Association between lung function and dyspnoea and its variation in the multinational Burden of Obstructive Lung Disease (BOLD) study.

BACKGROUND: Dyspnoea is a common symptom of respiratory disease. However, data on its prevalence in general populations and its association with lung function are limited and are mainly from high-income countries. The aims of this study were to estimate the prevalence of dyspnoea across several world regions, and to investigate the association of dyspnoea with lung function. METHODS: Dyspnoea was assessed, and lung function measured in 25,806 adult participants of the multinational Burden of Obstructive Lung Disease study. Dyspnoea was defined as ≥2 on the modified Medical Research Council (mMRC) dyspnoea scale. The prevalence of dyspnoea was estimated for each of the study sites and compared across countries and world regions. Multivariable logistic regression was used to assess the association of dyspnoea with lung function in each site. Results were then pooled using random-effects meta-analysis. RESULTS: The prevalence of dyspnoea varied widely across sites without a clear geographical pattern. The mean prevalence of dyspnoea was 13.7 % (SD=8.2 %), ranging from 0 % in Mysore (India) to 28.8 % in Nampicuan-Talugtug (Philippines). Dyspnoea was strongly associated with both spirometry restriction (FVC

Identification of chronic obstructive pulmonary disease subgroups in 13 Asian cities.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition that can differ in its clinical manifestation, structural changes and response to treatment. OBJECTIVE: To identify subgroups of COPD with distinct phenotypes, evaluate the distribution of phenotypes in four related regions and calculate the 1-year change in lung function and quality of life according to subgroup. METHODS: Using clinical characteristics, we performed factor analysis and hierarchical cluster analysis in a cohort of 1676 COPD patients from 13 Asian cities. We compared the 1-year change in forced expiratory volume in one second (FEV1), modified Medical Research Council dyspnoea scale score, St George's Respiratory Questionnaire (SGRQ) score and exacerbations according to subgroup derived from cluster analysis. RESULTS: Factor analysis revealed that body mass index, Charlson comorbidity index, SGRQ total score and FEV1 were principal factors. Using these four factors, cluster analysis identified three distinct subgroups with differing disease severity and symptoms. Among the three subgroups, patients in subgroup 2 (severe disease and more symptoms) had the most frequent exacerbations, most rapid FEV1 decline and greatest decline in SGRQ total score. CONCLUSION: Three subgroups with differing severities and symptoms were identified in Asian COPD subjects.

Sero-prevalence study of IgE responses to allergens from Malaysian house dust (HDM) and storage mites (SM).

Allergens of Dermatophagoides and Blomia species are well-characterized but not for other species. This study was conducted to determine the prevalence of allergic sensitization to house dust (HDM) and storage mites (SM). One hundred adult subjects (aged ≥ 18) were recruited. The mite specific IgE of all allergic subjects were higher compared with healthy subjetcs despite being not statistically significant except for D. farinae and G. malaysiensis. The mean serum IgE levels against HDM and SM for allergic subjects were significantly higher compared with those in healthy subjects. They were mainly sensitized to Dermatophagoides farinae (35%) and Glycycometus malaysiensis (37%). Immunoblots revealed not all allergic subjects showed positive immuno-reactivity against the mites tested. Single or multiple bands were observed for different species. The subjects were commonly sensitized to Group 2 (9-12 kDa), 10 (38 kDa) and 18 (40-48 kDa) allergens. Twenty-one out of 60 allergic subjects were sensitized to either one or more species. The majority of them (71%) were sensitized to single species. The allergic subjects were mainly sensitized to D. pteronyssinus, followed by Tyrophagus putrecentiae and Aleuroglyphus ovatus. Seven were solely sensitized to HDM while 10 were solely sensitized to SM. Four subjects were sensitized to both. Pre-adsorption study revealed no cross-reactivity. There was difference between the prevalence and reactivity to allergens of HDM and SM in these subjects. Both ELISA and immunoblot did not correlate well but can complement each other in improving the detection of mite allergens to the species level.

