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Background: Chronic cough is a common respiratory symptom with an impact on daily activities and quality of life. Global prevalence data are scarce and derive mainly from European and Asian countries and studies with outcomes other than chronic cough. In this study, we aimed to estimate the prevalence of chronic cough across a large number of study sites as well as to identify its main risk factors using a standardised protocol and definition., Methods: We analysed cross-sectional data from 33,983 adults (≥40 years), recruited between Jan 2, 2003 and Dec 26, 2016, in 41 sites (34 countries) from the Burden of Obstructive Lung Disease (BOLD) study. We estimated the prevalence of chronic cough for each site accounting for sampling design. To identify risk factors, we conducted multivariable logistic regression analysis within each site and then pooled estimates using random-effects meta-analysis. We also calculated the population attributable risk (PAR) associated with each of the identifed risk factors., Findings: The prevalence of chronic cough varied from 3% in India (rural Pune) to 24% in the United States of America (Lexington,KY). Chronic cough was more common among females, both current and passive smokers, those working in a dusty job, those with a history of tuberculosis, those who were obese, those with a low level of education and those with hypertension or airflow limitation. The most influential risk factors were current smoking and working in a dusty job., Interpretation: Our findings suggested that the prevalence of chronic cough varies widely across sites in different world regions. Cigarette smoking and exposure to dust in the workplace are its major risk factors., Funding: Wellcome Trust., Competing Interests: Fatima Rodrigues declares grants and personal fees from A. Menarini, Boehringer Ingelheim, Teva Pharma, Novartis, GlaxoSmithKline, AstraZeneca, VitalAire and Nippon Gases outside the submitted work. Wan C. Tan received grants from the Canadian Institute of Heath Research (CIHR/Rx&D Collaborative Research Program Operating Grants- 93,326) with industry partners Astra Zeneca Canada Ltd., Boehringer-Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Merck, Novartis Pharma Canada Inc., Nycomed Canada Inc., Pfizer Canada Ltd. for conducting the longitudinal population-based Canadian Cohort of Obstructive Lung Disease (CanCOLD) study on COPD. David Mannino is a consultant to GSK, AstraZeneca, Regeneron, Genentech, COPD Foundation, and expert witness on behalf of people suing Tobacco Industry (Schlesinger Law Firm). Sonia Buist is Chair of the Data Safety & Monitoring Board for the RELIANCE Clinical Trial. Frits Franssen declares personal fees from AstraZeneca, Chiesi, GlaxoSmithKline, MSD, Pieris, and Verona Pharma. Robab Breyer-Kohansal declares consulting fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Menarini, Novartis Pharma, and Sanofi, and participation on advisory boards for AstraZeneca, Menarini, and Sanofi. Thorarinn Gislason received a grant from the Icelandic Research Fund. Kevin Mortimer declares participation on advisory boards for AstraZeneca and GlaxoSmithKline. Sylvia Hartl declares grants from GSK, Chiesi Farma, Menarini Pharma, and AstraZeneca, and participation on advisory boards for Menarini Pharma and GSK. AFSA declares a grant from the COLT Foundation (CF/01/21)., (© 2024 The Author(s).)

Background: Spirometric small airways obstruction (SAO) is common in the general population. Whether spirometric SAO is associated with respiratory symptoms, cardiometabolic diseases, and quality of life (QoL) is unknown., Methods: Using data from the Burden of Obstructive Lung Disease study (N = 21,594), we defined spirometric SAO as the mean forced expiratory flow rate between 25 and 75% of the FVC (FEF 25-75 ) less than the lower limit of normal (LLN) or the forced expiratory volume in 3 s to FVC ratio (FEV 3 /FVC) less than the LLN. We analysed data on respiratory symptoms, cardiometabolic diseases, and QoL collected using standardised questionnaires. We assessed the associations with spirometric SAO using multivariable regression models, and pooled site estimates using random effects meta-analysis. We conducted identical analyses for isolated spirometric SAO (i.e. with FEV 1 /FVC ≥ LLN)., Results: Almost a fifth of the participants had spirometric SAO (19% for FEF 25-75 ; 17% for FEV 3 /FVC). Using FEF 25-75, spirometric SAO was associated with dyspnoea (OR = 2.16, 95% CI 1.77-2.70), chronic cough (OR = 2.56, 95% CI 2.08-3.15), chronic phlegm (OR = 2.29, 95% CI 1.77-4.05), wheeze (OR = 2.87, 95% CI 2.50-3.40) and cardiovascular disease (OR = 1.30, 95% CI 1.11-1.52), but not hypertension or diabetes. Spirometric SAO was associated with worse physical and mental QoL. These associations were similar for FEV 3 /FVC. Isolated spirometric SAO (10% for FEF 25-75 ; 6% for FEV 3 /FVC), was also associated with respiratory symptoms and cardiovascular disease., Conclusion: Spirometric SAO is associated with respiratory symptoms, cardiovascular disease, and QoL. Consideration should be given to the measurement of FEF 25-75 and FEV 3 /FVC, in addition to traditional spirometry parameters., (© 2023. The Author(s).)

