Updated consensus statements on COVID-19 Vaccine Allergy Safety in Hong Kong.

Due to global concerns over coronavirus disease 2019 (COVID-19) vaccine-associated allergic reactions; the Hong Kong Institute of Allergy (HKIA) formulated an initial set of consensus statements (CS) on COVID-19 Vaccine Allergy Safety (VAS) in early 2021. Following accumulation of both local and international experience on and COVID-19 VAS, the HKIA task force reformed to update the Hong Kong consensus on COVID-19 VAS. A nominated task force of experts managing patients with drug and vaccine allergies in Hong Kong formulated the updated CS by unanimous decision. A total of 9 new statements were established. Individuals with history of food allergies and anaphylaxis unrelated to the components of COVID-19 vaccines do not require allergist review prior to vaccination. Individuals with history suspicious of an excipient allergy may now be vaccinated with a non-PEG containing vaccine without prior allergist assessment. Individuals with suspected mild allergic reactions following prior COVID-19 vaccination can proceed with the next dose. Only individuals who present with immediate-type allergic reaction with systemic symptoms or more severe nonimmediate type reactions should defer their next dose until allergist review. The remaining statements regarding adequate safety during vaccination and advocation for legislative changes regarding excipient disclosure in Hong Kong remained unchanged from the prior CS. The updated CS are updated in accordance with local and international experience thus far and serve as guidance for local frontline healthcare providers to further promote safe COVID-19 vaccine uptake in Hong Kong.

Towards quality assurance: implementation of a POCUS image archiving system in a high-volume community emergency department.

BACKGROUND: Quality assurance review is an integral part of point-of-care ultrasound (POCUS) programs but may not be routine practice in community hospitals. Lack of image acquisition and documentation can result in suboptimal patient care. In cases with an adverse outcome and no record of images, there is no mechanism for quality improvement. OBJECTIVES: Our goal was to implement a system of POCUS image archiving in a community hospital. Our SMART (Specific, Measurable, Actionable, Realistic, Timely) aim was to have > 50% of emergency department (ED) POCUS users archiving scans, and > 80% of all billed POCUS scans archived, measuring improvements bi-weekly over a period of 9 months. METHODS: The study was conducted at a single-community ED between August 2020 and April 2021. The POCUS archiving workflow was developed and refined through multiple plan-do-study-act (PDSA) cycles. Surveys, stakeholder meetings, audits, and feedback were used to generate and re-evaluate the interventions. These included introduction of QPathE© software, streamlining of the workflow process, strategic machine placement, POCUS rounds, use of a website for POCUS workflow instructions, and dissemination of audit results. Scans were tracked biweekly, and indexed by the number of scans billed. The primary outcome measure was the number of POCUS scans archived per 100 scans billed. RESULTS: Over a 9-month period, spanning 72,986 ED visits, 550 scans were archived. The percentage of POCUS users who changed practice to consistently archiving scans was 51%. The rate of POCUS scans archived per 100 scans billed was > 80%, compared to no archiving at baseline. CONCLUSION: We were able to transition from a system with entirely unarchived POCUS scanning, to one with > 80% of scans archived over a period of 9 months. This is the first published paper documenting implementation of a POCUS image archiving system in a Canadian Community ED.

