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Wannada Laisuan,1 Chamard Wongsa,2 Chirawat Chiewchalermsri,3 Torpong Thongngarm,2 Ticha Rerkpattanapipat,1 Pansa Iamrahong,4 Chulapha Ruangwattanachok,4 Sira Nanthapisal,5 Mongkhon Sompornrattanaphan2 1Division of Allergy, Immunology and Rheumatology, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 2Division of Allergy and Clinical Immunology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; 3Department of Medicine, Panyananthaphikkhu Chonprathan Medical Center, Srinakharinwirot University, Nonthaburi, Thailand; 4Clinical Pharmacy Section, Pharmacy Division, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 5Department of Pediatrics, Faculty of Medicine, Thammasat University, Pathum Thani, ThailandCorrespondence: Mongkhon SompornrattanaphanDivision of Allergy and Clinical Immunology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandTel +66 2419 8263Fax +66 2419 8263Email mongkhon.som@mahidol.ac.thAbstract: Anaphylaxis to CoronaVac, an inactivated vaccine against COVID-19, is extremely rare. We report 12 cases of anaphylaxis after CoronaVac administration, focusing on clinical characteristics and management outcomes. Skin test and graded vaccine challenge were successfully performed in our cases and might be considered if an inactivated vaccine is the only remaining option.Keywords: anaphylaxis, COVID-19 vaccine, drug allergy, excipient, vaccine allergy, COVID-19, skin testing

Prapasri Kulalert,1 Phichayut Phinyo,2,3 Jayanton Patumanond,3 Chutima Smathakanee,4 Wantida Chuenjit,4 Sira Nanthapisal5 1Department of Clinical Epidemiology, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand; 2Department of Family Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 3Center for Clinical Epidemiology and Clinical Statistics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 4Department of Pediatrics, Hat Yai Hospital, Songkhla, Thailand; 5Department of Pediatrics, Faculty of Medicine, Thammasat University, Pathum Thani, ThailandCorrespondence: Phichayut PhinyoDepartment of Family Medicine, Faculty of Medicine, Chiang Mai University, 110/510 Intawaroros Road, Suthep, Mueang Chiang Mai District, Chiang Mai, Chiang Mai Province 50200, ThailandTel +66 89 850 1987Email phichayutphinyo@gmail.comPurpose: Intermittent nebulization of short-acting beta-agonists (SABA) is the initial treatment of choice for children with asthma exacerbation. However, children with severe asthma exacerbation (SAE) may not show an adequate response and need aggressive stepwise therapy. We aimed to explore factors associated with a poor response to intermittent nebulized SABA in children with SAE.Methods: A retrospective cohort study of children with SAE diagnosed according to the definition of the British Guidelines on the Management of Asthma, who were admitted at Hat Yai Hospital from January 1, 2015, to December 31, 2017. All children were treated with intermittent SABA nebulization. Treatment failure was defined as children needing escalated therapy. Logistic regression with confounding score adjustment was used to explore the predictors of treatment failure.Results: One hundred thirty-three children were included in the analysis, 59 were in the failure group and 74 were in the success group. After adjusting for potential confounders, they were significantly associated with a previous history of intubation (adjusted OR 6.46, 95% CI 1.13 to 36.79, p=0.036), receiving < 3 doses of nebulized salbutamol in the emergency room (ER, aOR 3.21, 95% CI 1.15 to 9.02, p=0.027), ER measured oxygen saturation (SpO2) < 92% (adjusted OR 3.02, 95% CI 1.18 to 7.75, p=0.022), and exacerbation triggered by pneumonia (adjusted OR 2.67, 95% CI 1.19 to 6.00, p=0.017).Conclusion: We identified four prognostic factors of treatment failure in children with SAE: a previous history of intubation; receiving < 3 doses of nebulized salbutamol in the ER, SpO2 at ER < 92%; and exacerbation triggered by pneumonia. Further prospective studies are required to confirm our findings before clinical implementation.Keywords: status asthmaticus, hospitalization, nebulization, treatment failure, prognosis

Background: Allergic rhinitis (AR) has a high burden of disease in the Asia-Pacific region (APAC). Although guidelines provide recommendations regarding the diagnosis and treatment of AR, it is increasingly being recognised that there are gaps in their implementation. Patient-centred care involves accounting for the specific needs and desires of patients as well as including the patient in the decision-making process, and this may provide a means to reduce these gaps and consequently the burden of AR., Methods: A group of 11 experts in immunology and otorhinolaryngology from APAC provided information regarding their practices and experiences in the management of AR through an online survey. The group then discussed the barriers and solutions for the implementation of patient-centred care across the patient journey in a face-to-face meeting., Results: Key barriers to the implementation of patient-centred care for AR in APAC included a lack of patient awareness of the condition and treatment options, low adherence to treatments, financial constraints for patients, and time constraints for physicians. The solutions proposed include improving the knowledge of the patients about their conditions, the use of shared decision-making, the consideration of patient characteristics when choosing treatments, and the use of outcome measures to aid the optimisation of patient care. We provide specific recommendations for clinical practice., Conclusion: A greater focus on patient-centred approaches has the potential to improve the management of AR in APAC. More emphasis should be placed on each patient's specific health needs and desired outcomes., (© 2024 The Authors.)

