Smoking-Related “Interstitial” Lung Disease

2014 ◽  
Vol 139 (8) ◽  
pp. 974-977 ◽  
Author(s):  
Teri J. Franks ◽  
Jeffrey R. Galvin
Keyword(s):  
Lung Injury ◽  
Cigarette Smoke ◽  
Cigarette Smoke Exposure ◽  
Wall Thickening ◽  
Alveolar Wall ◽  
Cigarette Smokers ◽  
Pulmonary Langerhans Cell Histiocytosis ◽  
Airway Injury ◽  
Wide Range ◽  
Arteriolar Wall

Context Emphysema, respiratory bronchiolitis, desquamative interstitial pneumonia, pulmonary Langerhans' cell histiocytosis, small-airway injury including submucosal and adventitial fibrosis, increased bronchus-associated lymphoid tissue, and small artery/arteriolar wall thickening are recognized histologic findings in cigarette smokers. It has only recently been acknowledged that the range of lung injury from cigarette smoke is wider than generally accepted, in particular, there is increasing recognition that fibrosis of alveolar walls occurs in smokers. Objectives To review the literature that describes the range of histologic findings in cigarette smokers and that links cigarette smoke exposure to the development of alveolar wall fibrosis. Data Sources Relevant peer-reviewed literature indexed in PubMed (National Library of Medicine) form the basis of this review. Conclusions Smokers demonstrate a wide range of lung injury at biopsy that defies simple placement within single categories, and the current categories do not adequately take into account the importance of alveolar wall and airway fibrosis.

Elastin protein levels are a vital modifier affecting normal lung development and susceptibility to emphysema

2007 ◽  
Vol 292 (3) ◽  
pp. L778-L787 ◽  
Author(s):  
Adrian Shifren ◽  
Anthony G. Durmowicz ◽  
Russell H. Knutsen ◽  
Eiichi Hirano ◽  
Robert P. Mecham
Keyword(s):  
Lung Injury ◽  
Cigarette Smoke ◽  
Lung Development ◽  
Normal Lung ◽  
Cigarette Smoke Exposure ◽  
Alveolar Wall ◽  
Protein Levels ◽  
Normal Lung Function ◽  
Low Levels ◽  
Genetic And Environmental Factors

Cigarette smoking is the strongest risk factor for emphysema. However, sensitivity to cigarette smoke-induced emphysema is highly variable, and numerous genetic and environmental factors are thought to mitigate lung response to injury. We report that the quantity of functional elastin in the lung is an important modifier of both lung development and response to injury. In mice with low levels of elastin, lung development is adversely affected, and mice manifest with congenital emphysema. Animals with intermediate elastin levels exhibit normal alveolar structure but develop worse emphysema than normal mice following cigarette smoke exposure. Mechanical testing demonstrates that lungs with low levels of elastin experience greater tissue strains for any given tissue stress compared with wild-type lungs, implying that force-mediated propagation of lung injury through alveolar wall failure may worsen the emphysema after an initial enzymatic insult. Our findings suggest that quantitative deficiencies in elastin predispose to smoke-induce emphysema in animal models and suggest that humans with altered levels of functional elastin could have relatively normal lung function while being more susceptible to smoke-induced lung injury.

scholarly journals Cigarette Smoke Exposure Worsens Endotoxin-Induced Lung Injury and Pulmonary Edema in Mice

2017 ◽  
Vol 19 (9) ◽  
pp. 1033-1039 ◽  
Author(s):  
Jeffrey E Gotts ◽  
Jason Abbott ◽  
Xiaohui Fang ◽  
Haru Yanagisawa ◽  
Naoki Takasaka ◽  
...  
Keyword(s):  
Lung Injury ◽  
Pulmonary Edema ◽  
Cigarette Smoke ◽  
Smoke Exposure ◽  
Cigarette Smoke Exposure

scholarly journals p53- and PAI-1-mediated induction of C-X-C chemokines and CXCR2: importance in pulmonary inflammation due to cigarette smoke exposure

2016 ◽  
Vol 310 (6) ◽  
pp. L496-L506 ◽  
Author(s):  
Nivedita Tiwari ◽  
Amarnath S. Marudamuthu ◽  
Yoshikazu Tsukasaki ◽  
Mitsuo Ikebe ◽  
Jian Fu ◽  
...  
Keyword(s):  
Lung Injury ◽  
Cigarette Smoke ◽  
Lung Inflammation ◽  
Cellular Adhesion ◽  
Alveolar Epithelial Cells ◽  
Cigarette Smoke Exposure ◽  
Chronic Obstructive ◽  
P53 Expression ◽  
Cellular Adhesion Molecule ◽  
Pai 1

