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1.
Int J Mol Sci ; 23(3)2022 Jan 19.
Article in English | MEDLINE | ID: covidwho-1625612

ABSTRACT

Repurposing of the anthelminthic drug niclosamide was proposed as an effective treatment for inflammatory airway diseases such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease. Niclosamide may also be effective for the treatment of viral respiratory infections, such as SARS-CoV-2, respiratory syncytial virus, and influenza. While systemic application of niclosamide may lead to unwanted side effects, local administration via aerosol may circumvent these problems, particularly when the drug is encapsulated into small polyethylene glycol (PEG) hydrospheres. In the present study, we examined whether PEG-encapsulated niclosamide inhibits the production of mucus and affects the pro-inflammatory mediator CLCA1 in mouse airways in vivo, while effects on mucociliary clearance were assessed in excised mouse tracheas. The potential of encapsulated niclosamide to inhibit TMEM16A whole-cell Cl- currents and intracellular Ca2+ signalling was assessed in airway epithelial cells in vitro. We achieved encapsulation of niclosamide in PEG-microspheres and PEG-nanospheres (Niclo-spheres). When applied to asthmatic mice via intratracheal instillation, Niclo-spheres strongly attenuated overproduction of mucus, inhibited secretion of the major proinflammatory mediator CLCA1, and improved mucociliary clearance in tracheas ex vivo. These effects were comparable for niclosamide encapsulated in PEG-nanospheres and PEG-microspheres. Niclo-spheres inhibited the Ca2+ activated Cl- channel TMEM16A and attenuated mucus production in CFBE and Calu-3 human airway epithelial cells. Both inhibitory effects were explained by a pronounced inhibition of intracellular Ca2+ signals. The data indicate that poorly dissolvable compounds such as niclosamide can be encapsulated in PEG-microspheres/nanospheres and deposited locally on the airway epithelium as encapsulated drugs, which may be advantageous over systemic application.


Subject(s)
Niclosamide/administration & dosage , Pneumonia/drug therapy , Respiratory System/drug effects , Animals , Asthma/drug therapy , Asthma/metabolism , Asthma/pathology , COVID-19/complications , COVID-19/drug therapy , Cells, Cultured , Disease Models, Animal , Drug Carriers/chemistry , Drug Compounding , Humans , Hydrogels/chemistry , Instillation, Drug , Mice , Microspheres , Mucus/drug effects , Mucus/metabolism , Nanospheres/administration & dosage , Nanospheres/chemistry , Niclosamide/chemistry , Niclosamide/pharmacokinetics , Pneumonia/pathology , Polyethylene Glycols/chemistry , Respiratory Mucosa/drug effects , Respiratory Mucosa/metabolism , Respiratory System/metabolism , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Trachea
2.
BMC Pulm Med ; 21(1): 278, 2021 Aug 31.
Article in English | MEDLINE | ID: covidwho-1381257

ABSTRACT

BACKGROUND: There are various reasons for delayed positive nasopharyngeal PCR tests for coronavirus disease 2019 (COVID19) in not only asymptomatic but also severely diseased patients. The pathophysiological attributes are not known. We explore this possibility through a case report. CASE PRESENTATION: A 64-year-old male with history of pulmonary fungal infection, asthma and chronic pulmonary obstructive disease (COPD), diabetes, coronary artery disease presented with shortness of breath, fever and chest image of ground opacity, reticular interstitial thickening, highly suspicious for COVID19. However, nasopharyngeal swab tests were discordantly negative for four times in two weeks, and IgG antibody for COVID19 was also negative. However, serum IgE level was elevated. No other pathogens are identified. His symptoms deteriorated despite corticosteroid, antibiotics and bronchodilator treatment. Bronchoalveolar lavage (BAL) and open lung wedge biopsy were performed for etiology diagnosis. They demonstrated COVID19 viral RNA positive fibrosing organizing pneumonia with respiratory tract damage characterized by suspicious viral cytopathic effect, mixed neutrophilic, lymphoplasmacytic, histiocytic and eosinophilic inflammation and fibrosis besides expected asthma and COPD change. One week later, repeated COVID19 nasopharyngeal tests on day 40 and day 49 became positive. CONCLUSION: Our case and literature review indicate that allergic asthma and associated high IgE level together with corticosteroid inhalation might contribute to the delayed positive nasopharyngeal swab in upper airway; COPD related chronic airways obstruction and the addition of fibrosis induced ventilator dependence and poor prognosis in COVID19 pneumonia, and should be therapeutically targeted besides antiviral therapy.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19/diagnosis , Delayed Diagnosis , Nasopharynx/virology , SARS-CoV-2/isolation & purification , Administration, Inhalation , Adrenal Cortex Hormones/therapeutic use , Asthma/complications , Asthma/drug therapy , Asthma/pathology , Bronchoalveolar Lavage , COVID-19/complications , COVID-19/therapy , Fatal Outcome , Humans , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/pathology , Reverse Transcriptase Polymerase Chain Reaction
3.
Int J Mol Sci ; 22(17)2021 Aug 24.
Article in English | MEDLINE | ID: covidwho-1374422

