Sankei Nishima

Prevalence and impact of rhinitis in asthma. SACRA, a cross-sectional nation-wide study in Japan

To cite this article: Ohta K, Bousquet P‐J, Aizawa H, Akiyama K, Adachi M, Ichinose M, Ebisawa M, Tamura G, Nagai A, Nishima S, Fukuda T, Morikawa A, Okamoto Y, Kohno Y, Saito H, Takenaka H, Grouse L, Bousquet J. Prevalence and impact of rhinitis in asthma: SACRA, a cross‐sectional nation‐wide study in Japan. Allergy 2011; 66: 1287–1295.

Japanese Guideline for Adult Asthma

Adult bronchial asthma (hereinafter, asthma) is characterized by chronic airway inflammation, reversible airway narrowing, and airway hyperresponsiveness. Long-standing asthma induces airway remodeling to cause an intractable asthma. The number of patients with asthma has increased, while the number of patients who die from asthma has decreased (1.7 per 100,000 patients in 2009). The aim of asthma treatment is to enable patients with asthma to lead a healthy life without any symptoms. A partnership between physicians and patients is indispensable for appropriate treatment. Long-term management with agents and elimination of causes and risk factors are fundamental to asthma treatment. Four steps in pharmacotherapy differentiate mild to intensive treatments; each step includes an appropriate daily dose of an inhaled corticosteroid (ICS), varying from low to high doses. Long-acting β(2) agonists (LABA), leukotriene receptor antagonists, and theophylline sustained-release preparation are recommended as concomitant drugs, while anti-IgE antibody therapy is a new choice for the most severe and persistent asthma. Inhaled β(2) agonists, aminophylline, corticosteroids, adrenaline, oxygen therapy, etc., are used as needed against acute exacerbations. Allergic rhinitis, chronic obstructive pulmonary disease (COPD), aspirin induced asthma, pregnancy, and cough variant asthma are also important factors that need to be considered.

Surveys on the Prevalence of Pediatric Bronchial Asthma in Japan: A Comparison between the 1982, 1992, and 2002 Surveys Conducted in the Same Region Using the Same Methodology

BACKGROUND We conducted and reported the first (1982; 55,388 subjects), and second (1992; 45,674 subjects), epidemiological surveys conducted on bronchial asthma in elementary students across 11 prefectures in western Japan. The 2 surveys were conducted in the same regions using the same methodology employing a modified Japanese version of the American Thoracic Society-Division of Lung Diseases (ATS-DLD) Epidemiology Questionnaire. We conducted the third survey in 2002, and compared the findings to those of previous studies. METHODS In the third survey, 37,036 students attending the same schools as in previous surveys (in 11 prefectures) were given the questionnaire. A total of 35,582 responses (96.1%) were collected. An ATS-DLD Epidemiology Questionnaire was also used in this study, and the findings were compared to those of previous studies. RESULTS 1. The prevalence of bronchial asthma (BA) in boys, girls, and all students was 3.8%, 2.5%, and 3.2%, respectively, for the first survey; 5.6%, 3.5%, and 4.6% for the second survey; and 8.1%, 4.9%, and 6.5% for the third survey. 2. A decline in the BA prevalence in older subjects which could be seen in the first survey was absent in the second and third surveys. There were no regional differences in the third survey. 3. The boys-to-girls ratio in the first, second, and third surveys was 1.5, 1.6, and 1.6, respectively. 4. BA was more prevalent among subjects with a past history of respiratory disease in infancy and those with a family history of allergic disease. 5. The prevalence of asthma symptoms and wheezing in the first, second, and third surveys was 7.1%, 9.8%, and 11.8%, respectively. 6. A comparison of the prevalence of other allergic diseases between the second and third surveys revealed a decrease in atopic dermatitis and an increase in allergic rhinitis, allergic conjunctivitis, and cedar pollinosis. CONCLUSIONS BA prevalence in the third survey increased 2.1 and 1.4 times respectively compared to the first survey and second survey, indicating an upward trend in all regions and age groups surveyed.

