Airway closure on imaging relates to airway hyperresponsiveness and peripheral airway disease in asthma

Farrow, Catherine; Salome, Cheryl M.; Harris, Benjamin; Bailey, Dale L.; Bailey, Elizabeth; Berend, Norbert; Young, Iven H.; King, Gregory G.

doi:10.1152/japplphysiol.01618.2011

Cited by 54 publications

(59 citation statements)

References 42 publications

(61 reference statements)

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“…115,118,119 Intriguingly, the degree of baseline heterogeneity appears to predict the severity of airway hyperresponsiveness in adults and children with asthma, [120][121][122] in a way that differs from subjects with COPD. 114,124 Further studies have identified relationships between heterogeneity and symptom control 125 ; clinical stability 118 ; and response to inhaled corticosteroids. 114,124 Further studies have identified relationships between heterogeneity and symptom control 125 ; clinical stability 118 ; and response to inhaled corticosteroids.…”

Section: Inert Gas Washout For Measurement Of Ventilation Inhomogeneitymentioning

confidence: 99%

Priorities for future research into asthma diagnostic tools: A PAN‐EU consensus exercise from the European asthma research innovation partnership (EARIP)

García‐Marcos

Edwards

Kennington

et al. 2018

Clin Experimental Allergy

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The diagnosis of asthma is currently based on clinical history, physical examination and lung function, and to date, there are no accurate objective tests either to confirm the diagnosis or to discriminate between different types of asthma. This consensus exercise reviews the state of the art in asthma diagnosis to identify opportunities for future investment based on the likelihood of their successful development, potential for widespread adoption and their perceived impact on asthma patients. Using a two-stage e-Delphi process and a summarizing workshop, a group of European asthma experts including health professionals, researchers, people with asthma and industry representatives ranked the potential impact of research investment in each technique or tool for asthma diagnosis and monitoring. After a systematic review of the literature, 21 statements were extracted and were subject of the two-stage Delphi process. Eleven statements were scored 3 or more and were further discussed and ranked in a face-to-face workshop. The three most important diagnostic/predictive tools ranked were as follows: "New biological markers of asthma (eg genomics, proteomics and metabolomics) as a tool for diagnosis and/or monitoring," "Prediction of future asthma in preschool children with reasonable accuracy" and "Tools to measure volatile organic compounds (VOCs) in exhaled breath."

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Section: Inert Gas Washout For Measurement Of Ventilation Inhomogeneitymentioning

confidence: 99%

Priorities for future research into asthma diagnostic tools: A PAN‐EU consensus exercise from the European asthma research innovation partnership (EARIP)

García‐Marcos

Edwards

Kennington

et al. 2018

Clin Experimental Allergy

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“…Similarly, CT imaging has demonstrated greater changes in peripheral airways after methacholine challenge in asthmatics [31]. Other studies using multiple breath nitrogen washout and imaging [32] have shown an increase in ventilation heterogeneity in individuals with hyper reactivity to methacholine which appeared to be independent of changes in airway resistance [33]. Modelling studies indicate that the most marked effect of airways constriction on FeNO50 is most likely to occur in generations 10-15 and that constriction in smaller airways is likely to increase FeNO50 due to interference with the NO back diffusion effect [34].…”

Section: Discussionmentioning

confidence: 97%

Untitled

2015

JLPRR

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Increased nitric oxide in exhaled gas in patients with asthma is thought to reflect the severity of airway inflammation and perhaps airway reactivity. Several studies attempted to identify a relationship between exhaled NO levels and airway reactivity or severity of airway inflammation for the purpose of finding out if exhaled NO could be used in place of pulmonary function testing and airway provocation test. Unfortunately, the relationship is not always evident. In recent years, it has become clearer that exhaled NO becomes elevated primarily in atopic asthma patients. All previous studies have used the single vital capacity slow exhalation maneuver to measure ENO (FeNO50). This method is subject to errors because it requires patient cooperation, is flow rate dependent and adds more stress on the patient. Recently, we showed that end tidal NO concentration (NOet) is clinically relevant, is much easier to measure and is not subject to flow variation or patient cooperation. We used NOet (ppb) measurement before and during methacholine challenge in patients with symptoms of mild, persistent asthma. In addition we calculated NO production (NOpr) (nmole/ min) to correct for possible changes in ventilation. Eleven patients exhibited hyper-responsiveness to methacholine (responders) and 17 exhibited negative response (non-responders). The responders had a slightly higher NO level than the non-responders whether expressed in ppb or in nmol/min but did not reach statistical significance: NOet values were 15.1±2.4 ppb (±SE) and 11.7±2.3 ppb respectively and NOpr values were 5.83±0.86 nmol/min and 5.12±1.13 nmol/min respectively.There was no correlation between baseline NOet levels and the change in FEV1 in the responders. Furthermore, there was no consistent change in NOet or NOpr levels during broncho-constriction with methacholine. We conclude that although exhaled NO levels may serve as a helpful adjunct in treatment of asthma, its level alone does not reflect severity of the disease in mild asthmatics nor the airway responsiveness to methacholine. Exhaled NO was estimated using the average NO value at end expiration during normal tidal breathing. This method was quicker, repeatable and much easier on the patients and none of the patients objected to doing the measurement. There was no need to put patients through the complicated single full vital capacity slow exhaled maneuver to obtain this information.

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“…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.…”

Section: @Erspublicationsmentioning

confidence: 99%

“…The main contribution of imaging studies to our understanding of ventilation distribution in asthma is the revelation of the presence of large and dramatic ventilation defects [3][4][5]14], caused presumably by both localised airway closure and severe airway narrowing. There has been very little analysis of the distribution of ventilation, i.e.…”

Section: @Erspublicationsmentioning

confidence: 99%

“…Perhaps this because researchers' attentions have been drawn to the visually dramatic nature of ventilation defects, which again have been elegantly demonstrated using hyperpolarised 3 He MRI by SVENNINGSEN et al [2] in this issue of the European Respiratory Journal. It is uncertain what causes these defects but the fact that they tend to persist over time [16] and can be induced acutely by bronchoconstriction [3,4,14], which is also repeatable between sessions [14], suggests a structural basis to their presence, rather than being due simply to mucus plugging. Computational modelling studies suggest that these ventilation defects arise from widespread small-airway narrowing combined with severe narrowing in some of the larger airways [17].…”

Section: @Erspublicationsmentioning

confidence: 99%

See 1 more Smart Citation

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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Airway closure on imaging relates to airway hyperresponsiveness and peripheral airway disease in asthma

Abstract: . Airway closure on imaging relates to airway hyperresponsiveness and peripheral airway disease in asthma.

Cited by 54 publications

References 42 publications

Priorities for future research into asthma diagnostic tools: A PAN‐EU consensus exercise from the European asthma research innovation partnership (EARIP)

Priorities for future research into asthma diagnostic tools: A PAN‐EU consensus exercise from the European asthma research innovation partnership (EARIP)

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Complex lung function in severe asthma: seeing is believing

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