Background: Chronic obstructive pulmonary disease has been associated with exposures in the workplace. We aimed to assess the association of respiratory symptoms and lung function with occupation in the Burden of Obstructive Lung Disease study., Methods: We analysed cross-sectional data from 28 823 adults (≥40 years) in 34 countries. We considered 11 occupations and grouped them by likelihood of exposure to organic dusts, inorganic dusts and fumes. The association of chronic cough, chronic phlegm, wheeze, dyspnoea, forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV 1 )/FVC with occupation was assessed, per study site, using multivariable regression. These estimates were then meta-analysed. Sensitivity analyses explored differences between sexes and gross national income., Results: Overall, working in settings with potentially high exposure to dusts or fumes was associated with respiratory symptoms but not lung function differences. The most common occupation was farming. Compared to people not working in any of the 11 considered occupations, those who were farmers for ≥20 years were more likely to have chronic cough (OR 1.52, 95% CI 1.19-1.94), wheeze (OR 1.37, 95% CI 1.16-1.63) and dyspnoea (OR 1.83, 95% CI 1.53-2.20), but not lower FVC (β=0.02 L, 95% CI -0.02-0.06 L) or lower FEV 1 /FVC (β=0.04%, 95% CI -0.49-0.58%). Some findings differed by sex and gross national income., Conclusion: At a population level, the occupational exposures considered in this study do not appear to be major determinants of differences in lung function, although they are associated with more respiratory symptoms. Because not all work settings were included in this study, respiratory surveillance should still be encouraged among high-risk dusty and fume job workers, especially in low- and middle-income countries., Competing Interests: Conflict of interest: J. Ratanachina, A.F.S. Amaral, S. De Matteis, H. Lawin, K. Mortimer, D.O. Obaseki, I. Harrabi, M. Denguezli, E.F.M. Wouters, C. Janson, A. Gulsvik, H.H. Cherkaski, F. Mejza, P.A. Mahesh, A. Elsony, R. Ahmed, W. Tan, L.C. Loh, A. Rashid, M. Studnicka, A.A. Nafees, T. Seemungal, A. Aquart-Stewart, M. Al Ghobain, J. Zheng, S. Juvekar, S. Salvi, R. Jogi, T. Gislason, A.S. Buist, P. Cullinan and P. Burney have no conflict of interest to disclose. R. Nielsen reports grants from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline and Novartis, and receipt of equipment/material/services from ResMed Norway; and is President of the Norwegian Respiratory Society. D. Mannino reports royalties from Up to Date; personal fees from GlaxoSmithKline, AstraZeneca and Schlesinger Law Firm; honoraria from American Association of Respiratory Care; and stock in GlaxoSmithKline; and is the Medical Director of the COPD Foundation., (Copyright ©The authors 2023.)

Background: Small airways obstruction is a common feature of obstructive lung diseases. Research is scarce on small airways obstruction, its global prevalence, and risk factors. We aimed to estimate the prevalence of small airways obstruction, examine the associated risk factors, and compare the findings for two different spirometry parameters., Methods: The Burden of Obstructive Lung Disease study is a multinational cross-sectional study of 41 municipalities in 34 countries across all WHO regions. Adults aged 40 years or older who were not living in an institution were eligible to participate. To ensure a representative sample, participants were selected from a random sample of the population according to a predefined site-specific sampling strategy. We included participants' data in this study if they completed the core study questionnaire and had acceptable spirometry according to predefined quality criteria. We excluded participants with a contraindication for lung function testing. We defined small airways obstruction as either mean forced expiratory flow rate between 25% and 75% of the forced vital capacity (FEF 25-75 ) less than the lower limit of normal or forced expiratory volume in 3 s to forced vital capacity ratio (FEV 3 /FVC ratio) less than the lower limit of normal. We estimated the prevalence of pre-bronchodilator (ie, before administration of 200 μg salbutamol) and post-bronchodilator (ie, after administration of 200 μg salbutamol) small airways obstruction for each site. To identify risk factors for small airways obstruction, we performed multivariable regression analyses within each site and pooled estimates using random-effects meta-analysis., Findings: 36 618 participants were recruited between Jan 2, 2003, and Dec 26, 2016. Data were collected from participants at recruitment. Of the recruited participants, 28 604 participants had acceptable spirometry and completed the core study questionnaire. Data were available for 26 443 participants for FEV 3 /FVC ratio and 25 961 participants for FEF 25-75 . Of the 26 443 participants included, 12 490 were men and 13 953 were women. Prevalence of pre-bronchodilator small airways obstruction ranged from 5% (34 of 624 participants) in Tartu, Estonia, to 34% (189 of 555 participants) in Mysore, India, for FEF 25-75 , and for FEV 3 /FVC ratio it ranged from 5% (31 of 684) in Riyadh, Saudi Arabia, to 31% (287 of 924) in Salzburg, Austria. Prevalence of post-bronchodilator small airways obstruction was universally lower. Risk factors significantly associated with FEV 3 /FVC ratio less than the lower limit of normal included increasing age, low BMI, active and passive smoking, low level of education, working in a dusty job for more than 10 years, previous tuberculosis, and family history of chronic obstructive pulmonary disease. Results were similar for FEF 25-75 , except for increasing age, which was associated with reduced odds of small airways obstruction., Interpretation: Despite the wide geographical variation, small airways obstruction is common and more prevalent than chronic airflow obstruction worldwide. Small airways obstruction shows the same risk factors as chronic airflow obstruction. However, further research is required to investigate whether small airways obstruction is also associated with respiratory symptoms and lung function decline., Funding: National Heart and Lung Institute and Wellcome Trust., Translations: For the Dutch, Estonian, French, Icelandic, Malay, Marathi, Norwegian, Portuguese, Swedish and Urdu translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests DM declares being a consultant to and receiving royalties from GlaxoSmithKline, AstraZeneca, and the COPD Foundation (royalty payments are up to date) and acting as an expert witness for Schlesinger Law Firm, outside of the submitted work. RN reports grants and personal fees from AstraZeneca and GlaxoSmithKline and grants from Boehringer Ingelheim and Novartis, outside of the submitted work. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To apply radiomics analysis for overall survival prediction in chronic obstructive pulmonary disease (COPD), and evaluate the performance of the radiomics signature (RS)., Methods: This study included 344 patients from the Korean Obstructive Lung Disease (KOLD) cohort. External validation was performed on a cohort of 112 patients. In total, 525 chest CT-based radiomics features were semi-automatically extracted. The five most useful features for survival prediction were selected by least absolute shrinkage and selection operation (LASSO) Cox regression analysis and used to generate a RS. The ability of the RS for classifying COPD patients into high or low mortality risk groups was evaluated with the Kaplan-Meier survival analysis and Cox proportional hazards regression analysis., Results: The five features remaining after the LASSO analysis were %LAA -950 , AWT&#95;Pi10&#95;6 th , AWT&#95;Pi10&#95;heterogeneity, %WA&#95;heterogeneity, and VA 18mm . The RS demonstrated a C-index of 0.774 in the discovery group and 0.805 in the validation group. Patients with a RS greater than 1.053 were classified into the high-risk group and demonstrated worse overall survival than those in the low-risk group in both the discovery (log-rank test, < 0.001; hazard ratio [HR], 5.265) and validation groups (log-rank test, < 0.001; HR, 5.223). For both groups, RS was significantly associated with overall survival after adjustments for patient age and body mass index., Conclusions: A radiomics approach for survival prediction and risk stratification in COPD patients is feasible, and the constructed radiomics model demonstrated acceptable performance. The RS derived from chest CT data of COPD patients was able to effectively identify those at increased risk of mortality., Key Points: • A total of 525 chest CT-based radiomics features were extracted and the five radiomics features of %LAA -950 , AWT&#95;Pi10&#95;6 th , AWT&#95;Pi10&#95;heterogeneity, %WA&#95;heterogeneity, and VA 18mm were selected to generate a radiomics model. • A radiomics model for predicting survival of COPD patients demonstrated reliable performance with a C-index of 0.774 in the discovery group and 0.805 in the validation group. • Radiomics approach was able to effectively identify COPD patients with an increased risk of mortality, and patients assigned to the high-risk group demonstrated worse overall survival in both the discovery and validation groups., (© 2021. European Society of Radiology.)

