The skin is continuously exposed to external pathogens, and its barrier function is critical for skin homeostasis. Previous studies have shown that the barrier dysfunction is one of the most predisposing factors for the development of skin allergic diseases such as atopic dermatitis. In this article, we summarize how the physical barrier of the skin is organized and review its link to the pathomechanism of skin allergic diseases. We describe the formation of the SC barrier in terms of the following five categories: 1) filaggrin metabolism; 2) cornified envelope; 3) intercellular lipids; 4) corneodesmosome; and 5) corneocyte desquamation. New approaches to restoring the skin barrier function are also discussed.

Bronchial asthma is characterized by persistent cough, increased sputum, and repeated wheezing. The pathophysiology underlying these symptoms is the hyper-responsiveness of the airway along with chronic airway inflammation. Repeated injury, repair, and regeneration of the airway epithelium following exposure to environmental factors and inflammation results in histological changes and functional abnormalities in the airway mucosal epithelium; such changes are believed to have a significant association with the pathophysiology of asthma. Damage to the barrier functions of the airway epithelium enhances mucosal permeability of foreign substances in the airway epithelium of patients with asthma. Thus, epithelial barrier fragility is closely involved in releasing epithelial cytokines (e.g., TSLP, IL-25, and IL-33) because of the activation of airway epithelial cells, dendritic cells, and innate group 2 innate lymphoid cells (ILC2). Functional abnormalities of the airway epithelial cells along with the activation of dendritic cells, Th2 cells, and ILC2 form a single immunopathological unit that is considered to cause allergic airway inflammation. Here we use the latest published literature to discuss the potential pathological mechanisms regarding the onset and progressive severity of asthma with regard to the disruption of the airway epithelial function.

Epithelial cells form the first physiological barrier against invasion by pathogens and the infiltration of allergens. Tight junctions (TJ), a cell-cell junctional complex located on the apical side of epithelial cells, have a critical role in the maintenance of epithelial barrier function. Impaired TJ structures are observed in patients with asthma, atopic dermatitis and nasal allergy; therefore, the dysfunction of epithelial barriers might be involved in the initiation or progression of allergic diseases. Protease-containing allergens and environmental pollutants enhance paracellular transport in epithelial cells through disruption of epithelial barrier function. This suggests that the disruption of TJ leads to the promotion of allergen delivery into the subepithelia, resulting in the progression of allergic diseases. Thus, protection of the epithelial barrier function might prevent or inhibit the development or exacerbation of allergic diseases. Recently, we reported that diesel exhaust particles (DEP), the main component of particulate patter 2.5, exacerbated allergic rhinitis (AR) in a mouse model through TJ disruption. In addition, we revealed that the oxidative stress-mediated pathway is involved in the effects caused by DEP and that nasal treatment with a reactive oxygen species (ROS) scavenger suppressed DEP-induced TJ disruption and exacerbation of AR. In this review, we focus on the relationship between TJ disruption and allergic disease. Furthermore, we discuss our recent findings regarding TJ disruption and the exacerbation of AR.

Therapeutic strategy in late 20th century to prevent allergic diseases was derived from a conceptual framework of allergens elimination which was as same as that of coping with them after their onset. Manifold trials were implemented; however, most of them failed to verify the effectiveness of their preventive measures. Recent advancement of epidemiological studies and cutaneous biology revealed epidermal barrier dysfunction plays a major role of allergen sensitization and development of atopic dermatitis which ignites the inception of allergy march. For this decade, therapeutic strategy to prevent the development of food allergy has been confronted with a paradigm shift from avoidance and delayed introduction of allergenic foods based on the theoretical concept to early introduction of them based on the clinical and epidemiological evidences. Especially, prevention of peanut allergy and egg allergy has been established with the highest evidence verified by randomized controlled trials, although application in clinical practice should be done with attention. This paradigm shift concerning food allergy was also due to the discovery of cutaneous sensitization risk of food allergens for an infant with eczema revealed by prospective studies. Here we have recognized the increased importance of prevention of eczema/atopic dermatitis in infancy. Two randomized controlled trials using emollients showed successful results in prevention of atopic dermatitis in infancy; however, longer term safety and prognosis including allergy march should be pursued. To establish more fundamental strategy for prevention of the development of allergy, further studies clarifying the mechanisms of interaction between barrier dysfunction and microbial milieu are needed with macroscope to understand the relationship between allergic diseases and a diversity of environmental influences.

