The objective of this study was to determine the relationship between asthma symptoms and the degree of airway obstruction as measured by the forced expiratory volume in one second (FEV1) and peak expiratory flow rate (PEFR) in a group of 64 asthmatic patients with clinically stable disease attending a university-based urban asthma clinic. Asthma symptoms did not correlate with the degree of airway obstruction as measured by prebronchodilator PEFR (total asthma symptom score vs PEFR: r = -0.214, p = 0.104, n = 59) and only correlated poorly with prebronchodilator FEV1 (total asthma symptom score vs FEV1: r = -0.256, p = 0.041, n = 64). These results lend support to the recommendation that airway obstruction should be measured objectively when assessing patients with chronic persistent asthma.
Study site: Asthma clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
Anti-nuclear antibody (ANA) negative systemic lupus erythematosus (SLE) occurs in about 4-13% of SLE cases. A small group of ANA negative SLE patients with positive anti-Ro antibodies usually present with typical vasculitic skin lesions which can be associated with photosensitivity, renal disease, congenital heart block or neonatal lupus. We present a case of a persistently ANA negative patient who presented with joint pain, rashes, mouth ulcer and alopecia. Clinical diagnosis of systemic lupus erythematosus was made even though ANA was negative. She was started on steroids and went into remission. Later, she developed several episodes of convulsions associated with fever and prominent vasculitic lesions. The patient was also found to have microscopic hematuria, proteinuria, anemia and thrombocytopenia. Renal biopsy showed lupus nephritis class 1B. Due to the prominent skin lesions, we performed anti-extractable nuclear antigens (ENA) antibodies test and anti-Ro turned out to be positive. The final diagnosis was ANA negative SLE (Ro lupus) with cutaneous, renal, musculoskeletal, hematological and cerebral Involvement.
Most children with asthma develop their symptoms before the age of 5 years and many preschool wheezers continue to wheeze in the early school years. It is thus important to investigate the factors that predispose young children to wheeze. The objective of this study was to investigate the relevant environmental and family influences on recent wheeze (wheeze within the last 12 months) in preschool children. A cross-sectional study was conducted in five primary health clinics in the district of Kota Bharu from April to October 1998. Nurses from these clinics distributed Bahasa Malaysia questionnaires containing questions on asthma symptoms, environmental risk factors, family's social status and family history of atopy and wheeze to preschool children aged 1-5 years during their home visits. The respondents were parent(s) or carer(s) of the children. A total of 2,524 (87.7%) complete questionnaires were available for analysis of risk factors. One hundred and fifty six (6.2%) children had current wheeze. Significant risk factors associated with current wheeze were a family history of asthma (O.R. = 6.36, 95% C.I. = 4.45-9.09), neonatal hospital admission (O.R. = 2.38, 95% C.I. = 1.51 - 3.75), and a maternal (O.R. = 2.12, 95% C.I. = 1.31-3.41) or paternal (O.R. = 1.52, 95% C.I. = 0.95-2.43) history of allergic rhinitis. Among environmental factors examined, namely, household pets, carpeting in bedroom, use of fumigation mats, mosquito coils and aerosol insect repellents, maternal and paternal smoking, and air conditioning, none were associated with an increased risk of wheeze. In conclusion, the strongest association with current wheeze was a family history of asthma. Also significant were neonatal hospital admission and a history of allergic rhinitis in either the mother or father. None of the environmental factors studied were related to current wheeze in preschool children.
Study site: Klinik Kesihatan, Kelantan, Malaysia
The aim of the present study was to determine whether Porphyromonas gingivalis-lipopolysaccharide (Pg-LPS) may stimulate nitric oxide (NO) production by murine spleen cells. Spleen cells derived from Balb/c mice were cultured in the presence of Pg-LPS or LPS from Salmonella Typhosa. The cell were also cultured in the presence of Pg-LPS with or without L-arginine, L-arginine plus NG-monomethyl-L-arginine (NMMA), or IFN-gamma. Furthermore, the plastic non-adherent spleen cells were stimulated with Pg-LPS and L-arginine. The results showed that Pg-LPS failed to stimulate splenic NO production by themselves. Exogenous L-arginine or IFN-gamma up-regulated the NO production of Pg-LPS-stimulated spleen cells, but the stimulatory effects of L-arginine were completely blocked by NMMA. It was also demonstrated that in the presence of Pg-LPS and L-arginine, splenic macrophages were the cellular source of NO. These results suggest, therefore, that P. gingivalis-LPS may induce murine splenic macrophages to produce NO in a L-arginine and an IFN-gamma-dependent mechanism.