Sero-prevalence study of IgE responses to allergens from Malaysian house dust (HDM) and storage mites (SM)

Allergens of Dermatophagoides and Blomia species are well-characterized but not for other species. This study was conducted to determine the prevalence of allergic sensitization to house dust (HDM) and storage mites (SM). One hundred adult subjects (aged > 18) were recruited. The mite specific IgE of all allergic subjects were higher compared with healthy subjetcs despite being not statistically significant except for D. farinae and G. malaysiensis. The mean serum IgE levels against HDM and SM for allergic subjects were significantly higher compared with those in healthy subjects. They were mainly sensitized to Dermatophagoides farinae (35%) and Glycycometus malaysiensis (37%). Immunoblots revealed not all allergic subjects showed positive immuno-reactivity against the mites tested. Single or multiple bands were observed for different species. The subjects were commonly sensitized to Group 2 (9-12 kDa), 10 (38 kDa) and 18 (40-48 kDa) allergens. Twenty-one out of 60 allergic subjects were sensitized to either one or more species. The majority of them (71%) were sensitized to single species. The allergic subjects were mainly sensitized to D. pteronyssinus, followed by Tyrophagus putrecentiae and Aleuroglyphus ovatus. Seven were solely sensitized to HDM while 10 were solely sensitized to SM. Four subjects were sensitized to both. Preadsorption study revealed no cross-reactivity. There was difference between the prevalence and reactivity to allergens of HDM and SM in these subjects. Both ELISA and immunoblot did not correlate well but can complement each other in improving the detection of mite allergens to the species level.

Awareness of diastolic heart failure as a disease entity among Malaysian doctors -- a questionnaire survey from three general hospitals.

The concept of diastolic heart failure (DHF) is not new. However awareness and understanding on this subject may remains uncertain among medical practitioners. We wished to examine the extent of awareness of such entity among doctors in Malaysia. A questionnaire was designed and distributed randomly during hospital Continuous Professional Development (CPD/CME) sessions and also in the respective outpatient departments (OPD) between July to October 2008. This cross-sectional survey in three urban-based general hospitals showed that there are a significant proportion of doctors who are lack of understanding and awareness of diastolic heart failure.

Significant resolution of tuberculous pleural effusion on chemotherapy alone.

BACKGROUND: As a standard, significant pleural effusion, whether tuberculous (TB) or not, requires therapeutic thoracocentesis. We tested the hypothesis that standard anti-TB chemotherapy alone can resolve significant pleural effusion. METHODS: 20 eligible patients with TB pleural effusion of at least 30% of the hemithorax (10 with moderate-size and 10 with large-size effusion, respectively) were retrospectively reviewed for radiological resolution of their effusions at two, six and 12 months after commencement of standard six-month therapy. RESULTS: The mean percentage resolutions in both groups were comparable (48% vs 46% at two months; 59% vs 85% at six months; 84% vs 95% at 12 months). The mean sizes of effusions were also comparable (18% vs 33% at two months; 14% vs 10% at six months; 6% vs 4% at 12 months). Cigarette smoking and Indian ethnicity were univariately associated with incomplete resolution of effusions. CONCLUSION: Standard anti-TB chemotherapy alone appears to be sufficient to resolve significant TB pleural effusion. An avoidance of therapeutic thoracocentesis may reduce the risk of infection exposure or allow better channelling of resources in certain clinical settings.

Budesonide/formoterol combination therapy as both maintenance and reliever medication in moderate-to-severe asthma: a real-life effectiveness study of Malaysian patients.