Psychological stress is recognized as a key factor in the exacerbation of allergic asthma, whereby brain responses to stress act as immunomodulators for asthma. In particular, stress-induced enhanced type 2 T-helper (Th2)-type lung inflammation is strongly associated with asthma pathogenesis. Psychological stress leads to eosinophilic airway inflammation through activation of the hypothalamic-pituitary-adrenal pathway and autonomic nervous system. This is followed by the secretion of stress hormones into the blood, including glucocorticoids, epinephrine, and norepinephrine, which enhance Th2 and type 17 T-helper (Th17)-type asthma profiles in humans and rodents. Recent evidence has shown that a defect of the μ-opioid receptor in the brain along with a defect of the peripheral glucocorticoid receptor signaling completely disrupted stress-induced airway inflammation in mice. This suggests that the stress response facilitates events in the central nervous and endocrine systems, thus exacerbating asthma. In this review, we outline the recent findings on the interplay between stress and neuroendocrine activities followed by stress-induced enhanced Th2 and Th17 immune responses and attenuated regulatory T (Treg) cell responses that are closely linked with asthma exacerbation. We will place a special focus on our own data that has emphasized the continuity from central sensing of psychological stress to enhanced eosinophilic airway inflammation. The mechanism that modulates psychological stress-induced exacerbation of allergic asthma through neuroendocrine activities is thought to involve a series of consecutive pathological events from the brain to the lung, which implies there to be a “neuropsychiatry phenotype” in asthma.

Primary immunodeficiencies (PIDs) are a heterogeneous group of inherited diseases of the immune system. The definite diagnosis of PID is ascertained by genetic analysis; however, this takes time and is costly. Flow cytometry provides a rapid and highly sensitive tool for diagnosis of PIDs.

Flow cytometry can evaluate specific cell populations and subpopulations, cell surface, intracellular and intranuclear proteins, biologic effects associated with specific immune defects, and certain functional immune characteristics, each being useful for the diagnosis and evaluation of PIDs. Flow cytometry effectively identifies major forms of PIDs, including severe combined immunodeficiency, X-linked agammaglobulinemia, hyper IgM syndromes, Wiskott-Aldrich syndrome, X-linked lymphoproliferative syndrome, familial hemophagocytic lymphohistiocytosis, autoimmune lymphoproliferative syndrome, IPEX syndrome, CTLA 4 haploinsufficiency and LRBA deficiency, IRAK4 and MyD88 deficiencies, Mendelian susceptibility to mycobacterial disease, chronic mucocuneous candidiasis, and chronic granulomatous disease. While genetic analysis is the definitive approach to establish specific diagnoses of PIDs, flow cytometry provides a tool to effectively evaluate patients with PIDs at relatively low cost.

Background: In September 2015, Japan experienced an unusual increase in acute asthma hospitalizations of children that coincided with an enterovirus D68 (EV-D68) epidemic. The objective of this study is to investigate whether EV-D68 had a causal relationship with the spike in asthma hospitalizations.

Methods: A nation-wide retrospective survey of asthma hospitalizations of children was performed for the period from January 2010 through October 2015. The Japanese Society of Pediatric Allergy and Clinical Immunology asked its affiliated hospitals to report monthly numbers of hospitalizations, ICU admissions and mechanical ventilations due to acute asthma exacerbation. The data were retrieved from medical databases using predefined search criteria: diagnosis of asthma or asthmatic bronchitis, admission, and age <20 years. Monthly numbers of EV-D68 detection were also obtained from the Infectious Disease Surveillance Center of Japan. A Granger causality test was used to analyze the association of EV-D68 detections for asthma exacerbation.

