A time-to-event modelling of sputum conversion within two months after antituberculosis initiation among drug-susceptible smear positive pulmonary tuberculosis patients: Implementation of internal and external validation.

Delayed sputum conversion has been associated with a higher risk of treatment failure or relapse among drug susceptible smear-positive pulmonary tuberculosis patients. Several contributing factors have been identified in many studies, but the results varied across regions and countries. Therefore, the current study aimed to develop a predictive model that explained the factors affecting time to sputum conversion within two months after initiating antituberculosis agents among Malaysian with drug-susceptible smear-positive pulmonary tuberculosis patients. Retrospective data of pulmonary tuberculosis patients followed up at a tertiary hospital in the Northern region of Malaysia from 2013 until 2018 were collected and analysed. Nonlinear mixed-effect modelling software (NONMEM 7.3.0) was used to develop parametric survival models. The final model was further validated using Kaplan-Meier-visual predictive check (KM-VPC) approach, kernel-based hazard rate estimation method and sampling-importance resampling (SIR) method. A total of 224 patients were included in the study, with 34.4 % (77/224) of the patients remained positive at the end of 2 months of the intensive phase. Gompertz hazard function best described the data. The hazard of sputum conversion decreased by 39 % and 33 % for moderate and advanced lesions as compared to minimal baseline of chest X-ray severity, respectively (adjusted hazard ratio (aHR), 0.61; 95 % confidence intervals (95 % CI), (0.44-0.84) and 0.67, 95 % CI (0.53-0.84)). Meanwhile, the hazard also decreased by 59 % (aHR, 0.41; 95 % CI, (0.23-0.73)) and 48 % (aHR, 0.52; 95 % CI, (0.35-0.79)) between active and former drug abusers as compared to non-drug abuser, respectively. The successful development of the internally and externally validated final model allows a better estimation of the time to sputum conversion and provides a better understanding of the relationship with its predictors.

Short-acting ß2-agonist prescription patterns and clinical outcomes in Malaysia: A nationwide cohort of the SABINA III study.

Introduction: SABINA III assessed short-acting ß2-agonist (SABA) prescription patterns and their association with asthma-related outcomes globally. Herein, we examined SABA prescription and clinical outcomes in the Malaysian cohort of SABINA III. Method: In this observational, cross-sectional study, patients (≥12 years) were recruited between July and December 2019 from 15 primary and specialty care centres in Malaysia. Prescribed asthma treatments and severe exacerbation history within 12 months prior and asthma symptom control during the study visit were evaluated. Associations of SABA prescription with asthma control and severe exacerbation were analysed using multivariable regression models. Results: Seven hundred thirty-one patients (primary care, n=265 [36.3%]; specialty care, n=466 [63.7%]) were evaluated. The prevalence of SABA over-prescription (≥3 SABA prescriptions/year) was 47.4% (primary care, 47.1%; specialty care, 47.6%), 51.8% and 44.5% among all patients and patients with mild and moderate-to-severe asthma, respectively. Altogether 9.0% (n=66) purchased SABA without a prescription; among them, 43.9% (n=29) purchased ≥3 inhalers. The mean (standard deviation) number of severe asthma exacerbations was 1.38 (2.76), and 19.7% (n=144) and 25.7% (n=188) had uncontrolled and partly controlled symptoms, respectively. Prescriptions of ≥3 SABA inhalers (vs 1-2) were associated with lower odds of at least partly controlled asthma (odds ratio=0.42; 95% confidence interval [CI]=0.27-0.67) and higher odds of having severe exacerbation(s) (odds ratio=2.04; 95% CI=1.44-2.89). Conclusion: The prevalence of SABA over-prescription in Malaysia is high, regardless of the prescriber type, emphasising the need for healthcare providers and policymakers to adopt latest evidence-based recommendations to address this public health concern.

Chronic obstructive pulmonary disease and emerging ER stress-related therapeutic targets.