ABSTRACT

The lungs play a very important role in the human respiratory system. However, many factors can destroy the structure of the lung, causing several lung diseases and, often, serious damage to people's health. Nerve growth factor (NGF) is a polypeptide which is widely expressed in lung tissues. Under different microenvironments, NGF participates in the occurrence and development of lung diseases by changing protein expression levels and mediating cell function. In this review, we summarize the functions of NGF as well as some potential underlying mechanisms in pulmonary fibrosis (PF), coronavirus disease 2019 (COVID-19), pulmonary hypertension (PH), asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. Furthermore, we highlight that anti-NGF may be used in future therapeutic strategies.


Subject(s)
Airway Remodeling/drug effects , Lung/pathology , Nerve Growth Factor/antagonists & inhibitors , Signal Transduction/drug effects , Asthma/drug therapy , Asthma/pathology , COVID-19/drug therapy , COVID-19/pathology , Humans , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/pathology , Lung/drug effects , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Molecular Targeted Therapy/methods , Nerve Growth Factor/metabolism , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/pathology , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/pathology
4.
J Ethnopharmacol ; 282: 114574, 2022 Jan 10.
Article in English | MEDLINE | ID: covidwho-1373117

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Gekko gecko is used as a traditional medicine for various diseases including respiratory disorders in northeast Asian countries, mainly Korea, Japan, and China. AIM OF THE STUDY: Allergic asthma is a chronic respiratory disease caused by an inappropriate immune response. Due to the recent spread of coronavirus disease 2019, interest in the treatment of pulmonary disorders has rapidly increased. In this study, we investigated the anti-asthmatic effects of G. gecko extract (GGE) using an established mouse model of ovalbumin-induced asthma. MATERIALS AND METHODS: To evaluate the anti-asthmatic effects of GGE, we evaluated histological changes and the responses of inflammatory mediators related to allergic airway inflammation. Furthermore, we investigated the regulatory effects of GGE on type 2 helper T (Th2) cell activation. RESULTS: Administration of GGE attenuated asthmatic phenotypes, including inflammatory cell infiltration, mucus production, and expression of Th2 cytokines. Furthermore, GGE treatment reduced Th2 cell activation and differentiation. CONCLUSIONS: These results indicate that GGE alleviates allergic airway inflammation by regulating Th2 cell activation and differentiation.


Subject(s)
Anti-Asthmatic Agents/therapeutic use , Asthma/drug therapy , Medicine, East Asian Traditional , Mucus/metabolism , Ovalbumin , Plant Extracts/therapeutic use , Animals , Asthma/chemically induced , Asthma/pathology , Bronchoalveolar Lavage Fluid , COVID-19 , Cytokines/metabolism , Female , Flow Cytometry , Immunoglobulin E/immunology , Inflammation Mediators/metabolism , Lung/pathology , Mice , Mice, Inbred BALB C , Pandemics , Th2 Cells/drug effects , Th2 Cells/immunology , Tryptamines/pharmacology
5.
BMC Complement Med Ther ; 21(1): 192, 2021 Jul 05.
Article in English | MEDLINE | ID: covidwho-1317123

