COPD, Pulmonary Fibrosis and ILAs in Aging Smokers: The Paradox of Striking Different Responses to the Major Risk Factors

Abstract

Aging and smoking are associated with the progressive development of three main pulmonary diseases: chronic obstructive pulmonary disease (COPD), interstitial lung abnormalities (ILAs), and idiopathic pulmonary fibrosis (IPF). All three manifest mainly after the age of 60 years, but with different natural histories and prevalence: COPD prevalence increases with age to >40%, ILA prevalence is 8%, and IPF, a rare disease, is 0.0005–0.002%. While COPD and ILAs may be associated with gradual progression and mortality, the natural history of IPF remains obscure, with a worse prognosis and life expectancy of 2–5 years from diagnosis. Acute exacerbations are significant events in both COPD and IPF, with a much worse prognosis in IPF. This perspective discusses the paradox of the striking pathological and pathophysiologic responses on the background of the same main risk factors, aging and smoking, suggesting two distinct pathophysiologic processes for COPD and ILAs on one side and IPF on the other side. Pathologically, COPD is characterized by small airways fibrosis and remodeling, with the destruction of the lung parenchyma. By contrast, IPF almost exclusively affects the lung parenchyma and interstitium. ILAs are a heterogenous group of diseases, a minority of which present with the alveolar and interstitial abnormalities of interstitial lung disease.

Interstitial lung abnormalities and interstitial lung diseases associated with cigarette smoking in a rural cohort undergoing surgical resection

“…To better explain the paradox of variable clinical and pathophysiologic responses to an identical risk factor (i.e. smoking), the need for studies characterizing interactions between emphysema, pulmonary fibrosis and ILAs have been acknowledged [ 2 ]. A clinical diagnosis of COPD, radiographic and histologic emphysema predicted a presence of ILA/ILD in our smoking cohort.…”

“…Cigarette smoking has been associated with the precursor lesions of interstitial lung abnormalities (ILAs) and a diversity of interstitial lung diseases (ILDs) including respiratory bronchiolitis–interstitial lung disease (RB-ILD), desquamative interstitial pneumonia (DIP), pulmonary Langerhans cell histiocytosis (PLCH), idiopathic pulmonary fibrosis (IPF), and combined pulmonary fibrosis and emphysema (CPFE) [ 1 ]. Penetration of smoking-related pulmonary injuries is variable with a prevalence of 3 to 17% (mean of 8%) for ILAs, < 1% for CPFE and 0.0005–0.002% for IPF [ 2 ]. Except for subclinical ILAs, these diseases often present with progressive dyspnea and some combination of other symptoms (cough, sputum and wheezing).…”

Identification and validation of genetic signature associated with aging in chronic obstructive pulmonary disease

“…Aging is a strong risk factor and independent prognostic biomarker for progressive COPD [15]. However, there is a lack of comprehensive analysis based on gene expression profiles to investigate the role of aging in COPD.…”

Inhibition of E3 ligase Pellino-1 attenuates chronic obstructive pulmonary disease and lung cellular senescence by promoting p21 degradation

“…Another important bridge linking COPD and lung cellular senescence is senescence-associated secretory phenotypes (SASPs). Senescent cells still maintain their metabolic functions and secrete SASPs, which alert their environments and senescent neighboring cells (Beghe, Cerri, Fabbri, & Marchioni, 2021;Salama, Sadaie, Hoare, & Narita, 2014). The SASPs, including IL-6, IL-8, and TNF-α, in COPD patients were significantly higher than those in the healthy (Hacievliyagil, Mutlu, & Temel, 2013).…”