Low-dose theophylline restores corticosteroid responsiveness in rats with smoke-induced airway inflammation

2012 ◽  
Vol 90 (7) ◽  
pp. 895-902 ◽  
Author(s):  
Xianwen Sun ◽  
Qingyun Li ◽  
Yi Gong ◽  
Lei Ren ◽  
Huanying Wan ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Low Dose ◽  
Corticosteroid Treatment ◽  
Lavage Fluid ◽  
Cell Counting ◽  
Chronic Obstructive ◽  
High Dose ◽  
Obstructive Pulmonary Disease ◽  
Histone Deacetylase 2 ◽  
Chemokine Ligand

Patients with chronic obstructive pulmonary disease (COPD) respond poorly to corticosteroids. Histone deacetylase-2 (HDAC-2) plays a pivotal role in many cases of steroid insensitivity. The main aim of this study was to restore the smoking-induced reduction in corticosteroid sensitivity by increasing HDAC-2 activity using low-dose theophylline. Rats were exposed to cigarette smoke (CS) and treated with budesonide and two doses of theophylline. Besides the pathologic examination and cell counting in the bronchoalveolar lavage fluid (BALF), the expression of HDAC-2 and CXC chemokine ligand-8 (CXCL-8) were measured. Airway inflammation induced by CS was demonstrated by pathologic changes of lung tissue and increased level of CXCL-8. CS exposure also markedly decreased HDAC-2 expression. Moreover, a negative correlation was found between HDAC-2 activity and a lung destruction index. The index was restored to control levels with inhaled corticosteroid treatment in combination with a low, not a high, dose of theophylline. These results indicate that low-dose theophylline might provide protection from smoke damage and improve the anti-inflammatory effects of steroids by increasing HDAC-2 activity.

scholarly journals FSTL1 aggravates cigarette smoke-induced airway inflammation and airway remodeling by regulating autophagy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ying Liu ◽  
Jiawei Xu ◽  
Tian Liu ◽  
Jinxiang Wu ◽  
Jiping Zhao ◽  
...  
Keyword(s):  
Lung Function ◽  
Airway Inflammation ◽  
Cigarette Smoke ◽  
Airway Remodeling ◽  
Critical Factor ◽  
Lavage Fluid ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Impaired Lung Function

Abstract Background Cigarette smoke (CS) is a major risk factor for Chronic Obstructive Pulmonary Disease (COPD). Follistatin-like protein 1 (FSTL1), a critical factor during embryogenesis particularly in respiratory lung development, is a novel mediator related to inflammation and tissue remodeling. We tried to investigate the role of FSTL1 in CS-induced autophagy dysregulation, airway inflammation and remodeling. Methods Serum and lung specimens were obtained from COPD patients and controls. Adult female wild-type (WT) mice, FSTL1± mice and FSTL1flox/+ mice were exposed to room air or chronic CS. Additionally, 3-methyladenine (3-MA), an inhibitor of autophagy, was applied in CS-exposed WT mice. The lung tissues and serum from patients and murine models were tested for FSTL1 and autophagy-associated protein expression by ELISA, western blotting and immunohistochemical. Autophagosome were observed using electron microscope technology. LTB4, IL-8 and TNF-α in bronchoalveolar lavage fluid of mice were examined using ELISA. Airway remodeling and lung function were also assessed. Results Both FSTL1 and autophagy biomarkers increased in COPD patients and CS-exposed WT mice. Autophagy activation was upregulated in CS-exposed mice accompanied by airway remodeling and airway inflammation. FSTL1± mice showed a lower level of CS-induced autophagy compared with the control mice. FSTL1± mice can also resist CS-induced inflammatory response, airway remodeling and impaired lung function. CS-exposed WT mice with 3-MA pretreatment have a similar manifestation with CS-exposed FSTL1± mice. Conclusions FSTL1 promotes CS-induced COPD by modulating autophagy, therefore targeting FSTL1 and autophagy may shed light on treating cigarette smoke-induced COPD.

scholarly journals Corticosteroid Resistant Pulmonary Fibrosis: Pathophysiology and Management

2021 ◽  
pp. 517-531
Author(s):  
Doha O. Alghamdi ◽  
Hala S. Abdel Kawy ◽  
Zoheir A. Damanhouri
Keyword(s):  
Side Effects ◽  
Pulmonary Fibrosis ◽  
Radiation Treatment ◽  
Corticosteroid Treatment ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Histone Deacetylase 2 ◽  
Anticancer Properties ◽  
Experimental Drugs ◽  
Anti Inflammatory

Pulmonary fibrosis is a disease of the lower respiratory system. It might be as Idiopathic fibrosis which is obscure reason for disease or might be as an optional impact from different causes, for example, the environmental causes, for example, toxins and smoking, some connective tissue illnesses., infection diseases, for example, tuberculosis (TB) and corona virus, a few medications, for example, bleomycin, methotrexate, and radiation treatment. Glucocorticoid are used for treating inflammatory and immune diseases, like asthma, but interstitial lung disease, cystic fibrosis, and chronic obstructive pulmonary disease (COPD) at some stage, may become resistant to corticosteroid treatment. Glucocorticoids inhibit inflammation by many mechanisms. The oxidative stress leads to significantly decrease in activity and expression of Histone deacetylase 2 (HDAC-2) which causes resistant to the action of glucocorticoid. However, the dissociated glucocorticoids have been developed to decrease side effects, the dissociated glucocorticoid receptor agonists (DIGRAs) are a class of experimental drugs designed to share many of the desirable anti-inflammatory,  immunosuppressive, or  anticancer  properties of classical glucocorticoid drugs with fewer side effects, but it is so difficult to dissociate anti-inflammatory effects from adverse effects. Patients with glucocorticoid resistance must use alternative anti-inflammatory treatments as well as drugs that may reverse the molecular mechanism of glucocorticoid resistant. Objective: This paper is to review the corticosteroid resistant pulmonary fibrosis and how overcome this resistance. The data was collected from December 2020 to September 2021.

