Epidemiology and current status of allergic rhinitis and asthma in Thailand- ARIA Asia-Pacific Workshop Report.

The allergic diseases of the airway, i.e. allergic rhinitis and asthma, are on the increase in Thailand and their prevalence shows no signs of abating. When compared with a previous study, the incidence of wheezing had increased 4 fold (from 4.2% to 18.3%), and allergic rhinitis increased nearly 3 fold (from 17.9% to 44.2%). The results of the ISAAC phase III study revealed that the frequency of allergic diseases of the respiratory tract in-creased significantly from the ISAAC phase I survey performed in 1995; i.e. asthma increased from 12.2% to 14.5%, and allergic rhinitis from 37.9% to 50.6%. Allergic rhinitis exerts a major impact on the quality of life of Thai patients. The results of skin prick testing have indicated the leading causes of indoor (house-dust mites, house dust, cock-roaches, dogs and cats) and outdoor pollen (Bermuda grass, para grass, sedge, careless weed) allergens. Molds (represented by Cladosporium), although prominent in an aeroallergen survey, returned a low percentage of posi-tive skin prick reactions, and therefore, were considered low in allergenicity. In Thailand, there are clinical practice guidelines for both allergic rhinitis and asthma which are comparable to the international guidelines like ARIA and GINA. Sufficient kinds of pharmacotherapy are on the National List of Es-sential Drugs. Yet due to the limited number of trained allergists, many patients are seen by general physicians, and often, the appropriate diagnostic tests and treatments are not provided. In addition, the financial burden for quality health care may be prohibitive for those without private health insurance in spite of the implementation of a universal health care system for all Thai citizens, which is less than optimal.

A case of IgG subclass deficiency with the initial presentation of transient hypogammaimmuno-globulinemia of infancy and a review of IgG subclass deficiencies.

Primary immunodeficiency diseases are not common in children. The possibility of an immunological defect should be considered in any individual with repeated infections. A definite diagnosis for immodeficiency is sometimes difficult to achieve because of overlapping clinical manifestations. Immunoglobulin subclass deficiency is an immunological deficiency disease with which, one or more IgG subclasses are deficient. T cell immunity is normal. Patients may develop recurrent bacterial and respiratory infections or could remain asymptomatic. OBJECTIVE: The authors report a case of immunoglobulin G subclass deficiency presenting initially as transient hypogammaglobulinemia of infancy. CASE REPORT: A 2 month-old boy presented to Siriraj Hospital with a history of chronic protracted diarrhea, disseminated scabies and sepsis. On presentation, he had generalized scaly and maculopapular rash with no palpable lymph nodes. CBC revealed WBC 22,100 cells/cm3 with PMN 42 per cent, lymphocytes 38 per cent, Eosinophils 4 per cent, Basophil 2 per cent and platelets 254,000/cm3. The immunoglobulin levels were as follows: IgG 181 mg/dl, IgA < 6.6 mg/dl, IgM 26.3 mg/dl. Lymphocyte enumerations revealed CD4 of 2,433 cells/cm3 (N 1,460-5,160); CD8 4,682 cells/cm3 (N 650-2,450); CD19 1,588 cell/cm3 (N 500-1,500); CD16 230 cell/cm3 (N 573 +/- 264). The initial diagnosis was X-linked agammaglobulinemia vs common variable immunodeficiency disease. His diarrhea and five courses of sepsis responded well to antibiotics administration and courses of intravenous immunoglobulin (IVIG) replacement. His through IgG became normal at 2 years of age (after 12 months of IVIG). IVIG was stopped and the diagnosis was changed to transient hypogammaglobulinemia of infancy (THI). Nevertheless, during his 4 month follow-up he developed recurrent sinopulmonary infections (i.e, otitis media and pneumonia). Repeated immunoglobulin profile showed IgG 1,200 mg/dl, IgA 135 mg/dl, IgM 26 mg/dl, IgG subclass were IgG, 1,030 mg/dl (N 280-830), IgG2 30 mg/dl (N 40-2,400), IgG3 22 mg/dl (N 6-130), IgG4 3 mg/dl (N 3-120). A diagnosis of IgG2 subclass deficiency presenting early as transient hypogammaglobulinemia of infancy was then made. Treatment with monthly IVIG was reinitiated and the patient is currently doing well. CONCLUSION: The authors present a case of IgG subclass deficiency presenting as transient hypogammaglbulinemia of infancy. Follow-up of the immune profile and clinical manifestation is necessary for a definite diagnosis.

