Epidemiology, Management, and Treatment Access of Hereditary Angioedema in the Asia Pacific Region: Outcomes From an International Survey.

BACKGROUND: Hereditary angioedema (HAE) is a rare genetic disease with significant morbidity and mortality for which early diagnosis and effective therapy are critical. Many Asia Pacific (AP) countries still lack access to diagnostic tests and evidence-based therapies. Epidemiologic data from the AP is needed to formulate regional guidelines to improve standards of care for HAE. OBJECTIVE: To investigate the estimated minimal prevalence, needs, and potential interventions for the diagnosis and management of HAE in the AP. METHODS: A structured questionnaire was distributed to representative experts from member societies of the Asia Pacific Association of Allergy, Asthma and Clinical Immunology. Patient profiles and the presence of diagnostic facilities or tests, regional and national HAE guidelines, and patient support groups were reported and compared. RESULTS: Completed questionnaires were received from 14 representatives of 12 member countries and territories, representing 46% of the world population. Overall minimal prevalence of HAE in the AP region was 0.02/100,000 population, with significant heterogeneity across different centers. Only one-half and one-third had registered on-demand and prophylactic medications, respectively. Few had patient support groups (58%) or regional guidelines (33%), and their existence was associated with the availability of HAE-specific medications. Availability of C1-inhibitor level testing was associated with a lower age at HAE diagnosis (P = .017). CONCLUSIONS: Hereditary angioedema in the AP differs from that in Western countries. Hereditary angioedema-specific medications were registered in only a minority of countries and territories, but those with patient support groups or regional guidelines were more likely to have better access. Asia Pacific-specific consensus and guidelines are lacking and urgently needed.

Guidelines for the management of asthma in adults: Evidence and recommendations.

The multidisciplinary experts in Thailand developed an asthma management recommendation that was relevant to low-middle income countries (LMICS). Populations level consideration about asthma management is emphasized. The healthcare systems, access to and availability of treatments as well as the asthma populations vary from country to country in LMICS. The feasibility in clinical practice for implementation is also a major issue. For these reasons, the practice guidelines that are relevant to local contexts are essential to improve better asthma control. Furthermore, integrative and collaboration between asthma experts and the public health sector to implement and discriminate such guidelines will help to achieve these challenging goals. The topics covered include the current asthma situation in Thailand and the Asia-Pacific region, the definition of asthma, asthma diagnosis, assessment of asthma patients, asthma treatment - both pharmacological and non-pharmacological, management of asthma exacerbation, management of asthma comorbidities, treatment of asthma in special conditions, severe and uncontrolled asthma, Thai alternative medicine and asthma, and asthma and coronavirus disease-19 (COVID-19).

Clinical practice guidelines for the diagnosis and management of atopic dermatitis.

Atopic dermatitis (AD), a chronic, relapsing dermatitis, is characterized by dry and pruritus skin in patients with a personal or family history of atopy. It affects up to 20% of children and 1-3% of adults in most countries worldwide, and leads to significant treatment costs and morbidity. These guidelines are developed in accordance with evidence-based publications and expert opinions. Following simple algorithms, the guidelines aim to assist adult and pediatric physicians in the better care of patients with AD. As with other diseases, there have been several diagnosis criteria proposed over time. Nonetheless, the classical Hanifin and Rajka criterion with no pathognomonic laboratory biomarkers is still the most widely used worldwide for the diagnosis of AD. The management of AD must be considered case by case to provide suitable care for each patient. Basic therapy is focused on avoiding specific/unspecific provoking factors and hydrating skin. Topical anti-inflammatory treatments such as glucocorticoids and calcineurin inhibitors are suggested for disease flare, and proactive therapy is best for long-term control. Other therapies, including antimicrobial agents, systemic antihistamines, systemic anti-inflammatory agents, immunotherapy, phototherapy, and psychotherapy, are reviewed in these guidelines. Crisaborole, a new topical phosphodiesterase 4 inhibitor, can be used twice daily in AD patients over three months old. Dupilumab, a biological drug for patients with moderate-to-severe AD, may be considered in patients with no improvement from other systemic treatments.

