Melbourne School of Health Sciences Collected Works - Research Publications
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ItemCardiogenic Airflow in the Lung Revealed Using Synchrotron-Based Dynamic Lung Imaging(NATURE PUBLISHING GROUP, 2018-03-21)The beating heart is known to produce pressure and airflow oscillations in the lungs of mammals. This phenomenon is often disregarded as detailed measurement of its effects in the lung have hitherto not been possible. Previous studies have attempted to measure the effect of these oscillations on gas mixing. However, the results have proven inconclusive, due to the lack of a direct measurement tool capable of flow measurement throughout the entire bronchial tree. Here we present the first detailed measurement of cardiogenic oscillations, using synchrotron-based dynamic lung imaging of live mechanically ventilated mice. The results demonstrate large flow oscillations and pendelluft in the airways due to the mechanical action of the beating heart. Using a virtual tracer modelling analysis we show that cardiogenic oscillations produced up to 4 times increased gas mixing, but only in the absence of tidal ventilation. The results highlight the importance of considering this often-disregarded phenomenon when investigating lung function, particularly in situations where tidal ventilation is reduced or absent.
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ItemThe Global Lung Function Initiative (GLI) Network: bringing the world's respiratory reference values together(EUROPEAN RESPIRATORY SOC JOURNALS LTD, 2017-09-01)UNLABELLED: The Global Lung Function Initiative (GLI) Network has become the largest resource for reference values for routine lung function testing ever assembled. This article addresses how the GLI Network came about, why it is important, and its current challenges and future directions. It is an extension of an article published in Breathe in 2013 [1], and summarises recent developments and the future of the GLI Network. KEY POINTS: The Global Lung Function Initiative (GLI) Network was established as a result of international collaboration, and altruism between researchers, clinicians and industry partners. The ongoing success of the GLI relies on network members continuing to work together to further improve how lung function is reported and interpreted across all age groups around the world.The GLI Network has produced standardised lung function reference values for spirometry and gas transfer tests.GLI reference equations should be adopted immediately for spirometry and gas transfer by clinicians and physiologists worldwide.The recently established GLI data repository will allow ongoing development and evaluation of reference values, and will offer opportunities for novel research. EDUCATIONAL AIMS: To highlight the advances made by the GLI Network during the past 5 years.To highlight the importance of using GLI reference values for routine lung function testing (e.g. spirometry and gas transfer tests).To discuss the challenges that remain for developing and improving reference values for lung function tests.
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ItemMaximal exercise does not increase ventilation heterogeneity in healthy trained adults(WILEY, 2016-04)The effect of exercise on ventilation heterogeneity has not been investigated. We hypothesized that a maximal exercise bout would increase ventilation heterogeneity. We also hypothesized that increased ventilation heterogeneity would be associated with exercise-induced arterial hypoxemia (EIAH). Healthy trained adult males were prospectively assessed for ventilation heterogeneity using lung clearance index (LCI), Scond, and Sacinat baseline, postexercise and at recovery, using the multiple breath nitrogen washout technique. The maximal exercise bout consisted of a maximal, incremental cardiopulmonary exercise test at 25 watt increments. Eighteen subjects were recruited with mean ± SDage of 35 ± 9 years. There were no significant changes inLCI, Scond, or Sacinfollowing exercise or at recovery. While there was an overall reduction in SpO2with exercise (99.3 ± 1 to 93.7 ± 3%,P < 0.0001), the reduction in SpO2was not associated with changes inLCI, Scondor Sacin Ventilation heterogeneity is not increased following a maximal exercise bout in healthy trained adults. Furthermore,EIAHis not associated with changes in ventilation heterogeneity in healthy trained adults.
