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 Tanimilast, A Novel Inhaled Pde4 Inhibitor for the Treatment of Asthma and Chronic Obstructive Pulmonary Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Fabrizio Facchinetti ◽  
Maurizio Civelli ◽  
Dave Singh ◽  
Alberto Papi ◽  
Aida Emirova ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Side Effects ◽  
Pulmonary Disease ◽  
Respiratory Diseases ◽  
Pde4 Inhibitor ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Chronic Respiratory Diseases ◽  
Copd Patients ◽  
Anti Inflammatory

Chronic respiratory diseases are the third leading cause of death, behind cardiovascular diseases and cancer, affecting approximately 550 million of people all over the world. Most of the chronic respiratory diseases are attributable to asthma and chronic obstructive pulmonary disease (COPD) with this latter being the major cause of deaths. Despite differences in etiology and symptoms, a common feature of asthma and COPD is an underlying degree of airways inflammation. The nature and severity of this inflammation might differ between and within different respiratory conditions and pharmacological anti-inflammatory treatments are unlikely to be effective in all patients. A precision medicine approach is needed to selectively target patients to increase the chance of therapeutic success. Inhibitors of the phosphodiesterase 4 (PDE4) enzyme like the oral PDE4 inhibitor roflumilast have shown a potential to reduce inflammatory-mediated processes and the frequency of exacerbations in certain groups of COPD patients with a chronic bronchitis phenotype. However, roflumilast use is dampened by class related side effects as nausea, diarrhea, weight loss and abdominal pain, resulting in both substantial treatment discontinuation in clinical practice and withdrawal from clinical trials. This has prompted the search for PDE4 inhibitors to be given by inhalation to reduce the systemic exposure (and thus optimize the systemic safety) and maximize the therapeutic effect in the lung. Tanimilast (international non-proprietary name of CHF6001) is a novel highly potent and selective inhaled PDE4 inhibitor with proven anti-inflammatory properties in various inflammatory cells, including leukocytes derived from asthma and COPD patients, as well as in experimental rodent models of pulmonary inflammation. Inhaled tanimilast has reached phase III clinical development by showing promising pharmacodynamic results associated with a good tolerability and safety profile, with no evidence of PDE4 inhibitors class-related side effects. In this review we will discuss the main outcomes of preclinical and clinical studies conducted during tanimilast development, with particular emphasis on the characterization of the pharmacodynamic profile that led to the identification of target populations with increased therapeutic potential in inflammatory respiratory diseases.

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.

Bronchodilator and anti-inflammatory therapy of chronic obstructive pulmonary disease from the position of interchangeability

2021 ◽  
Vol 31 (4) ◽  
pp. 518-529
Author(s):  
E. A. Orlova ◽  
I. P. Dorfman ◽  
M. A. Orlov ◽  
A. K. Andreeva ◽  
M. A. Abdullaev
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Generic Drugs ◽  
The State ◽  
Chronic Obstructive ◽  
Anticholinergic Drugs ◽  
Adherence To Treatment ◽  
Obstructive Pulmonary Disease ◽  
State Register ◽  
Anti Inflammatory

The choice of drugs used to treat patients with chronic obstructive pulmonary disease (COPD) (inhaled β-agonists, M-anticholinergic drugs, inhaled corticosteroids (ICS)) in view of their interchangeability is reviewed in this article. This aspect is especially important for clinicians when choosing an effective and safe treatment for COPD and for increasing patient adherence to treatment.The aim of this study was to assess the ratio of the number of reference (original), interchangeable, and generic drugs used in COPD.Methods. In accordance with the Russian clinical guidelines 2018 and GOLD 2019, modern drugs for the treatment of COPD with bronchodilator and anti-inflammatory activity were selected. All trade names of the corresponding drugs for each international non-proprietary name (INN) In the State Register of Medicines website were considered. The information on the availability of reference (original) drugs and the corresponding interchangeable products, as well as their presence in the List of vital and essential drugs was analyzed.Results. A large number of generic prodcuts are registered in the State Register of Medicines, and only a few of them are interchangeable with the corresponding reference (original) drug.Conclusion. The analysis will help widen the doctors’ choice of interchangeable drugs in treatment of COPD with an equivalent effect and safety of reference drugs, as well as to increase the patients’ adherence to treatment.

