Immunology and Respiratory Medicine

Melbourne, Australia

Immunology and Respiratory Medicine

Melbourne, Australia
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Lee A.L.,University of Melbourne | Lee A.L.,Institute for Breathing and Sleep | Button B.M.,Monash University | Denehy L.,University of Melbourne | And 10 more authors.
Respiratory Care | Year: 2015

BACKGROUND: Acid gastroesophageal reflux is a common problem in non-cystic fibrosis bronchiectasis and COPD. Invasive methods are used to diagnose gastroesophageal reflux, but the ability to detect pulmonary microaspiration of gastric contents using this method is unclear. A noninvasive option to detect pulmonary microaspiration is to measure pepsin in exhaled breath condensate (EBC), but this has not been related to esophageal pH monitoring in these lung conditions. This study aimed to measure pepsin concentrations and pH in EBC and to determine the relationship to gastroesophageal reflux in bronchiectasis or COPD. METHODS: Subjects with bronchiectasis (n = 10) or COPD (n = 10) and control subjects (n = 10) completed 24-h esophageal pH monitoring for detection of acid gastroesophageal reflux, measuring the percentage of reflux time in the proximal esophagus and the DeMeester score (DMS). Concurrently, 3 samples of EBC were collected from each subject, and pH was measured and pepsin concentrations were analyzed by enzyme-linked immunosorbent assay. RESULTS: EBC pepsin was detected in subjects with bronchiectasis (44%) or COPD (56%) and in control subjects (10%). A diagnosis of gastroesophageal reflux was not associated with a higher concentration of EBC pepsin in bronchiectasis (P = .21) or COPD (P = .11). EBC pepsin concentration did not correlate with DMS (rs = 0.36) or proximal reflux index (rs = 0.25) in subjects with bronchiectasis or with DMS (rs = 0.28) or proximal reflux index (rs = 0.21) in patients with COPD. EBC and sputum pepsin concentrations were moderately correlated in bronchiectasis (rs = 0.56) and in COPD (rs = 0.43). CONCLUSIONS: Pepsin is detectable in EBC samples in bronchiectasis and COPD. Although no association was found between pepsin concentrations and a diagnosis of gastroesophageal reflux, a moderate relationship between sputum and EBC pepsin concentrations suggests that EBC pepsin may be a useful noninvasive marker of pulmonary microaspiration. © 2015 by Daedalus Enterprises.

Kee K.,Immunology and Respiratory Medicine | Kee K.,Monash University | Stuart-Andrews C.,Monash University | Ellis M.J.,Monash University | And 8 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2016

Rationale: Patients with chronic heart failure have limited exercise capacity, which cannot be completely explained by markers of cardiac dysfunction. Reduced pulmonary diffusing capacity at rest and excessively high ventilation during exercise are common in heart failure. We hypothesized that the reduced pulmonary diffusing capacity in patients with heart failure would predict greater dead space ventilation during exercise and that this would lead to impairment in exercise capacity. Objectives: To determine the relationship between pulmonary diffusing capacity at rest and dead space ventilation during exercise, and to examine the influence of dead space ventilation on exercise in heart failure. Methods: We analyzed detailed cardiac and pulmonary data at rest and during maximal incremental cardiopulmonary exercise testing from 87 consecutive heart transplant assessment patients and 18 healthy control subjects. Dead space ventilation was calculated using the Bohr equation. Measurements and Main Results: Pulmonary diffusing capacity at rest was a significant predictor of dead space ventilation at maximal exercise (r =20.524, P,0.001) in heart failure but not in control subjects. Dead space at maximal exercise also correlated inversely with peak oxygen consumption (r =20.598, P,0.001), peak oxygen consumption per kilogram (r =20.474, P,0.001), and 6-minutewalk distance (r =20.317, P = 0.021) in the heart failure group but not in control subjects. Conclusions: Low resting pulmonary diffusing capacity in heart failure is indicative of high dead space ventilation during exercise, leading to excessive and inefficient ventilation. These findings would support the concept of pulmonary vasculopathy leading to altered ventilation perfusion matching (increased dead space) and resultant dyspnea, independent of markers of cardiac function. Copyright © 2016 by the American Thoracic Society.

