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      Treatable traits in acute exacerbations of chronic airway diseases

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          Abstract

          Acute exacerbations of chronic airway disease are common occurrences that cause a major burden of illness. Acute exacerbations are associated with impaired health status, increased lung function decline, hospitalization and increased risk of death. Exacerbation avoidance is a major priority. Despite this goal, exacerbations continue to occur and the need for effective models of care that optimize patient outcomes are urgently needed. ‘Treatable Traits’ is an approach to personalized medicine that has been proposed for the management of airway diseases. The treatable traits approach allows for the recognition of clinically important, identifiable and treatable disease characteristics, followed by targeted and individualized treatment interventions to address each trait. We review the literature relating to treatable traits in airway diseases; in particular, those traits that can predict exacerbations and approaches to management that aim to prevent exacerbations by using a treatable traits model of care. We propose this approach as a potentially useful model of care to both prevent and manage acute exacerbations.

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          Most cited references78

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          Susceptibility to exacerbation in chronic obstructive pulmonary disease.

          Although we know that exacerbations are key events in chronic obstructive pulmonary disease (COPD), our understanding of their frequency, determinants, and effects is incomplete. In a large observational cohort, we tested the hypothesis that there is a frequent-exacerbation phenotype of COPD that is independent of disease severity. We analyzed the frequency and associations of exacerbation in 2138 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Exacerbations were defined as events that led a care provider to prescribe antibiotics or corticosteroids (or both) or that led to hospitalization (severe exacerbations). Exacerbation frequency was observed over a period of 3 years. Exacerbations became more frequent (and more severe) as the severity of COPD increased; exacerbation rates in the first year of follow-up were 0.85 per person for patients with stage 2 COPD (with stage defined in accordance with Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages), 1.34 for patients with stage 3, and 2.00 for patients with stage 4. Overall, 22% of patients with stage 2 disease, 33% with stage 3, and 47% with stage 4 had frequent exacerbations (two or more in the first year of follow-up). The single best predictor of exacerbations, across all GOLD stages, was a history of exacerbations. The frequent-exacerbation phenotype appeared to be relatively stable over a period of 3 years and could be predicted on the basis of the patient's recall of previous treated events. In addition to its association with more severe disease and prior exacerbations, the phenotype was independently associated with a history of gastroesophageal reflux or heartburn, poorer quality of life, and elevated white-cell count. Although exacerbations become more frequent and more severe as COPD progresses, the rate at which they occur appears to reflect an independent susceptibility phenotype. This has implications for the targeting of exacerbation-prevention strategies across the spectrum of disease severity. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT00292552.)
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            Community study of role of viral infections in exacerbations of asthma in 9-11 year old children.

            To study the association between upper and lower respiratory viral infections and acute exacerbations of asthma in schoolchildren in the community. Community based 13 month longitudinal study using diary card respiratory symptom and peak expiratory flow monitoring to allow early sampling for viruses. 108 Children aged 9-11 years who had reported wheeze or cough, or both, in a questionnaire. Southampton and surrounding community. Upper and lower respiratory viral infections detected by polymerase chain reaction or conventional methods, reported exacerbations of asthma, computer identified episodes of respiratory tract symptoms or peak flow reductions. Viruses were detected in 80% of reported episodes of reduced peak expiratory flow, 80% of reported episodes of wheeze, and in 85% of reported episodes of upper respiratory symptoms, cough, wheeze, and a fall in peak expiratory flow. The median duration of reported falls in peak expiratory flow was 14 days, and the median maximum fall in peak expiratory flow was 81 l/min. The most commonly identified virus type was rhinovirus. This study supports the hypothesis that upper respiratory viral infections are associated with 80-85% of asthma exacerbations in school age children.
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              Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial.

              Treatment decisions in asthma are based on assessments of symptoms and simple measures of lung function, which do not relate closely to underlying eosinophilic airway inflammation. We aimed to assess whether a management strategy that minimises eosinophilic inflammation reduces asthma exacerbations compared with a standard management strategy. We recruited 74 patients with moderate to severe asthma from hospital clinics and randomly allocated them to management either by standard British Thoracic Society asthma guidelines (BTS management group) or by normalisation of the induced sputum eosinophil count and reduction of symptoms (sputum management group). We assessed patients nine times over 12 months. The results were used to manage those in the sputum management group, but were not disclosed in the BTS group. The primary outcomes were the number of severe exacerbations and control of eosinophilic inflammation, measured by induced sputum eosinophil count. Analyses were by intention to treat. The sputum eosinophil count was 63% (95% CI 24-100) lower over 12 months in the sputum management group than in the BTS management group (p=0.002). Patients in the sputum management group had significantly fewer severe asthma exacerbations than did patients in the BTS management group (35 vs 109; p=0.01) and significantly fewer patients were admitted to hospital with asthma (one vs six, p=0.047). The average daily dose of inhaled or oral corticosteroids did not differ between the two groups. A treatment strategy directed at normalisation of the induced sputum eosinophil count reduces asthma exacerbations and admissions without the need for additional anti-inflammatory treatment.
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                Author and article information

                Journal
                Chron Respir Dis
                Chron Respir Dis
                CRD
                spcrd
                Chronic Respiratory Disease
                SAGE Publications (Sage UK: London, England )
                1479-9723
                1479-9731
                13 August 2019
                Jan-Dec 2019
                : 16
                : 1479973119867954
                Affiliations
                [1 ]Priority Research Centre for Healthy Lungs and Centre of Excellence in Severe Asthma, Faculty of Health and Medicine, University of Newcastle, New South Wales, Australia
                [2 ]Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, Australia
                [3 ]Department of Physiotherapy, Monash University, Melbourne, Australia
                [4 ]Monash Lung and Sleep, Monash Health, Melbourne, Australia
                Author notes
                [*]Vanessa M McDonald, Priority Research Centre for Healthy Lungs and Centre of Excellence in Severe Asthma, Faculty of Health and Medicine, University of Newcastle, Level 2 West Wing, 1 Kookaburra Circuit, New Lambton Heights, New South Wales 2305, Australia. Email: vanessa.mcdonald@ 123456newcastle.edu.au
                Author information
                https://orcid.org/0000-0001-9890-3408
                https://orcid.org/0000-0001-9040-8007
                https://orcid.org/0000-0001-5865-489X
                Article
                10.1177_1479973119867954
                10.1177/1479973119867954
                6696844
                31409129
                798322d7-f634-46ee-8d1e-ae04410346d5
                © The Author(s) 2019

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 25 June 2019
                : 9 July 2019
                Categories
                Acute Exacerbations of Chronic Respiratory Diseases: Novel Insights and Emerging Therapeutic Targets
                Review
                Custom metadata
                January-December 2019

                Respiratory medicine
                acute exacerbations,chronic airway disease,asthma,copd,bronchiectasis,treatable traits

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