Pediatric allergy and immunology in Japan

The Japanese Society of Pediatric Allergy and Clinical Immunology (JSPACI) was started in 1966 and currently has 3613 members as of August 1, 2012. The number of pediatricians specializing in allergies who have been certified by the Japanese Society of Allergology is 817. Among these, there are 125 training directors and training facilities for allergy and clinical immunology. The JSPACI first published an asthma guideline specific for children in 2000, and this has been revised every 3 yrs, contributing to better control of pediatric asthma. Food allergy management guidelines were first developed in 2005, which have helped to improve the care of food allergy patients. Among 514 pediatric training programs by the Japanese Society of Pediatrics, there are 312 facilities routinely performing oral food challenges. Among these, there were already 53 facilities performing oral immunotherapy at the end of 2011, treating 1400 cases of food allergy. The prevalence of pediatric allergic diseases has increased in Japan over the past 50 yrs. A number of International Study of Asthma and Allergies in Childhood surveys have been conducted in the past at specific times. The prevalence of wheezing among children aged 13–14 yrs in 2002 was 13.0%. Multi‐year surveys found a 1.5‐ to 2‐fold increase every 10 yrs until 2002. However, according to the latest data in 2012, asthma prevalence seems to have slightly decreased in Japan. Food allergy mainly associated with infantile atopic eczema among infants younger than 1 yr of age is the most common form as with other developed countries. The estimated food allergy prevalence based on data from several surveys is 5–10% among infants (0–6 yrs) and 1–2% among schoolchildren (6–15 yrs). A variety of patients suffering from primary deficiency syndrome have been actively analyzed. Previously, antibody defects and well‐defined syndromes with immunodeficiency were analyzed, but recent research is focusing on not only acquired immune disorders but also on innate immune disorders. In contrast to the widespread use of oral immunotherapy, one immediate issue is to develop and reassess subcutaneous and sublingual immunotherapies for mite and Japanese cedar pollen antigens that have been disused in Japan since the 1990s.

Lack of association between CD28/CTLA-4 gene polymorphisms and atopic asthma in the Japanese population.

Atopic asthma occurs in genetically susceptible individuals in the presence of environmental factors. Recently, the costimulation signal from CD80-CD86 to CD28/CTLA-4 has been suggested to play an important role in the development of atopic asthma. In the present study, we analyzed three polymorphic regions within the CTLA-4 gene, an A/G substitution in exon 1 position 49, a C/T base exchange in the promoter position –318 and an (AT)n repeat polymorphism in the 3′-untranslated region of exon 4, and a CD28 gene polymorphism with a T/C substitution in intron 3 position +17 in 120 patients with atopic asthma and 200 normal controls. The polymorphism frequencies of CTLA-4/CD28 genes in patients did not differ from those in normal controls. Thus, the present study was unable to reveal any association between CTLA-4/CD28 gene polymorphisms and atopic asthma in the Japanese population.

Japanese pediatric guidelines for the treatment and management of bronchial asthma 2008

The fourth version of the Japanese Pediatric Guidelines for the Treatment and Management of Bronchial Asthma 2008 (JPGL 2008) was published by the Japanese Society of Pediatric Allergy and Clinical Immunology in December 2008. In JPGL 2008, the recommendations were revised on the basis of the JPGL 2005. The JPGL 2008 is different to the Global Initiative for Asthma guideline in that it contains the following items: a classification system of asthma severity; recommendations for long‐term management organized by age; a special mention of infantile asthma; and an emphasis on prevention and early intervention. Here we show a summary of the JPGL 2008 revising our previous report concerning JPGL 2005.

Usefulness of specific IgE antibodies to ω-5 gliadin in the diagnosis and follow-up of Japanese children with wheat allergy

BACKGROUND Gliadins have been implicated in IgE-mediated allergy to ingested wheat. ω-5 gliadin seems to be a clinically relevant allergen component in children with immediate wheat allergy (WA), but contradictory results have been published. OBJECTIVES To investigate whether specific IgE (sIgE) antibodies to recombinant ω-5 gliadin could be used as a marker for oral wheat challenge outcome in wheat-sensitized children and to study whether measurements of sIgE to ω-5 gliadin are useful in monitoring children with WA to assess whether the allergy is outgrown or persistent. METHODS Eighty-eight serum samples from children sensitized to wheat were collected consecutively. sIgE to ω-5 gliadin was related to a physicians diagnosis of WA. RESULTS Sixty-seven of 88 children sensitized to wheat were diagnosed as having WA. The geometric mean concentrations of sIgE to ω-5 gliadin were 2.04 kU(A)/L (range, <0.35-100 kU(A)/L) in children with WA and 0.40 kU(A)/L (range, <0.35-1.8 kU(A)/L) in children without WA. At follow-up, after being on a wheat-free diet for approximately 2 years, the sIgE titers to ω-5 gliadin were below 0.35 kU(A)/L (mean, 0.34 kU(A)/L; range, 0.34-2.3 kU(A)/L) in 10 of 15 children with outgrown WA. Conversely, in 12 of 14 children with persistent WA, the sIgE titers to ω-5 gliadin were still elevated (mean, 5.89 kU(A)/L; range, 0.34-16.3 kU(A)/L). CONCLUSIONS sIgE to ω-5 gliadin can be used as an accurate alternative to potentially dangerous wheat food challenges in monitoring WA.

