Background: The Modified Pulmonary Index Score (MPIS) is a highly objective and reproducible indicator for evaluating acute asthma exacerbation in children. It may help physicians in making clinical decisions about whether or not to hospitalize a patient with acute asthma exacerbation. However, one of the six items assessed by the MPIS is heart rate, which may be affected by fever.

Objective: To clarify whether the MPIS cutoff values used for predicting hospitalization are influenced by the presence or absence of fever.

Method: The relationship between MPIS scores at the time of medical examination and the decision to hospitalize the patient or not was evaluated for pediatric patients with acute asthma exacerbation presenting at our emergency outpatient ward in the period from November 2013 to October 2018. The MPIS of febrile patients was adjusted for body temperature and its relationship with hospitalization was re-evaluated.

Results: The cutoff value of the Modified Pulmonary Index Score (MPIS) at which the hospitalization probability of a patient with fever is 80% was 9.7 and 9.5 before and after correction for body temperature (95% confidence interval = 8.9-11.1 and 8.6-10.9), respectively.

Conclusion: The MPIS can be used an evaluation method for patients with acute exacerbation of asthma with fever.

Objective: The effect of omalizumab on lung function in children with severe asthma has not been elucidated. We evaluated the long-term changes in lung function of omalizumab-treated pediatric patients with asthma.

Methods: Pediatric patients with severe asthma who were treated with omalizumab for more than 1 year were enrolled in the study. Lung function measurements and other clinical data from medical records were retrospectively analyzed. Yearly changes in %FEV1 were estimated by linear regression analysis during two periods: before and during omalizumab treatment.

Results: Ten patients were enrolled. Six patients were followed up for more than 1 year before omalizumab treatment, and the yearly change in %FEV1 during the period was negative in all 6 patients, indicating a decline in %FEV1. The yearly change in %FEV1 before omalizumab was not evaluated in the remaining 4 patients because the observation period was too short. During omalizumab treatment, the yearly change in %FEV1 was positive in 5 patients but negative in the other 5 patients. However, in 3 patients in whom the yearly change in %FEV1 was able to be evaluated before treatment, the degree of decline during the treatment was less than before treatment. We were unable to identify factors associated with improvement in lung function during treatment with omalizumab.

Conclusions: Omalizumab may prevent lung function decline in children with severe asthma.

Background: The relevance between sublingual immunotherapy (SLIT) with Japanese cedar pollen extract and pollen-food allergy syndrome (PFAS) to tomato has not been reported.

Patient: A 12-year-old boy with Japanese cedar pollinosis, asthma, and PFAS to apple, kiwi, and avocado. He was able to eat tomato without symptoms. After 1 month of SLIT with Japanese cedar pollen extract, he experienced throat itching and dyspnea immediately after eating two small tomatoes. Serum-specific IgE antibody levels to Japanese cedar pollen and tomato increased, and prick-to-prick test (PPT) with tomato changed from negative to positive after 5 months of SLIT. Oral food challenge (OFC) of tomato was positive immediately after taking one small tomato with throat itching. By contrast, he was able to eat cooked and processed tomatoes without symptoms. Therefore, we considered he developed PFAS to tomato and instructed him not to eat fresh tomatoes.

Conclusion: The first case report of PFAS to tomato during SLIT for Japanese cedar pollen allergy. Patients receiving SLIT with any pollen should be paid attention when taking cross-reactive foods.

Microscopic colitis shows chronic diarrhea as a primary symptom with typical pathological inflammation in the large intestine despite other endoscopic findings being almost normal. It is caused by medicines, infections, genetic predisposition, allergies, autoimmunity, and according to previous reports, food allergies.

The patient was an 11-year-old boy who was negative in a specific IgE test performed for eggs and milk, which had induced allergic symptoms since his infancy. He was diagnosed as having immediate-type allergy based on the results of skin testing and started on egg and milk oral immunotherapy at age 5. Egg allergy was partially resolved at age 8. While milk oral immunotherapy was continued, however, digestive symptoms became significantly more frequent. An endoscopy was performed at age 11 for suspected complication of eosinophilic gastroenteritis. The diagnosis was microscopic colitis caused by milk protein. Eosinophilic gastroenteritis was negative. The possibility of Crohn's disease was also noted.