scholarly journals Chronic Obstructive Pulmonary Disease Combined With Interstitial Lung Disease

2021 ◽  
Author(s):  
Joon Young Choi ◽  
Jin Woo Song ◽  
Chin Kook Rhee
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Interstitial Lung Disease ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Pulmonary Disease ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Quit Smoking ◽  
Lung Abnormalities ◽  
Pharmacologic Agents

Although chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) have distinct clinical features, both diseases may coexist in a patient because they share similar risk factors such as smoking, male sex, and old age. Patients with both emphysema in upper lung fields and diffuse ILD are diagnosed with combined pulmonary fibrosis and emphysema (CPFE), which causes substantial clinical deterioration. Patients with CPFE have higher mortality compared with patients who have COPD alone, but results have been inconclusive compared with patients who have idiopathic pulmonary fibrosis (IPF). Poor prognostic factors for CPFE include exacerbation, lung cancer, and pulmonary hypertension. The presence of interstitial lung abnormalities, which may be an early or mild form of ILD, is notable among patients with COPD, and is associated with poor prognosis. Various theories have been proposed regarding the pathophysiology of CPFE. Biomarker analyses have implied that this pathophysiology may be more closely associated with IPF development, rather than COPD or emphysema. Patients with CPFE should be advised to quit smoking and undergo routine lung function tests, and pulmonary rehabilitation may be helpful. Various pharmacologic agents may be beneficial in patients with CPFE, but further studies are needed.

scholarly journals Low-dose theophylline in addition to ICS therapy in COPD patients: A systematic review and meta-analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251348
Author(s):  
Tiankui Shuai ◽  
Chuchu Zhang ◽  
Meng Zhang ◽  
Yalei Wang ◽  
Huaiyu Xiong ◽  
...  
Keyword(s):  
Low Dose ◽  
Hospitalization Rate ◽  
Current Evidence ◽  
Cochrane Library ◽  
Chronic Obstructive ◽  
Exacerbation Rate ◽  
Histone Deacetylase 2 ◽  
Copd Patients ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Background A synergism has been reported between theophylline and corticosteroids, wherein theophylline increases and restores the anti-inflammatory effect of inhaled corticosteroids (ICS) by enhancing histone deacetylase-2 (HDAC) activity. Several studies have explored the efficacy of low-dose theophylline plus ICS therapy on chronic obstructive pulmonary disease (COPD) but the results are discrepant. Method We conducted searches in electronic database such as PubMed, Web Of Science, Cochrane Library, and Embase to find out original studies. Stata/SE 15.0 was used to perform all data analysis. Result A total of 47,556 participants from 7 studies were included in our analysis and the sample size of each study varied from 24 to 10,816. Theophylline as an add-on therapy to ICS was not associated with the reduction of COPD exacerbations (HR: 1.08, 95% CI: 0.97 to 1.19, I2 = 95.2%). Instead, the theophylline group demonstrated a higher hospitalization rate (HR: 1.12, 95% CI: 1.10 to 1.15, I2 = 20.4%) and mortality (HR: 1.19, 95% CI: 1.14 to 1.25, I2 = 0%). Further, the anti-inflammatory effect of low-dose theophylline as an adjunct to ICS on COPD was controversial. Besides, the theophylline group showed significant improvement in lung function compared with the non-theophylline group. Conclusion Based on current evidence, low-dose theophylline as add-on therapy to ICS did not reduce the exacerbation rate. Instead, the hospitalization rate and mortality increased with theophylline. Thus, we do not recommend adding low-dose theophylline to ICS therapy in COPD patients. Trial registration PROSPERO Registration CRD42021224952.

scholarly journals The Effects of Corticosteroids on the Respiratory Microbiome: A Systematic Review

2021 ◽  
Vol 8 ◽  
Author(s):  
Julia E. Hartmann ◽  
Werner C. Albrich ◽  
Marija Dmitrijeva ◽  
Christian R. Kahlert
Keyword(s):  
Systematic Review ◽  
Research Question ◽  
Corticosteroid Treatment ◽  
Pulmonary Diseases ◽  
Chronic Obstructive ◽  
Cochrane Central Register ◽  
Obstructive Pulmonary Disease ◽  
Randomized Controlled Studies ◽  
Culture Independent ◽  
Respiratory Microbiome

