2019 |
Donovan C, Starkey MR, Kim RY, Rana BMJ, Barlow JL, Jones B, et al., 'Roles for T/B lymphocytes and ILC2s in experimental chronic obstructive pulmonary disease.', J Leukoc Biol, 105 143-150 (2019)
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2019 |
Wang H, FitzPatrick M, Wilson NJ, Anthony D, Reading PC, Satzke C, et al., 'CSF3R/CD114 mediates infection-dependent transition to severe asthma', Journal of Allergy and Clinical Immunology, 143 785-788.e6 (2019)
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2019 |
McDonald VM, Hiles SA, Godbout K, Harvey ES, Marks GB, Hew M, et al., 'Treatable traits can be identified in a severe asthma registry and predict future exacerbations.', Respirology, 24 37-47 (2019)
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2019 |
Lokwani R, Wark PAB, Baines KJ, Barker D, Simpson JL, 'Hypersegmented airway neutrophils and its association with reduced lung function in adults with obstructive airway disease: an exploratory study.', BMJ Open, 9 e024330 (2019)
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2019 |
Ng SW, Chan Y, Chellappan DK, Madheswaran T, Zeeshan F, Chan YL, et al., 'Molecular modulators of celastrol as the keystones for its diverse pharmacological activities', Biomedicine and Pharmacotherapy, 109 1785-1792 (2019)
© 2018 The Authors In the recent years, much attention has been focused on identifying bioactive compounds from medicinal plants that could be employed in therapeutics, which is a... [more]
© 2018 The Authors In the recent years, much attention has been focused on identifying bioactive compounds from medicinal plants that could be employed in therapeutics, which is attributed to their potent pharmacological actions and better toxicological profile. One such example that has come into the light with considerable interest is the pentacyclic triterpenoid, celastrol, which has been found to provide substantial therapeutic properties in a variety of diseases. In an effort to further accelerate its potential to be utilized in clinical practice in the future; along with advancing technologies in the field of drug discovery and development, different researchers have been investigating on the various mechanisms and immunological targets of celastrol that underlie its broad spectrum of pharmacological properties. In this review, we have collated the various research findings related to the molecular modulators responsible for different pharmacological activities shown by celastrol. Our review will be of interest to the herbal, biological, molecular scientist and by providing a quick snapshot about celastrol giving a new direction in the area of herbal drug discovery and development.
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2018 |
Reid AT, Veerati PC, Gosens R, Bartlett NW, Wark PA, Grainge CL, et al., 'Persistent induction of goblet cell differentiation in the airways: Therapeutic approaches', Pharmacology and Therapeutics, 185 155-169 (2018) [C1]
© 2017 Dysregulated induction of goblet cell differentiation results in excessive production and retention of mucus and is a common feature of several chronic airways diseases. To... [more]
© 2017 Dysregulated induction of goblet cell differentiation results in excessive production and retention of mucus and is a common feature of several chronic airways diseases. To date, therapeutic strategies to reduce mucus accumulation have focused primarily on altering the properties of the mucus itself, or have aimed to limit the production of mucus-stimulating cytokines. Here we review the current knowledge of key molecular pathways that are dysregulated during persistent goblet cell differentiation and highlights both pre-existing and novel therapeutic strategies to combat this pathology.
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2018 |
Ramsahai JM, Simpson J, Wark P, 'Eosinophilia as a treatable trait in three patients with asthma and copd', Respirology Case Reports, 6 (2018) [C1]
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2018 |
Hiles SA, Harvey ES, McDonald VM, Peters M, Bardin P, Reynolds PN, Upham JW, 'Working while unwell: Workplace impairment in people with severe asthma', CLINICAL AND EXPERIMENTAL ALLERGY, 48 650-662 (2018)
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2018 |
Ng ZY, Wong JY, Panneerselvam J, Madheswaran T, Kumar P, Pillay V, et al., 'Assessing the potential of liposomes loaded with curcumin as a therapeutic intervention in asthma', Colloids and Surfaces B: Biointerfaces, 172 51-59 (2018) [C1]
© 2018 Elsevier B.V. Curcumin a component of turmeric, which is derived from Curcuma longa is used as a colouring agent and as a dietary spice for centuries. Extensive studies hav... [more]
© 2018 Elsevier B.V. Curcumin a component of turmeric, which is derived from Curcuma longa is used as a colouring agent and as a dietary spice for centuries. Extensive studies have been done on the anti-inflammatory activity of curcumin along with its molecular mechanism involving different signalling pathways. However, the physicochemical and biological properties such as poor solubility and rapid metabolism of curcumin have led to low bioavailability and hence limits its application. Current therapies for asthma such as bronchodilators and inhaled corticosteroids (ICS) are aimed at controlling disease symptoms and prevent asthma exacerbation. However, this approach requires lifetime therapy and is associated with a constellation of side effects. This creates a clear unmet medical need and there is an urgent demand for new and more-effective treatments. The present study is aimed to formulate liposomes containing curcumin and evaluate for its anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation on BCi-NS1.1 cell line. Curcumin and salbutamol liposomes were formulated using lipid hydration method. The prepared liposomes were characterized in terms of particle size, zeta potential, encapsulation efficiency and in-vitro release profile. The liposomes were tested on BCI-NS1.1 cell line to evaluate its anti-inflammatory properties. The various pro-inflammatory markers studied were Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-1ß (IL-1ß) and Tumour Necrosis Factor-a (TNF-a). Additionally, molecular mechanics simulations were used to elucidate the positioning, energy minimization, and aqueous dispersion of the liposomal architecture involving lecithin and curcumin. The prepared curcumin formulation showed an average size and zeta potential of 271.3 ± 3.06 nm and -61.0 mV, respectively. The drug encapsulation efficiency of liposomal curcumin is 81.1%. Both curcumin-loaded liposomes formulation (1 µg/mL, 5 µg/mL) resulted in significant (p < 0.05) reduction in the level of pro-inflammatory marker expression such as IL-6, IL-8, IL-1ß and TNF-a compared to positive control group. Liposomal curcumin with the dose of 1 µg/mL reduced the inflammatory markers more effectively compared to that of 5 µg/mL. Liposomal curcumin could be a promising intervention for asthma therapy showing their efficacy in suppressing the important pro-inflammatory markers involved in the pathogenesis of asthma.
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2018 |
Pradeepan S, Wark P, 'Pseudomonas pharyngitis in a cystic fibrosis patient', RESPIROLOGY CASE REPORTS, 6 (2018)
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2018 |
Singanayagam A, Glanville N, Girkin JL, Ching YM, Marcellini A, Porter JD, et al., 'Corticosteroid suppression of antiviral immunity increases bacterial loads and mucus production in COPD exacerbations', NATURE COMMUNICATIONS, 9 (2018) [C1]
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2018 |
Robijn AL, Jensen ME, Gibson PG, Powell H, Giles WB, Clifton VL, et al., 'Trends in asthma self-management skills and inhaled corticosteroid use during pregnancy and postpartum from 2004 to 2017.', J Asthma, 1-9 (2018)
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2018 |
Kaiko GE, Wark PAB, 'Developments in cystic fibrosis personalised epithelial assays: Science and patient perspectives', JOURNAL OF CYSTIC FIBROSIS, 17 289-291 (2018)
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2018 |
Tan DBA, Teo T-H, Setiawan AM, Ong NE, Zimmermann M, Hsu AC-Y, et al., 'Impaired Th1 responses in patients with acute exacerbations of COPD are improved with PD-1 blockade', CLINICAL IMMUNOLOGY, 188 64-66 (2018)
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2018 |
Ramsahai JM, Wark PAB, 'Appropriate use of oral corticosteroids for severe asthma', MEDICAL JOURNAL OF AUSTRALIA, 209 S18-S21 (2018) [C1]
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2018 |
Wark P, McDonald VM, 'Nebulised hypertonic saline for cystic fibrosis', COCHRANE DATABASE OF SYSTEMATIC REVIEWS, (2018)
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2018 |
Wark PAB, Ramsahai JM, Pathinayake P, Malik B, Bartlett NW, 'Respiratory Viruses and Asthma', Seminars in Respiratory and Critical Care Medicine, 39 45-55 (2018) [C1]
© 2018 by Thieme Medical Publishers, Inc. Asthma remains the most prevalent chronic respiratory disorder, affecting people of all ages. The relationship between respiratory virus ... [more]
© 2018 by Thieme Medical Publishers, Inc. Asthma remains the most prevalent chronic respiratory disorder, affecting people of all ages. The relationship between respiratory virus infection and asthma has long been recognized, though remains incompletely understood. In this article, we will address key issues around this relationship. These will include the crucial role virus infection plays in early life, as a potential risk factor for the development of asthma and lung disease. We will assess the impact that virus infection has on those with established asthma as a trigger for acute disease and how this may influence asthma throughout life. Finally, we will explore the complex interaction that occurs between the airway and the immune responses that make those with asthma so susceptible to the effects of virus infection.
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2018 |
Pathinayake PS, Hsu AC-Y, Waters DW, Hansbro PM, Wood LG, Wark PAB, 'Understanding the Unfolded Protein Response in the Pathogenesis of Asthma', FRONTIERS IN IMMUNOLOGY, 9 (2018) [C1]
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2018 |
Moheimani F, Koops J, Williams T, Reid AT, Hansbro PM, Wark PA, Knight DA, 'Influenza A virus infection dysregulates the expression of microRNA-22 and its targets; CD147 and HDAC4, in epithelium of asthmatics', Respiratory Research, 19 (2018) [C1]
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2018 |
King GG, James A, Harkness L, Wark PAB, 'Pathophysiology of severe asthma: We¿ve only just started', Respirology, 23 262-271 (2018) [C1]
© 2018 Asian Pacific Society of Respirology Severe asthma is defined by the high treatment requirements to partly or fully control the clinical manifestations of disease. It remai... [more]
© 2018 Asian Pacific Society of Respirology Severe asthma is defined by the high treatment requirements to partly or fully control the clinical manifestations of disease. It remains a problem worldwide with a large burden for individuals and health services. The key to improving targeted treatments, reducing disease burden and improving patient outcomes is a better understanding of the pathophysiology and mechanisms of severe disease. The heterogeneity, complexity and difficulties in undertaking clinical studies in severe asthma remain challenges to achieving better understanding and better outcomes. In this review, we focus on the structural, mechanical and inflammatory abnormalities that are relevant in severe asthma.
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2018 |
Chellappan DK, Ng ZY, Wong JY, Hsu A, Wark P, Hansbro N, et al., 'Immunological axis of curcumin-loaded vesicular drug delivery systems', Future Medicinal Chemistry, 10 839-844 (2018) [C1]
© 2018 Newlands Press. Several vesicular systems loaded with curcumin have found their way in the therapeutic applications of several diseases, primarily acting through their immu... [more]
© 2018 Newlands Press. Several vesicular systems loaded with curcumin have found their way in the therapeutic applications of several diseases, primarily acting through their immunological pathways. Such systems use particles at a nanoscale range, bringing about their intended use through a range of complex mechanisms. Apart from delivering drug substances into target tissues, these vesicular systems also effectively overcome problems like insolubility and unequal drug distribution. Several mechanisms are explored lately by different workers, and interest over vesicular curcumin has been renewed in the past decade. This commentary discusses several immunological targets in which curcumin is employed in a vesicular form.
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2018 |
Hosseini B, Berthon BS, Saedisomeolia A, Starkey MR, Collison A, Wark PAB, Wood LG, 'Effects of fruit and vegetable consumption on inflammatory biomarkers and immune cell populations: a systematic literature review and meta-analysis.', The American journal of clinical nutrition, 108 136-155 (2018) [C1]
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2017 |
Conickx G, Mestdagh P, Cobos FA, Verhamme FM, Maes T, Vanaudenaerde BM, et al., 'MicroRNA profiling reveals a role for MicroRNA-218-5p in the pathogenesis of chronic obstructive pulmonary disease', American Journal of Respiratory and Critical Care Medicine, 195 43-56 (2017) [C1]
Rationale: Aberrant expression of microRNAs (miRNAs) can have a detrimental role in disease pathogenesis. Objectives: To identify dysregulated miRNAs in lung tissue of patients wi... [more]
Rationale: Aberrant expression of microRNAs (miRNAs) can have a detrimental role in disease pathogenesis. Objectives: To identify dysregulated miRNAs in lung tissue of patients with chronic obstructive pulmonary disease (COPD). Methods: We performed miRNA and mRNA profiling using high throughput stem-loop reverse-transcriptase quantitative polymerase chain reaction and mRNA microarray, respectively, on lung tissue of 30 patients (screening cohort) encompassing 8 never-smokers, 10 smokers without airflow limitation, and 12 smokers with COPD. Differential expression of miRNA-218-5p (miR-218-5p) was validated by reverse-transcriptase quantitative polymerase chain reaction in an independent cohort of 71 patients, an in vivo murine model of COPD, and primary human bronchial epithelial cells. Localization of miR-218-5p was assessed by in situ hybridization. In vitro and in vivo perturbation of miR-218-5p combined with RNA sequencing and gene set enrichment analysis was used to elucidate its functional role in COPD pathogenesis. Measurements and Main Results: Several miRNAs were differentially expressed among the different patient groups. Interestingly, miR-218-5p was significantly down-regulated in smokers without airflow limitation and in patients with COPD compared with never-smokers. Decreased pulmonary expression of miR-218-5p was validated in an independent validation cohort, in cigarette smoke-exposed mice, and in human bronchial epithelial cells. Importantly, expression of miR-218-5p strongly correlated with airway obstruction. Furthermore, cellular localization of miR-218-5p in human and murine lung revealed highest expression of miR-218-5p in the bronchial airway epithelium. Perturbation experiments with a miR-218-5p mimic or inhibitor demonstrated a protective role of miR-218-5p in cigarette smoke-induced inflammation and COPD. Conclusions: We highlight a role for miR-218-5p in the pathogenesis of COPD.