Clinical Characteristics, Urinary Leukotriene E4 Levels, and Aspirin Desensitization Results in Patients With NSAID-Induced Blended Reactions.

PURPOSE: Data on non-steroidal anti-inflammatory drug (NSAID) hypersensitivity in Southeast Asia are scarce. Increased urinary leukotriene E4 (uLTE4) levels have been suggested as a biomarker of NSAID-exacerbated respiratory disease (NERD). This study investigated clinical patterns of NSAID sensitivity in Thailand and the diagnostic roles of uLTE4 measurement in various phenotypes. METHODS: The clinical phenotypes in 92 Thai adults with cross-reactive NSAID hypersensitivity were characterized based on the clinical history and drug provocation. The uLTE4 levels were measured at baseline, after aspirin provocation and after desensitization. RESULTS: More than half of the patients (56.5%) presented with cutaneous symptoms (NSAID-exacerbated cutaneous disease), while one-third (33.7%) developed symptoms in at least 2 systems (NSAID-induced blended reactions; NIBR). Fifty-two patients underwent drug provocation and 59.6% of them yielded positive results. After drug provocation, a significant number of patients with confirmed NSAID cross-reactivity experienced clinical symptoms in more than one organ system. The uLTE4 levels at baseline were comparable between the NSAID-tolerant and NSAID-sensitive groups, but were substantially increased after aspirin provocation predominantly in NERD (983.4 pg/mg creatinine) and NIBR (501.0 pg/mg creatinine) compared to NSAID-tolerant subjects (122.1 pg/mg creatinine, P < 0.01 and 0.05, respectively). The uLTE4 levels were elevated after aspirin desensitization, although nasal polyposis and asthma were under control in 3 NERD and 3 NIBR subjects. CONCLUSIONS: NIBR is not uncommon among NSAID-sensitive patients in Thailand. The diagnostic value of basal uLTE4 levels was limited, but increased uLTE4 levels upon aspirin provocation suggest NSAID cross-reactivity with respiratory components. This study indicates that aspirin desensitization, if necessary, might be effective in both NERD and NIBR. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03849625.

Long-term effectiveness of omalizumab treatment in Thai severe asthmatic patients: A real-life experience.

BACKGROUND: To evaluate long-term effectiveness of omalizumab in 'real-life' setting of Thai asthmatic patients. METHODS: We conducted multi-center, observational study in severe asthma patients who received omalizumab in Thailand. Outcomes were asthma exacerbation (hospitalization and ER visit), asthma control test (ACT), and daily ICS dose. Data were evaluated at baseline, 16 Week, and 52 Week. RESULTS: A total of 78 patients received omalizumab treatment (average duration 16.9 months with range 16 weeks-2 years). The mean annualized rate of exacerbations was reduced from baseline (3.79) at Week 16 (3.54) and Week 52 (1.16), (p<0.05), respectively. The mean hospitalization rate was reduced from 0.49 in previous year to 0.15 at Week 16 and 0.19 at Week 52. A reduction in ER visit rates was observed at Week 16 (0.15) and Week 52 (0.97) respectively from baseline (1.44) (p<0.05). The ACT score increased from 15.4 at baseline to 20.6 at Week 16 (p<0.001) and increased to 21.5 at Week 52 (p<0.001). The number of patients with controlled asthma (ACT≥20) increased from 16 of 51 at baseline to 32 of 45 at Week 16 and 25 of 32 at week 52, respectively. The median daily dose of ICS equivalent to fluticasone was reduced from baseline 680 mcg to 500 mcg at Week 52. In all, 22 patients discontinued omalizumab after 1 year. Six patients who discontinued omalizumab were restarted due to relapse of symptoms. CONCLUSIONS: These data confirms the effectiveness of one-year duration of omalizumab treatment in Thai severe asthmatic patients. Furthermore, 27% of patients who discontinued treatment required restarting due to relapse of symptoms.

