Philip G Bardin

Monash University (Australia), Melbourne, Victoria, Australia

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Publications (104)496.13 Total impact

  • Paul T King · Philip G Bardin · Stephen R Holdsworth ·

    American Journal of Respiratory and Critical Care Medicine 10/2015; 192(7):902-903. DOI:10.1164/rccm.201506-1117LE · 13.00 Impact Factor
  • P G Bardin · K Low · L E Ruane ·

    Clinical & Experimental Allergy 09/2015; 45(9):1374-5. DOI:10.1111/cea.12593 · 4.77 Impact Factor
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    Paul Leong · Simon Joosten · Garun Hamilton · Philip G Bardin ·
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    ABSTRACT: Dear Editor, Dyspnoea and exercise intolerance in patients with COPD have a wide variety of aetiologies, with dynamic hyperinflation and resultant loss in inspiratory reserve volume recognised as important mechanisms. Baz et al1 show that dynamic laryngeal narrowing is present in patients with COPD and hypothesise that this generates intrinsic positive end-expiratory pressure (PEEPi), serving to ‘splint’ open … [Full text of this article]
    Thorax 04/2015; 70(7). DOI:10.1136/thoraxjnl-2015-206888 · 8.29 Impact Factor
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    ABSTRACT: Nontypeable Haemophilus influenzae (NTHi) is a prevalent bacterium found in a variety of chronic respiratory diseases. The role of this bacterium in the pathogenesis of lung inflammation is not well defined. In this study we examined the effect of NTHi on two important lung inflammatory processes 1), oxidative stress and 2), protease expression. Bronchoal-veolar macrophages were obtained from 121 human subjects, blood neutrophils from 15 subjects, and human-lung fibroblast and epithelial cell lines from 16 subjects. Cells were stimulated with NTHi to measure the effect on reactive oxygen species (ROS) production and extracellular trap formation. We also measured the production of the oxidant, 3-nitrotyr-osine (3-NT) in the lungs of mice infected with this bacterium. NTHi induced widespread production of 3-NT in mouse lungs. This bacterium induced significantly increased ROS production in human fibroblasts, epithelial cells, macrophages and neutrophils; with the highest levels in the phagocytic cells. In human macrophages NTHi caused a sustained, ex-tracellular production of ROS that increased over time. The production of ROS was associated with the formation of macrophage extracellular trap-like structures which co-expressed the protease metalloproteinase-12. The formation of the macrophage extracellular trap-like structures was markedly inhibited by the addition of DNase. In this study we have demonstrated that NTHi induces lung oxidative stress with macrophage extracellular trap formation and associated protease expression. DNase inhibited the formation of extracellular traps.
    PLoS ONE 03/2015; 10(3):1. DOI:10.1371/journal.pone.0120371 · 3.23 Impact Factor

  • Journal of Allergy and Clinical Immunology 02/2015; 135(2):AB381. DOI:10.1016/j.jaci.2014.12.1874 · 11.48 Impact Factor