ABSTRACT

BACKGROUND: Lippia javanica (lemon bush) is commonly used in the treatment of respiratory ailments, including asthma in southern African countries but there is no scientific evidence to support this claim. This study investigated the anti-inflammatory, antioxidant and anti-asthmatic effects of L. javanica using a rat model of asthma. METHODS: A 5% w/v L. javanica tea infusion was prepared and characterised by liquid chromatography-mass spectrometer (LC-MS). Animals were intraperitoneally sensitized with ovalbumin (OVA) and subsequently challenged intranasal with OVA on day 15 except the control group. Animals were grouped (n = 5/group) for treatment: unsensitised control, sensitised control, sensitised + prednisolone and sensitised + L. javanica at 50 mg/kg/day and 100 mg/kg/day - equivalent to 1 and 2 cups of tea per day, respectively. After 2 weeks of treatment, bronchoalveolar lavage fluid (BALF) was collected for total and differential white blood cell (WBC) count. Nitric oxide (NO), lipid peroxidation and antioxidants were also assessed in BALF. Ovalbumin specific IgE antibody and inflammatory cytokines: IL-4, IL-5, IL-13 and TNF-alpha were measured in serum. Lung and muscle tissues were histological examined. RESULTS: L. javanica was rich in phenolic compounds. OVA sensitisation resulted in development of allergic asthma in rats. L. javanica treatment resulted in a reduction in total WBC count as well as eosinophils, lymphocytes and neutrophils in BALF. L. javanica inhibited Th2-mediated immune response, which was evident by a decrease in serum IgE and inflammatory cytokines: IL-4, IL-5, IL-13 and TNF-α. L. javanica treatment also reduced malondialdehyde (MDA) and NO, and increased superoxide dismutase, glutathione and total antioxidant capacity. Histology showed significant attenuation of lung infiltration of inflammatory cells, alveolar thickening, and bronchiole smooth muscle thickening. CONCLUSION: L. javanica suppressed allergic airway inflammation by reducing Th2-mediated immune response and oxidative stress in OVA-sensitized rats which may be attributed to the presence of phenolic compound in the plant. This finding validates the traditional use of L. javanica in the treatment of respiratory disorders.


Subject(s)
Asthma/drug therapy , Lippia , Teas, Herbal , Animals , Antioxidants/metabolism , Asthma/pathology , Bronchoalveolar Lavage Fluid/cytology , Cytokines/blood , Disease Models, Animal , Eosinophils/metabolism , Glutathione/metabolism , Immunoglobulin E/blood , Leukocyte Count , Lung/pathology , Lymphocytes/metabolism , Malondialdehyde/metabolism , Neutrophils/metabolism , Nitric Oxide/metabolism , Oxidative Stress/drug effects , Rats, Wistar , Superoxide Dismutase/metabolism , Th2 Cells/drug effects
6.
BMC Complement Med Ther ; 21(1): 192, 2021 Jul 05.
Article in English | MEDLINE | ID: covidwho-1296592

ABSTRACT

BACKGROUND: Lippia javanica (lemon bush) is commonly used in the treatment of respiratory ailments, including asthma in southern African countries but there is no scientific evidence to support this claim. This study investigated the anti-inflammatory, antioxidant and anti-asthmatic effects of L. javanica using a rat model of asthma. METHODS: A 5% w/v L. javanica tea infusion was prepared and characterised by liquid chromatography-mass spectrometer (LC-MS). Animals were intraperitoneally sensitized with ovalbumin (OVA) and subsequently challenged intranasal with OVA on day 15 except the control group. Animals were grouped (n = 5/group) for treatment: unsensitised control, sensitised control, sensitised + prednisolone and sensitised + L. javanica at 50 mg/kg/day and 100 mg/kg/day - equivalent to 1 and 2 cups of tea per day, respectively. After 2 weeks of treatment, bronchoalveolar lavage fluid (BALF) was collected for total and differential white blood cell (WBC) count. Nitric oxide (NO), lipid peroxidation and antioxidants were also assessed in BALF. Ovalbumin specific IgE antibody and inflammatory cytokines: IL-4, IL-5, IL-13 and TNF-alpha were measured in serum. Lung and muscle tissues were histological examined. RESULTS: L. javanica was rich in phenolic compounds. OVA sensitisation resulted in development of allergic asthma in rats. L. javanica treatment resulted in a reduction in total WBC count as well as eosinophils, lymphocytes and neutrophils in BALF. L. javanica inhibited Th2-mediated immune response, which was evident by a decrease in serum IgE and inflammatory cytokines: IL-4, IL-5, IL-13 and TNF-α. L. javanica treatment also reduced malondialdehyde (MDA) and NO, and increased superoxide dismutase, glutathione and total antioxidant capacity. Histology showed significant attenuation of lung infiltration of inflammatory cells, alveolar thickening, and bronchiole smooth muscle thickening. CONCLUSION: L. javanica suppressed allergic airway inflammation by reducing Th2-mediated immune response and oxidative stress in OVA-sensitized rats which may be attributed to the presence of phenolic compound in the plant. This finding validates the traditional use of L. javanica in the treatment of respiratory disorders.


