• Combined Pulmonary Fibrosis and Emphysema: Pulmonary Function Testing and a Pathophysiology Perspective

      Amariei, D.E.; Dodia, N.; Deepak, J.; Hines, S.E.; Atamas, S.P.; Todd, N.W. (Kauno Medicinos Universitetas, 2019)
      Combined pulmonary fibrosis and emphysema (CPFE) has been increasingly recognized over the past 10-15 years as a clinical entity characterized by rather severe imaging and gas exchange abnormalities, but often only mild impairment in spirometric and lung volume indices. In this review, we explore the gas exchange and mechanical pathophysiologic abnormalities of pulmonary emphysema, pulmonary fibrosis, and combined emphysema and fibrosis with the goal of understanding how individual pathophysiologic observations in emphysema and fibrosis alone may impact clinical observations on pulmonary function testing (PFT) patterns in patients with CPFE. Lung elastance and lung compliance in patients with CPFE are likely intermediate between those of patients with emphysema and fibrosis alone, suggesting a counter-balancing effect of each individual process. The outcome of combined emphysema and fibrosis results in higher lung volumes overall on PFTs compared to patients with pulmonary fibrosis alone, and the forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio in CPFE patients is generally preserved despite the presence of emphysema on chest computed tomography (CT) imaging. Conversely, there appears to be an additive deleterious effect on gas exchange properties of the lungs, reflecting a loss of normally functioning alveolar capillary units and effective surface area available for gas exchange, and manifested by a uniformly observed severe reduction in the diffusing capacity for carbon monoxide (DLCO). Despite normal or only mildly impaired spirometric and lung volume indices, patients with CPFE are often severely functionally impaired with an overall rather poor prognosis. As chest CT imaging continues to be a frequent imaging modality in patients with cardiopulmonary disease, we expect that patients with a combination of pulmonary emphysema and pulmonary fibrosis will continue to be observed. Understanding the pathophysiology of this combined process and the abnormalities that manifest on PFT testing will likely be helpful to clinicians involved with the care of patients with CPFE.
    • A non-coding RNA landscape of bronchial epitheliums of lung cancer patients

      Lin, Y.; Holden, V.; Dhilipkannah, P.; Deepak, J.; Todd, N.W.; Jiang, F. (MDPI AG, 2020)
      We propose to systematically identify a non-coding RNA (ncRNA) profile of exfoliated bronchial epitheliums of sputum from lung cancer patients. Bronchial epithelial cells enriched from sputum of 32 lung cancer patients and 33 cancer-free smokers were analyzed by next-generation sequencing to comprehensively characterize the ncRNA profiles. In addition, 108 miRNAs, 88 small nucleolar RNAs, 13 piwi-interacting RNAs, 6 transfer RNAs, 4 ribosomal RNAs, 19 small nuclear RNAs, and 25 long-noncoding (lnc) RNAs displayed a significantly different level in bronchial epitheliums of sputum of lung cancer patients versus cancer-free smokers (all < 0.001). PCR analysis confirmed their different expression levels in the sputum specimens. A high expression of SNHG9, an lncRNA, was validated in 78 lung tumor tissues, and the expression was inversely associated with overall survival of lung cancer patients (p = 0.002). Knockdown of SNHG9 in cancer cells reduced the cell growth, proliferation, and invasion in vitro and tumorigenesis in vivo. The multiple differentially expressed ncRNAs in bronchial epitheliums may contribute to the development and progression of lung cancer and provide potential biomarkers and therapeutic targets for the disease. Copyright 2020 by the authors.