Heterogeneous clinical manifestations and progression of chronic obstructive pulmonary disease (COPD) affect patient health risk assessment, stratification, and management. Pulmonary function tests are used to diagnose and classify the severity of COPD, but they cannot fully represent the type or range of pathophysiologic abnormalities of the disease. To evaluate whether deep radiomics from chest computed tomography (CT) images can predict mortality in patients with COPD, we designed a convolutional neural network (CNN) model for extracting representative features from CT images and then performed random survival forest to predict survival in COPD patients. We trained CNN-based binary classifier based on six-minute walk distance results (> 440 m or not) and extracted high-throughput image features (i.e., deep radiomics) directly from the last fully connected layer of it. The various sizes of fully connected layers and combinations of deep features were experimented using a discovery cohort with 344 patients from the Korean Obstructive Lung Disease cohort and an external validation cohort with 102 patients from Penang General Hospital in Malaysia. In the integrative analysis of discovery and external validation cohorts, with combining 256 deep features from the coronal slice of the vertebral body and two sagittal slices of the left/right lung, deep radiomics for survival prediction achieved concordance indices of 0.8008 (95% CI, 0.7642-0.8373) and 0.7156 (95% CI, 0.7024-0.7288), respectively. Deep radiomics from CT images could be used to predict mortality in COPD patients., (© 2021. The Author(s).)

Rationale: The Global Burden of Disease program identified smoking and ambient and household air pollution as the main drivers of death and disability from chronic obstructive pulmonary disease (COPD). Objectives: To estimate the attributable risk of chronic airflow obstruction (CAO), a quantifiable characteristic of COPD, due to several risk factors. Methods: The Burden of Obstructive Lung Disease study is a cross-sectional study of adults, aged ≥40, in a globally distributed sample of 41 urban and rural sites. Based on data from 28,459 participants, we estimated the prevalence of CAO, defined as a postbronchodilator FEV 1 -to-FVC ratio less than the lower limit of normal, and the relative risks associated with different risk factors. Local relative risks were estimated using a Bayesian hierarchical model borrowing information from across sites. From these relative risks and the prevalence of risk factors, we estimated local population attributable risks. Measurements and Main Results: The mean prevalence of CAO was 11.2% in men and 8.6% in women. The mean population attributable risk for smoking was 5.1% in men and 2.2% in women. The next most influential risk factors were poor education levels, working in a dusty job for ≥10 years, low body mass index, and a history of tuberculosis. The risk of CAO attributable to the different risk factors varied across sites. Conclusions: Although smoking remains the most important risk factor for CAO, in some areas, poor education, low body mass index, and passive smoking are of greater importance. Dusty occupations and tuberculosis are important risk factors at some sites.