Subject(s)
Asthma/drug therapy , Lippia , Teas, Herbal , Animals , Antioxidants/metabolism , Asthma/pathology , Bronchoalveolar Lavage Fluid/cytology , Cytokines/blood , Disease Models, Animal , Eosinophils/metabolism , Glutathione/metabolism , Immunoglobulin E/blood , Leukocyte Count , Lung/pathology , Lymphocytes/metabolism , Malondialdehyde/metabolism , Neutrophils/metabolism , Nitric Oxide/metabolism , Oxidative Stress/drug effects , Rats, Wistar , Superoxide Dismutase/metabolism , Th2 Cells/drug effects
7.
Int J Mol Sci ; 22(13)2021 Jun 30.
Article in English | MEDLINE | ID: covidwho-1288907

ABSTRACT

Eosinophils are complex granulocytes with the capacity to react upon diverse stimuli due to their numerous and variable surface receptors, which allows them to respond in very different manners. Traditionally believed to be only part of parasitic and allergic/asthmatic immune responses, as scientific studies arise, the paradigm about these cells is continuously changing, adding layers of complexity to their roles in homeostasis and disease. Developing principally in the bone marrow by the action of IL-5 and granulocyte macrophage colony-stimulating factor GM-CSF, eosinophils migrate from the blood to very different organs, performing multiple functions in tissue homeostasis as in the gastrointestinal tract, thymus, uterus, mammary glands, liver, and skeletal muscle. In organs such as the lungs and gastrointestinal tract, eosinophils are able to act as immune regulatory cells and also to perform direct actions against parasites, and bacteria, where novel mechanisms of immune defense as extracellular DNA traps are key factors. Besides, eosinophils, are of importance in an effective response against viral pathogens by their nuclease enzymatic activity and have been lately described as involved in severe acute respiratory syndrome coronavirus SARS-CoV-2 immunity. The pleiotropic role of eosinophils is sustained because eosinophils can be also detrimental to human physiology, for example, in diseases like allergies, asthma, and eosinophilic esophagitis, where exosomes can be significant pathophysiologic units. These eosinophilic pathologies, require specific treatments by eosinophils control, such as new monoclonal antibodies like mepolizumab, reslizumab, and benralizumab. In this review, we describe the roles of eosinophils as effectors and regulatory cells and their involvement in pathological disorders and treatment.


Subject(s)
Eosinophils/physiology , Antibodies, Monoclonal/therapeutic use , Asthma/drug therapy , Asthma/immunology , Asthma/pathology , COVID-19/immunology , COVID-19/pathology , COVID-19/virology , Eosinophilic Esophagitis/drug therapy , Eosinophilic Esophagitis/immunology , Eosinophilic Esophagitis/pathology , Eosinophils/cytology , Eosinophils/immunology , Exosomes/metabolism , Extracellular Traps/metabolism , Humans , Plasma Cells/cytology , Plasma Cells/metabolism , SARS-CoV-2/isolation & purification
8.
Front Immunol ; 12: 645741, 2021.
Article in English | MEDLINE | ID: covidwho-1190313

ABSTRACT

Particulate matter (PM) induces neutrophilic inflammation and deteriorates the prognosis of diseases such as cardiovascular diseases, cancers, and infections, including COVID-19. Here, we addressed the role of γδ T cells and intestinal microbiome in PM-induced acute neutrophilia. γδ T cells are a heterogeneous population composed of Tγδ1, Tγδ2, Tγδ17, and naïve γδ T cells (TγδN) and commensal bacteria promote local expansion of Tγδ17 cells, particularly in the lung and gut without affecting their Vγ repertoire. Tγδ17 cells are more tissue resident than Tγδ1 cells, while TγδN cells are circulating cells. IL-1R expression in Tγδ17 cells is highest in the lung and they outnumber all the other type 17 cells such as Th17, ILC3, NKT17, and MAIT17 cells. Upon PM exposure, IL-1ß-secreting neutrophils and IL-17-producing Tγδ17 cells attract each other around the airways. Accordingly, PM-induced neutrophilia was significantly relieved in γδ T- or IL-17-deficient and germ-free mice. Collectively, these findings show that the commensal microbiome promotes PM-induced neutrophilia in the lung via Tγδ17 cells.


Subject(s)
Leukocytosis/etiology , Lung/immunology , Microbiota , Neutrophils/pathology , Particulate Matter/adverse effects , Receptors, Antigen, T-Cell, gamma-delta/metabolism , Th17 Cells/immunology , Th17 Cells/metabolism , Animals , Asthma/etiology , Asthma/metabolism , Asthma/pathology , Biomarkers , Cytokines/metabolism , Disease Models, Animal , Disease Susceptibility , Fluorescent Antibody Technique , Immunity, Innate , Immunophenotyping , Leukocytosis/metabolism , Leukocytosis/pathology , Lung/metabolism , Lung/pathology , Mice , Neutrophils/metabolism , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism
9.
Cells ; 10(4)2021 04 14.
Article in English | MEDLINE | ID: covidwho-1186898