COPD pathogenesis is frequently associated with endoplasmic reticulum stress (ER stress) progression. Targeting the major unfolded protein response (UPR) branches in the ER stress pathway may provide pharmacotherapeutic selection strategies for treating COPD and enable relief from its symptoms. In this study, we aimed to systematically review the potential role of the ER stress inhibitors of major UPR branches (IRE1, PERK, and ATF6) in COPD-related studies and determine the current stage of knowledge in this field. The systematic review was carried out adhering to the PRISMA checklist based on published studies obtained from specific keyword searches of three databases, namely PubMed, ScienceDirect and Springer Database. The search was limited to the year 2000-2022 which includes all in vitro studies, in vivo studies and clinical trials related to the application of ER stress inhibitors toward COPD-induced models and disease. The risk of bias was evaluated using the QUIN, SYRCLE, revised Cochrane risk of bias tool for randomized trials (RoB 2.0) and NIH tool respectively. A total of 7828 articles were screened from three databases and a final total of 37 studies were included in the review. The ER stress and UPR pathways are potentially useful to prevent COPD progression and attenuate the exacerbation of COPD and related symptoms. Interestingly, the off-target effects from inhibition of the UPR pathway may be desirable or undesirable depending on context and therapeutic applications. Targeting the UPR pathway could have complex consequences as the production of ER molecules involved in folding may be impaired which could continuously provoke misfolding of proteins. Although several emerging compounds were noted to be potentially useful for targeted therapy against COPD, clinical studies have yet to be thoroughly explored.

Survival Trend of Tuberculosis Patients and Risk Factors Associated with Mortality and Developing Drug-Resistant Tuberculosis in Hospital Pulau Pinang, Malaysia: A Retrospective Study.

BACKGROUND: Multidrug resistance TB (MDR-TB) has emerged as a public health issue worldwide, and the mortality rate is worrying. Therefore, this study was conducted to investigate the factors related to MDR-TB occurrence and the survival experience of TB patients. METHODS: A retrospective cohort study was conducted at Hospital Pulau Pinang in Malaysia. Medical records of active TB patients from 2014-2018 were reviewed. Cox regression was used to identify the factors associated with MDR-TB development and mortality among TB patients. RESULTS: The patients had a mean age of 48.84 ± 16.713 years, and a majority of the Chinese race (46.4%). Out of 351 TB patients, 325 (92.6%) were drug-susceptible TB, and 26 (7.4%) were diagnosed with MDR-TB. Among drug-susceptible TB patients, 245 (75.4%) achieved successful outcomes, and 73 (22.5%) passed away. In multivariable Cox regression, drug addiction, levels of white blood cells, urea, platelets, and albumin were significantly associated with death. Relapsed TB, alcohol consumption, and being single were significant risk factors for MDR-TB development. CONCLUSION: Patients achieved a success rate of 75.4%, which is encouraging but still far below the WHO target (at least an 85% success rate) and has room for further improvement.

A Cross-Sectional Assessment of Urinary Tract Infections Among Geriatric Patients: Prevalence, Medication Regimen Complexity, and Factors Associated With Treatment Outcomes.

Background: Urinary tract infections (UTIs) are the second most prevalent infection among the elderly population. Hence, the current study aimed to evaluate the prevalence of UTIs among older adults, medication regimen complexity, and the factors associated with the treatment outcomes of elderly patients infected with UTIs. Methods: A retrospective cross-sectional study was conducted at the Department of Urology, Hospital Pulau Pinang, Malaysia. The patients ≥65 years of age were included in the present study with a confirmed diagnosis of UTIs from 2014 to 2018 (5 years). Results: A total of 460 patients met the inclusion criteria and were included in the present study. Cystitis (37.6%) was the most prevalent UTI among the study population followed by asymptomatic bacteriuria (ASB) (31.9%), pyelonephritis (13.9%), urosepsis (10.2%), and prostatitis (6.4%). Unasyn (ampicillin and sulbactam) was used to treat the UTIs followed by Bactrim (trimethoprim/sulfamethoxazole), and ciprofloxacin. The factors associated with the treatment outcomes of UTIs were gender (odd ratio [OR] = 1.628; p = 0.018), polypharmacy (OR = 0.647; p = 0.033), and presence of other comorbidities (OR = 2.004; p = 0.002) among the study population. Conclusion: Cystitis is the most common UTI observed in older adults. Gender, the burden of polypharmacy, and the presence of comorbidities are the factors that directly affect the treatment outcomes of UTIs among the study population.

