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© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license., 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 (FEF25-75) less than the lower limit of normal or forced expiratory volume in 3 s to forced vital capacity ratio (FEV3/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 FEV3/FVC ratio and 25 961 participants for FEF25-75. 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 FEF25-75, and for FEV3/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 FEV3/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 FEF25-75, 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., National Heart and Lung Institute and Wellcome Trust. Supported by Wellcome Trust grant 085790/Z/08/Z for the BOLD study

To apply radiomics analysis for overall survival prediction in chronic obstructive pulmonary disease (COPD), and evaluate the performance of the radiomics signature (RS). 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. The five features remaining after the LASSO analysis were %LAA−950, AWT_Pi10_6th, AWT_Pi10_heterogeneity, %WA_heterogeneity, and VA18mm. 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. 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. • A total of 525 chest CT-based radiomics features were extracted and the five radiomics features of %LAA −950 , AWT_Pi10_6 th , AWT_Pi10_heterogeneity, %WA_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.

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 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.

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.

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). Objective: 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 FEV1-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.

To apply radiomics analysis for overall survival prediction in chronic obstructive pulmonary disease (COPD), and evaluate the performance of the radiomics signature (RS).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.The five features remaining after the LASSO analysis were %LAAA 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.• A total of 525 chest CT-based radiomics features were extracted and the five radiomics features of %LAA

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.

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 (FEV1) 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 FEV1, 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 FEV1% 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, FEV1, 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.

Rationale: Evidence supporting the association of chronic obstructive pulmonary disease or airflow obstruction with use of solid fuels is conflicting and inconsistent. Objectives: To assess the association of airflow obstruction with self-reported use of solid fuels for cooking or heating. Methods: We analyzed 18,554 adults from the BOLD (Burden of Obstructive Lung Disease) 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-analyzed. We performed 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 (odds ratio [OR] for men, 1.20 [95% confidence interval (CI), 0.94–1.53]; OR for women, 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 (OR for men, 1.00 [95% CI, 0.57–1.76]; OR for women, 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 or longer. Conclusions: 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

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.

Background: Detailed characterization of hospitalized COPD patients and their clinical outcomes in Malaysia is lacking. Such understanding is important to combat the rising COPD burden. Patients and Methods: 120 patients hospitalized for COPD exacerbation in an urban-based state hospital were consecutively recruited. Comprehensive data on socio-demographics, Bristol COPD Knowledge Questionnaire (BCKQ), Hospital Anxiety and Depression Score, clinical parameters, healthcare experiences and hospital outcomes was prospectively collected from medical records and interviews with patients and/or carers. Results: GOLD A, B, C and D categories consisted of 7 (5.8%), 76 (63.3%), 2 (1.6%), and 35 (29.1%) patients respectively. The mean age (SD) was 68 (10.2) years old and 91% were male. Most had only primary school education and low incomes. Most were smokers and frequent exacerbators. About half smoked ≥40 pack years and 10% had ≥5 exacerbations a year. 55% had no comorbidites. The commonest comorbidity was diabetes (20%). 15.8% had previous TB infection. 6.6% had probably ACOS. Over half were treated with inhaled corticosteroids for ≥6 months. Mean BCKQ score was

Yeon-Mok Oh,1 Arvind B Bhome,2 Watchara Boonsawat,3 Kirthi Dias Gunasekera,4 Dushantha Madegedara,5 Luisito Idolor,6 Camilo Roa,6 Woo Jin Kim,7 Han-Pin Kuo,8 Chun-Hua Wang,8 Le Thi Tuyet Lan,9 Li-Cher Loh,10 Choo-Khoon Ong,10 Alan Ng,11 Masaharu Nishimura,12 Hironi Makita,12 Edwin K Silverman,13 Jae Seung Lee,1 Ting Yang,14 Yingxiang Lin,14 Chen Wang,14 Sang-Do Lee1 1Department of Pulmonary and Critical Care Medicine and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 2Department of Pulmonary and Critical Care, "Friends of the Breathless" Foundation, Pune, India; 3Department of Medicine, Khon Kaen University, Khon Kaen, Thailand; 4Central Chest Clinic, Colombo and National Hospital of Sri Lanka; 5Respiratory Disease Treatment Unit and Teaching Hospital Kandy, Sri Lanka; 6Section of Respiratory Services and Physical Therapy and Rehabilitation Lung Center of the Philippines, Quezon City, Philippines; 7Department of Internal Medicine, Kangwon National University, Kang Won, Korea; 8Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan; 9Respiratory Care Center, University Medical Center Ho Chi Minh City, Vietnam; 10Department of Medicine, Penang Medical College, Penang, Malaysia; 11Department of Respiratory and Critical Care Medicine, Tan Tock Seng Hospital, Singapore; 12Division of Respiratory Medicine, Department of Internal Medicine, Hokkaido University Hospital, Sapporo, Japan; 13Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; 14Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaAll authors made an equal contribution to this studyBackground 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 [FEV1], 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 FEV1, 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.Keywords: COPD, Asia, biomass, dust