RéSUMé: CONTEXTE: L'examen de l'assurance qualité fait partie intégrante des programmes d'échographie au point d'intervention (POCUS), peut ne pas être une pratique courante dans les hôpitaux communautaires. L'absence d'acquisition et de documentation d'images peut entraîner des soins sous-optimaux pour le patient. Dans les cas où l'issue est défavorable et où il n'y a pas d'enregistrement des images, il n'existe aucun mécanisme d'amélioration de la qualité. OBJECTIFS: Notre objectif était de mettre en place un système d'archivage des images POCUS dans un hôpital communautaire. Notre objectif SMART (Specific, Measurable, Actionable, Realistic, Timely) était de faire en sorte que > 50% des utilisateurs de POCUS aux urgences archivent les scans, et que > 80% de tous les scans POCUS facturés soient archivés, en mesurant les améliorations toutes les deux semaines sur une période de 9 mois. MéTHODES: L'étude a été menée dans une seule urgence communautaire entre août 2020 et avril 2021. Le flux de travail de l'archivage POCUS a été développé et affiné à travers de multiples cycles Planification- Exécution­Étude­Action (PEEA) [en anglais Plan-Do-Study-Act (PDSA)]. Des sondages, des réunions de parties prenantes, des audits et des commentaires ont été utilisés pour générer et réévaluer les interventions. Il s'agit notamment de l'introduction du logiciel QPathE©, de la rationalisation du processus de flux de travail, de l'emplacement stratégique des machines, des tournées POCUS, de l'utilisation d'un site web pour les instructions de flux de travail POCUS et de la diffusion des résultats des audits. Les scans étaient suivis toutes les deux semaines et indexés en fonction du nombre de scans facturés. Le principal critère d'évaluation était le nombre de scans POCUS archivés pour 100 scans facturés. RéSULTATS: Sur une période de 9 mois, couvrant 72 986 visites aux urgences, 550 scanners ont été archivés. Le pourcentage d'utilisateurs de POCUS qui ont changé de pratique pour archiver systématiquement les scans était de 51 %. Le taux de scanners POCUS archivés pour 100 scanners facturés était > 80%, par rapport à l'absence d'archivage au départ. CONCLUSION: Nous avons pu passer d'un système où les scanners POCUS n'étaient pas du tout archivés à un système où plus de 80% des scanners ont été archivés sur une période de 9 mois. Il s'agit du premier article publié sur la mise en œuvre d'un système d'archivage d'images POCUS dans une urgence communautaire canadienne.

Long-term safety and effectiveness of berotralstat for hereditary angioedema: The open-label APeX-S study.

BACKGROUND: Berotralstat (BCX7353) is an oral, once-daily inhibitor of plasma kallikrein recently approved for prevention of angioedema attacks in adults and adolescents with hereditary angioedema (HAE). The objective of this report is to summarize results from an interim analysis of an ongoing long-term safety study of berotralstat in patients with HAE. METHODS: APeX-S is an ongoing, phase 2, open-label study conducted in 22 countries (ClinicalTrials.gov, NCT03472040). Eligible patients with a clinical diagnosis of HAE due to C1 inhibitor deficiency (HAE-C1-INH) were centrally allocated to receive berotralstat 150 or 110 mg once daily. The primary objective was to determine long-term safety and the secondary objective was to evaluate effectiveness. RESULTS: Enrolled patients (N = 227) received berotralstat 150 mg (n = 127) or 110 mg (n = 100) once daily. The median (range) duration of exposure was 342 (11-540) and 307 (14-429) days for the 150-mg and 110-mg groups, respectively. Treatment-emergent adverse events (TEAEs) occurred in 91% (n = 206) of patients. The most common TEAEs across treatment groups were upper respiratory tract infection (n = 91, 40%), abdominal pain (n = 57, 25%), headache (n = 40, 18%), and diarrhea (n = 31, 14%) and were mostly mild to moderate. Fifty percent (n = 113) of patients had at least one drug-related adverse event (AE; 150 mg, n = 57 [45%]; 110 mg, n = 56 [56%]), and discontinuations due to AEs occurred in 19 (8%) patients (150 mg, n = 13 [10%]; 110 mg, n = 6 [6%]). Three (1.3%) patients experienced a drug-related serious TEAE. Among patients who received berotralstat through 48 weeks (150 mg, n = 73; 110 mg, n = 30), median HAE attack rates were low in month 1 (150 mg, 1.0 attacks/month; 110 mg, 0.5 attacks/month) and remained low through 12 months (0 attacks/month in both dose groups). Mean HAE attack rates followed a similar trend, and no evidence for patient tolerance to berotralstat emerged. In both dose groups, angioedema quality of life scores showed clinically meaningful changes from baseline. CONCLUSIONS: In this analysis, both berotralstat doses, 150  and 110 mg once daily, were generally well tolerated. Effectiveness results support the durability and robustness of berotralstat as prophylactic therapy in patients with HAE. TRIAL REGISTRATION: The study is registered with ClinicalTrials.gov (NCT03472040).

Hong Kong Anaphylaxis Consortium Consensus Statements on prescription of adrenaline autoinjectors in the acute care setting.

