National expert consensus on short-acting beta2-agonist overreliance in asthma care in Malaysia.

OBJECTIVE: Inappropriate use of short-acting beta2-agonists (SABA) in asthma has been associated with undesired outcomes. This national expert consensus was developed to increase awareness of SABA overuse and provide recommendations on the ways to eliminate SABA overprescription and overreliance in Malaysia. DATA SOURCES: This expert consensus was developed by searching the PubMed database, using index terms to identify SABA overuse-related burden and recommendations made in asthma guidelines. Consensus recommendations were made via the Delphi method, involving a Malaysian expert committee comprising 13 healthcare professionals (five pulmonologists, four family medicine specialists, two emergency medicine physicians and two pharmacists). STUDY SELECTIONS: The articles reviewed include randomized controlled trials, systematic reviews, meta-analyses, observational studies, guidelines, and surveys, with abstracts in English and published up until June 2023. Relevant recommendations were also sourced from verified websites of medical organizations and societies. RESULTS: Eleven consensus statements were developed, each statement achieving a priori agreement level of at least 70%. The statements reflect SABA overreliance in asthma care, as well as recommendations to eliminate SABA overprescription and overreliance in Malaysia. Supporting evidence in the literature as well as expert committee discussions leading to the development of the finalized statements were elaborated. CONCLUSION: This national expert consensus discussed the burden of SABA overreliance and made specific recommendations to eliminate SABA overprescription and overreliance in the Malaysian context. This consensus document is anticipated to impart better awareness among Malaysian healthcare providers and contribute to the continuous improvement of asthma care in the country.

Protocol for a systematic review of the associations between inflammatory markers and lung function, muscle force and exercise capacity in people with COPD.

INTRODUCTION: The prevalence of chronic obstructive pulmonary disease (COPD) has been on the rise, with acute exacerbation of COPD associated with the highest burden and multiple pulmonary and systemic consequences. People with COPD have been found to have an abnormal response of systemic inflammation. To date, although limited, there are studies that suggest negative associations between inflammatory markers and important clinical outcomes such as exercise capacity and muscle force. This protocol aims to systematically review the evidence for (i) the associations between inflammatory markers and lung function, muscle force and exercise capacity and (ii) the influence of other factors (eg, hospitalisation, exercise programme) on the level of inflammatory markers in people with COPD. METHODS AND ANALYSIS: Scopus, PubMed, Cochrane, Web of Science and ProQuest will be searched from database inception to February 2023 using PEO search strategy (Population: adults with COPD; Exposure: inflammatory markers; Outcomes: lung function, muscle force and exercise capacity). Four reviewers working in pairs will independently screen articles for eligibility and extract data that fulfilled the inclusion criteria. Depending on the design of the included studies, either Cochrane risk-of-bias version 2 or the Newcastle-Ottawa Scale tools will be used to rate the methodological quality of the included studies. Effect sizes reported in each individual study will be standardised to Cohen's d and a random effects model will be used to calculate the pooled effect size for the association. ETHICS AND DISSEMINATION: Ethical approval is unnecessary as this study will only use publicly available data. The findings will be disseminated through publication in peer-reviewed journals and conferences. PROSPERO REGISTRATION NUMBER: CRD42022284446.

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.

Dearth of influenza among older adults admitted with respiratory symptoms in Malaysia during the coronavirus disease 2019 pandemic in 2021.

Introduction: Influenza is a common respiratory virus which leads to over 400,000 annual deaths globally. Mortality from influenza is highest among those aged 75 years and over living in Africa and Southeast Asia. Objective: To determine the burden of influenza among older adults presenting to public hospitals with severe acute respiratory infection (SARI) during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This multi-center, prospective, observational study recruited individuals aged 65 years and over who presented to four Malaysian hospitals with SARI from 1 January to 31 December 2021. Those with prior confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection were excluded. SARS-CoV-2 was detected through real-time polymerase chain reaction (PCR) with routine diagnostic kits. Influenza A, influenza B and respiratory syncytial virus (RSV) viruses were detected with Xpress Flu/RSV kits using the GeneXpert rapid real-time PCR system (Cepheid, USA). Results: Samples were obtained from 512 participants, comprising 296 (57.8%) men and 216 (42.2%) women, with a mean age (SD) of 74.0 (7.1) years. Inpatient death occurred in 48 (9.6%) individuals. Significant differences existed in age, ethnicity, and comorbidities across study sites. One (0.2%) case of influenza A, two (0.4%) cases of RSV and 63 (12.5%) cases of SARS-CoV-2 infection were detected over the 1-year period. Cases of COVID-19 mirrored national trends derived from open source data, while the dearth of influenza cases mirrored national and global Flunet figures. Conclusion: Our observational study conducted during the COVID-19 pandemic detected only one case of influenza, alongside a high SARS-CoV-2 positivity rate. The poor uptake of influenza vaccination nationally, worsened by the recent pandemic restrictions, could lead to waning immunity from the absence of seasonal exposure. Potentially deadly outbreaks may then occur when lockdown and infection control measures are eventually removed.