While many studies of the prevalence of wheeze have been conducted in schoolchildren, there have been few in pre-school children. Most children with asthma develop symptoms before the age of 5 years and many pre-school wheezers continue to wheeze in the early school years. Among the latter, those children who continue to wheeze at school age have poorer lung function than those who don't. It is thus appropriate to enquire more fully about wheeze in this age-group where its incidence is high and its relation with asthma less well defined. The objective of this study was to investigate the prevalences of wheeze, night cough and doctor diagnosed asthma in pre-school children. A cross-sectional study was conducted in five primary health clinics in the district of Kota Bharu from April to October 1998. Nurses from these clinics distributed Bahasa Malaysia questionnaires containing questions on asthma symptoms to preschool children aged 1-5 years during their home visits. The respondents were parent(s) or carer(s) of the child. The response rate was 100% and a total of 2,878 responses were analysed. The prevalence of symptoms and doctor diagnosed asthma were as follows: ever wheezed 9.4% (95% confidence interval (CI) 8.3-10.4%); current wheeze 6.2% (95% CI 5.2 to 7.0%); night cough 10.2% (95% CI 9.1 to 11.4%); and doctor diagnosed asthma 7.1% (95% CI 6.2 to 8.0%). There were no significant differences in prevalence between males and females, or among age groups. The prevalence of night cough in children with no history of wheeze was 6.9%. The cumulative and current prevalences of wheeze were similar to, and those of night cough and doctor-diagnosed asthma significantly lower than, those reported for Kelantan schoolchildren. These findings provide a baseline for assessing future symptoms trends, and perhaps also the validity of diagnosing asthma in this age group.
The significance of food specific serum IgG4 antibody in food allergy is unclear and this led us to investigate the relevance of specific IgG4, along with IgG and IgE antibodies to two common food allergens in Malaysia. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum antibodies in 143 allergic rhinitis patients' sera, of which 47 were from patients with clinical indication of shrimp allergy, 46 with clinical indication of crab allergy and 50 without indication to either allergy. Clinical indication of allergy was based on answers to a questionnaire or results of the skin prick test. We found that the elevation of specific IgE or IgG4 is associated with shrimp and crab allergies but elevation of specific IgG is not associated with either allergy. However, the clinical utility of elevated specific IgG and IgG4 levels is pending further investigation.
Study site: Allergic rhinitis clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
Deficiency of surfactant in alveoli leads to increased resistance to breathing. Histamine is a mediator in allergic respiratory diseases. Though the bronchoconstrictor effect of histamine is well recognised, histamine may have additional actions that contribute to pathogenesis in these diseases. The present study aimed to observe the effect of histamine on lecithin, a major component of alveolar surfactant. Lecithin content in broncho-alveolar lavage (BAL) fluid of healthy adult male rats was estimated by enzymatic method using Boehringer-Mannheim kits. Lecithin content in these control animals was compared with that in three groups of healthy adult male rats following subcutaneous administration of 0.06 mg of histamine diphosphate at 10 minutes, 30 minutes and 60 minutes intervals, respectively. A significant reduction in lecithin levels in BAL fluid was observed up to one hour after administration of histamine. The results indicate a possible additional action of histamine in the pathogenesis of allergic respiratory diseases.
We studied the prevalence of antinuclear (ANA), anti-double stranded DNA (dsDNA), anti-Sm and anti-RNP antibodies in a group of 93 blood donors (age range: 18-58 years). Antinuclear and anti-ds DNA antibodies were detected by immunofluorescence (IF) using HEp2 cells and Crithidia luciliae as substrates, respectively, while anti-Sm and anti-RNP antibodies were assayed by ELISA. ANA was found in 6.5% while anti-dsDNA antibodies were not detected in any of the subjects. The 98th percentile was used as cut off where values greater than 0.651 for anti-Sm and 0.601 for anti-RNP antibodies were taken to be positive. This gives a frequency of 1.1% for both antibodies. There was no significant association of antibody positivity with sex or race. We conclude that certain autoantibodies are present in low titres in the normal Malaysian Individuals, at a different frequency compared to other studies probably due to genetic, ethic or environmental factors.
The aim of this project was to compare dual and tri-colour reagents for lymphocyte immunophenotyping. A total of 37 patient and normal specimens were immunophenotyped concurrently with the following mean values (% dual vs tri-colour): CD3 (69.4 vs 68.3) CD4 (24.0 vs 24.2) and CD19 (13.9 vs 12.6). A comparison of the results obtained using the paired t test showed that there were no significant differences for cells expressing CD3, CD4 and CD19. However, there was a significant difference in the NK (18.3 vs 16.3) cell component. A major advantage in using 3 colour immunophenotyping is the ability to analyse specimens that cannot be analysed using dual colour reagents due to debris or contamination of the gate with non-lymphocytic cells.