Budesonide/Formoterol (Symbicort) combination therapy as both maintenance and reliever treatment (SMART) is a novel approach in asthma management. We examined its 'real-life effectiveness' in treating Malaysian patients with moderate-to-severe asthma in whom despite on combined inhaled corticosteroids and long-acting beta2-agonist, were still inadequately controlled. In a retrospective study, 22 eligible adult patients on SMART [mean (range) age: 49 (36-65) years; FEV1: 41 (21-74)% predicted] were identified from medical records of an urban-based university hospital chest clinic, and their clinical outcomes studied at three months. Another 16 patients [50 (14-66) years; 48 (20-91)% predicted] of similar severity and treatment (i.e. Symbicort maintenance treatment plus short-acting beta2-agonist as reliever), but not on SMART, were used as comparator over the same assessment period. In addition, the patients were separately interviewed with standard questionnaire on their satisfaction and compliance to the SMART approach. In SMART group, rescue treatment requirement (p<0.001) and FEV1 [median difference = 2.5%, p=0.015; mean difference: 90 ml, p=0.013] showed significant improvement while in comparator, there was significant improvement only in the requirement for rescue treatment (p=0.023). Hospital admission rates were significantly reduced in SMART group compared to the other (p=0.039), but not in emergency treatment. Five patients asked to discontinue SMART while all others were satisfied, compliant and perceived improvement of their asthma with SMART. The maximum daily doses of inhaled budesonide and formoterol were 1400 microg and 31.5 microg respectively. Our preliminary findings suggest that SMART approach can be attempted as an effective and safe treatment option for patients with inadequately controlled moderate-to-severe asthma in Malaysian setting.

Klebsiella pneumoniae respiratory isolates from 2000 to 2004 in a Malaysian hospital: characteristics and relation to hospital antibiotics consumption.

INTRODUCTION: Klebsiella pneumoniae ranks high as a cause of community-acquired pneumonia in hospitalised patients in Malaysia. METHODS: A retrospective study of 5,990 clinical respiratory specimens in patients, with a mean age of 54 (standard deviation 18.5) years, admitted to an urban-based general hospital between 2000 and 2004, was conducted. RESULTS: The percentages of K. pneumoniae isolates during these years were 11, 19.1, 41.4, 27.8 and 16.6 percent, respectively. During this time, the percentage of isolates resistant to ampicillin were consistently in excess of 80 percent, those resistant to cephalosporins were relatively stable between eight and 23 percent, while those resistant to beta-lactam/beta-lactamase inhibitors [amoxicillin clavulanic acid/ ampicillin-sulbactam] and aminoglycosides steadily increased between six and 58 percent. Compared with hospital consumption of these corresponding antibiotic classes, only beta-lactam/beta-lactamase inhibitors and aminoglycosides showed a clear trend of eight- and four-fold increases, respectively. Co-resistance rates in isolates resistant to ampicillin and amoxicillin-clavulanic acid/ampicillin-sulbactam were generally low to second to third generation cephalosporins (less than 20 percent). CONCLUSION: Our local findings highlighted the changing trend in respiratory K. pneumoniae over a five-year period, and its escalating resistance to beta-lactam/beta-lactamase inhibitors and aminoglycosides that is possibly attributable to the widespread use of these antibiotics in our hospital.

Lack of neutrophil degranulation in low-dose endotoxin inhalation based on a novel intracellular assay.

To study the nature of endotoxin or lipopolysaccharide (LPS) induced inflammation, we developed a method of quantifying intracellular human neutrophil elastase (HNE) in lysed sputum polymorphs as a means to study the degranulation status of LPS-recruited neutrophils. Induced sputum, blood and exhaled nitric oxide (NO) were collected from 10 healthy non-atopic human subjects after inhaling a single 15 microg dose of Escherichia coil LPS in an open study. At 6 hours, LPS inhalation caused significant increase of sputum and blood neutrophils but without parallel increase in myeloperoxidase, HNE or interleukin-8 (IL-8) in sputum sol and blood, or exhaled NO. Intracellular HNE in lysed sputum polymorphs or purified blood neutrophils did not show any significant changes between inhaled LPS and saline, nor was there any appreciable change in percentage HNE release induced by N-Formyl-Met-Leu-Phe (fMLP) in vitro. We concluded that in healthy humans, the transient neutrophilic inflammation induced by a single dose of inhaled 15 microg LPS is mainly characterized by cell recruitment, not enhanced secretion of granular mediators or increased exhaled NO based on our experimental conditions.

