A Proposed Approach to Chronic Airway Disease (CAD) Using Therapeutic Goals and Treatable Traits: A Look to the Future

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Abstract

Chronic airflow obstruction affects a wide range of airway diseases, the most frequent of which are asthma, COPD, and bronchiectasis; they are clearly identifiable in their extremes, but quite frequently overlap in some of their pathophysiological and clinical characteristics. This has generated the description of new mixed or overlapping disease phenotypes with no clear biological grounds. In this special article, a group of experts provides their perspective and proposes approaching the treatment of chronic airway disease (CAD) through the identification of a series of therapeutic goals (TG) linked to treatable traits (TT) – understood as clinical, physiological, or biological characteristics that are quantifiable using biomarkers. This therapeutic approach needs validating in a clinical trial with the strategy of identification of TG and treatment according to TT for each patient independently of their prior diagnosis.

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Most cited references 54

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Low-dose inhaled corticosteroids and the prevention of death from asthma.

S Benayoun, Brian B. Cai, Pierre Ernst … (2000)

Although inhaled corticosteroids are effective for the treatment of asthma, it is uncertain whether their use can prevent death from asthma. We used the Saskatchewan Health data bases to form a population-based cohort of all subjects from 5 through 44 years of age who were using antiasthma drugs during the period from 1975 through 1991. We followed subjects until the end of 1997, their 55th birthday, death, emigration, or termination of health insurance coverage; whichever came first. We conducted a nested case-control study in which subjects who died of asthma were matched with controls within the cohort according to the length of follow-up at the time of death of the case patient (the index date), the date of study entry, and the severity of asthma. We calculated rate ratios after adjustment for the subject's age and sex; the number of prescriptions of theophylline, nebulized and oral beta-adrenergic agonists, and oral corticosteroids in the year before the index date; the number of canisters of inhaled beta-adrenergic agonists used in the year before the index date; and the number of hospitalizations for asthma in the two years before the index date. The cohort consisted of 30,569 subjects. Of the 562 deaths, 77 were classified as due to asthma. We matched the 66 subjects who died of asthma for whom there were complete data with 2681 controls. Fifty-three percent of the case patients and 46 percent of the control patients had used inhaled corticosteroids in the previous year, most commonly low-dose beclomethasone. The mean number of canisters was 1.18 for the patients who died and 1.57 for the controls. On the basis of a continuous dose-response analysis, we calculated that the rate of death from asthma decreased by 21 percent with each additional canister of inhaled corticosteroids used in the previous year (adjusted rate ratio, 0.79; 95 percent confidence interval, 0.65 to 0.97). The rate of death from asthma during the first three months after discontinuation of inhaled corticosteroids was higher than the rate among patients who continued to use the drugs. The regular use of low-dose inhaled corticosteroids is associated with a decreased risk of death from asthma.

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Tiotropium in asthma poorly controlled with standard combination therapy.

Ekkehard Beck, Huib A M Kerstjens, Wolfgang Seibold … (2012)

Some patients with asthma have frequent exacerbations and persistent airflow obstruction despite treatment with inhaled glucocorticoids and long-acting beta-agonists (LABAs). In two replicate, randomized, controlled trials involving 912 patients with asthma who were receiving inhaled glucocorticoids and LABAs, we compared the effect on lung function and exacerbations of adding tiotropium (a total dose of 5 μg) or placebo, both delivered by a soft-mist inhaler once daily for 48 weeks. All the patients were symptomatic, had a post-bronchodilator forced expiratory volume in 1 second (FEV(1)) of 80% or less of the predicted value, and had a history of at least one severe exacerbation in the previous year. The patients had a mean baseline FEV(1) of 62% of the predicted value; the mean age was 53 years. At 24 weeks, the mean (±SE) change in the peak FEV(1) from baseline was greater with tiotropium than with placebo in the two trials: a difference of 86±34 ml in trial 1 (P=0.01) and 154±32 ml in trial 2 (P<0.001). The predose (trough) FEV(1) also improved in trials 1 and 2 with tiotropium, as compared with placebo: a difference of 88±31 ml (P=0.01) and 111±30 ml (P<0.001), respectively. The addition of tiotropium increased the time to the first severe exacerbation (282 days vs. 226 days), with an overall reduction of 21% in the risk of a severe exacerbation (hazard ratio, 0.79; P=0.03). No deaths occurred; adverse events were similar in the two groups. In patients with poorly controlled asthma despite the use of inhaled glucocorticoids and LABAs, the addition of tiotropium significantly increased the time to the first severe exacerbation and provided modest sustained bronchodilation. (Funded by Boehringer Ingelheim and Pfizer; ClinicalTrials.gov numbers, NCT00772538 and NCT00776984.).

