Melbourne School of Health Sciences Collected Works - Research Publications

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    Interrelationships Among Small Airways Dysfunction, Neutrophilic Inflammation, and Exacerbation Frequency in COPD
    Day, K ; Ostridge, K ; Conway, J ; Cellura, D ; Watson, A ; Spalluto, CM ; Staples, KJ ; Thompson, B ; Wilkinson, T (ELSEVIER, 2021-04)
    BACKGROUND: Small airways disease (SAD) is a key component of COPD and is a main contributing factor to lung function decline. RESEARCH QUESTION: Is SAD a key feature of frequent COPD exacerbators and is this related to airway inflammation? STUDY DESIGN AND METHODS: Thirty-nine COPD patients defined as either frequent exacerbator (FE) group (≥ 2 exacerbations/y; n = 17) and infrequent exacerbator (IFE) group (≤ 1 exacerbation/y; n = 22) underwent the forced oscillation technique (resistance at 5 Hz minus 19 Hz [R5-R19], area of reactance [AX]), multiple breath nitrogen washout (conducting airways ventilation heterogeneity, acinar ventilation heterogeneity [Sacin]), plethysmography (ratio of residual volume to total lung capacity), single-breath transfer factor of the lung for carbon monoxide, spirometry (FEV1, FEV1/FVC), and paired inspiratory-expiratory CT scans to ascertain SAD. A subpopulation underwent bronchoscopy to enable enumeration of BAL cell proportions. RESULTS: Sacin was significantly higher in the COPD FE group compared with the IFE group (P = .027). In the FE group, markers of SAD were associated strongly with BAL neutrophil proportions, R5-R19 (P = .001, r = 0.795), AX (P = .049, ρ = 0.560), residual volume to total lung capacity ratio (P = .004, r = 0.730), and the mean lung density of the paired CT scans (P = .018, r = 0.639). INTERPRETATION: Increased Sacin may be a consequence of previous exacerbations or may highlight a group of patients prone to exacerbations. Measures of SAD were associated strongly with neutrophilic inflammation in the small airways of FE patients, supporting the hypothesis that frequent exacerbations are associated with SAD related to increased cellular inflammation.
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    Putting lung function reference equations into context
    Borg, BM ; Thompson, BR (EUROPEAN RESPIRATORY SOC JOURNALS LTD, 2021-09-01)
    Knowing the limitations of reference equations is essential to minimising errors in diagnosis and clinical management. Choice of reference sets may impact access to treatment options where lung function based eligibility criteria exist. https://bit.ly/2WdOFDj.
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    COVID-19 pneumonia and the pulmonary vasculature: a marriage made in hell
    George, PM ; Desai, SR (EUROPEAN RESPIRATORY SOC JOURNALS LTD, 2021-09-01)
    Quantitative CT of the pulmonary vasculature is potentially important in COVID-19 associated pneumonia https://bit.ly/3vUTTRM
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    Dysregulation of COVID-19 related gene expression in the COPD lung
    Watson, A ; Oberg, L ; Angermann, B ; Spalluto, CM ; Huhn, M ; Burke, H ; Cellura, D ; Freeman, A ; Muthas, D ; Etal, D ; Belfield, G ; Karlsson, F ; Nordstrom, K ; Ostridge, K ; Staples, KJ ; Wilkinson, T (BMC, 2021-05-29)
    BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients are at increased risk of poor outcome from Coronavirus disease (COVID-19). Early data suggest elevated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) receptor angiotensin converting enzyme 2 (ACE2) expression, but relationships to disease phenotype and downstream regulators of inflammation in the Renin-Angiotensin system (RAS) are unknown. We aimed to determine the relationship between RAS gene expression relevant to SARS-CoV-2 infection in the lung with disease characteristics in COPD, and the regulation of newly identified SARS-CoV-2 receptors and spike-cleaving proteases, important for SARS-CoV-2 infection. METHODS: We quantified gene expression using RNA sequencing of epithelial brushings and bronchial biopsies from 31 COPD and 37 control subjects. RESULTS: ACE2 gene expression (log2-fold change (FC)) was increased in COPD compared to ex-smoking (HV-ES) controls in epithelial brushings (0.25, p = 0.042) and bronchial biopsies (0.23, p = 0.050), and correlated with worse lung function (r = - 0.28, p = 0.0090). ACE2 was further increased in frequent exacerbators compared to infrequent exacerbators (0.51, p = 0.00045) and associated with use of ACE inhibitors (ACEi) (0.50, p = 0.0034), having cardiovascular disease (0.23, p = 0.048) or hypertension (0.34, p = 0.0089), and inhaled corticosteroid use in COPD subjects in bronchial biopsies (0.33, p = 0.049). Angiotensin II receptor type (AGTR)1 and 2 expression was decreased in COPD bronchial biopsies compared to HV-ES controls with log2FC of -0.26 (p = 0.033) and - 0.40, (p = 0.0010), respectively. However, the AGTR1:2 ratio was increased in COPD subjects compared with HV-ES controls, log2FC of 0.57 (p = 0.0051). Basigin, a newly identified potential SARS-CoV-2 receptor was also upregulated in both brushes, log2FC of 0.17 (p = 0.0040), and bronchial biopsies, (log2FC of 0.18 (p = 0.017), in COPD vs HV-ES. Transmembrane protease, serine (TMPRSS)2 was not differentially regulated between control and COPD. However, various other spike-cleaving proteases were, including TMPRSS4 and Cathepsin B, in both epithelial brushes (log2FC of 0.25 (p = 0.0012) and log2FC of 0.56 (p = 5.49E-06), respectively) and bronchial biopsies (log2FC of 0.49 (p = 0.00021) and log2FC of 0.246 (p = 0.028), respectively). CONCLUSION: This study identifies key differences in expression of genes related to susceptibility and aetiology of COVID-19 within the COPD lung. Further studies to understand the impact on clinical course of disease are now required.