Despite the fact that not all medical institutions can provide endoscopic examination for pediatric patients, it is useful to observe lesions directly and obtain information.

Endoscopic examination should be considered in patients who have treatment-resistant food allergies.

Non-IgE-mediated food protein-induced gastroenteropathy that exhibits relatively acute symptoms is classified as food protein-induced enterocolitis syndrome. The cause of most cases is infant formula, as solid food is rarely a causative antigen. However, there have been several reports of cases resulting from fish consumption in Japan. Case 1 was a seven-year-old male who repeatedly experienced vomiting after eating swordfish since the age of two. The specific IgE antibody against each fish was negative, the lymphocyte stimulation test for swordfish was positive, and the oral food challenge test for swordfish was positive. Case 2 was a two-year-old female who repeatedly experienced vomiting after salmon, flounder, and sawara (Spanish mackerel) consumption during the weaning period. The specific IgE antibody against each fish was negative, and the lymphocyte stimulation tests for tuna, flounder, sawara, and salmon were all positive. Both cases showed reproducible symptoms, and the patients were diagnosed based on their history. The results of the oral food challenge tests and lymphocyte stimulation tests were also used to help in diagnosis. Reports of solid food cases, especially with fish as a causative antigen, are rare, and the non-specific symptoms are likely to cause a delay in diagnosis. Prompt diagnosis is essential as symptoms may become chronic depending on the disease type. Therefore, it should be recognized that solid foods can be causative antigens, and that non-IgE-mediated food protein-induced gastroenteropathy should be considered for the differential diagnosis of repetitive digestive symptoms.

Background: There is little evidence on the methods of intake management for infants who are sensitized to hen's egg (HE). We prospectively analyzed the safety of early introducing small quantities of HE and ingestion at home in infants.

Methods: An oral food challenge (1st OFC) with 0.2 g of HE was administered to 6-month-old infants who were egg-sensitized at the time. Those with negative 1st OFC results began ingesting 0.2 g of HE at home. A 2nd OFC using one quarter of egg white was administered at 9-11 months of age. We evaluated the OFC results and the safety of ingesting HE at home.

Results: Fifteen of 63 infants (23.8%) had positive 1st OFC results. Among the 48 negative cases, 42 ingested HE at home; 1 was lost to follow-up. Acute skin symptoms developed in 8 of 41 cases (19.5%). Four of 41 cases (9.8%) had positive 2nd OFC results. Ovomucoid-specific IgE levels were higher in OFC-positive cases.

Conclusions: A high proportion of egg-sensitized infants had positive 1st OFC results. Acute symptoms after HE ingestion at home occurred in several cases with negative 1st OFC results. Further studies are needed to identify safer and more practicable HE intake management methods.

[Background] Different methods of oral food challenges (OFCs) may lead to different outcomes.

[Subject and Methods] We performed an OFC in which 8 g of egg white, boiled for 20 min, was fed to children with class 3 or 4 egg white-specific IgE. Furthermore, we compared an escalating 2-dose method involving an interval of 60 min with an escalating 3-dose method involving an interval of 30 min to examine the rate of OFC positivity and symptom severity.

[Results] No significant differences were observed in the OFC-positive rates between the 2-dose and 3-dose methods (21 [30.4%] and 24 [38.6%] [P=0.72], respectively). The threshold values at which symptoms were induced were 8 g and 3 g, respectively (P=0.76). All symptoms observed in both methods were Grade III or less according to modified Sampson classification. Moreover, there was no significant difference between the two methods in terms of organ symptoms or neurologic and circulatory organ symptoms.

[Conclusion] There were no significant differences in the safety and efficacy between the 2- and 3-dose methods for hen's egg allergy in children with class 3 or 4 egg white-specific IgE.

We report a pediatric case of anaphylaxis caused by line marking powder made of eggshell. A 6-year-old boy, who has an egg allergy and atopic dermatitis, rubbed his face with line marker powdered hands during practice of a sports festival. Soon, he developed cough and urticaria. After that, his mother found that the line marking powder was made of eggshell and suspected that the powder caused his symptoms. And she put the powder on his both upper and lower limbs and back neck at home. Because dyspnea, wheezing, urticaria and redness developed at the affected area and face within 5 minutes, he took antihistamines. When he visited our emergency department in 1 hour after taking medication, dyspnea and skin symptoms were improved. Although wheezing remained, SpO₂ was 100% and so no additional treatment was needed. We analyzed the properties of the powder. As a result, the ovalbumin concentration was more than 20μg/g, the particle size was distributed in the range of 0.5~1000μm, and about 10% of them had a particle size of 5μm or less. We concluded that his immediate reaction occurred when the powder was inhaled into the trachea and absorbed into the atopic skin.