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2017 |
McDonald VM, Maltby S, Reddel HK, King GG, Wark PAB, Smith L, et al., 'Severe asthma: Current management, targeted therapies and future directions¿A roundtable report', Respirology, 22 53-60 (2017) [C1]
© 2016 Asian Pacific Society of Respirology Asthma is a chronic respiratory disease characterized by respiratory symptoms, airway inflammation, airway obstruction and airway hyper... [more]
© 2016 Asian Pacific Society of Respirology Asthma is a chronic respiratory disease characterized by respiratory symptoms, airway inflammation, airway obstruction and airway hyper-responsiveness. Asthma is common and directly affects 10% of Australians, 1¿5% of adults in Asia and 300 million people worldwide. It is a heterogeneous disorder with many clinical, molecular, biological and pathophysiological phenotypes. Current management strategies successfully treat the majority of patients with asthma who have access to them. However, there is a subset of an estimated 5¿10% of patients with asthma who have severe disease and are disproportionately impacted by symptoms, exacerbations and overall illness burden. The care required for this relatively small proportion of patients is also significant and has a major impact on the healthcare system. A number of new therapies that hold promise for severe asthma are currently in clinical trials or are entering the Australian and international market. However, recognition of severe asthma in clinical practice is variable, and there is little consensus on the best models of care or how to integrate emerging and often costly therapies into current practice. In this article, we report on roundtable discussions held with severe asthma experts from around Australia, and make recommendations about approaches for better patient diagnosis and assessment. We assess current models of care for patient management and discuss how approaches may be optimized to improve patient outcomes. Finally, we propose mechanisms to assess new therapies and how to best integrate these approaches into future treatment.
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2017 |
McElvaney NG, Burdon J, Holmes M, Glanville A, Wark PAB, Thompson PJ, et al., 'Long-term efficacy and safety of a1 proteinase inhibitor treatment for emphysema caused by severe a1 antitrypsin deficiency: an open-label extension trial (RAPID-OLE)', The Lancet Respiratory Medicine, 5 51-60 (2017) [C1]
© 2017 Elsevier Ltd Background Purified a1 proteinase inhibitor (A1PI) slowed emphysema progression in patients with severe a1 antitrypsin deficiency in a randomised controlled tr... [more]
© 2017 Elsevier Ltd Background Purified a1 proteinase inhibitor (A1PI) slowed emphysema progression in patients with severe a1 antitrypsin deficiency in a randomised controlled trial (RAPID-RCT), which was followed by an open-label extension trial (RAPID-OLE). The aim was to investigate the prolonged treatment effect of A1PI on the progression of emphysema as assessed by the loss of lung density in relation to RAPID-RCT. Methods Patients who had received either A1PI treatment (Zemaira or Respreeza; early-start group) or placebo (delayed-start group) in the RAPID-RCT trial were included in this 2-year open-label extension trial (RAPID-OLE). Patients from 22 hospitals in 11 countries outside of the USA received 60 mg/kg per week A1PI. The primary endpoint was annual rate of adjusted 15th percentile lung density loss measured using CT in the intention-to-treat population with a mixed-effects regression model. This trial is registered with ClinicalTrials.gov, number NCT00670007. Findings Between March 1, 2006, and Oct 13, 2010, 140 patients from RAPID-RCT entered RAPID-OLE: 76 from the early-start group and 64 from the delayed-start group. Between day 1 and month 24 (RAPID-RCT), the rate of lung density loss in RAPID-OLE patients was lower in the early-start group (-1·51 g/L per year [SE 0·25] at total lung capacity [TLC]; -1·55 g/L per year [0·24] at TLC plus functional residual capacity [FRC]; and -1·60 g/L per year [0·26] at FRC) than in the delayed-start group (-2·26 g/L per year [0·27] at TLC; -2·16 g/L per year [0·26] at TLC plus FRC, and -2·05 g/L per year [0·28] at FRC). Between months 24 and 48, the rate of lung density loss was reduced in delayed-start patients (from -2·26 g/L per year to -1·26 g/L per year), but no significant difference was seen in the rate in early-start patients during this time period (-1·51 g/L per year to -1·63 g/L per year), thus in early-start patients the efficacy was sustained to month 48. Interpretation RAPID-OLE supports the continued efficacy of A1PI in slowing disease progression during 4 years of treatment. Lost lung density was never recovered, highlighting the importance of early intervention with A1PI treatment. Funding CSL Behring.
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2017 |
Hosseini B, Berthon BS, Wark P, Wood LG, 'Effects of Fruit and Vegetable Consumption on Risk of Asthma, Wheezing and Immune Responses: A Systematic Review and Meta-Analysis', NUTRIENTS, 9 (2017) [C1]
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2017 |
Murray LA, Grainge C, Wark PA, Knight DA, 'Use of biologics to treat acute exacerbations and manage disease in asthma, COPD and IPF', Pharmacology and Therapeutics, 169 1-12 (2017) [C1]
© 2016 Elsevier Inc. A common feature of chronic respiratory disease is the progressive decline in lung function. The decline can be indolent, or it can be accelerated by acute ex... [more]
© 2016 Elsevier Inc. A common feature of chronic respiratory disease is the progressive decline in lung function. The decline can be indolent, or it can be accelerated by acute exacerbations, whereby the patient experiences a pronounced worsening of disease symptoms. Moreover, acute exacerbations may also be a marker of insufficient disease management. The underlying cause of an acute exacerbation can be due to insults such as pathogens or environmental pollutants, or the cause can be unknown. For each acute exacerbation, the patient may require medical intervention such as rescue medication, or in more severe cases, hospitalization and ventilation and have an increased risk of death. Biologics, such as monoclonal antibodies, are being developed for chronic respiratory diseases including asthma, COPD and IPF. This therapeutic approach is particularly well suited for chronic use based on the route and frequency of delivery and importantly, the potential for disease modification. In recent clinical trials, the frequency of acute exacerbation has often been included as an endpoint, to help determine whether the investigational agent is impacting disease. Therefore the significance of acute exacerbations in driving disease, and their potential as a marker of disease activity and progression, has recently received much attention. There is also now a need to standardize the definition of an acute exacerbation in specific disease settings, particularly as this endpoint is increasingly used in clinical trials to also assess therapeutic efficacy. Moreover, specifically targeting exacerbations may offer a new therapeutic approach for several chronic respiratory diseases.
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2017 |
Huff RD, Hsu ACY, Nichol KS, Jones B, Knight DA, Wark PAB, et al., 'Regulation of xanthine dehydrogensase gene expression and uric acid production in human airway epithelial cells', PLoS ONE, 12 1-17 (2017) [C1]
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2017 |
Liu G, Cooley MA, Nair PM, Donovan C, Hsu AC, Jarnicki AG, et al., 'Airway remodelling and inflammation in asthma are dependent on the extracellular matrix protein fibulin-1c', JOURNAL OF PATHOLOGY, 243 510-523 (2017) [C1]
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2017 |
Ferreira D, Davies A, Thiruchelvam T, Wark P, 'Acutemyocardial infarction in disseminatedmucormycosis infection', European Heart Journal, 38 838 (2017)
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2017 |
Kim RY, Pinkerton JW, Essilfie AT, Robertson AAB, Baines KJ, Brown AC, et al., 'Role for NLRP3 inflammasome-mediated, IL-1ß-dependent responses in severe, steroid-resistant asthma', American Journal of Respiratory and Critical Care Medicine, 196 283-297 (2017) [C1]
© 2017 by the American Thoracic Society. Rationale: Severe, steroid-resistant asthma is the major unmet need in asthma therapy. Disease heterogeneity and poor understanding of pat... [more]
© 2017 by the American Thoracic Society. Rationale: Severe, steroid-resistant asthma is the major unmet need in asthma therapy. Disease heterogeneity and poor understanding of pathogenic mechanisms hampers the identification of therapeutic targets. Excessive nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome and concomitant IL-1ß responses occur in chronic obstructive pulmonary disease, respiratory infections, and neutrophilic asthma. However, the direct contributions to pathogenesis, mechanisms involved, and potential for therapeutic targeting remain poorly understood, and are unknown in severe, steroid-resistant asthma. Objectives: To investigate the roles and therapeutic targeting of the NLRP3 inflammasome and IL-1ß in severe, steroid-resistant asthma. Methods: We developed mouse models of Chlamydia and Haemophilus respiratory infection-mediated, ovalbumin-induced severe, steroid-resistant allergic airway disease. These models share the hallmark features of human disease, including elevated airway neutrophils, and NLRP3 inflammasome and IL-1ß responses. The roles and potential for targeting of NLRP3 inflammasome, caspase-1, and IL-1ß responses in experimental severe, steroid-resistant asthma were examined using a highly selective NLRP3 inhibitor, MCC950; the specific caspase-1 inhibitor Ac-YVAD-cho; and neutralizing anti-IL-1ß antibody. Roles for IL-1ß-induced neutrophilic inflammation were examined using IL-1ß and anti-Ly6G. Measurements and Main Results: Chlamydia and Haemophilus infections increase NLRP3, caspase-1, IL-1ß responses that drive steroid-resistant neutrophilic inflammation and airway hyperresponsiveness. Neutrophilic airway inflammation, disease severity, and steroid resistance in human asthma correlate with NLRP3 and IL-1ß expression. Treatment with anti-IL-1ß, Ac- YVAD-cho, and MCC950 suppressed IL-1ß responses and the important steroid-resistant features of disease in mice, whereas IL-1ß administration recapitulated these features. Neutrophil depletion suppressed IL-1ß-induced steroid-resistant airway hyperresponsiveness. Conclusions: NLRP3 inflammasome responses drive experimental severe, steroid-resistant asthma and are potential therapeutic targets in this disease.
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2017 |
Negewo NA, Gibson PG, Wark PAB, Simpson JL, McDonald VM, 'Treatment burden, clinical outcomes, and comorbidities in COPD: An examination of the utility of medication regimen complexity index in COPD', International Journal of COPD, 12 2929-2942 (2017) [C1]
© 2017 Negewo et al. Background: COPD patients are often prescribed multiple medications for their respiratory disease and comorbidities. This can lead to complex medication regim... [more]
© 2017 Negewo et al. Background: COPD patients are often prescribed multiple medications for their respiratory disease and comorbidities. This can lead to complex medication regimens resulting in poor adherence, medication errors, and drug-drug interactions. The relationship between clinical outcomes and medication burden beyond medication count in COPD is largely unknown. Objectives: The aim of this study was to explore the relationships of medication burden in COPD with clinical outcomes, comorbidities, and multidimensional indices. Methods: In a cross-sectional study, COPD patients (n=222) were assessed for demographic information, comorbidities, medication use, and clinical outcomes. Complexity of medication regimens was quantified using the validated medication regimen complexity index (MRCI). Results: Participants (58.6% males) had a mean (SD) age of 69.1 (8.3) years with a postbronchodilator forced expiratory volume in 1 second % predicted of 56.5 (20.4) and a median of five comorbidities. The median (q1, q3) total MRCI score was 24 (18.5, 31). COPD-specific medication regimens were more complex than those of non-COPD medications (median MRCI: 14.5 versus 9, respectively; P<0.0001). Complex dosage formulations contributed the most to higher MRCI scores of COPD-specific medications while dosing frequency primarily drove the complexity associated with non-COPD medications. Participants in Global Initiative for Chronic Obstructive Lung Disease quadrant D had the highest median MRCI score for COPD medications (15.5) compared to those in quadrants A (13.5; P=0.0001) and B (12.5; P<0.0001). Increased complexity of COPD-specific treatments showed significant but weak correlations with lower lung function and 6-minute walk distance, higher St George¿s Respiratory Questionnaire and COPD assessment test scores, and higher number of prior year COPD exacerbations and hospitalizations. Comorbid cardiovascular, gastrointestinal, or metabolic diseases individually contributed to higher total MRCI scores and/or medication counts for all medications. Charlson Comorbidity Index and COPD-specific comorbidity test showed the highest degree of correlation with total MRCI score (¿=0.289 and ¿=0.326; P<0.0001, respectively). Conclusion: In COPD patients, complex medication regimens are associated with disease severity and specific class of comorbidities.
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2017 |
Cheng AC, Holmes M, Dwyer DE, Irving L, Korman T, Senenayake S, et al., 'Influenza epidemiology in patients admitted to sentinel Australian hospitals in 2016: the Influenza Complications Alert Network (FluCAN).', Communicable Diseases Intelligence Quarterly Report, 41 E337-E347 (2017) [C1] |
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2017 |
Kedzierski L, Tate MD, Hsu AC, Kolesnik TB, Linossi EM, Dagley L, et al., 'Suppressor of cytokine signaling (SOCS)5 ameliorates influenza infection via inhibition of EGFR signaling', eLife, 6 1-27 (2017) [C1]
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2017 |
Hsu AC-Y, Dua K, Starkey MR, Haw T-J, Nair PM, Nichol K, et al., 'MicroRNA-125a and -b inhibit A20 and MAVS to promote inflammation and impair antiviral response in COPD', JCI INSIGHT, 2 (2017) [C1]
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2016 |
Tay H, Wark PAB, Bartlett NW, 'Advances in the treatment of virus-induced asthma', Expert Review of Respiratory Medicine, 10 629-641 (2016) [C1]
© 2016 Informa UK Limited, trading as Taylor & Francis Group. ABSTRACT: Viral exacerbations continue to represent the major burden in terms of morbidity, mortality and healt... [more]
© 2016 Informa UK Limited, trading as Taylor & Francis Group. ABSTRACT: Viral exacerbations continue to represent the major burden in terms of morbidity, mortality and health care costs associated with asthma. Those at greatest risk for acute asthma are those with more severe airways disease and poor asthma control. It is this group with established asthma in whom acute exacerbations triggered by virus infections remain a serious cause of increased morbidity. A range of novel therapies are emerging to treat asthma and in particular target this group with poor disease control, and in most cases their efficacy is now being judged by their ability to reduce the frequency of acute exacerbations. Critical for the development of new treatment approaches is an improved understanding of virus-host interaction in the context of the asthmatic airway. This requires research into the virology of the disease in physiological models in conjunction with detailed phenotypic characterisation of asthma patients to identify targets amenable to therapeutic intervention.