  • 2nd Annual Meeting of the International-Cytokine-and-Interferon-Society; 11/2014
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    ABSTRACT: Glucocorticosteroids (GCS) are used on a daily basis to reduce airway inflammation in asthma and chronic obstructive pulmonary disease (COPD). This treatment is usually escalated during acute disease exacerbations, events often associated with virus infections. We examined the impact of GCS on anti-viral defences and virus replication and assessed supplementary interferon (IFN) treatment. Here, we report that treatment of primary human airway cells in vitro with GCS prior to rhinovirus (RV) or influenza A virus (IAV) infection significantly reduces the expression of innate anti-viral genes and increases viral replication. Mice given intranasal treatment with GCS prior to IAV infection developed more severe disease associated with amplified virus replication and elevated inflammation in the airways. Adjuvant IFN treatment markedly reduced GCS-amplified infections in human airway cells and in mouse lung. This study demonstrates that GCS cause an extrinsic compromise in anti-viral defences, enhancing respiratory virus infections and provides a rationale for adjuvant IFN treatment. I nfluenza A virus (IAV) and rhinovirus (RV) cause human respiratory infections leading to acute exacerbations of chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). These infections place patients at increased risk of severe lung disease, often requiring hospitalization 1,2 . For example, during the 2009 IAV H1N1 pandemic, pneumonia occurred chiefly in persons who had exacerbations of pre-existing asthma or COPD 3,4
    Scientific Reports 11/2014; 4:7176. DOI:10.1038/srep07176 · 5.58 Impact Factor
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    ABSTRACT: Background and Objective Abnormal vocal cord movement may coexist with asthma and cause additional upper/middle airway obstruction. The condition may be a form of muscular dystonia that could contribute to asthma resistant to optimised treatments. Botulinum toxin causes temporary paralysis of muscle and may be an effective local treatment that improves asthma control.Methods In an observational study, we evaluated the benefits of unilateral vocal cord injection with botulinum toxin in 11 patients (total 24 injections). Subjects had asthma resistant to optimised treatment and abnormal vocal cord movement. Responses after botulinum toxin treatment were assessed using asthma control test (ACT) scores, vocal cord narrowing quantified by computerised tomography (CT) of the larynx and spirometry. Side-effects were recorded.ResultsACT scores improved overall (9.1 ± 2.4 before and 13.5 ± 4.5 after treatment; difference 4.4 ± 4.2; P < 0.001). There was also an improvement in airway size on CT larynx (time below lower limit of normal at baseline 39.4 ± 37.63% and improved to 17.6 ± 25.6% after injection; P = 0.032). Spirometry was not altered. One patient experienced an asthma exacerbation but overall side-effects were moderate, chiefly dysphonia and dysphagia.Conclusions Although a placebo effect cannot be ruled out, local injection of botulinum toxin may be an effective treatment for intractable asthma associated with abnormal vocal cord movement. Further mechanistic studies and a double-blind randomised controlled trial of botulinum toxin treatment are merited.
    Respirology 04/2014; 19(4). DOI:10.1111/resp.12271 · 3.35 Impact Factor
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    ABSTRACT: Idiopathic bilateral vocal cord paralysis (VCP) is a rare and difficult condition often undiagnosed and frequently confused with asthma and other respiratory conditions. Accurate diagnosis is crucial since 80% of cases patients require surgical intervention, such as tracheostomy or laser surgery, to relieve symptoms. The “gold standard” for diagnosing VCP has been laryngoscopy. In this case study, we demonstrate for the first time that idiopathic bilateral VCP can be accurately diagnosed by means of a novel noninvasive methodology: dynamic volume 320-slice computed tomography larynx. Three-dimensional reconstruction of laryngeal motion during the breathing cycle permitted functional assessment of the larynx showing absence of vocal cord movements. The new methodology may be valuable for noninvasive diagnosis of vocal cord movement disorders before and for follow-up after surgery.
    03/2014; 2(1). DOI:10.1002/rcr2.37