Allergic conjunctivitis.

The purpose of this research is to study the clinical features and risk factors of various types of allergic conjunctivitis. Four hundred and forty-five patients with a history of itching, foreign body sensation, lacrimation and red eyes were examined, and a skin test was performed and assessed to grade the severity. The mean age of the subjects was 24.5 +/- 16.3 years with female preponderance, except for vernal keratoconjunctivitis. The majority of the patients had perennial allergic conjunctivitis. Ninety-five percent of the patients had associated allergic diseases, especially allergic rhinitis. Sixty-six percent of the patients had a family history of atopy. Most patients had symptoms at night. Symptoms persisted throughout the year and were generally triggered by exposure to house dust. The allergy skin tests to common aero-allergens were positive in 95% of patients tested. Common allergens causing sensitization were house-dust mites, house dust, cockroaches, and grass pollen. Environmental control and avoidance of these allergens should be stressed in the management of these conditions.

X-linked hyper IgM syndrome: a report of the first case in Thailand with a confirmed mutation of CD40 ligand gene.

X-linked hyper IgM (XHIM) syndrome is a rare congenital immunodeficiency disease caused by failure of B cell to isotype switch from IgM to other classes of immunoglobulins in response to infections. Recently, a molecular cloning of the gene responsible for the syndrome, the CD40L gene has been accomplished and the gene was successfully mapped to the long arm of X chromosome at the position Xq26. We, herein, report the first case of molecular proven XHIM in a Thai boy with a classic presentation and with a confirmed mutation of the CD40L gene. Case Report: A.S. was a 1 year 7 month old boy referred from Buriram Provincial Hospital for a work up and treatment for his recurrent infections consisted of chronic respiratory tract infections with otitis media (since 6 months of age), chronic diarrhea (since 9 months of age) and malnutrition (marasmus) secondary to his longstanding illnesses. He was a product of a consanguineous marriage but without history of similar illness observed in his pedigree. Abnormal laboratory works up included IgG of 300 mg/dl, IgA 10 mg/dl, IgM 1,635 mg/dl, positive stool examinations for Cryptosporidium, chronic colitis on radiographic gastrointestinal follow through study, a positive acid fast bacillus (AFB) stain of gastric aspirate and multiple positive bacterial cultures from various body sources. His anti-HIV serology was negative. His hospital course was significant for several bouts of infections of gastrointestinal, respiratory, and genitourinary systems. His treatment consisted of multiple courses of antibiotics, antituberculous drugs and IVIG administrations. His hospital course was complicated with feeding problem from an esophageal stricture requiring several esophageal dilatations. The analysis of CD40L gene revealed a point mutation of exon 5 (A619T) of the CD40L gene resulting in a stop codon confirming that indeed he had XHIM. He died with Pseudomonas septicemia during the waiting period for a bone marrow transplantation from a cord-blood stem cell.

Prevalence of asthma, rhinitis and eczema in children from the Bangkok area using the ISAAC (International Study for Asthma and Allergy in Children) questionnaires.