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2016 |
Dentice RL, Elkins MR, Middleton PG, Bishop JR, Wark PAB, Dorahy DJ, et al., 'A randomised trial of hypertonic saline during hospitalisation for exacerbation of cystic fibrosis', Thorax, 71 141-147 (2016) [C1]
Background: The mucoactive effects of hypertonic saline should promote exacerbation resolution in people with cystic fibrosis (CF). Objectives: To determine the effects of hyperto... [more]
Background: The mucoactive effects of hypertonic saline should promote exacerbation resolution in people with cystic fibrosis (CF). Objectives: To determine the effects of hypertonic saline inhalation during hospitalisation for exacerbation of CF on length of stay, lung function, symptoms, oxygenation, exercise tolerance, quality of life, bacterial load and time to next hospitalisation. Methods: 132 adults with an exacerbation of CF were randomised to inhale three nebulised doses a day of either 4 mL 7% saline or a taste-masked control of 0.12% saline, throughout the hospital admission. The primary outcome measure was length of hospital stay. Results: All participants tolerated their allocated saline solution. There was no significant difference in length of stay, which was 12 days in the hypertonic saline group and 13 days in controls, with a mean between-group difference (MD) of 1 day (95% CI 0 to 2). The likelihood of regaining pre-exacerbation FEV1 by discharge was significantly higher in the hypertonic saline group (75% vs 57%), and the number needed to treat was 6 (95% CI 3 to 65). On a 0-100 scale, the hypertonic saline group had significantly greater reduction in symptom severity than the control group at discharge in sleep (MD=13, 95% CI 4 to 23), congestion (MD=10, 95% CI 3 to 18) and dyspnoea (MD=8, 95% CI 1 to 16). No significant difference in time to next hospitalisation for a pulmonary exacerbation was detected between groups (HR=0.86 (CI 0.57 to 1.30), p=0.13). Other outcomes did not significantly differ. Conclusions: Addition of hypertonic saline to the management of a CF exacerbation did not reduce the length of hospital stay. Hypertonic saline speeds the resolution of exacerbation symptoms and allows patients to leave hospital with greater symptom resolution.
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2016 |
Haw TJ, Starkey MR, Nair PM, Pavlidis S, Liu G, Nguyen DH, et al., 'A pathogenic role for tumor necrosis factor-related apoptosis-inducing ligand in chronic obstructive pulmonary disease', Mucosal Immunology, 9 859-872 (2016) [C1]
Chronic obstructive pulmonary disease (COPD) is a life-Threatening inflammatory respiratory disorder, often induced by cigarette smoke (CS) exposure. The development of effective ... [more]
Chronic obstructive pulmonary disease (COPD) is a life-Threatening inflammatory respiratory disorder, often induced by cigarette smoke (CS) exposure. The development of effective therapies is impaired by a lack of understanding of the underlining mechanisms. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine with inflammatory and apoptotic properties. We interrogated a mouse model of CS-induced experimental COPD and human tissues to identify a novel role for TRAIL in COPD pathogenesis. CS exposure of wild-Type mice increased TRAIL and its receptor messenger RNA (mRNA) expression and protein levels, as well as the number of TRAIL + CD11b + monocytes in the lung. TRAIL and its receptor mRNA were also increased in human COPD. CS-exposed TRAIL-deficient mice had decreased pulmonary inflammation, pro-inflammatory mediators, emphysema-like alveolar enlargement, and improved lung function. TRAIL-deficient mice also developed spontaneous small airway changes with increased epithelial cell thickness and collagen deposition, independent of CS exposure. Importantly, therapeutic neutralization of TRAIL, after the establishment of early-stage experimental COPD, reduced pulmonary inflammation, emphysema-like alveolar enlargement, and small airway changes. These data provide further evidence for TRAIL being a pivotal inflammatory factor in respiratory diseases, and the first preclinical evidence to suggest that therapeutic agents that target TRAIL may be effective in COPD therapy.
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2016 |
Cousins JL, Wark PAB, McDonald VM, 'Acute oxygen therapy: A review of prescribing and delivery practices', International Journal of COPD, 11 1067-1075 (2016) [C1]
© 2016 Cousins et al. Oxygen is a commonly used drug in the clinical setting and like other drugs its use must be considered carefully. This is particularly true for those patient... [more]
© 2016 Cousins et al. Oxygen is a commonly used drug in the clinical setting and like other drugs its use must be considered carefully. This is particularly true for those patients who are at risk of type II respiratory failure in whom the risk of hypercapnia is well established. In recent times, several international bodies have advocated for the prescription of oxygen therapy in an attempt to reduce this risk in vulnerable patient groups. Despite this guidance, published data have demonstrated that there has been poor uptake of these recommendations. Multiple interventions have been tested to improve concordance, and while some of these interventions show promise, the sustainability of these interventions are less convincing. In this review, we summarize data that have been published on the prevalence of oxygen prescription and the accurate and appropriate administration of this drug therapy. We also identify strategies that have shown promise in facilitating changes to oxygen prescription and delivery practice. There is a clear need to investigate the barriers, facilitators, and attitudes of clinicians in relation to the prescription of oxygen therapy in acute care. Interventions based on these findings then need to be designed and tested to facilitate the application of evidence-based guidelines to support sustained changes in practice, and ultimately improve patient care.
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2016 |
Wark P, Frith P, 'Asthma, COPD and when they coexist', Medicine Today, 17 16-24 (2016) [C1] |
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2016 |
Cheng AC, Holmes M, Dwyer DE, Irving LB, Korman TM, Senenayake S, et al., 'Influenza epidemiology in patients admitted to sentinel Australian hospitals in 2015: the Influenza Complications Alert Network.', Commun Dis Intell Q Rep, 40 E521-E526 (2016) [C1]
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2016 |
Hew M, Gillman A, Sutherland M, Wark P, Bowden J, Guo M, et al., 'Real-life effectiveness of omalizumab in severe allergic asthma above the recommended dosing range criteria', Clinical and Experimental Allergy, 46 1407-1415 (2016) [C1]
© 2016 John Wiley & Sons Ltd Background: Omalizumab (Xolair) dosing in severe allergic asthma is based on serum IgE and bodyweight. In Australia, patients eligible for omali... [more]
© 2016 John Wiley & Sons Ltd Background: Omalizumab (Xolair) dosing in severe allergic asthma is based on serum IgE and bodyweight. In Australia, patients eligible for omalizumab but exceeding recommended ranges for IgE (30¿1500 IU/mL) and bodyweight (30¿150 kg) may still receive a ceiling dose of 750 mg/4 weeks. About 62% of patients receiving government-subsidized omalizumab are enrolled in the Australian Xolair Registry (AXR). Objectives: To determine whether AXR participants above the recommended dosing ranges benefit from omalizumab and to compare their response to within-range participants. Methods: Data were stratified according to dose range status (above-range or within-range). Further sub-analyses were conducted according to the reason for being above the dosing range (IgE only vs. IgE and weight). Results: Data for 179 participants were analysed. About 55 (31%) were above recommended dosing criteria; other characteristics were similar to within-range participants. Above-range participants had higher baseline IgE [812 (IQR 632, 1747) IU/mL vs. 209 (IQR 134, 306) IU/mL] and received higher doses of omalizumab [750 (IQR 650, 750) mg] compared to within-range participants [450 (IQR, 300, 600) mg]. At 6 months, improvements in Juniper 5-item Asthma Control Questionnaire (ACQ-5, 3.61 down to 2.01 for above-range, 3.47 down to 1.93 for within-range, P < 0.0001 for both) and Asthma Quality of Life Questionnaire (AQLQ mean score (3.22 up to 4.41 for above-range, 3.71 up to 4.88 for within-range, P < 0.0001) were observed in both groups. Forced expiratory volume in one second (FEV1) improved among above-range participants. There was no difference in response between above-range and within-range participants. Above-range participants due to either IgE alone or IgE and weight had similar improvements in ACQ-5, AQLQ and FEV1. Conclusions and Clinical Relevance: Patients with severe allergic asthma above recommended dosing criteria for omalizumab have significantly improved symptom control, quality of life and lung function to a similar degree to within-range participants, achieved without dose escalation above 750 mg.
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2016 |
Loo S-L, Wark PAB, 'Recent advances in understanding and managing asthma.', F1000Res, 5 (2016) [C1]
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2016 |
Sin DD, Miravitlles M, Mannino DM, Soriano JB, Price D, Celli BR, et al., 'What is asthma?COPD overlap syndrome? Towards a consensus definition from a round table discussion', European Respiratory Journal, 48 664-673 (2016) [C1]
Patients with asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) have been largely excluded from pivotal therapeutic trials and, as a result, its treatment remai... [more]
Patients with asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) have been largely excluded from pivotal therapeutic trials and, as a result, its treatment remains poorly defined and lacking firm evidence. To date, there is no universally accepted definition of ACOS, which has made it difficult to understand its epidemiology or pathophysiology. Despite many uncertainties, there is emerging agreement that some of the key features of ACOS include persistent airflow limitation in symptomatic individuals 40 years of age and older, a well-documented history of asthma in childhood or early adulthood and a significant exposure history to cigarette or biomass smoke. In this perspective, we propose a case definition of ACOS that incorporates these key features in a parsimonious algorithm that may enable clinicians to better diagnose patients with ACOS and most importantly enable researchers to design therapeutic and clinical studies to elucidate its epidemiology and pathophysiology and to ascertain its optimal management strategies.
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2016 |
Hsu ACY, Parsons K, Moheimani F, Knight DA, Hansbro PM, Fujita T, Wark PA, 'Impaired antiviral stress granule and IFN-ß enhanceosome formation enhances susceptibility to influenza infection in chronic obstructive pulmonary disease epithelium', American Journal of Respiratory Cell and Molecular Biology, 55 117-127 (2016) [C1]
Chronic obstructive pulmonary disease (COPD) is a serious lung disease that progressively worsens lung function. Those affected are highly susceptible to influenza virus infection... [more]
Chronic obstructive pulmonary disease (COPD) is a serious lung disease that progressively worsens lung function. Those affected are highly susceptible to influenza virus infections that result in exacerbations with exaggerated symptoms with increased mortality. The mechanisms underpinning this increased susceptibility to infection in COPD are unclear. In this study, we show that primary bronchial epithelial cells (pBECs) from subjects with COPD have impaired induction of type I IFN (IFN-ß) and lead to heightened viral replication after influenza viral infection. COPD pBECs have reduced protein levels of protein kinase (PK) R and decreased formation of PKR-mediated antiviral stress granules, which are critical in initiating type I IFNinductions. In addition, reduced protein expression of p300 resulted in decreased activation of IFN regulatory factor 3 and subsequent formation of IFN-ß enhanceosome in COPD pBECs. The decreased p300 induction was the result of enhanced levels of microRNA (miR)-132. Ectopic expression of PKR or miR-132 antagomiR alone failed to restore IFN-ß induction, whereas cotreatment increased antiviral stress granule formation, induction of p300, and IFN-ß in COPD pBECs. This study reveals that decreased induction of both PKR and p300 proteins contribute to impaired induction of IFN-ß in COPD pBECs upon influenza infection.
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2016 |
Negewo NA, McDonald VM, Baines KJ, Wark PAB, Simpson JL, Jones PW, Gibson PG, 'Peripheral blood eosinophils: A surrogate marker for airway eosinophilia in stable COPD', International Journal of COPD, 11 1495-1504 (2016) [C1]
© 2016 Negewo et al. Introduction: Sputum eosinophilia occurs in approximately one-third of stable chronic obstructive pulmonary disease (COPD) patients and can predict exacerbati... [more]
© 2016 Negewo et al. Introduction: Sputum eosinophilia occurs in approximately one-third of stable chronic obstructive pulmonary disease (COPD) patients and can predict exacerbation risk and response to corticosteroid treatments. Sputum induction, however, requires expertise, may not always be successful, and does not provide point-of-care results. Easily applicable diagnostic markers that can predict sputum eosinophilia in stable COPD patients have the potential to progress COPD management. This study investigated the correlation and predictive relationship between peripheral blood and sputum eosinophils. It also examined the repeatability of blood eosinophil counts. Methods: Stable COPD patients (n=141) were classified as eosinophilic or noneosinophilic based on their sputum cell counts (=3%), and a cross-sectional analysis was conducted comparing their demographics, clinical characteristics, and blood cell counts. Receiver operating characteristic curve analysis was used to assess the predictive ability of blood eosinophils for sputum eosinophilia. Intraclass correlation coefficient was used to examine the repeatability of blood eosinophil counts. Results: Blood eosinophil counts were significantly higher in patients with sputum eosinophilia (n=45) compared to those without (0.3×109/L vs 0.15×109/L; P<0.0001). Blood eosinophils correlated with both the percentage (¿=0.535; P<0.0001) and number of sputum eosinophils (¿=0.473; P<0.0001). Absolute blood eosinophil count was predictive of sputum eosinophilia (area under the curve =0.76, 95% confidence interval [CI] =0.67¿0.84; P<0.0001). At a threshold of =0.3×109/L (specificity =76%, sensitivity =60%, and positive likelihood ratio =2.5), peripheral blood eosinophil counts enabled identification of the presence or absence of sputum eosinophilia in 71% of the cases. A threshold of =0.4×109/L had similar classifying ability but better specificity (91.7%) and higher positive likelihood ratio (3.7). In contrast, =0.2×109/L offered a better sensitivity (91.1%) for ruling out sputum eosinophilia. There was a good agreement between two measurements of blood eosinophil count over a median of 28 days (intraclass correlation coefficient =0.8; 95% CI =0.66¿0.88; P<0.0001). Conclusion: Peripheral blood eosinophil counts can help identify the presence or absence of sputum eosinophilia in stable COPD patients with a reasonable degree of accuracy.