Results: A total of 157 hospitals reported 87,189 asthma hospitalizations, including 477 ICU admissions and 1193 mechanical ventilations, during the survey period of 5 years and 10 months. The numbers of these events increased drastically in September 2015. The Granger causality test verified the association between EV-D68 and asthma hospitalizations/mechanical ventilations. The most-affected age group was 3-6 years old.

Conclusions: The spike in pediatric asthma hospitalizations in Japan in September 2015 was found to be associated with the EV-D68 epidemic. Respiratory pathogens can cause “epidemics” of asthma exacerbation. Coordinated surveillance of infectious diseases and asthma may be beneficial for prevention and better control of both illnesses.

Background: Allergic rhinitis (AR) is a heterogeneous disorder that significantly affects daily activity, work productivity, sleep, learning, and quality of life in all generations. Japanese cedar (JC) pollen is the most common allergen responsible for the development of AR in Japan. AR caused by JC pollen is considered to be a multifactorial inheritance disease that is caused by both environmental and genetic factors. The aim of this study was to investigate whether Human Leukocyte Antigen-DPB1 (HLA-DPB1) is associated with JC sensitization/pollinosis.

Methods: Subjects in the present study were 544 students at the University of Tsukuba from 2013 to 2015. PCR-SSOP was performed to determine each individual's HLA-DPB1 alleles. Logistic regression analysis was performed to examine relationships between JC-related phenotypes and alleles/amino acid polymorphisms of HLA-DPB1.

Results: HLA-DPB1^*02 allele were significantly associated with both JC sensitization/pollinosis (q < 0.05). Furthermore, HLA-DPB1^*02:01 and HLA-DPB1^*02:02 had a protective tendency for JC sensitization/pollinosis, and HLA-DPB1^*05:01 had a susceptible tendency for sensitization (P < 0.05). In amino acid polymorphism analyses, Glutamic acid in position 69, Glycine-Glycine-Proline-Methionine in positions 84-87, Threonine in position 170 and Methionine in position 205 were also observed to have a protective tendency for JC sensitization (P < 0.05). Amino acid positions 69 and 84-87 were located in binding pocket 5 and 1 of HLA-DPβ1, respectively.

Conclusions: Amino acid changes in the allergen-binding pocket of HLA-DPβ1 are likely to influence pollinosis/sensitization to the allergenic peptide of JC pollen and determine the pollinosis risk for each individual exposed to JC pollen.

Background: Buckwheat (BW) is a potentially life-threatening allergen. Usefulness of BW-specific immunoglobulin-E (BW-sIgE) level for diagnosis of BW allergy is controversial, while the skin prick test (SPT) is widely used because of its less invasive procedure and immediate results. However, there are no data comparing usefulness of the SPT and BW-sIgE level. Therefore, our study aimed to clarify efficacy of the SPT for diagnosis of BW allergy.

Methods: This retrospective cross-sectional study evaluated patients who underwent an oral food challenge (OFC) for diagnosis or confirmation of acquired tolerance using 3072 mg of BW protein between July 2006 and April 2014. We then compared the diagnostic performance of BW sIgE and SPT to predict positive OFC results.

Results: We analyzed 126 patients aged 2-16 years (median, 7.7 years), 18 (14%) of whom showed positive OFC results. Between patients with positive and negative OFC results, there was no significant difference in BW-sIgE level. However, patients with positive OFC results had a larger SPT wheal diameter. Area under the curve for positive OFC results for BW-sIgE level and SPT wheal diameter were 0.583 and 0.791, respectively. The 5%, 10%, 50%, and 90% positive predictive values of SPT wheal diameter were 2.0 mm, 5.2 mm, 14.7 mm, and 24.1 mm, respectively.

Conclusions: Our study revealed that the SPT was more useful than BW-sIgE level for diagnosis of BW allergy. Thus, an OFC may be avoided if the patient's SPT wheal diameter is at least 24.1 mm.

Background: While Japanese guideline recommends initial control treatment for preschool children with asthma symptoms more than once a month, Western guidelines do not. To determine whether control treatment with montelukast was more effective than as-needed β₂-agonists in this population, we conducted a randomized controlled trial.