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    Factors associated with antihypertensive medication use and blood pressure control in a rural area in Bangladesh: baseline data from a cluster randomised control trial
    Islam, FMA ; Lambert, EA ; Islam, SMS ; Islam, MA ; Maddison, R ; Thompson, B ; Lambert, GW (BMC, 2021-12-23)
    BACKGROUND: The use of antihypertensive medications is critical for controlling high blood pressure. We aimed to investigate associations between socio-demographic factors and antihypertensive medications use, and antihypertensive medications use with different types of drugs use with levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP). METHODS: For the present report we derived data from the baseline measurements of a cluster randomised control trial on 307 participants with previously diagnosed hypertension from the rural district of Narial in Bangladesh. We measured the participant's current blood pressure levels and recorded antihypertensive medications uses. Associated factors included socio-economic status, diabetes, antihypertensive medications use, and types of drugs and doses used for controlling blood pressure. We applied analysis of variance and logistic regression techniques to identify factors associated with blood pressure. RESULTS: Of the total participants, 144 (46.9%) were on antihypertensive medications. After multivariate adjustment, binary logistic regression revealed that employees (odds ratio, (95% confidence interval (CI)) (OR 3.58, 95%CI 1.38-9.28) compared to farmers, and people with diabetes (OR 2.43, 95%CI 1.13-5.26) compared to people without diabetes were associated with a higher proportion of antihypertensive medications use. Of 144 participants on antihypertensive medications, 7 (5%) had taken two doses, 114 (79%) had taken one dose per day and the rest were irregular in medication use. The mean (standard deviation) [min, max] SBP and DBP were 149 (19) mmHg [114, 217] and 90 (10) mmHg [75, 126], respectively. Overall, there was no significant difference in SBP (p = 0.10) or DBP (p = 0.67) between participants with or without antihypertensive medications or using any type of medications (p = 0.54 for SBP and 0.76 for DBP). There was no significant association between antihypertensive medications use and elevated BP levels SBP/DBP≥140/90 mmHg (p = 0.42) CONCLUSION: Less than half of the people with hypertension were on medication. Irrespective of the antihypertensive medications use, most of the participant's blood pressure was high. Further study is needed with a large sample to understand the factors and aetiology of unmanaged hypertension in rural areas of Bangladesh where the prevalence of hypertension is very high.