BACKGROUND: Adrenaline autoinjectors (AAInj) facilitates early administration of adrenaline and remains the first-line treatment for anaphylaxis. However, only a minority of anaphylaxis survivors in Hong Kong are prescribed AAInj and formal guidance do not exist. International anaphylaxis guidelines have been largely based on Western studies, which may not be as relevant for non-Western populations. OBJECTIVE: To formulate a set of consensus statements on the prescription of AAInj in Hong Kong. METHODS: Consensus statements were formulated by the Hong Kong Anaphylaxis Consortium by the Delphi method. Agreement was defined as greater than or equal to 80% consensus. Subgroup analysis was performed to investigate differences between allergy and emergency medicine physicians. RESULTS: A total of 7 statements met criteria for consensus with good overall agreement between allergy and emergency medicine physicians. AAInj should be used as first-line treatment and prescribed for all patients at risk of anaphylaxis. This should be prescribed prior to discharge from the Accident and Emergency Department together with an immediate referral to an allergy center. The decision for prescribing AAInj should be based on the severity of previous reactions; including objective signs of respiratory involvement, objective signs of cardiovascular involvement and multiorgan involvement (regardless of severity). Patient demographics and comorbidities, specifically history of asthma or chronic obstructive pulmonary disease, should also be considered. Patients deemed eligible for AAInj should be offered avoidance advice and prescribed one AAInj while awaiting review by allergists. AAInj technique should be demonstrated by a healthcare professional or instruction video, and a return demonstration by the patient is required. The patient should also be counseled that the decision on the continued need of AAInj prescription in the long-term should be reviewed by an allergist. CONCLUSION: Consensus statements support the prescription of AAInj by front-line physicians with subsequent allergist review when treating patients at risk of anaphylaxis in Hong Kong.

Consensus Statements on the Approach to COVID-19 Vaccine Allergy Safety in Hong Kong.

Background: Mass coronavirus disease 2019 (COVID-19) vaccination to achieve herd immunity is an effective means to mitigate the current COVID-19 pandemic. Reports of COVID-19 vaccine-associated allergic reactions and lack of clear local guidance are contributing factors leading to a low vaccine acceptance rate in the community. A task force of experts from the Hong Kong Institute of Allergy (HKIA) has been formed to address current needs. Objective: To formulate a set of consensus statements (CS) on COVID-19 vaccine allergy safety (VAS) in Hong Kong. Methods: A nominated task force of experts managing patients with drug and vaccine allergies in Hong Kong formulated the CS by the Delphi method. An agreement was a priori defined as ≥80% consensus. Results: A total of 11 statements met the criteria for consensus with good overall agreement among task force members, including seven statements on pre-vaccination recommendations and four statements on vaccination and post-vaccination guidance. Individuals with a history of suspected allergic reaction to prior COVID-19 vaccination should not receive further COVID-19 vaccination, and other groups at risk of COVID-19 vaccine-associated allergic reactions have been identified. The importance of pre-vaccination and post-vaccination assessment by frontline healthcare workers and evaluation by allergists are highlighted. Conclusion: The CS provides pragmatic and timely guidance for local frontline healthcare providers on decisions regarding COVID-19 VAS.

The POCUS Pulse Check: A Case Series on a Novel Method for Determining the Presence of a Pulse Using Point-of-Care Ultrasound.

BACKGROUND: During cardiopulmonary resuscitation, pulse checks must be rapid and accurate. Despite the importance placed on the detection of a pulse, several studies have shown that health care providers have poor accuracy for detection of central pulses by palpation. To date, the use of point-of-care ultrasound (POCUS) in cardiac arrest has focused on the presence of cardiac standstill and diagnosing reversible causes of the arrest. OBJECTIVE: This case series highlights a simple, novel approach to determine whether pulses are present or absent by using POCUS compression of the central arteries. DISCUSSION: Using this technique, we found that a POCUS pulse check can be consistently performed in < 5 s and is clearly determinate, even when palpation yields indeterminate results. CONCLUSIONS: In this case series, the POCUS pulse check was a valuable adjunct that helped to change management for critically ill patients. Future prospective studies are required to determine the accuracy of this technique and the impact on patient outcomes in a larger cohort.

The unmet provision of allergy services in Hong Kong impairs capability for allergy prevention-implications for the Asia Pacific region.