Methods: Eligible patients were children aged 1-5 years who had asthma symptoms more than once a month but less than once a week. Patients were randomly assigned in a 1:1 ratio to receive montelukast 4 mg daily for 48 weeks or as-needed β₂-agonists. The primary endpoint was the number of acute asthma exacerbations before starting step-up treatment with inhaled corticosteroids. This study is registered with the University Hospital Medical Information Network clinical trials registry, number UMIN000002219.

Results: From September 2009 to November 2012, 93 patients (47 in the montelukast group and 46 in the no-controller group) were enrolled into the study. All patients were included in the analysis. During the study, 13 patients (28%) in the montelukast group and 23 patients (50%) in the no-controller group had acute exacerbations with the mean numbers of 0.9 and 1.9/year, respectively (P = 0.027). In addition, 10 (21%) and 19 (41%) patients received step-up treatment, respectively. Cumulative incidence of step-up treatment was significantly lower in the montelukast group (hazard ratio 0.45, 95% confidence interval 0.21 to 0.92; P = 0.033).

Conclusions: Montelukast is an effective control treatment for preschool children who had asthma symptoms more than once a month but less than once a week.

Background: Allergic bronchopulmonary aspergillosis (ABPA) is an allergic pulmonary disease characterized by a hypersensitivity reaction to Aspergillus species colonizing the airways. The clinical characteristics of ABPA may differ depending on genetic and environmental background. We performed a nationwide survey to determine the clinical characteristics of ABPA in Japan.

Methods: In 2013, a questionnaire on physician-diagnosed ABPA/allergic bronchopulmonary mycosis was sent to 903 medical centers specializing in respiratory or allergic diseases. Cases fulfilling the following criteria were categorized as possible ABPA-central bronchiectasis (ABPA-CB): 1) presence of specific serum immunoglobulin E (IgE) antibodies or a positive skin reaction to Aspergillus, and 2) bronchiectasis or mucoid impaction in the central bronchi.

Results: Of 499 physician-diagnosed cases reported by 132 clinical centers, 358 cases met the criteria for possible ABPA-CB. Median age of ABPA-CB onset was 57 (interquartile range, 44-68) years; later-onset disease, developing ≥50 years of age, accounted for 66% of the cases and was associated with female sex, delayed onset of asthma, and lower levels of serum IgE. A third of the patients (120 patients, 34%) exhibited low levels of serum total IgE (<1000 IU/mL). Aspergillus species were isolated from sputum in 126/213 cases (59%), and Schizophyllum commune was identified in 12 (6%) patients. During the course of the treatment, ABPA recurred in 169 (48%) cases.

Conclusions: This nationwide survey identified several unique clinical characteristics of ABPA in Japan, such as late-onset, relatively lower serum IgE levels, and frequent recurrences/flares.

Background: Previous data have shown the high efficacy of omalizumab in chronic spontaneous urticaria (CSU). However, factors that may be effective on the response to therapy, relapse rates after drug discontinuation, and efficacy of retreatment remain unclear. This study aimed to determine the efficacy of omalizumab in CSU refractory to conventional therapy, to identify possible factors affecting treatment response and relapse, and also to evaluate the efficacy of retreatment on relapsed disease.

Methods: The data of CSU patients treated with 300 mg/month omalizumab for at least 3 months were retrospectively analyzed. In order to evaluate the efficacy of treatment and retreatment, baseline and follow-up concomitant medication score (CMS) and urticaria activity score (UAS) were calculated. Possible factors affecting treatment response and relapse were identified.

Results: Twenty-five patients were included. The median duration of omalizumab therapy was 6 (6-12) months. Of the patients with baseline UAS 6 (5.5-6) and CMS 13 (10-15), 8 (32%) had complete response (UAS = 0) and 2 (8%) were non-responders after 3 months of therapy. None of the complete responders were positive for IgG-anti-TPO. After discontinuation of omalizumab therapy, 11 (61%) patients experienced relapse and 10 of them received retreatment with omalizumab. Half of the patients had complete response, and half had partial response (UAS = 1-4) after retreatment. No treatment related adverse events were documented.