Background: It is uncertain whether peak flow measurement is best done in the standing or sitting position., Methods: In this cross-over study, study participants were randomized to perform the initial peak expiratory flow (PEF) measurement in either standing or sitting position. The highest of three readings in each position were compared using paired t-test. A mean difference of <±25 l/min was set as the equivalence limits. Test of equivalence of standing and sitting PEF measurements was done using MedCalc Software. Test of agreement of standing and sitting PEF was assessed by Lin's concordance correlation coefficient and Bland-Altman limits of agreement., Results: Of the 100 study participants, 50% of them had asthma. There was a statistically significant difference between the standing and sitting PEF in adults suffering from asthma [mean difference 11 l/min, 95% confidence interval (CI) = 4 to 19], but not in the healthy individuals (mean difference 3 l/min, 95% CI = -6 to 12). The observed differences in PEF were small and may not be clinically important. In adults with and without asthma, the standing and sitting PEF were highly correlated and satisfied the test of equivalence., Conclusions: The PEF in the standing and sitting positions was equivalent in adults. Therefore, performing PEF in either position is acceptable. However, health care practitioners should be aware of the small reduction in PEF when it is done in the sitting position. It is desirable that the position used is documented and the same position is used wherever possible., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: COPD is a heterogeneous disease demonstrating inter-individual variation. A high COPD prevalence in Chinese populations is described, but little is known about disease clusters and prognostic outcomes in the Chinese population across Southeast Asia. We aim to determine if clusters of Chinese patients with COPD exist and their association with systemic inflammation and clinical outcomes., Research Question: We aim to determine if clusters of Chinese patients with COPD exist and their association with clinical outcomes and inflammation., Study Design and Methods: Chinese patients with stable COPD were prospectively recruited into two cohorts (derivation and validation) from six hospitals across three Southeast Asian countries (Singapore, Malaysia, and Hong Kong; n = 1,480). Each patient was followed more than 2 years. Clinical data (including co-morbidities) were employed in unsupervised hierarchical clustering (followed by validation) to determine the existence of patient clusters and their prognostic outcome. Accompanying systemic cytokine assessments were performed in a subset (n = 336) of patients with COPD to determine if inflammatory patterns and associated networks characterized the derived clusters., Results: Five patient clusters were identified including: (1) ex-TB, (2) diabetic, (3) low comorbidity: low-risk, (4) low comorbidity: high-risk, and (5) cardiovascular. The cardiovascular and ex-TB clusters demonstrate highest mortality (independent of Global Initiative for Chronic Obstructive Lung Disease assessment) and illustrate diverse cytokine patterns with complex inflammatory networks., Interpretation: We describe clusters of Chinese patients with COPD, two of which represent high-risk clusters. The cardiovascular and ex-TB patient clusters exhibit high mortality, significant inflammation, and complex cytokine networks. Clinical and inflammatory risk stratification of Chinese patients with COPD should be considered for targeted intervention to improve disease outcomes., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: COPD-associated mortality was examined using a novel approach of phenotyping COPD based on computed tomography (CT)-emphysema index from quantitative CT (QCT) and post-bronchodilator (BD) forced expiratory volume in 1 second (FEV 1 ) in a local Malaysian cohort., Patients and Methods: Prospectively collected data of 112 eligible COPD subjects (mean age, 67 years; male, 93%; mean post-BD FEV 1 , 45.7%) was available for mortality analysis. Median follow-up time was 1,000 days (range, 60-1,400). QCT and clinicodemographic data were collected at study entry. Based on CT-emphysema index and post-BD FEV 1 % predicted, subjects were categorized into "emphysema-dominant," "airway-dominant," "mild mixed airway-emphysema," and "severe mixed airway-emphysema" diseases., Results: Sixteen patients (14.2%) died of COPD-associated causes. There were 29 (25.9%) "mild mixed," 23 (20.5%) "airway-dominant," 15 (13.4%) "emphysema-dominant," and 45 (40.2%) "severe mixed" cases. "Mild mixed" disease was proportionately more in Global Initiative for Chronic Obstructive Lung Disease (GOLD) Group A, while "severe mixed" disease was proportionately more in GOLD Groups B and D. Kaplan-Meier survival estimates showed increased mortality risk with "severe mixed" disease (log rank test, p =0.03) but not with GOLD groups ( p =0.08). Univariate Cox proportionate hazard analysis showed that age, body mass index, long-term oxygen therapy, FEV 1 , forced volume capacity, COPD Assessment Test score, modified Medical Research Council score, St Georges' Respiratory Questionnaire score, CT-emphysema index, and "severe mixed" disease (vs "mild mixed" disease) were associated with mortality. Multivariate Cox analysis showed that age, body mass index, and COPD Assessment Test score remain independently associated with mortality., Conclusion: "Severe mixed airway-emphysema" disease may predict COPD-associated mortality. Age, body mass index, and COPD Assessment Test score remain as key mortality risk factors in our cohort., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Rationale: Evidence supporting the association of COPD or airflow obstruction with use of solid fuels is conflicting and inconsistent., Objective: To assess the association of airflow obstruction with self-reported use of solid fuels for cooking or heating., Methods: We analysed 18,554 adults from the BOLD study, who had provided acceptable post-bronchodilator spirometry measurements and information on use of solid fuels. The association of airflow obstruction with use of solid fuels for cooking or heating was assessed by sex, within each site, using regression analysis. Estimates were stratified by national income and meta-analysed. We carried out similar analyses for spirometric restriction, chronic cough and chronic phlegm., Measurements and Main Results: We found no association between airflow obstruction and use of solid fuels for cooking or heating (ORmen=1.20, 95%CI 0.94-1.53; ORwomen=0.88, 95%CI 0.67-1.15). This was true for low/middle and high income sites. Among never smokers there was also no evidence of an association of airflow obstruction with use of solid fuels (ORmen=1.00, 95%CI 0.57-1.76; ORwomen=1.00, 95%CI 0.76-1.32). Overall, we found no association of spirometric restriction, chronic cough or chronic phlegm with the use of solid fuels. However, we found that chronic phlegm was more likely to be reported among female never smokers and those who had been exposed for ≥20 years., Conclusion: Airflow obstruction assessed from post-bronchodilator spirometry was not associated with use of solid fuels for cooking or heating.

Background and Objective: As a Burden of Obstructive Lung Disease (BOLD) collaboration, we studied the prevalence of chronic obstructive pulmonary disease (COPD) and its associated risk factors in a suburban population in Malaysia., Methods: Nonhospitalized men or women of age ≥ 40 years from a Penang district were recruited by stratified simple random sampling. Participants completed detailed questionnaires on respiratory symptoms and exposure to COPD risk factors. Prebronchodilator and post-bronchodilator spirometry conducted was standardized across all international BOLD sites in device and data quality control., Results: Of the 1218 individuals recruited for the study, 663 (340 men and 323 women) had complete questionnaire data and acceptable post-bronchodilator spirometry. The estimated population prevalence of Global Initiative for Chronic Obstructive Lung Disease (GOLD) ≥ stage I was 6.5% or 3.4% based on either fixed forced expiratory volume in 1 s/forced vital capacity ratio of <0.7 or National Health and Nutritional Examination Survey-derived lower limit of normal ratio while the prevalence of GOLD ≥ stage II was either 4.6% or 3.1%, respectively. Multivariate logistic regression analysis showed independent association between all stages of COPD with cigarette smoking pack years (adjusted odds ratio per 10-year increase: 1.73; 95% confidence interval: 1.09-2.75), use of biomass fuel for cooking (1.61; 1.10-2.36) and exposure to dusty job (1.50; 1.09-2.06)., Conclusion: This study represented the first robust population-based epidemiology data on COPD for Malaysia. Compared with other sites globally, our estimated population prevalence was relatively low. In addition to cigarette smoking, use of biomass fuel and exposure to dusty job represented significant risk to the development of COPD., (© 2016 Asian Pacific Society of Respirology.)