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    ABSTRACT: Pulmonary emphysema is linked to T cell-mediated autoimmune inflammation, although the pathogenic role of specific pro-inflammatory cytokines remains unclear. The Th17 type response, characterized by the production of the cytokine interleukin (IL)-17A, is modulated in part by the IL-6/signal transducer and activator of transcription (Stat)3 signalling axis and is associated with numerous autoimmune diseases. We therefore evaluated a causal role for IL-17A in the IL-6-driven gp130(F) (/) (F) mouse model for spontaneous pulmonary inflammation and emphysema. The expression of Th17-related factors was quantified in the lungs of gp130(F) (/) (F) mice and emphysematous patients, and the degree of pulmonary inflammation and emphysema was measured in gp130(F) (/) (F) : Il17a(-/-) mice by immunohistochemistry, stereology and respiratory mechanics. In gp130(F) (/) (F) mice, lung gene expression of Il17a and other Th17-related factors was augmented compared with gp130(+/+) (wild-type), gp130(F) (/) (F) : Il6(-/-) and gp130(F) (/) (F) : Stat3(-/+) mice displaying normalized Stat3 activity and no lung inflammation. Importantly, genetic ablation of Il17a in gp130(F) (/) (F) : Il17a(-/-) mice prevented lung inflammation; however, emphysema still developed. Additionally, messenger RNA expression of inflammatory genes Cxcl1, Cxcl2, Ccl2 and Tnfα; as well as Il6 and the Stat3-target gene, Socs3, were upregulated in the lungs of gp130(F) (/) (F) mice compared with gp130(F) (/) (F) : Il17a(-/-) and gp130(+/+) mice. Consistent with these findings, augmented IL17A expression was observed in emphysema patients presenting with inflammation compared with inflammation-free individuals. Collectively, our data suggest that the integration of IL-17A into the IL-6/Stat3 signalling axis mediates lung inflammation, but not emphysema, and that discrete targeting of IL-17A may alleviate pulmonary inflammatory-related diseases.
    Respirology 02/2014; 19(3). DOI:10.1111/resp.12243 · 3.35 Impact Factor
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    Martin Macdonald · Tony Korman · Paul King · Kais Hamza · Philip Bardin ·
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    ABSTRACT: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are crucial events but causes remain poorly defined. A method to clinically 'phenotype' AECOPD have been proposed, and 52 hospitalized chronic obstructive pulmonary disease exacerbations according to underlying aetiology have now been prospectively phenotyped. Multiple exacerbation phenotypes were identified. A subpopulation coinfected with virus and bacteria had a significantly longer length of hospital stay, and this pilot study indicates that exacerbation phenotyping may be advantageous.
    Respirology 11/2013; 18(8):1280-1. DOI:10.1111/resp.12197 · 3.35 Impact Factor
  • P Leong · P.G. Bardin · K.K. Lau ·
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    ABSTRACT: Tracheomalacia, tracheobronchomalacia, and excessive dynamic airway collapse are all terms used to describe tracheal narrowing in expiration. The first two describe luminal reduction from cartilage softening and the latter refers to luminal reduction from exaggerated posterior membrane movement. Expiratory tracheal narrowing is a frequent occurrence that can cause symptoms of airway obstruction, such as dyspnoea, wheeze, and exercise intolerance. The accurate diagnosis and quantification of expiratory tracheal narrowing has important aetiological, therapeutic, and prognostic implications. The reference standard for diagnosis has traditionally been bronchoscopy; however, this method has significant limitations. Expiratory tracheal disorders are readily detected by four-dimensional dynamic volume multidetector computed tomography (4D-CT), an emerging, non-invasive method that will potentially enable detection and quantification of these conditions. This review discusses the morphological forms of expiratory tracheal narrowing and demonstrates the utility of 4D-CT in the diagnosis, quantification, and treatment of these important conditions.
    Clinical Radiology 08/2013; 68(12). DOI:10.1016/j.crad.2013.06.017 · 1.76 Impact Factor
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    ABSTRACT: Human Rhinovirus (HRV) infection results in shut down of essential cellular processes, in part through disruption of nucleocytoplasmic transport by cleavage of the nucleoporin proteins (Nups) that make up the host cell nuclear pore. Although the HRV genome encodes two proteases (2A and 3C) able to cleave host proteins such as Nup62, little is known regarding the specific contribution of each. Here we use transfected as well as HRV-infected cells to establish for the first time that 3C protease is most likely the mediator of cleavage of Nup153 during HRV infection, while Nup62 and Nup98 are likely to be targets of HRV2A protease. HRV16 3C protease was also able to elicit changes in the appearance and distribution of the nuclear speckle protein SC35 in transfected cells, implicating it as a key mediator of the mislocalisation of SC35 in HRV16-infected cells. In addition, 3C protease activity led to the redistribution of the nucleolin protein out of the nucleolus, but did not affect nuclear localisation of hnRNP proteins, implying that complete disruption of nucleocytoplasmic transport leading to relocalisation of hnRNP proteins from the nucleus to the cytoplasm in HRV-infected cells almost certainly requires 2A in addition to 3C protease. Thus, a specific role for HRV 3C protease in cleavage and mislocalisation of host cell nuclear proteins, in concert with 2A, is implicated for the first time in HRV pathogenesis.
    PLoS ONE 08/2013; 8(8):e71316. DOI:10.1371/journal.pone.0071316 · 3.23 Impact Factor
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    Philip G Bardin · Peter W Holmes · Garun Hamilton ·