INTRODUCTION: There is a high and rising prevalence of many allergic diseases in the Asia Pacific, including Hong Kong (HK), which is unmatched by a commensurate provision of clinical allergy services. METHOD: This review highlights progress and deficiencies in allergy service and training in HK. The allergy work force was estimated from the numbers of doctors practicing allergy registered with the HK Medical Council Specialist Register in Immunology and Allergy; Paediatric Immunology and Infectious Diseases (includes allergy); Paediatrics; and Immunology (as a discipline of Pathology). The numbers of trainees were estimated from the trainee lists of the Hong Kong Colleges of Physicians, Paediatrics and Pathology. The numbers of allergy clinics were estimated from existing services in Hospital Authority public hospitals in HK. RESULTS: In the last 3 years, two new drug allergy clinics have been established in public hospitals, and for the first time in 20 years, Hong Kong has a trainee in adult allergy. The current ratio of allergists per head of population has improved slightly from 1:1.46 million in 2014 to 1:1.17 million, but it is still low compared to many countries. There are 5-fold more paediatric allergists than adult allergists per head of population in HK. DISCUSSION: Hong Kong is not equipped to take advantage of major public health advances in allergy prevention. If the unbalance of adult to paediatric allergists remains uncorrected, continuing care for allergic children as they grow into adulthood will be an increasing problem. CONCLUSION: Hong Kong still has an unmet need for allergy specialists and is ill equipped to exploit recently discovered public health opportunities to prevent allergy. This review provides recommendations to improve allergy service provision and training, including the creation of Centres of Excellence in allergy to drive the growth of the specialty.

Vestibular function following unilateral cochlear implantation for profound sensorineural hearing loss.

BACKGROUND: Many Canadians are affected by sensorineural hearing loss (SNHL) and those with severe or profound hearing loss may have poor hearing function despite optimized hearing aids. Cochlear implants (CI) offer effective hearing rehabilitation for these patients, however, concern continues to exist regarding possible effects of CI on the vestibular system and balance. The objective of this study was to conduct a pilot study assessing the effects of unilateral cochlear implantation (CI) on balance and the vestibular system in post-lingually deafened adults. METHODS: Twelve patients were included in this pilot study and were assessed pre-operatively and at immediate, 1 week, and 1 month post-operative intervals. Assessments consisted of the dizziness handicap inventory (DHI), subjective visual vertical (SVV), and timed up-and-go testing (TUG). When applicable, testing was repeated with the CI on and off. RESULTS: Many patients were found to have deviated SVV at pre-operative and post-operative assessments. However, statistically significant changes were not seen when comparing pre-operative and post-operative SVV or when comparing SVV with the CI on and with the CI off. DHI was found to improve in five patients and worsen in two patients, however, no statistically significant change was found in DHI scores or with TUG testing. CONCLUSIONS: This current pilot study does not indicate that CI surgery or implant activity influence vestibular or balance function, however, this pilot study is underpowered and greater numbers of patients would need be assessed to confirm these findings.

Immunotherapy - Vaccines for allergic diseases.

Allergic diseases are some of the most commonly encountered problems in clinical practice. Drugs such as corticosteroids and antihistamines can provide effective symptomatic relief, but do not alter the course of the disease. Specific immunotherapy (SIT) was first used to treat pollen allergy in 1911, and has since evolved into an effective treatment for allergic rhinitis and asthma. SIT has been shown in clinical studies to reduce symptoms and medication use in patients with allergic rhinitis and asthma. Recent studies also showed that the therapeutic benefit is long-lasting after the completion of three to five years of treatment. SIT can also effectively reduce the risk of developing asthma and new allergic sensitizations in children with allergic rhinitis.

[Effect of 1-year specific immunotherapy with standardized house dust mite vaccine on mild to moderate allergic asthmatic patients].