Prevalence, risk assessment, and predictors of osteoporosis among chronic obstructive pulmonary disease patients.

The link between chronic obstructive pulmonary disease (COPD) and osteoporosis is unclear and yet to be understood. The study goals were to detect the prevalence of osteoporosis and investigate its predictors among COPD patients. This is a longitudinal study conducted in a tertiary care setting. During the study, patients' bone mineral density was checked, pulmonary parameters were recorded, and a risk assessment tool was validated. Based on T-score, more than 50% of subjects were osteoporotic. Spirometric parameters were significantly lower among osteoporotic patients. For the risk assessment tool, a cutoff point of 34 made the optimum balance between sensitivity and specificity (0.867 and 0.087, respectively) with a generated area under the curve of 0.934. Severe COPD patients were four times at higher risk of getting osteoporosis, forced expiratory volume (FEV) % predicted, and FEV/forced vital capacity was inversely related to the risk of osteoporosis. Patients with severe dyspnea had twice the risk of getting osteoporosis. Osteoporosis was prevalent among COPD patients, and severe COPD patients were at higher risk of getting osteoporosis.

Determining the risk factors associated with delayed sputum conversion at the end of the intensive phase among tuberculosis patients.

BACKGROUND: In pulmonary tuberculosis (PTB), the sputum conversion rate at 2 months is frequently used to evaluate treatment outcomes and effectiveness of a TB control programme. AIMS: The study aimed to estimate the rate of delayed sputum conversion and explore its predicting factors at the end of the intensive phase among smear-positive PTB (PTB +ve) patients. METHODS: A 3-year retrospective study was conducted in the government hospital in Pulau Pinang from 2016 to 2018. During the study, a standardized, data collection form was used to collect data from the patient record. Patients aged over 18 years were recruited. Multivariable logistic regression analysis was used to identify significant independent variables associated with delayed sputum conversion. RESULTS: A total 1128 of PTB patients were recorded visiting the TB clinic, 736 (65.2%) were diagnosed as PTB +ve; of these, 606 (82.3%) PTB +ve had a record of sputum conversion at the end of the intensive phase. Age ≥ 50 years, blue-collar jobs, smoking, heavy bacillary load, relapsed and treatment interrupted were significantly (P < 0.05) associated with delayed sputum conversion. Delayed sputum conversion rate at the end of the intensive phase was 30.5%. CONCLUSION: The rate of sputum smear conversion in the intensive phase of treatment was independently associated with high sputum smear grading at diagnosis, relapsed and treatment interrupted categories, old age and blue-collar occupations.

Tracheobronchopathia osteochondroplastica-stalactite of airways.

A case of tracheobronchopathia osteochondroplastica (TO) was diagnosed in a 53-year-old man, who presented with prolonged cough and recurrent respiratory tract infection. Bronchoscopy revealed exostosis over the anterolateral wall of trachea and main bronchi sparing the posterior membranous wall. The endobronchial biopsy subsequently revealed ossification of the cartilage. To date, the aetiology of this condition remains unknown, and treatment is mainly symptomatic, emphasizing on timely management of recurrent respiratory infections. Bronchoscopy or surgical intervention is usually reserved for symptomatic patients with severe airway narrowing and airflow obstruction.

Respiratory-tract infections among geriatrics: prevalence and factors associated with the treatment outcomes.

