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      Dismantling airway disease with the use of new pulmonary function indices

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          Abstract

          We are currently limited in our abilities to diagnose, monitor disease status and manage chronic airway disease like asthma and chronic obstructive pulmonary disease (COPD). Conventional lung function measures often poorly reflect patient symptoms or are insensitive to changes, particularly in the small airways where disease may originate or manifest. Novel pulmonary function tests are becoming available which help us better characterise and understand chronic airway disease, and their translation and adoption from the research arena would potentially enable individualised patient care.

          In this article, we aim to describe two emerging lung function tests yielding novel pulmonary function indices, the forced oscillation technique (FOT) and multiple breath nitrogen washout (MBNW). With a particular focus on asthma and COPD, this article demonstrates how chronic airway disease mechanisms have been dismantled with the use of the FOT and MBNW. We describe their ability to assess detailed pulmonary mechanics for diagnostic and management purposes including response to bronchodilation and other treatments, relationship with symptoms, evaluation of acute exacerbations and recovery, and telemonitoring. The current limitations of both tests, as well as open questions/directions for further research, are also discussed.

          Abstract

          Spirometry is used to diagnose and manage airway disease such as asthma and COPD, but relates poorly to symptoms, lacks sensitivity and is effort dependent. FOT and MBNW are emerging clinical lung function tests that help us dismantle disease mechanisms. http://ow.ly/nM0G30nS6Ct

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          Most cited references98

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          The nature of small-airway obstruction in chronic obstructive pulmonary disease.

          Chronic obstructive pulmonary disease (COPD) is a major public health problem associated with long-term exposure to toxic gases and particles. We examined the evolution of the pathological effects of airway obstruction in patients with COPD. The small airways were assessed in surgically resected lung tissue from 159 patients--39 with stage 0 (at risk), 39 with stage 1, 22 with stage 2, 16 with stage 3, and 43 with stage 4 (very severe) COPD, according to the classification of the Global Initiative for Chronic Obstructive Lung Disease (GOLD). The progression of COPD was strongly associated with an increase in the volume of tissue in the wall (P<0.001) and the accumulation of inflammatory mucous exudates in the lumen (P<0.001) of the small airways. The percentage of the airways that contained polymorphonuclear neutrophils (P<0.001), macrophages (P<0.001), CD4 cells (P=0.02), CD8 cells (P=0.038), B cells (P<0.001), and lymphoid aggregates containing follicles (P=0.003) and the absolute volume of B cells (P=0.03) and CD8 cells (P=0.02) also increased as COPD progressed. Progression of COPD is associated with the accumulation of inflammatory mucous exudates in the lumen and infiltration of the wall by innate and adaptive inflammatory immune cells that form lymphoid follicles. These changes are coupled to a repair or remodeling process that thickens the walls of these airways. Copyright 2004 Massachusetts Medical Society
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            The forced oscillation technique in clinical practice: methodology, recommendations and future developments

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              Small-airway obstruction and emphysema in chronic obstructive pulmonary disease.

              The major sites of obstruction in chronic obstructive pulmonary disease (COPD) are small airways (<2 mm in diameter). We wanted to determine whether there was a relationship between small-airway obstruction and emphysematous destruction in COPD. We used multidetector computed tomography (CT) to compare the number of airways measuring 2.0 to 2.5 mm in 78 patients who had various stages of COPD, as judged by scoring on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) scale, in isolated lungs removed from patients with COPD who underwent lung transplantation, and in donor (control) lungs. MicroCT was used to measure the extent of emphysema (mean linear intercept), the number of terminal bronchioles per milliliter of lung volume, and the minimum diameters and cross-sectional areas of terminal bronchioles. On multidetector CT, in samples from patients with COPD, as compared with control samples, the number of airways measuring 2.0 to 2.5 mm in diameter was reduced in patients with GOLD stage 1 disease (P=0.001), GOLD stage 2 disease (P=0.02), and GOLD stage 3 or 4 disease (P<0.001). MicroCT of isolated samples of lungs removed from patients with GOLD stage 4 disease showed a reduction of 81 to 99.7% in the total cross-sectional area of terminal bronchioles and a reduction of 72 to 89% in the number of terminal bronchioles (P<0.001). A comparison of the number of terminal bronchioles and dimensions at different levels of emphysematous destruction (i.e., an increasing value for the mean linear intercept) showed that the narrowing and loss of terminal bronchioles preceded emphysematous destruction in COPD (P<0.001). These results show that narrowing and disappearance of small conducting airways before the onset of emphysematous destruction can explain the increased peripheral airway resistance reported in COPD. (Funded by the National Heart, Lung, and Blood Institute and others.).
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                Author and article information

                Journal
                Eur Respir Rev
                Eur Respir Rev
                ERR
                errev
                European Respiratory Review
                European Respiratory Society
                0905-9180
                1600-0617
                31 March 2019
                27 March 2019
                : 28
                : 151
                : 180122
                Affiliations
                [1 ]Airway Physiology and Imaging Group, Woolcock Institute of Medical Research, The University of Sydney, Sydney, Australia
                [2 ]Dept of Respiratory Medicine, Royal North Shore Hospital, Sydney, Australia
                [3 ]Sydney Medical School Northern, The University of Sydney, Sydney, Australia
                [4 ]Woolcock Emphysema Centre, Woolcock Institute of Medical Research, The University of Sydney, Sydney, Australia
                [5 ]Dept of Thoracic and Transplant Medicine, St Vincent's Hospital, Sydney, Australia
                [6 ]Faculty of Medicine, The University of New South Wales, Sydney, Australia
                Author notes
                Cindy Thamrin, Woolcock Institute of Medical Research, 431 Glebe Point Road, Glebe NSW 2037, Australia. E-mail: cindy.thamrin@ 123456sydney.edu.au
                Author information
                https://orcid.org/0000-0002-0658-9552
                https://orcid.org/0000-0002-8594-366X
                https://orcid.org/0000-0003-3284-3558
                Article
                ERR-0122-2018
                10.1183/16000617.0122-2018
                9488242
                30918023
                b54b6a09-1cc0-46c9-91e0-cf31a0762ff4
                Copyright ©ERS 2019.

                This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.

                History
                : 22 December 2018
                : 15 February 2019
                Categories
                Series
                Dismantling Airway Disease
                1
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