We previously demonstrated that tumor suppressor protein p53 augments plasminogen activator inhibitor-1 (PAI-1) expression in alveolar epithelial cells (AECs) during chronic cigarette smoke (CS) exposure-induced lung injury. Chronic lung inflammation with elevated p53 and PAI-1 expression in AECs and increased susceptibility to and exacerbation of respiratory infections are all associated with chronic obstructive pulmonary disease (COPD). We recently demonstrated that preventing p53 from binding to the endogenous PAI-1 mRNA in AECs by either suppressing p53 expression or blockading p53 interactions with the PAI-1 mRNA mitigates apoptosis and lung injury. Within this context, we now show increased expression of the C-X-C chemokines (CXCL1 and CXCL2) and their receptor CXCR2, and the intercellular cellular adhesion molecule-1 (ICAM-1), in the lung tissues of patients with COPD. We also found a similar increase in lung tissues and AECs from wild-type (WT) mice exposed to passive CS for 20 wk and in primary AECs treated with CS extract in vitro. Interestingly, passive CS exposure of mice lacking either p53 or PAI-1 expression resisted an increase in CXCL1, CXCL2, CXCR2, and ICAM-1. Furthermore, inhibition of p53-mediated induction of PAI-1 expression by treatment of WT mice exposed to passive CS with caveolin-1 scaffolding domain peptide reduced CXCL1, CXCL2, and CXCR2 levels and lung inflammation. Our study reveals that p53-mediated induction of PAI-1 expression due to chronic CS exposure exacerbates lung inflammation through elaboration of CXCL1, CXCL2, and CXCR2. We further provide evidence that targeting this pathway mitigates lung injury associated with chronic CS exposure.

Structural and functional remodeling of the female Apoe-/- mouse aorta due to chronic cigarette smoke exposure

2021 ◽  
Author(s):  
Yasmeen M. Farra ◽  
Jacqueline Matz ◽  
Bhama Ramkhelawon ◽  
Jessica M. Oakes ◽  
Chiara Bellini
Keyword(s):  
Cigarette Smoking ◽  
Cigarette Smoke ◽  
Cigarette Smoke Exposure ◽  
Wall Thickening ◽  
Cross Sectional ◽  
Fibrous Cap ◽  
Cardiovascular Morbidity And Mortality ◽  
Chronic Smoking ◽  
And Function ◽  
Thoracic And Abdominal

Despite a decline in popularity over the last several decades, cigarette smoking remains a leading cause of cardiovascular morbidity and mortality. Yet, the effects of cigarette smoking on vascular structure and function are largely unknown. To evaluate changes in the mechanical properties of the aorta that occur with chronic smoking, we exposed female Apolipoprotein E-deficient mice to mainstream cigarette smoke daily for 24 weeks, with room air as control. By the time of sacrifice, cigarette-exposed mice had lower body mass, but experienced larger systolic/diastolic blood pressure when compared to controls. Smoking was associated with significant wall thickening, reduced axial stretch, and circumferential material softening of the aorta. While this contributed to maintaining intrinsic tissue stiffness at control levels despite larger pressure loads, the structural stiffness became significantly larger. Furthermore, the aorta from cigarette-exposed mice exhibited decreased ability to store elastic energy and augment diastolic blood flow. Histological analysis revealed a region-dependent increase in the cross-sectional area due to smoking. Increased smooth muscle and extracellular matrix content led to medial thickening in the ascending aorta, while collagen deposition increased the thickness of the descending thoracic and abdominal aorta. Atherosclerotic lesions were larger in exposed vessels and featured a necrotic core overlaid by a thinned fibrous cap and macrophage infiltration, consistent with a vulnerable phenotype. Collectively, our data indicate that cigarette smoking decreases the mechanical functionality of the aorta, inflicts morphometric alterations to distinct segments of the aorta, and accelerates the progression of atherosclerosis.

scholarly journals Endogenous Hydrogen Sulfide Is an Important Factor in Maintaining Arterial Oxygen Saturation

2021 ◽  
Vol 12 ◽  
Author(s):  
Yan Huang ◽  
Gang Wang ◽  
Zhan Zhou ◽  
Zhengshan Tang ◽  
Ningning Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lung Injury ◽  
Arterial Oxygen Saturation ◽  
Arterial Oxygen ◽  
Wall Thickening ◽  
Alveolar Wall ◽  
Leukocyte Infiltration ◽  
Wild Type ◽  
Interstitial Edema ◽  
And Oxidative Stress

The gasotransmitter H2S is involved in various physiological and pathophysiological processes. The aim of this study was to investigate the physiological functions of H2S in the lungs. In the model of mouse with genetic deficiency in a H2S natural synthesis enzyme cystathionine-γ-lyase (CSE), we found that arterial oxygen saturation (SaO2) was decreased compared with wild type mice. Hypoxyprobe test showed that mild hypoxia occurred in the tissues of heart, lungs and kidneys in Cse-/- mice. H2S donor GYY4137 treatment increased SaO2 and ameliorated hypoxia state in cardiac and renal tissues. Further, we revealed that lung blood perfusion and airway responsiveness were not linked to reduced SaO2 level. Lung injury was found in Cse-/- mice as evidenced by alveolar wall thickening, diffuse interstitial edema and leukocyte infiltration in pulmonary tissues. IL-8, IL-1β, and TNF-α levels were markedly increased and oxidative stress levels were also significantly higher with increased levels of the pro-oxidative biomarker, MDA, decreased levels of the anti-oxidative biomarkers, T-AOC and GSH/GSSG, and reduced superoxide dismutase (SOD) activity in lung tissues of Cse-/- mice compared with those of wild type mice. GYY4137 treatment ameliorated lung injury and suppressed inflammatory state and oxidative stress in lung tissues of Cse-/- mice. A decrease in SaO2 was found in normal mice under hypoxia. These mice displayed lung injury as evidenced by alveolar wall thickening, interstitial edema and leukocyte infiltration. Increased levels of inflammatory cytokines and oxidative stress were also found in lung tissues of the mice with hypoxia insult. GYY4137 treatment increased SaO2 and ameliorated lung injury, inflammation and oxidative stress. Our data indicate that endogenous H2S is an important factor in maintaining normal SaO2 by preventing oxidative stress and inflammation in the lungs.