Lactose contains only trace amounts of cow's milk protein but, in rare cases, children with cow's milk allergy experience an immediate allergic reaction to lactose present in processed foods. Here, we report the case of an 11-month-old milk-allergic child, who tested positive for lactose by an oral challenge test, suspected of undergoing an immediate allergic reaction to lactose contained within Chinese soup. Her medical history revealed an outbreak of hives at 8 months of age after eating a small amount of yogurt. Blood tests revealed high levels of milk-specific IgE and she was diagnosed with cow's milk allergy. Her parents were advised to completely exclude cow's milk and dairy products from her diet. However, after eating Chinese soup for the first time at nursery school, she presented with urticaria and hoarseness at our emergency department. We performed an oral challenge test and the result was positive for lactose of pharmaceutical use. Patients with cow's milk allergy rarely experience an immediate allergic reaction to lactose, so such patients are not generally advised to avoid lactose. When patients are suspected of having lactose-induced symptoms, it is important to confirm this intolerance by an oral challenge test. If a positive result is obtained, patients and their families should be advised about the lactose-containing foods and medicines to avoid.

Cystic fibrosis (CF), a rare disease with poor prognosis in Japan, requires early detection and intervention. A 2-year-old boy with no perinatal medical history had developed post-influenza wheezing and pneumonia at 11 months of age. The administration of inhaled corticosteroids for bronchial asthma did not improve his symptoms. Low-dose macrolide therapy was initiated for suspected ciliary dysfunction and chronic bronchitis, but his symptoms still did not improve. The patient developed respiratory syncytial virus pneumonia at 2 years and 2 months of age, and retractive breathing continued. At 2 years and 3 months of age, he was hospitalized for wheezing and hypoxemia. Chest computed tomography scans revealed pulmonary hyperinflation and peripheral bronchial wall thickening. Also, Pseudomonas aeruginosa was detected from his sputum culture. CF was suspected due to hepatomegaly and poor weight gain, and a CF transmembrane conductance regulator (CFTR) gene test was performed. The test confirmed c.2989-2A>G mutation of the CFTR gene in both alleles, and a diagnosis of CF was given. At present, the patient is in good condition under treatment with dornase alfa and tobramycin. In similar cases where infants with asthma do not respond to corticosteroids, physicians should consider the possibility of rare diseases such as CF.

Kawasaki disease (KD) was reported as a novel disease in The Japanese Journal of Allergology in 1967. Although many causative pathogens have been proposed, the cause of KD remains unknown. The guidelines for the diagnosis of KD using clinical symptoms were revised in 2019. The purpose of this 6th revision is to focus on the prompt diagnosis for KD for not delaying treatment. The treatment for intravenous immunoglobulin-resistant acute KD is important. The pathogenesis of KD is vasculitis caused by systemic inflammation in genetically susceptible children.

During the recent and ongoing coronavirus disease 2019 (COVID-2019) pandemic, the pediatric severe cases showing features similar to KD were reported in Europe and US. Further studies will be needed to clarify the involvement of COVID-19 in the pathogenesis of KD.

Avoiding sensitization to food antigens and inducing oral immune tolerance are the main two strategies for preventing the onset of immediate food allergy. Recent researches have revealed that percutaneous sensitization occurs in infants with eczema due to skin barrier dysfunction, but the effective method for preventing food sensitization has not been reported. Even after the sensitization, however, oral immune tolerance induction may be enough for preventing food allergy. A meta-analysis of recent randomized controlled trials indicated that the introduction of peanut and hen' egg as early as age 4 to 6 months decreased the onset of allergy to these foods. During the past few decades in Japan, the timing of introducing hen's egg has become later, and the previous guideline (Heisei 19) accordingly recommended introducing egg into the diet of infants at age 7 or 8 months. Based on recent evidence this age has been revised to 5 to 6 months in the "Guideline for Supporting Breast Feeding and Weaning" (2019 revised edition). Early introduction of complementary food is a promising strategy for preventing food allergy though the induction of oral immune tolerance, although extreme caution is needed for allergic reactions in patients who have already developed food allergy.

