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Kelly V.J.,Massachusetts General Hospital | Kelly V.J.,Monash University | Kelly V.J.,Alfred Hospital | Sands S.A.,Harvard University | And 10 more authors.
Journal of Applied Physiology | Year: 2013

The mechanisms underlying not well-controlled (NWC) asthma remain poorly understood, but accumulating evidence points to peripheral airway dysfunction as a key contributor. The present study tests whether our recently described respiratory system reactance (Xrs) assessment of peripheral airway dysfunction reveals insight into poor asthma control. The aim of this study was to investigate the contribution of Xrs to asthma control. In 22 subjects with asthma, we measured Xrs (forced oscillation technique), spirometry, lung volumes, and ventilation heterogeneity (inert-gas washout), before and after bronchodilator administration. The relationship between Xrs and lung volume during a deflation maneuver yielded two parameters: the volume at which Xrs abruptly decreased (closing volume) and Xrs at this volume (Xrscrit). Lowered (more negative) Xrscrit reflects reduced apparent lung compliance at high lung volumes due, for example, to heterogeneous airway narrowing and unresolved airway closure or near closure above the critical lung volume. Asthma control was assessed via the 6-point Asthma Control Questionnaire (ACQ6). NWC asthma was defined as ACQ6 > 1.0. In 10 NWC and 12 well-controlled subjects, ACQ6 was strongly associated with postbronchodilator (post-BD) Xrscrit (R2 = 0.43, P < 0.001), independent of all measured variables, and was a strong predictor of NWC asthma (receiver operator characteristic area = 0.94, P < 0.001). By contrast, Xrs measures at lower lung volumes were not associated with ACQ6. Xrscrit itself was significantly associated with measures of gas trapping and ventilation heterogeneity, thus confirming the link between Xrs and airway closure and heterogeneity. Residual airway dysfunction at high lung volumes assessed via Xrscrit is an independent contributor to asthma control. Copyright © 2013 the American Physiological Society.

Crane M.A.,Cooperative Research Center for Asthma and Airways | Crane M.A.,Co operative Research Center for Asthma and Airways | Douglass J.A.,Monash University | Goeman D.P.,Cooperative Research Center for Asthma and Airways | And 4 more authors.
Respiratory Medicine | Year: 2012

Background: Tools which assist practitioners to identify patient concerns and increase understanding of their needs can improve both the delivery of care and adherence to treatment. The aim of this study was to test the validity and reliability of a 14-item tool, to identify the unmet needs and concerns of older people with asthma. Methods: The Patient Asthma Concerns Tool (PACT) was developed from a pool of 55 items derived from a comprehensive literature review. After pilot and field testing, the initial 55 item questionnaire was administered to a community sample (n = 193), psychometrically tested, and refined to a 14 item PACT tool which was evaluated by a group of clinicians. Results: The PACT was shown to have good content and construct validity and was well received by clinicians. The PACT also correlated well with the Juniper ACQ and Brooks' adherence score on related variables and showed good reliability with good-excellent Kappa and ICC scores. Internal consistency of factors was high, and the overall Cronbach's α was 0.70. Conclusion: The PACT questionnaire was shown to be a valid and reliable tool clinically and psychometrically. We intend to test it in primary care settings and anticipate that its use will assist health professionals to identify the needs and concerns of older patients with asthma and direct tailored asthma management accordingly. © 2012 Elsevier Ltd. All rights reserved.

Kelly V.J.,Monash University | Kelly V.J.,Co operative Research Center for Asthma and Airways | Kelly V.J.,Woolcock Institute of Medical Research | Brown N.J.,Co operative Research Center for Asthma and Airways | And 6 more authors.
Medical and Biological Engineering and Computing | Year: 2010

In order to understand the pathophysiology of diseases such as asthma and chronic obstructive pulmonary disease, it is essential to measure the mechanical properties of the airways. Currently, there are no methods to measure and quantify in vivo airway compliance in humans. In order to develop a method, we generated a curve-fitting algorithm that combines airway diameter measurements by high resolution computed tomography with pressure-volume curves obtained by the esophageal balloon technique. Our method allows the description of diameter-pressure curves for airways of varying size, presented as a 3D surface, from which specific airway compliance can be determined at any transpulmonary pressure. Applying this method to data from two healthy subjects, we found that small airways are more compliant than large airways and specific airway compliance was greatest at low transpulmonary pressures. In conclusion, our 3D surface is a useful tool to measure and quantify in vivo specific airway compliance in humans. © International Federation for Medical and Biological Engineering 2010.

Kelly V.J.,Monash University | Kelly V.J.,Co operative Research Center for Asthma and Airways | Kelly V.J.,Woolcock Institute of Medical Research | Kelly V.J.,Alfred Hospital | And 7 more authors.
Annals of Biomedical Engineering | Year: 2011

A new technique has been developed to determine in vivo airway compliance in humans that is specific to airway size and transpulmonary pressure, and can be represented as a three-dimensional surface. As yet, the ability of this technique to detect changes in specific airway compliance with disease status has not been demonstrated. The aim of this study was to assess whether this technique could determine changes in airway compliance which are thought to occur with altered smooth muscle tone in adults with asthma. Airway compliance was measured and displayed as a surface in adults with asthma before and after a reduction in smooth muscle tone by bronchodilator administration. Compliance, with respect to airway size, was calculated at three specific lung volumes; functional residual capacity (FRC), total lung capacity (TLC), and midway between FRC and TLC (MID). After bronchodilator, airway compliance increased at FRC and MID in the smaller airways (<3 mm). Furthermore, airway compliance under both conditions was greater in the smaller airways compared to the larger airways. In conclusion, our method may have future utility in assessing changes in airway compliance in respiratory diseases such as asthma. © 2010 Biomedical Engineering Society.