Burge A.T.,The Alfred | Holland A.E.,The Alfred | Holland A.E.,Austin Hospital | Holland A.E.,La Trobe University | And 9 more authors.
Physiotherapy (United Kingdom) | Year: 2015

Objectives: To determine the prevalence and impact of urinary incontinence (UI) in men with cystic fibrosis (CF). Design: Prospective observational study. Setting: Adult CF clinics at tertiary referral centres. Participants: Men with CF (. n=. 80) and age-matched men without lung disease (. n=. 80). Interventions: Validated questionnaires to identify the prevalence and impact of UI. Main outcome measures: Prevalence of UI and relationship to disease specific factors, relationship of UI with anxiety and depression. Results: The prevalence of UI was higher in men with CF (15%) compared to controls (10%) (. p=. 0.339). Men with CF and UI had higher scores for anxiety than those without UI (mean 9.1 (SD 4.8) vs 4.7 (4.1), p=. 0.003), with similar findings for depression (6.8 (4.6) vs 2.8 (3.4), p=. 0.002) using the Hospital Anxiety and Depression Scale. Conclusions: Incontinence is more prevalent in adult men with CF than age matched controls, and may have an adverse effect on mental health. The mechanisms involved are still unclear and may differ from those reported in women. © 2014 Chartered Society of Physiotherapy.

Sands S.A.,Monash Institute of Medical Research | Sands S.A.,Harvard University | Edwards B.A.,Harvard University | Kee K.,Immunology and Respiratory Medicine | And 11 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2011

Rationale: Patients with heart failure (HF) and Cheyne-Stokes respiration or periodic breathing (PB) often demonstrate improved cardiac function when treatment with continuous positive airway pressure (CPAP) resolves PB. Unfortunately, CPAP is successful in only 50% of patients, and no known factor predicts responders to treatment. Because PB manifests from a hypersensitive ventilatory feedback loop (elevated loop gain [LG]), we hypothesized that PB persists on CPAP when LG far exceeds the critical threshold for stable ventilation (LG = 1). Objectives: To derive, validate, and test the clinical utility of a mathematically precise method that quantifies LG from the cyclic pattern of PB, where LG = 2π/(2πDR - sin2πDR) and DR (i.e., duty ratio) = (ventilatory duration)/(cycle duration) of PB. Methods: After validation in a mathematical model of HF, we tested whether our estimate of LG changes with CPAP (n = 6) and inspired oxygen (n = 5) as predicted by theory in an animal model of PB. As a first test in patients with HF (n = 14), we examined whether LG predicts the first-night CPAP suppression of PB. Measurements and Main Results: In lambs, as predicted by theory, LG fell as lung volume increased with CPAP (slope = 0.9 ± 0.1; R 2 = 0.82; P < 0.001) and as inspired-arterial P O2 difference declined (slope = 1.05 ± 0.12; R 2 = 0.75; P < 0.001). In patients with HF, LG was markedly greater in 8 CPAP nonresponders versus 6 responders (1.29 ± 0.04 versus 1.10 ± 0.01; P < 0.001); LG predicted CPAP suppression of PB in 13/14 patients. Conclusions: Our novel LG estimate enables quantification of the severity of ventilatory instability underlying PB, making possible a priori selection of patients whose PB is immediately treatable with CPAP therapy.

Naughton M.T.,Immunology and Respiratory Medicine | Naughton M.T.,Monash University
Journal of Thoracic Disease | Year: 2015

Respiratory sleep disorders (RSD) occur in about 40-50% of patients with symptomatic congestive heart failure (CHF). Obstructive sleep apnea (OSA) is considered a cause of CHF, whereas central sleep apnea (CSA) is considered a response to heart failure, perhaps even compensatory. In the setting of heart failure, continuous positive airway pressure (CPAP) has a definite role in treating OSA with improvements in cardiac parameters expected. However in CSA, CPAP is an adjunctive therapy to other standard therapies directed towards the heart failure (pharmacological, device and surgical options). Whether adaptive servo controlled ventilatory support, a variant of CPAP, is beneficial is yet to be proven. Supplemental oxygen therapy should be used with caution in heart failure, in particular, by avoiding hyperoxia as indicated by SpO2 values > 95%. © Journal of Thoracic Disease.