Extranasal symptoms of allergic rhinitis are difficult to treat and affect quality of life.

BACKGROUND: Total nasal symptom score is widely used to evaluate the severity of allergic rhinitis, but the clinical significance of extranasal symptoms is largely unknown. We wished to analyze the presenting symptoms in allergic rhinitis, as well as their relationship with quality of life (QoL) and therapeutic outcomes. METHODS: Presenting symptoms and QoL were assessed using the Optum™ SF-12v2(®) Health Survey in 260 patients with allergic rhinitis. Clinical response at 3 months after treatment was measured. RESULTS: Ten most common symptoms presenting with at least moderate severity in allergic rhinitis were: blocked nose (82.7%), rhinorrhea (75.0%), sneeze (70.9%), itchy nose (68.5%), fatigue (63.6%), mouth breathing (61.1%), daytime somnolence (52.7%), postnasal drip (49.1%), itchy eyes (47.3%), and dry mouth (46.3%). Severity of sneeze was correlated with physical component summary (PCS) whereas postnasal drip and daytime somnolence were correlated with mental component summary (MCS). Severity of dry mouth was correlated with PCS and MCS. The symptoms with the highest severity scores after treatment were blocked nose, postnasal drip, fatigue, and dry mouth, respectively. CONCLUSIONS: Extranasal symptom scores correlated well with physical health and mental health in allergic rhinitis patients. Assessment of extranasal symptoms should be included to evaluate disease severity and assess therapeutic outcomes. Clinical trial NCT02000648, http://www.clinicaltrials.gov.

Fixed-Dose combination of the inhaled corticosteroid and long-acting beta2-agonist therapy in adults with persistent asthma.

INTRODUCTION: Asthma is a respiratory condition characterized by airway inflammation, airflow obstruction, and bronchial hyperresponsiveness. The standard treatment of asthma comprises inhaled corticosteroid and beta2-agonist. Inhaled short-acting-beta2-agonists have been used as rescue medication for exacerbation. However, long-acting-beta2-agonists (LABA) used as monotherapy for asthma had been reported for having a safety concern. Consequently, it had been recommended as an add-on treatment to inhaled corticosteroid (ICS) in moderate to severe persistent asthma. The fixed-dose combination (FDC) of ICS and LABA has been approved since the year 2000. Evidences revealed using the combination of these medications is more effective in asthma control. AREAS COVERED: The rational and phase III onward randomized-controlled studies were reviewed. Sources of evidences were from studies published in Medline until November 2015. EXPERT OPINION: There are six FDC inhaler regimens approved worldwide. The significant synergistic effects of ICS and LABA in one device are well evidenced. A FDC reduces the daily dosage of ICS and asthma exacerbation. It is safe to use regularly as controller. The efficacy of each individual combination on asthma treatment is generally similar. Clinical experience, ease of use, cost and side effects of medication would guide the clinician's preferences.