Within the past three decades, there has been a rising trend for prevalences of asthma and allergic diseases worldwide, particularly from developed and industrializing countries. In Thailand, limited studies on epidemiology of atopic diseases have indicated relatively low prevalences of these conditions among the Thais. Recently, a standardized phase I questionnaire of the International Study of Asthma and Allergies in Childhood (ISAAC) has been developed to study and to compare geographical and temporal trend for prevalences of asthma, allergic rhinitis and eczema in children. The objectives of phase I ISAAC study in Thailand are to study prevalence of the three most common allergic diseases i.e. asthma, allergic rhinitis and eczema among Thai children of the two age groups (i.e., 6-7 and 13-14 years) living in the Bangkok metropolitan area and to collect basic epidemiologic data of these diseases among these children. The Thai translated version of phase I ISAAC questionnaires was administered to Thai children of the two age groups as above. Questionnaires were answered by parents of younger children, whereas, they were self-administered by 13-14 years old children. In addition, the validated international video questionnaires were used with older children. Fourteen primary schools and 13 secondary schools were randomly selected to cover the entire Bangkok metropolitan area. A total of 7341 questionnaires were eligible for the analysis (3628 from the younger age group and 3713 from the older age group). Data were entered and analysed by the Epi-Info program. The cumulative and 12 month period prevalences of the three conditions for all children were as follows; wheezing, 18.3 per cent, 12.7 per cent; rhinitis, 44.2 per cent, 38.7 per cent; and eczema, 15.4 per cent, 14.0 per cent, respectively. The period prevalence of wheezing for older children (13.6%) was higher than for younger children (11.7%). Prevalences of severe wheeze and exercise wheeze were more common among older children (4.0% and 15.7%). Both age groups reported high percentages for night cough (23.6% and 28.6%). A significantly large number of children from both groups reported symptoms of rhinitis with the majority indicating that symptoms were severe enough to limit their daily activities. Nevertheless, when confined only to those with eye symptoms, the prevalence decreased to 13.1 per cent. Eczema, in contrast to the other two conditions, occurred more frequently among younger children than among older children (period prevalence of 16% vs 9.1%). The rash was of a relatively mild nature since 77 per cent of children reporting symptoms indicated that the rash had cleared within the past 12 months. Allergic conditions are very common among children residing in Bangkok. Compared to the last survey in 1990, the period prevalence of wheezing has increased 4 fold, allergic rhinitis has increased nearly 3 fold whereas, eczema has remained stable. A large number of children in Bangkok are suffering from rhinitis symptoms. Results of this phase I ISAAC study indicate that allergic diseases are perhaps the most common childhood diseases in Thailand and could lead to a substantial economical loss for the country. There is an urgent need for an in-depth study to define epidemiological factors responsible for this increase.

Allergen skin test reactivities among asthmatic Thai children.

Skin prick tests with 14 selected local aeroallergens were performed on 100 asthmatic children aged 0-16 years attending the Pediatric Allergy Clinic, Faculty of Medicine, Siriraj Hospital. The 14 allergens included Dermatophagoides farinae, Dermatophagoides pteronyssinus, American cockroach (Periplaneta americana), Johnson grass (Sorghum halopense), Cladosporium clarosporoides, Alternaria tenuis, Penicillium mix, Aspergillus mix, cat dander, dog dander, milk, egg white, soy and shrimp. Positive skin test reactivity was defined as a mean wheal diameter > or = 3 mm at the 20 minute reading. There were 68 males and 32 females. Their ages were between 0-2 years (n = 1), 2-5 years (n = 19), 5-10 years (n = 49) and 10-16 years (n = 31). Of all the subjects, 22 were classified as having mild asthma, 74 with moderate asthma and 4 with severe asthma. At least one skin prick test was positive in 74 subjects (74%) and two positive tests in 66 subjects (66%). The prevalence of sensitization to various allergens was as follows; Dermatophagoides pteronyssinus 67%, Dermatophagoides farinae 62%, American cockroach 44%, shrimp 14%, Johnson grass 14%, cat dander 10%, Alternaria 7%, Cladosporium 7%, dog dander 5%, soy 4%, Penicillium 3%, Aspergillus 2%, milk 2% and egg white 1%. The wheal size to Dermatophagoides pteronyssinus did not correlate with age. In this group of asthmatic Thai children, house dust mites are the most important allergen causing sensitization.

Cold urticaria in Thai children: comparison between cyproheptadine and ketotifen in the treatment.

The study was performed in 6 Thai children with primary acquired cold urticaria. They all suffered from generalized urticaria and two of them also had angioedema. All of them had normal erythrocyte sedimentation rate, complement 3 and negative VDRL, TPHA, hepatitis B screen and cold agglutinin titer. Cryoglobulin was checked in 3 cases and showed negative results A double-blind cross-over study to compare the effectiveness of cyproheptadine and ketotifen demonstrated that the efficacy of cyproheptadine and ketotifen on clinical symptoms and ice cube test was not significantly different (p > 0.05). Both of them showed good results in the treatment of cold urticaria with mild side effects. During the follow up, 5 cases showed complete recovery while the other one developed one or two exacerbations per year upon cold exposure. However, the symptoms were mild and subsided on administration of one or two doses of H1 antihistamine. Our data demonstrated that ketotifen was as effective as cyproheptadine in the treatment of cold urticaria in Thai children.

