Ventilation heterogeneity predicts asthma control in adults following inhaled corticosteroid dose titration

Farah, Claude S.; King, Gregory G.; Brown, Nathan J.; Peters, Matthew J.; Berend, Norbert; Salome, Cheryl M.

doi:10.1016/j.jaci.2012.02.015

Cited by 80 publications

(83 citation statements)

References 52 publications

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“…On the lung function side, TLCO and the ratio of residual volume (RV) over total lung capacity (TLC) are particularly relevant to COPD and asthma. On the ventilation distribution side, indices of acinar and conductive (Sacin, Scond) ventilation heterogeneity derived from the normalised phase III slope analysis of the multiple-breath washout (MBW) have been used to characterise bronchial hyperresponsiveness in asthma [8] or asthma control [9], or to pick up different stages of smoking-induced lung disease [10]. In more severe lung disease such as in patients with COPD or patients with CF, the lung clearance index (LCI) [11] and the curvilinearity (Curv) derived from the MBW concentration curve [12] may suffice to quantify degree of heterogeneity.…”

Section: Introductionmentioning

confidence: 99%

Transfer factor, lung volumes, resistance and ventilation distribution in healthy adults

et al. 2015

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Monitoring of chronic lung disease requires reference values of lung function indices, including putative markers of small airway function, spanning a wide age range.We measured spirometry, transfer factor of the lung for carbon monoxide (TLCO), static lung volume, resistance and ventilation distribution in a healthy population, studying at least 20 subjects per sex and per decade between the ages of 20 and 80 years.With respect to the Global Lung Function Initiative reference data, our subjects had average z-scores for forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC of −0.12, 0.04 and −0.32, respectively. Reference equations were obtained which could account for a potential dependence of index variability on age and height. This was done for (but not limited to) indices that are pertinent to asthma and chronic obstructive pulmonary disease studies: forced expired volume in 6 s, forced expiratory flow, TLCO, specific airway conductance, residual volume (RV)/total lung capacity (TLC), and ventilation heterogeneity in acinar and conductive lung zones.Deterioration in acinar ventilation heterogeneity and lung clearance index with age were more marked beyond 60 years, and conductive ventilation heterogeneity showed the greatest increase in variability with age. The most clinically relevant deviation from published reference values concerned RV/TLC values, which were considerably smaller than American Thoracic Society/European Respiratory Society-endorsed reference values. @ERSpublications We present reference equations for median and variability of most lung function indices, in the age range 20-80 years http://ow.ly/SsZFW

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Section: Introductionmentioning

confidence: 99%

Transfer factor, lung volumes, resistance and ventilation distribution in healthy adults

et al. 2015

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“…One could argue that the differences in results may be related to the fact that the newer hs-TnT assay is more sensitive than traditional TnT assays for identifying myocardial injury. However, in a recent study by Randby and colleagues (14) in which hs-TnT was measured in a community-based sample of middle-aged patients (30-65 yr) without known CHD, the association of OSA with hs-TnT did not remain significant after adjusting for potential confounders.…”

Section: Idiopathic Pulmonary Fibrosis: Time To Get Personal?mentioning

confidence: 85%

“…In study participants with asthma, the magnitude of ventilation heterogeneity measured by lung clearance highly informs the degree of bronchial hyperresponsiveness, better than biomarkers of inflammation, and predicts asthma control after up-and down-titration of inhaled corticosteroid treatment (13,14). Repeated exposure of individuals with stable asthma to methacholine-induced bronchospasm induced early structural changes of airway wall thickening (15).…”

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confidence: 99%

Idiopathic Pulmonary Fibrosis: Time to Get Personal?

