.6% for CMA, and 70.7% for WA. CONCLUSIONS: We conclude that the HRT threshold measurement for egg white, milk, and wheat antigen is related to outcomes of OFCs and is useful in determining when OFCs should be performed.

Basophil activation marker CD203c is useful in the diagnosis of hen's egg and cow's milk allergies in children.

BACKGROUND: The diagnosis of food allergy (FA) is usually based on oral food challenge tests (OFC). However, OFCs occasionally induce severe adverse reactions. CD203c expression on basophils is emerging as a potential diagnostic index. We evaluated whether CD203c expression on basophils would be a useful marker of OFC-associated symptoms in hen's egg and cow's milk allergies in children. METHODS: Seventy-one patients who had been diagnosed with FA based on OFCs or a convincing history of FA symptoms in the Department of Pediatrics, Sagamihara National Hospital, were recruited. CD203c expression was assessed after stimulation with antigens (egg white, ovomucoid, milk or casein) using allergenicity kits. The CD203c stimulation index (SI = the allergen-induced CD203c expression level divided by the baseline expression level) and the threshold of CD203c expression (the minimum concentration of antigen to induce CD203c SI >or=2) were analyzed in association with tolerance acquisition. RESULTS: For the CD203c SI, the areas under the receiver-operating characteristic curve were 0.72 for egg white, 0.82 for ovomucoid, 0.84 for milk and 0.67 for casein. The positive predictive value for the threshold of CD203c expression was 94.7% for egg white, 100% for ovomucoid, 85.7% for milk and 75.0% for casein. CONCLUSIONS: Assessment of food antigen-induced CD203c expression on basophils is useful to determine if children will outgrow FA as well as in decision making regarding whether or not to perform OFCs.

Associations of functional NLRP3 polymorphisms with susceptibility to food-induced anaphylaxis and aspirin-induced asthma.

BACKGROUND: NLR family, pyrin domain containing 3 (NLRP3), controls the activity of inflammatory caspase-1 by forming inflammasomes, which leads to cleavage of the procytokines IL-1beta and IL-18. Recent studies have shown associations of human NLRP3 polymorphisms with susceptibility to various inflammatory diseases; however, the association with allergic diseases remains unclear. OBJECTIVE: We sought to examine whether NLRP3 polymorphisms are associated with susceptibility to food allergy, food-induced anaphylaxis, and aspirin-induced asthma (AIA). METHODS: We selected 15 tag single nucleotide polymorphisms (SNPs) of NLRP3 and conducted association analyses of NLRP3 using 574 and 1279 samples for food allergy and AIA, respectively. We further performed functional analyses of the susceptible SNPs. RESULTS: Two NLRP3 SNPs (rs4612666 and rs10754558) were significantly associated with susceptibility to food-induced anaphylaxis (P = .00086 and P = .00068, respectively). The NLRP3 haplotype of the 2 SNPs also showed a significant association (P = .000098). We could confirm the association with susceptibility to another hypersensitivity phenotype, AIA (rs4612666, P = .0096). Functional analysis revealed that the risk alleles of rs4612666 and rs10754558 increased the enhancer activity of NLRP3 expression and NLRP3 mRNA stability, respectively. CONCLUSION: Our results indicate that the NLRP3 SNPs might play an important role in the development of food-induced anaphylaxis and AIA in a gain-of-function manner. Further research on the NLRP3 inflammasome will contribute to the development of novel diagnostic and therapeutic methods for food-induced anaphylaxis and AIA.

[Prolonged type of food allergy].

OBJECT: Prevalence of food allergy is the most frequent during infancy, and it is gradually decreasing with age. We can not distinguish patients developing tolerance from those with persistent food allergy, therefore we are unable to advice patients accelerating the development of tolerance. To clarify the factors developing tolerance or intolerance, we conducted the following study. METHOD: Patients who were diagnosed as food allergy to hen's egg, or cow's milk or wheat in infancy by the definitive history of positive food allergic reactions or food provocation tests were recruited to this study. Patients were divided into two groups; one (prolonged group, n=27) is those who needed to eliminate some of the main offending foods even at the age of 6 years old and the other (tolerized group, n=37) is those who had released all main offending foods by the age of 6 years old. RESULT: The factors which distinguished the prolonged group from the tolerized group were the positive clinical history of the atopic dermatitis and its prolonged clinical course, past history of anaphylactic shock, and maximum number of offending foods in the past clinical history. The specific IgE against main antigens such as egg white, cow's milk and wheat in the tolerized group was lower compared to that in the prolonged group, whereas no significant difference was found in non specific IgE value, peripheral eosinophil counts, and specific IgE against other antigens. CONCLUSION: We could find the clinical factors discriminating food allergy patients against three major food allergen among children developing tolerance by the age of 6 years old form those without tolerance.

Increased leukotriene E4 in the exhaled breath condensate of children with mild asthma.