The specific serum IgE levels to 20 allergens were determined by enzyme immunoassay in 90 Malaysian patients with allergic rhinitis. Ninety-two percent of patients had elevated IgE to at least 1 of the allergens. The housedust mites D. pteronyssinus and D. farinae were the major allergens, elevated IgE to either allergen being present in 86% of the patients. Prick skin tests were carried out in some of the patients, housedust mites, cat fur, dog hair and shrimp were the allergens used. Close correspondence was found between IgE and prick skin tests to the mites.
Aerosampling using Rotorod samplers was conducted in the Institute for Medical Research, Kuala Lumpur, Malaysia, from December 1991 to November 1993. Samples were collected twice a week between 10.00 hours to 12.00 hours. Rods were stained and examined microscopically. A total of 8 and 20 types of pollens and mold spores were collected, respectively. More mold spores were collected than pollens. Grass pollen constituted more than 40 percent of total pollen counts. Gramineae pollen counts peaked in March and September. The most abundant mold spore was Cladosporium followed by Rust, Nigrospora, Curvularia and Smut. Cladosporium counts peaked in February and August. Rust counts peaked in June and December whereas counts for Nigrospora peaked in February and October. Highest counts of Smut were recorded in March and October. Curvularia counts peaked in January, June and September.
This study was conducted to determine the seasonal prevalence of allergies to house dust, D. pteronyssinus, D. farinae, cat fur, dog hair, mixed moulds, mixed grass pollens and American cockroach. A total of 314 patients with clinically suspected allergic rhinitis was examined by prick test using commercial preparations of the above allergens. Total serum IgE of the patients was determined by a Sandwich ELISA. Ninety-six percent of the patients tested positive to more than one allergen. Most were positive to a combination of 4 allergens. More than 70% of the patients were positive to house dust, D. pteronyssinus, D. farinae and cat fur. Analysis indicates that for an individual who tests positive for house dust, there is a very high risk of the person being allergic to the dust mites and cat fur too. Most of the allergens had 2 peak period of high positive PT rates; mixed moulds and mixed grass pollens had 3 peaks. There was significant positive correlation between the monthly positive PT rates against mixed moulds and mixed grass pollens with maximum daily mean temperature and mean temperature at 14.00 hours.
An indirect ELISA was used to detect antibodies against outer membrane protein preparations (OMPs) from Salmonella typhi. Sera from patients with a definitive diagnosis of typhoid fever (TF) gave a mean absorbance reading, at 414 nm, of 1.52 +/- 0.23 as compared to 0.30 +/- 0.11 for sera from healthy individuals. This gave a positive to negative ratio of absorbance readings of approximately 5.1. Suspected TF patients (no isolation of S. typhi), with positive and negative Widal titers had mean absorbance readings of 1.282 +/00.46 and 0.25 +/- 0.19, respectively. Sera from patients with leptospirosis, rickettsial typhus, dengue fever, and other infections gave mean absorbances of 0.20 +/- 0.08, 0.24 +/- 0.08, 0.27 +/- 0.08, and 0.31 +/- 0.16, respectively. The sensitivity, specificity, positive and negative predictive values were 100%, 94%, 80% and 100%, respectively. The antibody response detected in the definitive TF cases was predominantly IgG in nature and no cross-reactivity was seen with OMP preparations extracted from E. coli. Variable reactivity was noted with OMP preparations obtained from other Salmonella spp. Three major OMPs are presented in the antigen preparation and strong binding of positive sera was detected to all three bands.
The MAST CLA system was evaluated against skin prick test (SPT) for diagnosis of allergies to house dust mites (Dermatophagoides pteronyssinus, Dermatophagoides farinae) and cats. Forty three asthmatic children were examined by SPT and MAST CLA. Chi-square analysis indicated significant association between SPT and MAST CLA results for the house dust mites but not for cats. The sensitivities of MAST CLA for house dust mites and cats were 100 and 25% respectively; specificities were all less than 50%. The efficiency of MAST CLA for detection of allergy to the house dust mites was 88% and 44% for cats. A significant linear correlation was found between SPT wheal size and MAST CLA grade for D. farinae but not for D. pteronyssinus and cats. It is concluded that the MAST CLA allergy system can be used to supplement SPT for diagnosis of allergies to house dust mites but not to cats.
