Natural history and mechanisms of COPD

Abstract

The natural history of COPD is complex, and the disease is best understood as a syndrome resulting from numerous interacting factors throughout the life cycle with smoking being the strongest inciting feature. Unfortunately, diagnosis is often delayed with several longitudinal cohort studies shedding light on the long ‘preclinical’ period of COPD. It is now accepted that individuals presenting with different COPD phenotypes may experience varying natural history of their disease. This includes its inception, early stages and progression to established disease. Several scenarios regarding lung function course are possible, but it may conceptually be helpful to distinguish between individuals with normal maximally attained lung function in their early adulthood who thereafter experience faster than normal FEV1 decline, and those who may achieve a lower than normal maximally attained lung function. This may be the main mechanism behind COPD in the latter group, as the decline in FEV1 during their adult life may be normal or only slightly faster than normal. Regardless of the FEV1 trajectory, continuous smoking is strongly associated with disease progression, development of structural lung disease and poor prognosis. In developing countries, factors such as exposure to biomass and sequelae after tuberculosis may lead to a more airway‐centred COPD phenotype than seen in smokers. Mechanistically, COPD is characterized by a combination of structural and inflammatory changes. It is unlikely that all patients share the same individual or combined mechanisms given the heterogeneity of resultant phenotypes. Lung explants, bronchial biopsies and other tissue studies have revealed important features. At the small airway level, progression of COPD is clinically imperceptible, and the pathological course of the disease is poorly described. Asthmatic features can further add confusion. However, the small airway epithelium is likely to represent a key focus of the disease, combining impaired subepithelial crosstalk and structural/inflammatory changes. Insufficient resolution of inflammatory processes may facilitate these changes. Pathologically, epithelial metaplasia, inversion of the goblet to ciliated cell ratio, enlargement of the submucosal glands and neutrophil and CD8‐T‐cell infiltration can be detected. Evidence of type 2 inflammation is gaining interest in the light of new therapeutic agents. Alarmin biology is a promising area that may permit control of inflammation and partial reversal of structural changes in COPD. Here, we review the latest work describing the development and progression of COPD with a focus on lung function trajectories, exacerbations and survival. We also review mechanisms focusing on epithelial changes associated with COPD and lack of resolution characterizing the underlying inflammatory processes.

Epilogue to contemporary perspectives in COPD: New Horizons

“…A targeted approach to medication choice, based on the frequency of exacerbations and the presence of eosinophilia, has enabled recommendations which narrow the most suitable population for inhaled corticosteroids (ICS) and should reduce the use of unnecessary and ineffective treatments, and significantly prevent some of the adverse effects associated with continuous high-dose ICS. 16 This series, encompassing patient burden, 17 the role of gender, the trajectories of multimorbidity, the causes and consequences of exacerbations, 18 the role of pharmacotherapy, 19 the lifetime evolution and mechanisms for COPD, 20 points out that we still have a long way to go in achieving optimal outcomes for patients with COPD. Although pharmacotherapy is a vital tool in reducing exacerbations, and although we talk about it as preventing exacerbations, it only does this to a certain degree 18 and we have few clinical indicators of the key characteristics of the majority of patients with COPD who are not frequent exacerbators and are not proportionately represented in clinical trials.…”

“…COPD is, as the papers in this Respirology series show, a disease of the whole of lifespan, but also heterogeneous in relation to its lifetime trajectory. 20,28 Although we now know that prenatal and early life events contribute to suboptimal achievement of lung function, 29 it seems improbable that there is any stage of life in which further exposures and nutritional deprivation could not influence lung function. 30 In an analysis of a UK population cohort, the forced expiratory volume in 1 s at age 43 in never smokers was not significantly related to early life exposures, whereas in those who had ever smoked, childhood disadvantages significantly contributed to lung function impairment.…”

The “Slow Horse Racing Effect” on Lung Function in Adult Life in Chronic Obstructive Pulmonary Disease Associated to Biomass Exposure

“…Natural history of COPD has evolved regarding the concept as an isolated disease. In this sense, recent evidence shows that the disease, in terms of clinical characteristics and lung function, is much more heterogeneous than previously thought (4)(5)(6). COPD encompasses a complex and heterogeneous group of disorders resulting from different risk factors that lead to different clinical courses and therefore different natural histories of the disease (7)(8)(9), such as COPD associated to biomass smoke (BE-COPD) (10,11).…”

Platelet Rich Plasma- Platelet Concentrate Therapy in COPD: An Observational Cohort Study

“…Though overall mortality from COPD in the United States has declined somewhat since 2004, there remains an annual mortality rate of 47.8 per 100,000 people or 0.047%, and COPD remains the third leading cause of death [3]. COPD is best described as the chronic limitation of outward airflow arising from a mixture of inflammation, tissue remodelling, and tissue destruction [4,5].…”

“…Lung reduction surgery may be considered in patients with emphysema, and lung transplantation may be an option though the availability for donor lungs is scarce. Pharmacologic treatments are aimed at improving symptoms, improving exercise tolerance, and reducing exacerbations, though none have proven to alter the natural course of the disease [4][5][6].…”