BACKGROUND: Geriatric individuals are more susceptible to different infections, especially respiratory-tract infections (RTIs) due to their compromised immune system. Hence, the objectives of the present study were to evaluate the prevalence, medication regimen complexity and factors associated with the treatment outcomes of different RTIs among geriatrics. METHODS: A retrospective cross-sectional study (5 years) was conducted at the respiratory department, Hospital Pulau Pinang. Patients aged ⩾65 years with confirmed diagnosis of RTI were included in the study. RESULTS: A total of 474 patients were included, and the most prevalent RTIs were community-acquired pneumonia (65.6%) followed by chronic obstructive pulmonary disease (20.7%), bronchitis (8.2%) and hospital-acquired pneumonia (5.5%). Amoxicillin/clavulanate (69.8%), ampicillin/sulbactam (9.1%) and cefuroxime (6.5%) are the most common antibiotics prescribed to treat RTIs among geriatrics. Smoking, alcohol consumption, polypharmacy and presence of other co-morbidities are statistically significant factors associated with treatment outcomes of RTIs among geriatrics. CONCLUSION: Prevalence of community-acquired pneumonia (65.6%) among older patients aged 65 years and older higher than other RTIs. Smoking, alcohol use, presence of polypharmacy and other co-morbidities are important factors associated with the treatment outcomes of RTIs.The reviews of this paper are available via the supplemental material section.

Efficacy, Safety and Immunogenicity of MB02 (Bevacizumab Biosimilar) versus Reference Bevacizumab in Advanced Non-Small Cell Lung Cancer: A Randomized, Double-Blind, Phase III Study (STELLA).

BACKGROUND: MB02 (bevacizumab biosimilar) showed similar structural, functional, and pharmacokinetic properties to reference bevacizumab (Avastin®; EU-bevacizumab). OBJECTIVES: To confirm clinical similarity between MB02 and EU-bevacizumab, a comparability study was undertaken in the first-line treatment of stage IIIB/IV non-squamous non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: This multinational, double-blind, randomized, phase III study (STELLA) compared MB02 or EU-bevacizumab (15 mg/kg) administered with chemotherapy (paclitaxel 200 mg/m2 and carboplatin AUC6) on Day 1 of every 3-week cycle for 6 cycles (Week 18), followed by MB02/EU-bevacizumab in blinded monotherapy until disease progression, unacceptable toxicity, death, withdrawal of consent or end of study (Week 52). The primary efficacy endpoint was objective response rate (ORR) evaluated by an independent radiological review committee (IRC) at Week 18 (intent-to-treat population). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety and immunogenicity. RESULTS: A total of 627 subjects were randomized 1:1 to MB02 (n = 315) or EU-bevacizumab (n = 312). ORR, assessed by the IRC at Week 18, was comparable in MB02 (40.3%) and EU-bevacizumab (44.6%) groups. ORR risk ratio of 0.910 (90% CI 0.780 to 1.060; 95% CI 0.758 to 1.092) and ORR risk difference of -4.02 (90% CI -10.51 to 2.47; 95% CI -11.76 to 3.71) were within the similarity predefined margins. There were no significant differences between MB02 and EU-bevacizumab groups in median PFS (36.0 vs 37.3 weeks, respectively; HR 1.187; 95% CI 0.98 to 1.44) and median OS (not achieved; HR 1.108; 95% CI: 0.83 to 1.49) at the end of study. The safety profile of MB02 and EU-bevacizumab regarding nature, frequency and severity of the adverse events (AE) was comparable. The most frequent grade ≥3 investigational-product-related AEs were hypertension and anemia, with a difference between treatment groups of <5%. Anti-drug antibodies (ADA) and neutralizing ADA (NAb) incidence were similar in both treatment groups. CONCLUSION: MB02 demonstrated similar efficacy to EU-bevacizumab, in combination with carboplatin and paclitaxel, in subjects with advanced non-squamous NSCLC, with comparable safety and immunogenicity profiles. CLINICAL TRIAL REGISTRATION: EudraCT No. 2017-001769-26; ClinicalTrials.gov: NCT03296163.