Managing Post COVID-19 Patient with Breathlessness.

Background: Chronic respiratory disease may be associated with severity of coronavirus disease 2019 (COVID-19) infection. We review a case of chronic obstructive pulmonary disease (COPD) patient who developed acute breathlessness post COVID-19 infection, also focusing on the diagnostic approach. Case: A 69-year-old gentleman with background history of COPD GOLD D and ischemic heart disease was admitted with severe COVID-19 infection. He required high-flow nasal cannula upon presentation. A computed tomography pulmonary angiography (CTPA) thorax at day 10 of illness revealed moderate organizing pneumonia (OP) with emphysematous changes, without pulmonary embolism. He received oral baricitinib and intravenous methylprednisolone for 3 days, which was then followed by tapering prednisolone starting dose of 1 mg/kg/day (60 mg/day) with reduction of 10 mg prednisolone every 3 days. COPD pharmacotherapy was optimized with early utilization of dual bronchodilators and inhaled corticosteroid was withheld. He underwent inpatient pulmonary rehabilitation and was discharged with home oxygen therapy. Unfortunately, he was re-admitted after 2 weeks with shortness of breath and fever for 3 days. Blood results revealed leucocytosis with raised C-reactive protein. A repeat CTPA showed increase reticulations and crazy paving pattern with reduction in lung volume. Multidisciplinary team discussion concluded it as interstitial pneumonia with COVID-19 OP and fibrosis progression. Prednisolone was stopped and he responded well with antibiotics. A follow-up at 3 months post COVID-19 infection showed improvement of clinical symptoms with radiological resolution of ground glass changes. Conclusion: Corticosteroid inhaler should be cautioned in this case, in view of recent pneumonia and non-elevated serum eosinophil count. These groups of patients should be closely followed up to unmask interstitial lung disease that may present prior to COVID-19 and worsen post-infection. Optimizing pre-existing medical conditions should be the paramount intervention.

Development of bullous lung disease with pneumothorax following SARS-CoV-2 infection.

Cystic lung formation secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was described during coronavirus disease pandemic, but with relatively low prevalence. A rare yet under-recognized complication is that these cystic areas may progress to bullae, cavities and pneumothorax. We reported two cases of ruptured bullae with pneumothorax following SARS-CoV-2 infection. Two patients were discharged following SARS-CoV-2 pneumonia, which did not require invasive mechanical ventilation (IMV). However, both patients presented again a month later with shortness of breath. Repeated computed tomography (CT) thorax showed development of bullous lung disease and pneumothorax. The first patient underwent surgical intervention whilst the second patient was treated conservatively. Development of bullous lung disease following SARS-CoV-2 infection is rare but may be associated with serious morbidity. Patients whose general condition permits should be offered surgical intervention whilst conservative management is reserved for non-surgical candidates.

Primary Systemic Amyloidosis With Cardiac and Renal Involvement.

Systemic amyloidosis is a life-threatening disorder with a poor prognosis. Accurate and early diagnosis of the condition is of paramount importance as early initiation of therapy improves the prognosis and survival rate. A 49-year-old gentleman presented with recurrent right exudative pleural effusion. Thoracocentesis revealed unexplained exudative pleural effusion. Pleuroscopy and pleural biopsy showed chronic inflammatory changes with no atypical cells. Echocardiography revealed global dilated cardiomyopathy with an ejection fraction (EF) of 35%. He also had nephrotic range proteinuria of 2.83g/dL. A cystoscopy examination was performed due to macroscopic haematuria, and the bladder biopsy revealed focal acellular eosinophilic material within the stroma. Salmon red staining and apple-green birefringence were noticed under polarizing microscopy, suggestive of amyloidosis. Serum protein electrophoresis revealed raised alpha 1 globulin and alpha 2 globulins which support the diagnosis of primary systemic amyloidosis. Unfortunately, the patient passed away before the initiation of treatment due to cardiogenic shock. Early and less invasive tests for diagnosing systemic amyloidosis, such as abdominal fat pad aspiration and salivary gland biopsy, can be done. Given its systemic nature, early complications screening may benefit patients whereby targeted treatment can be given.

NAT2 polymorphism and clinical factors that increase antituberculosis drug-induced hepatotoxicity.

