Recent Advances in Pharmacology of Chronic Respiratory Diseases

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 17307

Special Issue Editor


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Guest Editor
Department of Physiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia
Interests: bronchial asthma; lung silicosis; acute lung injury; anti-inflammatory treatment

Special Issue Information

Dear Colleagues,

Chronic respiratory diseases (CRDs) represent the third leading cause of death worldwide. According to data from the Global Burden of Disease Study 2017, the total number of deaths due to CRD generally increased between 1990 and 2017. Trends in mortality and disability-adjusted life years (DALYs) due to CRD vary according to the type of the disease, socio-demographic conditions, air pollution, etc. However, the annual decline in mortality rates for chronic obstructive pulmonary disease (COPD) and reductions in DALYs for bronchial asthma indicate that the decreasing tendency may be related to thorough considerations of the pathophysiological background of the diseases, including analyses of proinflammatory, oxidative and fibrotic processes and their interactions, role of genetic factors, gut microbiota, etc. This knowledge has resulted in the introduction of novel strategies of treatment such as the use of synthetic or natural antioxidants and phosphodiesterase inhibitors, as well as the introduction of different therapies including biological treatments for different endotypes and phenotypes of asthma, etc. Similarly to chronic non-communicable respiratory diseases, the incidence and mortality of chronic lung infections, particularly Mycobacterium tuberculosis, is still significant, with an alarming increase in multidrug-resistant forms. This Special Issue aims to present the latest findings on the novel therapeutic approaches in CRD of both non-infectious and infectious etiology, covering a broad field from the study of pathogenetic mechanisms to therapeutic interventions.  Reviews, clinical studies, original experimental studies as well as articles concerning basic research are welcome. 

Prof. Dr. Daniela Mokra
Guest Editor

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Keywords

  • chronic respiratory diseases
  • bronchial asthma
  • chronic obstructive pulmonary disease
  • lung fibrosis
  • silicosis
  • lung tuberculosis
  • treatment

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Published Papers (3 papers)

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Research

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17 pages, 2681 KiB  
Article
Combination of Niclosamide and Pirfenidone Alleviates Pulmonary Fibrosis by Inhibiting Oxidative Stress and MAPK/Nf-κB and STATs Regulated Genes
by Hanaa Wanas, Hossein M. Elbadawy, Mohannad A. Almikhlafi, Amany E. Hamoud, Eid N. Ali and Amr M. Galal
Pharmaceuticals 2023, 16(5), 697; https://doi.org/10.3390/ph16050697 - 4 May 2023
Cited by 2 | Viewed by 2013
Abstract
The pathogenesis of pulmonary fibrosis (PF) is extremely complex and involves numerous intersecting pathways. The successful management of PF may require combining multiple agents. There is a growing body of evidence that suggests the potential benefits of niclosamide (NCL), an FDA-approved anthelminthic drug, [...] Read more.
The pathogenesis of pulmonary fibrosis (PF) is extremely complex and involves numerous intersecting pathways. The successful management of PF may require combining multiple agents. There is a growing body of evidence that suggests the potential benefits of niclosamide (NCL), an FDA-approved anthelminthic drug, in targeting different fibrogenesis molecules. This study aimed at investigating the anti-fibrotic potential of NCL alone and in combination with pirfenidone (PRF), an approved drug for PF, in a bleomycin (BLM) induced PF experimental model. PF was induced in rats by intratracheal BLM administration. The effect of NCL and PRF individually and in combination on different histological and biochemical parameters of fibrosis was investigated. Results revealed that NCL and PRF individually and in combination alleviated the histopathological changes, extracellular matrix deposition and myofibroblastic activation induced by BLM. NCL and PRF either individually or in combination inhibited the oxidative stress and subsequent pathways. They modulated the process of fibrogenesis by inhibiting MAPK/NF-κB and downstream cytokines. They inhibited STATs and downstream survival-related genes including BCL-2, VEGF, HIF-α and IL-6. Combining both drugs showed significant improvement in the tested markers in comparison to the monotherapy. NCL, therefore, has a potential synergistic effect with PRF in reducing the severity of PF. Full article
(This article belongs to the Special Issue Recent Advances in Pharmacology of Chronic Respiratory Diseases)
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17 pages, 1777 KiB  
Article
N-Acetyl Cysteine Restores the Diminished Activity of the Antioxidant Enzymatic System Caused by SARS-CoV-2 Infection: Preliminary Findings
by María Elena Soto, Linaloe Manzano-Pech, Adrían Palacios-Chavarría, Rafael Ricardo Valdez-Vázquez, Verónica Guarner-Lans and Israel Pérez-Torres
Pharmaceuticals 2023, 16(4), 591; https://doi.org/10.3390/ph16040591 - 14 Apr 2023
Cited by 5 | Viewed by 3634
Abstract
SARS-CoV-2 infects type II pneumocytes and disrupts redox homeostasis by overproducing reactive oxygen species (ROS). N-acetyl cysteine (NAC) is a precursor of the synthesis of glutathione (GSH) and it restores the loss of redox homeostasis associated to viral infections. The aim of the [...] Read more.
SARS-CoV-2 infects type II pneumocytes and disrupts redox homeostasis by overproducing reactive oxygen species (ROS). N-acetyl cysteine (NAC) is a precursor of the synthesis of glutathione (GSH) and it restores the loss of redox homeostasis associated to viral infections. The aim of the study is to evaluate the effect of the treatment with NAC on the enzymatic antioxidant system in serum from patients infected by SARS-CoV-2. We evaluated the enzymatic activities of thioredoxin reductase (TrxR), glutathione peroxidase (GPx), -S-transferase (GST), and reductase (GR) by spectrophotometry and the concentrations of the glutathione (GSH), total antioxidant capacity (TAC), thiols, nitrites (NO2), and lipid peroxidation (LPO) in serum. The activity of the extracellular super oxide dismutase (ecSOD) was determined by native polyacrylamide gels, and 3-nitrotyrosine (3-NT) was measured by ELISA. A decrease in the activities of the ecSOD, TrxR, GPx, GST GR, (p = 0 ≤ 0.1), and the GSH, TAC, thiols, and NO2 (p ≤ 0.001) concentrations and an increase in LPO and 3-NT (p = 0.001) concentrations were found in COVID-19 patients vs. healthy subjects. The treatment with NAC as an adjuvant therapy may contribute to a reduction in the OS associated to the infection by SARS-CoV-2 through the generation of GSH. GSH promotes the metabolic pathways that depend on it, thus contributing to an increase in TAC and to restore redox homeostasis. Full article
(This article belongs to the Special Issue Recent Advances in Pharmacology of Chronic Respiratory Diseases)
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Review