The Association between Chronic Heroin Smoking and Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Little is known about the correlation between chronic obstructive pulmonary disease (COPD) and heroin smoking. Heroin smoking is a recent underinvestigated problem. The goal of this study is to study the impact of heroin smoking among COPD patients. METHODS: This is a descriptive clinical study. A combination of self-reporting questionnaires and data extraction tools were used to collect information during baseline tests, interviews, and follow-ups. Patients' medical, clinical, and socioeconomic history were recorded. Participants were recruited using random sampling from multiple centers. RESULTS: Out of 1034 COPD patients, heroin smokers represented the vast majority of addiction cases (n = 133). Heroin smokers were leaner than non-addicts (19.78 ± 4.07 and 24.01 ± 5.6, respectively). The most common type of comorbidities among heroin smokers was emphysema (27%). Both the forced expiratory volume (FEV1)/forced vital capacity ratio and FEV1% predicted were lower among heroin smokers than non-addicts (52.79 ± 12.71 and 48.54 ± 14.38, respectively). The majority of heroin smokers (55%) had advanced COPD, and at least 15% of heroin smokers suffered from frequent respiratory failure. The mean ± SD for COPD onset age among heroin smokers was 44.23 ± 5.72, and it showed a statistically significant correlation (P < 0.001). CONCLUSION: Heroin smoking might be linked to the onset of COPD. Heroin smokers showed a significantrespiratory impairment compared to tobacco smokers of the same age group.

Translation and validation of the Test of Adherence to Inhalers (TAI) questionnaire among adult patients with asthma in Malaysia.

OBJECTIVE: The Test of Adherence to Inhalers (TAI) is a validated self-reported questionnaire that can reliably assess adherence to inhalers through patient self-report. However, it was not available in Bahasa Melayu (BM) language, nor has it been validated for use in the Malaysian population. The study aimed, therefore, to translate the 10-item TAI questionnaire into BM and evaluate its psychometric properties. METHODS: The translation of the English version of the valid 10-item TAI questionnaire into BM was followed by subjecting it to a series of tests establishing factorial, concurrent and known group validities. Concurrent validity was assessed through Spearman's rank correlation coefficient against pharmacy refill-based adherence scores. Known group validity was assessed by cross-tabulation against asthma symptom control and using chi-square test. The internal consistency of the test scale was determined by a test-retest method using Cronbach's alpha (α) value and intraclass correlation coefficients. RESULTS: A total of 120 adult asthma patients participated in the study. A 2-factor structure was obtained and confirmed with acceptable fit indices; CFI, NFI, IFI, TLI >0.9 and, RMSEA was 0.08. The reliability of the scale was 0.871. The test-retest reliability coefficient for the total sum score was 0.832 (p < 0.01), which indicated good reliability. The 10-item TAI-BM established concurrent and known group validities. The sensitivity and specificity of the tool were >85%. CONCLUSIONS: The scale successfully translated into BM and validated. The 10-item TAI-BM appears fit for use in testing inhaler adherence of Malaysian patients with asthma.

Economic Burden of Chronic Obstructive Pulmonary Disease Patients in Malaysia: A Longitudinal Study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) requires long-term pharmacological and non-pharmacological management that encompasses continuous economic burden on patients and society, and also results in productivity losses due to compromised quality of life. Among working-age patients, COPD is the 11th leading cause of work productivity loss. OBJECTIVE: The aim of this study was to assess the economic burden of COPD in Malaysia, including direct costs for the management of COPD and indirect costs due to productivity losses for COPD patients. METHODOLOGY: Overall, 150 patients with an established diagnosis of COPD were followed-up for a period of 1 year from August 2018 to August 2019. An activity-based costing, 'bottom-up' approach was used to calculate direct costs, while indirect costs of patients were assessed using the Work Productivity and Activity Impairment Questionnaire. RESULTS: The mean annual per-patient direct cost for the management of COPD was calculated as US$506.92. The mean annual costs per patient in the management phase, emergency department visits, and hospital admissions were reported as US$395.65, US$86.4, and US$297.79, respectively; 31.66% of COPD patients visited the emergency department and 42.47% of COPD patients were admitted to the hospital due to exacerbation. The annual mean indirect cost per patient was calculated as US$1699.76. Productivity losses at the workplace were reported as 31.87% and activity limitations were reported as 17.42%. CONCLUSION: Drugs and consumables costs were the main cost-driving factors in the management of COPD. The higher ratio of indirect cost to direct medical costs shows that therapeutic interventions aimed to prevent work productivity losses may reduce the economic burden of COPD.