ABSTRACT

Macrophages play an important role in the innate and adaptive immune responses of organ systems, including the lungs, to particles and pathogens. Cumulative results show that macrophages contribute to the development and progression of acute or chronic inflammatory responses through the secretion of inflammatory cytokines/chemokines and the activation of transcription factors in the pathogenesis of inflammatory lung diseases, such as acute lung injury (ALI), acute respiratory distress syndrome (ARDS), ARDS related to COVID-19 (coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), allergic asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). This review summarizes the functions of macrophages and their associated underlying mechanisms in the development of ALI, ARDS, COVID-19-related ARDS, allergic asthma, COPD, and IPF and briefly introduces the acute and chronic experimental animal models. Thus, this review suggests an effective therapeutic approach that focuses on the regulation of macrophage function in the context of inflammatory lung diseases.


Subject(s)
Acute Lung Injury/pathology , COVID-19/pathology , Macrophages/pathology , Pneumonia/pathology , Pulmonary Disease, Chronic Obstructive/pathology , Respiratory Distress Syndrome/pathology , Acute Lung Injury/immunology , Animals , Asthma/immunology , Asthma/pathology , COVID-19/immunology , Chronic Disease , Humans , Idiopathic Pulmonary Fibrosis/immunology , Idiopathic Pulmonary Fibrosis/pathology , Lung/immunology , Lung/pathology , Macrophages/immunology , Pneumonia/immunology , Pulmonary Disease, Chronic Obstructive/immunology , Respiratory Distress Syndrome/immunology , SARS-CoV-2/immunology
11.
Int Immunopharmacol ; 91: 107309, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1002653

ABSTRACT

BACKGROUND: COVID-19 is considered the most critical health pandemic of 21st century. Due to extremely high transmission rate, people are more susceptible to viral infection. COVID-19 patients having chronic type-2 asthma prevails a major risk as it may aggravate the disease and morbidities. OBJECTIVE: The present review mainly focuses on correlating the influence of COVID-19 in type-2 asthmatic patients. Besides, it delineates the treatment measures and drugs that can be used to manage mild, moderate, and severe symptoms of COVID-19 in asthmatic patients, thus preventing any exacerbation. METHODS: An in-depth research was carried out from different peer-reviewed articles till September 2020 from several renowned databases like PubMed, Frontier, MEDLINE, and related websites like WHO, CDC, MOHFW, and the information was analysed and written in a simplified manner. RESULTS: The progressive results were quite conflicting as severe cases of COVID-19 shows an increase in the level of several cytokines that can augment inflammation to the bronchial tracts, worsening the asthma attacks. Contradicting to this, certain findings reveal the decrease in the severity of COVID-19 due to the elevation of T-cells in type-2 asthmatic patients, as prominent reduction of T-cell is seen in most of the COVID-19 positive patients. This helps to counteract the balance of immune responses and hence ameliorate the disease progression. CONCLUSION: Asthmatic patients must remain cautious during the COVID-19 pandemic by maintaining all the precautions to stay safe due to limited research data. Future strategies should include a better understanding of asthmatic exacerbation and its relation to COVID-19.


Subject(s)
Asthma/pathology , Asthma/virology , COVID-19/pathology , Animals , Asthma/metabolism , COVID-19/metabolism , Cytokines , Disease Progression , Humans , Pandemics/prevention & control , Risk Factors , SARS-CoV-2/pathogenicity
16.
J Allergy Clin Immunol ; 146(6): 1295-1301, 2020 12.
Article in English | MEDLINE | ID: covidwho-812091

ABSTRACT

The newly described severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for a pandemic (coronavirus disease 2019 [COVID-19]). It is now well established that certain comorbidities define high-risk patients. They include hypertension, diabetes, and coronary artery disease. In contrast, the context with bronchial asthma is controversial and shows marked regional differences. Because asthma is the most prevalent chronic inflammatory lung disease worldwide and SARS-CoV-2 primarily affects the upper and lower airways leading to marked inflammation, the question arises about the possible clinical and pathophysiological association between asthma and SARS-CoV-2/COVID-19. Here, we analyze the global epidemiology of asthma among patients with COVID-19 and propose the concept that patients suffering from different asthma endotypes (type 2 asthma vs non-type 2 asthma) present with a different risk profile in terms of SARS-CoV-2 infection, development of COVID-19, and progression to severe COVID-19 outcomes. This concept may have important implications for future COVID-19 diagnostics and immune-based therapy developments.


Subject(s)
Asthma , COVID-19 , SARS-CoV-2/immunology , Asthma/epidemiology , Asthma/immunology , Asthma/pathology , COVID-19/epidemiology , COVID-19/immunology , COVID-19/pathology , Humans , Pandemics
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