Background: Inactivated whole-virus vaccination elicits immune responses to both SARS-CoV-2 nucleocapsid (N) and spike (S) proteins, like natural infections. A heterologous Ad26.COV2.S booster given at two different intervals after primary BBIBP-CorV vaccination was safe and immunogenic at days 28 and 84, with higher immune responses observed after the longer pre-boost interval. We describe booster-specific and hybrid immune responses over 1 year., Methods: This open-label phase 1/2 study was conducted in healthy Thai adults aged ≥ 18 years who had completed primary BBIBP-CorV primary vaccination between 90-240 (Arm A1; n = 361) or 45-75 days (Arm A2; n = 104) before enrolment. All received an Ad26.COV2.S booster. We measured anti-S and anti-N IgG antibodies by Elecsys®, neutralizing antibodies by SARS-CoV-2 pseudovirus neutralization assay, and T-cell responses by quantitative interferon (IFN)-γ release assay. Immune responses were evaluated in the baseline-seronegative population (pre-booster anti-N < 1.4 U/mL; n = 241) that included the booster-effect subgroup (anti-N < 1.4 U/mL at each visit) and the hybrid-immunity subgroup (anti-N ≥ 1.4 U/mL and/or SARS-CoV-2 infection, irrespective of receiving non-study COVID-19 boosters)., Results: In Arm A1 of the booster-effect subgroup, anti-S GMCs were 131-fold higher than baseline at day 336; neutralizing responses against ancestral SARS-CoV-2 were 5-fold higher than baseline at day 168; 4-fold against Omicron BA.2 at day 84. IFN-γ remained approximately 4-fold higher than baseline at days 168 and 336 in 18-59-year-olds. Booster-specific responses trended lower in Arm A2. In the hybrid-immunity subgroup at day 336, anti-S GMCs in A1 were 517-fold higher than baseline; neutralizing responses against ancestral SARS-CoV-2 and Omicron BA.2 were 28- and 31-fold higher, respectively, and IFN-γ was approximately 14-fold higher in 18-59-year-olds at day 336. Durable immune responses trended lower in ≥ 60-year-olds., Conclusion: A heterologous Ad26.COV2.S booster after primary BBIBP-CorV vaccination induced booster-specific immune responses detectable up to 1 year that were higher in participants with hybrid immunity., Clinical Trials Registration: NCT05109559., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S.M., R.W., S.K., S.L., A.J., A.T., V.L., P.C., N.T., N.C. report no potential conflicts of interest. S.N. has received honoraria for lectures from GSK, Zuellig Pharma, Astra Zeneca, Novartis, Abbot, Sanofi, Organon and Takeda and has participated in advisory boards for GlaxoSmithKline and Takeda. J.K.L. and T.A.W. and received institutional funding from Mahidol University to support study conduct, and T.A.W. supported management of Data Safety Monitoring Board activities and meetings. J-L.E. has no competing interests to declare.. M.F.R. is an employee of Janssen Pharmaceuticals and holds restricted stock units in the company. C.L. is an employee of Janssen Pharmaceuticals. T.K.M. has received consulting fees from Janssen Pharmaceuticals. P.P. has received funding from Mahidol University and Johnson & Johnson for study support., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Zingiber cassumunar Roxb. (Phlai) has been used for the treatment of allergies including allergic rhinitis (AR). Although the anti-histamine effects have been reported, assessment of nasal cytokine and eosinophil production had not been investigated., Objective: This study aimed to examine the effect of Phlai on alterations in nasal pro-inflammatory cytokine levels and eosinophil counts in nasal mucosa., Methods: This was a randomized, double-blind, three-way crossover study. Nasal concentrations of cytokines, namely interleukin (IL)-4, IL-5, IL-13 and interferron-gamma (IFN-γ), nasal smear eosinophilia as well as total nasal symptom score (TNSS) were evaluated before and after a 4 weeks treatment with 200 mg Phlai capsules or placebo in 30 AR patients., Results: We observed significant (p < 0.05) reduction in IL-5, IL-13 as well as the number of eosinophils in subjects given Phlai. The degree of improvement of TNSS after Phlai treatment was initially manifested in week 2 with the greatest effect in week 4. In contrast, there were no significant differences in all nasal cytokines, eosinophil counts or TNSS between before and after receiving placebo., Conclusions: These findings provided the first evidence for the anti-allergic effect of Phlai which possibly involved inhibition of nasal pro-inflammatory cytokines production and eosinophilic recruitment. Phlai thus represents a promising herbal medicine for alleviating inflammation and AR symptoms.

The surge in coronavirus disease 2019 (COVID-19) caused by the Omicron variants of the severe acute respiratory syndrome coronavirus 2 necessitates researches to inform vaccine effectiveness (VE) and other preventive measures to halt the pandemic. A test-negative case-control study was conducted among adults (age ≥18 years) who were at-risk for COVID-19 and presented for nasopharyngeal real-time polymerase chain reaction testing during the Omicron variant-dominant period in Thailand (1 January 2022-15 June 2022). All participants were prospectively followed up for COVID-19 development for 14 days after the enrolment. Vaccine effectiveness was estimated and adjusted for characteristics associated with COVID-19. Of the 7971 included individuals, there were 3104 cases and 4867 controls. The adjusted VE among persons receiving 2-dose, 3-dose, and 4-dose vaccine regimens for preventing infection and preventing moderate-to-critical diseases were 33%, 48%, 62% and 60%, 74%, 76%, respectively. The VE were generally higher among those receiving the last dose of vaccine within 90 days compared to those receiving the last dose more than 90 days prior to the enrolment. The highest VE were observed in individuals receiving the 4-dose regimen, CoronaVac-CoronaVac-ChAdOx1 nCoV-19-BNT162b2 for both preventing infection (65%) and preventing moderate-to-critical diseases (82%). Our study demonstrated increased VE along with an increase in number of vaccine doses received. Current vaccination programmes should focus on reducing COVID-19 severity and mandate at least one booster dose. The heterologous boosters with viral vector and mRNA vaccines were highly effective and can be used in individuals who previously received the primary series of inactivated vaccine.