Background and Objectives: Chronic obstructive pulmonary disease (COPD) is responsible for significant morbidity and mortality worldwide. We evaluated the characteristics of stable COPD patients in the pulmonology clinics of seven Asian cities and also evaluated whether the exposure to biomass fuels and dusty jobs were related to respiratory symptoms, airflow limitation, and quality of life in the COPD patients., Methods: This cross-sectional observational study recruited 922 COPD patients from seven cities of Asia. The patients underwent spirometry and were administered questionnaires about their exposure to cigarette smoking, biomass fuels, and dusty jobs in addition to respiratory symptoms and health related quality of life., Results: Of the patients, there appeared to be variations from city to city in the history of exposure to biomass fuels and dusty jobs and also in respiratory symptoms of cough, phlegm, wheeze, and dyspnea. These symptoms were more frequent in those COPD patients with a history of exposure to biomass fuels than without and those with a history of exposure to dusty jobs than without (P < 0.01 for all comparisons). Airflow limitation was more severe in those COPD patients with a history of exposure to biomass fuels than without (52.2% predicted versus 55.9% of post-bronchodilator forced expiratory volume in 1 second [FEV(1)], P = 0.009); quality of life was poorer in those with exposure to biomass fuels than without (40.4 versus 36.2 of the St George's Respiratory Questionnaire [SGRQ] total score, P = 0.001). Airflow limitation was more severe in those COPD patients with a history of exposure to dusty jobs than without (51.2% predicted versus 57.3% of post-bronchodilator FEV(1), P < 0.001); quality of life was poorer in those with dusty jobs than without (41.0 versus 34.6 of SGRQ score, P = 0.006)., Conclusion: In Asian cities, the characteristics of COPD patients vary and the history of exposure to biomass fuels or dusty jobs was related to frequency of symptoms, severe airflow limitation, and poor quality of life.

Background: Budesonide/formoterol used for both maintenance and reliever therapy has been shown to benefit patients with persistent asthma. We evaluated patient satisfaction and asthma control among Malaysian patients prescribed budesonide/formoterol as single maintenance and reliever therapy in a real-life clinical practice., Methods: Adult patients diagnosed with partially controlled or uncontrolled asthma were recruited in a 6-month, prospective, open-label study involving ten hospital-based chest clinics in Malaysia. Patients were prescribed one or two inhalations of budesonide/formoterol Turbuhaler (160/4.5 μg per inhalation) twice daily as maintenance therapy and additional inhalation as reliever therapy. Maintenance doses were decided by physicians based on Global Initiative for Asthma-defined treatment objectives. The primary outcome measure was the change in mean Satisfaction with Asthma Treatment Questionnaire (SATQ) scores from baseline to an average of 3 months and 6 months. Secondary outcome was the change in mean Asthma Control Questionnaire 5-item version (ACQ-5) scores from baseline to an average of 3 months and 6 months and the proportion of patients achieving the minimum clinically important difference., Results: Of 201 eligible patients recruited, 195 completed the study. Overall, SATQ mean (standard deviation) score was significantly improved from 5.1 (0.76) at baseline to 5.5 (0.58) (P < 0.001). The increase was observed in all domains of SATQ and had occurred at 3 months for most patients. ACQ-5 mean (standard deviation) score was significantly reduced from 2.2 (1.13) at baseline to 1.2 (0.95) (P < 0.001). A total of 132 (67.7.1%) patients had achieved the minimal clinically important difference (≥0.5) of ACQ-5 scores at study end., Conclusion: In a nationwide study, budesonide/formoterol maintenance and reliever therapy achieved greater patient satisfaction and better asthma control compared with previous conventional asthma regimes among Malaysian patients treated in a real-life practice setting. Such an approach may represent an important treatment alternative for our local patients with persistent asthma.

We prospectively evaluated the use of a simple 3-Minute Respiratory Exerciser Test (3MRET) that estimates perception of dyspnea to identify patients at risk of asthma exacerbations. A total of 146 stable asthmatics (42 under-perceivers, 69 normal perceivers, and 35 over-perceivers) received follow-up for 12 months. The mean (SD) unscheduled visits to doctors among under-, normal, and over-perceivers were 1.8 (1.2), 2.2 (1.8), and 3.1 (2.3), respectively (p = 0.008). The mean (SD) hospital admissions among the groups were 1.3 (0.5), 1.2 (0.6), and 1.7 (1.3), respectively (p = 0.026). Compared to normal perceivers, over-perceivers had increased risks of unscheduled visits (OD: 5.12; 95% CI = 1.59 to 16.47) and hospital admissions (OD: 0.31; 95% CI = 0.23 to 0.41), defined as > or =2 events in 12 months. The association between over-perceiver and unscheduled visits remained significant after adjusting for forced expiratory volume in 1 second (FEV(1)). Sensitivity and specificity of over-perceivers are 77% and 47%, respectively, for unscheduled visits and 37% and 78%, respectively, for hospital admissions, with significantly better area under ROC for unscheduled visits (0.67 [95% CI = 0.56 to 0.77]; p = 0.003) than for hospital admissions (0.58 [0.471 to 0.70]; p = 0.127). We conclude that the 3MRET may have a role in identifying asthmatic patients with over-perception of dyspnea at risk of clinically important asthma exacerbations.