Noth

Kaminski²

2013

Am J Respir Crit Care Med

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in the CF piglet. Because the timing of fetal CFTR expression in the mammalian lung is synchronous with the branch development of the large airways, the authors submit that the findings observed in the CF piglet are a direct correlate of CFTR dysfunction and not reduced fetal lung liquid or impaired chloride secretion. They also suggest that absent CFTR function affects a host of cells, including chondrocytes, smooth muscle, and neural cells.The findings of Adams and colleagues (10), if they indeed occur in young children with CF, support a growing concept that ventilation heterogeneity per se is fundamental to the pathobiology of lung disease. In study participants with asthma, the magnitude of ventilation heterogeneity measured by lung clearance highly informs the degree of bronchial hyperresponsiveness, better than biomarkers of inflammation, and predicts asthma control after up-and down-titration of inhaled corticosteroid treatment (13,14). Repeated exposure of individuals with stable asthma to methacholine-induced bronchospasm induced early structural changes of airway wall thickening (15). The results of this study suggest that the compressive mechanical forces attendant to bronchospasm support regional airway remodeling independent of inflammation. These provocative findings highlight the fact that the relationship between regional lung inflammation and lung function is not well understood. The mandate is clear for innovative studies examining such relationships (16). Exciting new imaging methods, including positron emission tomography, hyperpolarized noble gas MRI, and single-photon emission computed tomography, coupled to image-guided bronchoalveolar lavage and biopsy, will foster new understanding of the pathobiology of lung disease. The result will be a paradigm shift away from the conception of diseases like CF and asthma as involving the entire lung to an informed understanding of regional pathology linked to significant ventilation heterogeneity.

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“…Ventilation distribution measured from inert-gas washouts is determined by the small airways; studies in smokers [7] and bone marrow transplant recipients [8] suggest it to be a highly sensitive test of small-airway function. Furthermore, analysis of the washout pattern over the course of the washout has allowed compartmentalisation of function into acinar and conductive small airways, which has also been shown to have separate clinical associations in airway diseases [9][10][11][12]. The lung clearance index (LCI) is a simpler and "aggregate" measure of airway function, and represents the number of breaths, adjusted for lung size, required to clear the lungs of a gas.…”

Section: @Erspublicationsmentioning

confidence: 99%

Complex lung function in severe asthma: seeing is believing

King

Thamrin

2016

Eur Respir J

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@ERSpublicationsTechniques to partition airway dysfunction could improve understanding of severe asthma http://ow.ly/N7zD301wFn6Difficult-to-treat or severe asthma remains a common problem and a challenge for healthcare providers. It affects up to 10% of asthmatic individuals, who continue to suffer high disease burden and healthcare costs [1]. This clinical problem still exists despite many advances in the understanding of the underlying basis of asthma and improved management strategies, which include targeted anti-inflammatory therapy with monoclonal antibodies. Research effort continues, with exploration of different aspects of pathophysiology such as genomics, proteomics, inflammation, airway remodelling and airway smooth muscle abnormalities. In this context, the examination of complex lung function at the whole-organ level becomes increasingly important. There have been many technical advances in functional imaging and in complex measures of lung function that can now be used to explore the pathophysiology of asthma at the whole-organ level, and which can be more directly related to clinical manifestations of disease such as symptoms and airway hyperresponsiveness.Measuring patterns of ventilation (ventilation distribution) is a way to characterise lung function that is highly relevant in obstructive lung diseases, and goes far beyond spirometry, peak flow and lung volumes. Ventilation distribution can be quantified visually using three-dimensional (tomographic) ventilation imaging techniques as well as functionally using inert-gas washout tests. Tomographic imaging methods include hyperpolarised noble gas magnetic resonance imaging (MRI) (e.g. helium-3 or xenon) [2], positron emission tomography [3], single photon emission computed tomography (CT) [4,5] and oxygen enhanced MRI [6], where the distribution of a tracer gas is imaged. Inert-gas washout tests are based on the simple principle that regions of the lung that ventilate poorly or not at all (i.e. altered distribution) delay the clearance (i.e. washout) of a marker gas from the lung during normal tidal breathing. Thus, 100% oxygen can be used to "wash out" the resident nitrogen over multiple breaths, which is the basis of the multiple-breath nitrogen washout (MBNW). Similarly, if low concentrations of inert gases such as sulfur hexafluoride or helium are introduced into the lung, then their pattern of clearance from the lung reflects ventilation distribution.Ventilation imaging and inert-gas washout tests are thus two different yet complementary methods for characterising ventilation distribution. Ventilation imaging shows where functional abnormalities occur, how extensive they are and how they are colocated. Conversely, inert-gas washout measures ventilation that has been averaged across the entire lung but probes much finer length scales than those afforded by the resolution of modern imaging techniques. Ventilation distribution measured from inert-gas washouts is determined by the small airways; studies in smokers [7] and bone marrow transplant...

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Ventilation heterogeneity predicts asthma control in adults following inhaled corticosteroid dose titration

Cited by 80 publications

References 52 publications

Transfer factor, lung volumes, resistance and ventilation distribution in healthy adults

Transfer factor, lung volumes, resistance and ventilation distribution in healthy adults

Idiopathic Pulmonary Fibrosis: Time to Get Personal?

Complex lung function in severe asthma: seeing is believing

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