182
Letters / Ann Allergy Asthma Immunol 112 (2014) 175e183
Table 1 Prevalence of allergic symptoms, proportion of agreement, and k coefficients Variable
Current wheeze Asthma ever Current allergic rhinoconjunctivitis Pollinosis ever Current eczema Eczema ever
Prevalence, % Time 1
Retest
12.5 18.5 13.6 15.2 13.0 39.7
14.7 19.0 14.7 14.1 13.6 41.8
the ISAAC written questionnaire have produced similar k coefficients to our results. A test-retest study of the ISAAC written questionnaire conducted in Malaysian children aged 7 to 12 years after a 1-month interval demonstrated that the k coefficients for the questions on asthma, rhinitis, and eczema were 0.63 to 0.81, 0.49 to 0.52, and 0.34 to 0.83, respectively.4 In an Italian study performed 3 months apart in adolescents, the ISAAC written questionnaire revealed k coefficients between 0.41 and 0.86 for the questions on asthma.5 Furthermore, a randomized study that compared web-based and written ISAAC questionnaires on respiratory symptoms found that both questionnaires yielded equal results in adolescents.6 For the questions regarding respiratory or nose and/or eye symptoms, the questions using “ever” as a reference period tended to have higher reliability than those using “in the past 12 months.” Similar results were found in the Malaysian and Italian studies.4,5 In contrast, the reliability of the question on eczema ever tended to be lower than that on current eczema. The prevalence of current eczema was one-third of that of eczema ever, which means that many children diagnosed as having eczema in infancy outgrow it when they reach school age. Although recalling symptoms experienced during a lifetime might be easier than recalling symptoms during specific intervals, recalling the symptoms only seen in infancy might be less likely to be reliable in a study conducted in schoolchildren. Compared with higher reliability of the questions on respiratory and nose and/or eye symptoms, reliability of the questions on eczema was lower, consistent with the results of the Malaysian study.4 This lower reliability might be explained by languages and cultural backgrounds. The ISAAC phase 3 study group reported that some English terms were difficult to translate into other languages despite a detailed protocol.7 Terms such as itchy rash and eczema might have their own interpretation problems in Japanese along with Bahasa Malaysia.4 Although the Japanese version of the ISAAC questionnaire used footnotes to describe skin lesions, our results suggested that the language problems persisted. The limitation of this study was the concern about generalizability; people who did not have access to computers with Internet connections could not participate in this study. The Ministry of Internal Affairs and Communications in Japan (http://www.soumu.go. jp/johotsusintokei/english/) revealed that the Internet diffusion rate among people aged 20 to 49 years exceeded 90%, which means that most parents of schoolchildren currently use the Internet in Japan. The web-based ISAAC questionnaire was found to be as reliable as the written one and could become a new research tool when the target population has a high Internet penetration rate. Further
Proportion of Agreement, %
k Coefficient (95% Confidence Interval)
91.3 94.0 91.3 94.6 89.7 75.0
0.63 0.80 0.64 0.78 0.55 0.48
(0.46-0.80) (0.69-0.92) (0.48-0.80) (0.65-0.91) (0.37-0.73) (0.35-0.61)
studies are needed to create a web-based questionnaire using multimedia, such as sound and visual content, which would lead to further improvement in the reliability of questionnaires. Koichi Yoshida, MD* Yuichi Adachi, MD, PhDy Mari Sasaki, MD* Mayumi Furukawa, MD* Toshiko Itazawa, MD, PhDy Koji Hashimoto, MD, PhDz Hiroshi Odajima, MD, PhDx Akira Akasawa, MD, PhD* *Division of Allergy Tokyo Metropolitan Children’s Medical Center Tokyo, Japan y Department of Pediatrics University of Toyama Toyama, Japan z Department of Pediatrics and Child Health Nihon University School of Medicine Tokyo, Japan x Department of Pediatrics Fukuoka National Hospital Fukuoka, Japan [email protected]
References [1] Asher MI, Keil U, Anderson HR, et al. International Study of Asthma and Allergies in Childhood (ISAAC): rationale and methods. Eur Respir J. 1995;8: 483e491. [2] Ellwood P, Asher MI, Stewart AW. The impact of the method of consent on response rates in the ISAAC time trends study. Int J Tuberc Lung Dis. 2010;14: 1059e1065. [3] van Gelder MM, Bretveld RW, Roeleveld N. Web-based questionnaires: the future in epidemiology? Am J Epidemiol. 2010;172:1292e1298. [4] Norzila MZ, Haifa AL, Deng CT, Azizi BH. Prevalence of childhood asthma and allergy in an inner city Malaysian community: intra-observer reliability of two translated international questionnaires. Med J Malaysia. 2000;55:33e39. [5] Fuso L, de Rosa M, Corbo GM, et al. Repeatability of the isaac video questionnaire and its accuracy against a clinical diagnosis of asthma. Respir Med. 2000; 94:397e403. [6] Raat H, Mangunkusumo RT, Mohangoo AD, Juniper EF, Van Der Lei J. Internet and written respiratory questionnaires yield equivalent results for adolescents. Pediatr Pulmonol. 2007;42:357e361. [7] Ellwood P, Williams H, Ait-Khaled N, Bjorksten B, Robertson C. Translation of questions: the International Study of Asthma and Allergies in Childhood (ISAAC) experience. Int J Tuberc Lung Dis. 2009;13:1174e1182.