Objective: To evaluate immunogenicity and safety of heterologous COVID-19 primary vaccination regimens of CoronaVac with fractional and standard BNT162b2 dosages in 5-11-year-old Thai children., Methods: This prospective, multicenter, double-blind, randomized control trial divided participants 1:1:1:1 to receive a second dose of either standard (10-μg) or half-dose (5-μg) BNT162b2 vaccines as follows: CoronaVac/10-μg-BNT162b2 (Group 1), CoronaVac/5-μg-BNT162b2 (Group 2), 10-μg-BNT162b2/10-μg-BNT162b2 (Group 3), or 10-μg-BNT162b2/5-μg-BNT162b2 (Group 4). A subset of participants from each arm received 10-μg-BNT162b2 booster (third) doses 16 weeks after their second vaccination. Humoral and cellular immunogenicity were assessed and adverse events (AEs) digitally self-reported., Results: Of 553 enrolled participants, 50 % were male, the median (interquartile range) age was 8.65 (7.00, 10.00) years, and a majority (91 %) had normal weight-for-height. All participants exhibited similarly robust neutralizing antibodies (NAb) against the ancestral Wuhan strain two weeks after the second vaccination, with titers highest in Group 1 (737.60, 95% CI [654.80, 830.88]), followed by Groups 3 (630.42, 95% CI [555.50, 715.45]), 2 (593.98, 95% CI [506.02, 697.23]), and 4 (451.79, 95% CI [388.62, 525.23]), as well as 56.01 % and 49.68 % seroconversion for BA.1 and BA.5, respectively. Half-dose BNT162b2 as a second dose induced significantly lower NAb titers compared to their respective full-dose regimens (p = 0.03 for Groups 1 vs 2 and p < 0.001 for Groups 3 vs 4). 77.71 % of participants developed SARS-CoV-2 ancestral spike protein-specific T-cell responses two weeks after the second vaccination. This was similar across arms. Booster doses generated NAb titers 5.69-11.51-folds higher than the second vaccination against BA.1. AEs were similar across arms, all mild or moderate, and fully resolved 2-3 days thereafter., Conclusion: Standard and fractional heterologous regimens of CoronaVac-BNT162b2 induced similar or higher humoral immunity than homologous BNT162b2 and represent alternative vaccine regimens for children. These findings are highly relevant in settings concurrently using both vaccines., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Fluticasone propionate/salmeterol xinafoate (FP/SAL) is an inhaled corticosteroid (ICS) and long-acting β 2 -agonist (LABA) combination, indicated for the regular treatment of children (aged >4 years) with asthma that is inadequately controlled with ICS monotherapy plus as-needed short-acting β 2 -agonists, or already adequately controlled with ICS/LABA., Objective: Compared with the adult population, fewer clinical studies have investigated the efficacy of FP/SAL in paediatric patients with moderate and moderate-to-severe asthma. In this review, we synthesise the available evidence for the efficacy and safety of FP/SAL in the paediatric population, compared with other available therapies indicated for asthma in children., Eligibility Criteria: A literature review identified randomised controlled trials and observational studies of FP/SAL in the paediatric population with moderate-to-severe asthma., Sources of Evidence: The Medline database was searched using PubMed (https://pubmed.ncbi.nlm.nih.gov/), with no publication date restrictions. Search strategies were developed and refined by authors., Charting Methods: Selected articles were screened for clinical outcome data (exacerbation reduction, nocturnal awakenings, lung function, symptom control, rescue medication use and safety) and a table of key parameters developed., Results: Improvements in asthma outcomes with FP/SAL include reduced risk of asthma-related emergency department visits and hospitalisations, protection against exercise-induced asthma and improvements in measures of lung function. Compared with FP monotherapy, greater improvements in measures of lung function and asthma control are reported. In addition, reduced incidence of exacerbations, hospitalisations and rescue medication use is observed with FP/SAL compared with ICS and leukotriene receptor antagonist therapy. Furthermore, FP/SAL therapy can reduce exposure to both inhaled and oral corticosteroids., Conclusions: FP/SAL is a reliable treatment option in patients not achieving control with ICS monotherapy or a different ICS/LABA combination. Evidence shows that FP/SAL is well tolerated and has a similar safety profile to FP monotherapy. Thus, FP/SAL provides an effective option for the management of moderate-to-severe asthma in the paediatric population., Competing Interests: Competing interests: PMP has acted as a speaker/consultant for AstraZeneca, GSK, Novartis, Boehringer Ingelheim and Sanofi. SN has acted as a speaker/consultant for AstraZeneca, GSK, Novartis, Boehringer Ingelheim and Sanofi. APMC has acted as a speaker/consultant for Danone, Nutricia, AbbVie and Sanofi. CT and APG are full-time employees of GSK and hold shares in GSK., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The inactivated COVID-19 whole-virus vaccine BBIBP-CorV has been extensively used worldwide. Heterologous boosting after primary vaccination can induce higher immune responses against SARS-CoV-2 than homologous boosting. The safety and immunogenicity after 28 days of a single Ad26.COV2.S booster dose given at different intervals after 2 doses of BBIBP-CorV are presented., Methods: This open-label phase 1/2 trial was conducted in healthy adults in Thailand who had completed 2-dose primary vaccination with BBIBP-CorV. Participants received a single booster dose of Ad26.COV2.S (5 × 10 10 virus particles) 90-240 days (Group A1; n = 360) or 45-75 days (Group A2; n = 66) after the second BBIBP-CorV dose. Safety and immunogenicity were assessed over 28 days. Binding IgG antibodies to the full-length pre-fusion Spike and anti-nucleocapsid proteins of SARS-CoV-2 were measured by enzyme-linked immunosorbent assay. The SARS-CoV-2 pseudovirus neutralization assay and live virus microneutralization assay were used to quantify the neutralizing activity of antibodies against ancestral SARS-CoV-2 (Wuhan-Hu-1) and the delta (B.1.617.2) and omicron (B.1.1.529/BA.1 and BA.2) variants. The cell-mediated immune response was measured using a quantitative interferon (IFN)-γ release assay in whole blood., Results: Solicited local and systemic adverse events (AEs) on days 0-7 were mostly mild, as were unsolicited vaccine-related AEs during days 0-28, with no serious AEs. On day 28, anti-Spike binding antibodies increased from baseline by 487- and 146-fold in Groups A1 and A2, and neutralizing antibodies against ancestral SARS-CoV-2 by 55- and 37-fold, respectively. Humoral responses were strongest against ancestral SARS-CoV-2, followed by the delta, then the omicron BA.2 and BA.1 variants. T-cell-produced interferon-γ increased approximately 10-fold in both groups., Conclusions: A single heterologous Ad26.COV2.S booster dose after two BBIBP-CorV doses was well tolerated and induced robust humoral and cell-mediated immune responses measured at day 28 in both interval groups., Clinical Trials Registration: NCT05109559., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S.M., R.W., S.K., S.L., A.J., A.T., V.L., P.C., N.T., N.C. report no potential conflicts of interest. S.N. has received honoraria for lectures from GSK, Zuellig Pharma, Astra Zeneca, Novartis, Abbot, Sanofi, Organon and Takeda and has participated in advisory boards for GlaxoSmithKline and Takeda. J.K.L. and T.A.W. and received institutional funding from Mahidol University to support study conduct, and T.A.W. supported management of Data Safety Monitoring Board activities and meetings. J-L.E. has received funding from Mahidol University and Johnson & Johnson for study support, and is the coordinator of the study Data Safety Monitoring Board. M.F.R. is an employee of Janssen Pharmaceuticals and holds restricted stock units in the company. C.L. is an employee of Janssen Pharmaceuticals. T.K.M. has received consulting fees from Janssen Pharmaceuticals. P.P. has received funding from Mahidol University and Johnson & Johnson for study support., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Infants with cow's milk protein allergy (CMPA) are at risk for nutrient inadequacy and impaired growth., Objective: To evaluate the effect of a new amino acid-based formula (nAAF) compared with commercial amino acid-based formula (cAAF) on growth and protein status of cow's milk protein (CMP)-allergic infants and to compare their growth with those of healthy infants., Methods: Infants less than 6 months of age with CMPA were enrolled in the nAAF or cAAF groups. Healthy infants fed breast milk (BM) or infant formula (IF) were controls. They remained on their formula/milk until day 28 of the study. Anthropometric evaluation was performed at birth, day 0 and day 28 of the study and calculated to z-scores of weight-for-age (WAZ), length-for-age (LAZ) and head circumference-for-age (HAZ). Plasma amino acids, albumin, urea nitrogen, and creatinine were assessed for infants with CMPA on day 0 and day 28., Results: The nAAF and cAAF groups did not differ in increases in WAZ [regression coefficient (95%CI): 0.088 (-0.619, 0.796), p = 0.791], LAZ [0.045 (-0.789, 0.880, p = 0.909], and HAZ [-0.645 (-2.082, 0.793), p = 0.337] between day 0 and day 28. The increases in WAZ and LAZ during 28 days in the nAAF group did not differ from the controls. The changes in the blood chemistry values, except albumin, were not different between CMPA groups., Conclusions: The nAAF, similar to the cAAF, supports growth and protein status for infants with CMPA, and it might be used as a substitute for the cAAF.