Kelly V.J.,Monash University | Kelly V.J.,Co operative Research Center for Asthma and Airways | Kelly V.J.,Woolcock Institute of Medical Research | Kelly V.J.,Alfred Hospital | And 11 more authors.
Journal of Applied Physiology | Year: 2012

Airway distensibility appears to be unaffected by airway smooth muscle (ASM) tone, despite the influence of ASM tone on the airway diameter-pressure relationship. This discrepancy may be because the greatest effect of ASM tone on airway diameter-pressure behavior occurs at low transpulmonary pressures, i.e., low lung volumes, which has not been investigated. Our study aimed to determine the contribution of ASM tone to airway distensibility, as assessed via the forced oscillation technique (FOT), across all lung volumes with a specific focus on low lung volumes. We also investigated the accompanying influence of ASM tone on peripheral airway closure and heterogeneity inferred from the reactance versus lung volume relationship. Respiratory system conductance and reactance were measured using FOT across the entire lung volume range in 22 asthma subjects and 19 healthy controls before and after bronchodilator. Airway distensibility (slope of conductance vs. lung volume) was calculated at residual volume (RV), functional residual capacity (FRC), and total lung capacity. At baseline, airway distensibility was significantly lower in subjects with asthma at all lung volumes. After bronchodilator, distensibility significantly increased at RV (64.8%, P < 0.001) and at FRC (61.8%, P < 0.01) in subjects with asthma but not in control subjects. The increased distensibility at RV and FRC in asthma were not associated with the accompanying changes in the reactance versus lung volume relationship. Our findings demonstrate that, at low lung volumes, ASM tone reduces airway distensibility in adults with asthma, independent of changes in airway closure and heterogeneity. Copyright © 2012 the American Physiological Society.

Kermode J.A.,Woolcock Institute of Medical Research | Kermode J.A.,University of Sydney | Kermode J.A.,Co operative Research Center for Asthma and Airways | Brown N.J.,Woolcock Institute of Medical Research | And 18 more authors.
Respiratory Medicine | Year: 2011

Rationale: The mechanisms of airway hyper-responsiveness are only partially understood and the contribution of airway remodelling is unknown. Airway remodelling can be assessed by measuring airway distensibility, which is reduced in asthma, even when lung function is normal. We hypothesised that airway remodelling contributes to airway hyper-responsiveness in asthma, independent of steroid-responsive airway inflammation. Objectives: To determine the relationship between airway distensibility and airway responsiveness at baseline and after 12 weeks of inhaled corticosteroid therapy in a group of asthmatics with airway hyper-responsiveness. Methods: Nineteen doctor-diagnosed asthmatics had airway distensibility measured as the slope of the relationship between conductance and lung volume by the forced oscillation technique. Lung function, exhaled nitric oxide and methacholine challenge were also measured. Subjects had inhaled corticosteroid therapy for 12 weeks after which all measurements were repeated. Results: At baseline, airway distensibility (mean, 95%CI) was 0.19(0.14-0.23) cm H 2O -1 s -1, exhaled nitric oxide was 13.1(10.3-16.6) ppb and airway distensibility correlated with eNO (p = 0.04) and disease duration (p = 0.02) but not with airway responsiveness (p = 0.46), FEV 1 (p = 0.09) or age (p = 0.23). After treatment, exhaled nitric oxide decreased (p = 0.0002), FEV 1 improved (p = 0.0001), airway responsiveness improved (p = 0.0002), and there was a small improvement in airway distensibility but it did not normalise (p = 0.05). Airway distensibility was not correlated with either exhaled nitric oxide (p = 0.49) or airway responsiveness (p = 0.20). Conclusions: Uncontrolled airway inflammation causes a small decrease in the distensibility of the airways of asthmatics with airway hyper-responsiveness. The lack of association between airway responsiveness and airway distensibility, both before and after 12 weeks ICS treatment, suggests that airway remodelling does not contribute to airway hyper-responsiveness in asthma. © 2011 Elsevier Ltd. All rights reserved.

Brown N.J.,The Woolcock Institute of Medical Research | Brown N.J.,University of Sydney | Brown N.J.,Co operative Research Center for Asthma and Airways | Xuan W.,The Woolcock Institute of Medical Research | And 16 more authors.
Respiratory Physiology and Neurobiology | Year: 2010

Aim: To determine reference equations for respiratory system resistance and reactance in a large randomly selected sample from a general, predominantly Caucasian population. Methods: A prospective respiratory health survey of the general population in Busselton, Western Australia, was conducted between 2005 and 2007. Subjects had measures of spirometry, and resistance and reactance at 6, 11, 19. Hz. Eligible subjects were never smokers, with no history of respiratory disease, no symptoms of cough, shortness of breath or chest tightness in the previous 12 months, and no respiratory tract infections in the previous 4 weeks. Results: 904 Eligible subjects (341 male) aged 18-92 years had technically satisfactory measurements. Reference equations were established for males and females separately. Both resistance and reactance were predicted by height and weight. Age was a predictor of reactance only. Conclusions: These data provide reference equations for forced oscillatory parameters, in well-characterized Caucasian subjects, with no respiratory symptoms, from a large general population. © 2010 Elsevier B.V.

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