Urinary biopyrrin: a potential inflammatory marker of atopic dermatitis Atopic dermatitis (AD) is a chronic and relapsing eczematous disease that is generally associated with allergen-induced skin inflammation. Chronic persistent inflammation by free radicals is postulated Disclosures: Authors have nothing to disclose.
to impair skin barrier function, leading to dry skin and sustained pruritus; therefore, excessive oxidative stress is postulated to exacerbate the inflammatory process of AD.1 In children with AD, levels of urinary 8-hydroxydeoxyguanosine, a product of nucleic acid oxidation, are indeed elevated according to disease severity.2
Letters / Ann Allergy Asthma Immunol 112 (2014) 175e183
Figure 1. Urinary biopyrrin levels in patients with atopic dermatitis (AD) by SCORing of Atopic Dermatitis classification of AD severity. Cre indicates creatinine.
Biopyrrin, one of the oxidative metabolites of bilirubin, is excreted into the urine and measured using enzyme-linked immunosorbent assay. Urinary biopyrrin levels have recently gained attention as an indicator of the internal oxidative stress associated with heart disease and aggressive physical exercise.3 In asthma, urinary biopyrrin levels are known to be elevated and correlated with clinical severity.4 However, no report has documented AD. We collected urine samples from 33 patients with AD without other allergic diseases (16 men and 17 women; age range, 22e78 years) and 20 healthy control subjects (10 men and 10 women; age range, 25e65 years). No significant difference was found in age or sex between the AD and control groups. AD was diagnosed based on the Japanese Dermatological Association criteria. Disease severity was classified into 3 groups using SCORing Atopic Dermatitis (SCORAD): mild (score, 40; 13 patients). The mean total IgE level was 28,645.63 IU/mL in patients with allergic AD (n ¼ 30) and 59.33 IU/mL in patients with nonallergic AD (n ¼ 3) (Fig 1). Urinary biopyrrin levels were measured using an enzyme-linked immunosorbent assay kit (Shino-test Co, Tokyo, Japan) according to the manufacturer’s recommendation. The concentration of urinary biopyrrin was adjusted by the urinary creatinine concentration.5 Statistical analysis was performed using the t test and Spearman correlation analysis, and P < .01 was considered statistically significant. All the results were expressed as mean (SD). Urinary biopyrrin levels in patients with AD were significantly elevated compared with those of healthy subjects
183
(2.65 [1.32] vs 1.53 [0.39]). Furthermore, urinary biopyrrin levels in patients with moderate and severe AD were significantly higher than those in patients with mild AD or in the healthy group (Fig 1). Urinary biopyrrin levels were also positively correlated with the SCORAD score in patients with AD (r ¼ 0.5553, P < .01). We first proved that the urinary biopyrrin levels were elevated in patients with AD compared with those of the healthy age- and sex-matched individuals. A significant correlation between biopyrrin level and AD disease severity further stressed the active involvement of oxidative stress in the inflammatory process of AD. However, there was a poor correlation between urinary biopyrrin levels and serum IgE levels in patients with AD, although most patients had allergic AD (r ¼ 0.1597, P ¼ .45). IgE is an important diagnostic verification and diseasemodifying factor in AD. In fact, mast cell and eosinophil activation via IgE culminates in the release of inflammatory mediators, such as histamine and cytokines or chemokines, that involve those promoting the TH2-polarized T-cell response.6 The results could be due to the development of AD. TH1/TH2 cell dysregulation, barrier dysfunction, and oxidative and IgE signaling stress play key roles in the evolution of the chronic, pruritic, inflammatory dermatosis that characterizes AD. Because urinary sampling is noninvasive, urinary biopyrrin levels may be potentially useful for monitoring AD progression. Takahito Chiba, MD, PhD* Saori Tatematsu, MD* Masayoshi Nakao, MD* Masutaka Furue, MD, PhDy *Department of Dermatology Iizuka Hospital Fukuoka, Japan y Department of Dermatology Graduate School of Medical Sciences Kyushu University Fukuoka, Japan [email protected]