Physicians' Perspective on Prescribing Patterns and Knowledge on Antimicrobial Use and Resistance in Penang, Malaysia: A Qualitative Study.

Background: Unnecessary antimicrobial use is an emerging problem throughout the world. To design future interventions to ensure rational antimicrobial use and decrease the risk of antimicrobial resistance, physician's knowledge and prescribing practices of antimicrobials should be assessed. Therefore, the main objective of this study is to investigate the physician's knowledge along with their prescribing patterns of antimicrobials in their health care system. Methods: The present qualitative study was conducted in a tertiary care public hospital located at Penang island, situated in Northwest of Malaysia. A total of 12 semi-structured, face to face interviews were conducted with purposive sampling technique. Physicians recruited had different specialties. All interviews were audio recorded, then transcribed into English language and analyze by thematic content analysis. Results: Four major themes were identified: (1) prescribing patterns of physicians regarding antimicrobials; (2) physician's knowledge about antimicrobials; (3) antimicrobial resistance; (4) satisfaction with management of infections. Physicians believed in regular educational activities and updates about the latest antimicrobial guidelines may change the prescribing behavior of physicians to optimize the use of antimicrobials. This may lead to decrease in burden of antimicrobial resistance in their health care system. Physicians emphasized that stricter rules and regular monitoring of antimicrobial use should be implemented to overcome the main challenges of antimicrobial resistance. Conclusion: Different factors were identified to assist optimized use of antimicrobials and decrease the risk of antimicrobial resistance. The present study helps to design targeted future interventions to ensure rational antimicrobial use and decrease the impact of antimicrobial resistance in Malaysia.

Effectiveness of Home Visits in Adult Patients with Asthma: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: The effectiveness of home visits is well discussed for children with asthma, but limited in adults. OBJECTIVE: The present systematic review aimed to investigate the potential role of home visits in improving outcomes among adult patients with asthma. METHODS: The systematic review was performed in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. An extensive literature search was conducted using databases such as PubMed, ProQuest, CINAHL, The Cochrane Library, PsycINFO, and Google Scholar from inception to June 2019. The studies included were randomized controlled trials, which reported asthma outcomes in adult patients. RESULTS: The literature search yielded 8331 publications, of which 63 studies were selected for full-text review, and of these studies, 9 studies with a total of 2011 patients were included in the final analysis. The included randomized controlled trials reported quality of life, asthma symptoms, exacerbations, health care utilization, and pulmonary function. Improvements in asthma outcomes were observed predominantly in quality of life. The effects on asthma symptom control were inconsistent. The evidence on the impact of home visits in asthma exacerbations and health care utilization was rather limited. There were no significant differences observed between intervention versus control arms in terms of pulmonary function; however, 1 study reported significant improvements in peak expiratory flow rate. CONCLUSIONS: Home visits may serve as an adjuvant activity that complements the existing health care system-based initiatives. It may be concluded that home visits have the potential to improve outcomes in adult patients with asthma; however, the randomized controlled trials reviewed in the present systematic review reported several limitations that warrant further investigation.

Validation and clinical interpretation of the St George's respiratory questionnaire for COPD (SGRQ-C) after adaptation to Malaysian language and culture, in patients with COPD.