Japanese Guideline for Childhood Asthma 2014

The Japanese Guideline for the Diagnosis and Treatment of Allergic Diseases 2013 (JAGL 2013) describes childhood asthma after the Japanese Pediatric Guideline for the Treatment and Management of Asthma 2012 (JPGL 2012) by the Japanese Society of Pediatric Allergy and Clinical Immunology. JAGL 2013 provides information on diagnosis by age group from infancy to puberty (0-15 years of age), treatment for acute exacerbations, long-term management by anti-inflammatory drugs, daily life guidance, and patient education to allow non-specialist physicians to refer to this guideline for routine medical treatment. JAGL differs from the Global Initiative for Asthma Guideline (GINA) in that JAGL emphasizes early diagnosis and intervention at <2 years and 2-5 years of age. A management method, including step-up or step-down of long-term management drugs based on the status of asthma control levels, as in JAGL, is easy to understand, and thus the Guideline is suitable as a frame of reference for routine medical treatment. JAGL has also introduced treatment and management using a control test on children, recommending that the physician aim at complete control by avoiding exacerbation factors and by appropriate use of anti-inflammatory drugs.The Japanese Guideline for the Diagnosis and Treatment of Allergic Diseases 2013 (JAGL 2013) describes childhood asthma after the Japanese Pediatric Guideline for the Treatment and Management of Asthma 2012 (JPGL 2012) by the Japanese Society of Pediatric Allergy and Clinical Immunology. JAGL 2013 provides information on diagnosis by age group from infancy to puberty (0-15 years of age), treatment for acute exacerbations, long-term management by anti-inflammatory drugs, daily life guidance, and patient education to allow non-specialist physicians to refer to this guideline for routine medical treatment. JAGL differs from the Global Initiative for Asthma Guideline (GINA) in that JAGL emphasizes early diagnosis and intervention at <2 years and 2-5 years of age. A management method, including step-up or step-down of long-term management drugs based on the status of asthma control levels, as in JAGL, is easy to understand, and thus the Guideline is suitable as a frame of reference for routine medical treatment. JAGL has also introduced treatment and management using a control test on children, recommending that the physician aim at complete control by avoiding exacerbation factors and by appropriate use of anti-inflammatory drugs.

Exhaled nitric oxide and exercise-induced bronchospasm assessed by FEV1, FEF25-75% in childhood asthma.

The relationship between exhaled nitric oxide (eNO) and bronchial hyperresponsiveness (BHR) should be clarified. The aim of this study was to determine the relationship between eNO and exercise-induced bronchospasm (EIB) by estimation of the each lung parameter in asthmatic children who performed a bicycle ergometer exercise test. Twenty children with asthma were recruited. eNO concentration was examined by the recommended online method. To evaluate BHR, an exercise stress test was performed on a bicycle ergometer. The mean baseline eNO value was significantly correlated with the mean maximum % fall in forced expiratory volume in 1 second (FEV1), forced expiratory flow between 25% and 75% (FEF25-75%) after exercise (r = 0.53, r = 0.65, respectively). eNO in the EIB-positive group was significantly higher than that in the EIB-negative group by assessing FEV1, FEF25−75% (p < 0.005, p = 0.005). We demonstrated that the most important lung parameter assessed the occurrence of EIB by a bicycle ergometer exercise test was not only FEV1 but FEF25−75%, which significantly correlated with eNO. This suggests that not only FEV1 but FEF25−75% can be used to evaluate the correlations between BHR (EIB) and airway inflammation (eNO) in asthmatic children. A low eNO is useful for a negative predictor for EIB.

Novel polymorphism in the coding region of the IL-13 receptor alpha' gene: association study with atopic asthma in the Japanese population.

Interleukin (IL)-4 and IL-13 play key roles in the development of atopic asthma. The IL-13 receptor (R) α′ chain is a component of both IL-4R and IL-13R complexes. By screening the whole coding region of the IL-13Rα′ gene for polymorphisms, we identified a new polymorphism at nucleotide position 1050 from the ATG start codon. The allelic frequency of the C/T polymorphism in the Japanese population was found to be 0.97:0.03. Because of the low frequency of the T allele, the association study failed to indicate any significant association between this polymorphism and atopic asthma in the Japanese population. Further studies are required in other racial groups with higher frequencies of this polymorphism to elucidate the association.