The aim of clinical research is to benefit patients. Researchers should conduct research based on clinical needs as well as their own particular interests. Healthcare professionals who apply the results of research to clinical practice (evidence-based medicine) are able to make more informed treatment choices for patients. Unfortunately, patients are not usually able to access research results directly themselves. Medical articles are normally written using technical terms. Cochrane systematic reviews have plain language summary for non-professionals reading and science journals may put plain language summaries on their articles for patients in the near future. In addition, patients should participate in clinical studies not only as participants but in the design and conduct of these studies as well.

View full abstract

This clinical study was initiated through our experience of relatively rare cases with post-influenza vaccine-induced anaphylaxis. We had a chance to start the study from several local patients with the anaphylaxis and then expanded the study at the national level. Through the further investigation of causes of the anaphylaxis, we were able to re-think the general precaution of vaccination to children with egg allergy, and gave the attention to the HA antigen itself not on the egg-derived antigens. While we were lucky enough to perform the study with sufficient supports from the patients and the medical staff, it is noted that a good clinical study should be conducted based on questions arose from the clinical practice without any biases, and sufficient communication and cooperation with patients.

View full abstract

How can we connect the clinical issues for patients and the advanced sciences? When we think about this question, we need to distinguish the sciences by the degree of its establishment. This article discusses an approach from the structural medicine, especially about the technical and historical aspects of our studies, to activate a discussion by the readers: how we can commit to the state-of-the-art sciences and how our medical society can facilitate the young medical doctors to jump into the unrevealed fields to explore a new fascinating era.

View full abstract

Oral food challenge (OFC) is the gold standard clinical diagnostic method for food allergies. However, because an OFC often induces anaphylaxis and other risks, a safer method for patients is desirable. Although tests using specific IgE to crude extracts have a high degree of clinical sensitivity, they have low specificity, which in most cases results in low diagnostic efficiency. Specific IgE to some allergen components have been associated with symptoms. In the present study, components that are effective in the diagnosis have been elucidated using allergic patients diagnosed by OFC. Here, an overview of the allergen components of plant seeds and the components useful for diagnosis are described.

View full abstract

Food allergic children are recently allowed to consume the causative food within safety limits that are set based on their oral food challenge (OFC) results. In this article, we review the results of tolerance induction effect by avoiding complete elimination. 1) Early introduction of one cooked egg yolk with slight contamination of egg white: Subjects who consumed the egg starting at age 0 to 1 had a higher rate of egg tolerance at age 5 than subjects starting at age 2 to 3. 2) Small amount induction of cow's milk or wheat: One year after passing small amount OFC, approximately 10% of cow's milk allergy and 30% of wheat allergy achieved tolerance. 3) Small amount induction oral immunotherapy: We enrolled children who failed in small amount OFC. The maintenance dose was smaller compared with that of reported oral immunotherapy. One year after small amount induction oral immunotherapy started, approximately 30% of cow's milk allergy, 50% of hen's egg allergy, and 100% of peanut allergy achieved moderate amount tolerance. Our studies suggest that avoidance of complete elimination would induce tolerance of food allergy. In comparison with natural outgrow, we need to investigate the effect in a prospective study.

View full abstract

In recent years, children with food allergy not to improve spontaneously increase. These children and their families are forced to great illness burdens in everyday life because they always hold fear and risk for anaphylactogenesis by the false intake in addition to the inconvenience of the elimination diet of the day after day. The establishment of the definitive therapy for food allergy is desired earnestly, and it is a top priority subject in the allergy medical field. Therefore, by utilizing the transcutaneous antigen delivery device (hydrogel patch) brought from our transcutaneous vaccine research, we are attempting to develop the epicutaneous immunotherapy for milk- and chicken egg-allergy and elucidate its response mechanisms. Here, we first give an outline about characteristics and performances of our original hydrogel patch, and then introduce potential and promise of the epicutaneous immunotherapy applied with the hydrogel patch.

View full abstract

The lung auscultation is a very important technique for physical assessment of children with respiratory diseases. Pediatricians are required to record lung auscultation findings using standard nomenclature and there are a lot of techniques to learn in order to make the most of lung auscultation. However, there are not many chances to get formal education on lung auscultation, nowadays. As the introduction to this symposium on lung sounds, I presented here the fundamentals and application of lung auscultation skills and demonstrated a number of video clips recorded from real patients in order to show usefulness of the teaching materials using digital video equipment.