Objective: Written action plans are regarded as an important part of asthma self-management education and yet they may not be understood by those with limited literacy skills. This study was designed to produce an understandable pictorial asthma action plan., Methods: With advice from a group of doctors and nurses a "standard" written action plan was translated by a medical artist into a series of pictorial images. These were assessed using the techniques of guessability and translucency by a series of adults attending a specialist asthma clinic in London and the same process was subsequently used to assess comprehensibility of the images and plans amongst a group of Somalis living in Manchester, UK and Malaysians in Seremban, Malaysia., Results: Guessability testing showed that the majority of pictograms were well understood by each of the study groups. Translucency testing revealed close agreement with intended meaning for the majority of the images. One image, depicting extra use of reliever medication scored less well in all populations; two other images scored less well in the Somali and Malaysian groups and reflect less use of certain inhaler devices in other countries. The overall plan was well understood by all patients who were able to adequately recount the appropriate actions to take in different clinical scenarios., Conclusion: We have developed a pictorial asthma action plan understandable by 3 different populations of patients with asthma., Practice Implications: Pictorial representations have been shown by other studies in other situations to be an effective method of reinforcing the spoken word. The pictorial asthma action plan developed for this study has been shown to be comprehensible, personalised to the individual in the usual fashion. It is now suitable for further evaluation in clinical practice.

A self-answered, anonymously completed, nationwide questionnaire survey was conducted between June 2002 and May 2003 among Malaysian doctors through post and at medical meetings. Findings based on 116 government and 110 private doctors who satisfactorily completed the forms (effective respondent rate: 30.1%) showed that more than 70% of government and private doctors claimed familiarity with asthma CPGs but proportionately more private doctors considered them "unworkable" and were reluctant to adopt them in their practice setting, quoting cost as the primary reason. Between those who frequently adopted the CPGs and those who did not, there was an equally high proportion of inappropriate prescribing. Despite the shortcomings of such a survey, our findings suggest that medicinal cost and practitioner's prescribing practices are important in the acceptance and execution of asthma CPGs recommendations.

Introduction: In Malaysia, Klebsiella pneumoniae ranks high as a cause of adult pneumonia requiring hospitalisation., Patients and Methods: With concern over its rising microbial resistance, we explored the association of empiric antibiotics choices with the hospital outcomes of patients treated for microbial proven K. pneumoniae pneumonia in an urban-based teaching hospital., Results: In 313 eligible cases reviewed retrospectively, hospital mortality and requirement for ventilation were 14.3% and 10.8% respectively. Empiric regimes that had in vitro resistance to at least one empiric antibiotic (n = 90) were associated with higher hospital mortality (23.3% vs. 10.8%, P = 0.004) with risk increased by about two-fold [Odds ratio (OR), 2.5; 95% confidence interval (CI), 1.3 to 4.8]. Regimes (n = 84) other than the commonly recommended "standard" regimes (a beta-lactam stable antibiotic with or without a acrolide) were associated with higher ventilation rates (16.7% vs. 8.8%, P = 0.047) with similar increased risk [OR, 2.0; 95% CI, 1.0 to 4.3]., Conclusions: Our findings reiterate the clinical relevance of in vitro microbial resistance in adult K. pneumoniae pneumonia and support empiric regimes that contain beta-lactam stable antibiotics.

Klebsiella pneumoniae ranks high as a cause of adult pneumonia requiring hospitalization in Malaysia. To study whether extended-spectrum b-lactamase (ESBL) producing K. pneumoniae was linked to hospital outcomes, we retrospectively studied 441 cases of adult respiratory tract infections with microbial proven K. pneumoniae from an urban-based university teaching hospital between 2003 and 2004. 47 (10.6%) cases had ESBL. Requirement for ventilation and median length of hospital stay, were greater in 'ESBL' than in 'non-ESBL' group [34% vs. 7.4%, p<0.001; 14 days vs. 5 days, p<0.001 respectively] but not crude hospital mortality rate [21.3% vs. 12.4%, p=0.092]. There was a four-fold increased risk of requiring ventilation [4.61 (2.72-7.85)] when ESBL was present. Our findings support the association of ESBL producing K. pneumoniae with adversed hospital outcomes and reiterate the need for vigilance on the part of treating clinicians.

Introduction: Medical talks, newsletter circulars, scientific meetings and conferences, and interaction with members of the pharmaceutical industry, have become convenient means of carrying out continuing medical education (CME) for many busy doctors., Materials and Methods: To study the perceived importance of these various CME activities, a self-completed posted questionnaire survey was conducted among registered practitioners of a densely populated urban state in Malaysia., Results: Of the 172 respondents [male, 77%; hospital-based, 37%; general practitioner (GP), 55%; private practice, 70%; respondent rate of 19.5%], most preferred local conferences and endorsements by local experts to their foreign counterparts. Meetings or conferences sponsored by the pharmaceutical industry were ranked similarly with those without such links, while the reputation of the pharmaceutical firms was of foremost importance. Among GPs (n = 95) and non-GPs (n = 77), medical society newsletters were rated significantly higher by GPs while overseas conferences were rated higher by non-GPs., Conclusion: Our findings provide an important first look at this under-explored area among Malaysian doctors and described a high degree of acceptance for the involvement of the pharmaceutical industry in CME activities.

In Malaysia, many patients opted out of cancer-specific treatment for various reasons. This study was undertaken to investigate the survival rate of patients with stages I to III non-small cell lung cancer (NSCLC) who opted out of treatment, compared with those who accepted treatment. Case records of 119 patients diagnosed with NSCLC between 1996 and 2003 in two urban-based hospitals were retrospectively examined. Survival status was ascertained from follow-up medical clinic records or telephone contact with patients or their next-of-kin. Median (25-75% IQR) survival rate for 79 patients who accepted and 22 patients who opted out of treatment, were 8.6 (16.0-3.7) and 2.2 (3.5-0.8) months respectively [log rank p< 0.001, Kaplan-Meier survival analysis]. Except for proportionately more patients with large cell carcinoma who declined treatment, there was no significant difference between the two groups in relation with age, gender, ethnicity, tumour stage, and time delays between symptom onset and treatment or decision-to-treat. We concluded that there was a small but significant survival benefit in accepting cancer-specific treatment. The findings imply that there is no effective alternative therapy to cancer-specific treatment in improving survival. However, overall prognosis for patients with NSCLC remains dismal.

