Title |
At the Root: Defining and Halting Progression of Early Chronic Obstructive Pulmonary Disease
|
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Published in |
American Journal of Respiratory & Critical Care Medicine, February 2018
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DOI | 10.1164/rccm.201710-2028pp |
Pubmed ID | |
Authors |
Fernando J Martinez, MeiLan K Han, James P Allinson, R Graham Barr, Richard C Boucher, Peter M A Calverley, Bartolome R Celli, Stephanie A Christenson, Ronald G Crystal, Malin Fagerås, Christine M Freeman, Lars Groenke, Eric A Hoffman, Mehmet Kesimer, Kostantinos Kostikas, Robert Paine, Shahin Rafii, Stephen I Rennard, Leopoldo N Segal, Renat Shaykhiev, Christopher Stevenson, Ruth Tal-Singer, Jørgen Vestbo, Prescott G Woodruff, Jeffrey L Curtis, Jadwiga A Wedzicha |
Abstract |
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder with varying presentations and progression, but limited disease-modifying therapies. Trajectories of lung function decline in COPD differ significantly between individuals, with differences detectable in young adulthood. "Early disease" (initial manifestations in young individuals) should be distinguished from "late mild disease" (disease of mild severity in older individuals potentially present for decades). For research purposes, we propose an operational definition of early COPD: ever-smokers (≥10 pack-years) younger than 50 years with any of these abnormalities: (1) FEV1/FVC< lower limit of normal; (2) compatible CT abnormalities (airway abnormality and/or emphysema); or (3) FEV1 decline (≥60 mL/year). Biological underpinnings of early COPD are quite complex. Recent evidence implies that cigarette smoke-exposure induces sequential, stereotypical changes in distal airways, initially without inflammatory cell infiltration. Epithelial reprogramming is associated with mucus that is less readily cleared and with polymeric immunoglobulin receptor down-regulation accompanied by focal airway injury. Resulting differences in the community structure of the lung microbiome may be mechanistically important. Global gene analysis suggests that tissue degradation around small airways predominates over repair. Emphysema might also develop in early COPD due to loss of pulmonary endothelial cell-derived factors. To reduce COPD's long-term societal impact, the goal of interventions must change, from solely focusing on reducing symptoms and exacerbations in advanced disease, to halting pathological progression in early disease. This review attempts to stimulate studies investigating younger smokers to understand the causes, progression, clinical expression and potential therapeutic targets of early COPD. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 9 | 15% |
United States | 8 | 14% |
Spain | 4 | 7% |
Australia | 4 | 7% |
France | 2 | 3% |
Mexico | 2 | 3% |
Ireland | 1 | 2% |
Moldova, Republic of | 1 | 2% |
Colombia | 1 | 2% |
Other | 9 | 15% |
Unknown | 18 | 31% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 27 | 46% |
Practitioners (doctors, other healthcare professionals) | 14 | 24% |
Scientists | 14 | 24% |
Science communicators (journalists, bloggers, editors) | 4 | 7% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 145 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 26 | 18% |
Student > Ph. D. Student | 18 | 12% |
Student > Master | 18 | 12% |
Other | 10 | 7% |
Student > Doctoral Student | 9 | 6% |
Other | 24 | 17% |
Unknown | 40 | 28% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 48 | 33% |
Biochemistry, Genetics and Molecular Biology | 11 | 8% |
Immunology and Microbiology | 8 | 6% |
Nursing and Health Professions | 6 | 4% |
Agricultural and Biological Sciences | 5 | 3% |
Other | 18 | 12% |
Unknown | 49 | 34% |