BACKGROUND: Cultural differences affect the administration and results of health status questionnaires. "Cross cultural adaptation" ensures retention of psychometric properties such as validity and reliability at an item and/or scale level. OBJECTIVE: To develop a Malaysian version of St George's respiratory COPD specific questionnaire (SGRQ-CM), to evaluate the full spectrum of psychometric properties (reliability, validity and responsiveness), to test the factor structure and to assess minimum clinically important difference for the SGRQ-CM, to be used in population of Malaysia. METHODOLOGY: SGRQ-C was translated to Bahasa Malaysia using a standard protocol. 240 COPD patients were included in the study. All patients were followed-up for six months. Construct validity, internal consistency, item convergent validity, test-retest ability, responsiveness, factor analysis and MCID of the Malaysian version of SGRQ-C to be used in population of Malaysia were evaluated. RESULTS: The Cronbach alpha coefficient and intraclass correlation coefficients (ICC) for SGRQ-CM were reported as 0.87, and 0.88 respectively. Correlation of SGRQ-CM with CAT, EQ-5D-5 L, mMRC dyspnea scales and FEV1%predicted were reported as 0.86, - 0.82, 0.72 and - 0.42 respectively. Correlation coefficient between the subscales and other clinical and health status measures ranged from r = - 0.35 to r = - 0.87. The MCID was reported as 5.07 (- 2.54-12.67). CONCLUSION: The Malaysian version of SGRQ-C has a good psychometric property comparable to those of the original version and has a strong evidence of validity, reliability and responsiveness towards disease severity in Malaysian COPD patients. It can be recommended as a reliable quality of life measure for future research.

The economic burden of chronic obstructive pulmonary disease (COPD) in the USA, Europe, and Asia: results from a systematic review of the literature.

Background: Lack of information about economic burden of COPD is a major cause of lack of attention to this chronic condition from governments and policymakers. Objective: To find the economic burden of COPD in Asia, USA and Europe, and to identify the key cost driving factors in management of COPD patients. Methodology: Relevant studies assessing the cost of COPD from patient perspective or societal perspective were retrieved by thoroughly searching PUBMED, SCIENCE DIRECT, GOOGLE SCHOLAR, SCOPUS, and SAGE Premier Databases. Results: In the USA annual per patient direct medical cost and hospitalization cost were reported as $10,367 and $6852, respectively. In Asia annual per patient direct medical cost in Iran, Korea and Singapore was reported as $1544, $3077, and $2335, respectively. However, annual per patient hospitalization cost in Iran, Korea, Singapore, India, China, and Turkey was reported as $865, $1371, $1868, $296, $1477 and $1031, respectively. In Europe annual per patient direct medical cost was reported as $11,787, $10,552, $8644, $8203, $7760, $3190, $1889, $2162, and $2254 in Norway, Denmark, Germany, Italy, Sweden, Greece, Spain, Belgium, and Serbia, respectively. Conclusion: Limiting the disease to early stage and preventing exacerbations may reduce the cost of management of COPD.

Osteoporosis among Patients with Chronic Obstructive Pulmonary Disease: Systematic Review and Meta-analysis of Prevalence, Severity, and Therapeutic Outcomes.

Chronic obstructive pulmonary disease (COPD) can be associated with systemic inflammatory trademarks and can coexist with other chronic debilitating diseases such as osteoporosis, which is considered among the most serious comorbidities of COPD. In this review, we aimed at finding answers for the following questions and tried to encapsulate the available literature: (1) how prevalent is osteoporosis among patients with COPD? (2) What are severity patterns of osteoporosis in case of COPD? (3) What are the therapeutic outcomes for patients with osteoporotic COPD? The total number of patients with COPD from all studies was 3815, majority of which were male (2658) representing 69.67% of patients. The mean ± standard deviation for percentage of forced expiratory volume in 1s (FEV1%) was 55.43 ± 14.62%, body mass index for almost 91.29% of patients was 24.4 ± 4.45 kg/m2, whereas fat-free mass index (FFMI) was 17 ± 0.93 kg/m2 for 17.66%. The percentage of patients with COPD having osteoporosis varied in the analyzed studies from 14% up to 66.6%. The mean prevalence of reported osteopenia from 14 studies (n = 2107) was 39.91%, whereas for osteoporosis, the mean prevalence was 37.62% for all included studies. Osteoporosis was highly prevalent among patients with COPD. It is reasonable to call for osteoporosis screening in patients with COPD who are above 65 years, in advanced stages, with BMI lower than 21 kg/m2 or with FFMI lower than 16 kg/m2 for males and 15 kg/m2 for females. There is a lack of research investigating severity and treatments of osteoporosis in patients with COPD.