The emergence of severe acute respiratory syndrome (SARS) had caused fear and anxiety of unprecedented proportion. To examine the impact of SARS on the medical students in a private medical university, a self-reporting questionnaire study was carried out to assess the factual knowledge, anxiety level and perception of the crisis, among the students. The two-week study (between 12 and 23 May, 2003) was carried out three weeks after the first reported SARS-related death in Malaysia. Ninety-one Phase I (junior) and 113 Phase II (senior) students completed the questionnaires. A large majority of students of Phase I and II were correct in their factual knowledge and were sensible in their perception of the future and the handling of the crisis by government(s). However, phase 1 students expressed significantly greater degree of anxiety compared to Phase II in relation to attendance and personal protection in hospital, and in meeting people coughing in public places. The lesser degree of anxiety expressed by phase II senior students may be due in part, to a more realistic assessment of SARS risk brought about by maturity, time spent in hospital and interaction with clinical lecturers and medical staff.

While evidence indicates that early stage disease has better prognosis, the effect of delay in presentation and treatment of patients with non-small cell lung cancer (NSCLC) on survival is debatable. A retrospective study of 122 Malaysian patients with NSCLC was performed to examine the presentation and treatment delay, and its relation with patient survival. Median (25-75% IQR) interval between onset of symptoms and first hospital consultation (patient delay) and between first hospital consultation and treatment or decision to treat (doctor delay) were 2 (1.0- 5.0) and 1.1 (0.6-2.4) months respectively. The median survival rates in patient delay of <1, 1 to 3, and >3 months were 4.1 (9.9-1.7), 5.1 (10.9-3.2) and 5.7 (12.3-2.1) months respectively (log rank p=0.648), while in doctor delay, <30, 30-60, >60 days, the rates were 4.1 (10.8-1.8), 7.6 (13.7-3.2) and 5.3 (16.0-3.0) months respectively (p=0.557). Most patients presented and were treated in a relatively short time, and delays did not appear to influence survival. This Asian data is consistent with those from Western population, reiterating the need for public health measures that can identify disease early..

Measurement of disability and breathlessness in asthma is important to guide treatment. Using an incentive spirometer, Triflo II (Tyco Healthcare, Mansfield, MA, USA), we developed a three-minute respiratory exercise test (3-MRET) to score the maximal breathing capacity (MBC) and perception of dyspnea (POD) index by means of repetitive inspiratory efforts achieved within 3 minutes. POD index was calculated based on the ratio of breathlessness on visual analogue scale over MBC score. In 175 normal healthy subjects and 158 asthmatic patients of mild (n = 26), moderate (n = 78), and severe (n = 54), severity, the mean (95% CI) MBC scores in mild, moderate, and severe asthma patients were 168 (145-192), 153 (136-169), and 125 (109-142) respectively, and 202 (191-214) in normal subjects (p < 0.001). The mean POD index in mild, moderate, and severe asthma patients was 16 (9-23), 25 (14-37), and 57 (14-100), respectively, and 6 (4-7) in normal subjects (p < 0.001). Intraclass correlation coefficients for MBC score and POD index in 17 asthmatic and 20 normal subjects were high. In 14 asthmatic patients randomized to receiving nebulized beta2-agonist or saline in a cross-over, double-blind study, % forced expiratory volume in one second (FEV1) change correlated with % change in MBC score [r(s) = 0.49, p < 0.01] and POD index [r(s)-0.46, p = 0.012]. In 21 asthmatic and 26 normal subjects, the MBC score and POD index correlated with the walking distance and walking POD index of the six-minute walking test (6MWT). We conclude that 3MRET is discriminative between asthmatic patients of varying severity and normal subjects, is reproducible, is responsive to bronchodilator effect, and is comparable with 6MWT. Taken together, it has the potential to score disability and POD in asthma simply and effectively.

The emergence of severe acute respiratory syndrome (SARS) had caused fear and anxiety of unprecedented proportion. To examine the impact of SARS on the medical students in a private medical university, a self-reporting questionnaire study was carried out to assess the factual knowledge, anxiety level and perception of the crisis, among the students. The two-week study (between 12 and 23 May, 2003) was carried out three weeks after the first reported SARS-related death in Malaysia. Ninety-one Phase I (junior) and 113 Phase II (senior) students completed the questionnaires. A large majority of students of Phase I and II were correct in their factual knowledge and were sensible in their perception of the future and the handling of the crisis by government(s). However, phase 1 students expressed significantly greater degree of anxiety compared to Phase II in relation to attendance and personal protection in hospital, and in meeting people coughing in public places. The lesser degree of anxiety expressed by phase II senior students may be due in part, to a more realistic assessment of SARS risk brought about by maturity, time spent in hospital and interaction with clinical lecturers and medical staff.

