Medicine (RMH) - Research Publications

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    Egg provoked food protein-induced enterocolitis-like syndrome in an adult.
    Zubrinich, C ; Hew, M ; O'Hehir, R (Wiley, 2016-09)
    Food protein-induced enterocolitis syndrome is a non-IgE-mediated food allergy usually diagnosed in infancy. We report a case of a similar syndrome in an adult, following ingestion of egg. We remind clinicians to consider this diagnosis which may present to emergency physicians and gastroenterologists long before an allergist is consulted.
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    Corticosteroid suppression of lipoxin A4 and leukotriene B4 from alveolar macrophages in severe asthma.
    Bhavsar, PK ; Levy, BD ; Hew, MJ ; Pfeffer, MA ; Kazani, S ; Israel, E ; Chung, KF (Springer Science and Business Media LLC, 2010-06-07)
    BACKGROUND: An imbalance in the generation of pro-inflammatory leukotrienes, and counter-regulatory lipoxins is present in severe asthma. We measured leukotriene B4 (LTB4), and lipoxin A4 (LXA4) production by alveolar macrophages (AMs) and studied the impact of corticosteroids. METHODS: AMs obtained by fiberoptic bronchoscopy from 14 non-asthmatics, 12 non-severe and 11 severe asthmatics were stimulated with lipopolysaccharide (LPS,10 microg/ml) with or without dexamethasone (10(-6)M). LTB4 and LXA4 were measured by enzyme immunoassay. RESULTS: LXA4 biosynthesis was decreased from severe asthma AMs compared to non-severe (p < 0.05) and normal subjects (p < 0.001). LXA4 induced by LPS was highest in normal subjects and lowest in severe asthmatics (p < 0.01). Basal levels of LTB4 were decreased in severe asthmatics compared to normal subjects (p < 0.05), but not to non-severe asthma. LPS-induced LTB4 was increased in severe asthma compared to non-severe asthma (p < 0.05). Dexamethasone inhibited LPS-induced LTB4 and LXA4, with lesser suppression of LTB4 in severe asthma patients (p < 0.05). There was a significant correlation between LPS-induced LXA4 and FEV1 (% predicted) (r(s) = 0.60; p < 0.01). CONCLUSIONS: Decreased LXA4 and increased LTB4 generation plus impaired corticosteroid sensitivity of LPS-induced LTB4 but not of LXA4 support a role for AMs in establishing a pro-inflammatory balance in severe asthma.
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    The diagnostic accuracy of chest ultrasound for CT-detected radiographic consolidation in hospitalised adults with acute respiratory failure: a systematic review.
    Hew, M ; Corcoran, JP ; Harriss, EK ; Rahman, NM ; Mallett, S (BMJ, 2015-05-19)
    OBJECTIVES: (1) Summarise chest ultrasound accuracy to diagnose radiological consolidation, referenced to chest CT in patients with acute respiratory failure (ARF). (2) Directly compared ultrasound with chest X-ray. SETTING: Hospitalised patients. PARTICIPANTS: Studies were eligible if adult participants in respiratory failure underwent chest ultrasound to diagnose consolidation referenced to CT. Exclusion: (1) not primary study, (2) not respiratory failure, (3) not chest ultrasound, (4) not consolidation, (5) translation unobtainable, (6) unable to extract data, (7) unable to obtain paper. 4 studies comprising 224 participants met inclusion. OUTCOME MEASURES: As planned, paired forest plots display 95% CIs of sensitivity and specificity for ultrasound and chest X-ray. Sensitivity and specificity from each study are plotted in receiver operator characteristics space. Meta-analysis was planned if studies were sufficiently homogeneous and numerous (≥4). Although this numerical requirement was met, meta-analysis was prevented by heterogeneous units of analysis between studies. RESULTS: All studies were in intensive care, with either a high risk of selection bias or high applicability concerns. Studies had unclear or high risk of bias related to use of ultrasound. Only 1 study clearly performed ultrasound within 24 h of respiratory failure diagnosis. Ultrasound sensitivity ranged from 0.91 (95% CI 0.81 to 0.97) to 1.00 (95% CI 0.95 to 1.00). Specificity ranged from 0.78 (95% CI 0.52 to 0.94) to 1.00 (0.99 to 1.00). In two studies, chest X-ray had lower sensitivity than ultrasound, but there were insufficient patients to compare specificity. CONCLUSIONS: Four small studies suggest ultrasound is highly sensitive and specific for consolidation in ARF, but high risk of bias and concerns about applicability in all studies may have inflated diagnostic accuracy. Further robustly designed studies are needed to define the role of ultrasound in this setting. TRIAL REGISTRATION NUMBER: http://www.crd.york.ac.uk/PROSPERO/ (CRD42013006472).