Theophylline pharmacokinetics in Thai children.

To validate a previously suggested dosing regimen of aminophylline administration for Thai children, we enrolled 13 asthmatic Thai children (5 girls and 8 boys) between the ages of 7.5-13.4 years (mean = 10.4 years) into a 36-hour, multiple-dose, oral theophylline pharmacokinetic study using plain aminophylline tablets at a dosage of 5 mg of theophylline base/kg every 8 hours. All patients were studied in the steady state. Blood samples were obtained every 2 hours for 24 hours; thereafter, samples were obtained more frequently for another 12 hours to determine theophylline pharmacokinetic parameters. Serum theophylline concentrations (STC) were assayed with a fluorescence polarization immunoassay method (TDX). Significant interpatient variations in STCs were observed. Five patients had peak STCs in the toxic range (> 20 micrograms/ml). Most patients had reproducible STC patterns during the study period; however, marked variations of STCs were observed with a mean percent of fluctuations [(Cmax-Cmin)/Cmin *100] of 535.6%. Using the PC Nonlin computer interpolation program by a modification with a baseline decay method and the Lagrange polynominal interpolation technique, approximate pharmacokinetic parameters were calculated and the results were as follows: plasma half life (t1/2) = 3.08 hours, elimination rate constant (Kel) = 0.26 hour-1, absorption rate constant (Ka) = 2.21 hour-1, volume of distribution (Vd) = 0.23 l/kg and plasma clearance (CI) = 56 ml/kg/hour. Since these calculated parameters could be imprecise due to delayed absorption of oral theophylline dosages, a single-dose intravenous theophylline pharmacokinetic study was further examined in another 18 patients (age range = 7-12 years, mean = 8.9 years) to determine more accurate pharmacokinetic data using intravenous aminophylline at dosage of 5.8 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Measurements of the ear pinna in Thais: The first report.

The contour of the normal ear pine was studied in 434 Thai people i.e. 686 ears. The subjects were 219 males and 215 females who had never had sever injury or ear surgery. There age group’s were studied years, 3-5 years and 18-20 years. Four measurements were done i.e. ear width and ear length using a sliding caliper and auriculo-cephalic angle and concho-scaphalic angle using a goneometer. The results of the study revealed that the average ear width in Thais of different age groups differed little : was not much different (2.9 + 0.3 cm. At aged 0 - 2 years, 3.3 + 0.4 cm. At age 18-20 years in males and 2.8 + 0.3 cm. To 3.0 + 0.2 cm. in females. However the average ear height increased significantly with age (4.8 + 0.6 cm. At 0-2 years, 6.2 + 0.2 cm. At 18 -20 years in males and 4.7 + 0.5 cm, 6.1 + 0.2 cm. In females). The average auriculo-cephalic angle increased rapid during the early period. The increment of this angle exceeded 85 per cent of adult size at the age of 3 - 5 years (22.3 + 3.8 degrees, at aged 0 - 2 years, 28.0 + 2.5 degrees at aged 3-5 years, 28.4 + 3.1 degrees at aged 18 - 20 years in males and 21.8 + 3.6 degrees, 27.1 + 2.6 degrees and 28.2 + 1.6 degrees respectively in females). In contrast, the concho-scaphalic angle increased gradually with age (79.0 + 4.9 degrees at age 0 -2 years, 82.1 + 4.1 degrees at aged 18.20 years in males, and 79.4 + 4.6 degrees, 82.2 + 4.2 degrees in females). Statistical analysis of all the measurements of the ear pinna showed that the ear width in man at age 18 -20 years is wider than in women (3.3 + 0.4 cm. Versus 3.0 + 0.2 cm.), the ear height was significantly different (between the sexes) from aged 9 -11 years onward (5.9 + 0.4 cm. Versus 5.6 + 0.4 cm.) but there were no significant differences in either the suriculo-cephalic or the concho-scaphalic angles between males and females. Thai ear measurements when comparined with ear measurements in Caucasians were significantly smaller. This may be attributed to the different body structure of the different races. However, the percentage ratio of ear width to ear height was similar i.e. 50.60 per cent in both populations. The auriculo-cephalic angles in Thais were in the same range as western people.