OBJECTIVE: To evaluate the clinical efficacy and safety of specific immunotherapy (SIT) with standardized house dust mite (HDM) vaccine on allergic asthmatic patients. METHODS: The investigation was a multicentre, randomized, double-blind, placebo-controlled clinical study. 132 patients with mild to moderate asthma who were allergic to HDM, recruited from three hospitals of China (The First Affiliated Hospital of Guangzhou Medical College, Shenyang General Military Hospital, Suzhou Children's Hospital), were randomly allocated to the active group (n = 66) or the control group (n = 66) respectively. The active group received SIT with a standardized depot Dermatophagoides pteronyssinus (Der p) extract absorbed to aluminium hydroxide (Alutard SQ, ALK-Abelló, Denmark), while the control group received a placebo containing histamine dihydrochloride by subcutaneous injections for 1 year. Treatment of each group was started from the initial concentration. Updosing was performed with weekly injections from four 10-fold dose-increase vials (active group: 100, 1,000, 10,000, 100,000 SQ-U/ml, control group: 0.01, 0.1, 1.0, 10 microg/ml. 100,000 SQ-U/ml of Der p extract contains 9.8 microg/ml of the majoy allergen Der p1). The single-dose was injected weekly with 0.2, 0.4, 0.8 ml of each concentration in turn from the preceding 3 vials, totally for 9 weeks. Subsequently, the dose with 0.1, 0.2, 0.4, 0.6, 0.8 ml of the highest concentration was injected weekly from the 10th-14th week and a maintenance dose with 1 ml was reached at the 15th week. The dosing interval was then gradually increased to 2, 4, 6 weeks until the end of the first 26-weeks updosing phase (phase I, H(1)). Thereafter, the dosing continued at 6-week intervals for maintenance phase (phase II, H(2)) till the end of the complete treatment. The patient was observed for at least 30 minutes in the clinic after each injection. RESULTS: A total of 132 subjects were randomized and 129 subjects (64 in the active group, 65 in the control group) completed the whole study. Dropouts included three females because of poor compliance, being afraid of the epidemic of Severe Acute Respiratory Syndrome (SARS) and emigration respectively. Both groups were comparable at baseline in all clinical and laboratory parameters. The mean daily symptom scores in 4-weekly began to diverge at the 29th-32nd week with the active group showing a significant lower scores (0.17 +/- 0.33) than the control group (0.39 +/- 0.74, Z = 2.031, P < 0.05) till the end of the study. Significant difference was found in average daily symptom scores between H(1) (0.29 +/- 0.39) and H(2) (0.19 +/- 0.27) in the active group (Z = 2.923, P < 0.01), while no significant difference was found between H(1) (0.45 +/- 0.62) and H(2) (0.40 +/- 0.68) in the placebo group (Z = 1.885, P > 0.05). There were significant differences in subjective judgement of the improvement about overall asthmatic symptoms, exacerbation severity and exacerbation frequency between the active group (96.9%, 95.3%, 95.4%) and the control group (80.0%, 75.4%, 83.1%) with the self-evaluation questionnaire (chi(2) = 13.246, 11.576, 16.204, all P < 0.01). The trend line of daily medication scores in weekly intervals showed a significant decline. The mean daily medication score of phase II (0.20 +/- 0.36) was significant lower than that of phase I (0.33 +/- 0.67, Z = 3.344, P < 0.01), whereas the control group did not show a significant difference between phase II (0.35 +/- 0.96) and phase I (0.32 +/- 0.95, Z = 0.744, P > 0.05). After 1-year treatment, no significant differences were found in morning and evening peak expiratory flow of predicted value (PEF%), forced expiratory volume in one second of predicted value (FEV(1)/FVC), forced vital capacity of predicted value (FVC%), forced expiratory volume in one second to forced vital capacity ratio (FEV(1)/FVC), provoking dose decreasing FEV(1) by 20% (PD(20)-FEV(1)) between the active group [(97 +/- 17)%, (98 +/- 18)%, (91 +/- 11)%, (98 +/- 9)%, (82 +/- 10)%, 2.35 (7.9) micromol] and the control group [(99 +/- 19)%, (100 +/- 19)%, (90 +/- 14)%, (99 +/- 13)%, (82 +/- 9)%, 1.80 (7.8) micromol] (t = 0.170 - 0.630, Z = 0.264, all P > 0.05). Skin index (SI) to Der p in the active group (1.2 +/- 0.5) was significantly lower than that of the control group (1.5 +/- 0.6) after treatment (t = 2.395, P < 0.05). There was no significant difference in the level of serum sIgE against Der p between groups, which was 76.80 (97.0) kU/L in active group and 66.50 (99.3) kU/L in the control group (Z = 0.232, P > 0.05). The frequency of systemic adverse reactions graded by guidelines based on the position paper of European Academy of Allergology and Clinical Immunology (EAACI), was 5.7% and 1.8% of the total injections in the active group and the control group, respectively. Although significant difference was found in adverse reactions between groups (chi(2) = 4.705, P < 0.05), all were mild or moderate. The majority occurred within 30 minute after injection and were controlled well with symptomatic therapy. No any severe systemic adverse reaction was shown in the study. CONCLUSION: One year specific immunotherapy with standardized house dust mite (HDM) vaccine significantly improved symptoms and reduced medication use in mild to moderate allergic asthmatic patients. SIT also reduced skin prick test reactivity to Der p. Complying with the EAACI immunotherapy guidelines, SIT with standardized HDM vaccine was a safe treatment.