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2016 |
Wark P, Hsu A, Starkey M, Hansbro P, 'Micro-RNA-125a/b target A20 and MAVS to promote inflammatory and impair antiviral responses in chronic obstructive pulmonary disease', EUROPEAN RESPIRATORY JOURNAL, 48 (2016)
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2016 |
Gibson PG, Reddel H, McDonald VM, Marks G, Jenkins C, Gillman A, et al., 'Effectiveness and response predictors of omalizumab in a severe allergic asthma population with a high prevalence of comorbidities: the Australian Xolair Registry', INTERNAL MEDICINE JOURNAL, 46 1054-1062 (2016) [C1]
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2016 |
Gang L, Hsu A, Cooley MA, Jarnicki AG, Nair PM, Haw TJ, et al., 'Fibulin-1 regulates the pathogenesis of tissue remodeling in respiratory diseases', Journal of Clinical Investigation Insight, 1 (2016) [C1]
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2016 |
Wark PAB, Hew M, Maltby S, McDonald VM, Gibson PG, 'Diagnosis and investigation in the severe asthma clinic.', Expert Rev Respir Med, 10 491-503 (2016) [C1]
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2016 |
Moheimani F, Hsu AC-Y, Reid AT, Williams T, Kicic A, Stick SM, et al., 'The genetic and epigenetic landscapes of the epithelium in asthma', RESPIRATORY RESEARCH, 17 (2016) [C1]
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2015 |
Wark PAB, McDonald VM, Gibson PG, 'Adjusting prednisone using blood eosinophils reduces exacerbations and improves asthma control in difficult patients with asthma.', Respirology, 20 1282-1284 (2015) [C1]
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2015 |
Vanders RL, Murphy VE, Gibson PG, Hansbro PM, Wark PAB, 'CD8 T cells and dendritic cells: Key players in the attenuated maternal immune response to influenza infection', Journal of Reproductive Immunology, 107 1-9 (2015) [C1]
© 2014 Elsevier Ireland Ltd. Pregnancy provides a unique challenge for maternal immunity, requiring the ability to tolerate the presence of a semi-allogeneic foetus, and yet still... [more]
© 2014 Elsevier Ireland Ltd. Pregnancy provides a unique challenge for maternal immunity, requiring the ability to tolerate the presence of a semi-allogeneic foetus, and yet still being capable of inducing an immune response against invading pathogens. To achieve this, numerous changes must occur in the activity and function of maternal immune cells throughout the course of pregnancy. Respiratory viruses take advantage of these changes, altering the sensitive balance of maternal immunity, leaving the mother with increased susceptibility to viral infections and increased disease severity. Influenza virus is one of the most common respiratory virus infections during pregnancy, leading to an increased risk of ICU hospitalisations, pneumonia, acute respiratory distress syndrome and even death. Whilst much research has been performed to understand the changes that must take place in maternal immunity during pregnancy, considerable work is still needed to fully comprehend this tremendous feat. To date, few studies have focused on the alterations that occur in maternal immunity during respiratory virus infections. This review highlights the role of dendritic cells (DCs) and CD8 T cells during pregnancy, and the changes that occur in these antiviral cells following influenza virus infections.
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2015 |
Kumar RK, Shadie AM, Bucknall MP, Rutlidge H, Garthwaite L, Herbert C, et al., 'Differential injurious effects of ambient and traffic-derived particulate matter on airway epithelial cells', RESPIROLOGY, 20 73-79 (2015) [C1]
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2015 |
Wark P, Hilton J, 'Minimising the risk of acute asthma in children', Medicine Today, 16 35-44 (2015)
© MedicineToday 2015. A diagnosis of asthma is important before preventive treatment can be commenced in children after an acute asthma episode. Careful continuing assessment of t... [more]
© MedicineToday 2015. A diagnosis of asthma is important before preventive treatment can be commenced in children after an acute asthma episode. Careful continuing assessment of the severity of the child's condition is needed to determine the risk of future episodes.
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2015 |
Cheng AC, Holmes M, Senenayake S, Dwyer DE, Hewagama S, Korman T, et al., 'Influenza epidemiology in adults admitted to sentinel Australian hospitals in 2014: the Influenza Complications Alert Network (FluCAN).', Communicable diseases intelligence quarterly report, 39 E355-E360 (2015) [C1]
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2015 |
Pathinayake PS, Hsu A, wark PA, 'Innate Immunity and Immune Evasion by Enterovirus 71', Viruses, 7 (2015) [C1]
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2015 |
Hatchwell L, Collison A, Girkin J, Parsons K, Li J, Zhang J, et al., 'Toll-like receptor 7 governs interferon and inflammatory responses to rhinovirus and is suppressed by IL-5-induced lung eosinophilia', Thorax, (2015) [C1]
© 2015 BMJ Publishing Group Ltd & British Thoracic Society.Background Asthma exacerbations represent a significant disease burden and are commonly caused by rhinovirus (RV), w... [more]
© 2015 BMJ Publishing Group Ltd & British Thoracic Society.Background Asthma exacerbations represent a significant disease burden and are commonly caused by rhinovirus (RV), which is sensed by Toll-like receptors (TLR) such as TLR7. Some asthmatics have impaired interferon (IFN) responses to RV, but the underlying mechanisms of this clinically relevant observation are poorly understood. Objectives To investigate the importance of intact TLR7 signalling in vivo during RV exacerbation using mouse models of house dust mite (HDM)-induced allergic airways disease exacerbated by a superimposed RV infection. Methods Wild-type and TLR7-deficient (Tlr7<sup>-/-</sup>) BALB/c mice were intranasally sensitised and challenged with HDM prior to infection with RV1B. In some experiments, mice were administered recombinant IFN or adoptively transferred with plasmacytoid dendritic cells (pDC). Results Allergic Tlr7<sup>-/-</sup> mice displayed impaired IFN release upon RV1B infection, increased virus replication and exaggerated eosinophilic inflammation and airways hyper reactivity. Treatment with exogenous IFN or adoptive transfer of TLR7-competent pDCs blocked these exaggerated inflammatory responses and boosted IFN? release in the absence of host TLR7 signalling. TLR7 expression in the lungs was suppressed by allergic inflammation and by interleukin (IL)-5-induced eosinophilia in the absence of allergy. Subjects with moderate-to-severe asthma and eosinophilic but not neutrophilic airways inflammation, despite inhaled steroids, showed reduced TLR7 and IFN?2/3 expression in endobronchial biopsies. Furthermore, TLR7 expression inversely correlated with percentage of sputum eosinophils. Conclusions This implicates IL-5-induced airways eosinophilia as a negative regulator of TLR7 expression and antiviral responses, which provides a molecular mechanism underpinning the effect of eosinophil-targeting treatments for the prevention of asthma exacerbations.
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2015 |
Hsu ACY, Starkey MR, Hanish I, Parsons K, Haw TJ, Howland LJ, et al., 'Targeting PI3K-p110a suppresses influenza virus infection in chronic obstructive pulmonary disease', American Journal of Respiratory and Critical Care Medicine, 191 1012-1023 (2015) [C1]
Copyright © 2015 by the American Thoracic Society. Rationale: Chronic obstructive pulmonary disease (COPD) and influenza virus infections are major global health issues. Patients ... [more]
Copyright © 2015 by the American Thoracic Society. Rationale: Chronic obstructive pulmonary disease (COPD) and influenza virus infections are major global health issues. Patients with COPD are more susceptible to infection, which exacerbates their condition and increases morbidity and mortality. The mechanisms of increased susceptibility remain poorly understood, and current preventions and treatments have substantial limitations. Objectives: To characterize the mechanisms of increased susceptibility to influenza virus infection in COPD and the potential for therapeutic targeting. Methods: We used a combination of primary bronchial epithelial cells (pBECs) from COPD and healthy control subjects, a mouse model of cigarette smoke-induced experimental COPD, and influenza infection. The role of the phosphoinositide-3-kinase (PI3K) pathway was characterized using molecular methods, and its potential for targeting assessed using inhibitors. Measurements and Main Results: COPDpBECs were susceptible to increased viral entry and replication. Infected mice with experimental COPD also had more severe infection (increased viral titer and pulmonary inflammation, and compromised lung function). These processes were associated with impaired antiviral immunity, reduced retinoic acid-inducible gene-I, and IFN/cytokine and chemokine responses. Increased PI3K-p110a levels and activity inCOPDpBECs and/or mice were responsible for increased infection and reduced antiviral responses. Global PI3K, specific therapeutic p110a inhibitors, or exogenous IFN-b restored protective antiviral responses, suppressed infection, and improved lung function. Conclusions: The increased susceptibility of individuals with COPD to influenza likely results from impaired antiviral responses, which are mediated by increased PI3K-p110a activity. This pathway may be targeted therapeutically in COPD, or in healthy individuals, during seasonal or pandemic outbreaks to prevent and/or treat influenza.
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2015 |
Carlet J, Aaron L, Abassi MS, Abbo L, Aboderin O, Abraham E, et al., 'World alliance against antibiotic resistance: The WAAAR declaration against antibiotic resistance', Medicina Intensiva, 39 34-39 (2015)
© 2014 Elsevier España, S.L.U. and SEMICYUC. We must change how antibiotics are used and adopt proactive strategies, similar to those used to save endangered species. Preservation... [more]
© 2014 Elsevier España, S.L.U. and SEMICYUC. We must change how antibiotics are used and adopt proactive strategies, similar to those used to save endangered species. Preservation of the efficacy of antibiotics and to stabilization of antibiotic-susceptible bacterial ecosystems should be global goals.
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2015 |
Kidd TJ, Magalhães RJS, Paynter S, Bell SC, Grimwood K, Armstrong DS, et al., 'The social network of cystic fibrosis centre care and shared Pseudomonas aeruginosa strain infection: A cross-sectional analysis', The Lancet Respiratory Medicine, 3 640-650 (2015)
© 2015 Elsevier Ltd. Background: Person-to-person transmission is a potential pathway of Pseudomonas aeruginosa acquisition in cystic fibrosis. Reports of cross-infection of share... [more]
© 2015 Elsevier Ltd. Background: Person-to-person transmission is a potential pathway of Pseudomonas aeruginosa acquisition in cystic fibrosis. Reports of cross-infection of shared cystic-fibrosis-specific P aeruginosa strains across large geographical distances are concerning. Therefore, we aimed to assess the extent to which patient movement between cystic fibrosis centres contributes to dissemination. Methods: We did a cross-sectional study to assess movement of patients with cystic fibrosis who were infected with P aeruginosa between Sept 3, 2007, and June 16, 2010, at 18 Australian cystic fibrosis centres. We applied social network analysis to patient movement data from P aeruginosa-infected patients to assess the role of patient mobility in P aeruginosa genotype prevalence. We generated networks linking treatment centres based on the movement of patients attending adult and paediatric cystic fibrosis centres, and compared these with the movement of patients infected with all P aeruginosa strains, unique strains, and predominant Australian shared strains (AUST-01 and AUST-02). We summarised connectivity using degree centrality, in-degree centrality, out-degree centrality, and k-core estimates. Infection control and surveillance practices were also assessed by use of a questionnaire. Findings: 983 patients (mean age 25 years [SD 10]; 551 [56%] male) provided 2887 P aeruginosa isolates for ERIC-PCR genotyping, which yielded 531 distinct genotypes: 493 unique strains in 373 patients and 38 shared strains in 610 patients. AUST-01 infections were associated with higher in-degree centrality (p=0·004) and k-core (p=0·005) estimates and AUST-02 infections with higher degree centrality (p=0·002), out-degree centrality (p=0·002), and k-core (p=0·007) estimates for the previous health-care facilities; associations for the present cystic fibrosis centre were not significant. These findings were significant for adult patients (AUST-01 in-degree centrality p=0·004 and k-core p=0·005; AUST-02 degree centrality p=0·004, out-degree centrality p=0·003, and k-core p=0·007), but not for paediatric patients. By contrast, infections with unique strains were associated with a lower k-core estimate for the present cystic fibrosis centre overall (p<0·0001); this finding was significant in adults (p<0·0001), but not in paediatric patients. Interpretation: Our results show that the connectivity of cystic fibrosis centres, as measured by the movement of patients, seems to be an important risk factor for the acquisition of shared P aeruginosa strain infections. These results show the importance of prioritising infection control interventions (eg, prospective molecular surveillance for shared P aeruginosa strains, strict universal infection control precautions, and hospital design and ventilation) to limit P aeruginosa cross-infection between patients with cystic fibrosis. Funding: Australian National Health and Medical Research Council; Children's Health Foundation Queensland; Office of Health and Medical Research, Queensland Health; European Respiratory Society-European Union; Australian Cystic Fibrosis Research Trust; Prince Charles Hospital Foundation; and Rotary Australia.