Background: The accuracy of an atopy patch test (APT) for fresh cow's milk allergy is controversial. Few studies have focused on commercial extract solutions. We aimed to evaluate the diagnostic performance of the APT in cow's milk allergic children using fresh cow's milk and commercial extracts of cow's milk and its components including casein, α-lactalbumin, and β-lactoglobulin., Methods: A prospective study was carried out in children with a history of cow's milk allergy. Children underwent the skin prick test (SPT) and APT with fresh cow's milk, powdered cow's milk, and commercial extracts of cow's milk, casein, α-lactalbumin, and β-lactoglobulin. Oral food challenge (OFC) was confirmed in all children., Results: A total of 37 patients participated (mean age 13.14 ± 7.26 months). Only 5 (13.51%) patients had positive OFC to cow's milk. The sensitivity of the APT using fresh cow's milk was 40%, specificity was 65.6%, PPV was 15.4%, and NPV was 87.5%. The sensitivity of the APT using powdered cow's milk was 40%, 60.7% for specificity, 15.4% for PPV, and 58% for NPV. The sensitivity and PPV of the APT using commercial solutions of cow's milk, casein, α-lactalbumin, and β-lactoglobulin were zero. The specificities were 90.6%, 93.8%, 100%, and 100% for α-lactalbumin, cow's milk, casein, and β-lactoglobulin, respectively., Conclusions: APT using commercial solutions showed higher specificity than fresh milk. The specificity increased using a protein component allergen., (© 2023. The Author(s).)

Objectives: The study aimed to compare the immunogenicity and safety of fractional (half) third doses of heterologous COVID-19 vaccines (AZD1222 or BNT162b2) to full doses after the two-dose CoronaVac and when boosting after three different extended intervals., Methods: At 60-<90, 90-<120, or 120-180 days intervals after the two-dose CoronaVac, participants were randomized to full-dose or half-dose AZD1222 or BNT162b2, followed up at day 28, 60, and 90. Vaccination-induced immune responses to Ancestral, Delta, and Omicron BA.1 strains were evaluated by antispike, pseudovirus, and microneutralization and T cell assays. Descriptive statistics and noninferiority cut-offs were reported as geometric mean concentration or titer and concentration or titer ratios comparing baseline to day 28 and day 90 and different intervals., Results: No safety concerns were detected. All assays and intervals showed noninferior immunogenicity between full doses and half doses. However, full-dose vaccines and/or longer 120-180-day intervals substantially improved the immunogenicity (measured by antispike or measured by pseudotyped virus neutralizing titers 50; P <0.001). Seroconversion rates were over 90% against the SARS-CoV-2 strains by all assays. Immunogenicity waned more quickly with half doses than full doses but remained high against the Ancestral or Delta strains. Against Omicron, the day 28 immunogenicity increased with longer intervals than shorter intervals for full-dose vaccines., Conclusion: Immune responses after day 28 when boosting at longer intervals after the two-dose CoronaVac was optimal. Half doses met the noninferiority criteria compared with the full dose by all the immune assays assessed., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The changes in the severe acute respiratory syndrome coronavirus 2 and the tapering of immunity after vaccination have propelled the need for a booster dose vaccine. We aim to evaluate B and T cell immunogenicity and reactogenicity of mRNA-1273 COVID-19 vaccine (100 µg) as a third booster dose after receiving either two doses of inactivated COVID-19 vaccine (CoronaVac) or two doses of viral vector vaccine (AZD1222) in adults not previously infected with COVID-19. The anti-receptor-binding-domain IgG (anti-RBD IgG), surrogate virus neutralization test (sVNT) against the Delta variant, and Interferon-Gamma (IFN-γ) level were measured at baseline, day (D)14 and D90 after vaccination. In D14 and D90, the geometric means of sVNT were significantly increased to 99.4% and 94.5% inhibition in CoronaVac, respectively, whereas AZD1222 showed inhibition of 99.1% and 93%, respectively. Anti-RBD IgG levels were 61,249 to 9235 AU/mL in CoronaVac and 38,777 to 5877 AU/mL in AZD1222 after D14 and D90 vaccination. Increasing median frequencies of S1-specific T cell response by IFN-γ concentration were also elevated in D14 and were not significantly different between CoronaVac (107.8-2035.4 mIU/mL) and AZD1222 (282.5-2001.2 mIU/mL). This study provides evidence for the high immunogenicity of the mRNA-1273 booster after two doses of CoronaVac or AZD1222 in the Thai population.

Data on real-life vaccine effectiveness (VE), against the delta variant (B.1.617.2) of the severe acute respiratory syndrome coronavirus 2 among various coronavirus disease 2019 (COVID-19) vaccine regimens are urgently needed to impede the COVID-19 pandemic. We conducted a test-negative case-control study to assess the VE of various vaccine regimens for preventing COVID-19 during the period when the delta variant was the dominant causative virus (≥ 95%) in Thailand (25 July 2021-23 Oct 2021). All individuals (age ≥18 years) at-risk for COVID-19, presented for nasopharyngeal real-time polymerase chain reaction (RT-PCR) testing, were prospectively enrolled and followed up for disease development. Vaccine effectiveness was estimated with adjustment for individual demographic and clinical characteristics. Of 3353 included individuals, there were 1118 cases and 2235 controls. The adjusted VE among persons receiving two-dose CoronaVac plus one BNT162b2 booster was highest (98%; 95% confidence interval [CI] 87-100), followed by those receiving two-dose CoronaVac plus one ChAdOx1 nCoV-19 booster (86%; 95% CI 74-93), two-dose ChAdOx1 nCoV-19 (83%; 95% CI 70-90), one CoronaVac dose and one ChAdOx1 nCoV-19 dose (74%; 95% CI 43-88) and two-dose CoronaVac (60%; 95% CI 49-69). One dose of CoronaVac or ChAdOx1 nCoV-19 had a VE of less than 50%. Our study demonstrated the incremental VE with the increase in the number of vaccine doses received. The two-dose CoronaVac plus one BNT162b2 or ChAdOx1 nCoV-19 booster regimens was highly effective in preventing COVID-19 during the rise of delta variant.

Background: Patterns of aeroallergen sensitization vary by countries. Testing with the minimum number of allergens is important to identify sensitized patients for a cost-effective approach. We aimed to assess the minimal skin prick test (SPT) panel to identify sensitized children with allergic respiratory diseases., Methods: The SPT results from January 2020 to December 2021 in children aged 2-18 years with symptoms of asthma or allergic rhinitis or both were retrospectively reviewed. All children received 11 allergen extracts (Dermatophagoides pteronyssinus [Der p], Dermatophagoides farinae [Der f], American cockroach, German cockroach, cat, dog, Bermuda grass, careless weed, Timothy, Acacia, and molds). The conditional approach was used to determine the allergen selection for the SPT panel., Results: A total of 688 children were enrolled (mean age = 8.14 ± 3.91 years). The sensitization results were Der p (57.85%), Der f (55.09%), German cockroach (18.02%), American cockroach (17.01%), cat (11.77%), Acacia (3.49%), Bermuda grass (3.34%), molds (3.05%), Timothy (2.33%), dog (1.89%), and careless weed (1.60%). Der p, Der f, and German cockroach were required to detect at least 95% of sensitized children. If the SPT panel added Acacia, cat, American cockroach, Bermuda grass, and careless weed, sensitization was detected in 99-100% of cases., Conclusions: Indoor allergens (Der p, cockroach, and cat) were common causes of sensitization in Thai children with allergic respiratory diseases. Eight allergens were sufficient for sensitization identification in Thai children with asthma or allergic rhinitis or both in clinical practice., (© 2022. The Author(s).)