Our study showed that mouthpiece size does not affect the consistency of measurement in either spirometry or peak flow meter in healthy adults. This is not surprising as mouthpiece diameter size of 30 mm and 22 mm are well attested in science and experience to be used for channeling unimpeded flow in lung function tests. Mouthpiece with size smaller than 22 mm like the spirettes used in EasyOne® Plus spirometry has also been long used in international multi-center studies like Burden of Obstructive Lung Disease (BOLD) [1] and presents no measurement problems. Our study however showed a clear preference for smaller size mouthpiece compared to the standard 30 mm one that is commonly used. We assume that this is due to the ease of making a tight lip seal over the mouthpiece with smaller ones. While this is observed in healthy subjects without lung conditions, it is possible that subjects who are breathless or with chronic lung diseases may also have such preference since making such maneuver can be even more difficult.

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 asor =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. Recombinant human (rHu) interleukin (IL)-12 has been shown to reduce levels of blood and sputum eosinophils in patients with mild allergic asthma in a randomized controlled study. The aim of the study was to investigate whether four escalating weekly subcutaneous injections of rHuIL-12 in allergic asthmatic patients could induce changes in the intracellular cytokine profile of the circulating blood CD4+ and CD8+ T cells. Material and methods. Purified CD4+ and CD8+ T cells from peripheral blood mononuclear cells of 11 patients (six received rHuIL-12 and five received placebo) were collected before and after 4 weeks of treatment, and cultured in the presence of phorbol myristate acetate for 4 days, with or without the addition of IL-12 in vitro. Expression of various intracellular cytokines was determined using flow cytometry following treatment with brefeldin-A and saponin. Results. Compared to placebo, the proportions of peripheral blood interferon-γ-, IL-4-, IL-2- or IL-10-producing CD4+ or C...

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.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.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 of0.7 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).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.

Summary 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 15μg \( n = 1 0 \) or 50μg \( n = 8 \) 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 50μg than 15μg LPS group. Similarly, the increase in sputum and blood total cell and neutrophil counts at 6h following inhaled LPS were greater in the 50μg group. Myeloperoxidase, human neutrophil elastase and interleukin-8 in sputum sol, but not blood, showed a trend towards greater increase following 50μg LPS. All these changes were resolved at one week. In the 50μg dose group alone, there was a reduction in the proportion of peripheral blood interferon (IFN)- γ -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- γ -producing T cells into tissue from inhaled 50μg LPS, followed by reappearance of these cells in blood 1 week later.

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.

AM J RESPIR CRIT CARE MED 1999;160:S33−S37.COPD is a debilitating and progressive condition in which the airways become irreversibly obstructed and the lungs progressively damaged. Unlike asthma, we know little about the cells that initiate and drive this process. Research has shown that CD8+ T cells are overrepresented in the lungs of patients with COPD and that they are inversely related to lung function. However, not all CD8+ T cells are alike and subsets that make IFN- γ but not IL-4 (Tc1), IL-4 but not IFN- γ (Tc2) as well as those that make both (Tc0) have been described. This article focuses on the characteristics of CD8+ T cell subsets and considers their potential contribution to chronic obstructive pulmonary disease (COPD). Kemeny DM, Vyas B, Vukmanovic-Stejic M, Thomas M, Noble A, Loh LC, O'Connor BJ. CD8+ T cell subsets and chronic obstructive pulmonary disease.