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    Comorbid "treatable traits" in difficult asthma: Current evidence and clinical evaluation.
    Tay, TR ; Hew, M (Wiley, 2018-07)
    The care of patients with difficult-to-control asthma ("difficult asthma") is challenging and costly. Despite high-intensity asthma treatment, these patients experience poor asthma control and face the greatest risk of asthma morbidity and mortality. Poor asthma control is often driven by severe asthma biology, which has appropriately been the focus of intense research and phenotype-driven therapies. However, it is increasingly apparent that extra-pulmonary comorbidities also contribute substantially to poor asthma control and a heightened disease burden. These comorbidities have been proposed as "treatable traits" in chronic airways disease, adding impetus to their evaluation and management in difficult asthma. In this review, eight major asthma-related comorbidities are discussed: rhinitis, chronic rhinosinusitis, gastroesophageal reflux, obstructive sleep apnoea, vocal cord dysfunction, obesity, dysfunctional breathing and anxiety/depression. We describe the prevalence, impact and treatment effects of these comorbidities in the difficult asthma population, emphasizing gaps in the current literature. We examine the associations between individual comorbidities and highlight the potential for comorbidity clusters to exert combined effects on asthma outcomes. We conclude by outlining a pragmatic clinical approach to assess comorbidities in difficult asthma.
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    The Melbourne thunderstorm asthma event: can we avert another strike?
    Hew, M ; Sutherland, M ; Thien, F ; O'Hehir, R (Wiley, 2017-05)
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    Accuracy and safety of ward based pleural ultrasound in the Australian healthcare system
    Hammerschlag, G ; Denton, M ; Wallbridge, P ; Irving, L ; Hew, M ; Steinfort, D (WILEY, 2017-04)
    BACKGROUND AND OBJECTIVE: Ultrasound has been shown to improve the accuracy and safety of pleural procedures. Studies to date have been performed in large, specialized units, where pleural procedures are performed by a small number of highly specialized physicians. There are no studies examining the safety and accuracy of ultrasound in the Australian healthcare system where procedures are performed by junior doctors with a high staff turnover. METHODS: We performed a retrospective review of the ultrasound database in the Respiratory Department at the Royal Melbourne Hospital to determine accuracy and complications associated pleural procedures. RESULTS: A total of 357 ultrasounds were performed between October 2010 and June 2013. Accuracy of pleural procedures was 350 of 356 (98.3%). Aspiration of pleural fluid was successful in 121 of 126 (96%) of patients. Two (0.9%) patients required chest tube insertion for management of pneumothorax. There were no recorded pleural infections, haemorrhage or viscera puncture. CONCLUSION: Ward-based ultrasound for pleural procedures is safe and accurate when performed by appropriately trained and supported junior medical officers. Our findings support this model of pleural service care in the Australian healthcare system.
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    Comorbidities in difficult asthma are independent risk factors for frequent exacerbations, poor control and diminished quality of life.