BACKGROUND: Chronic airway inflammation is a feature of asthma. Increased levels of cysteinyl leukotrienes (cys-LTs; leukotriene [LT]C(4), LTD(4), LTE(4)) have been shown in the exhaled breath condensate (EBC) of children with moderate-to-severe asthma. The aim of this study was to examine the relationship between EBC cys-LTs (LTE(4)) levels and bronchial hyperreactivity in children with mild asthma in order to evaluate the clinical utility of measuring EBC cys-LTs levels. METHODS: We measured LTE(4) levels in the EBC of children aged 8 to 18 years, including healthy nonasthmatic children (n = 6) and children with mild asthma (n = 37). Patients with mild asthma were classified into the following three groups: group 1, participants who had been asymptomatic (no wheezing/symptoms of asthma) for > 6 months prior to examination (n = 12); group 2, participants who were asymptomatic but had had wheezing/symptoms of asthma within 6 months before examination (n = 18); and group 3, patients with current wheeze and/or mild symptoms of asthma exacerbation at the time of examination. RESULTS: Exhaled LTE(4) levels were increased in all children with mild asthma compared with nonasthmatic control subjects (5.69 +/- 9.62 pg/20 min vs 0.74 +/- 0.79 pg/20 min, p < 0.05) [mean +/- SD]. In particular, the EBC LTE(4) levels in group 2 (4.99 +/- 6.70 pg/20 min) and group 3 (14.66 +/- 17.11 pg/20 min) were increased compared with control subjects and group 1 (1.50 +/- 1.69 pg/20 min). The EBC LTE(4) levels negatively correlated with the provocative concentration of methacholine causing a 15% fall in FEV(1) (r = - 0.454, p = 0.012). CONCLUSION: EBC cys-LTs may be useful as a noninvasive marker assessing airway inflammation and hyperreactivity in children with asthma.

[Characteristics of shrimp allergy from childhood to adulthood in Japan].

OBJECTIVE: We examined profiles and clinical symptoms of shrimp allergy patients and investigated the correlation of shrimp-specific IgE to crustaceans-specific IgE, mollusks-specific IgE and shellfish-specific IgE. In addition, symptoms when eating crustaceans other than shrimp, mollusks and shellfish were examined, because they shared tropomyosin as a major allergen. METHODS: We examined 99 definitive shrimp allergy cases with questionnaire. RESULTS: Their onset started during either childhood or young adulthood. Symptoms appeared within an hour after ingestion of shrimp in 87.9% cases. The most common symptoms were skin symptoms, followed by oral allergic syndrome (OAS) like symptoms, respiratory symptoms. Anaphylaxis were observed in 61 cases including 2 anaphylactic shock cases. Among 99 shrimp allergy cases, 44 cases (64.7%) showed positive reaction to crabs out of 68 cases experiencing crab ingestion. Only 11 cases (17.5%) reacted against squid out of 63 cases with the experience in squid ingestion. Crab-specific IgE (C.I. 0.954, p < 0.001) and squid-specific IgE (C.I. 0.582, p > 0.001) were strongly correlated with shrimp-specific IgE. CONCLUSION: We conclude that a lot of cases with shrimp allergy react to crabs clinically, and which seem to be different from the reaction against mollusk and shellfish intake in spite of sharing tropomyosin as a major allergen among them.

[Rhythmic fast activity on EEG in a patient with Mollaret's meningitis].

Mollaret's meningitis is a rare disease of unknown etiology, characterized by repeated aseptic meningitis with transient neurological symptoms and quick recovery. The patient, a 16-year-old boy, had episodes of acute encephalitis followed by complete recovery every year from the age of 13 to 16 years. The symptoms at onset were loss of consciousness, a generalized tonic clonic seizure and pyramidal signs. He was first admitted to our hospital at the age of 15 years. EEG in the early stage showed diffuse low-voltage rhythmic fast actvity. He recovered consciousness after a week. At the age of 16 years, he was admitted again because of high fever (39 degrees C). Soon after admission, he had generalized tonic-clonic seizure and was accompanied by alternating deep coma and delirium. Cerebrospinal fluid examination during early stage revealed mild leukocytic pleocytosis, elevation of protein and a high level of IL-6. although brain CT and MRI showed no abnormal findings. EEG showed intermittent, diffuse, middle-voltage, rhythmic fast activity. After 5 days, the neurological symptoms completely disappeared with EEG normalization. To our knowledge, this is the first report of rhythmic fast activity on EEG in Mollaret's meningitis. The clinical pictures of this case suggest a transient functional disorder of brainstem or cerebrum may occur in this condition.

Hypoproteinemia in severe childhood atopic dermatitis: a serious complication.

As a complication of atopic dermatitis (AD), the incidence of hypoproteinemia is increasing among infants with severe AD in Japan. It can be a life-threatening condition owing to hypovolemic shock as a result of hypoproteinemia and vascular infarction as a result of thrombocythemia. However, the pathophysiology of this condition remains unclear. The objectives of the present study were two-fold. The first objective was to determine the main route of protein loss, i.e. through the damaged skin or the gastrointestinal tract, or as a result of insufficient food intake. The second objective was to identify whether allergy or infection was the cause of severe skin inflammation. Fifteen patients with AD were enrolled who had serum protein levels of 3.2-5.8 g/dl. Specific immunoglobulin E (IgE) and skin test to allergens, stool eosinophils, alpha1-antitrypsin clearance, skin Staphylococcus aureus colonization and superantigens (SAgs) produced by the organism, serum SAg-specific IgE antibodies, serum interleukin (IL)-5, IL-6, IL-12, and interferon-gamma (IFN-gamma) were evaluated. Prominent serous skin discharge was seen in all of the patients and was found to have almost the same protein concentration as serum. Marked thrombocytosis, with a maximum of 1,060 x 103/ml, was seen. Skin culture revealed S. aureus colonization in all patients. SAg-producing S. aureus were found in 84.6% of the patients. The concentration of serum IL-5 was significantly increased and correlated well with the blood eosinophil count. Hence, the main route of protein loss was believed to be through damaged skin. The cause of severe inflammation was thought to be a combination of allergic inflammation and skin colonization by SAg-producing S. aureus. Serum cytokines showed a T helper 2 (Th2) T-cell-mediated pattern. To prevent hypovolemic shock, vascular occlusion, and growth retardation, it is of vital importance to diagnose hypoproteinemia at an early stage and start appropriate therapy.