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2015 |
Cheng AC, Kotsimbos T, Kelly PM, Wark P, Hunter C, Hewagama S, et al., 'Influenza vaccine effectiveness against hospitalisation with influenza in adults in Australia in 2014', Vaccine, 33 7352-7356 (2015) [C1]
© 2015 Elsevier Ltd. We provide estimates of the influenza vaccine protection against hospitalisation with laboratory-confirmed influenza in the 2014 Australian season where the A... [more]
© 2015 Elsevier Ltd. We provide estimates of the influenza vaccine protection against hospitalisation with laboratory-confirmed influenza in the 2014 Australian season where the A/H1N1/pdm09 strain predominated. This was performed using a case-test negative study design as part of a national sentinel surveillance system in Australia. Vaccine effectiveness was estimated as (1-OR). ×. 100% where the odds ratio of vaccination in cases vs test negative participants was estimated from a conditional logistic regression. Between April and November, 1692 adult patients were admitted with laboratory-confirmed influenza. Vaccine effectiveness was estimated from 1283 patients with influenza and 1116 test negative patients where vaccination status was ascertained. Vaccination was associated with a reduction in the risk of hospitalisation with influenza of 51.5% (95% CI: 41.6%, 59.7%) in all patients, and a reduction of 50.7% (95% CI: 40.1%, 59.3%) in the target population for vaccination. We estimate that the influenza vaccine was moderately protective against hospitalisation with laboratory-confirmed influenza during the 2014 influenza season in Australia.
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2015 |
Tolosa JM, Parsons KS, Hansbro PM, Smith R, Wark PB, 'The placental protein syncytin-1 impairs antiviral responses and exaggerates inflammatory responses to influenza', PLoS ONE, 10 (2015) [C1]
© 2015 Tolosa et al. Background Pregnancy increases susceptibility to influenza. The placenta releases an immunosuppressive endogenous retroviral protein syncytin-1.We hypothesise... [more]
© 2015 Tolosa et al. Background Pregnancy increases susceptibility to influenza. The placenta releases an immunosuppressive endogenous retroviral protein syncytin-1.We hypothesised that exposure of peripheral monocytes (PBMCs) to syncytin-1 would impair responses to H1N1pdm09 influenza. Methods and Findings Recombinant syncytin-1 was produced. PBMCs from non-pregnant women (n=10) were exposed to H1N1pdm09 in the presence and absence of syncytin-1 and compared to responses of PBMCs from pregnant women (n=12). PBMCs were characterised using flow cytometry, release of interferon (IFN)-a, IFN-¿, IFN-¿, IL-10, IL-2, IL-6 and IL-1ß were measured by cytometric bead array or ELISA. Exposure of PBMCs to H1N1pdm09 resulted in the release of IFN-a, (14,787 pg/mL, 95% CI 7311-22,264 pg/mL) IFN-¿ (1486 pg/mL, 95% CI 756-2216 pg/mL) and IFN-¿ (852 pg/mL, 95% CI 193-1511 pg/mL) after 48 hours. This was significantly impaired in pregnant women (IFN-a; p<0.0001 and IFN-¿; p<0.001). Furthermore, in the presence of syncytin-1, PBMCs demonstrated marked reductions in IFN-a and IFN-¿, while enhanced release of IL-10 as well as IL-6 and IL-1ß. Conclusions Our data indicates that a placental derived protein, syncytin-1 may be responsible for the heightened vulnerability of pregnant women to influenza.
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2015 |
Wark P, 'Bronchitis (acute)', BMJ clinical evidence, 2015 (2015)
INTRODUCTION: Acute bronchitis affects more than 40 in 1000 adults per year in the UK. The causes are usually considered to be infective, but only around half of people have ident... [more]
INTRODUCTION: Acute bronchitis affects more than 40 in 1000 adults per year in the UK. The causes are usually considered to be infective, but only around half of people have identifiable pathogens. The role of smoking or of environmental tobacco smoke inhalation in predisposing to acute bronchitis is unclear. One third of people may have longer-term symptoms or recurrence.METHODS AND OUTCOMES: We conducted a systematic review, aiming to answer the following clinical question: What are the effects of treatments for acute bronchitis in people without chronic respiratory disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2015 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview).RESULTS: At this update, searching of electronic databases retrieved 420 studies. After deduplication and removal of conference abstracts, 306 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 245 studies and the further review of 61 full publications. Of the 61 full articles evaluated, three updated systematic reviews and three RCTs were added at this update. We performed a GRADE evaluation for 12 PICO combinations.CONCLUSIONS: In this systematic review we categorised the efficacy for six intervention-comparison combinations, based on information about the effectiveness and safety of the following interventions: antibiotics, antihistamines, antitussives, beta2 agonists (inhaled), and expectorants/mucolytics.
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2015 |
Baines KJ, Wright TK, Simpson JL, McDonald VM, Wood LG, Parsons KS, et al., 'Airway beta-Defensin-1 Protein Is Elevated in COPD and Severe Asthma', MEDIATORS OF INFLAMMATION, (2015) [C1]
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2014 |
Djukanovic R, Harrison T, Johnston SL, Gabbay F, Wark P, Thomson NC, et al., 'The Effect of Inhaled IFN-beta on Worsening of Asthma Symptoms Caused by Viral Infections A Randomized Trial', AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 190 145-154 (2014) [C1]
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2014 |
Cheng AC, Dwyer DE, Holmes M, Irving LB, Brown SGA, Waterer GW, et al., 'Influenza epidemiology, vaccine coverage and vaccine effectiveness in sentinel Australian hospitals in 2013: the Influenza Complications Alert Network', Communicable diseases intelligence quarterly report, 38 E143-E149 (2014)
This work is copyright. You may download, display, print and reproduce the whole or part of this work in unaltered form for your own personal use or, if you are part of an organis... [more]
This work is copyright. You may download, display, print and reproduce the whole or part of this work in unaltered form for your own personal use or, if you are part of an organisation, for internal use within your organisation, but only if you or your organisation do not use the reproduction for any commercial purpose and retain this copyright notice and all disclaimer notices as part of that The National Influenza Program aims to reduce serious morbidity and mortality from influenza by providing public funding for vaccination to at-risk groups. The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at 14 sites in all states and territories in Australia. This report summarises the epidemiology of hospitalisations with confirmed influenza, estimates vaccine coverage and influenza vaccine protection against hospitalisation with influenza during the 2013 influenza season. In this observational study, cases were defined as patients admitted to one of the sentinel hospitals, with influenza confirmed by nucleic acid testing. Controls were patients who had acute respiratory illnesses who were test-negative for influenza. Vaccine effectiveness was estimated as 1 minus the odds ratio of vaccination in case patients compared with control patients, after adjusting for known confounders. During the period 5 April to 31 October 2012, 631 patients were admitted with confirmed influenza at the 14 FluCAN sentinel hospitals. Of these, 31% were more than 65 years of age, 9.5% were Indigenous Australians, 4.3% were pregnant and 77% had chronic co-morbidities. Influenza B was detected in 30% of patients. Vaccination coverage was estimated at 81% in patients more than 65 years of age but only 49% in patients aged less than 65 years with chronic comorbidities. Vaccination effectiveness against hospitalisation with influenza was estimated at 50% (95% confidence interval: 33%, 63%, P<0.001). We detected a significant number of hospital admissions with confirmed influenza in a national observational study. Vaccine coverage was incomplete in at-risk groups, particularly non-elderly patients with medical comorbidities. Our results suggest that the seasonal influenza vaccine was moderately protective against hospitalisation with influenza in the 2013 season.
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2014 |
Wark PAB, Murphy V, Mattes J, 'The interaction between mother and fetus and the development of allergic asthma', Expert Review of Respiratory Medicine, 8 57-66 (2014) [C1]
The rising prevalence of asthma and atopic disease in industrialized countries in the last 50 years has raised important questions about how and why the disease develops in suscep... [more]
The rising prevalence of asthma and atopic disease in industrialized countries in the last 50 years has raised important questions about how and why the disease develops in susceptible populations. Most asthma begins in childhood in association with allergic sensitization and the development of a TH2 phenotype. It is recognized that asthma arises in the context of a complex interaction between genetic factors and the evolving immune system of the infant and the environment to which it is exposed, which now includes its in utero exposure. Early life exposures that lead to allergen sensitization and airway damage, especially in the form of viral respiratory tract infections, may lead to disease induction that commence the process that leads in some to asthma. Asthma models and early life observations suggest that repeated exposure to allergens and viral infection perpetuate a state of chronic airway inflammation leading to a maladaptive innate immune response that fails to resolve, characterized by chronic airway inflammation, airway remodeling and airway hyperresponsiveness. This article will concentrate on the development of asthma in the context of early life and maternal influences, including the effect of asthma on both the fetus and the mother. © 2014 Informa UK Ltd.
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2014 |
Parsons KS, Hsu AC, Wark PAB, 'TLR3 and MDA5 signalling, although not expression, is impaired in asthmatic epithelial cells in response to rhinovirus infection', Clinical and Experimental Allergy, 44 91-101 (2014) [C1]
Summary: Background: Rhinoviruses (RV) are the most common acute triggers of asthma, and airway epithelial cells are the primary site of infection. Asthmatic bronchial epithelial ... [more]
Summary: Background: Rhinoviruses (RV) are the most common acute triggers of asthma, and airway epithelial cells are the primary site of infection. Asthmatic bronchial epithelial cells (BECs) have been found to have impaired innate immune responses to RV. RV entry and replication is recognized by pathogen recognition receptors (PRRs), specifically toll-like receptor (TLR)3 and the RNA helicases; retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5). Objective: Our aim was to assess the relative importance of these PRRs in primary bronchial epithelial cells (pBEC) from healthy controls and asthmatics following RV infection and determine whether deficient innate immune responses in asthmatic pBECs were due to abnormal signalling via these PRRs. Methods: The expression patterns and roles of TLR3 and MDA5 were investigated using siRNA knock-down, with subsequent RV1B infection in pBECs from each patient group. We also used BX795, a specific inhibitor of TBK1 and IKKi. Results: Asthmatic pBECs had significantly reduced release of IL-6, CXCL-8 and IFN-¿ in response to RV1B infection compared with healthy pBECs. In healthy pBECs, siMDA5, siTLR3 and BX795 all reduced release of IL-6, CXCL-10 and IFN-¿ to infection. In contrast, in asthmatic pBECs where responses were already reduced, there was no further reduction in IL-6 and IFN-¿, although there was in CXCL-10. Conclusion and Clinical Relevance: Impaired antiviral responses in asthmatic pBECs are not due to deficient expression of PRRs; MDA5 and TLR3, but an inability to later activate types I and III interferon immune responses to RV infection, potentially increasing susceptibility to the effects of RV infection. © 2013 John Wiley & Sons Ltd.
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2013 |
Murphy VE, Powell H, Wark PAB, Gibson PG, 'A Prospective Study of Respiratory Viral Infection in Pregnant Women With and Without Asthma', CHEST, 144 420-427 (2013) [C1]
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2013 |
Hansbro P, Beckett E, Stevens R, Jarnicki A, Wark P, Foster P, 'A short-term model of COPD identifies a role for mast cell tryptase', EUROPEAN RESPIRATORY JOURNAL, 42 (2013) [C3]
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2013 |
Vanders RL, Gibson PG, Murphy VE, Wark PAB, 'Plasmacytoid Dendritic Cells and CD8 T Cells From PregnantWomen Show Altered Phenotype and Function Following H1N1/09 Infection', JOURNAL OF INFECTIOUS DISEASES, 208 1062-1070 (2013) [C1]
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2013 |
Beckett EL, Stevens RL, Jarnicki AG, Kim RY, Hanish I, Hansbro NG, et al., 'A new short-term mouse model of chronic obstructive pulmonary disease identifies a role for mast cell tryptase in pathogenesis', The Journal of Allergy and Clinical Immunology, 131 752-762 (2013) [C1]
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2013 |
Kidd TJ, Ramsay KA, Hu H, Marks GB, Wainwright CE, Bye PT, et al., 'Shared Pseudomonas aeruginosa genotypes are common in Australian cystic fibrosis centres', European Respiratory Journal, 41 1091-1100 (2013) [C1]
Recent molecular-typing studies suggest cross-infection as one of the potential acquisition pathways for Pseudomonas aeruginosa in patients with cystic fibrosis (CF). In Australia... [more]
Recent molecular-typing studies suggest cross-infection as one of the potential acquisition pathways for Pseudomonas aeruginosa in patients with cystic fibrosis (CF). In Australia, there is only limited evidence of unrelated patients sharing indistinguishable P. aeruginosa strains. We therefore examined the point-prevalence, distribution, diversity and clinical impact of P. aeruginosa strains in Australian CF patients nationally. 983 patients attending 18 Australian CF centres provided 2887 sputum P. aeruginosa isolates for genotyping by enterobacterial repetitive intergenic consensus-PCR assays with confirmation by multilocus sequence typing. Demographic and clinical details were recorded for each participant. Overall, 610 (62%) patients harboured at least one of 38 shared genotypes. Most shared strains were in small patient clusters from a limited number of centres. However, the two predominant genotypes, AUST-01 and AUST-02, were widely dispersed, being detected in 220 (22%) and 173 (18%) patients attending 17 and 16 centres, respectively. AUST-01 was associated with significantly greater treatment requirements than unique P. aeruginosa strains. Multiple clusters of shared P. aeruginosa strains are common in Australian CF centres. At least one of the predominant and widespread genotypes is associated with increased healthcare utilisation. Longitudinal studies are now needed to determine the infection control implications of these findings. Copyright ©ERS 2013.