The major allergen in fish is parvalbumin which is a muscle protein. It is resistant to heat and easily soluble in water. Due to cross-reactivity among different fish species, the patients with fish allergy may have allergic symptoms in multiple fish species. As a second allergen, collagen also has cross-reactivity. There are reports of multiple allergens such as aldolase and enolase as minor allergens. Allergens of fish roe have been analyzed in salmon roe, roe of Gadus chalcogrammus, and caviar. The β'-component of egg yolk protein is the major allergen in salmon roe. Detailed analysis of the β'-component has not been performed to date.

IgE-mediated allergic reactions to crustaceans are relatively common and have been confirmed to occur in patients worldwide including Japan, although the prevalence varies regionally. Among crustaceans, shrimps and prawns are the most predominant cause of allergy and are thus studied most frequently. Tropomyosin is the major allergen in crustaceans. However, the tropomyosin-sensitized rate in allergic patients varies regionally, and low sensitization rates are observed in Japan. Tropomyosin in crustaceans has a highly conserved amino acid sequence, which is responsible for the cross-reactivity among the species. The cross-reactivity has been confirmed not only among crustaceans but also between crustaceans and mollusks and between crustaceans and mites. Region-based differences in the consumption of the crustaceans and the sensitization rates to the tropomyosin of the mites might contribute to the regional differences in the prevalence of the crustacean allergy and the tropomyosin sensitization rates in crustacean allergy, respectively. In addition to tropomyosin, arginine kinase, myosin light chain, sarcoplasmic calcium-binding protein, triosephosphate isomerase, hemocyanin, and troponin have also been identified as allergens. This review summarizes the allergens present in crustaceans and mollusks.

Background & Aims: The efficacy of tailoring asthma medication based on fractional exhaled nitric oxide (NO) levels for children with asthma is not clear. Therefore, we performed systematic review to determine whether tailoring asthma medication based on fractional exhaled NO (FeNO) can be recommended as general practice. Methods: We extracted randomize controlled trials met following criteria; including patients aged ≤18 years, comparing adjustment of asthma medications by FeNO and clinical symptoms (or only FeNO) versus by only clinical symptoms. The primary endpoint of this SR was the number of patients with acute exacerbation during study. Results: Nine studies met the criteria for the SR. Most patients have atopic asthma. These studies differed in a variety of FeNO cut-off level used. Tailoring asthma medication based on exhaled NO significantly decreased the number of patients with acute exacerbation (OR 0.63, 95% CI 0.49 to 0.81, P = 0.0003, N=1279).

Conclusion: Tailoring asthma medication based on FeNO and clinical symptoms may useful in asthmatic children. However, specific reference value of FeNO is unclear and FeNO levels can be affected by complicating allergic diseases. Therefore, we do not recommend tailoring asthma medication based on FeNO and clinical symptoms as general practice, only suggest as one of the management options.

Currently, there are sixteen randomized controlled trial (RCT) s comparing the effects of house dust mite (HDM) -specific immunotherapy with placebo in children with bronchial asthma. Subcutaneous immunotherapy (SCIT) with HDM resulted in reduction in asthma symptoms, improvements in respiratory functions, diminished use of rescue drugs and systemic steroids, and reductions in both the overall use and doses of drugs prescribed for long-term asthma management. Sublingual immunotherapy (SLIT) with HDM resulted in a reduction in asthma symptoms and improved respiratory function. However, the RCTs evaluated in this systematic review generally provided low levels of evidence and none specifically addressed the impact of HDM-specific immunotherapy in asthmatic Japanese children.

In Japan, SCIT (but not SLIT) is covered by national health insurance for the treatment of asthma. Interestingly, SLIT is covered by insurance for the treatment of allergic rhinitis, although this modality should also be effective for the treatment of asthma. The adverse effects of allergen-specific immunotherapy were reviewed to some extent, as was the fact that one needs to consider the critical balance between potential therapeutic vs. adverse impact of this type of therapy.

Cumulatively, the results suggested that HDM-specific immunotherapy is effective for the treatment of childhood asthma. We suggest that this modality be considered among the standard treatments for the long-term management of asthma in children who have been sensitized to HDM.