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Previous research has established a bidirectional interaction between the brain and the skin, the so-called 'brain-skin axis'; novel aspects of which were explored in human subjects in this thesis. Study 1 used positron emission tomography (PET) with the radioligand [11C]-(R)-PK11195 co-registered with magnetic resonance imaging (MRI) to investigate the relationship between systemic inflammation and neuroinflammation of the brain in psoriasis. Patients with chronic plaque psoriasis (n=12) and Healthy controls (n=12) underwent brain scanning and measurement of their peripheral inflammatory markers. Inflammatory markers were increased (significantly for interleukin-8) in psoriasis patients when compared with controls but brain neuroinflammation was not. There was heterogeneity in the degree of neuroinflammation in both groups which did not correlate with any measured variables. These findings suggest that in this population, the systemic inflammation associated with chronic plaque psoriasis does not induce brain neuroinflammation. Study 2 investigated the impact of psychosocial stress on cutaneous mast cell (MC) function. In sub-study 2.1, Healthy subjects were exposed to either the modified Trier paradigm (an acute, experimental psychosocial stressor, n=12) or sat quietly for an equivalent period of time (controls, n=12). The stressor did not affect MC density but significantly reduced MC degranulation, suggesting that acute psychosocial stress confers a degree of resilience to MC degranulation in heathy human skin. Sub-study 2.2 employed corticotropin-releasing hormone (CRH) as a surrogate 'chemical stressor' in an ex vivo full-thickness human skin organ culture model (n=5). Significant MC degranulation was induced by CRH, an effect replicated by Etanercept (tumour necrosis factor (TNF)-alpha inhibitor) supplementation of the culture medium. It is plausible that Etanercept triggers MC degranulation and TNF-alpha release which is subsequently neutralised by Etanercept binding; although this remains speculative. Both MC and Langerhans' cells (LC) are important in the cutaneous stress response. Study 3 investigated the effect of histamine, the prototypical granule-associated MC mediator on LC migration. Healthy human subjects (n=20) underwent skin prick testing (SPT) with histamine and normal saline (control). Two and four hours post-SPT biopsies were taken and analysed for the presence of LC. Histamine SPT had no impact on LC migration when compared to normal saline SPT. These findings suggest that histamine at this concentration does not directly influence LC migration. This thesis enhances our knowledge of brain-skin interactions which I hope will ultimately benefit patients with skin disease.

Allergic rhinitis (AR) is an IgE-mediated disease of the upper respiratory tract characterized by symptoms of rhinorrhea, nasal obstruction, itching, and sneezing in response to allergen exposure. Allergic rhinitis is common in childhood, affecting 42% of six year old children, and is associated with an increased risk of asthma. Thus, determining early childhood risk factors may be important for not only AR, but also asthma. The study hypothesis is that size of the specific aeroallergen wheal area in ages one through three is significantly associated with AR at age four.Two specific aims were completed to test this hypothesis. The first specific aim of this study was to determine the size of the skin prick test (SPT) wheal area from 15 individual aeroallergens during early childhood (age one through three) and its association with AR at age four. The second aim was to determine if any individual age-specific aeroallergen wheal area association persisted in a multivariate logistic regression model after controlling for covariates and multiple testing. The analysis was extended further to address a more specific phenotype, allergic eosinophilic rhinitis (AER), defined as AR with nasal eosinophilia. We examined if the individual aeroallergen wheal areas were associated with AER in univariate and multivariate analysis.This study was part of the Cincinnati Childhood Asthma and Air Pollution Study where allergen skin prick tests (SPT) were performed at ages one through four at annual clinical visits. SPT wheal circumferences were traced, recorded on transpore tape, and digitized which allowed accurate estimates of wheal areas by planimetry. Timothy and Alternaria wheal areas at age two were significantly associated to AR at age four (aOR 1.06; 95% CI, 1.02 - 1.11; p = 0.01) and (aOR 1.07; 95% CI 1.0-1.15; p = 0.04), respectively. Fescue, dog, and Penicillium wheal areas at age three were significantly associated with AR at age four (aOR 1.08; 95% CI, 1.02 - 1.15; p = 0.02), (aOR 1.06; 95% CI, 1.01 - 1.12; p = 0.03) and (aOR 1.14; 95% CI, 1.06 - 1.23; p = 0.001), respectively. At age three, maple and Penicillium wheal areas were significantly associated with AER at age four, (aOR 1.07; 95% CI, 1.01 - 1.13; p = 0.02) and (aOR 1.18; 95% CI, 1.06 - 1.32; p = 0.002), respectively. The conclusion of this study is that the size of aeroallergen wheal area during the first three years of life predicts AR phenotypes at age four. The significance of this finding is that the risk of AR at age four can be attributed to the wheal area of a few aeroallergens. This finding can be used to refine high-risk populations in AR intervention trials. Future studies should investigate if this AR finding extend to earlier into preschool years, to school age children, why these allergens are immunogenic and if wheal area predicts lower respiratory (ex. asthma) phenotypes.