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2013 |
Collison AM, Hatchwell LM, Verrills NM, Wark PA, Pereira De Siqueira AL, Tooze MK, et al., 'The E3 ubiquitin ligase midline 1 promotes allergen and rhinovirus-induced asthma by inhibiting protein phosphatase 2A activity', Nature Medicine, 19 232-237 (2013) [C1]
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2013 |
Frith P, Thompson P, Wark P, Lindstrom S, Bateman E, 'BENEFITS OF DUAL BRONCHODILATION WITH QVA149 ONCE DAILY VERSUS PLACEBO, INDACATEROL, NVA237 AND TIOTROPIUM IN PATIENTS WITH COPD: THE SHINE STUDY', RESPIROLOGY, 18 20-20 (2013)
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2013 |
Cheng AC, Brown S, Waterer G, Holmes M, Senenayake S, Friedman ND, et al., 'Influenza epidemiology, vaccine coverage and vaccine effectiveness in sentinel Australian hospitals in 2012: the Influenza Complications Alert Network (FluCAN)', Communicable diseases intelligence quarterly report, 37 E246-E252 (2013)
This work is copyright. Apart from any use as permitted under the Copyright Act 1968, no part may be reproduced by any process without prior written permission from the Commonweal... [more]
This work is copyright. Apart from any use as permitted under the Copyright Act 1968, no part may be reproduced by any process without prior written permission from the Commonwealth. Requests and inquiries concerning reproduction and rights should be addressed to the Commonwealth Copyright Administration, Attorney General's Department, Robert Garran Offices, National Circuit, Barton ACT 2600 or Influenza is mostly a mild, self-limiting infection and severe infection requiring hospitalisation is uncommon. Immunisation aims to reduce serious morbidity and mortality. The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at 15 sites across all states and territories in Australia. This study reports on the epidemiology of hospitalisation with confirmed influenza, estimate vaccine coverage and influenza vaccine protection against hospitalisation with influenza during the 2012 influenza season. In this observational study, cases were defined as patients admitted to one of the sentinel hospitals with influenza confirmed by nucleic acid detection. Controls were patients who had acute respiratory illnesses who were test-negative for influenza. Vaccine effectiveness was estimated as 1¿minus the odds ratio of vaccination in case patients compared with control patients, after adjusting for known confounders. During the period 9 April to 31 October 2012, 1,231 patients were admitted with confirmed influenza at the 15 FluCAN sentinel hospitals. Of these, 47% were more than 65 years of age, 8% were Indigenous Australians, 3% were pregnant and 76% had chronic co-morbidities. Influenza A was detected in 83% of patients. Vaccination coverage was calculated from the vaccination status of 1,216 test negative controls and was estimated at 77% in patients 65 years or over and 61% in patients with chronic comorbidities. Vaccination effectiveness was estimated at 41% (95% CI: 28%, 51%, P<0.001). Vaccine coverage was incomplete in at-risk groups, particularly non-elderly patients with medical comorbidities. The study results suggest that the seasonal influenza vaccine was moderately protective against hospitalisation with influenza during the 2012 season.
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2013 |
Vanders RL, Gibson PG, Wark PAB, Murphy VE, 'Alterations in inflammatory, antiviral and regulatory cytokine responses in peripheral blood mononuclear cells from pregnant women with asthma', RESPIROLOGY, 18 827-833 (2013) [C1]
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2013 |
Wark PAB, Tooze M, Powell H, Parsons K, 'Viral and bacterial infection in acute asthma and chronic obstructive pulmonary disease increases the risk of readmission', RESPIROLOGY, 18 996-1002 (2013) [C1]
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2013 |
Baines KJ, Hsu AC-Y, Tooze M, Gunawardhana LP, Gibson PG, Wark PAB, 'Novel immune genes associated with excessive inflammatory and antiviral responses to rhinovirus in COPD', RESPIRATORY RESEARCH, 14 (2013) [C1]
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2013 |
Cheng AC, Holmes M, Irving LB, Brown SGA, Waterer GW, Korman TM, et al., 'Influenza Vaccine Effectiveness against Hospitalisation with Confirmed Influenza in the 2010-11 Seasons: A Test-negative Observational Study', PLOS ONE, 8 (2013) [C1]
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2012 |
Sukkar MB, Ullah MA, Gan WJ, Wark PA, Chung KF, Hughes JM, et al., 'RAGE: a new frontier in chronic airways disease', British Journal of Pharmacology, 167 1161-1176 (2012) [C1]
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2012 |
Hurt AC, Hardie K, Wilson NJ, Deng YM, Osbourn M, Leang SK, et al., 'Characteristics of a widespread community cluster of H275Y Oseltamivir-Resistant A (H1N1)pdm09 influenza in Australia', Journal of Infectious Diseases, 206 148-157 (2012) [C1]
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2012 |
Vanders RL, Wark PA, Murphy VE, Gibson PG, 'Pregnant women have attenuated innate interferon responses to 2009 pandemic influenza a virus subtype H1N1', Journal of Infectious Diseases, 206 646-653 (2012) [C1]
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2012 |
Bozinovski S, Uddin M, Vlahos R, Thompson M, McQualter JL, Merritt A-S, et al., 'Serum amyloid A opposes lipoxin A(4) to mediate glucocorticoid refractory lung inflammation in chronic obstructive pulmonary disease', Proceedings of the National Academy of Sciences of the United States of America, 109 935-940 (2012) [C1]
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2012 |
Vanders RL, Gibson PG, Murphy VE, Wark PAB, 'Impaired type I and III interferon response to rhinovirus infection during pregnancy and asthma', Thorax, 67 209-214 (2012) [C1]
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2012 |
Sukkar MB, Wood LG, Tooze MK, Simpson JL, McDonald VM, Gibson PG, Wark PA, 'Soluble RAGE is deficient in neutrophilic asthma and COPD', European Respiratory Journal, 39 721-729 (2012) [C1]
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2012 |
Wark PA, Tooze M, Cheese L, Whitehead BF, Gibson PG, Wark K, McDonald VM, 'Viral infections trigger exacerbations of cystic fibrosis in adults and children', European Respiratory Journal, 40 510-512 (2012) [C1]
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2012 |
Ryan NM, Vertigan AE, Ferguson JK, Wark PA, Gibson PG, 'Clinical and physiological features of postinfectious chronic cough associated with H1N1 infection', Respiratory Medicine, 106 138-144 (2012) [C1]
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2012 |
Wark PA, 'Airway inflammation in asthma, a single measurement is not enough', Respirology, 17 393-394 (2012) [C3]
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2012 |
Hsu A, See HV, Hansbro PM, Wark PA, 'Innate immunity to influenza in chronic airways diseases', Respirology, 17 1166-1175 (2012) [C1]
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2012 |
Pretto JJ, McDonald VM, Wark PA, Hensley MJ, 'Multicentre audit of inpatient management of acute exacerbations of chronic obstructive pulmonary disease: Comparison with clinical guidelines', Internal Medicine Journal, 42 380-387 (2012) [C1]
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2012 |
Vlahos R, Wark PAB, Anderson GP, Bozinovski S, 'Glucocorticosteroids Differentially Regulate MMP-9 and Neutrophil Elastase in COPD', PLOS ONE, 7 (2012) [C1]
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2012 |
Hsu A, Parsons KS, Barr I, Lowther S, Middleton D, Hansbro PM, Wark PA, 'Critical role of constitutive type I interferon response in bronchial epithelial cell to influenza infection', PLoS One, 7 (2012) [C1]
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2011 |
Wark PA, 'Tiotropium reduced exacerbations more than salmeterol in moderate-to-very severe COPD', Annals of Internal Medicine, 155 3 (2011) [C3] |
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2011 |
Cheng AC, Kotsimbos T, Kelly HA, Irving LB, Bowler SD, Brown SGA, et al., 'Effectiveness of H1N1/09 monovalent and trivalent influenza vaccines against hospitalization with laboratory-confirmed H1N1/09 influenza in Australia: A test-negative case control study', Vaccine, 29 7320-7325 (2011) [C1]
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2011 |
Wood LG, Simpson JL, Wark PA, Powell H, Gibson PG, 'Characterization of innate immune signalling receptors in virus-induced acute asthma', Clinical and Experimental Allergy, 41 640-648 (2011) [C1]
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2011 |
Katelaris CH, Linneberg A, Magnan A, Thomas WR, Wardlaw AJ, Wark PA, 'Developments in the field of allergy in 2010 through the eyes of Clinical and Experimental Allergy', Clinical and Experimental Allergy, 41 1690-1710 (2011) [C3]
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2011 |
Hsu A, Barr I, Hansbro PM, Wark PA, 'Human influenza is more effective than Avian influenza at antiviral suppression in airway cells', American Journal of Respiratory Cell and Molecular Biology, 44 906-913 (2011) [C1]
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2010 |
Wood LG, Wark PA, Garg ML, 'Antioxidant and anti-inflammatory effects of resveratrol in airway disease', Antioxidants & Redox Signaling, 13 1535-1548 (2010) [C1]
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2010 |
Wark PA, 'Viral and bacterial interactions in pneumonia', Expert Review of Respiratory Medicine, 4 221-228 (2010) [C1]
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2010 |
Reddel HK, Gibson PG, Peters MJ, Wark PA, Sand IB, Hoyos CM, Jenkins CR, 'Down-titration from high-dose combination therapy in asthma: Removal of long-acting b2-agonist', Respiratory Medicine, 104 1110-1120 (2010) [C1]
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2010 |
Osei-Kumah A, Wark PA, Smith R, Clifton VL, 'Asthma during pregnancy alters immune cell profile and airway epithelial chemokine release', Inflammation Research, 59 349-358 (2010) [C1]
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2009 |
Wark PA, McDonald VM, 'Nebulised hypertonic saline for cystic fibrosis', Cochrane Database of Systematic Reviews, - CD001506 (2009) [C1]
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2009 |
Saedi Some Olia A, Wood LG, Garg ML, Gibson PG, Wark PA, 'Anti-inflammatory effects of long-chain n-3 PUFA in rhinovirus-infected cultured airway epithelial cells', British Journal of Nutrition, 101 533-540 (2009) [C1]
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2009 |
Ramirez-Farias C, Slezak K, Fuller Z, Duncan A, Holtrop G, Louis P, 'Effect of inulin on the human gut microbiota: stimulation of Bifidobacterium adolescentis and Faecalibacterium prausnitzii.', The British journal of nutrition, 101 541-550 (2009)
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2009 |
Kidd TJ, Ramsay KA, Hu H, Bye PTP, Elkins MR, Grimwood K, et al., 'Low Rates of Pseudomonas aeruginosa Misidentification in Isolates from Cystic Fibrosis Patients', JOURNAL OF CLINICAL MICROBIOLOGY, 47 1503-1509 (2009)
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2009 |
Saedi Some Olia A, Wood LG, Garg ML, Gibson PG, Wark PA, 'Lycopene enrichment of cultured airway epithelial cells decreases the inflammation induced by rhinovirus infection and lipopolysaccharide', Journal of Nutritional Biochemistry, 20 577-585 (2009) [C1]
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2009 |
Wark PA, Grissell TV, Davies BL, See HV, Gibson PG, 'Diversity in the bronchial epithelial cell response to infection with different rhinovirus strains', Respirology, 14 180-186 (2009) [C1]
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2008 |
Saedi Some Olia A, Wood LG, Garg ML, Gibson PG, Wark PA, 'Supplementation of long chain N-3 polyunsaturated fatty acids increases the utilization of lycopene in cultured airway epithelial cells', Journal of Food Lipids, 15 421-432 (2008) [C1]
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2008 |
Wark PA, 'Guest editorial', Paediatric Respiratory Reviews, 9 233-235 (2008) [C3]
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2008 |
See HV, Wark PA, 'Innate immune response to viral infection of the lungs', Paediatric Respiratory Reviews, 9 243-250 (2008) [C1]
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2008 |
Simpson JL, Wark PA, 'The role of exhaled nitric oxide and exhaled breath condensates in evaluating airway inflammation in asthma', Expert Opinion on Medical Diagnostics, 2 607-620 (2008) [C1]
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2008 |
Oliver BGG, Lim S, Wark PA, Laza-Stanca V, King N, Black JL, et al., 'Rhinovirus exposure impairs immune responses to bacterial products in human alveolar macrophages', Thorax, 63 519-525 (2008) [C1]
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2008 |
Hansbro NG, Horvat JC, Wark PA, Hansbro PM, 'Understanding the mechanisms of viral induced asthma: New therapeutic directions', Pharmacology & Therapeutics, 117 313-353 (2008) [C1]
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2008 |
Wark P, 'Bronchitis (acute)', BMJ clinical evidence, 2008 (2008)
INTRODUCTION: Acute bronchitis, with transient inflammation of the trachea and major bronchi, affects over 40/1000 adults a year in the UK. The causes are usually considered to be... [more]
INTRODUCTION: Acute bronchitis, with transient inflammation of the trachea and major bronchi, affects over 40/1000 adults a year in the UK. The causes are usually considered to be infective, but only around half of people have identifiable pathogens. The role of smoking or of environmental tobacco smoke inhalation in predisposing to acute bronchitis is unclear. A third of people may have longer-term symptoms or recurrence.METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for acute bronchitis in people without chronic respiratory disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2007 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).RESULTS: We found 19 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics (amoxicillin [with or without clavulanic acid], cephalosporins, or macrolides), antihistamines, antitussives, beta(2) agonists (inhaled or oral), cephalosporins, expectorants, and analgesics.
