Fig. 1

Rationale and design of a novel prognosis-based intervention strategy for COPD-emphysema. a Exposure to tobacco, e-cigarette vapor (eCV) or nicotine leads to oxidative-nitrative stress that mediates autophagy-impairment initiating aggresome formation, which acts as a central mechanism regulating COPD-emphysema pathogenesis. Thus, aggresome-bodies are implicated in triggering multifarious pathogenic mechanisms such as chronic inflammatory-apoptotic responses that drives the initiation and progression of emphysema in COPD subjects. b The proposed application of a non-invasive high throughput screening methodology for detecting aggresome-bodies in the cells derived from induced-sputum or bronchoalveolar lavage fluid (BALF/or lung biopsy sections) to predict COPD-like symptoms in non-smokers or smokers without any clinical signs of the lung disease. The high throughput flow cytometry and microscopy will assist in rapid screening of multiple samples for the presence and quantification of aggresome-bodies. The data generated from such high throughput assay will be analyzed by coupled software that assists in determining the severity of aggresome pathology and COPD-emphysema lung disease. This will allow categorization of subjects into different stages of the disease, based on the levels of aggresomes, which statistically correlates with the lung function decline and COPD-emphysema GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage. Furthermore, the proposed prognosis-based personalized intervention strategy will utilize autophagy augmentation based on the levels of aggresomes that quantifies both the extent of autophagy-impairment and lung function decline. Overall, timely detection and treatment of emphysema or lung function decline by proposed prognosis based intervention strategy will help reduce current mortality rates in this fatal lung condition