Skin prick test (SPT) response is often the main outcome used to summarize sensitization to allergens in childhood atopic epidemiological studies. The first study objective was to characterize the development of atopy from patterns of SPT responses using Item Response Theory (IRT) models. In the IRT framework, the latent variable was assumed to be the underlying atopic state, where atopic state refers to the familially related trait of hypersensitivity to environmental allergens and is therefore not directly measured. The Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS), a prospective birth cohort study, provides an ideal population in which to examine longitudinal SPT results. SPTs were performed using a panel of 15 aeroallergens and two foods including: two grass pollens: Timothy and fescue; four tree pollens: white oak, maple mix, American elm, and red cedar; short ragweed; four mold spore extracts: Alternaria alternata, Aspergillus fumigatus, Penicillium mix, and Cladosporium herbarum; four indoor aeroallergens: house dust mite mixture of Dermaphagoids (D.) farinae and D. pterynissinus, German cockroach, cat dander, dog dander; and two foods: milk and egg. A total of 537 children had SPT results available at ages one, two, three, and four, and were included in this analysis. Using IRT modeling, at age one, the highest associations between SPT positivity and atopy were found for indoor allergens, whereas, at age four, the highest associations between SPT positivity and atopy were observed for outdoor allergens. Atopy scores were obtained using the posterior distribution of the latent variable and were used to predict age four allergic symptoms. Atopy scores computed at ages one through four were associated with year four allergic symptoms. This novel modeling approach provides a unique way of assessing atopy based on SPT responses.The second study objective was to apply two types of transition Markov models, marginalized transition models (MTM) and continuous time Markov models (CTMM), to describe SPT responses during the first four years of life. These models showed the serial dependence of the current outcome on previous outcomes. The estimated first-order coefficient was statistically significant for Alternaria alternata, Cladosporium herbarum, Penicillium mix, dust mite, German cockroach, meadow fescue, red cedar, American elm, maple mix, white oak, and milk. Second-order MTM models were fit for cat, dog, Timothy, and egg based on the score test for a second-order parameter. In these models, both the first-order and second-order coefficients were significant. The MTM models showed no sign of SPT stabilization for all 17 allergens over the four years. The comparison of the MTM and CTMM estimates showed similar results. The CTMM was expanded to include a multivariate response and a simulation experiment was conducted to assess the model. The simulation revealed that the multivariate model did well at capturing the true parameters when the transition probabilities were high. However, the model fails to capture the true correlation between processes when the transition probabilities are low. This study provides a first step in defining a multivariate transition model that is relatively simple to apply using standard statistical software.

Objectives: Characterize the natural history of allergic sensitization and compare three definitions of skin prick test (SPT) positivity in infants born to an atopic parent. Study Design: Secondary data analysis of a prospective, high-risk birth cohort. Results: In a cohort of 477 infants, food allergen sensitization decreased from 11.7% at 12 months to 8.6% at 24 months while aeroallergen sensitization increased from 15.9% to 34.0%. Individual food allergen and aeroallergen persistence rates ranged from 0-55.6% but overall aeroallergen sensitization persisted at 61.8%. There was no statistical difference between the three SPT positivity definitions. Conclusions: Food allergen and aeroallergen sensitization begin in infancy. Although individual allergen sensitization was largely transient, overall aeroallergen sensitization persisted at 24 months. High-risk infants should be screened using the standard definition of a positive SPT to identify those at increased risk for the development of allergic disease.