Ease of handling and efficacy of Bricanyl Turbuhaler in Asian asthmatic children.

Ease of handling as well as efficacy of a new terbutaline inhalation device--Bricanyl Turbuhaler--were evaluated among eighty-six Asian children with mild to moderate asthma with a mean age of 8.7 years (range 5 to 14 years) in an open, non-comparative trial. Clinical evaluations were performed on four occasions, ie at the beginning of the run-in period, at the start of the study medication, after 2 weeks of treatment and after a total of 4 weeks of treatment. Appraisal of handling technique was performed by the investigator at the start and end of treatment. Peak expiratory flow rate (PEF) was determined at each visit. Diaries were also kept throughout this time; PEF and asthma symptom scores were recorded every morning and evening. Maximum scores for inhalation technique were achieved by 73% of patients after combined written and verbal instructions at the start of the study and 99% of patients achieved this score at the end of the 4 week treatment period with Bricanyl Turbuhaler. Assessment revealed that approximately 90% of the patients considered loading, inhalation and handling of the Turbuhaler device to be easy, and 90% considered it to be effective in affording symptom relief. Improvements in PEF and reductions in asthma symptoms were observed during the Bricanyl Turbuhaler treatment, as compared to baseline values. All patients tolerated the study medication well without any serious adverse events. We concluded that this group of Asian children were able to use this new "Turbuhaler" device of terbutaline without any difficulty.(ABSTRACT TRUNCATED AT 250 WORDS)

Nebulized salbutamol (Asmasal) in Thai children with asthma: comparison of three doses.

Eleven moderate-to-severe asthmatic children 5-11 years of age who were in stable condition were given (randomly, double-blind) nebulized salbutamol sulfate (Asmasal) inhalation therapy at doses of 0.1, 0.2 and 0.3 mg/kg body weight on separated days. All three doses of nebulized solution resulted in clinical improvement and improvement of lung function (FEV1, FVC, PEFR and FEF25-75%). A dose of 0.3 mg/kg produced greatest improvement and longest duration of improvement in FEV1 and PEFR, but the change was statistically significant only in PEFR at 60 minutes (p < 0.05). Five children experienced mild tremors. There were no significant changes in heart rate or blood pressure at any dose. It is concluded that a nebulized solution of salbutamol sulfate at a dose of 0.1-0.3 mg/kg is useful for treatment of asthma in Thai children, with very mild side effects.

Ultrastructural defects of the ciliary epithelium in a child with Kartagener's syndrome.

Kartagener's syndrome is a well known classical triad of presentations consisting of bronchiectasis, sinusitis and situs inversus. It is now recognized that the syndrome is an extreme presentation of primary ciliary dyskinesia, a large group of conditions with ultrastructural ciliary defects, leading to poor ciliary motility in various organ systems. A case of Kartagener's syndrome is presented in an eight year old Thai boy in whom the ultrastructural ciliary defects have been examined and described in detail for the first time in Thailand. Incomplete lack of dynein arms was recognized. In addition, disorientation of ciliary axis was noticed. Due to severe bronchiectatic changes of the right lower lobe and right lingular lobe which did not improve despite adequate antibiotics, these lobes were surgically removed. The child has done well since, but still suffers occasional and recurrent bouts of sinusitis.

Sinusitis in Thai asthmatic children.

The radiographic appearance of sinuses was studied in 146 Thai asthmatic patients aged 1-13 years. Forty-eight percent of cases showed sinusitis by the radiographic criteria. The maxillary sinus was most commonly involved (98.6%). Thirty-three percent had ethmoidal sinusitis and 7% of those with developed frontal sinuses had frontal sinusitis. Thirty-three percent had more than one sinus involved. Those with frontal sinusitis always had maxillary and/or ethmoidal involvement. Sixteen cases had signs and symptoms of sinusitis and all of the cases had the radiographic appearance of sinusitis. There was no correlation between the occurrence of sinusitis and duration or severity of asthma. There was no difference in the occurrence of sinusitis between those with or without allergic rhinitis. No correlation between severity of sinusitis and age of patients was observed.