    Respirology 06/2013; 18(6). DOI:10.1111/resp.12135 · 3.35 Impact Factor
  • Paul T King · Martin MacDonald · Philip G Bardin ·

    01/2013; 1(1):13. DOI:10.1186/2213-0802-1-13
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    ABSTRACT: BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary inflammation that persists after the cessation of smoking. T cells have a major role in driving inflammation in patients with COPD and are activated by specific antigens to produce mediators, such as cytokines. The antigens that activate lung T cells have not been clearly defined. Nontypeable Haemophilus influenzae (NTHi) is the dominant bacterium isolated from the lungs of patients with COPD. Objective: We sought to measure the response of lung tissue T cells to stimulation with NTHi. METHODS: We obtained lung tissue from 69 subjects having lobectomies for lung cancer. Of the group, 39 subjects had COPD, and 30 without COPD were classified as control subjects. The lung tissue was dispersed into single-cell suspensions and stimulated with live NTHi. Cells were labeled with antibodies for 5 important inflammatory mediators in patients with COPD and analyzed by using flow cytometry. RESULTS: NTHi produced strong activation of both T(H) cells and cytotoxic T cells in the COPD cohort. The COPD cohort had significantly higher levels of cells producing TNF-α, IL-13, and IL-17 in both T-cell subsets. When control subjects were divided into those with and without a significant smoking history and compared with patients with COPD, there was a progressive increase in the numbers of T cells producing cytokines from nonsmoking control subjects to smoking control subjects to patients with COPD. CONCLUSION: NTHi activates lung T cells in patients with COPD. This proinflammatory profibrotic response might be a key cause of inflammation in patients with COPD and has implications for treatment.
    The Journal of allergy and clinical immunology 11/2012; 131(5). DOI:10.1016/j.jaci.2012.09.030 · 11.48 Impact Factor
  • Philip G Bardin · Sebastian L Johnston · Garun Hamilton ·
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    ABSTRACT: Background: Lower airway obstruction has evolved to denote pathologies associated with diseases of the lung, whereas, conditions proximal to the lung embody upper airway obstruction. This approach has disconnected diseases of the larynx and trachea from the lung, and removed the 'middle airway' from the interest and involvement of respiratory physicians and scientists. However, recent studies have indicated that dysfunction of this anatomical region may be a key component of overall airway obstruction, either independently or in combination with lung disease. New diagnostic modalities to effectively diagnose middle airway obstruction are being developed, and it has become feasible to identify and quantify middle airway obstruction. Conclusion: We, therefore, propose adding 'middle airway obstruction' to our nomenclature to embed it in diagnostic approaches, and to allow due emphasis on this neglected anatomical region.
    Thorax 07/2012; 68(4). DOI:10.1136/thoraxjnl-2012-202221 · 8.29 Impact Factor

  • Movement Disorders 06/2012; 27. · 5.68 Impact Factor

  • American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California; 05/2012

  • American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California; 05/2012

Publication Stats

3k Citations
496.13 Total Impact Points


  • 2001-2015
    • Monash University (Australia)
      • • Department of Medicine
      • • Centre for Innate Immunity and Infectious Diseases
      • • Monash Medical Centre
      • • Monash Centre for Inflammatory Diseases
      Melbourne, Victoria, Australia
  • 2011-2014
    • University of Vic
      Vic, Catalonia, Spain
  • 2010
    • Victoria University Melbourne
      Melbourne, Victoria, Australia
  • 1987-2006
    • Tygerberg Hospital
      Kaapstad, Western Cape, South Africa
  • 2004
    • University of Melbourne
      Melbourne, Victoria, Australia
  • 1993-2003
    • University of Southampton
      • Faculty of Medicine
      Southampton, England, United Kingdom
  • 1990-2003
    • Stellenbosch University
      • • Division of Medical Virology
      • • Division of General Internal Medicine
      Stellenbosch, Western Cape, South Africa
  • 2002
    • Molecular and Cellular Biology Program
      Seattle, Washington, United States