It is time to change the way we manage mild asthma: an update in GINA 2019.

Asthma is a heterogeneous lung disease, usually characterised by chronic airway inflammation. Although evidence-based treatments are available in most countries, asthma control remains suboptimal, and asthma-related deaths continue to be an ongoing concern. Generally, it is believed that between 50 to 75% of patients with asthma can be considered as having mild asthma.Previous versions of Global Initiative for Asthma (GINA) suggested that mild asthma in adults can be well managed with either reliever medications, for example, short-acting beta2 agonists (SABA) alone or with the additional use of controllers such as regular low-dose inhaled corticosteroids (ICS). Given the low frequency or non-bothersome nature of symptoms in mild asthma, patients' adherence towards their controller medications, especially to ICS is usually not satisfactory. Such patients often rely on SABA alone to relieve symptoms, which may contribute to SABA over-reliance. Overuse of relievers such as SABAs has been associated with poor asthma outcomes, such as exacerbations and even deaths. The new GINA 2019 asthma treatment recommendations represent significant shifts in asthma management at Steps 1 and 2 of the 5 treatment steps. The report acknowledges an emerging body of evidence suggesting the non-safety of SABAs overuse in the absence of concomitant controller medications, therefore does not support SABA-only therapy in mild asthma and has included new off-label recommendations such as symptom-driven (as-needed) low dose ICS-formoterol and "low dose ICS taken whenever SABA is taken".The GINA 2019 report highlights significant updates in mild asthma management and these recommendations represent a clear deviation from decades of clinical practice mandating the use of symptom-driven SABA treatment alone in those with mild asthma. While the new inclusions of strategies such as symptom-driven (as-needed) ICS-formoterol and "ICS taken whenever SABA is taken" are based on several key trials, data in this context are still only emergent data, with clear superiority of as needed ICS-formoterol combinations over maintenance ICS regimens yet to be established for valid endpoints. Nevertheless, current and emerging data position the clinical asthma realm at a watershed moment with imminent changes for the way we manage mild asthma likely in going forward.

Assessing Airflow Limitation among Smokers in a Primary Care Setting.

BACKGROUND: Many smokers have undiagnosed chronic obstructive pulmonary disease (COPD), and yet screening for COPD is not recommended. Smokers who know that they have airflow limitation are more likely to quit smoking. This study aims to identify the prevalence and predictors of airflow limitation among smokers in primary care. METHODS: Current smokers ≥ 40 years old who were asymptomatic clinic attendees in a primary care setting were recruited consecutively for two months. We used a two-step strategy. Step 1: participants filled in a questionnaire. Step 2: Assessment of airflow limitation using a pocket spirometer. Multiple logistic regression was utilised to determine the best risk predictors for airflow limitation. RESULTS: Three hundred participants were recruited. Mean age was 58.35 (SD 10.30) years old and mean smoking history was 34.56 pack-years (SD 25.23). One in two smokers were found to have airflow limitation; the predictors were Indian ethnicity, prolonged smoking pack-year history and Lung Function Questionnaire score ≤ 18. Readiness to quit smoking and the awareness of COPD were low. CONCLUSIONS: The high prevalence of airflow limitation and low readiness to quit smoking imply urgency with helping smokers to quit smoking. Identifying airflow limitation as an additional motivator for smoking cessation intervention may be considered. A two-step case-finding method is potentially feasible.