Ethnicity as a determinant of asthma-related quality of life in a multiracial country.

In a multiracial country like Malaysia, ethnicity may influence the measurement of health-related quality of life (HRQL) in asthmatic patients. We invited 131 adult patients [44 Malays, 42 Chinese and 45 Indians; mean (95% CI) age: 43 (40.2-45.7) yrs; 28.2% male] with moderate-to-severe persistent asthma followed up in an urban-based hospital outpatient clinic to complete a disease-specific HRQL questionnaire [St Georges' Respiratory Questionnaire (SGRQ)] and to provide socio-demographic and asthma-related data. Indians reported significantly worse SGRQ total score, compared to Malays [mean (95% CI) difference: 10.15 (0.51-19.78); p = 0.037] and SGRQ activity score, compared to Malays [13.50 (1.95-25.05); p = 0.019] and Chinese [11.88 (0.19-25.05); p = 0.046]. Further analysis using multivariate linear regression showed that Indian ethnicity remained independently associated with SGRQ scores. Our finding highlights the relevance of ethnicity in assessing HRQL of asthmatic patients in a multiracial country such as Malaysia.

Effect of time delay on survival in patients with non-small cell lung cancer--a Malaysian study.

The prognosis of lung cancer remains poor with overall five year survival figures varying between five and 10% worldwide, However, it has been shown that surgery in patients with early stage disease in non-small cell lung cancer can achieve five year survival rates up to 80%, suggesting that early or delay diagnosis can influence prognosis. Nevertheless, studies addressing this have been inconclusive and mostly derived from Western countries.

Inhaled endotoxin in healthy human subjects: a dose-related study on systemic effects and peripheral CD4+ and CD8+ T cells.

BACKGROUND: Inhaled endotoxin or lipopolysaccharide (LPS) is implicated in the pathogenesis of pulmonary diseases. We investigated the inhalation effects of two different doses of LPS in healthy human subjects. METHODS: Eighteen healthy non-atopic human subjects inhaled either 15 microg (n=10) or 50 microg (n=8)Escherichia coli LPS in an open study. As control, each subject had isotonic saline inhalation 1 week before (baseline) and after LPS inhalation. Data collected included those of clinical parameter, induced sputum and peripheral blood CD4+ and CD8+ T cells. RESULTS: Acute flu-like symptoms and pyrexia were significantly greater in the 50 microg than 15 microg LPS group. Similarly, the increase in sputum and blood total cell and neutrophil counts at 6h following inhaled LPS were greater in the 50 microg group. Myeloperoxidase, human neutrophil elastase and interleukin-8 in sputum sol, but not blood, showed a trend towards greater increase following 50 microg LPS. All these changes were resolved at one week. In the 50 microg dose group alone, there was a reduction in the proportion of peripheral blood interferon (IFN)-gamma-producing CD4+ and CD8+ T cells at 6h followed by an increase at 1 week after inhaled LPS. CONCLUSIONS: The airway and systemic effects of inhaled LPS are dose-related and predominantly neutrophilic. The changes in the proportions of circulating CD4+ and CD8+ T cells suggests preferential recruitment of IFN-gamma-producing T cells into tissue from inhaled 50 microg LPS, followed by reappearance of these cells in blood 1 week later.

"Discovery to treatment" window in patients with smear-positive pulmonary tuberculosis.