Objectives: Current clinical practice guidelines, including those in south Asia, recommend the addition of a macrolide to a broad-spectrum antibiotic for the treatment of severe hospitalized community-acquired pneumonia (CAP). The aim of this study was to observe the influence of macrolide addition on clinical outcomes of hospitalized adult patients with CAP., Methodology: Over a 16-month period between 2002 and 2004, 141 eligible patients were prospectively recruited from an urban-based teaching hospital in Malaysia., Results: Of the 141 patients, 63 (44.7%) patients (age (standard deviation (SD)) 56 (20.0) years; 50.8% male) received a macrolide-containing antibiotic regimen, while 78 (55.3%; age (SD) 57 (20.2) years; 52.6% male) were on a single broad-spectrum antibiotic only. In total, 39 (27.7%) and 102 (72.3%) patients had severe and 'non-severe' pneumonia, respectively. Irrespective of whether they had severe or non-severe pneumonia, there were no significant differences in mortality (non-severe pneumonia, 6.5% vs. 5.4%, P = 0.804; severe pneumonia, 17.6% vs. 18.2%, P = 0.966), need of ventilation (non-severe pneumonia, 8.7% vs. 3.6%, P = 0.274; severe pneumonia, 23.5% vs. 13.6%, P = 0.425) or median length of hospital stay (non-severe pneumonia, 5.5 vs. 5 days, P = 0.954; severe pneumonia, 7 vs. 6 days, P = 0.401) between the two treatment regimens., Conclusion: This observational, non-randomized study suggests that addition of a macrolide may not convey any extra clinical benefits in adult hospitalized patients with CAP.

A self-answered, anonymously completed questionnaire survey was performed between June 2002 and May 2003 where doctors from government and private sectors in Malaysia were invited to participate by post or during medical meetings. One hundred and sixteen government doctors and 110 private doctors provided satisfactorily completed questionnaires (effective respondent rate: 30.1%). The most preferred medications for 'first-line', 'second-line' and 'third-line' treatment were for government doctors: inhaled short-acting beta2-agonist (SABA) (98%), inhaled corticosteroids (CS) (75%), and leukotriene antagonist (52%); and for private doctors: oral SABA (81%), inhaled CS (68%), and oral CS (58%). The first choice inhaler device for most government and private doctors were metered dose inhalers, with cost and personal preferences (for private doctors), and technical ability (for government doctors) as the key considerations when deciding on the choice of device. This benchmark data on the asthma prescribing practices of a healthcare delivery system fully dichotomized into government and private sector, provides evidence for practice differences affected by the nature of the healthcare system, and might have implications on healthcare systems of other countries that share similarities with that of Malaysia.

Perceived breathlessness played an important role in guiding treatment in asthma. We developed a simple, user-friendly method of scoring perception of dyspnoea (POD) using an incentive spirometer, Triflo II (Tyco Healthcare, Mansfield, USA) by means of repetitive inspiratory efforts achieved within three minutes in 175 normal healthy subjects and 158 asthmatic patients of mild (n=26), moderate (n=78) and severe (n=54). Severity was stratified according to GINA guideline. The mean POD index in normal subjects, and asthmatic patients of mild, moderate and severe severity were: 6 (4-7) 16 (9-23), 25 (14-37), and 57 (14-100) respectively (p<0.001 One-Way ANOVA). Based on 17 asthmatic and 20 normal healthy subjects, intraclass correlation coefficients for POD index within subjects were high. In 14 asthmatic patients randomized to receiving nebulised b(2)-agonist or saline in a crossover, double-blind study, % FEV(1) change correlated with % changes in POD index [r(s) -0.46, p=0.012]. Finally, when compared with 6-minutes walking test (6MWT) in an open label study, respiratory POD index correlated with walking POD index in 21 asthmatic patients [r(s)= 0.58 (0.17 to 0.81) (p=0.007] and 26 normal subjects [0.50 (0.13 to 0.75) (p=0.008)]. We concluded that this test is discriminative between asthmatic patients of varying severity and from normal subjects, is reproducible, responsive to bronchodilator effect, and comparable with 6MWT. Taken together, it has the potential to score disability and POD in asthma effectively and simply.

Objectives: Prediction of mortality in patients with community-acquired pneumonia (CAP) can be assessed using clinical severity scores on admission to hospital. The clinical benefit of such tools is untested in Asian countries. The aim of this study was to determine the early adverse prognostic factors in patients hospitalized with CAP in Malaysia and to assess the usefulness of the British Thoracic Society (BTS) severity criteria., Methodology: A prospective study was undertaken of all adult patients admitted between August 2002 and March 2003 in an urban-based university teaching hospital., Results: One hundred and eight patients (mean +/- SD age 55 +/- 20 years; 58% men) were eligible for the study. Thirteen patients (12%) died in hospital and 95 (88%) survived to hospital discharge. Older age, the presence of chronic illness, severity of comorbidity, reduced oxygen saturation and higher blood urea were associated with mortality during admission. Multivariate logistic regression of these variables identified reduced oxygen saturation as the only independently associated variable. BTS criteria fared poorly in predicting mortality compared with clinical assessment by attending clinicians (36-fold increased risk of death by 'clinical assessment' vs two-threefold by 'BTS criteria')., Conclusions: In hospitalized patients with CAP, certain factors are adversely associated with mortality during admission. Severity criteria validated in specific countries might not be universally applicable.

In practice, asthmatic patients whose metered-dose inhaler (MDI) technique is inefficient are either corrected or changed to dry powder breath-actuated or spacer device that is easier to handle. Based on 'real life clinic circumstances', we studied 15 symptomatic asthmatic patients whose MDI techniques were inefficient that either received correction in their technique (n=9) or were changed to turbohaler (n=6). For comparison, we also studied a similar group of symptomatic asthmatic patients (n=6) with appropriate MDI techniques that were treated by doubling of inhaled corticosteroid (ICS) dose. After 4 weeks, FEV(1) and symptom scores in the turbohaler group was significantly improved from baseline but not in the corrected MDI group. The group whose ICS dose was doubled also showed significant improvement in symptom scores but not in FEV(1). We question the benefit gained by correcting MDI technique in some asthmatic patients compared to that of switching over to more user-friendly devices such as turbohaler. In our study, the improvement observed with turbohaler appears to be more than a mere doubling of drug delivery to the lungs and may relate to the recognized greater consistency of drug delivery by turbohaler compared to MDI device.