scholarly journals Exhaled Nitric Oxide in COPD

2019 ◽  
Vol 15 (2) ◽  
pp. 71-78 ◽  
Author(s):  
Andras Bikov ◽  
Martina Meszaros ◽  
Zsofia Lazar
Keyword(s):  
Nitric Oxide ◽  
Airway Inflammation ◽  
Corticosteroid Treatment ◽  
Clinical Findings ◽  
Exhaled Nitric Oxide ◽  
Chronic Obstructive ◽  
Mathematical Methods ◽  
Clinical Value ◽  
Obstructive Pulmonary Disease ◽  
Steroid Responsiveness

Chronic obstructive pulmonary disease (COPD) is a common and progressive disorder which is characterised by pathological abnormalities driven by chronic airway inflammation. The assessment of airway inflammation in routine clinical practice in COPD is limited to surrogate blood markers. Fractional exhaled nitric oxide (FENO) is a marker of eosinophilic airway inflammation in asthma, and it can predict steroid responsiveness and help tailor corticosteroid treatment. The clinical value of FENO in COPD is less evident, but some studies suggest that it may be a marker of the eosinophilic endotype. More importantly, mathematical methods allow investigation of the alveolar/small airway production of NO which potentially better reflects inflammatory changes in anatomical sites, most affected by COPD. This review summarises the pathophysiological role of nitric oxide in COPD, explains the methodology of its measurement in exhaled air and discusses clinical findings of FENO in COPD.

Optimal glucocorticoid dose and the effects on mortality, length of stay, and readmission rates in patients diagnosed with acute exacerbation of chronic obstructive pulmonary disease (AECOPD)

2019 ◽  
Vol 67 (8) ◽  
pp. 1161-1164
Author(s):  
Asim Kichloo ◽  
Michael Aljadah ◽  
Navya Vipparla ◽  
Farah Wani
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Acute Exacerbation ◽  
Low Dose ◽  
Future Research ◽  
Chronic Obstructive ◽  
High Dose ◽  
Readmission Rates ◽  
Glucocorticoid Treatment ◽  
Obstructive Pulmonary Disease

The burden of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is staggering on a national and global level. Yet, surprisingly, there is a profound lack of treatment standardization with glucocorticoids in the treatment of AECOPD. In this review, we bring attention to specific literature that use a cut-off of 60 mg prednisone equivalent per day when distinguishing between high-dose and low-dose glucocorticoid treatment. We hope this review encourages future research to begin incrementally lowering the cut-off dose of 60 mg to discover if mortality, length of hospital stays, and readmission rates change between high-dose and low-dose glucocorticoid treatment. The final hope would be to establish an optimal glucocorticoid dose to treat AECOPD and eliminate treatment ambiguity.

scholarly journals Evaluation of Corticosteroid Dose in Acute Exacerbation of Chronic Obstructive Pulmonary Disease

2017 ◽  
Vol 52 (8) ◽  
pp. 546-550 ◽  
Author(s):  
Alice N. Hemenway ◽  
Alexandra M. Terry
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Blood Glucose ◽  
Length Of Stay ◽  
Readmission Rate ◽  
Dose Group ◽  
Low Dose ◽  
Dose Range ◽  
Chronic Obstructive ◽  
High Dose ◽  
Obstructive Pulmonary Disease

Background: Several recent studies have shown that both lower doses and shorter durations of systemic corticosteroids have similar efficacy for treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, each trial has limitations that constrain direct applicability to a US hospital population. Objective: The aim of this study was to determine whether, in a US community hospital, low doses of corticosteroids provide the lowest risk of adverse effects without increasing length of stay or readmission rate. Methods: A single-center retrospective cohort was performed using patients meeting criteria for AECOPD. Primary endpoints included length of hospitalization, proportion of patients with >30% increase in blood glucose from baseline, and rate of 30-day readmission; multivariable regression analysis was used for comparison. The 3 inpatient cumulative dose range groups were low: ≤250-mg prednisone equivalents, medium: 251 to 500 mg, and high: ≥501 mg. Results: A total of 665 records were evaluated, with 369 records included. As the corticosteroid dose ranges increased, there were more patients with increased blood glucose (33.3%, 54.4%, 59.9%). When holding all other factors constant, there was a statistically significant increase in patients with elevated blood glucose with the medium- and high-dose groups as compared with the low-dose group ( P < .009, P < .001), the average length of stay was 21.3 hours higher in the high-dose group as compared with the low-dose group ( P < .001), and there were no significant differences in readmission rates between the dose groups. Conclusions: The lowest dose range of corticosteroids was associated with the lowest rate of impaired blood glucose without a statistically significant increase in length of stay or readmission rate.

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