Aim: Hepatotoxicity is a known adverse effect of antituberculosis drugs. The NAT2 gene polymorphism has been associated with an increased risk of antituberculosis drug-induced hepatotoxicity (ATDIH). Materials & methods: This study investigates the association of NAT2 polymorphism and clinical risk factors that may contribute to the development of ATDIH. The authors sequenced the NAT2 region of 33 tuberculosis patients who developed ATDIH and 100 tuberculosis patients who did not develop ATDIH during tuberculosis treatment. NAT2 haplotypes were inferred and NAT2 acetylator status was predicted from the combination of the inferred haplotypes. Multiple logistic regression was performed to identify possible factors that are associated with ATDIH. Results: The TT genotype of NAT2*13A and the AA genotype of NAT2*6B were found to be substantially linked with the risk of ATDIH, with odds ratios of 3.09 (95% CI: 1.37-6.95) and 3.07 (95% CI: 1.23-7.69), respectively. NAT2 slow acetylators are 3.39-times more likely to develop ATDIH. Factors that were associated with ATDIH include underlying diabetes mellitus (adjusted odds ratio [AOR]: 2.96; 95% CI: 1.05-8.37), pre-treatment serum bilirubin (AOR: 1.09; 95% CI: 1.02-1.16) and NAT2 slow acetylator (AOR: 3.77; 95% CI: 1.51-9.44). Conclusion: Underlying diabetes mellitus, having a higher baseline bilirubin and being a slow acetylator are identified as the risk factors associated with ATDIH among patients in Malaysia.

Bronchoscopic Features and Morphology of Endobronchial Tuberculosis: A Malaysian Tertiary Hospital Experience.

The diagnosis of endobronchial tuberculosis (EBTB) is difficult as it is not well visualized radiologically, and bronchoscopy is not routinely performed for tuberculosis (TB) patients. Bronchoscopic characterization via endoscopic macroscopic features can speed up the diagnosis of EBTB and prompt immediate treatment. In this study, we identified the clinical and bronchoscopic morphology of 17 patients who were diagnosed with EBTB from 2018 to 2020. Demographics, radiological, microbiological and histopathological data were recorded. Endobronchial lesions were classified according to Chung classification. The diagnosis was made based on a histopathological examination (HPE) of endobronchial biopsy, and/or positive 'Acid-fast bacilli' (AFB) microscopy/Mycobacterium tuberculosis (MTB) culture on microbiological examination of bronchial alveolar lavage (BAL) and/or positive MTB culture on endobronchial biopsy specimens. Furthermore, EBTB was predominant in young women, age 20 to 49 years old, with a male to female ratio of 1 to 2. Underlying comorbidities were found in 53% of the patients. Cough, fever and weight loss were the main symptoms (23.5%). The indications for bronchoscopy are smear-negative TB and persistent consolidation on chest radiographs. Consolidation was the main radiological finding (53%). An active caseating lesion was the main EBTB endobronchial subtype (53%). The leading HPE finding was caseating granulomatous inflammation (47%). All patients showed good clinical response to TB treatment. Repeated bronchoscopy in six patients post TB treatment showed a complete resolution of the endobronchial lesion. EBTB bronchoscopic characterization is paramount to ensure correct diagnosis, immediate treatment and to prevent complication.

Linguistic validation of stigmatisation degree, self-esteem and knowledge questionnaire among asthma patients using Rasch analysis.

BACKGROUND AND OBJECTIVE: The stigmatisation degree, self-esteem and knowledge either directly or indirectly influence the control and self-management of asthma. To date, there is no valid and reliable instrument that can assess these key issues collectively. The main aim of this study was to test the reliability and validity of the newly devised and translated "Stigmatisation Degree, Self-Esteem and Knowledge Questionnaire" among adult asthma patients using the Rasch measurement model. METHODOLOGY: This cross-sectional study recruited thirty adult asthma patients from two respiratory specialist clinics in Selangor, Malaysia. The newly devised self-administered questionnaire was adapted from relevant publications and translated into the Malay language using international standard translation guidelines. Content and face validation was done. The data were extracted and analysed for real item reliability and construct validation using the Rasch model. RESULTS AND CONCLUSION: The translated "Stigmatisation Degree, Self-Esteem and Knowledge Questionnaire" showed high real item reliability values of 0.90, 0.86 and 0.89 for stigmatisation degree, self-esteem, and knowledge of asthma, respectively. Furthermore, all values of point measure correlation (PTMEA Corr) analysis were within the acceptable specified range of the Rasch model. Infit/outfit mean square values and Z standard (ZSTD) values of each item verified the construct validity and suggested retaining all the items in the questionnaire. The reliability analyses and output tables of item measures for construct validation proved the translated Malaysian version of "Stigmatisation Degree, Self-Esteem and Knowledge Questionnaire" as a valid and highly reliable questionnaire.