References [1] Bito T, Nishigori C. Impact of reactive oxygen species on keratinocyte signaling pathways. J Dermatol Sci. 2012;68:3e8. [2] Omata N, Tsukahara H, Ito S, et al. Increased oxidative stress in childhood atopic dermatitis. Life Sci. 2001;69:223e228. [3] Yamaguchi T, Shioji I, Sugimoto A, et al. Epitope of 24G7 anti-bilirubin monoclonal antibody. Biochim Biophys Acta. 1996;1289:110e114. [4] Ito W, Tanigai S, Ueki S, et al. Increased urinary biopyrrins in patients with asthma. Allergy. 2010;65:1343e1344. [5] Hokamaki J, Kawano H, Yoshimura M, et al. Urinary biopyrrins levels are elevated in relation to severity of heart failure. J Am Coll Cardiol. 2004;43: 1880e1885. [6] Liu FT, Goodarzi H, Chen HY. IgE, mast cells and eosinophils in atopic dermatitis. Clin Rev Allergy Immunol. 2011;41:298e310.
Letters / Ann Allergy Asthma Immunol 112 (2014) 175e183
Table 1 Prevalence of allergic symptoms, proportion of agreement, and k coefficients Variable
Current wheeze Asthma ever Current allergic rhinoconjunctivitis Pollinosis ever Current eczema Eczema ever
Prevalence, % Time 1
Retest
12.5 18.5 13.6 15.2 13.0 39.7
14.7 19.0 14.7 14.1 13.6 41.8
the ISAAC written questionnaire have produced similar k coefficients to our results. A test-retest study of the ISAAC written questionnaire conducted in Malaysian children aged 7 to 12 years after a 1-month interval demonstrated that the k coefficients for the questions on asthma, rhinitis, and eczema were 0.63 to 0.81, 0.49 to 0.52, and 0.34 to 0.83, respectively.4 In an Italian study performed 3 months apart in adolescents, the ISAAC written questionnaire revealed k coefficients between 0.41 and 0.86 for the questions on asthma.5 Furthermore, a randomized study that compared web-based and written ISAAC questionnaires on respiratory symptoms found that both questionnaires yielded equal results in adolescents.6 For the questions regarding respiratory or nose and/or eye symptoms, the questions using “ever” as a reference period tended to have higher reliability than those using “in the past 12 months.” Similar results were found in the Malaysian and Italian studies.4,5 In contrast, the reliability of the question on eczema ever tended to be lower than that on current eczema. The prevalence of current eczema was one-third of that of eczema ever, which means that many children diagnosed as having eczema in infancy outgrow it when they reach school age. Although recalling symptoms experienced during a lifetime might be easier than recalling symptoms during specific intervals, recalling the symptoms only seen in infancy might be less likely to be reliable in a study conducted in schoolchildren. Compared with higher reliability of the questions on respiratory and nose and/or eye symptoms, reliability of the questions on eczema was lower, consistent with the results of the Malaysian study.4 This lower reliability might be explained by languages and cultural backgrounds. The ISAAC phase 3 study group reported that some English terms were difficult to translate into other languages despite a detailed protocol.7 Terms such as itchy rash and eczema might have their own interpretation problems in Japanese along with Bahasa Malaysia.4 Although the Japanese version of the ISAAC questionnaire used footnotes to