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2007 |
Weckmann M, Collison A, Simpson JL, Kopp MV, Wark PA, Smyth MJ, et al., 'Critical link between TRAIL and CCL20 for the activation of T(H)2 cells and the expression of allergic airway disease', Nature Medicine, 13 1308-1315 (2007) [C1]
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2007 |
Wark PA, Bucchieri F, Johnston SL, Gibson PG, Hamilton L, Mimica J, et al., 'IFN-gamma-induced protein 10 is a novel biomarker of rhinovirus-induced asthma exacerbations', Journal of Allergy and Clinical Immunology, 120 586-593 (2007) [C1]
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2006 |
Wark PA, Gibson PG, 'Asthma exacerbations 3: Pathogenesis', Thorax, 61 909-915 (2006) [C1]
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2006 |
Wark PA, 'Safety concerns with salmeterool', Australian Prescriber, 29 118-119 (2006) [C3] |
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2006 |
Wark P, 'Bronchitis (acute).', Clinical evidence, 1996-2005 (2006)
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2006 |
Contoli M, Message SD, Laza-Stanca V, Edwards MR, Wark PA, Bartlett N, et al., 'Role of eficient type III interferon-lambda production in asthma exacerbations', Nature Medicine, 12 1023-1026 (2006) [C1]
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2005 |
Wark PAB, McDonald V, Jones AP, 'Nebulised hypertonic saline for cystic fibrosis', COCHRANE DATABASE OF SYSTEMATIC REVIEWS, (2005)
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2005 |
Wood LG, Garg ML, Simpson JL, Mori TA, Croft KD, Wark PA, Gibson PG, 'Induced sputum 8-isoprostane concentrations in inflammatory airway diseases', American Journal of Respiratory and Critical Care Medicine, 171 426-430 (2005) [C1]
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2005 |
Wark P, 'Bronchitis (acute).', Clinical evidence, 1844-1852 (2005) |
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2005 |
Wark PA, Johnston S, Bucchieri F, Powell R, Puddicombe S, Laza-Stanca V, et al., 'Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus', Journal of Experimental Medicine, 201 937-947 (2005) [C1]
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2004 |
Wark P, Gibson PG, Wilson A, 'Azoles for allergic bronchopulmonary aspergillosis associated with asthma', COCHRANE DATABASE OF SYSTEMATIC REVIEWS, (2004)
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2004 |
Wark PA, 'Bronchitis (acute)', AMERICAN FAMILY PHYSICIAN, 70 557-558 (2004) |
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2004 |
Walter E, Gibbins N, Vandersteen A, Kinton L, Wark P, Jonas M, 'Hyperkalaemic ascending paralysis', JOURNAL OF THE ROYAL SOCIETY OF MEDICINE, 97 330-331 (2004)
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2004 |
Wark PA, 'Pathogenesis of allergic bronchopulmonary aspergillosis and an evidence-based review of azoles in treatment', Respiratory Medicine, 98 915-923 (2004) [C1]
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2004 |
Wark P, 'Bronchitis (acute).', Clinical evidence, 1923-1932 (2004) |
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2004 |
Wark P, Gibson PG, Wilson A, 'Azoles for allergic bronchopulmonary aspergillosis associated with asthma', Cochrane Database of Systematic Reviews, 2017 (2004)
© 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Background: Allergic bronchopulmonary aspergillosis is hypersensitivity to the fungus Aspergillus fum... [more]
© 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Background: Allergic bronchopulmonary aspergillosis is hypersensitivity to the fungus Aspergillus fumigatus that complicates patients with asthma and cystic fibrosis. The mainstay of treatment for allergic bronchopulmonary aspergillosis remains oral corticosteroids, though this does not completely prevent exacerbations and may not prevent the decline in lung function. Objectives: The purpose of this review was to determine the efficacy of azoles in the treatment of allergic bronchopulmonary aspergillosis. Search methods: We searched the Cochrane Airways Group Asthma trials register, CENTRAL, MEDLINE and EMBASE. Searches are current as of May 2008. Selection criteria: All controlled trials that assessed the effect of azole antifungal agents compared to placebo or other standard therapy for allergic bronchopulmonary aspergillosis were reviewed. Patients with cystic fibrosis were not included. Data collection and analysis: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. Main results: Twelve trials were identified, but only three were prospective, randomised and controlled. A total of 94 participants were included. One demonstrated a reduction in immunological markers of disease activity and symptom scores using ketoconazole 400 mg daily for 12 months. There was no significant improvement in lung function. The other two examined the use of itraconazole for 16 weeks. In one there was a reduction in sputum eosinophils by 35% compared to 19% with placebo (p < 0.01). In the same trial, the number of exacerbations requiring oral corticosteroids was 0.4 per patient with itraconazole compared with 1.3 per patient with placebo (p < 0.03). Meta-analysis of data from both trials showed that itraconazole treated patients were more likely to have decline in serum IgE over 25% or more (Peto OR 3.30; 95% confidence intervals 1.30 to 8.15). Authors' conclusions: Itraconazole modifies the immunologic activation associated with allergic bronchopulmonary aspergillosis and improves clinical outcome, at least over the period of 16 weeks. Adrenal suppression with inhaled corticosteroids and itraconazole is a potential concern.
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2004 |
Wark PA, 'Bronchitis (acute)', Clinical Evidence, 12 (2004) [C3]
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2003 |
Simpson JL, Moric I, Wark PA, Johnston S, Gibson PG, 'Use of induced sputum for the diagnosis of influenza and infections in asthma: a comparison of diagnostic techniques', Journal of Clinical Virology, 339-346 (2003) [C1]
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2003 |
Wark P, 'Drug treatment for chronic obstructive pulmonary disease', IDRUGS, 6 874-879 (2003) |
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2003 |
Wark P, 'Acute bronchitis.', Clinical evidence, 1716-1723 (2003) |
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2003 |
Wark PA, McDonald V, 'Nebulised hypertonic saline for cystic fibrosis.', Cochrane database of systematic reviews (Online), (2003)
BACKGROUND: The lung disease in cystic fibrosis is characterised by impaired mucociliary clearance. Hypertonic saline (HS) has been shown to enhance mucociliary clearance in-vitro... [more]
BACKGROUND: The lung disease in cystic fibrosis is characterised by impaired mucociliary clearance. Hypertonic saline (HS) has been shown to enhance mucociliary clearance in-vitro and this may act to lessen the destructive inflammatory process in the airways. OBJECTIVES: To investigate the effects of treatment with nebulised hypertonic saline on people with CF compared to placebo and or other treatments that enhance mucociliary clearance. SEARCH STRATEGY: 'We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings. Date of the most recent search of the Group's register: October 2001. SELECTION CRITERIA: All controlled trials (any language) assessing the effect of hypertonic saline compared to placebo or other mucolytic therapy, for any duration or dose regimen in people with cystic fibrosis of any age or severity. DATA COLLECTION AND ANALYSIS: All identified trials were independently reviewed by both reviewers & all data collected. Trial quality was assessed along with allocation concealment. MAIN RESULTS: Fourteen controlled trials were identified. Nine trials met the inclusion criteria; these involved 235 participants with an age range of 6 to 46 years. Two short-term trials of immediate effect on mucociliary clearance demonstrated that HS increased isotope clearance compared to control. Lung function as measured by improvement in Forced Expiratory Volume at one second (FEV1 l/min) was observed in four trials. When 3% to 7% saline was used in a volume of 10mls twice a day, in comparison to placebo, HS led to a significant increase in FEV1, WMD 12.20 (95%CI 4.30 to 20.10). In comparison to deoxyribonuclease (DNase) two trials used a similar concentration and volume of HS. Over a three week period the groups showed a similar increase in FEV1, WMD -1.60 (95%CI -11.16 to 7.96). However after 12 weeks treatment in participants with moderate to severe lung disease compared to DNase, HS 5mls twice a day showed less benefit to FEV1, WMD -13.00 (95%CI -22.46 to -3.54). No serious adverse events were noted. REVIEWER'S CONCLUSIONS: Nebulised hypertonic saline improves mucociliary clearance in short term clinical trials and appears to increase lung function compared to control. In comparison to DNase it may be less effective at improving lung function, after three months. At this stage there is insufficient evidence to support the use of hypertonic saline as routine treatment for people with cystic fibrosis.
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2003 |
Wark PA, Gibson PG, Wilson AJ, 'Azoles for allergic bronchopulmonary aspergillosis associated with asthma.', Cochrane database of systematic reviews (Online), (2003)
BACKGROUND: Allergic bronchopulmonary aspergillosis is hypersensitivity to the fungus Aspergillus fumigatus that complicates patients with asthma and cystic fibrosis. The mainstay... [more]
BACKGROUND: Allergic bronchopulmonary aspergillosis is hypersensitivity to the fungus Aspergillus fumigatus that complicates patients with asthma and cystic fibrosis. The mainstay of treatment for allergic bronchopulmonary aspergillosis remains oral corticosteroids, though this does not completely prevent exacerbations and may not prevent the decline in lung function. OBJECTIVES: The purpose of this review was to determine the efficacy of azoles in the treatment of allergic bronchopulmonary aspergillosis. SEARCH STRATEGY: We searched the Cochrane Airways Group Asthma trials register using the terms: (allergic bronchopulmonary aspergillosis OR aspergillosis OR allergic pulmonary aspergillosis OR allergic fungal and disease OR allergic mycotic and disease) AND (azole OR triazole OR itraconazole OR ketoconazole). Date of last search January 2003. SELECTION CRITERIA: All controlled trials that assessed the effect of azole antifungal agents compared to placebo or other standard therapy for allergic bronchopulmonary aspergillosis were reviewed. Patients with cystic fibrosis were not included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. MAIN RESULTS: Twelve trials were identified, but only three were prospective, randomised and controlled. A total of 94 participants were included. One demonstrated a reduction in immunological markers of disease activity and symptom scores using ketoconazole 400 mg daily for 12 months. There was no significant improvement in lung function. The other two examined the use of itraconazole for 16 weeks. In one there was a reduction in sputum eosinophils by 35% compared to 19% with placebo (p < 0.01). In the same trial, the number of exacerbations requiring oral corticosteroids was 0.4 per patient with itraconazole compared with 1.3 per patient with placebo (p < 0.03). Meta-analysis of data from both trials showed that itraconazole treated patients were more likely to have decline in serum IgE over 25% or more (Peto OR 3.30; 95% confidence intervals 1.30 to 8.15). REVIEWER'S CONCLUSIONS: Itraconazole modifies the immunologic activation associated with allergic bronchopulmonary aspergillosis and improves clinical outcome, at least over the period of 16 weeks. Adrenal suppression with inhaled corticosteroids and itraconazole is a potential concern.
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2003 |
Wark PA, Hensley MJ, Saltos N, Boyle MJ, Toneguzzi R, Simpson JL, et al., 'Anti-inflammatory effect of itraconazole in stable allergic bronchopulmonary aspergillosis: A randomized controlled trial', The Journal of Allergy and Clinical Immunology, 111 952-957 (2003) [C1]
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2003 |
Gibson PG, Wark PA, Simpson JL, Meldrum CJ, Meldrum S, Saltos N, Boyle MJ, 'Induced sputum IL-8 gene expression, neutrophil influx and MMP-9 in allergic bronchopulmonary aspergillosis', European Respiratory Journal, 21 582-588 (2003) [C1]
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2003 |
Wark PAB, Gibson PG, 'Clinical Usefulness of Inflammatory Markers in Asthma', American Journal of Respiratory & Critical Care Medicine, 2 11-19 (2003) [C1]
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2002 |
Wark PA, Johnston S, Simpson JL, Hensley MJ, Gibson PG, 'Chlamydia pneumoniae immunoglobulin A reactivation and airway inflammation in acute asthma', The European Respiratory Journal, 20 834-840 (2002) [C1]
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2002 |
Wark PA, Johnston S, Moric I, Simpson JL, Hensley MJ, Gibson PG, 'Neutrophil degranulation and cell lysis is associated with clinical severity in virus-induced asthma', The European Respiratory Journal, 19 68-75 (2002) [C1]
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2002 |
Gibson PG, Grootendor D, Henry R, Pin I, Rytila P, Wark P, et al., 'Sputum induction in children', European Respiratory Journal, 37 44s-46s (2002) [C3]
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2002 |
Wark PA, Simpson JL, Hensley MJ, Gibson PG, 'Airway inflammation in thunderstorm asthma', Clinical and Experimental Allergy, 32 1750-1756 (2002) [C1]
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2002 |
Wark PAB, 'DX-890 Dyax', IDrugs, 5 586-589 (2002)
Dyax (formerly Protein Engineering Corp) and Debiopharm are developing DX-890, an inhibitor of human ncutrophil elastase (HNE),for the potential treatment of pulmonary diseases su... [more]
Dyax (formerly Protein Engineering Corp) and Debiopharm are developing DX-890, an inhibitor of human ncutrophil elastase (HNE),for the potential treatment of pulmonary diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). In December 1999, Debiopharm initiated phase I trials with an aerosol formulation of DX-890; studies were completed by October 2000. By August 2000, DX-890 was in phase II evaluation for the potential treatment of CF, and in May 2002, Dyax planned to initiate a further study, in children with CF, within the year. By June 2002, phase II trials in CF were ongoing in France and Spain, with results expected soon after this date. In September 2000, JP Morgan predicted a 2005 launch for this drug, with estimated sales in that year of US $23 million rising to US $63 million in 2007. © PharmaPress Ltd.