Fungi are one of the indoor biocontaminants that can cause allergic symptoms and diseases. Moreover, fungal fragments are emerging as a potential allergenic airborne contaminant, but their health-related characteristics and methods for exposure assessment are poorly explored. On-site home visits were conducted in 777 homes enrolled in the Cincinnati Childhood Allergy and Air Pollution Study. The relationship between home characteristics and level of dustborne Alternaria allergen was investigated by using both concentration (µg/g) and loading (µg/m2). Home characteristics that were most strongly associated with the Alternaria allergen levels were those affecting the transport and penetration of particles from outdoors to indoors, and those related with the indoor microclimate. Visible mold was not associated with Alternaria allergen level. Allergen levels measured in concentration and loading units were associated with different home characteristics, and therefore, both of these units deserve to be included in the future studies. Airborne and dustborne allergen levels of Alternaria were examined using 48-hour air sampling. A poor correlation was found between airborne concentration and dustborne concentration/loading [R = 0.47 (Airconcentration vs. Dustconcentration) and 0.28 (Airconcentration vs. Dustloading)]. Therefore, both air and dust sampling are recommended at this time. Fungal fragments were investigated through a laboratory study including characterization of their size distribution and respiratory deposition. Fungal fragments of Stachybotrys chartarum (in the range of aerodynamic diameters of 0.03-0.79 µm) were released in 514 times larger quantities than spores (3.12-5.11 µm). The model calculation indicated that 60% of fragments that were retained in the respiratory tract were deposited in lower airways in infants. The number of deposited fragments in the bronchiolar and alveolar region was 4500-6200 times greater than that of spores in infants. Considering their biological origin as well as small size and large quantity, fungal fragments could cause allergic lower respiratory symptoms in infants. Finally, a preliminary analysis of an association between mold exposure and health outcomes in infants was performed. Visible mold was shown to be a significant risk factor for lower respiratory symptoms increasing the risk of persistent wheezing, atopic persistent wheezing , and allergic persistent wheezing in infants whose parent is atopic.