describe skin lesions, our results suggested that the language problems persisted. The limitation of this study was the concern about generalizability; people who did not have access to computers with Internet connections could not participate in this study. The Ministry of Internal Affairs and Communications in Japan (http://www.soumu.go. jp/johotsusintokei/english/) revealed that the Internet diffusion rate among people aged 20 to 49 years exceeded 90%, which means that most parents of schoolchildren currently use the Internet in Japan. The web-based ISAAC questionnaire was found to be as reliable as the written one and could become a new research tool when the target population has a high Internet penetration rate. Further
Proportion of Agreement, %
k Coefficient (95% Confidence Interval)
91.3 94.0 91.3 94.6 89.7 75.0
0.63 0.80 0.64 0.78 0.55 0.48
(0.46-0.80) (0.69-0.92) (0.48-0.80) (0.65-0.91) (0.37-0.73) (0.35-0.61)
studies are needed to create a web-based questionnaire using multimedia, such as sound and visual content, which would lead to further improvement in the reliability of questionnaires. Koichi Yoshida, MD* Yuichi Adachi, MD, PhDy Mari Sasaki, MD* Mayumi Furukawa, MD* Toshiko Itazawa, MD, PhDy Koji Hashimoto, MD, PhDz Hiroshi Odajima, MD, PhDx Akira Akasawa, MD, PhD* *Division of Allergy Tokyo Metropolitan Children’s Medical Center Tokyo, Japan y Department of Pediatrics University of Toyama Toyama, Japan z Department of Pediatrics and Child Health Nihon University School of Medicine Tokyo, Japan x Department of Pediatrics Fukuoka National Hospital Fukuoka, Japan [email protected]
References [1] Asher MI, Keil U, Anderson HR, et al. International Study of Asthma and Allergies in Childhood (ISAAC): rationale and methods. Eur Respir J. 1995;8: 483e491. [2] Ellwood P, Asher MI, Stewart AW. The impact of the method of consent on response rates in the ISAAC time trends study. Int J Tuberc Lung Dis. 2010;14: 1059e1065. [3] van Gelder MM, Bretveld RW, Roeleveld N. Web-based questionnaires: the future in epidemiology? Am J Epidemiol. 2010;172:1292e1298. [4] Norzila MZ, Haifa AL, Deng CT, Azizi BH. Prevalence of childhood asthma and allergy in an inner city Malaysian community: intra-observer reliability of two translated international questionnaires. Med J Malaysia. 2000;55:33e39. [5] Fuso L, de Rosa M, Corbo GM, et al. Repeatability of the isaac video questionnaire and its accuracy against a clinical diagnosis of asthma. Respir Med. 2000; 94:397e403. [6] Raat H, Mangunkusumo RT, Mohangoo AD, Juniper EF, Van Der Lei J. Internet and written respiratory questionnaires yield equivalent results for adolescents. Pediatr Pulmonol. 2007;42:357e361. [7] Ellwood P, Williams H, Ait-Khaled N, Bjorksten B, Robertson C. Translation of questions: the International Study of Asthma and Allergies in Childhood (ISAAC) experience. Int J Tuberc Lung Dis. 2009;13:1174e1182.
Urinary biopyrrin: a potential inflammatory marker of atopic dermatitis Atopic dermatitis (AD) is a chronic and relapsing eczematous disease that is generally associated with allergen-induced skin inflammation. Chronic persistent inflammation by free radicals is postulated Disclosures: Authors have nothing to disclose.
to impair skin barrier function, leading to dry skin and sustained pruritus; therefore, excessive oxidative stress is postulated to exacerbate the inflammatory process of AD.1 In children with AD, levels of urinary 8-hydroxydeoxyguanosine, a product of nucleic acid oxidation, are indeed elevated according to disease severity.2
Letters / Ann Allergy Asthma Immunol 112 (2014) 175e183
Figure 1. Urinary biopyrrin levels in patients with atopic dermatitis (AD) by SCORing of Atopic Dermatitis classification of AD severity. Cre indicates creatinine.