Suppressive effects of histamine skin reactivity by a nonsedating antihistamine-mequitazine.

The suppressive activity of mequitazine (MQZ) on histamine skin reactivity was evaluated in 29 healthy subjects (age 22-25 years) in a single-blind study. Fifteen subjects received MQZ, at a dosage of 5 mg BID, for 7 days while 14 served as controls. A prick skin test with saline or histamine hydrochloride (1 mg/ml and 10 mg/ml) was performed in duplicate, on both forearms, starting from the baseline day and continuing for 4 days after medication had been discontinued (total of 11 days). The skin-test subject and the reader was unaware of the randomization process. Mean diameters of wheal and flare as well as the skin index scores (after Voorhost) were used in the analysis. Maximal flare suppression (as compared to the baseline values) was observed on day 6 (97% suppression for 1 mg/ml and 54% suppression for 10 mg/ml, p less than 0.01). Suppression of wheal size was significant (19% for 1 mg/ml and 28% for 10 mg/ml) but was not clinically relevant. Suppression of skin index scores was maximal on day 6 (71% for 1 mg/ml and 43% for 10 mg/ml, p less than 0.01). After MQZ had been discontinued, all measurements gradually returned to baseline values and were not different therefrom within 3 days. However, final measurements of wheal and flare were smaller than baseline values (60-94% of baselines). We conclude that MQZ, at the manufacturers's recommended dose of 5 mg BID, significantly suppressed flare size of histamine skin tests and recommend that MQZ be discontinued for at least 3 days prior to performing allergy skin tests.

The role of disodium cromoglycate-metered dose aerosol inhaler in the management of asthma in Thai children.

Metered dose aerosol inhaler of disodium cromoglycate (Intal) has been recently introduced to facilitate the ease of administration of the drug over its previous spincap formulation. We evaluated the efficacy of regular use of metered dose inhaler of disodium cromoglycate (DSCG-MDI) in the daily management of Thai asthmatic children. The study comprised nineteen children with the age range of 8-15 years (mean 11.6 years). During a two week baseline period, the patients recorded their baseline symptom scores, requirement of their asthma medications (medication scores) and their morning/evening peak flow (PEFR) readings. Thereafter, DSCG-MDI was prescribed at the dosage of two puffs (1 mg/puff) four times daily for eight weeks. Patients were examined at two week intervals at which daily score cards along with PEFR records were collected. Significant reduction in the medication scores and in the requirement for maintenance bronchodilators were noted (p less than 0.01) within two weeks of use of the DSCG-MDI. Morning and evening PEFR's increased significantly and this increase reached statistical significance at 4 weeks after the initiation of the treatment (p less than 0.01). No side effects were reported throughout the study; the aerosol was well tolerated. In this open study DSCG-MDI, at a dose of 1 mg four times daily, significantly improved asthma symptoms along with PEFR readings in Thai asthmatic children and reduced the need for concomitant asthma medications.

Wheat-induced anaphylaxis.

A 13 year old boy suffered two separate episodes of severe anaphylaxis after consuming sandwiches and a piece of bread. Prick skin testings with available food allergens only revealed a positive reaction to a 1:10 w/v of wheat flour extract. A diagnosis of wheat-induced anaphylaxis was made and a double blind food challenge was suggested however was declined by the family. The patient was instructed to avoid all wheat containing foods and to carry a kit containing an epinephrine pre-loaded syringe and an antihistamine tablet to be used in the event of inadvertant consumption with an instruction to seek medical assistance as soon as possible. Thus far, no further recurrence of anaphylaxis was encountered. A review of the current literature discloses that wheat-induced anaphylaxis is an uncommon event and could occur either immediately after the ingestion or with a concomitant exercise. The natural history of wheat allergy is currently not fully understood but may possibly be a life long event.