PubMed | Immunology and Respiratory Medicine and Monash University
Type: Journal Article | Journal: Physiological reports | Year: 2015

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 (5710years, 83% male, left ventricular ejection fraction 3112%) as well as 10 healthy controls (5113years, 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 45min 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 (9.61.2 vs. 8.61.4 lung turnovers, P=0.034) and Scond (0.0290.014 vs. 0.0060.016/L, P=0.007) were higher in the heart failure patients. There was no difference in Sacin (0.1970.171 vs. 0.1250.081/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 45min in the supine position.

Peyton P.J.,Austin Hospital | Peyton P.J.,University of Melbourne | Chao I.,Austin Hospital | Weinberg L.,Austin Hospital | And 2 more authors.
Anesthesiology | Year: 2011

BACKGROUND: Rapid elimination of nitrous oxide from the lungs at the end of inhalational anesthesia dilutes alveolar oxygen, producing "diffusion hypoxia." A similar dilutional effect on accompanying volatile anesthetic agent has not been evaluated and may impact the speed of emergence. METHODS: Twenty patients undergoing surgery were randomly assigned to receive an anesthetic maintenance gas mixture of sevoflurane adjusted to bispectral index, in air-oxygen (control group) versus a 2:1 mixture of nitrous oxide-oxygen (nitrous oxide group). After surgery, baseline arterial and tidal gas samples were taken. Patients were ventilated with oxygen, and arterial and tidal gas sampling was repeated at 2 and 5 min. Arterial sampling was repeated 30 min after surgery. Sevoflurane partial pressure was measured in blood by the double headspace equilibration technique and in tidal gas using a calibrated infrared gas analyzer. Time to eye opening and time extubation were recorded. The primary endpoint was the reduction in sevoflurane partial pressures in blood at 2 and 5 min. RESULTS: Relative to baseline, arterial sevoflurane partial pressure was 39% higher at 5 min in the control group (P < 0.04) versus the nitrous oxide group. At 30 min the difference was not statistically significant. Time to eye opening (8.7 vs. 10.1 min) and time to extubation (11.0 vs.13.2 min) were shorter in the nitrous oxide group versus the control group (P < 0.04). CONCLUSIONS: Elimination of nitrous oxide at the end of anesthesia produces a clinically significant acceleration in the reduction of concentrations of the accompanying volatile agents, contributing to the speed of emergence observed after inhalational nitrous oxide anesthetic. © 2011 American Society of Anesthesiologists, Inc.

Borchard K.,Occupational Dermatology Research | Puy R.,Immunology and Respiratory Medicine | Nixon R.,Occupational Dermatology Research
Australasian Journal of Dermatology | Year: 2010

Hyaluronidase is a bovine or ovine testicular protein that is used as an adjunct to co-administered medicaments and fluids to enhance their dispersion and absorption through the degradation of hyaluronan. While it is a known potential allergen, there are few reports of hyaluronidase hypersensitivity. A 56-year-old lady presented 8 hours post glaucoma surgery with ipsilateral lacriminorrhoea, periorbital erythema, oedema, proptosis, pruritis and conjunctival chemosis. Right ocular motility was restricted and visual acuity was reduced. The reaction settled with oral corticosteroids and antihistamines. Hyaluronidase allergy was confirmed on skin prick testing. Hyaluronidase allergy is rare. In the few cases reported, reactions occurred at various doses and were acute (intraoperative), early (within hours), intermediate (within days) or delayed (within weeks). Anaphylaxis has also been described. Primary sensitization appears to be a prerequisite for most reactions. The variability in onset of symptoms and the response to skin testing would suggest that type I and type IV hypersensitivity may both contribute to this response. In this case, the timing fitted with a late phase type 1 reaction. This case shows that despite being less common than haemorrhage for acute reactions and infection for delayed reactions, allergy can account for orbital inflammation following ophthalmic surgery. © 2010 The Australasian College of Dermatologists.

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