Seafood allergy: lessons from clinical symptoms, immunological mechanisms and molecular biology.

Food allergy consists of a wide range of disorders that result from adverse immune responses to dietary antigens. Manifestations of allergic response includes acute, potentially fatal anaphylactic reactions and a variety of chronic diseases that mainly affect the gastrointestinal tract, skin, and respiratory tract. Tools for clinical diagnosis and management, which have not changed much in the past two decades, include the clinical history, tests for specific IgE antibody to suspected foods, elimination diets, oral food challenges, and provision of medications such as epinephrine for emergency treatment. On the other hand, recent immunological and molecular biological research have enhanced our understanding of the mechanisms of these disorders and revealed the identities of many food allergens. Here, we will discuss seafood allergies with respect to the clinical manifestations, diagnosis, immunological mechanisms, and molecular biology of seafood allergens. Furthermore, potential applications and future directions in the clinical management of seafood allergies are discussed.

Systemic autoimmune disease induced by dendritic cells that have captured necrotic but not apoptotic cells in susceptible mouse strains.

Systemic lupus erythematosus (SLE) is an autoimmune disorder of a largely unknown etiology. Anti-double-stranded (ds) DNA antibodies are a classic hallmark of the disease, although the mechanism underlying their induction remains unclear. We demonstrate here that, in both lupus-prone and normal mouse strains, strong anti-dsDNA antibody responses can be induced by dendritic cells (DC) that have ingested syngeneic necrotic (DC/nec), but not apoptotic (DC/apo), cells. Clinical manifestations of lupus were evident, however, only in susceptible mouse strains, which correlate with the ability of DC/nec to release IFN-gamma and to induce the pathogenic IgG2a anti-dsDNA antibodies. Injection of DC/nec not only accelerated disease progression in the MRL/MpJ-lpr/lpr lupus-prone mice but also induced a lupus-like disease in the MRL/MpJ-+/+ wild-type control strain. Immune complex deposition was readily detectable in the kidneys, and the mice developed proteinuria. Strikingly, female MRL/MpJ-+/+ mice that had received DC/nec, but not DC/apo, developed a 'butterfly' facial lesion resembling a cardinal feature of human SLE. Our study therefore demonstrates that DC/nec inducing a Th1 type of responses, which are otherwise tightly regulated in a normal immune system, may play a pivotal role in SLE pathogenesis.

House dust mite allergen (Derp1 and Blot5) levels in asthmatics' home in Hongkong.

OBJECTIVE: To measure Derp1 and Blot5 allergen levels in asthmatics' homes in Hongkong. METHODS: Seventy houses were enrolled for a mite indoor environment study. Dust samples were obtained from two sites of each patients' house: bed and floor. Derp1 and Blot5 levels were quantified by a two-site monoclonal antibody-based ELISA technique. RESULTS: The levels of Derp1 allergens found in bed (geometric mean (GM) 3.43 microg/g of dust; 95%CI, 1.89-4.96 microg/g) and on the floor (GM 1.12 microg/g of dust; 95%CI, 0.71-1.53 microg/g) indicated significant differences (P=0.005). However, the levels of Blot5 allergens found in bed (GM 19.00 microg/g of dust; 95%CI, 0.89-38.90 microg/g) and on the floor (GM 6.14 microg/g of dust; 95%CI, 0.40-11.90 microg/g) showed no statistically significant difference. In addition, in regards to the exposure index for Derp1 and Blot5 allergens found in bed and on the floor, 17.6% in bed and 8.6% on the floor had levels of Blot5 > or = 10 microg/g of dust, higher than those obtained for Derp1 (7.2% and 0% in bed and on the floor respectively, P<0.05); higher percentages in bed and on the floor (25.0% and 35.7%) were observed for levels of Blot5 = 0 microg/g of dust as compared with Derp1 in bed and on the floor (4.3% and 14.5% respectively, P<0.05). CONCLUSIONS: Derp1 and Blot5 are the major allergens found in this regional study, Blot5 is a more potent allergen in Hongkong, probably reflecting the high level of exposure to Blomia tropicalis (Bt). Bt and Dermatophagoides pteronyssinus (Dp) allergens should be included for precise diagnosis and effective immuno-therapeutic treatment of mite allergy in Hongkong.