View full abstract

Auscultation is the most effective and simple method to detect abnormality of the lung respiration invasively. Recently attempts have been made to innovate the quantitative measurements and frequency analyses of the lung sound for the diagnosis. However, the physical mechanisms of the sound generation and its propagation in the lung are still uncovered. In this report, we introduce our recent engineering studies on the aeroacoustics of bronchial sounds and show some results obtained by the experiments using both the simplified and the realistic models of branching airway and the computational analyses of sound propagation through the airway wall.

View full abstract

A simple and accurate airway evaluation method for infants remains elusive. Lung sound analysis is a non-invasive method of bronchial condition assessment not requiring the infant's cooperation. Airway inflammation and airflow limitation affect breath sounds, even in the absence of adventitious sounds. Recent developments in signal processing methods have improved the possibility of extracting physiologically and clinically relevant information from lung sounds. We developed a new technology for analyzing lung sounds involving an index, named ic700 (index chest wall at 700 Hz), which shows the intensity difference at 700 Hz. The ic700 can overcome the effects of body size and flow. Our method of lung sound recording involves a sound sensor fixed with tape on the chest wall for 20 seconds while the children, without requiring a mouthpiece and/or nose-clip, are able to breathe quietly. We showed that ic700 is for infants who are unable to perform forced breathing. Moreover, ic700 could evaluate the effect of ICS treatment and airflow limitation in asymptomatic asthmatic children, even including infants. We suggest that ic700 reflects breath sound generation and transmission in asthmatic children. We found that ic700 is a useful index for the management and daily monitoring of asthma in infants.

View full abstract

Cough is said to be one of the chief complaints which are encountered in everyday practice. Cough deteriorates not only children's life, but also their parents' QOL. In recent years, asthma guidelines are published, and the QOL of asthma patients has improved by them. However, it can not be said that treatment of chronic cough is enough. Recently, "Guidelines for the Treatment and Management of Pediatric Cough" was published by the Japanese society of pediatric pulmonology. In the guidelines, childhood cough is classified into three categories; an acute cough, a prolonged cough, and a chronic cough, according to adult cough classification by continuing period. Clinical features of pediatric cough resemble those of adult cough basically, but allergic diseases such as asthma and allergic rhinitis are common cause of chronic cough continued more than 8 weeks in children. It has been speculated that there is a different mechanism among childhood cough and adult cough, and the main cause is different in each childhood period; neonate, infant, school child, and puberty. Thus, objective method is need.

View full abstract

Evidence based medicine (EBM) has been described as a new approach to teaching and practicing clinical medicine. Statistical methods are useful for the correct interpretation of the results in proof of the evidence; therefore biostatistics is an important element of EBM. Furthermore, maintaining and fostering good communication between medical doctors and biostatisticians will lead to good relationships and success. In this article, we highlight several important aspects related to the design and statistical analysis for clinical research. First, we focus on a special type of bias called 'confounding'. Next we present concerns regarding misuse of statistical software. Finally, we review what statistical methods are frequently being used in clinical research, then present recent trends and perspectives of statistical methods.

View full abstract

There are only a few reports on allergen-free elimination diet menus provided by hospitals. It is important to provide meals without causative foods for hospitalized children with food allergies. We prepared routine allergen-free elimination diet menus for food-allergic children, and compared the number of adverse events that occurred before (April 2006 to March 2009) and after the implementation of the routine allergen-free elimination diet menu (April 2009 to March 2014). The routine allergen-free elimination diet menu was implemented for 14 days, from which 11 food items (hen's egg, cow's milk, wheat, peanut, tree nut, squid, octopus, fish roe, yam, and sesame) were eliminated beforehand. After preparing routine allergen-free elimination diet menus, the number of allergy-related adverse events reduced significantly from 7 cases from 8,013 meals to 0 case from 22,002 meals (p<0.001). We believe that routine allergen-free elimination diet menus might reduce the number of adverse events that occur from consuming the meals provided in the children's lunch boxes, and may also decrease the risk of accidents that occur during meal time.

View full abstract

We experienced a 8 year-old girl with acute generalized exanthematous pustulosis (AGEP) who fulfilled with the diagnostic criteria of Kawasaki disease (KD). On admission, she had fever, generalized erythema, injected eyes, flushed lip, swelling of extremities. We found elevated white blood cell count, C-reactive protein and reduced concentration of serum albumin, and sodium. We suspected KD, but administered antimicrobials intravenously because of day 2 of fever and no abnormality finding of echocardiographic examination. The following day, we reached a diagnosis of AGEP for many small pustules on generalized erythema. She brought down fever on the 3th day after admission. We discontinued antimicrobials on the 4th day. Erythema and pustules gradually disappeared. Desquamation appeared on the 5th day. She discharged hospital on the 6th day. We considered acetaminophen as a causative drug from the positive results of drug lymphocyte stimulation test in 4th day and 2 months after onset. It might happen that AGEP would be worsening from misdiagnosis and administer of offending drug because of clinical resemblance to KD and sepsis. We need to recognize it a type of severe eruption while rare with child.

