Early Diagnosis and Real-Time Monitoring of Regional Lung Function Changes to Prevent Chronic Obstructive Pulmonary Disease Progression to Severe Emphysema

Abstract

First- and second-hand exposure to smoke or air pollutants is the primary cause of chronic obstructive pulmonary disease (COPD) pathogenesis, where genetic and age-related factors predispose the subject to the initiation and progression of obstructive lung disease. Briefly, airway inflammation, specifically bronchitis, initiates the lung disease, leading to difficulty in breathing (dyspnea) and coughing as initial symptoms, followed by air trapping and inhibition of the flow of air into the lungs due to damage to the alveoli (emphysema). In addition, mucus obstruction and impaired lung clearance mechanisms lead to recurring acute exacerbations causing progressive decline in lung function, eventually requiring lung transplant and other lifesaving interventions to prevent mortality. It is noteworthy that COPD is much more common in the population than currently diagnosed, as only 16 million adult Americans were reported to be diagnosed with COPD as of 2018, although an additional 14 million American adults were estimated to be suffering from COPD but undiagnosed by the current standard of care (SOC) diagnostic, namely the spirometry-based pulmonary function test (PFT). Thus, the main issue driving the adverse disease outcome and significant mortality for COPD is lack of timely diagnosis in the early stages of the disease. The current treatment regime for COPD emphysema is most effective when implemented early, on COPD onset, where alleviating symptoms and exacerbations with timely intervention(s) can prevent steep lung function decline(s) and disease progression to severe emphysema. Therefore, the key to efficiently combatting COPD relies on early detection. Thus, it is important to detect early regional pulmonary function and structural changes to monitor modest disease progression for implementing timely interventions and effectively eliminating emphysema progression. Currently, COPD diagnosis involves using techniques such as COPD screening questionnaires, PFT, arterial blood gas analysis, and/or lung imaging, but these modalities are limited in their capability for early diagnosis and real-time disease monitoring of regional lung function changes. Hence, promising emerging techniques, such as X-ray phase contrast, photoacoustic tomography, ultrasound computed tomography, electrical impedance tomography, the forced oscillation technique, and the impulse oscillometry system powered by robust artificial intelligence and machine learning analysis capability are emerging as novel solutions for early detection and real time monitoring of COPD progression for timely intervention. We discuss here the scope, risks, and limitations of current SOC and emerging COPD diagnostics, with perspective on novel diagnostics providing real time regional lung function monitoring, and predicting exacerbation and/or disease onset for prognosis-based timely intervention(s) to limit COPD–emphysema progression.

Pulmonary rehabilitation ameliorates regional lung function in chronic obstructive pulmonary disease: a prospective single-arm clinical trial

“…Milne et al developed time-based features of regional ventilation using EIT measurements, which exhibited significant regional heterogeneity in COPD compared with healthy controls ( 29 ). A previous study also indicated that those with COPD had an overall increased ventilation heterogeneity and CV ( 26 ), and we found that PR can make the regional distribution of spatial and temporal ventilation show less heterogeneity than pre-rehabilitation.…”

“…(12). The use of EIT is useful for clinicians to observe changes in regional lung function over a period of time to quantify pulmonary disease progression, which may be beneficial to patients with COPD with their heterogeneous pattern of structural and functional lung damage (26). Therefore, in the present study, we adopted EIT technology to assess the regional lung function in COPD patients.…”

The evaluation of regional lung function in COPD before and after pulmonary rehabilitation: a prospective clinical study

“…This study found that PR can improve FEV Effects of pulmonary rehabilitation on regional lung function COPD is characterized by regionally dissimilar evolution of the underlying morphological and pathophysiological lung changes [12]. EIT has the capability in observing changes in regional lung function over a period of time to quantify pulmonary diseases progression, which may be bene cial in patients with COPD with their heterogeneous pattern of structural and functional lung damage [29]. Therefore, we evaluated the patients according to this characteristic of EIT.…”

Identification of Dysregulated Mechanisms and Candidate Gene Markers in Chronic Obstructive Pulmonary Disease

“… 10 At the onset of COPD, timely intervention to relieve symptoms and exacerbations can prevent an acute decline in lung function and progression of the condition to severe emphysema. 11 Current treatments of COPD involve long-term inhalation therapy with bronchodilators, corticosteroids, or a combination of these agents. 12 Combination therapy may be more effective than monotherapies for relieving COPD exacerbations, but the evidence is inconclusive.…”