The percentage of lymphocyte subsets from the peripheral blood of healthy adults and hepatitis B surface antigen (HBsAg) carriers were analyzed by flow cytometry. The five lymphocyte subsets studied were:- T (CD3) cells, B (CD19) cells, CD4 cells, CD8 cells, Natural Killer (CD3- CD16+/CD56+) cells (NK cells) and the CD4/CD8 ratio. The percentage (mean +/- SD) for the five lymphocyte subsets from the healthy adults were (67.5 +/- 8.5)%, (12.4 +/- 4.5)%, (35.5 +/- 7.8)%, (36.8 +/- 8.5)%, (17.9 +/- 8.1)% and 1.1 +/- 0.6, respectively. HBsAg carriers positive for HBV-DNA had a lower CD4/CD8 ratio than the healthy population (P = 0.030). The percentage of CD8 cells in HBsAg carriers increased significantly (r = 0.28; P = 0.019) with an increase in ALT levels but the values remained within normal range. The percentage of NK cells and CD4/CD8 ratio in HBsAg carriers positive for anti-HBe were higher than HBsAg carriers negative for anti-HBe (92% of which are HBeAg positive) (P = 0.045 and P = 0.035, respectively). The CD4/CD8 ratio in HBsAg carriers negative for anti-HBe (92% positive for HBeAg) was also lower than in the healthy population (P = 0.042). HBsAg carriers positive for HBV-DNA, HBeAg and raised ALT levels had a lower CD4/ CD8 ratio than did the healthy population. The lower ratio was due to an increase in the percentage of CD8 cells. This suggests an activated immune response triggered by the infection in an attempt to clear the virus. HBsAg carriers with normal ALT levels and who are negative for HBV-DNA may be in a state of tolerance.
We investigated the aeroallergens affecting 200 asthmatics from the University Hospital in Kuala Lumpur, Malaysia and found 164 (82%) patients with skin prick test (SPT) reactivity to one or more of a panel of 14 allergens, which included indoor and outdoor animal and plant aeroallergens. Reactivity was most frequent to the indoor airborne allergens, with 159 (79.5%) reacting to either or both house dust mite (Dermatophagoides) species and 87 (43.5%) to cockroach. The SPT reactivity to house dust mites corresponded with the finding that patients found house dust to be the main precipitant of asthmatic attacks.
In this paper we report results of skin prick tests (SPT) using pollen extracts on 200 patients with clinical symptoms of asthma, and results of a parallel study in which pollen was collected and classified over a period of 18 months. The patients were outpatients from the University Hospital in Kuala Lumpur, Malaysia, while the pollen grains were collected with a spore trap placed in the campus of the University of Malaya, approximately one kilometer from the University Hospital. Pollen extracts of 3 grasses (Bahia, Bermuda, rough pigweed) and 2 flowering trees, Acacia and Melaleuca, were used in the SPT. Of the 29.5% asthmatics with positive SPT reactions, 21.5% were to one or more of the grass pollens, 21.5% to Acacia and 7.5% to Melaleuca pollen. Acacia and Bermuda grass extracts were the most allergenic, which agreed with results of the pollen collection which showed grass and Acacia pollen grains to be the two most commonly found pollens.
Study site: University Malaya Medical Centre (UMMC)
As future health care providers medical students should acquire an adequate knowledge of bronchial asthma before graduation from medical school. The aim of this study was to assess whether knowledge about childhood asthma increased during the medical course. The 590 medical students enrolled in the School of Medical Sciences, University of Science Malaysia during the 1995/96 session were studied utilizing a validated questionnaire. There was a significant increase in the mean total scores from 11 (95% CI 10.5-11.6) in Year 1 to 23.4 (95% CI 22.9-24) in Year 5. Questions about symptoms of asthma, pathogenesis of airway narrowing during acute exacerbations, preventive and reliever medications, side effects of steroids, addiction to asthma drugs and assessment of severity revealed a progressive increase in knowledge over the five years. Among 5th year medical students 44.6% named infection and 65.1% named exercise as two common triggers of childhood asthma; only 30.1% could name two prophylactic drugs for asthma. Although the asthma knowledge of medical students increased progressively during the five year curriculum, their knowledge regarding trigger factors and preventive medications were deficient. As childhood asthma affects some 10% of Malaysian children its importance requires greater emphasis in the medical curriculum.
In a study of 124 adult patients with bronchial asthma, 65% of them had associated rhinitis. In the asthmatics who had associated rhinitis, both diseases usually started within two years of one another but either disease might develop first. In 21% of the patients, asthmatic attacks were preceded or precipitated by rhinitis symptoms. In the patients who had asthma alone or those associated with rhinitis, no significant difference were found in terms of age and sex distribution, age of onset, and a positive family history of asthma, rhinitis or allergic diseases. Response to skin prick test using six different types of allergens also showed no difference in the two groups of patients. Sensitivity to house dust was common among both groups of patients as well as in the normal controls suggesting a common occurrence of house dust mite in our community and making the skin prick test using this allergen unsuitable as a test for atopy in our population.
Study site: Chest clinic, Hospital Universiti Sains Malaysia (HUSM), Kelantan, Malaysia