Purpose: To evaluate and compare antimicrobial stewardship program (ASP) guideline adherence (primary outcome) as well as length of stay, 30-day all-cause mortality, clinical cure, antimicrobial consumption, and incidence of multidrug-resistant (MDR) pathogens (secondary outcomes) between an infectious diseases (ID) pharmacist-led intervention group and a standard ASP group., Methods: A quasi-experimental study was performed at Thammasat University Hospital between August 2019 and April 2020. Data including baseline characteristics and primary and secondary outcomes were collected from the electronic medical record by the ID pharmacist., Results: The ASP guideline adherence in the ID pharmacist-led intervention group was significantly higher than in the standard ASP group (79% vs 56.6%; P < 0.001), especially with regard to appropriate indication (P < 0.001), dosage regimen (P = 0.005), and duration (P = 0.001). The acceptance rate of ID pharmacist recommendations was 81.8% (44/54). The most common key barriers to following recommendations were physician resistance (11/20; 55%) and high severity of disease in the patient (6/20; 30%). Compared to the standard ASP group, there was a trend toward clinical cure in the ID pharmacist-led intervention group (63.6% vs 56.1%; P = 0.127), while 30-day all-cause mortality (15.9% vs 1.5%; P = 0.344) and median length of stay (20 vs 18 days; P = 0.085) were similar in the 2 groups. Carbapenem (P = 0.042) and fosfomycin (P = 0.014) consumption declined in the ID pharmacist-led intervention group. A marginally significant decrease in the overall incidence of MDR pathogens was also observed in the ID pharmacist-led intervention group (coefficient, -5.93; P = 0.049)., Conclusion: Our study demonstrates that an ID pharmacist-led intervention can improve ASP guideline adherence and may reduce carbapenem consumption., (© American Society of Health-System Pharmacists 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In the era of globally predominant omicron strains, a COVID-19 booster vaccine is needed. Our study aimed to evaluate the immunogenicity of a half-dose BNT162b2 booster after AZD1222 in healthy adults. A randomized trial of volunteers aged 18-69 years who received two-dose AZD1222 was conducted. The participants were randomized to receive the BNT162b2 vaccine intramuscularly-half (15 µg) vs. standard dose (30 µg). The immunogenicity was evaluated by a surrogate virus neutralization test (sVNT) against omicron variants and anti-spike-receptor-binding-domain IgG (anti-S-RBD IgG). From November-December 2021, 100 adults with a median age of 59.3 years (IQR 33.4-65.5) were enrolled. A booster dose was given at median of 98 days (IQR 92-128) after AZD1222. At day 14, the geometric means (GMs) of anti-S-RBD IgG in half- vs. standard-dose group were 2329.8 vs. 2574.7 BAU/mL, with a geometric mean ratio (GMR) of 0.90 (0.77-1.06). The GMs of sVNT against the omicron variant in the half- and standard-dose groups were 74.4% inhibition (95% CI 68.8-80.5) and 67.3% inhibition (57.9-78.1), respectively, with GMR of 0.95 (0.69-1.30). At day 90, the sVNT indicated 22.3% inhibition (95% CI 14.9-33.4) and 20.4% inhibition (13.1-32.0), respectively, with GMR of 1.09 (0.60-1.98). The fractional low-dose BNT162b2 mRNA booster vaccine provided non-inferior immunogenicity responses. During a shortage of vaccine supply, a fractional low dose should be considered for a booster vaccination program.

Background: Nasal irrigation is an effective component of sino-nasal disease management. Nonetheless, bacterial contamination is worrisome., Objective: To study bacterial colonization incidence using squeeze-bottle nasal irrigation devices, after disinfection with soap or soap-plus-microwave technique, in pediatric acute rhinosinusitis., Methods: A randomized, prospective, controlled study was conducted on acute rhinosinusitis children, aged 2-15 years. Each participant was randomized into a soap-cleaning or soap-plus- microwave group. For a two-week period, participants irrigated their nostrils with NSS twice daily and cleaned the bottle after each use. In the end, bottles were sent to a microbiological laboratory for bacterial identification., Results: The mean 5S Score and satisfaction score gradually improved in both groups with no significant differences between groups. Bacterial identification frequency in the soap group was slightly higher than in the soap-plus-microwave one, without statistical significance. For safety and tolerability, all participants reported 100% adherence to nasal irrigation. The soap-plus-microwave group reported more minor adverse outcomes than the soap-cleaning one. No thermal deformation of irrigation bottles was observed., Conclusions: Regular cleaning of nasal irrigation devices is needed to minimize bacterial contamination. Only soap or soap plus microwave disinfection appeared simple and safe for disinfection. Both techniques can equally minimize the rate of bacterial contamination. Although no gross thermal deformation at optimal power and duration, chemical irritants after high power or long microwave durations may be a concern.

