Yoshiyuki Kanagawa

A survey of patients with self-reported severe food allergies in Japan

Food allergies have increased in recent years in Japan. Details of causative foods, places where anaphylaxis developed, and other allergic factors remain unknown, and we investigated them. A‘questionnaire survey for the prevention of food allergies’ was conducted using a nationwide group of patients with food allergies. A total of 1383 patients from 878 families (including 319 patients who experienced anaphylaxis) provided valid answers to the questionnaire. The average age of the first anaphylactic attack was 3.20 ± 6.327 yr. The most common allergens causing anaphylaxis were in order milk, eggs, wheat, peanuts, and soybeans, followed by sesame and buckwheat. The most common place where anaphylaxis developed was the patient’s own home, followed by fast food restaurants, places visited, restaurants, and schools. In patients’ own homes, fast food restaurants (buffet), places visited and schools, the most common allergens were milk, eggs, and wheat. In restaurants and accommodation facilities, eggs were the most common allergen followed by milk. As possible food allergies can cause anaphylaxis, it is necessary to provide precise information for consumers regarding packaged and processed foods.

Association of clinical findings in Yusho patients with serum concentrations of polychlorinated biphenyls, polychlorinated quarterphenyls and 2,3,4,7,8-pentachlorodibenzofuran more than 30 years after the poisoning event

BackgroundThe Yusho poisoning incident, which was caused by rice bran oil contaminated with polychlorinated biphenyls (PCBs), polychlorinated quarterphenyls (PCQs) and polychlorinated dibenzofurans (PCDFs) generated by heat denaturation of PCB, occurred in 1968 in western Japan. Annual physical, dermatological, dental, ophthalmological and laboratory examinations were conducted for Yusho patients after the incident. From 2001, blood levels of individual PCDF congeners were also measured. The blood levels of 2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PeCDF), PCBs and PCQs in Yusho patients were found to be significantly higher than those of the general population. We investigated the relationships between blood concentrations of 2,3,4,7,8-PeCDF, PCBs and PCQs in Yusho patients and the items measured in the annual medical examination.MethodsMedical and laboratory examination data from 501 Yusho patients enrolled in the study from 2001 to 2004 were analyzed. The relationships between blood 2,3,4,7,8-PeCDF, PCB and PCQ concentrations and medical/laboratory examination data were investigated using principal components and logistic regression analyses.ResultsSerum Concentrations of 2,3,4,7,8-PeCDF, PCBs and PCQs in blood tended to correlate with either acneform eruptions, black comedones, cutaneous and mucosal pigmentation, and hypersecretion of meibomian glands as well as general fatigue, headaches, cough/sputum, abdominal pain, arthralgia, increased blood sugar, increased serum γ-GTP and decreased total bilirubin. The majority of these signs and symptoms are included in the diagnostic criteria for Yusho.ConclusionAfter Yusho patients had suffered chronic exposure to these chlorinated compounds for more than 35 years, the serum concentration of 2,3,4,7,8-PeCDF in blood was significantly related to arthralgia and decreased albumin/globulin (A/G) ratio; the serum concentration of PCBs was significantly related to ophthalmologic symptoms; and the serum concentration of PCQ to increased total cholesterol. These findings suggest that the co-contaminants may affect other functions than those originally associated with Yusho.

A technique for identifying three diagnostic findings using association analysis

In diagnosing diseases in clinical practice, a combination of three clinical findings is often used to represent each disease. This is largely because it is often difficult or impractical to assess for all possible combinations of symptoms and abnormal exam findings that occur in any particular disease. For most diseases, diagnostic triads are based on empirical observations. In this study, we determined diagnostic triads for chronic diseases using data mining procedures. We also verified the combinations’ validity as well as our procedure for determining them. We used symptoms and examination findings from 477 patients with chronic diseases, collected as part of a 35-year longitudinal study begun in 1968. For each patient there were 295 items from examinations in internal medicine, dermatology, ophthalmology, dentistry and blood tests. We judged each item to be either normal or abnormal, and restricted the analysis to the abnormal findings. To analyze such an exhaustive assortment, we used the data mining technique of association analysis. The analysis generated three clinical findings for each disease. Diseases were defined based on blood tests. Searching through all 295 items to find the three most useful clinical findings would be impractical on a commodity PC. However, by excluding normal items, we were able to sufficiently reduce the total number of combinations so as to make combinatorial analysis on a PC feasible. In addition to more accurate diagnoses, we believe our technique can identify those diagnostic data that are more cost effective in terms of time and other resources required for their collection.

Variation in half-life of penta-chlorodibenzofuran (PeCDF) blood level among Yusho patients

Yusho (oil disease) is the name given to a food poisoning incident caused by rice bran oil that occurred in west Japan in 1968. The causative agents of Yusho are currently considered to be polychlorinated biphenyls (PCBs) and their by-products, such as dioxin like compounds. The levels of 2,3,4,7,8-penta-cholorodibenzofuran (PeCDF) are measured in the blood of Yusho patients who attend medical check-ups. The objectives of this study were to determine the half-life of PeCDF in these patients. Linear regression analysis was performed with the binary logarithm of PeCDF blood levels in Yusho patients as the dependent variable and the measurement year as the independent variable. The linear coefficient determined in this analysis is the reciprocal of the half-life. The half-life of PeCDF varied among patients. Among patients with PeCDF blood levels of 50pgg(-1) or higher, there were two groups: one showing a half-life of approximately 7 years and the other showing no reduction in PeCDF levels over time. The results indicate that there is a group of patients whose PeCDF levels are maintained at a high level. Our study suggests that a more complicated model is required to explain PeCDF excretion in humans.

Change in decay rates of dioxin-like compounds in Yusho patients.