บทนำ: จากรายงานการศึกษาก่อนหน้านี้พบว่า ความชุกของโรคเยื่อบุจมูกอักเสบจากภูมิแพ้ โรคหืด และผื่นผิวหนังอักเสบจากภูมิแพ้ มีอัตราเพิ่มสูงขึ้นทั่วโลกรวมทั้งประเทศไทย ภาวะการแพ้สารก่อภูมิแพ้ในอากาศเป็นปัจจัยหลักที่มีผลต่อการเกิดโรคภูมิแพ้ โดยความชุกของสารก่อภูมิแพ้ในอากาศ มีความแตกต่างกันตามภูมิประเทศและระดับความสูงของพื้นที่ วัตถุประสงค์: เพื่อศึกษาความชุกของสารก่อภูมิแพ้ในอากาศจากผลการทดสอบภูมิแพ้ทางผิวหนัง (Skin prick test) ในผู้ใหญ่ที่ป่วยเป็นโรคภูมิแพ้และเข้ารับการรักษา ณ คลินิกโรคภูมิแพ้ โรงพยาบาลรามาธิบดี วิธีการศึกษา: การวิจัยเชิงพรรณนา ณ จุดเวลาใดเวลาหนึ่ง แบบตัดขวาง เก็บรวบรวมข้อมูลย้อนหลังจากเวชระเบียนและข้อมูลผลการทดสอบภูมิแพ้ทางผิวหนังต่อสารก่อภูมิแพ้ในอากาศของผู้ป่วย ตั้งแต่เดือนมกราคม พ.ศ. 2547 ถึงเดือนธันวาคม พ.ศ. 2558 ผลการศึกษา: ผู้ป่วยทั้งหมด จำนวน 1,516 คน เป็นเพศหญิง จำนวน 1,118 คน คิดเป็นร้อยละ 73.7 มีอายุเฉลี่ย 41.34 ± 16.5 ปี ได้รับการวินิจฉัยเป็นโรคเยื่อบุจมูกอักเสบจากภูมิแพ้ร้อยละ 58 โรคหืดร้อยละ 19.7 ผื่นผิวหนังอักเสบจากภูมิแพ้ร้อยละ 3.2 และภาวะลมพิษเรื้อรังร้อยละ 9.2 โดยผู้ป่วยทุกรายได้รับการทดสอบทางผิวหนังต่อสารก่อภูมิแพ้ทางอากาศ ซึ่งพบว่า ไรฝุ่นเป็นสารก่อภูมิแพ้ที่พบมากที่สุด คิดเป็นร้อยละ 64.8 รองลงมา ได้แก่ เกสรหญ้าร้อยละ 36.0 แมลงสาบร้อยละ 32.3 ฝุ่นบ้านร้อยละ 31.5 รังแคแมวร้อยละ 12.9 และรังแคหมาร้อยละ 10 สรุป: ไรฝุ่นเป็นสารก่อภูมิแพ้ทางอากาศที่พบบ่อยที่สุดในการศึกษานี้ รองลงมาได้แก่ เกสรหญ้า แมลงสาบและรังแคสัตว์

บทนำ: อาการของโรคเยื่อบุจมูกอักเสบเรื้อรัง มีความแตกต่างกันในแต่ละคน ตั้งแต่มีอาการเล็กน้อยจนถึงรุนแรงมาก และมีผลกระทบในการดำเนินชีวิตประจำวัน วัตถุประสงค์: เพื่อศึกษาความสัมพันธ์ระหว่างชนิดและขนาดของปฏิกิริยาผลบวกจากสารก่อภูมิแพ้ และปัจจัยที่มีผลกระทบต่อคุณภาพชีวิตของผู้ป่วยโรคเยื่อจมูกอักเสบเรื้อรัง วิธีการศึกษา: การศึกษาเชิงพรรณนา ณ จุดเวลาใดเวลาหนึ่งแบบตัดขวาง เก็บข้อมูลคุณภาพชีวิต คะแนนการประเมินอาการทางจมูก อาการอื่นๆ และผลทดสอบภูมิแพ้ทางผิวหนังของผู้ป่วยรายใหม่ที่ได้รับการวินิจฉัยว่าเป็นโรคเยื่อบุจมูกอักเสบเรื้อรัง ณ คลินิกโรคภูมิแพ้ โรงพยาบาลรามาธิบดี ตั้งแต่เดือนสิงหาคมถึงเดือนธันวาคม พ.ศ. 2560 ผลการศึกษา: ผู้ป่วย จำนวน 130 คน เป็นเพศหญิง จำนวน 85 คน คิดเป็นร้อยละ 65 พบว่า ชนิดและขนาดของปฏิกิริยาทดสอบภูมิแพ้ทางผิวหนังที่ให้ผลบวก มีความสัมพันธ์กับคุณภาพชีวิตแบบแปรผกผันเฉพาะไรฝุ่นชนิด Der f และแมลงสาบ (r = - 0.283 ถึง - 0.234, P < 0.05) อย่างไรก็ตาม คะแนนอาการทางจมูก (Total nasal symptom score, TNSS) และคะแนนอาการแสดงในระบบอื่นๆ (Total other symptom score, TOSS) มีความแตกต่าง ระหว่าง TNSS > 6 กับ TNSS ≤ 6 และ TOSS> 6 กับ TOSS ≤ 6 โดยพบว่า กลุ่มที่มีคะแนน มากกว่า 6 จะมีคุณภาพชีวิตต่ำกว่าทุกมิติอย่างมีนัยสำคัญทางสถิติ (P < 0.05) ยกเว้นคุณภาพชีวิตด้านการหยุดงาน(P = 0.16) สรุป: การศึกษานี้แสดงให้เห็นว่าชนิดและขนาดของปฏิกิริยาการทดสอบภูมิแพ้ทางผิวหนังที่ให้ผลบวกไม่มีความสัมพันธ์กับคุณภาพชีวิตของผู้ป่วย อย่างไรก็ตาม ความรุนแรงของอาการของโรคมีผลกระทบต่อระดับคุณภาพชีวิตอย่างมีนัยสำคัญ