Clinical characteristics and treatment outcome of Stevens-Johnson syndrome and toxic epidermal necrolysis.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are erythematous skin lesions with blister formation accompanied by mucosal involvement. These conditions are considered to be life-threatening illnesses. Understanding the clinical presentation, risk factors, treatment options and results will be advantageous for physicians in the management of patients in the future. The aim of the present study was to review and analyze the clinical manifestations, drug implications, treatment and outcome of patients with SJS and/or TEN who had been hospitalized in a tertiary care center. All hospitalized patients with SJS and/or TEN during a 5-year period were retrospectively reviewed. The clinical severity was graded according to the score of toxic epidermal necrolysis (SCORTEN) scale. Clinical symptoms, diagnosis, possible precipitating factors, management and outcome data were collected for analysis. A total of 43 patients (mean age, 49.5 years) were hospitalized and classified into the SJS group (55.8%), SJS/TEN overlap group (20.9%) and TEN group (23.3%). The majority of the patients (90.7%) had mucocutaneous eruptions associated with oral drug administration. Allopurinol, anticonvulsants and antibiotics were the most common causative agents for the mucocutaneous eruption. Twenty-eight patients (65.1%) were treated with corticosteroids. The mortality rate was 6.9%. Comparison between the survival group and the non-survival group revealed that patient age >70 years (P=0.014) and body surface area involvement >20% (P<0.01) were the significant factors associated with mortality. The use of systemic steroids was higher in the survival group in comparison with the non-survival group (65.1 vs. 0%, respectively; P=0.014). The mucocutaneous eruptions in SJS and TEN are mostly caused by medication. With early recognition and treatment, the mortality rate in this study was lower than that in previous reports. Patient age and the area of mucocutaneous involvement were significant factors associated with mortality.

Jackfruit anaphylaxis in a latex allergic patient.

Several fruits have been reported to crossreact with latex antigen in latex allergy patients but little is known regarding tropical fruits in particular. Here we report the case of a 34-year old nurse who developed anaphylaxis following the ingestion of dried jackfruit (Artocarpus heterophyllus). The patient had a history of chronic eczema on both hands resulting from a regular wear of latex gloves. She and her family also had a history of atopy (allergic rhinitis and/or atopic dermatitis). The results of skin prick tests were positive for jackfruit, latex glove, kiwi and papaya, but the test was negative for banana. While we are reporting the first case of jackfruit anaphylaxis, further research needs to be conducted to identify the mechanisms underlying it. In particular, in-vitro studies need to be designed to understand if the anaphylaxis we describe is due to a cross reactivity between latex and jackfruit or a coincidence of allergy to these 2 antigens.

Reactivity of allergy skin test in healthy volunteers.

INTRODUCTION: Healthy individuals may be exposed and sensitised to allergens, and have a positive response to a skin prick test despite being asymptomatic. The objectives of this study were to evaluate the prevalence of atopic sensitisation and identify the reactivity of healthy volunteers to common aeroallergens. METHODS: Healthy volunteers with no known allergic symptoms were recruited in this study. All volunteers were scheduled to undergo a skin prick test with 16 common aeroallergens that were previously identified among atopic patients. RESULTS: A total of 100 volunteers (mean age 28 years) were enrolled in this study. 42 volunteers had positive skin prick tests for at least one allergen. The median number of sensitised allergen was 2 (range 1-7). Volunteers with positive skin tests (n = 42) were younger than those with negative skin tests (n = 58) (mean age 25.5 vs. 29.2 years; p < 0.05). The group with positive skin tests also had a higher proportion of males (57.1% vs. 31.0%; p < 0.01) and first-degree relatives with a history of atopic diseases (31.0% vs. 10.3%; p < 0.05). The most common sensitised allergens in these healthy asymptomatic volunteers were mite (n = 33), house dust (n = 23) and American cockroach (n = 20). CONCLUSION: In this study, up to 42% of healthy volunteers, particularly those with a family history of atopy, were sensitised to allergens. Reactivity of the skin test without allergic symptoms, however, does not indicate allergic disease. Therefore, the skin test should only be indicated in atopic symptomatic individuals.

Inpatient asthma mortality in a tertiary referral hospital from 2000 to 2010.