Antibiotics have been extensively used in COVID-19 patients without a clear indication. We conducted a study to evaluate the feasibility of procalcitonin along with the "Clinical Pulmonary for Infection Score" (CPIS) as a strategy to reduce inappropriate antibiotic use. Using procalcitonin and CPIS score (PCT-CPIS) successfully reduced inappropriate antibiotics use among severe-critically ill COVID-19 pneumonia patients (45% vs 100%; P < .01). Compared to "non PCT-CPIS" group, "PCT-CPIS" group was associated with a reduction in the incidence of multidrug-resistant organisms and invasive fungal infections (18.3% vs 36.7%; P = .03), shorter antibiotic duration (2 days vs 7 days; P < .01) and length of hospital stay (10 days vs 16 days; P < .01)., (Copyright © 2022 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Immunogenicity of inactivated SARS-CoV-2 vaccine has waning antibody over time. With the emergence of the SARS-CoV-2 delta variant, which requires higher neutralizing antibody to prevent infection, a booster dose is needed., Objective: To evaluate immunogenicity and reactogenicity of standard- versus low-dose ChAdOx1 nCoV-19 vaccine booster after CoronaVac in healthy adults., Methods: A double-blinded, randomized, controlled trial of adult, aged 18-59 years, with completion of 2-dose CoronaVac at 21-28 days apart for more than 2 months was conducted. Participants were randomized to receive AZD1222 (Oxford/AstraZeneca) intramuscularly; standard dose (SD, 5x10 10 viral particles) or low dose (LD, 2.5x10 10 viral particles). Surrogate virus neutralization test (sVNT) against wild type and delta variant, and anti-spike-receptor-binding-domain IgG (anti-S-RBD IgG) were compared as geometric mean ratio (GMR) at day 14 and 90 between LD and SD arms., Results: From July-August 2021, 422 adults with median age of 44 (IQR 36-51) years were enrolled. The median interval from CoronaVac to AZD1222 booster was 77 (IQR 64-95) days. At baseline, geometric means (GMs) of sVNT against delta variant and anti-S-RBD IgG were 18.1%inhibition (95% CI 16.4-20.0) and 111.5 (105.1-118.3) BAU/ml. GMs of sVNT against delta variant and anti-S-RBD IgG in SD were 95.6%inhibition (95% CI 94.3-97.0) and 1975.1 (1841.7-2118.2) BAU/ml at day 14, and 89.4%inhibition (86.4-92.4) and 938.6 (859.9-1024.4) BAU/ml at day 90, respectively. GMRs of sVNT against delta variant and anti-S-RBD IgG in LD compared to SD were 1.00 (95% CI 0.98-1.02) and 0.84 (0.76-0.93) at day 14, and 0.98 (0.94-1.03) and 0.89 (0.79-1.00) at day 90, respectively. LD recipients had significantly lower rate of fever (6.8% vs 25.0%) and myalgia (51.9% vs 70.7%) compared to SD., Conclusion: Half-dose AZD1222 booster after 2-dose inactivated SARS-CoV-2 vaccination had non-inferior immunogenicity, yet lower systemic reactogenicity. Fractional low-dose AZD1222 booster should be considered especially in resource-constrained settings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Background: In vitro studies have demonstrated cross-reactivity among indoor allergen proteins in children with allergic respiratory diseases. However, there are only few studies evaluating in vivo response. A skin prick test (SPT) with commercial indoor solutions is widely used in clinical practice. We aimed to evaluate SPT agreement in children with allergic respiratory disease between pairs of common indoor allergens., Methods: We reviewed SPT results of children 2 to 18 years old, diagnosed with respiratory allergic disease. Results from house dust mite (Dermatophagoides farinae, Dermatophagoides pteronyssinus), cockroach (Periplaneta americana, Blatella germanica), cat and dog were collected. Sensitization was defined as ≥ 3 mm in wheal diameter. Kappa coefficient (κ) was used to analyze sensitization concordance for each allergen pair., Results: The charts of 300 children, 187 (62.33%) males, were reviewed. Mean age was 7.43 ± 3.29 years with 183 (61%), 140 (46.67%), 45 (15%), 30 (10%) sensitizations to house dust mite (HDM), cockroach, cat and dog, respectively. Sensitization concordance between HDM and cockroach was moderate: κ = 0.53 (95% CI: 0.42-0.64). Moderate agreement occurred between dog and cat: κ = 0.41 (95%CI: 0.30-0.52). HDM-sensitized children showed poor concordance with both cat κ = 0.17 (95%CI: 0.09-0.24) and dog κ = 0.09 (95%CI: 0.03-0.14). There was also poor concordance between cockroach-sensitized children to cat κ = 0.19 (95%CI; 0.11-0.28) and dog κ = 0.11 (95%CI; 0.04-0.18)., Conclusion: We demonstrated moderate agreement of SPT response between HDM and cockroach as well as dog and cat. This may be due to cross-reactivity. Component-resolved diagnosis should be considered in children with co-sensitization of these allergen pairs., (© 2021. The Author(s).)

Background: Short-acting β2-agonist (SABA) nebulization is commonly prescribed for children hospitalized with severe asthma exacerbation. Either intermittent or continuous delivery has been considered safe and efficient. The comparative efficacy of these two modalities is inconclusive. We aimed to compare these two modalities as the first-line treatments., Methods: An efficacy research with a retrospective cohort study design was conducted. Hospital records of children with severe asthma exacerbation admitted to Hat Yai Hospital between 2015 and 2017 were retrospectively collected. Children initially treated with continuous salbutamol 10 mg per hour or intermittent salbutamol 2.5 mg per dose over 1-4 h nebulization were matched one-to-one using the propensity score. Competing risk and risk difference regression was applied to evaluate the proportion of children who succeeded and failed the initial treatment. Restricted mean survival time regression was used to compare the length of stay (LOS) between the two groups., Results: One-hundred and eighty-nine children were included. Of these children, 112 were matched for analysis (56 with continuous and 56 with intermittent nebulization). Children with continuous nebulization experienced a higher proportion of success in nebulization treatment (adjusted difference: 39.5, 95% CI 22.7, 56.3, p  < 0.001), with a faster rate of success (adjusted SHR: 2.70, 95% CI 1.73, 4.22, p  < 0.001). There was a tendency that LOS was also shorter (adjusted mean difference - 9.9 h, 95% CI -24.2, 4.4, p  = 0.176)., Conclusion: Continuous SABA nebulization was more efficient than intermittent nebulization in the treatment of children with severe asthma exacerbation., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2020.)

Monogenic forms of vasculitis are rare but increasingly recognized. Furthermore, genetic immunodeficiency is increasingly associated with inflammatory immune dysregulatory features, including vasculitis. This case report describes a child of non-consanguineous parents who presented with chronic digital vasculitis early in life, is of short stature, has facial dysmorphia, immunodeficiency (low serum IgA, high serum IgM), recurrent bacterial infections, lymphoproliferation, absence of detectable serum C1q, and low classical complement pathway activity. We identified a previously reported de novo heterozygous pathogenic splice mutation in PIK3R1 (c.1425 + 1G > A), resulting in the skipping of exon 11 of the p85α subunit of phosphatidylinositol 3-kinase and causing activated PI3Kδ syndrome type II (APDS2). This explained the phenotype, with the exception of digital vasculitis and C1q deficiency, which have never been described in association with APDS2. No mutations were identified in C1QA, B , or C , their promoter regions, or in any other complement component. Functional studies indicated normal monocytic C1q production and release, suggesting that the observed C1q deficiency was caused by peripheral consumption of C1q. Since C1q deficiency has never been associated with APDS2, we assessed C1q levels in two unrelated patients with genetically confirmed APDS2 and confirmed C1q deficiency in those two cases as well. This observation suggests C1q deficiency to be an inherent but previously unrecognized feature of APDS2. We speculate that the consumption of C1q is driven by increased apoptotic bodies derived from immune cellular senescence, combined with elevated IgM production (both inherent features of APDS2). Secondary C1q deficiency in APDS2 may further contribute to immunodeficiency and could also be associated with inflammatory immune dysregulatory phenotypes, such as the digital vasculitis observed in our case., (Copyright © 2019 Hong, Nanthapisal, Omoyinmi, Olbrich, Neth, Speckmann, Lucena, Gilmour, Worth, The Genomics England Research Consortium, Klein, Eleftheriou and Brogan.)