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    Understanding the sociodemographic factors associated with intention to receive SMS messages for health information in a rural area of Bangladesh
    Islam, FMA ; Lambert, EA ; Islam, SMS ; Hosen, MA ; Thompson, BR ; Lambert, GW (BMC, 2021-12-30)
    BACKGROUND: The use of digital interventions for managing chronic diseases is significantly increasing. The aim of this study was to estimate the proportion of ownership of a mobile phone, and factors associated with the ability to read and access SMS delivered health information, and willingness to pay for it among people with hypertension in a rural area in Bangladesh. METHODS: Data were collected from 307 participants aged 30 to 75 years with hypertension from a rural area in Bangladesh from December 2020 to January 2021. Outcome measures included ownership of a mobile phone, ability to read SMS, willingness to receive and pay for health information by SMS. Associated factors included age, gender, level of education, occupation, and socioeconomic status. We used regression analysis to identify variables associated with the outcome variables. RESULTS: Overall, 189 (61.6%) people owned a mobile phone which was higher in men (73.3% vs. 50%, p < 0.001), younger people (82.6% aged 30-39 years vs. 53.5% aged 60-75 years, p < 0.001). Of the total participants, 207 (67.4%) were willing to receive SMS, and 155 (50.5%) were willing to pay for receiving SMS for health information. The prevalence was significantly higher among professionals (odds ratio (OR), 95% confidence interval (CI): 4.58, 1.73-12.1) and businesspersons (OR 3.68, 95% CI 1.49-9.10) compared to farmers, respectively. The median (interquartile range [IQR]) of willingness to pay for health information SMS was 10 (28) Bangladesh Taka (BDT) (1 BDT ~ 0.013 US$), and there were no specific factors that were associated with the willingness of any higher amounts of payment. In terms of reading SMS of people who own a mobile, less than half could read SMS. The proportion of people who could read SMS was significantly higher among men, younger people, educated people, middle class or rich people, professionals or businesspersons. Of people who could read SMS, the majority read SMS occasionally. CONCLUSION: A significant proportion of people are unable to read SMS. However, people are willing to receive and pay to receive SMS for health information. Education and awareness programs should be conducted among targeted groups, including people with low education and women.
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    Knowledge of and Intention to Participate in Physical Activity Programs and Their Associated Sociodemographic Factors in People with High Blood Pressure in a Rural Area of Bangladesh: Initial Investigation from a Cluster Randomized Controlled Trial
    Islam, FMA ; Hosen, MA ; Islam, MA ; Lambert, EA ; Thompson, BR ; Lambert, GW ; Maddison, R (MDPI, 2021-09)
    This initial investigation aimed to investigate the knowledge of the health benefits of physical activity (PA) and attitudes towards participation in PA. The study recruited 307 people aged 30-75 years with hypertension as part of a cluster randomized controlled trial from a rural area in Bangladesh. Of the 307 participants, 135 participated less than 2.5 h of physical activity per week, from which we collected data on attitudes toward PA. Regression analysis and Rasch analysis were used. More than 85% of homemakers, employees or businesspersons were willing to take part in PA. Based on the combined score from the knowledge and attitude items, 46% of people endorsed PA programs; proportions were higher in men than women (53% vs. 41%). After adjusting for covariates, men (odds ratio, 95% confidence interval (CI) 3.50, 1.72-7.11) compared to women and people with at least primary levels of schooling (OR 3.06, 95% CI, 1.27-7.38) compared with those with no education were more likely to organize or take part in any PA programs. People have positive attitudes towards PA but do not feel obligated to participate in PA programs. Future programs are needed to promote awareness and motivational interventions for PA, especially targeting women and people with low education levels, should be developed and implemented.
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    Lowering blood pressure by changing lifestyle through a motivational education program: a cluster randomized controlled trial study protocol
    Islam, FMA ; Lambert, EA ; Islam, SMS ; Islam, MA ; Biswas, D ; McDonald, R ; Maddison, R ; Thompson, B ; Lambert, GW (BMC, 2021-07-08)
    BACKGROUND: High blood pressure is an independent risk factor of cardiovascular disease (CVD) and is a major cause of disability and death. Managing a healthy lifestyle has been shown to reduce blood pressure and improve health outcomes. We aim to investigate the effectiveness of a lifestyle modification intervention program for lowering blood pressure in a rural area of Bangladesh. METHODS: A single-center cluster randomized controlled trial (RCT). The study will be conducted for 6 months, a total of 300 participants of age 30 to 75 years with 150 adults in each of the intervention and the control arms. The intervention arm will involve the delivery of a blended learning education program on lifestyle changes for the management of high blood pressure. The education program comprises evidence-based information with pictures, fact sheets, and published literature about the effects of high blood pressure on CVD development, increased physical activity, and the role of a healthy diet in blood pressure management. The control group involves providing information booklets and general advice at the baseline data collection point. The primary outcome will be the absolute difference in clinic SBP and DBP. Secondary outcomes include the difference in the percentage of people adopting regular exercise habits, cessation of smoking and reducing sodium chloride intake, health literacy of all participants, and the perceived barriers and enablers to adopt behavior changes by collecting qualitative data. Analyses will include analysis of covariance to report the mean difference in blood pressure between the control and the intervention group and the difference in change in blood pressure due to the intervention. DISCUSSION: The study will assess the effects of physical activity and lifestyle modification in controlling high blood pressure. This study will develop new evidence as to whether a simple lifestyle program implemented in a rural region of a low- and middle-income country will improve blood pressure parameters for people with different chronic diseases by engaging community people. TRIAL REGISTRATION: ClinicalTrials.gov NCT04505150 . Registered on 7 August 2020.