OBJECTIVE: Asthma is a common respiratory disease, the prevalence of which varies according to multiple demographic and economic factors. The availability of therapy and implimentation of treatment guidelines has made the asthma mortality rate stable or gradually in decline. This study was conducted to evaluate the mortality trend of asthmatic patients who died during hospitalization in a tertiary care center. METHODS: A retrospective study of hospitalized asthmatic patients was conducted by reviewing medical records selected on the basis of primary or secondary diagnosis of asthma, between January 2000 and December 2010. The record review focused on the patients admitted to the institution who died with the principal diagnosis of asthma or having asthma as a co-morbidity. RESULTS: Between January 2000 and December 2010, a total of 540,365 patients were hospitalized. Of these, 553 patients were admitted with their primary or the co-principal diagnosis of asthma. In the asthma group that were admitted, 3 male and 9 female patients died during this period, or 2.17% of asthma admissions. Eight patients died in the first five years of the study, compared to 4 in the second half. CONCLUSION: The mortality rate of asthma in hospitalized patients has been declining in the last ten years. This finding has shown the importance of long-term medication used to provide good disease control and the use of asthma treatment guidelines which may lead to the overall decreases in mortality rate.

Alkali-treated penicillin G solution is a better option than penicillin G as an alternative source of minor determinants for penicillin skin test.

Both benzylpenicilloyl-polylysine (PPL) and minor determinant mixture (MDM) are the recommended standard reagents for penicillin skin testing. However, penicillin G is commonly suggested as an alternative source of minor determinants. This study evaluated the accuracy of penicillin G and alkali-treated penicillin G compared with the standardized MDM for skin testing. Sixty-eight patients with histories of allergies to penicillin or semisynthetic penicillins were skin tested with commercial Kit penicillin allergenic determinants (DAP) (PPL and DAP-MDM; Diater Laboratorios, Madrid, Spain). The in-house MDM (IH-MDM), prepared by alkali-treated aged penicillin, and fresh penicillin G sodium (PGs) were tested alongside DAP-MDM. Positive penicillin skin test results were identified in 22 patients (32.4%) using commercial reagents (PPL+ DAP-MDM) and 19 of them reacted to DAP-MDM alone or together with PPL. The accuracy of IH-MDM and PGs compared with DAP-MDM was 89.7 and 76.5%, respectively. Our study shows that alkali-treated penicillin G is a better option than penicillin G as an alternative source of MDM for skin testing in case the commercialized MDM is not available. Minor determinants play a significant role for penicillin allergy in Thailand and should be included in the penicillin skin test panel to verify suspected cases of penicillin allergy. (ClinicalTrials.gov number: NCT00789217).

No effect of interleukin-2 on IgE levels given in addition to antiretroviral therapy in HIV-infected adults with CD4 >300 cells/mm3.

HIV-infected patients may have frequent atopy caused by an imbalance of Th1 and Th2 cytokines. The objective of the present study was to investigate whether IL-2 given in addition to antiretrovirals (ARV) would result in lower IgE levels and less allergic symptoms. Patients naive to IL-2 (n=28) began IL-2 plus ARV and were followed for 12 months. IgE, eosinophil and CD4 counts, HIV RNA, symptom scoring, PFT and skin prick test (SPT) were performed. It was found that the baseline median CD4 and IgE were 386.5 cells/mm3 and 63.5 IU/ml, respectively. Four patients had allergic rhinitis (AR) and 61% had a positive SPT to at least 1 antigen. At month 12, patients had higher CD4 counts (p < 0.001) compared to the baseline; however, there were no differences in IgE levels, allergic symptom scores or HIV RNA. The eosinophil count was higher after IL-2 administration. It was concluded that IL-2 plus ARV resulted in higher CD4 counts but had no effect on atopy.

Investigation and treatment of asthma.

Asthma is one of the most common chronic respiratory diseases presenting with a variety of symptoms from cough, chest tightness, wheeze, difficulty breathing and in many cases persistent dyspnea. The individual has been effected usually spends a significant amount of time and financial resources in order to control the symptoms. Even though asthma has been known for more than several decades, the medications for the condition are relatively limited. This article has reviewed currently available guidelines, classifications, investigations for the diagnosis and treatment recommendations of asthma for both the general practitioners and the specialists who mainly taking care of patients with this chronic airway condition.