A poorly reversible and chronic airflow obstruction is the cardinal feature of chronic obstructive pulmonary disease (COPD). However, the condition is heterogeneous in many other ways. Our vigorous attempt to phenotype or endotype COPD testifies this fact. It is not the disease entity mechanism alone but its interaction with a whole host of socio-environmental factors that have created the kind of COPD burden we see today. Some years ago, Tan et al . highlighted that there were more deaths and disability suffered in COPD in Asia region than developed western countries1 and showed high and varied trends of hospital admissions and mortality in the various Asia countries.2 The emphasis was on confronting the high smoking prevalence in Asia as well as optimal deployment of health care resources. The picture is obviously larger than this. In Burden of Obstructive Lung Disease (BOLD) analysis of 22 study sites (including those in Asia), Burney et al. 3 showed that poverty, not cigarette consumption, has greater association with lung function restriction that correlates significantly with COPD mortality. This finding thrusts forward poverty as a bigger threat than does cigarette smoking in COPD. Byrne et al. 4 showed …

Background: In ventilated patients already critically ill, isolation of Acinetobacter baumannii from lower respiratory tract may have clinical importance and the differentiation between infection and colonization can be difficult. Aim: We sought to overcome the confounding element of critical illness by using Simplified Acute Physiology score (SAPS II) to predict mortality risk and comparing this in critically ill ventilated patients between those with A. baumannii alone and those entirely negative lower respiratory tract cultures. Methods: 138 eligible cases from an urban-based tertiary hospital intensive care unit (ICU) were retrospectively reviewed. Results: Between 43 patients with A. baumannii [mean age (SD): 47 (18.5) yrs; 65% male] and 95 matched patients with negative cultures [51 (17.5); 53%], median risks of hospital mortality were not significant different but the median (IQR 25-75 ) length of total hospital stay [19 (11-32) vs. 14 (9-21) days, p=0.022] and ICU [8 (4-19) vs. 7 (3-9), p=0.010] were significantly longer in A. baumannii group. Such findings occur irrespective of whether the underlying lungs were diseased or not and whether the isolates were resistant (except for cefepime-resistance). Conclusion:Isolation of lower respiratory tract A. baumannii alone in critically ill patients is no more likely to cause increased mortality risk than in those with negative culture, and prolonged ICU stay is likely responsible for the acquisition of A. baumannii .

Background: COPD is associated with cardiovascular co-morbidities. We examined the prevalence of undiagnosed COPD in our local population of patients with stable cardiovascular diseases and the profile of their respiratory symptoms and functional status. Methods: Eligible patients with established stable cardiovascular diseases were prospectively recruited from the cardiology outpatient clinic of an urban-based university teaching hospital and evaluated with pre- and post- bronchodilator spirometry testing and interview using standard questionnaire. Results: Of the 501 subjects recruited, 113 (22.6%) had COPD defined on post-bronchodilator fixed FEV 1 /FVC ratio

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.

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.

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 popu-lated 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. Key words: Clinical practice, Continuing medical education, Doctors, Malaysia, Pharmaceutical industry

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

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 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, 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..

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.

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 (p0.001 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.

Roslina Abdul Manap,1 Li Cher Loh,2 Tengku Saifudin Tengku Ismail,3 Abdul Razak Muttalif,4 George Kutty Simon,5 Rosalind Beng Hong Toh,6 Mohd Razali Norhaya,7 Noor Aliza Md Tarekh,8 Che Wan Aminuddin Hashim,9 Mohammad Fauzi Abdul Rani,10 Aziah Ahmad Mahayiddin111Department of Medicine, UniversitiKebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia; 2Department of Medicine, Penang Medical College, Penang, Malaysia; 3Department of Medicine, Faculty of Medicine UniversitiInstitutTeknologi MARA, Selangor, Malaysia; 4Department of Respiratory Medicine, Penang Hospital, Penang, Malaysia; 5Department of Respiratory Medicine, Hospital SultanahBahiyah, Alor Star, Kedah, Malaysia; 6Hospital Ipoh, Ipoh, Malaysia; 7Hospital SultanahNurZahirah, Kuala Terengganu, Malaysia; 8Hospital SultanahAminah, Johor Bahru, Malaysia; 9Hospital UniversitiSains Malaysia, Kelantan, Malaysia; 10Hospital TengkuAmpuanAfzan, Kuantan, Malaysia; 11Institute of Respiratory Medicine, Kuala Lumpur, MalaysiaBackground: 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.Keywords: asthma, asthma control, Malaysia, maintenance and reliever therapy, satisfaction, Symbicort, budesonide/formoterol