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ItemVentilation heterogeneity is increased in patients with chronic heart failure(WILEY, 2015-10)In the healthy lung, ventilation is distributed heterogeneously due to factors such as anatomical asymmetry and gravity. This ventilation heterogeneity increases pathologically in conditions such as asthma, chronic obstructive lung disease, and cystic fibrosis. In chronic heart failure, lung biopsy demonstrates evidence of peripheral lung fibrosis and small airways narrowing and distortion. We hypothesized that this would lead to increased ventilation heterogeneity. Furthermore, we proposed that rostral fluid shifts when seated patients lie supine would further increase ventilation heterogeneity. We recruited 30 ambulatory chronic heart failure patients (57 ± 10 years, 83% male, left ventricular ejection fraction 31 ± 12%) as well as 10 healthy controls (51 ± 13 years, 90% male). Heart failure patients were clinically euvolemic. Subjects underwent measurement of ventilation heterogeneity using the multiple-breath nitrogen washout technique in the seated position, followed by repeat measurements after 5 and 45 min in the supine position. Ventilation heterogeneity was calculated using the lung clearance index (LCI), Sacin and Scond which represent overall, acinar, and small conducting airway function, respectively. Lung clearance index (9.6 ± 1.2 vs. 8.6 ± 1.4 lung turnovers, P = 0.034) and Scond (0.029 ± 0.014 vs. 0.006 ± 0.016/L, P = 0.007) were higher in the heart failure patients. There was no difference in Sacin (0.197 ± 0.171 vs. 0.125 ± 0.081/L, P = 0.214). Measures of ventilation heterogeneity did not change in the supine position. This study confirms the presence of peripheral airway pathology in patients with chronic heart failure. This leads to subtle but detectable functional abnormalities which do not change after 45 min in the supine position.
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ItemA spirometric journey following lung transplantation(WILEY, 2014-09)Spirometry is regarded as the primary tool for the evaluation of lung function in lung transplant (LTx) recipients. Spirometry is crucial in detecting the various phenotypes of chronic lung allograft dysfunction (CLAD), including restrictive allograft syndrome (RAS) and bronchiolitis obliterans syndrome (BOS) - note that these phenotypes potentially have different etiologies and therapies. Following LTx for idiopathic pulmonary fibrosis, a 60-year-old male recipient's lung function began to gradually improve, peaking at 5 months post-LTx. Subsequently, with increasing impairment of graft function, the diagnosis of BOS was made. A second LTx was performed and lung function subsequently began to increase again. Unfortunately, another year on, lung function deteriorated again - this time due to the development of RAS, antibody-mediated rejection was implicated as the possible underlying cause. This case report highlights the importance of spirometry in assessing the patterns of CLAD following LTx.
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ItemThe safety and efficacy of inhaled dry powder mannitol as a bronchial provocation test for airway hyperresponsiveness: a phase 3 comparison study with hypertonic (4.5%) saline(BMC, 2005-12-09)BACKGROUND: Inhaled mannitol is a new bronchial provocation test (BPT) developed to improve portability and standardisation of osmotic challenge testing. Osmotic challenge tests have an advantage over the traditional methods of measuring airway hyperresponsiveness using methacholine as they demonstrate higher specificity to identify asthma and thus the need for treatment with inhaled corticosteroids (ICS). The safety and the efficacy of mannitol (M) as a BPT to measure airway hyperresponsiveness were compared to hypertonic (4.5%) saline (HS) in people both with and without signs and symptoms of asthma. METHODS: A phase III, multi-centre, open label, operator-blinded, crossover design, randomised trial, with follow-up. Asthmatics and non-asthmatics (6-83 yr) were recruited and 592 subjects completed the study. Mannitol was delivered using a low resistance dry powder inhaler and HS was delivered using an ultrasonic nebuliser. The FEV1 was measured 60 seconds after each dose of mannitol (5,10,20,40,80,160,160,160 mg) and after each exposure to HS (0.5,1.0,2.0,4.0,8.0 minutes). A 15% fall in FEV1 defined a positive test. Adverse events were monitored and diaries kept for 7 days following the tests. RESULTS: Mean pre-test FEV1 (mean +/- SD) was 95.5 +/- 14% predicted. 296 were positive to mannitol (M+) and 322 positive to HS (HS+). A post study physician conducted clinical assessment identified 82.3% asthmatic (44% classified mild) and 17.7% non-asthmatic. Of those M+, 70.1% were taking ICS and of those mannitol negative (M-), 81.1 % were taking ICS. The % fall in FEV1 for mannitol in asthmatics was 21.0% +/- 5.7 and for the non-asthmatics, 5.5% +/- 4.8. The median PD15 M was 148 mg and PD15 HS 6.2 ml. The sensitivity of M to identify HS+ was 80.7% and the specificity 86.7%. The sensitivity of M compared with the clinical assessment was 59.8% and specificity 95.2% and increased to 88.7% and 95.0% respectively when the M- subjects taking ICS were excluded. Cough was common during testing. There were no serious adverse events. The diarised events were similar for mannitol and HS, the most common being headache (17.2%M, 19%HS), pharyngolaryngeal pain (5.1%M, 3%HS), nausea (4.3%M, 3%HS), and cough (2.2%M, 2.4%HS). CONCLUSION: The efficacy and safety of mannitol was demonstrated in non-asthmatic and clinically diagnosed asthmatic adults and children.