To determine the degree of resolution in pleural effusions treated with anti-tuberculosis treatment alone without thoracentesis, 62 eligible adult cases [mean age (SD), 46 (17) yrs; 77% male] of tuberculosis pleural effusions treated in two urban-based university teaching hospitals were retrospectively reviewed for changes in effusion size at 2, 6 and 12 months after initiation of treatment. The proportions of patients in whom resolution were complete, partial and unchanged were 64.5%, 27.4% and 8.1%. Effusions with size smaller than three tenth of hemithorax were at three-fold increased likelihood of complete resolution, compared with those with larger effusions [Odds ratio (95% CI): 3.295 (1.033 to 10.514); p=0.04]. Consideration for thoracentesis is therefore still important in certain patients.
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.
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.
Study site: Hospital Pulau Pinang, Georgetown, Pulau Pinang, Hospital Tuanku Ja’afar Seremban, Bukit Rasah, Seremban, Hospital Ampuan Najihah Kuala Pilah, Negeri Sembilan.
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.
Study site: Chest clinic, Hospital Tuanku Jaafar, Seremban, Negeri Sembilan, Malaysia
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.
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.
Study site: chest clinic of an urban-based
university teaching hospital
Sputum induction with nebulized hypertonic saline is increasingly being used to evaluate airway inflammation. We investigated the procedure-associated risk in 16 asthmatics that were still symptomatic despite on high doses of regular corticosteroid (CS) therapy (7 on daily inhaled CS > or = 800 microg budesonide or equivalent; 9 on additional daily oral CS) and their sputum cellular profile. For comparison, 12 mild stable asthmatics and 10 normal healthy subjects were included. All subjects inhaled 3%, 4% and 5% hypertonic saline sequentially via ultrasonic nebulizer as a means to induce sputum. Maximal percentage fall of Forced Expiratory Volume on One Second (FEV1) during sputum induction was significantly greater in CS-dependent asthmatics (median % [IQR]: 16.0 [11.0-32.3]) than in mild asthmatics (5.3 [4.2-10.8], p = 0.002] and in normal subjects (4.6 [3.4-6.4]), p = 0.0001). The maximal percentage FEV1 fall was inversely correlated with baseline FEV1 (Rs= -0.69; p < 0.0001). Compared to mild asthmatics, induced sputum from CS-dependant asthmatics had proportionately fewer eosinophils (2.2 [0.8-7.0] versus 23.3% [10.7-46.3], p = 0.003) and greater neutrophils (64.2 [43.9-81.2] versus 28.7 [19.0-42.6], p = 0.009). Sputum neutrophils showed a significant inverse correlation to FEV1 (Rs = -0.51, p = 0.01). We concluded that sputum induction using nebulized hypertonic saline should be performed with caution in CS-dependant asthmatics. The airway cellular profile observed suggests that the immunopathology underlying CS-dependant asthmatics may be different or a consequence of CS therapy.
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.
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.
Keywords: Smear positive, pulmonary tuberculosis, treatment delay, traditional medicine, Malaysia, Seremban, Negeri Sembilan
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.
Severe Acute Respiratory Syndrome (SARS) epidemic illustrated the crucial role of infection surveillance and control measures in the combat of any highly transmissible disease. We conducted an interview survey of 121 medical staff 145 doctors, 46 staff nurses and 30 medical assistants) in a state hospital in Malaysia three months after the end of SARS epidemic (from October to December 2003). Staff was grouped according to those directly involved in the care of suspected SARS patients [S+ group n=41] and those who were not [S- group; n=80]. On hand washing following sneezing, coughing and touching patients, the proportions of medical staff that reported an increase after the SARS crisis were 22.3%, 16.5% and 45.5% respectively. On wearing masks, gloves, and aprons when meeting potentially infectious patients, the proportions that reported an increase were 39.7%, 47.1% and 32.2% respectively. Significantly more staff in S+ than S- group reported these increases. Sixty percent of staff was aware of changes in hospital infection control policies after SARS; 93.4% was aware of notifying procedures, and 81.8% was aware of whom to notify in the hospital. Regarding infection isolation ward, Infectious Control Nurse and Infection Control Committee Chairman in the hospital, the proportions of staff that could correctly name them were 39.7%, 38.3% and 15.7% respectively. Significantly more in S+ than S- group could do so. However, more than half the staff claimed ignorance on the knowledge of infection isolation ward (56.2%), Infection Control Nurse (57.9%) and Chairman (65.3%). Our findings demonstrated that SARS crisis had some positive impact on the infection control practices and awareness of medical staff especially on those with direct SARS involvement. Implications for future control of infectious diseases are obvious.
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.
In the Malaysian setting of multi-ethnicity and high BCG coverage, interpretation of Tuberculin Skin Testing (TST) may be difficult. Between January 2001 and December 2003, a retrospective study on all adult patients with documented TST results treated for tuberculosis (TB) in chest clinics of two government hospitals was conducted to determine the reliability of TST and factors affecting its interpretation. One hundred and three patients [mean age (SD): 43 (17); male: 67%] were eligible for data collection: 72% and 57% of patients had positive TST results based on cut-off points of 10mm and 15mm respectively. The only significant univariate association with TST results was the severity of co-morbidity. A patient with co-morbidity score of 3 defined as those with any cancer, end-stage renal or liver disease, or HIV disease, was more likely to have a negative TST results [10mm cut-off point: Odd Ratio (95% CI) 6.6 (1.82 to 24.35), p = 0.003; 15mm cut-off point: 4.8 (1.21 to 18.95), p = 0.012]. A TST reading of 10mm had a higher sensitivity than 15mm as the cut-off point in diagnosing TB infection. Considering all possible confounding factors like ethnicity, prior BCG vaccination and TB burden in the population, severity of co-morbidity remains strongly predictive of a negative TST. Caution should be exercised in interpreting TST in these patients.
Study site: Chest clinic, Hospital Seremban, Hospital Kuala Pilah, Negeri Sembilan, Malaysia
Inefficient metered-dose inhaler (MDI) technique results in poor drug delivery, suboptimal disease control a possibility of inhaled medication overuse. The MDI technique of 134 government hospital and clinic followed-up adult asthmatic patients followed-up in a government hospital and a heath clinic was pragmatically assessed based on the 3 obligatory steps of adequate lip seal, appropriate hand-breath coordination and sufficient breath holding after inhalation. The relationship between technique efficiency and frequency of daily short-acting beta2-agonist (SABA) use via the MDI and asthma exacerbations over a 12-month period was also assessed. Fifty-six patients (42%) had inefficient MDI technique. All demographic and asthma-related variables between the 'efficient' and 'inefficient' technique groups of patients were comparable except for significantly longer mean years of MDI use in the 'efficient' technique group [mean (SD): 10 (7) vs. 7 (5); p=0.003]. There were no significant differences between the two groups in relation to frequency of daily SABA use or asthma exacerbations over the past 12 months. Despite having been available in Malaysia for a considerable period of time, the MDI device is still poorly handled by a large proportion of adult asthmatic patients. Changing to other more user-friendly devices or use of spacer devices to facilitate delivery should be considered for these patients.
Study site: Hospital Tuanku Jaafar, Seremban, Negeri Sembilan; Klinik Kesihatan Seremban, Malaysia
Airway inflammation can be demonstrated by the modem method of sputum induction using ultrasonic nebulizer and hypertonic saline. We studied whether compressed-air nebulizer and isotonic saline which are commonly available and cost less, are as effective in inducing sputum in normal adult subjects as the above mentioned tools. Sixteen subjects underwent weekly sputum induction in the following manner: ultrasonic nebulizer (Medix Sonix 2000, Clement Clarke, UK) using hypertonic saline, ultrasonic nebulizer using isotonic saline, compressed-air nebulizer (BestNeb, Taiwan) using hypertonic saline, and compressed-air nebulizer using isotonic saline. Overall, the use of an ultrasonic nebulizer and hypertonic saline yielded significantly higher total sputum cell counts and a higher percentage of cell viability than compressed-air nebulizers and isotonic saline. With the latter, there was a trend towards squamous cell contaminations. The proportion of various sputum cell types was not significantly different between the groups, and the reproducibility in sputum macrophages and neutrophils was high (Intraclass correlation coefficient, r [95%CI]: 0.65 [0.30-0.91] and 0.58 [0.22-0.89], p < 0.001). Overall changes in median FEV, were small and comparable between all groups. Induction using ultrasonic nebulizers together with hypertonic saline was generally less well tolerated than compressed-air nebulizers and isotonic saline. We conclude that in normal subjects, although both nebulizers and saline types can induce sputum with reproducible cellular profile, ultrasonic nebulizers and hypertonic saline are more effective but less well tolerated.
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.