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42 pages, 1251 KiB  
Review
Elexacaftor-Tezacaftor-Ivacaftor: A Life-Changing Triple Combination of CFTR Modulator Drugs for Cystic Fibrosis
by Mafalda Bacalhau, Mariana Camargo, Grace A. V. Magalhães-Ghiotto, Sybelle Drumond, Carlos Henrique M. Castelletti and Miquéias Lopes-Pacheco
Pharmaceuticals 2023, 16(3), 410; https://doi.org/10.3390/ph16030410 - 8 Mar 2023
Cited by 36 | Viewed by 11061
Abstract
Cystic fibrosis (CF) is a potentially fatal monogenic disease that causes a progressive multisystemic pathology. Over the last decade, the introduction of CF transmembrane conductance regulator (CFTR) modulator drugs into clinical practice has profoundly modified the lives of many people with CF (PwCF) [...] Read more.
Cystic fibrosis (CF) is a potentially fatal monogenic disease that causes a progressive multisystemic pathology. Over the last decade, the introduction of CF transmembrane conductance regulator (CFTR) modulator drugs into clinical practice has profoundly modified the lives of many people with CF (PwCF) by targeting the fundamental cause of the disease. These drugs consist of the potentiator ivacaftor (VX-770) and the correctors lumacaftor (VX-809), tezacaftor (VX-661), and elexacaftor (VX-445). In particular, the triple combination of CFTR modulators composed of elexacaftor, tezacaftor, and ivacaftor (ETI) represents a life-changing therapy for the majority of PwCF worldwide. A growing number of clinical studies have demonstrated the safety and efficacy of ETI therapy in both short- and long-term (up to two years of follow-up to date) and its ability to significantly reduce pulmonary and gastrointestinal manifestations, sweat chloride concentration, exocrine pancreatic dysfunction, and infertility/subfertility, among other disease signs and symptoms. Nevertheless, ETI therapy-related adverse effects have also been reported, and close monitoring by a multidisciplinary healthcare team remains vital. This review aims to address and discuss the major therapeutic benefits and adverse effects reported by the clinical use of ETI therapy for PwCF. Full article
(This article belongs to the Special Issue Recent Advances in Pharmacology of Chronic Respiratory Diseases)
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