Effects of lung volume, bronchoconstriction, and cigarette smoke on morphometric airway dimensions

1988 ◽  
Vol 64 (3) ◽  
pp. 913-919 ◽  
Author(s):  
A. L. James ◽  
P. D. Pare ◽  
J. C. Hogg
Keyword(s):  
Smooth Muscle ◽  
Cigarette Smoke ◽  
Lung Volume ◽  
Muscle Tone ◽  
Cigarette Smoke Exposure ◽  
Wall Thickening ◽  
Airway Wall ◽  
Lung Inflation ◽  
Wall Area ◽  
Airway Dimensions

To examine the role of airway wall thickening in the bronchial hyperresponsiveness observed after exposure to cigarette smoke, we compared the airway dimensions of guinea pigs exposed to smoke (n = 7) or air (n = 7). After exposure the animals were anesthetized with urethan, pulmonary resistance was measured, and the lungs were removed, distended with Formalin, and fixed near functional residual capacity. The effects of lung inflation and bronchoconstriction on airway dimensions were studied separately by distending and fixing lungs with Formalin at total lung capacity (TLC) (n = 3), 50% TLC (n = 3), and 25% TLC (n = 3) or near residual volume after bronchoconstriction (n = 3). On transverse sections of extraparenchymal and intraparenchymal airways the following dimensions were measured: the internal area (Ai) and internal perimeter (Pi), defined by the epithelium, and the external area (Ae) and external perimeter (Pe), defined by the outer border of smooth muscle. Airway wall area (WA) was then calculated, WA = Ae - Ai. Ai, Pe, and Ae decreased with decreasing lung volume and after bronchoconstriction. However, WA and Pi did not change significantly with lung volume or after bronchoconstriction. After cigarette smoke exposure airway resistance was increased (P less than 0.05); however, there was no difference in WA between the smoke- and air-exposed groups when the airways were matched by Pi. We conclude that Pi and WA are constant despite changes in lung volume and smooth muscle tone and that airway hyperresponsiveness induced by cigarette smoke is not mediated by increased airway wall thickness.

scholarly journals Direct exposure to SARS-CoV-2 and cigarette smoke increases infection severity and alters the stem cell-derived airway repair response

2020 ◽  
Author(s):  
Arunima Purkayastha ◽  
Chandani Sen ◽  
Gustavo Garcia ◽  
Justin Langerman ◽  
Preethi Vijayaraj ◽  
...  
Keyword(s):  
Viral Infection ◽  
Cigarette Smoke ◽  
Smoke Exposure ◽  
Disease Spread ◽  
Interferon Response ◽  
Cigarette Smoke Exposure ◽  
Airway Epithelial ◽  
Airway Injury ◽  
Increased Risk ◽  
Airway Cells

SUMMARYMost demographic studies are now associating current smoking status with increased risk of severe COVID-19 and mortality from the disease but there remain many questions about how direct cigarette smoke exposure affects SARS-CoV-2 airway cell infection. We directly exposed mucociliary air-liquid interface (ALI) cultures derived from primary human nonsmoker airway basal stem cells (ABSCs) to short term cigarette smoke and infected them with live SARS-CoV-2. We found an increase in the number of infected airway cells after cigarette smoke exposure as well as an increased number of apoptotic cells. Cigarette smoke exposure alone caused airway injury that resulted in an increased number of ABSCs, which proliferate to repair the airway. But we found that acute SARS-CoV-2 infection or the combination of exposure to cigarette smoke and SARS-CoV-2 did not induce ABSC proliferation. We set out to examine the underlying mechanism governing the increased susceptibility of cigarette smoke exposed ALI to SARS-CoV-2 infection. Single cell profiling of the cultures showed that infected airway cells displayed a global reduction in gene expression across all airway cell types. Interestingly, interferon response genes were induced in SARS-CoV-2 infected airway epithelial cells in the ALI cultures but smoking exposure together with SARS-CoV-2 infection reduced the interferon response. Treatment of cigarette smoke-exposed ALI cultures with Interferon β-1 abrogated the viral infection, suggesting that the lack of interferon response in the cigarette smoke-exposed ALI cultures allows for more severe viral infection and cell death. In summary, our data show that acute smoke exposure allows for more severe proximal airway epithelial disease from SARS-CoV-2 by reducing the mucosal innate immune response and ABSC proliferation and has implications for disease spread and severity in people exposed to cigarette smoke.

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