Conclusions: Omalizumab has high efficacy in both the treatment and retreatment of CSU; however, relapse rates after discontinuation are high. Autoimmune markers may be helpful in predicting treatment response and relapse.

Background: In severe drug eruptions, precise evaluation of disease severity at an early stage is needed to start appropriate treatment. It is not always easy to diagnose these conditions at their early stage. In addition, there are no reported prognostic biomarkers of disease severity in drug eruptions. The aim of this study was to test whether the thymus and activation-regulated chemokine (TARC) level in serum at an early stage of a drug eruption can serve as a prognostic biomarker of systemic inflammation.

Methods: Study participants included 76 patients who received a diagnosis of a drug eruption, one of the following: drug rash with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome, maculopapular exanthema, and erythema multiforme. Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) was eliminated in this study because scoring system for evaluating the severity was established. Correlation coefficients between serum TARC levels and indicators of systemic inflammation, including the neutrophil-to-lymphocyte ratio, Glasgow prognostic score, modified systemic inflammatory response syndrome (mSIRS) score, and C-reactive protein in serum were evaluated.

Results: Serum TARC levels positively correlated with the neutrophil-to-lymphocyte ratio, Glasgow prognostic score, mSIRS score, C-reactive protein, albumin, white blood cell count, body temperature, and pulse rate. TARC levels negatively correlated with systolic blood pressure. Among these parameters, the mSIRS score showed strong correlation (correlation coefficient: 0.68).

Conclusions: Serum TARC levels correlate well with indicators of systemic inflammation and of disease severity among patients with a drug eruption except SJS/TEN. Serum TARC may be a prognostic biomarker of severity of inflammation in drug eruptions.

Background: Anaphylaxis is a life-threatening allergic reaction. Several studies reported different anaphylactic reactions according to the causative substances. However, a comparison of anaphylaxis for each cause has not been done. This study was conducted to identify common causes of anaphylaxis, characteristics of anaphylactic reaction for each cause and to analyze the factors related to the severity of the reaction.

Methods: Medical records of patients who visited the emergency room of Ewha Womans University Mokdong Hospital from March 2003 to April 2016 and diagnosed with anaphylactic shock were retrospectively reviewed. We compared the clinical features of anaphylaxis according to the cause. In addition, the severity of anaphylaxis was analyzed and contributing factors for severe anaphylaxis were reviewed.

Results: A total of 199 patients with anaphylaxis were analyzed. Food was the most common cause (49.7%), followed by drug reaction (36.2%), bee venom (10.1%), and unknown cause (4.0%). Cardiovascular symptoms of syncope and hypotension were more common in drug-induced anaphylaxis. The incidence of severe anaphylaxis was the highest in anaphylaxis due to drugs (54.2%). Urticaria and other skin symptoms were significantly more common in food-induced anaphylaxis. Risk factors for severe anaphylaxis included older age, male, and drug-induced one. Epinephrine treatment of anaphylaxis was done for 69.7% and 56.9% of patients with food-induced and drug-induced anaphylaxis, respectively.

Conclusions: More severe anaphylaxis developed with drug treatment and in males. Low rate of epinephrine prescription was also observed. Male patients with drug induced anaphylaxis should be paid more attention.

Background: Atopic dermatitis (AD) is exacerbated by sweating, and the skin of most patients with AD are resided by Malassezia (M.) fungi. Recently, MGL_1304 produced by Malassezia globosa was identified as the major histamine releasing antigen in human sweat.

Methods: The full length cDNA of the counterpart of MGL_1304 in Malassezia restricta (Mala r 8), was cloned by degenerate PCR and rapid identification of cDNA ends (RACE). Recombinant MGL_1304, and its counterparts, Mala s 8 (produced by Malassezia sympodialis) and Mala r 8 were prepared, and compared in their allergenicities by dot blot analysis and histamine release tests with sera and basophils of patients with AD.