    Tay, TR ; Radhakrishna, N ; Hore-Lacy, F ; Smith, C ; Hoy, R ; Dabscheck, E ; Hew, M (Wiley, 2016-11)
    BACKGROUND AND OBJECTIVE: Little is known about how comorbidities affect difficult asthma patients across different domains of asthma outcomes. We hypothesized that comorbidities in difficult asthma significantly influence asthma outcomes. METHODS: We analysed 90 consecutive patients who underwent systematic assessment at our hospital's difficult asthma clinic. Eight comorbidities were assessed in all patients. They were allergic rhinitis, chronic rhinosinusitis (CRS), gastroesophageal reflux disease, obesity, obstructive sleep apnoea, anxiety or depression, dysfunctional breathing (DB) and vocal cord dysfunction (VCD). Asthma outcomes examined were exacerbation frequency (≥3/year vs <3/year), asthma control using the Asthma Control Test (ACT) and quality of life using the Asthma Quality of Life Questionnaire (AQLQ). Multivariate logistic regression was performed for dichotomous outcomes and linear regression for continuous outcomes. Analyses were adjusted for lung function and absolute blood eosinophils. RESULTS: Increasing BMI was an independent risk factor for exacerbations (OR: 1.1, 95% CI: 1-1.1, P = 0.042), lower ACT score (β coefficient: -0.25, 95% CI: -0.37 to -0.12, P < 0.001) and poorer AQLQ (β coefficient: -0.05, 95% CI: -0.09 to -0.02, P = 0.006). DB predicted lower ACT (β coefficient: -2.85, 95% CI: -5 to -0.7, P = 0.01) and AQLQ scores (β coefficient: -0.73, 95% CI: -1.34 to -0.12, P = 0.02). Patients with CRS had more exacerbations (OR: 4, 95% CI: 1.5-10.9, P = 0.006). Patients with VCD had lower AQLQ scores (β coefficient: -0.78, 95% CI: -1.38 to -0.18, P = 0.012). CONCLUSION: Comorbidities independently impact a broad spectrum of outcomes in difficult asthma. Systematic evaluation of these conditions is essential in difficult asthma.
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    A prospective cohort study of thoracic ultrasound in acute respiratory failure: the C3PO protocol.
    Wallbridge, PD ; Joosten, SA ; Hannan, LM ; Steinfort, DP ; Irving, L ; Goldin, J ; Hew, M (SAGE Publications, 2017-05)
    OBJECTIVES: This study was performed to assess the clinical utility of a standardised thoracic ultrasound examination when added to standard care in patients with acute respiratory failure admitted to an intermediate care unit. This study aimed to assess the impact on clinical diagnosis, clinician confidence and management. Ultrasound has been shown to have utility in patients admitted to intensive care and emergency; however, utility in a ward setting is unknown. DESIGN: Prospective cohort study. SETTING: Tertiary hospital in Melbourne, Australia. PARTICIPANTS: 50 patients with acute respiratory failure requiring admission to an intermediate care unit. MAIN OUTCOME MEASURES: (1) Change in clinical diagnosis or additional clinical diagnosis following thoracic ultrasound. (2) Change in diagnostic confidence following thoracic ultrasound. (3) Change to management following thoracic ultrasound. RESULTS: In 34% of patients, ultrasound detected unexpected findings that changed or added to the clinical diagnosis. Diagnostic confidence was increased in 44%, and the treating clinician altered the management plan in 30% as a result of the ultrasound. Ultrasound was particularly useful in clarifying the diagnosis in patients with multiple initial diagnoses, reducing to a single diagnosis in 69%. CONCLUSIONS: Thoracic ultrasound has clinical utility in non-intubated adults with acute respiratory failure managed outside intensive care settings. It changed aetiological diagnosis, increases diagnostic confidence and altered clinical management in one out of three patients scanned. Our results suggest extended utility of thoracic ultrasound in acute respiratory failure to a broader context outside the intensive care unit population.
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    Anaphylaxis presentations to the emergency department: impending Victorian reporting legislation
    Zubrinich, C ; Douglass, J ; Bartlett, J ; Patel, M ; Hew, M (WILEY, 2019-01)
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