Competing Interests: Competing interests: None declared.

Cutaneous leukocytoclastic vasculitis arises from immune complex deposition and dysregulated complement activation in small blood vessels. There are many causes, including dysregulated host response to infection, drug reactions, and various autoimmune conditions. It is increasingly recognised that some monogenic autoinflammatory diseases cause vasculitis, although genetic causes of vasculitis are extremely rare. We describe a child of consanguineous parents who presented with chronic cutaneous leukocytoclastic vasculitis, recurrent upper respiratory tract infection, and hypocomplementaemia. A homozygous p.His380Arg mutation in the complement factor I (CFI) gene CFI was identified as the cause, resulting in complete absence of alternative complement pathway activity, decreased classical complement activity, and low levels of serum factor I, C3, and factor H. C4 and C2 levels were normal. The same homozygous mutation and immunological defects were also identified in an asymptomatic sibling. CFI deficiency is thus now added to the growing list of monogenic causes of vasculitis and should always be considered in vasculitis patients found to have persistently low levels of C3 with normal C4.

Background: The association that exists between livedo reticularis (LR) and stroke is known as Sneddon's syndrome (SnS). The disorder is classified as primary SnS (PSnS), if the cause remains unknown and secondary SnS. The condition is rare and it occurs mainly sporadically. In 2014, 2 independent teams described a new genetic disorder with childhood-onset, which was called deficiency of adenosine deaminase 2 (DADA2), characterized by recurrent fevers and vascular pathologic features that included LR and stroke. All the patients carried recessively inherited mutations in cat eye syndrome chromosome region candidate 1 gene (CECR1), encoding the adenosine deaminase 2 (ADA2) protein. Genetic testing is the standard for the diagnosis of DADA2. However, the diagnostic accuracy of more affordable laboratorial analysis in CECR1-mutated individuals remains to be established. We aim to determine whether plasma ADA2 activity and serum immunoglobulin M (IgM) levels can distinguish (1) DADA2 from other adult patients within the SnS spectrum, and (2) healthy CECR1 heterozygous (HHZ) from healthy controls (HC)., Methods: ADA2 activity in plasma and serum IgM concentrations was measured in adult patients within the SnS spectrum, healthy first-degree relatives and HC. Genetic results were used as the reference standard. The primary outcome measures were sensitivity and specificity derived from receiver operating curve analysis., Results: A total of 73 participants were included in the study: 26 patients with PSnS with no CECR1 mutation (PSnS), 6 bi-allelic (DADA2 patients) and 7 HHZ CECR1 mutations and 34 HC. Plasma ADA2 activity and serum IgM levels were significantly lower in DADA2 patients than in PSnS. With the use of the best indexes, plasma ADA2 activity differentiated PSnS from DADA2 with a sensitivity and specificity of 100.0% and HHZ from HC with a sensitivity of 97.1% and specificity of 85.7%. Serum IgM levels also differentiated PSnS from DADA2 with a sensitivity of 85.2% and specificity of 83.3%., Conclusion: Serum IgM levels might be used as a triage tool and plasma ADA2 activity performs perfectly as a diagnostic test for DADA2 in adult patients within the SnS spectrum. ADA2 activity in plasma also reliably distinguishes HHZ from HC., (© 2019 S. Karger AG, Basel.)

Background: Monogenic autoinflammatory diseases (AID) are a rapidly expanding group of genetically diverse but phenotypically overlapping systemic inflammatory disorders associated with dysregulated innate immunity. They cause significant morbidity, mortality and economic burden. Here, we aimed to develop and evaluate the clinical impact of a NGS targeted gene panel, the "Vasculitis and Inflammation Panel" (VIP) for AID and vasculitis., Methods: The Agilent SureDesign tool was used to design 2 versions of VIP; VIP1 targeting 113 genes, and a later version, VIP2, targeting 166 genes. Captured and indexed libraries (QXT Target Enrichment System) prepared for 72 patients were sequenced as a multiplex of 16 samples on an Illumina MiSeq sequencer in 150bp paired-end mode. The cohort comprised 22 positive control DNA samples from patients with previously validated mutations in a variety of the genes; and 50 prospective samples from patients with suspected AID in whom previous Sanger based genetic screening had been non-diagnostic., Results: VIP was sensitive and specific at detecting all the different types of known mutations in 22 positive controls, including gene deletion, small INDELS, and somatic mosaicism with allele fraction as low as 3%. Six/50 patients (12%) with unclassified AID had at least one class 5 (clearly pathogenic) variant; and 11/50 (22%) had at least one likely pathogenic variant (class 4). Overall, testing with VIP resulted in a firm or strongly suspected molecular diagnosis in 16/50 patients (32%)., Conclusions: The high diagnostic yield and accuracy of this comprehensive targeted gene panel validate the use of broad NGS-based testing for patients with suspected AID.

The importance of actin dynamics in the activation of the inflammasome is becoming increasingly apparent. IL-1β, which is activated by the inflammasome, is known to be central to the pathogenesis of many monogenic autoinflammatory diseases. However, evidence from an autoinflammatory murine model indicates that IL-18, the other cytokine triggered by inflammasome activity, is important in its own right. In this model, autoinflammation was caused by mutation in the actin regulatory gene WDR1 We report a homozygous missense mutation in WDR1 in two siblings causing periodic fevers with immunodeficiency and thrombocytopenia. We found impaired actin dynamics in patient immune cells. Patients had high serum levels of IL-18, without a corresponding increase in IL-18-binding protein or IL-1β, and their cells also secreted more IL-18 but not IL-1β in culture. We found increased caspase-1 cleavage within patient monocytes indicative of increased inflammasome activity. We transfected HEK293T cells with pyrin and wild-type and mutated WDR1 Mutant protein formed aggregates that appeared to accumulate pyrin; this could potentially precipitate inflammasome assembly. We have extended the findings from the mouse model to highlight the importance of WDR1 and actin regulation in the activation of the inflammasome, and in human autoinflammation., (© 2017 Standing et al.)

Juvenile systemic lupus erythematosus (jSLE) is rare before 5 years of age. Monogenic causes are suspected in cases of very early onset jSLE particularly in the context of a family history and/or consanguinity. We performed whole-exome sequencing and homozygosity mapping in the siblings presented with early-onset jSLE. A novel homozygous missense mutation in protein kinase C delta (c.1294G>T; p.Gly432Trp) was identified in both patients. One patient showed a marked clinical response and resolution inflammation with rituximab therapy. This report demonstrates the clinical importance of identifying monogenic causes of rare disease to provide a definitive diagnosis, help rationalize treatment, and facilitate genetic counseling., (Copyright © 2017 by the American Academy of Pediatrics.)