Clinical characteristics and pattern of skin test reactivities in shellfish allergy patients in Hong Kong.

Allergens from crustaceans and mollusks exhibit extensive cross-reactivity in vitro. However, the degree and pattern of cross-reactivity between different shellfish species in vivo is still unclear. The objective of this study was to determine the clinical characteristics of shellfish allergic patients in Hong Kong and the pattern of skin test reactivities to the different species. This cohort study involves patients attending the allergy clinic of a large teaching hospital for suspected shellfish allergy. Each subject underwent skin-prick tests to eight species of shellfish and house-dust mites. Eighty-four consecutive patients were tested. Twenty-eight patients reported a history of severe anaphylaxis. Fourteen patients had no positive shellfish skin test and were excluded. There were 183 positive shellfish skin tests, with an average of 2.61 positive tests per subject. Ninety percent of subjects also had positive skin tests to house-dust mites. Overall, 65. 7% of subjects had more than one positive skin test to shellfish. There were strong statistical associations between species belonging to the same order but also between some mollusks and crustaceans. We found a high degree of skin test cross-reactivity between different species of shellfish and between shellfish and house-dust mites. Therefore, patients with a history of shellfish allergy should be cautious with all types of shellfish.

The use of proteomics in the discovery of serum biomarkers from patients with severe acute respiratory syndrome.

Severe acute respiratory syndrome (SARS) is a new infectious disease with a global impact. Understanding its pathogenesis and developing specific diagnostic methods for its early diagnosis are crucial for the effective management and control of this disease. By using proteomic technology, truncated forms of alpha(1)-antitrypsin (TF-alpha(1)-AT) were found to increase significantly and consistently in sera of SARS patients compared to control subjects. The result showed a sensitivity of 100% for SARS patients and a specificity of 92.8% for controls. Furthermore, the levels of these proteins significantly correlated with certain clinico-pathological parameters. The dramatic increase in TF-alpha(1)-AT may be the result of degradation of alpha(1)-AT. As alpha(1)-AT plays an important role in the protection of lung function, its degradation may be an important factor in the pathogenesis of SARS. These findings indicate that increased TF-alpha(1)-AT may be therapeutically relevant, and may also be a useful biological marker for the diagnosis of SARS.

Increased apoptotic neutrophils and macrophages and impaired macrophage phagocytic clearance of apoptotic neutrophils in systemic lupus erythematosus.

OBJECTIVE: To evaluate whether patients with systemic lupus erythematosus (SLE) have a higher rate of apoptosis in and secondary necrosis of polymorphonuclear neutrophils (PMNs) and macrophages compared with controls; to compare the rate of macrophage phagocytic clearance of apoptotic PMNs in patients with SLE and healthy controls; to evaluate whether in vitro PMN and macrophage apoptosis and secondary necrosis, and the ability of macrophages to phagocytose apoptotic bodies, are correlated with lupus disease activity; and to determine whether macrophage clearance of apoptotic bodies in patients with SLE and normal controls is related to certain serum factors. METHODS: Thirty-six patients with SLE and 18 healthy, nonsmoking volunteers were studied. PMNs and monocytes were isolated from fresh blood and cultured in the presence of different sources of serum. Apoptotic PMNs and macrophages were examined by annexin V binding and morphology on May-Giemsa-stained cytopreparations, at different time points. The presence of secondary necrotic PMNs and macrophages was verified by staining with trypan blue. Macrophage phagocytosis of apoptotic PMNs was measured using a coded, observer-blinded, microscopically quantified phagocytosis assay. Cells were cultured in the presence of serum obtained from healthy subjects or from patients with SLE. RESULTS: At 5 and 24 hours, the percentage of apoptotic PMNs from patients with SLE was significantly higher than that of PMNs from healthy subjects. At 24 and 48 hours, the percentage of secondary necrotic PMNs from patients with SLE was also significantly higher than the percentage of necrotic PMNs from controls. Serum from patients with SLE accelerated the rate of apoptosis in and secondary necrosis of PMNs from healthy subjects. Macrophages from SLE patients were less capable of phagocytosing apoptotic PMNs compared with macrophages obtained from controls. Macrophages from patients with active SLE were less capable of phagocytosing apoptotic PMNs than were macrophages from patients with inactive SLE, but the difference was not statistically significant. The percentage of phagocytosis of apoptotic PMNs by macrophages from SLE patients correlated negatively with the SLE Disease Activity Index, serum levels of anti-double-stranded DNA, and the erythrocyte sedimentation rate, and correlated positively with serum levels of C3, C4, and albumin, the hemoglobin level, and the leukocyte count. Serum from SLE patients not only significantly increased macrophage apoptosis in cells from healthy subjects but also remarkably down-regulated the clearance of apoptotic PMNs by macrophages from healthy subjects. In contrast, serum from healthy subjects significantly increased phagocytosis of apoptotic PMNs by macrophages from SLE patients. CONCLUSION: The observed increase of apoptotic PMNs and macrophages and the poor ability of macrophages from patients with SLE to phagocytose apoptotic bodies may indicate an impaired clearance mechanism, which may be mediated by factors in a patient's serum.