Delay in commencing treatment in patients diagnosed with smear-positive pulmonary tuberculosis (PTB) may promote the spread of PTB in the community. Socio-demographic and clinical data from 169 patients (119 retrospectively and 50 prospectively collected) treated for smear-positive PTB in our hospital Chest Clinic from June 2002 to February 2003 were analysed. One hundred and fifty eight (93.5%) patients were started on treatment in less than 7 days from the time when the report first became available while 11 (6.5%) patients had their treatment started > or = 7 days. The median 'discovery to treatment' window was 1 day (range, 0 to 24 days). Of the factors studied, longevity of symptoms, absence of fever or night sweats and having sought traditional medicine were associated with delay in treatment commencement. The urgency and importance of anti-TB treatment should be emphasized especially to patients who are inclined towards treatment with traditional medicine.

Pulmonary disease empirically treated as tuberculosis-a retrospective study of 107 cases.

Pulmonary disease is sometimes treated empirically as tuberculosis (TB) in the absence of microbial confirmation if the clinical suspicion of active TB is high. In a country of relatively high TB and low HIV burden, we retrospectively studied 107 patients (69.2% male; mean age (SD): 45 (17) years) who received empirical anti-TB treatment for intrapulmonary opacities or pleural effusions suspected of active TB in our hospitals between 1998 and 2002. The diagnosis of definite or probable 'smear-negative' pulmonary TB was made based on treatment outcome at two months with rifampicin, isoniazid, pyrazinamide and ethambutol (or streptomycin). At this end-point, 81 patients (84.4%) had both clinical and radiological improvement (definite cases), 12 (12.5%) had clinical improvement alone and 3 (3.1%) had radiological improvement alone (probable cases). Confirmation of acid-fast bacilli was subsequently obtained in 12 patients (all definite cases) from culture of initial pulmonary specimens. Eleven patients (10.5%) were diagnosed as 'non-TB' based on absence of both clinical and radiological improvement or discovery of another cause for the pulmonary condition at or before this two-month study end-point. In the 'non-TB' group, 2 had carcinoma, 2 had HIV-related pulmonary diseases, 1 had bronchiectasis, while in 6 causes were indeterminate. Six (6.3%) and 3 (27.3%) patients reported adverse effects from anti-TB drugs from the 'TB' and 'non-TB' groups respectively. Our findings suggest that empirical anti-TB treatment is an acceptable practice if clinical suspicion is high in patients coming in our region.

Symptomatology and health status in patients with chronic obstructive pulmonary disease.

Chronic Obstructive Pulmonary Disease (COPD) is a growing health problem worldwide and in Malaysia. Until recently, research on COPD has been slow and difficult, partly due to the huge heterogeneity of this disease, and its variable and imprecise definitions. To perform a descriptive study on a convenient sample of local patients with COPD treated in a state hospital in Malaysia. Fifty-two patients [mean (95% CI) age: 67 (63-70) years; 86% male: 38% Malays, 36% Chinese, 25% Indians; mean (95% CI) PEFR: 45 (40-51) % predicted normal] were interviewed. Clinico-demographic data was collected using a structured questionnaire and health-related quality of life was scored using St George's Respiratory Questionnaire (SGRQ). For analysis, patients were also divided into moderate (n=17) [PEFR 50% to 80%] and severe (n=35) [PEFR < 50%] disease groups. Except for education and total family income, demographic and comorbidity variables were comparable between the two groups of COPD severity. All except 9% of patients were current or ex-smokers. Breathlessness, not chronic bronchitis (i.e. cough and sputum), was the first ranking respiratory symptom in over 70% of the patients, whether currently or at early disease manifestation. Between 5 and 15% of the patients denied any symptom of chronic bronchitis as current or early stage symptoms. Duration of symptoms prior to the diagnosis varied considerably with about 9% having symptoms for over 10 years. Over 80% of the patients smoked for over 15 years before the onset of symptoms. Quality of life in patients with COPI) was generally poor and similar between both COPD severity groups. About one fifth of the patients had exacerbations more than 12 times a year. While many features described in our local patients are well recognized in COPD, the finding that 'chronic bronchitis' is not a prominent symptom in the current or past history may have important implications in the diagnosis of at risk individuals and patients with early disease requiring attention. More research is required to confirm and to understand this.