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Outcomes in patients with chronic obstructive pulmonary disease and obstructive sleep apnea: the overlap syndrome.

Santiago Carrizo, Ray M. Marín, Bartolome R Celli … (2010)

Patients with chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) (overlap syndrome) are more likely to develop pulmonary hypertension than patients with either condition alone. To assess the relation of overlap syndrome to mortality and first-time hospitalization because of COPD exacerbation and the effect of continuous positive airway pressure (CPAP) on these major outcomes. We included 228 patients with overlap syndrome treated with CPAP, 213 patients with overlap syndrome not treated with CPAP, and 210 patients with COPD without OSA. All were free of heart failure, myocardial infarction, or stroke. Median follow-up was 9.4 years (range, 3.3-12.7). End points were all-cause mortality and first-time COPD exacerbation leading to hospitalization. After adjustment for age, sex, body mass index, smoking status, alcohol consumption, comorbidities, severity of COPD, apnea-hypopnea index, and daytime sleepiness, patients with overlap syndrome not treated with CPAP had a higher mortality (relative risk, 1.79; 95% confidence interval, 1.16-2.77) and were more likely to suffer a severe COPD exacerbation leading to hospitalization (relative risk, 1.70; 95% confidence interval, 1.21-2.38) versus the COPD-only group. Patients with overlap syndrome treated with CPAP had no increased risk for either outcome compared with patients with COPD-only. The overlap syndrome is associated with an increased risk of death and hospitalization because of COPD exacerbation. CPAP treatment was associated with improved survival and decreased hospitalizations in patients with overlap syndrome.

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Author and article information

Journal

Journal ID (nlm-ta): Int J Chron Obstruct Pulmon Dis

Journal ID (iso-abbrev): Int J Chron Obstruct Pulmon Dis

Journal ID (publisher-id): copd

Journal ID (pmc): copd

Title: International Journal of Chronic Obstructive Pulmonary Disease

Publisher: Dove

ISSN (Print): 1176-9106

ISSN (Electronic): 1178-2005

Publication date (Electronic): 04 September 2020

Publication date Collection: 2020

Volume: 15

Pages: 2091-2100

Affiliations

[1 ]Pneumology Service, University Hospital Lucus Augusti , Lugo, EOXI Cervo, Lugo, Monforte, Spain

[2 ]Pneumology Service, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, CIBERES , Barcelona, Spain

[3 ]Pneumology Service, Hospital Universitario Virgen del Rocio , Seville, Spain

[4 ]Pneumology Service, La Princesa University Hospital, Madrid, Research Institute La Princesa IIP , Madrid, Spain

[5 ]Pneumology Service, Ramón y Cajal Hospital (Ramon y Cajal Health Research Institute, IRYCIS) , Madrid, Spain

[6 ]Pneumology Service, Hospital Universitario Dr Peset , Valencia, Spain

[7 ]Faculty of Medicine at the University of Santiago de Compostela, Pneumology Service of the University Clinical Hospital of Santiago de Compostela, CIBERES , Santiago de Compostela, Spain

[8 ]Pneumology Service, Hospital de la Santa Creu i Sant Pau , Barcelona, Spain

[9 ]Division of Respirology and Sleep Medicine, Queen's University , Canada, ON, Canada

[10 ]Pneumology Service, Hospital Universitario Nuestra Señora de Candelaria , Santa Cruz De Tenerife, Spain

[11 ]Pneumology Service, Hospital de Laredo , Laredo, Spain

[12 ]Pneumology Service and Faculty of Medicine, Hospital Clínico San Carlos, Complutense University of Madrid , Madrid, Spain

[13 ]Pneumology Service, Hospital Arnau de Vilanova , Valencia, Spain

[14 ]Pneumology Service, Son Espases University Hospital, IdISBa, CIBERES, Clínica Quirón-Rotger , Palma, Spain

Author notes

Correspondence: Borja G Cosio Pneumology Service, Hospital Universitario Son Espases, IdISBa, CIBERES, Clínica Quirón-Rotger , Ctra. de Valldemossa 79, Palma de Mallorca07010, SpainTel +34 871 206714 Ext 76714Fax +34 871 909724 Email borja.cosio@ssib.es

Article

Publisher ID: 263430

DOI: 10.2147/COPD.S263430

PMC ID: 7481271

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This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

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Figures: 1, Tables: 2, References: 81, Pages: 10

A Proposed Approach to Chronic Airway Disease (CAD) Using Therapeutic Goals and Treatable Traits: A Look to the Future

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Abstract

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International Journal of COPD

Most cited references 54

Low-dose inhaled corticosteroids and the prevention of death from asthma.

Tiotropium in asthma poorly controlled with standard combination therapy.

Outcomes in patients with chronic obstructive pulmonary disease and obstructive sleep apnea: the overlap syndrome.

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