DNA immunization using a secreted cell wall antigen Mp1p is protective against Penicillium marneffei infection.

None of the vaccines used in dimorphic fungal infections utilized the mucosal route for immunization, whereas only one utilized a secreted protein as antigen, despite knowing that infections caused by dimorphic fungi are usually acquired through inhalation. In this study, we investigated the usefulness of Mp1p (a secreted cell wall antigen encoded by MP1)-based vaccines for generation of protective immune responses against Penicillium marneffei infection using a mouse model, and compared the relative effectiveness of intramuscular MP1 DNA vaccine, oral mucosal MP1 DNA vaccine delivered by live-attenuated Salmonella typhimurium, and intraperitoneal recombinant Mp1p protein vaccine. The serum IgM level of the Mp1p protein vaccine group at day 7 and the serum IgG levels of the Mp1p protein vaccine group at days 7 and 21 were significantly higher than those of the other groups (P<0.0001). The serum IgG level of the MP1 DNA vaccine group was significantly higher than that of the corresponding control group and oral mucosal MP1 DNA vaccine group (one dose) at day 21 (P<0.0001 and <0.05, respectively). The groups of mice immunized with intramuscular MP1 DNA vaccine, oral mucosal MP1 DNA vaccine, and intraperitoneal Mp1p protein vaccine showed significantly higher Mp1p-specific lymphocyte proliferation index (LPI) than the control groups. The interferon-gamma (IF-gamma) levels of supernatant of splenic cell cultures obtained from mice after intramuscular MP1 DNA vaccine, mucosal MP1 DNA vaccine (three doses), or intraperitoneal Mp1p protein vaccine administration were higher than that which occurred after mucosal MP1 DNA vaccine (one dose) administration or those of controls. Interleukin-4 (IL-4) was not detectable in the supernatant of splenic cell cultures obtained from all groups of mice. The percentage survival of the mice immunized with intramuscular MP1 DNA vaccine, oral mucosal MP1 DNA vaccine (three doses), oral mucosal MP1 DNA vaccine (one dose), intraperitoneal recombinant Mp1p protein, oral live-attenuated S. typhimurium control, and intramuscular pJW4303 DNA control at day 60 after wild type P. marneffei challenge were 100, 60, 40, 40, 40, and 0%, respectively. The survival of mice in the MP1 DNA vaccine group was significantly better than those of the oral mucosal MP1 DNA vaccine (three doses) group (P<0.05), oral mucosal MP1 DNA vaccine (one dose) group (P<0.005), recombinant Mp1p protein group (P<0.005), S. typhimurium aroA strain group (P<0.05), and pJW4303 group (P<0.00001). Although, the mechanism by which intramuscular MP1 DNA vaccine offered the best protection against P. marneffei infection remains to be elucidated, the present observation prompted further clinical trials on the use of MP1 DNA immunization on asymptomatic human immunodeficiency virus carriers in P. marneffei endemic areas.