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2002 |
Simpson JL, Gibson PG, Wark PA, 'Optimization of sputum-processing methods for the measurement of interleukin-5: Effects of protease inhibition', Respirology, 7 111-116 (2002) [C1]
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2001 |
Wark PA, Simpson J, Hensley MJ, Gibson PG, 'Safety of sputum induction with isotonic saline in adults with acute severe asthma', Clinical and Experimental Allergy, 31 1745-1753 (2001) [C1]
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2001 |
Gibson PG, Simpson J, Chalmers AC, Toneguzzi R, Wark PA, Wilson AJ, Hensley MJ, 'Airway Eosinophilia is associated with Wheeze but is uncommon in Children with Persistent Cough and Frequent Chest Colds', American Journal of Respiratory and Critical Care Medicine, 164 977-981 (2001) [C1]
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2001 |
Wark PA, 'Sputum lactate dehydrogenase, a marker of cell necrosis, is elevated in acute asthma', Respirology, 6 (2001)
Rationale: The role of neutrophils in airway inflammation in acute asthma is unclear. Lactate dehydrogenase (LDH) is a marker of cell necrosis. The aim of this study was to determ... [more]
Rationale: The role of neutrophils in airway inflammation in acute asthma is unclear. Lactate dehydrogenase (LDH) is a marker of cell necrosis. The aim of this study was to determine if levels of LDH were elevated in acute asthma and to determine how this related to airway inflammation and the clinical severity of acute asthma. Methods: Subjects with acute asthma had spirometry and sputum induction. Infection was determined using sputum PCR for common respiratory viruses. Sputum supernatant LDH activity was measured using the enzymatic rate method with isoenzyme pattern determined by gel electrophoresis. Results: We recruited 37 subjects with acute severe asthma: 12 had infection with respiratory syncytial virus (RSV), 9 with influenza, 6 picornaviruses, 10 non-infective exacerbations. There were 8 healthy controls. Sputum LDH was highest in those with RSV (653.1 lU/mL), influenza infection (549.5 lU/raL) and picornaviruses (501.2 lU/mL) compared to those with no infection (182 lU/mL), while all those with acute asthma were higher than the controls (25 lU/mL, p 0.01). LDH-5 was the main isoenzyme present suggesting neutrophil lysis with elevated LDH-5. Sputum LDH was associated with elevated sputum neutrophils (r = 0.8), a lower FEV| (r = -0.5), more severe acute symptoms (r = 0.6) and a longer length of hospital stay (r = 0.4). Conclusion: Sputum LDH is elevated in acute asthma with viral infection. Cell necrosis in acute asthma may potentiate neutrophilic airway inflammation and more severe clinical disease.
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2001 |
Wark P, Wilson AJ, Gibson PG, 'Azoles for allergic bronchopulmonary aspergillosis', Praxis, 90 1780 (2001)
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2001 |
Wark PA, Gibson PG, Johnston S, 'Exacerbations of asthma: addressing the triggers and treatments', Monaldi Archives for Chest Disease, 56 429-435 (2001) [C1]
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2001 |
Wark PA, Gibson PG, 'Allergic bronchopulmonary aspergillosis: New concepts of pathogenesis and treatment', Respirology, 6 1-7 (2001) [C2]
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2000 |
Wark PA, Saltos N, Simpson J, Slater S, Hensley MJ, Gibson PG, 'Induced sputum easinophils and neutrophils and bronchiectasis severity in allergic bronchopulmonary aspergillosis', European Respiratory Journal, 16 1095-1101 (2000) [C1]
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2000 |
Wark PA, Gibson PG, Fakes K, 'Induced sputum eosinophils in the assessment of asthma and chronic cough*', Respirology, 5 51-57 (2000) [C1]
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2000 |
Wark PA, Wilson A, Gibson PG, 'Azoles for allergic bronchopulmonary aspergillosis', The Cochrane Library, 1-9 (2000) [C1]
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2000 |
Wark PA, McDonald V, 'Nebulised hypertonic saline for cystic fibrosis.', Cochrane database of systematic reviews (Online : Update Software), (2000)
BACKGROUND: The lung disease in cystic fibrosis is characterised by impaired mucociliary clearance, recurrent bronchial infection and airway inflammation. Hypertonic saline has be... [more]
BACKGROUND: The lung disease in cystic fibrosis is characterised by impaired mucociliary clearance, recurrent bronchial infection and airway inflammation. Hypertonic saline has been shown to enhance mucociliary clearance in-vitro and this may act to lessen the destructive inflammatory process in the airways. OBJECTIVES: To determine if nebulised hypertonic saline treatment improved lung function, exercise tolerance, quality of life and decreased the incidence of exacerbations of respiratory infections in patients with cystic fibrosis. SEARCH STRATEGY: Studies were identified from the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register. Titles and abstracts were reviewed to identify all controlled trials. Review articles and bibliographies identified from this process were surveyed for additional citations & RCTs. Identification of unpublished work was obtained from abstract books from the three major Cystic Fibrosis conferences (International Cystic Fibrosis Conference, The European Cystic Fibrosis Conference and the North American Cystic Fibrosis Conference). Trial authors were contacted for additional information when only abstracts were available to review. Date of the most recent search of the Group's specialised register: November 1999. SELECTION CRITERIA: All controlled trials that assessed the effect of hypertonic saline compared to placebo or other mucolytic therapy, for any duration or dose regimen in subjects with cystic fibrosis of any age or severity were reviewed. Studies in languages other than English were included. DATA COLLECTION AND ANALYSIS: All identified trials were independently reviewed by both reviewers & all data collected. Trial quality was scored by the Cochrane assessment of allocation concealment & the Jadad scale of methodological quality. MAIN RESULTS: Twelve controlled trials of hypertonic saline were identified. Seven trials met the inclusion criteria; these involved 143 subjects with an age range of 6 to 46 years. Of these, six were published studies and one in abstract form. The durations of the trials were limited to immediate effects on mucociliary clearance to a maximum of three weeks. In two studies, involving thirty five subjects, a score for the feeling of cleared chest was made using visual analogue scales. This analysis showed a weighted mean difference of -0.98 (95% confidence Interval -1.6, -0.34), favouring hypertonic saline over isotonic saline. In two trials with 22 subjects hypertonic saline improved mucociliary clearance as measured by isotope clearance from the lungs in 90 minutes demonstrating a weighted mean difference of -11.3 (95% confidence Interval -18.6, -4.0), and as area under the clearance time curve; weighted mean difference of -212 (95%CI -272, -152), also favouring hypertonic saline over isotonic saline. Lung function as measured by improvement in FEV1 was observed in one study of 27 subjects. The percentage increase in FEV1 at two weeks increased by a mean 15.0% with hypertonic saline and 2.8% with isotonic saline (p=0.004). Adverse events were adequately described in only one trial and none were serious. REVIEWER'S CONCLUSIONS: Nebulised hypertonic saline improves mucociliary clearance immediately after administration which may have a longer term beneficial effect in cystic fibrosis. The maximum time data were recorded for was only three weeks. Most of the patients had mild to moderate lung disease and the effect on severe lung disease remains unclear. Further studies of hypertonic saline should be carried out to determine the effect on pulmonary function tests, quality of life, frequency of exacerbations of respiratory disease and efficacy comparisons with nebulised deoxyribonuclease, with larger numbers and for longer duration. At this stage there is insufficient evidence to support the use of hypertonic saline in routine treatment for patients with cystic fibrosis.
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2000 |
Wark P, Wilson AW, Gibson PG, 'Azoles for allergic bronchopulmonary aspergillosis.', Cochrane database of systematic reviews (Online), (2000)
BACKGROUND: Allergic Broncho-pulmonary Aspergillosis (ABPA) is hypersensitivity to the fungus Aspergillus Fumigatus that complicates patients with asthma and cystic fibrosis. The ... [more]
BACKGROUND: Allergic Broncho-pulmonary Aspergillosis (ABPA) is hypersensitivity to the fungus Aspergillus Fumigatus that complicates patients with asthma and cystic fibrosis. The condition usually results in an increase in symptoms, a greater reliance on corticosteroids to control the disease process and may lead to a progressive decline in lung function. The mainstay of treatment for ABPA remains oral corticosteroids, though this does not completely prevent exacerbations and may not prevent the decline in lung function. OBJECTIVES: The purpose of this review is to determine the efficacy of azoles in the treatment of ABPA SEARCH STRATEGY: An initial search was carried out using the Cochrane Airways Group Asthma RCT register. The register was searched using the following terms: (asthma or wheeze) and (allergic bronchopulmonary aspergillosis or aspergillosis or allergic pulmonary aspergillosis or allergic fungal and disease or allergic mycotic and disease) and (azole or triazole or itraconazole or ketoconazole). SELECTION CRITERIA: All controlled trials that assessed the effect of azole antifungal agents compared to placebo or other standard, for any duration or dose regimen in subjects with ABPA of any age or severity were reviewed. Studies in languages other than English were included. DATA COLLECTION AND ANALYSIS: All identified trials were independently reviewed by both reviewers & all data collected. Trial quality was scored by the Cochrane assessment of allocation concealment & the Jadad scale of methodological quality. MAIN RESULTS: A total of 11 trials were identified concerning the use of azoles in ABPA. Only two prospective controlled trials were identified. The first trial examined the use of Ketoconazole 400 mg daily for 12 months and demonstrated a reduction in immunological markers of disease activity and symptom scores, there was no significant improvement in lung function. The other trial examined the use of itraconazole for 16 weeks. This demonstrated a reduction in corticosteroid usage, an improvement in immunological markers, an improvement in pulmonary function and exercise tolerance. This study was only available as an abstract and limited details were available. REVIEWER'S CONCLUSIONS: There is insufficient information available to recommend the use of azole anti-fungal agents in the routine treatment of patients with ABPA.
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1999 |
Wark P, Simpson J, Fakes K, Burgess H, Timmins N, Hensley M, Gibson PG, 'Airway inflammation in allergic bronchopulmonary aspergillosis', Respirology, 4 (1999)
Allergic bronchopulmonary aspergillosis (ABPA) is a serious complication of asthma. In uncomplicated asthma airway inflammation(ai) is characterised by sputum eosinophilia without... [more]
Allergic bronchopulmonary aspergillosis (ABPA) is a serious complication of asthma. In uncomplicated asthma airway inflammation(ai) is characterised by sputum eosinophilia without an increase in the total cell count (TCC). In bronchiectasis the intensity of ai increased and there is a neutrophil infiltrate. Airway inflammation in ABPA is not well defined. This study tested the hypothesis that ai in ABPA would be of increased intensity with a mixed eosinophil/neutrophil pattern. Methods: In subjects with asthma, ABPA was assessed by 5 criteria; 1. positive allergy skin test to Aspergillus Fumigatus (Af); 2. raised specific serum IgE to Af; 3. positive precipitating antibodies to Af; 4. total IgE > 10001U/ml and 5. bronchiectasis (CT scan). Subjects were classified as definite ABPA (n=13) with criteria 1, 2, 3 and either 4 or 5; or as probable ABPA (n=18) with 1 and 2 and either 3, 4 or 5 (n=13). These groups were combined for analysis. Af sensitised subjects (n=19 with positive skin testing alone), were compared to a matched group with asthma (negative to Af on skin test) (n=15) and healthy controls (n=8). Spirometry, saline challenge and sputum induction were performed, with results reported as medians and interquartile ranges. Results: Patients with ABPA had an increased TCC (4.6, 0.9-29.6) compared to: Af sensitised (3.6, 1.4-7.4), asthma (1.5, 0.8-3.2), and controls (1.35, 1.3-1.4) (p<0.05). Those with ABPA had increased sputum eosinophils (3.8, 0.3-16.3), compared to: Af sensitised (1.4, 0.1-6), asthma (1.6, 0.01-3), and controls (0.3, 0.3-0.31 ) (p=0.001). Those with ABPA had increased levels of eosinophil cationic protein(ng/ml) (5471, 311-42485) compared to: Af sensitised (1432, 338-6902), asthma (244, 78-857), and controls (110, 99-121 ) (p<0.001). Neutrophil counts were similar in all groups. Myeloperoxidase was similar in ABPA (232, 66-454) and asthma (177, 57-318) (p=0.3) but greater than in healthy controls (76, 76-89) Conclusion: Airway inflammation in ABPA is of increased intensity compared to that of chronic asthma. Unlike bronchiectasis, the cellular infiltrate is predominantly eosinophilic. The eosinophils demonstrate increased activation.
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1999 |
Wark P, McDonald V, 'The effectiveness of nebulised hypertonic saline on lung function, exercise tolerance and quality of life in cystic fibrosis', Respirology, 4 (1999)
Thick tenacious secretions that are difficult to expectorate and recurrent infection that leads to progressive end stage fibrotic disease typify lung disease in cystic fibrosis (C... [more]
Thick tenacious secretions that are difficult to expectorate and recurrent infection that leads to progressive end stage fibrotic disease typify lung disease in cystic fibrosis (CF). Mucolytic treatment can improve expectoration of sputum and lung function in CF. Our aim was to examine the efficacy of hypertonic saline (HS) in CF as an alternative or supplementary treatment. Methods: A meta-analysis of controlled trials was done. A search was carried out via the Cochrane Cystic Fibrosis Group specialist trials register. The titles and abstracts were reviewed to identify all potential controlled trials, articles were surveyed for additional citations. Identification of unpublished work was obtained from abstract books from (The International CF Conference, The European CF Conference and the North American CF Conference). All controlled trials that assessed the efficacy of Hypertonic Saline in subjects with cystic fibrosis were reviewed. The reviewers independently reviewed all trials. Data was analysed and compared using Revman. Results: A total of ten controlled trials were identified. Adequate data was available for analysis from seven of the studies, n = 166, age range (7-36years). Two studies showed that hypertonic saline (HS) improved lung function at two weeks by increasing the percentage change in FEV1. This showed a weighted mean difference (WMD) of +12.2 (95%CI +13.860, +10.540), favouring HS over isotonic saline (IS). An immediate effect on mucociliary clearance as measured by radioisotope was assessed in two trials. Analysis of isotope clearance at 90 mins found a WMD of +11.28 (95%CI +18.562, +3.998), favouring HS over IS. Measuring clearance as area under the curve showed a WMD of +212.059 (95%CI +271.641, +152.477), favouring HS over IS. Nebulised hypertonic saline appears to have a beneficial effect in cystic fibrosis, improving muco-ciliary clearance immediately after administration and lung function after two weeks of administration in combination with chest physiotherapy. Comparative data was not available to assess outcomes such as improvement in objective exercise testing, effect on symptom scores, quality of life measures or long term efficacy.
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1998 |
Wark P, Goldberg H, Ferson M, McKenzie D, Lau E, Rivas K, 'Mycobacterial lymphadenitis in eastern Sydney', AUSTRALIAN AND NEW ZEALAND JOURNAL OF MEDICINE, 28 453-458 (1998)
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