Early intervention with suplatast tosilate for prophylaxis of pediatric atopic asthma: A pilot study

The onset of asthma may be related to Th2 cytokine dominance at the time when food allergies occur several months after birth. This study investigated the effectiveness of early intervention with a Th2 cytokine inhibitor (suplatast tosilate) for prevention of asthma in infants with food allergies and atopic dermatitis. Suplatast tosilate dry syrup (6 mg/kg daily) or a histamine H1‐blocker (ketotifen fumarate dry syrup: 0.06 mg/kg daily) was administered randomly to 53 infants with atopic dermatitis caused by food allergies. The primary endpoints were the incidence of asthma and the time to the onset of wheezing. The peripheral blood Th1/Th2 ratio, total IgE level, and eosinophil count were measured before and after treatment. After 24 months of treatment, the prevalence of asthma was significantly lower in the suplatast group (20.8%) than in the ketotifen group (65.6%, p < 0.01). Additionally, the time from the start of treatment to the initial episode of wheezing for infants who developed asthma was significantly longer in the suplatast group than the ketotifen group (p < 0.01). Furthermore, the eosinophil count was significantly decreased by suplatast treatment (p < 0.05), and there was a significant difference between the suplatast and ketotifen groups with respect to both the eosinophil count (p < 0.01) and the Th1/Th2 ratio (p < 0.05). The results of the present pilot study suggest that suplatast tosilate is useful for the primary prevention of wheezing and asthma in children.

[1]  Y. Sano,et al.  Progress in suplatast tosilate research , 2007, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[2]  S. Holgate,et al.  Early life risk factors for adult asthma: a birth cohort study of subjects at risk. , 2001, The Journal of allergy and clinical immunology.

[3]  G. Roberts,et al.  Food allergy as a risk factor for life-threatening asthma in childhood: a case-controlled study. , 2003, The Journal of allergy and clinical immunology.

[4]  Laan,et al.  Markers for early sensitization and inflammation in relation to clinical manifestations of atopic disease up to 2 years of age in 133 high‐risk children , 2000, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[5]  E. Tagaya,et al.  Effect of suplatast tosilate, a Th2 cytokine inhibitor, on steroid-dependent asthma: a double-blind randomised study , 2000, The Lancet.

[6]  S. Holgate,et al.  A birth cohort study of subjects at risk of atopy: twenty-two-year follow-up of wheeze and atopic status. , 2002, American journal of respiratory and critical care medicine.

[7]  M. Ohtsuki,et al.  Guidelines for management of atopic dermatitis , 2009, The Journal of dermatology.

[8]  J. Castro‐Rodriguez,et al.  A clinical index to define risk of asthma in young children with recurrent wheezing. , 2000, American journal of respiratory and critical care medicine.

[9]  J. Warner,et al.  A double-blinded, randomized, placebo-controlled trial of cetirizine in preventing the onset of asthma in children with atopic dermatitis: 18 months' treatment and 18 months' posttreatment follow-up. , 2001, The Journal of allergy and clinical immunology.

[10]  K. Ohta,et al.  Effects of suplatast tosilate on allergic eosinophilic airway inflammation in patients with mild asthma. , 2003, The Journal of allergy and clinical immunology.

[11]  S T Holgate,et al.  Exposure to house-dust mite allergen (Der p I) and the development of asthma in childhood. A prospective study. , 1990, The New England journal of medicine.

[12]  A. Yamada,et al.  Early sensitization to house dust mite is a major risk factor for subsequent development of bronchial asthma in Japanese infants with atopic dermatitis: results of a 4-year followup study. , 2002, Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology.

[13]  U. Wahn,et al.  Long‐lasting sensitization to food during the first two years precedes allergic airway disease , 1998, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[14]  J. Warner,et al.  Prenatal origins of allergic disease. , 2000, The Journal of allergy and clinical immunology.

[15]  Y. Yanagihara,et al.  新しいジメチルスルホニウム剤であるIPD‐1151T(スプラタストトシレート)によるIgE産生の抑制 II ヒトIgE反応の調節 , 1993 .

[16]  Ayne,et al.  ASTHMA AND WHEEZING IN THE FIRST SIX YEARS OF LIFE , 1995 .

[17]  K. Shirato,et al.  Suplatast tosilate inhibits late response and airway inflammation in sensitized guinea pigs. , 1999, American journal of respiratory and critical care medicine.

[18]  J. Warner,et al.  Eosinophil cationic protein and interleukin‐8 levels in bronchial lavage fluid from children with asthma and infantile wheeze , 2001, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[19]  J. Warner,et al.  Markers of eosinophilic inflammation and tissue re‐modelling in children before clinically diagnosed bronchial asthma , 2005, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[20]  B. Kjellman,et al.  Respiratory syncytial virus bronchiolitis in infancy is an important risk factor for asthma and allergy at age 7. , 2000, American journal of respiratory and critical care medicine.

[21]  W. Morgan,et al.  Asthma and wheezing in the first six years of life. The Group Health Medical Associates. , 1995, The New England journal of medicine.

[22]  C. Naspitz,et al.  Prevention of asthma by ketotifen in infants with atopic dermatitis. , 1992, Annals of allergy.

[23]  Bergmann,et al.  Atopic dermatitis in early infancy predicts allergic airway disease at 5 years , 1998, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[24]  N. Kohno,et al.  Effect of Suplatast Tosilate (IPD-1151T) on a Mouse Model of Asthma: Inhibition of Eosinophilic Inflammation and Bronchial Hyperresponsiveness , 2000, International Archives of Allergy and Immunology.

[25]  M. Kiniwa,et al.  Suppression of IgE production by IPD-1151T (suplatast tosilate), a new dimethylsulfonium agent: (2). Regulation of human IgE response. , 1994, Japanese journal of pharmacology.

[26]  J. Bousquet,et al.  Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. VI. Specific immunotherapy prevents the onset of new sensitizations in children. , 1997, The Journal of allergy and clinical immunology.

[27]  J. Warner.  Early treatment of the atopic child. , 1997, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[28]  Marilyn Halonen,et al.  Tucson Children's Respiratory Study: 1980 to present. , 2003, The Journal of allergy and clinical immunology.

[29]  J. Tamaoki,et al.  A TH2 cytokine inhibitor for airway inflammation in mild asthma. , 2003, The Journal of allergy and clinical immunology.

[30]  C. Sorkness,et al.  Atopic characteristics of children with recurrent wheezing at high risk for the development of childhood asthma. , 2004, The Journal of allergy and clinical immunology.

[31]  C. Prussin,et al.  Detection of Intracellular Cytokines by Flow Cytometry , 2002 .

[32]  K. Dabbagh,et al.  Suplatast tosilate inhibits goblet-cell metaplasia of airway epithelium in sensitized mice. , 2000, The Journal of allergy and clinical immunology.

[33]  Y. Nakai,et al.  Suplatast tosilate affects the initial increase in specific IgE and interleukin-4 during immunotherapy for perennial allergic rhinitis. , 1998, Acta oto-laryngologica. Supplementum.

[34]  M. Hoshino,et al.  Effect of suplatast tosilate on goblet cell metaplasia in patients with asthma , 2005, Allergy.

[35]  P. Sly,et al.  Development of allergen-specific T-cell memory in atopic and normal children , 1999, The Lancet.

[36]  R. Sly.  Changing prevalence of allergic rhinitis and asthma. , 1999, Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology.