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.

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.

"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.

Influence of co-morbidity in the interpretation of tuberculin skin reactivity in multi-ethnic adult patients with tuberculosis.

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.

A comparison of sputum induction methods: ultrasonic vs compressed-air nebulizer and hypertonic vs isotonic saline inhalation.

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.

Metered-dose inhaler technique in asthmatic patients--a revisit of the Malaysian scene.

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.

Disease impact and patient insight--a study on a local population of asthmatics.

The cornerstone of asthma management is achieving adequate symptom control and patient education. We studied in our local population of asthmatic patients how well their symptoms were controlled with currently prescribed treatment and their insight into the disease and its management. Over a 6-month period, 93 asthmatics recruited from two local government health clinics and a state hospital were interviewed using a standard questionnaire. Patients were classified into 4 groups based on the treatment they were on according to Global Initiative for Asthma (GINA) treatment guidelines. The number of patients in Step 1 (rescue medication alone), Step 2 (1 controller medication), Step 3 (2 controller medications) and Step 4 (at least 3 controller medications) were 8, 39, 34 and 12, respectively. Except for day symptoms in Step 1 group, fewer than 50% achieved minimum day or night symptoms and no restriction of daily activities. Questions on patient insight were only available for 50 patients. Weather change (74%), air pollution (66%) and physical stress (46%) were the three highest ranked common asthma triggers. More than half correctly recognized the important symptoms of a serious asthma attack but fewer than 15% were familiar with the peak flow meter and its use or with the asthma self-management plan. Most patients perceived that their treatment had helped reduce disease severity and exacerbations. We conclude that symptom control and some aspect of patient education are still lacking in our local asthmatics.

A study of admission criteria and early management of adult patients with acute asthma.

We studied the admission criteria and first 24-hour management of 62 asthmatic patients admitted from Accident and Emergency (A&E) department of a state hospital. Data was collected prospectively over a 6-month period from the doctors' medical records with reference to recommendations of the Malaysian Thoracic Society (MTS) on management of acute asthma. Peak Expiratory Flow Rate (PEFR) records were present in only 14.5% of the A&E notes and 54.8% of the ward notes. Most of these readings were below 75% of predicted normal values. Over half of the patients had records on ability to speak full sentences, and respiratory and pulse rates. Based on other records on criteria for life-threatening features (including arterial blood gases), 42% of patients studied had life threatening asthma exacerbations. Most received appropriate treatment as recommended by the MTS. We conclude that while most patients were admitted and treated appropriately, medical documentation regarding acute asthma assessment were inadequate in some.

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.

A comparison of sputum induction methods: ultrasonic vs compressed-air nebulizer and hypertonic vs isotonic saline inhalation.

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.