BackgroundOnce ingested, dioxins and dioxin-like compounds are excreted extremely slowly. Excretion can be evaluated by its half-life. Half-lives estimated from observed concentrations are affected by excretion and ongoing exposure. We investigated the change in apparent half-life using a theoretical model based on exposure to dioxin and dioxin-like compounds.MethodsWe carried out longitudinal measurements of the blood concentration of dioxins and dioxin-like compounds in a Yusho cohort during 2002 to 2010. We estimated the change in decay rates of 2,3,4,7,8-PeCDF and octachlorodibenzodioxin (OCDD) using a second-order equation.ResultsWe found that the decay rate of OCDD increased, whereas the decay rate of 2,3,4,7,8-PeCDF of patients with a relatively high concentration of 2,3,4,7,8-PeCDF decreased. OCDD results were in accordance with decreasing levels of dioxin and dioxin-like compounds in the environment. The decay rate of OCDD in the body was affected by the decay rate of OCDD in the environment by ingestion because it was near the steady-state. In contrast, the decay rate of 2,3,4,7,8-PeCDF in the body was affected less by ingestion from the environment because it was far higher than in the steady-state.ConclusionWe demonstrated that the level of 2,3,4,7,8-PeCDF in the environment is decreasing. The excretion half-life is longer than the environmental half-life, thus the excretion half-life in a Yusho patient is increased.

Association analysis of food allergens

Food allergy patients are known to present with allergic reactions to multiple allergens, but extrapolating these associations is difficult. Data mining, a procedure that analyzes characteristic combinations among large amounts of information, is often used to analyze and predict consumer purchasing behaviour. We applied this technique to the extrapolation of food allergen associations in allergy patients. We sent 1510 families our ‘Questionnaire survey for the prevention of food allergies’. Responses noting 6549 allergens came from 878 families with 1383 patients, including 402 with anaphylaxis. Some results of the survey have already been published and here we presented the results of our association analysis of combinations of food allergens. Egg, milk, wheat, peanuts, and buckwheat are the most common food allergens. The most common simultaneous combinations of these allergens were ‘egg‐milk’, ‘egg‐wheat’, and ‘milk‐wheat’. The occurrence probability of a combination (i.e. one person suffering from a certain allergen also suffers from another) is called ‘confidence’. Confidence was higher for ‘chicken‐egg’, ‘abalone‐salmon eggs’, and ‘matsutake mushroom‐milk’. As well, the combinations of ‘crab‐shrimp’, ‘squid‐shrimp’, and ‘squid‐crab’ also indicated higher values in a statistical examination of the occurrence probabilities of these allergen combinations (Z‐score). From the results of the association analysis, we speculated that some food allergens, such as abalone, orange, salmon, chicken, pork, matsutake mushroom, peach and apple did not independently induce food allergies. We also found that combinations, such as ‘crab‐shrimp’, ‘squid‐shrimp’, ‘squid‐crab’, ‘chicken‐beef’, and ‘salmon‐mackerel’ had strong associations.

Twenty-year changes of penta-chlorodibenzofuran (PeCDF) level and symptoms in Yusho patients, using association analysis

BackgroundRecently, methods for measurement of dioxins in the blood have improved. Also, techniques for analyzing large quantities of data have been developed, such as data mining. Even in subjects with elusive characteristics, it is becoming possible to find previously unknown characteristics by checking all combinations of symptoms.FindingsUsing association analysis of the data mining technique, we extracted and compared combinations with a strong relationship between recent symptoms (2001-2004) and recent blood PeCDF levels, and between past symptoms (1986-1989) and recent PeCDF levels, in physical, blood, dermatological, dental and ophthalmological examinations.Patients with a higher PeCDF level were more likely to present with symptoms included in the diagnostic criteria, such as pigmentation. In addition, we obtained evidence that recent PeCDF levels had a stronger relationship with recent than past symptoms.ConclusionsRecent PeCDF levels should not be compared directly with past symptoms. However, as the excretion rate of PeCDF has been constant, it is probable that PeCDF levels were higher in the past if recent PeCDF levels were also high. The study confirmed a relationship between past PeCDF levels and past clinical symptoms. For symptoms included in the diagnostic criteria, there was a stronger relationship between PeCDF levels and past symptoms than recent symptoms. Alleviation of symptoms in each patient or aging weakened the relationship between PeCDF levels and symptoms.

Erratum to: Change in decay rates of dioxin-like compounds in Yusho patients

Background: Once ingested, dioxins and dioxin-like compounds are excreted extremely slowly. Excretion can be evaluated by its half-life. Half-lives estimated from observed concentrations are affected by excretion and ongoing exposure. We investigated the change in apparent half-life using a theoretical model based on exposure to dioxin and dioxin-like compounds. Methods: We carried out longitudinal measurements of the blood concentration of dioxins and dioxin-like compounds in a Yusho cohort during 2002 to 2010. We estimated the change in decay rates of 2,3,4,7,8PeCDF and octachlorodibenzodioxin (OCDD) using a second-order equation. Results: We found that the decay rate of OCDD increased, whereas the decay rate of 2,3,4,7,8-PeCDF of patients with a relatively high concentration of 2,3,4,7,8-PeCDF decreased. OCDD results were in accordance with decreasing levels of dioxin and dioxin-like compounds in the environment. The decay rate of OCDD in the body was affected by the decay rate of OCDD in the environment by ingestion because it was near the steady-state. In contrast, the decay rate of 2,3,4,7,8-PeCDF in the body was affected less by ingestion from the environment because it was far higher than in the steady-state. Conclusion: We demonstrated that the level of 2,3,4,7,8-PeCDF in the environment is decreasing. The excretion half-life is longer than the environmental half-life, thus the excretion half-life in a Yusho patient is increased.