Background: Since its discovery, the respiratory microbiome has been implicated in the pathogenesis of multiple pulmonary diseases. Even though corticosteroid treatments are widely prescribed for pulmonary diseases, their effects on the respiratory microbiome are still poorly understood. This systematic review summarizes the current understanding of the effects of corticosteroids on the microbiome of the airways.Research Question: How does treatment with corticosteroids impact the respiratory microbiome?Study Design and Methods: According to the PRISMA guidelines, Embase, Medline, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were systematically searched for all observational or randomized-controlled studies comparing the microbiome parameters of patients receiving corticosteroids to those of controls. The primary outcomes of interest were changes in the diversity, composition and total burden of the respiratory microbiome as assessed by culture-independent molecular methods.Results: Out of 1,943 identified reports, five studies could be included: two on patients with asthma, two on patients with chronic obstructive pulmonary disease and one on patients with chronic rhinosinusitis. The studies were highly heterogeneous with regards to the methods used and the populations investigated. Microbiome diversity increased with corticosteroids at least transiently in three studies and decreased in one study. The effects of corticosteroids on the composition of the respiratory microbiome were significant but without a clear shared direction. A significant increase in microbial burden after corticosteroids was seen in one study.Interpretation: Data on the effect of corticosteroids on the respiratory microbiome are still limited, with considerable heterogeneity between studies. However, available data suggest that corticosteroid treatment may have significant effects on the composition and possibly the diversity of the respiratory microbiome. Further research is needed to better understand the influence of corticosteroids on the respiratory microbiome and thus better target its widespread therapeutic use.

Social class based on occupation is associated with hospitalization for A(H1N1)pdm09 infection. Comparison between hospitalized and ambulatory cases

2015 ◽  
Vol 144 (4) ◽  
pp. 732-740 ◽  
Author(s):  
J. PUJOL ◽  
P. GODOY ◽  
N. SOLDEVILA ◽  
J. CASTILLA ◽  
F. GONZÁLEZ-CANDELAS ◽  
...  
Keyword(s):  
Social Class ◽  
Influenza Vaccination ◽  
Protective Factor ◽  
Conditional Logistic Regression ◽  
Corticosteroid Treatment ◽  
Chronic Obstructive ◽  
Occupational Class ◽  
Obstructive Pulmonary Disease ◽  
Conditional Logistic Regression Analysis ◽  
Occupational Social Class

SUMMARYThis study aimed to analyse the existence of an association between social class (categorized by type of occupation) and the occurrence of A(H1N1)pmd09 infection and hospitalization for two seasons (2009–2010 and 2010–2011). This multicentre study compared ambulatory A(H1N1)pmd09 confirmed cases with ambulatory controls to measure risk of infection, and with hospitalized A(H1N1)pmd09 confirmed cases to asses hospitalization risk. Study variables were: age, marital status, tobacco and alcohol use, pregnancy, chronic obstructive pulmonary disease, chronic respiratory failure, cardiovascular disease, diabetes, chronic liver disease, body mass index >40, systemic corticosteroid treatment and influenza vaccination status. Occupation was registered literally and coded into manual and non-manual worker occupational social class groups. A conditional logistic regression analysis was performed. There were 720 hospitalized cases, 996 ambulatory cases and 1062 ambulatory controls included in the study. No relationship between occupational social class and A(H1N1)pmd09 infection was found [adjusted odds ratio (aOR) 0·97, 95% confidence interval (CI) 0·74–1·27], but an association (aOR 1·53, 95% CI 1·01–2·31) between occupational class and hospitalization for A(H1N1)pmd09 was observed. Influenza vaccination was a protective factor for A(H1N1)pmd09 infection (aOR 0·41, 95% CI 0·23–0·73) but not for hospitalization. We conclude that manual workers have the highest risk of hospitalization when infected by influenza than other occupations but they do not have a different probability of being infected by influenza.

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