View full abstract

Background: The burdens families and children experience because of food allergy can reduce by increasing egg product intake. We report the usefulness of an oral food challenge (OFC) test with an egg product processed with wheat and investigate the results using a questionnaire on egg product intake after the OFC. Subjects and Methods: Between January 2011 and July 2013, we sent a questionnaire on egg product intake to parents of 94 patients at the Tsukuba Medical Center Hospital. These patients had an egg allergy and had undergone an OFC with Japanese sponge cake. Seventy-two parents returned the questionnaire, and we analyzed their answers. Result: Thirty-nine patients were male, and 33 were female. Egg white specific IgE was ranged from 0.34 to 100 U_A/ml. Twelve patients were OFC-positive, and 58 were OFC-negative. After the OFC, 60 patients started to ingest egg products which contain wheat, 54 said the number of commercial egg products they could purchase increased, and 69 reported that the OFC with egg products was beneficial. Conclusion: Many patients with egg allergy were able to consume egg products at home after an OFC with Japanese sponge cake, indicating that an OFC with egg products processed with wheat is useful for relaxing their elimination diet.

View full abstract

Gastrointestinal food allergy in newborns and infants is usually caused by cow's milk. Here, we describe a case of an infant who presented with continuous bloody stool. Contrast enema showed an irregular narrowing of the intestinal lumen from the rectum to the sigmoid colon. The infant tested negative for serum IgE for cow's milk and its proteins, namely, casein, α-lactalbumin, and β-lactoglobulin. The allergen-specific lymphocyte stimulation tests for casein and lactoglobulin were positive. Upon cessation of the cow's milk-based formula, the infant's bloody stool improved. This study suggests the importance of not only making the correct diagnosis of food allergy but also knowing its gastrointestinal manifestations.

View full abstract

A questionnaire survey was conducted for 20 pediatric facilities in Hiroshima prefecture where the Oral Food Challenge Test (OFC) is carried out, regarding the actual methods used to implement the OFC (survey conducted Feb-Mar, 2012, with a collection rate of 83.3%). The results were that OFC was implemented using an open method, mainly with the objective of ascertaining tolerance, and the challenge foods were brought in by parents, the implementation foods (foods used) were mostly egg (hard-boiled egg), milk (raw milk) and wheat (fresh udon), and the food challenge was carried out at 15-30 minutes intervals, 3-5 times for outpatients and 6-10 times for hospitalized patients. The increase in sample weight was by means of increasing the weight of the previous challenge by 100% at a time, and the infusion pathway was prepared, depending on the case, with most cases involving observation by 1 doctor and 1 nurse. In the past year, the critical evoked responses in OFC were few, with the total number of cases being 7.2%, and there were no facilities that had to struggle to handle critical evoked responses. Among the 20 facilities, at 15 facilities, there were cases where OFC medical fees could not be charged, the reasons given by many facilities being limits on age and the number of visits for insurance assessment purposes.

View full abstract

Therapeutic purpose and efficacy of salmeterol/fluticasone propionate combination (SFC) for management of asthma were retrospectively assessed in children. Subjects were sixty-two asthmatic patients (43 boys and 19 girls) prescribed SFC from October through December 2011. The median age of subjects at introduction of SFC was 11 years. Total of 41 subjects were introduced SFC at the same dose of pre-administrated inhaled corticosteroids, and both number of asthma exacerbations per year and respiratory function has been significantly improved. The purposes of SFC introduction were as follows: control of asthmatic symptom, 36 subjects (58.1%); suppressed respiratory function, 32 subjects (51.6%); and presence of exercise-induced asthma (EIA), 11 subjects (17.7%). The number of asthma exacerbations per year was decreased in the subjects with poorly controlled asthma after SFC induction. The respiratory function was improved in the subjects with suppressed respiratory function after SFC induction. The value of %V50 and %V25 in the subjects with EIA were improved by switching to SFC. Taken together, consideration above 3 factors for the indication of SFC resulted in significant efficacy. Uncontrolled asthma subjects, complication of EIA, and suppressed respiratory function in spite of treatment above step 3 in JPGL 2012 would be indication for introduction of SFC.

View full abstract

[in Japanese]

View full abstract