Biopyrrin, one of the oxidative metabolites of bilirubin, is excreted into the urine and measured using enzyme-linked immunosorbent assay. Urinary biopyrrin levels have recently gained attention as an indicator of the internal oxidative stress associated with heart disease and aggressive physical exercise.3 In asthma, urinary biopyrrin levels are known to be elevated and correlated with clinical severity.4 However, no report has documented AD. We collected urine samples from 33 patients with AD without other allergic diseases (16 men and 17 women; age range, 22e78 years) and 20 healthy control subjects (10 men and 10 women; age range, 25e65 years). No significant difference was found in age or sex between the AD and control groups. AD was diagnosed based on the Japanese Dermatological Association criteria. Disease severity was classified into 3 groups using SCORing Atopic Dermatitis (SCORAD): mild (score, 40; 13 patients). The mean total IgE level was 28,645.63 IU/mL in patients with allergic AD (n ¼ 30) and 59.33 IU/mL in patients with nonallergic AD (n ¼ 3) (Fig 1). Urinary biopyrrin levels were measured using an enzyme-linked immunosorbent assay kit (Shino-test Co, Tokyo, Japan) according to the manufacturer’s recommendation. The concentration of urinary biopyrrin was adjusted by the urinary creatinine concentration.5 Statistical analysis was performed using the t test and Spearman correlation analysis, and P < .01 was considered statistically significant. All the results were expressed as mean (SD). Urinary biopyrrin levels in patients with AD were significantly elevated compared with those of healthy subjects
183
(2.65 [1.32] vs 1.53 [0.39]). Furthermore, urinary biopyrrin levels in patients with moderate and severe AD were significantly higher than those in patients with mild AD or in the healthy group (Fig 1). Urinary biopyrrin levels were also positively correlated with the SCORAD score in patients with AD (r ¼ 0.5553, P < .01). We first proved that the urinary biopyrrin levels were elevated in patients with AD compared with those of the healthy age- and sex-matched individuals. A significant correlation between biopyrrin level and AD disease severity further stressed the active involvement of oxidative stress in the inflammatory process of AD. However, there was a poor correlation between urinary biopyrrin levels and serum IgE levels in patients with AD, although most patients had allergic AD (r ¼ 0.1597, P ¼ .45). IgE is an important diagnostic verification and diseasemodifying factor in AD. In fact, mast cell and eosinophil activation via IgE culminates in the release of inflammatory mediators, such as histamine and cytokines or chemokines, that involve those promoting the TH2-polarized T-cell response.6 The results could be due to the development of AD. TH1/TH2 cell dysregulation, barrier dysfunction, and oxidative and IgE signaling stress play key roles in the evolution of the chronic, pruritic, inflammatory dermatosis that characterizes AD. Because urinary sampling is noninvasive, urinary biopyrrin levels may be potentially useful for monitoring AD progression. Takahito Chiba, MD, PhD* Saori Tatematsu, MD* Masayoshi Nakao, MD* Masutaka Furue, MD, PhDy *Department of Dermatology Iizuka Hospital Fukuoka, Japan y Department of Dermatology Graduate School of Medical Sciences Kyushu University Fukuoka, Japan [email protected]
References [1] Bito T, Nishigori C. Impact of reactive oxygen species on keratinocyte signaling pathways. J Dermatol Sci. 2012;68:3e8. [2] Omata N, Tsukahara H, Ito S, et al. Increased oxidative stress in childhood atopic dermatitis. Life Sci. 2001;69:223e228. [3] Yamaguchi T, Shioji I, Sugimoto A, et al. Epitope of 24G7 anti-bilirubin monoclonal antibody. Biochim Biophys Acta. 1996;1289:110e114. [4] Ito W, Tanigai S, Ueki S, et al. Increased urinary biopyrrins in patients with asthma. Allergy. 2010;65:1343e1344. [5] Hokamaki J, Kawano H, Yoshimura M, et al. Urinary biopyrrins levels are elevated in relation to severity of heart failure. J Am Coll Cardiol. 2004;43: 1880e1885. [6] Liu FT, Goodarzi H, Chen HY. IgE, mast cells and eosinophils in atopic dermatitis. Clin Rev Allergy Immunol. 2011;41:298e310.