There are currently limited data regarding paediatric Behçet's disease (BD), particularly in the UK. We describe the clinical spectrum, treatment and outcome of BD, and explore the relative sensitivities of the criteria for the diagnosis of BD in a UK paediatric cohort. Single retrospective case note review of children with a clinical diagnosis of BD presenting between 1987 and 2012. Demographics, clinical features, treatment and outcomes were recorded. The sensitivities of the International Study Group (ISG) and International Criteria for BD (ICBD) criteria were explored. BD disease activity was calculated using the Behçet's Disease Activity Index (BDAI). Forty-six patients (22 male) were identified. Median age of onset was 4.87 (0.04-15.71) years; median time to diagnosis was 3.74 (0.25-13.48) years. Clinical features were recurrent oral ulceration (97.8 %), recurrent genital ulceration (73.9 %), gastrointestinal (58.7 %), musculoskeletal (47.83 %), cutaneous (23.9 %) involvement and uveitis (2 %). Recurrent genital ulceration was more common in female patients (P = 0.044). Thirty-seven patients (80.4 %) fulfilled the ICBD criteria; only 12 patients (26.1 %) fulfilled the ISG criteria. BDAI score at diagnosis was 7/20 (0-10/20) and significantly decreased to 5/20 (0-9/20) (P < 0.0001) at latest follow-up. The commonest systemic treatment was colchicine (76.1 %); anti-TNFα treatment was reserved for severe cases (15.5 %). Paediatric BD in the UK may present very early in life, sometimes with a family history, and with a low incidence of ocular involvement. Diagnostic delay is common. The majority of our patients required systemic therapy; anti-TNFα was reserved for severe cases and has largely superseded the use of thalidomide., Competing Interests: Compliance with ethical standards Ethical approval was given by our Institution’s Research Ethics Committee for a retrospective case note review; thus, no written consent from patients was required. Disclosures None.

Objective: To describe the clinical features, genotype, and treatment in a series of subjects with confirmed adenosine deaminase 2 (ADA2) deficiency., Methods: All symptomatic subjects were referred for genetic testing for suspected ADA2 deficiency; relatives of index cases were also screened. Demographic, clinical, and laboratory characteristics and treatments were recorded. Genetic analyses included whole-exome sequencing in 4 subjects and Sanger sequencing of CECR1 (the gene for cat eye syndrome chromosome region candidate 1) in all subjects. Assays for ADA2 enzyme activity and quantitative polymerase chain reaction analysis of CECR1 messenger RNA (mRNA) were also performed., Results: We identified 15 subjects with ADA2 deficiency, 5 of whom were asymptomatic (relatives of index cases; ages 5-42 years). Homozygous or compound heterozygous mutations in CECR1 were identified in all subjects. Phenotypic manifestations in the patients with symptomatic ADA2 deficiency included livedo racemosa (73.3%), neurologic involvement (53.3%), and immunodeficiency (46.7%). CECR1 mRNA expression in 8 subjects, including 5 who were presymptomatic, was significantly lower than in healthy controls (P = 0.0016). Subjects with ADA2 deficiency (with or without symptoms) also had lower ADA2 enzyme activity compared to healthy pediatric controls (P < 0.0001) and patients with sporadic (nonfamilial) childhood polyarteritis nodosa (PAN) without CECR1 mutation (P = 0.0108). Anti-tumor necrosis factor therapy was required in 9 of the 10 symptomatic subjects., Conclusion: The clinical manifestations of ADA2 deficiency ranged in severity from limited cutaneous involvement to severe multisystemic vasculitis; one-third of our cases (5 of 15) were currently asymptomatic, and required close monitoring. We recommend CECR1 screening for unaffected siblings of index cases, cases of familial vasculitis, and cases of PAN that is resistant to standard treatment., (© 2016, American College of Rheumatology.)

Background: Despite an increasing recognition that both asthma and allergic rhinitis are serious health disorders in Thailand, their combined effects on patients' quality of life in the Thai population has not been reported., Objective: The study aimed to evaluate the impacts of allergic rhinitis and asthma on the quality of life of young adolescents in Thailand., Methods: A total of 1,440 pupils, aged 12-14 years, were randomly recruited from 4 schools located in Bangkok and Pathum Thani Province. Allergic rhinitis and asthmatic symptoms were identified by the International Study of Asthma and Allergies in Childhood (ISAAC) written questionnaire. The Pediatric Quality of Life Inventory (PedsQL) questionnaire was used to evaluate their quality of life., Results: There were 1,230 completed questionnaires for analysis. The prevalence of allergic rhinitis alone, asthma alone and diseases co-occurrence was 32.8%, 7.2%, and 12.7% respectively. Pupils with respiratory allergy had significantly lower PedsQL mean scores than healthy pupils, for all dimensions (p < 0.006). The greatest reduction of the PedsQL mean score was for emotional functioning. Among pupils with allergic rhinitis, those who were also affected with asthma had significantly lower mean scores, for all quality of life domains (all p < 0.001). Compared to allergic rhinitis, asthma significantly reduced PedsQL mean scores in almost all domains (p < 0.001), except for physical health., Conclusions: Allergic rhinitis and asthma have a significant influence on the quality of life in young Thai adolescents, in particular regarding emotional functioning. Asthma has stronger negative effects on life quality than allergic rhinitis, especially regarding psychosocial health.

Background: Rhinosinusitis (RS) is a common problem in children. There are very few published studies comparing acute rhinosinusitis (ARS) and chronic rhinosinusitis (CRS) in children., Objective: To determine the clinical manifestations in children with ARS and CRS., Methods: One hundred and fifty-four patients with a clinical diagnosis of RS were enrolled. ARS was defined as persistent symptoms for more than 10 days but less than 4 weeks and CRS was defined as persistent symptoms for longer than 8 weeks. Patients were interviewed to obtain demographic and clinical data. Physical findings and medications were recorded. All patients underwent radiographic studies. Allergy and immunological testing were done in selected case. All data were compared between the ARS and CRS groups., Results: One hundred and three patients were classified as having ARS and fifty-one had CRS. Their mean (+/- SD) age was 5.9 +/- 3.3 years. Allergic rhinitis was common in the chronic rhinosinusitis group. The most common main complaints in acute and chronic rhinosinusitis were cough and rhinorrhea. There was no significant difference in symptoms between both groups, except for periorbital pain and sleep apnea which were found more frequently in the chronic group. Sixty five percents of ARS and 58.8% of CRS had abnormal x-ray findings. Adenoid hypertrophy was found in the CRS group. There was overall improvement after 14.6 +/- 3.82 days and 22.35 +/- 5.04 days (mean) of antibiotic treatment in the ARS and CRS groups, respectively. None of the patient underwent sinus surgery., Conclusion: The most common RS symptoms were rhinorrhea and cough. Patients with allergic rhinitis had a higher risk of developing chronic rhinosinusitis. Patients with ARS and CRS were successfully treated with medical treatment.