Results: The identities between MGL_1304 and Mala s 8, MGL_1304 and Mala r 8, and Mala s 8 and Mala r 8 were 68%, 78%, and 76%, respectively, in protein sequences. Dot blot analysis revealed that the level of IgE binding to Mala s 8 was higher than that of MGL_1304. However, histamine release tests revealed that MGL_1304 and Mala r 8 possessed higher activity than Mala s 8. In addition, the crude lysate of M. globosa showed higher histamine release ability than that of M. sympodialis.

Conclusions: Patients with AD showed hypersensitivities against MGL_1304 and its homologs. However, the allergenicities of the homologs are variable and the histamine release activities may be different from the solid-phase binding activities for IgE. Sweat allergy should be carefully evaluated with biological activities of MGL_1304 and its homologs of other Malassezia fungi residing on the skin.

Background: Interleukin-17 (IL-17A) is a mainly pro-inflammatory cytokine, and IL-17 signaling implicates in the development of allergic asthma. The polymorphism rs2275913 in the promoter region of the IL-17A gene has in previous studies been associated with asthma susceptibility. The objective was to evaluate the association between IL-17A rs2275913 (-197G>A) polymorphism and post-bronchiolitis asthma and/or allergic rhinitis in a prospective 11-13 years post-bronchiolitis follow-up.

Methods: 166 previously healthy full-term infants, hospitalized for bronchiolitis at age less than 6 months, were invited to follow-up visits at the ages of 5-7 years and 11-13 years. Asthma diagnoses and presumptive symptoms, allergic rhinitis and use of inhaled corticosteroids (ICS) were registered. Blood samples for IL-17A rs2275913 (-197G>A) polymorphism were obtained during hospitalization or at the 5-7 years control visit.

Results: There were no significant differences between children with the wild GG and variant GA or AA genotype in the severity of bronchiolitis during hospitalization or in the outcomes until the age 5-7 years. At 11-13 years of age, children with the variant GA or AA genotype had significantly less often current asthma, use of ICSs during last 12 months or allergic rhinitis than those with the wild GG genotype. The ICS use during last 12 months retained the statistical significance in adjusted analyses (adjusted OR 0.25), whereas current asthma and allergic rhinitis marginally lost it.

Conclusions: The IL-17A rs2275913 (-197G>A) polymorphism decreased the risk of post-bronchiolitis asthma at 11-13 years of age, but not earlier in life, in the present prospective, long-term follow-up study.

Background: Chronic urticaria has an expressive prevalence in general population, especially in adults, and is defined by the presence of intermittent hives for six weeks or longer. Our study aims to characterize the histological patterns of chronic spontaneous urticaria, based on the inflammatory cell infiltrate, and correlate them to laboratory exams.

Methods: It was performed a retrospective analysis of laboratory, histopathology and direct immunofluorescence data of 93 patients with chronic urticaria. For histopathological analysis, cell count was performed in four fields at high magnification (×400) for each specimen. The resulting cell count medians were submitted to statistical analysis and, then, were correlated to laboratorial findings.

Results: We found a female predominance (76.34%) of chronic urticaria cases, and an average age of 42.5 years (SD ± 15). Two histological groups were distinctive: 1) chronic urticaria with predominance of neutrophils or eosinophils - N (%) = 39 (42.4%) - and 2) chronic urticaria with predominance of lymphocytes - N (%) = 53 (57.6%). There was not significant correlation between histological groups and laboratorial tests. Moreover, direct immunofluorescence was positive in 21 (33,87%) from 62 patients.

Conclusions: There is not enough scientific evidence to support neutrophilic urticaria as a solid, separate entity.

Background: We have previously shown that prophylactic oral administration of transgenic rice seeds expressing hypoallergenic modified antigens suppressed the development of allergic conjunctivitis induced by Japanese cedar pollen. We have now investigated the efficacy of oral immunotherapy with such transgenic rice for established allergic conjunctivitis in mice.

Methods: BALB/c mice were sensitized with two intraperitoneal injections of Japanese cedar pollen in alum, challenged with pollen in eyedrops, and then fed for 16 days with transgenic rice seeds expressing modified Japanese cedar pollen allergens Cry j 1 and Cry j 2 or with nontransgenic rice seeds as a control. They were then challenged twice with pollen in eyedrops, with clinical signs being evaluated at 15 min after the first challenge and the eyes, blood, spleen, and lymph nodes being isolated at 24 h after the second challenge.

Results: The number of eosinophils in the conjunctiva and the clinical score for conjunctivitis were both significantly lower in mice fed the transgenic rice than in those fed nontransgenic rice. Oral vaccination with transgenic rice seeds also resulted in a significant increase in the production of IFN-γ by splenocytes, whereas it had no effect on the number of CD4⁺CD25⁺Foxp3⁺ regulatory T cells in the spleen or submandibular or mesenteric lymph nodes.

Conclusions: Oral administration of transgenic rice seeds expressing hypoallergenic allergens ameliorated allergic conjunctivitis in the established setting. Such a rice-based edible vaccine is potentially both safe and effective for oral immunotherapy in individuals with allergic conjunctivitis.

Background: Recent studies have indicated that serum levels of squamous cell carcinoma antigen (SCCA) 1 and 2 induced by type 2 cytokines such as IL-4 and IL-13, are increased in patients with atopic dermatitis (AD). However, no clinical studies have analyzed serum levels of SCCA2 in larger series of AD patients or their association with various clinical characteristics. This study was performed to clarify whether serum levels of SCCA2 are associated with disease severity and clinical phenotypes of adult AD patients.

Methods: An enzyme-linked immunosorbent assay was performed to examine serum SCCA2 levels in 240 adult patients with AD and 25 healthy controls in this study. Serum SCCA2 levels were analyzed with clinical characteristics and laboratory parameters including thymus and activation-regulated chemokine (TARC), lactate dehydrogenase (LDH), blood eosinophils, total IgE, and specific IgE (Japanese cedar pollen, Dermatophagoides farina, Candida, malassezia, Staphylococcal enterotoxin B). Expression of SCCA2 in AD eruption was examined by immunohistochemistry. The effect of treatment on serum SCCA2 was also assessed.

Results: Serum SCCA2 level showed a positive correlation with disease severity, levels of TARC, LDH, eosinophil counts, and IgE levels. Robust expression of SCCA2 was detected in the supra basal keratinocytes in the epidermis of AD patients. Serial measurements of serum SCCA2 revealed decreased levels of SCCA2 after treatment for AD.

Conclusions: Serum SCCA2 levels reflected disease severity and clinical type of AD. Serum SCCA2 may thus be a relevant biomarker for AD.

Background: The asthma control questionnaires used in Japan are Japanese translations of those developed outside Japan, and have some limitations; a questionnaire designed to optimally evaluate asthma control levels for Japanese may be necessary. The present study was conducted to validate the Japan Asthma Control Survey (JACS) questionnaire in Japanese asthma patients.

Methods: A total of 226 adult patients with mild to severe persistent asthma were enrolled and responded to the JACS questionnaire, asthma control questionnaire (ACQ), and Mini asthma quality of life questionnaire (Mini AQLQ) at Weeks 0 and 4. The reliability, validity, and sensitivity/responsiveness of the JACS questionnaire were evaluated.

Results: The intra-class correlation coefficients (ICCs) were within the range of 0.55-0.75 for all JACS scores, indicating moderate/substantial reproducibility. For internal consistency, Cronbach's alpha coefficients ranged from 0.76 to 0.92 in total and subscale scores, which were greater than the lower limit of internal consistency. As for factor validity, the cumulative contribution ratio of four main factors was 0.66. For criterion-related validity, the correlation coefficients between the JACS total score and ACQ5, ACQ6, and Mini AQLQ scores were ?0.78, ?0.78, and 0.77, respectively, showing a significant correlation (p < 0.0001).

Conclusions: The JACS questionnaire was validated in terms of reliability and validity. It will be necessary to evaluate the therapeutic efficacy measured by the JACS questionnaire and calculate cutoff values for the asthma control status in a higher number of patients.