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European Respiratory Review : An... Jun 2023Bronchiectasis is a common progressive respiratory disease with recognisable radiological abnormalities and a clinical syndrome of cough, sputum production and recurrent...
Bronchiectasis is a common progressive respiratory disease with recognisable radiological abnormalities and a clinical syndrome of cough, sputum production and recurrent respiratory infections. Inflammatory cell infiltration into the lung, in particular neutrophils, is central to the pathophysiology of bronchiectasis. Herein we explore the roles and relationships between infection, inflammation and mucociliary clearance dysfunction in the establishment and progression of bronchiectasis. Microbial and host-mediated damage are important processes underpinning bronchiectasis and the relative contribution of proteases, cytokines and inflammatory mediators to the propagation of inflammation is presented. We also discuss the emerging concept of inflammatory endotypes, defined by the presence of neutrophilic and eosinophilic inflammation, and explore the role of inflammation as a treatable trait. Current treatment for bronchiectasis focuses on treatment of underlying causes, enhancing mucociliary clearance, controlling infection and preventing and treating complications. Data on airway clearance approaches exercise and mucoactive drugs, pharmacotherapy with macrolides to decrease exacerbations and the usefulness of inhaled antibiotics and bronchodilators are discussed, finishing with a look to the future where new therapies targeting host-mediated immune dysfunction hold promise.
Topics: Humans; Adult; Bronchiectasis; Inflammation; Cough; Anti-Bacterial Agents; Macrolides
PubMed: 37286220
DOI: 10.1183/16000617.0015-2023 -
Journal of Controlled Release :... Nov 2023RNA therapies have recently taken a giant leap forward with the approval of Onpattro™, a siRNA therapy delivered using a lipid nanoparticle (LNP), and the LNP-enabled...
RNA therapies have recently taken a giant leap forward with the approval of Onpattro™, a siRNA therapy delivered using a lipid nanoparticle (LNP), and the LNP-enabled mRNA vaccines against COVID-19, which are the first mRNA drugs to reach the marketplace. The latter medicines have illustrated that stability is a significant challenge in the distribution of RNA drugs using non-viral delivery systems, particularly in areas without cold chain storage. Here, we describe a proof-of-concept study on the engineering of an LNP mRNA formulation suitable for spray drying. This process produced a dry powder formulation that maintained stability and preserved mRNA functionality with increased performance compared to liquid formulations stored two weeks at 4 °C. Intratracheal delivery of spray dried LNPs loaded with eGFP mRNA to rats resulted in the production of the eGFP protein in a range of cell types including bronchiolar epithelial cells, macrophages and type II pneumocytes; cell types involved in adaptive immunity and which would be valuable targets for inhaled vaccines against respiratory pathogens. Together, these data show that spray drying of LNPs enhances their stability and may enable RNA delivery to the lung for protein replacement therapy, gene editing, vaccination, and beyond.
Topics: Rats; Animals; Humans; RNA, Messenger; COVID-19 Vaccines; Liposomes; Nanoparticles
PubMed: 37741463
DOI: 10.1016/j.jconrel.2023.09.031 -
Clinical Cancer Research : An Official... Sep 2023The FDA granted accelerated approval for amivantamab-vmjw (hereafter referred to as amivantamab), a bispecific antibody directed against EGFR and mesenchymal-epithelial... (Clinical Trial)
Clinical Trial
The FDA granted accelerated approval for amivantamab-vmjw (hereafter referred to as amivantamab), a bispecific antibody directed against EGFR and mesenchymal-epithelial transition receptor, on May 21, 2021, for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy. Approval was based on results of an ongoing, multicenter, nonrandomized, open-label, multicohort clinical trial (CHRYSALIS, NCT02609776), demonstrating a substantial overall response rate (ORR) and durable responses, with an ORR of 40% [95% confidence interval (CI): 29-51] and a median response duration of 11.1 months (95% CI: 6.9-not evaluable). Guardant360 CDx was contemporaneously approved as a companion diagnostic for this indication to identify EGFR exon 20 insertion mutations in plasma specimens. The most notable safety finding was the high incidence (66%) of infusion-related reactions, which is addressed in both the Dosage and Administration and Warnings and Precautions sections of the product label. Other common adverse reactions (occurring in ≥20% of patients) were rash, paronychia, musculoskeletal pain, dyspnea, nausea and vomiting, fatigue, edema, stomatitis, cough, and constipation. The approval of amivantamab was the first approval of a targeted therapy for patients with advanced NSCLC harboring EGFR exon 20 insertion mutations.
Topics: Adult; Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Mutagenesis, Insertional; ErbB Receptors; Exons; Mutation; Protein Kinase Inhibitors
PubMed: 37022784
DOI: 10.1158/1078-0432.CCR-22-3713 -
Current Opinion in Pulmonary Medicine Jan 2024Chronic bronchitis is a phenotype of chronic obstructive pulmonary disease (COPD), characterized by chronic cough and sputum production, associated with an increased... (Review)
Review
PURPOSE OF REVIEW
Chronic bronchitis is a phenotype of chronic obstructive pulmonary disease (COPD), characterized by chronic cough and sputum production, associated with an increased rate of COPD exacerbations and hospital admissions, a more rapid decline in lung function and reduced life expectancy. Despite optimal medical therapy, chronic bronchitis remains difficult to treat. Interventional bronchoscopic procedures offer novel therapeutic approaches to this highly symptomatic condition.
RECENT FINDINGS
A characteristic feature of chronic bronchitis is the presence of an abnormal epithelium with excessive mucus producing cells, parasympathetic overactivity, and airway inflammation. Metered cryospray and bronchial rheoplasty are designed to target this abnormal epithelium to reduce mucus production and inflammation. Targeted lung denervation aims to reduce parasympathetic overactivity, which may drive mucus hypersecretion. Here, we review the available evidence to determine the safety and efficacy across the bronchoscopic interventions.
SUMMARY
Interventional bronchoscopy is a rapidly expanding field and its application in the treatment of chronic bronchitis has been recognized by the Global initiative for chronic Obstructive Lung Disease (GOLD). The outcomes from the latest clinical trials will guide future treatment approaches in patients with difficult to treat chronic bronchitis.
Topics: Humans; Bronchitis, Chronic; Pulmonary Disease, Chronic Obstructive; Lung; Chronic Disease; Inflammation; Bronchitis
PubMed: 37942820
DOI: 10.1097/MCP.0000000000001036 -
Respiratory Care Jul 2023Many patients suffer from complaints of dyspnea, cough, and sputum production, clinical symptoms that hallmark the structural abnormalities that are present in patients... (Review)
Review
Many patients suffer from complaints of dyspnea, cough, and sputum production, clinical symptoms that hallmark the structural abnormalities that are present in patients with COPD. Although pharmacologic and non-pharmacologic medical therapies help reduce these symptoms, many of these symptoms, especially dyspnea, remain unchecked and contribute to the burden of disease in patients with COPD. Over the last 3 decades, several surgical and interventional treatments delivered via a bronchoscopic approach have been developed to complement medical therapies and show promise to improve patient outcomes. Surgical and interventional treatments target structural abnormalities of the airway and lung parenchyma that can be identified with a combination of imaging and physiological testing, factors that are key to select patients most likely to benefit from these treatments. This paper reviews surgical and bronchoscopic interventional treatment options for patients with emphysema and airways disorders.
Topics: Humans; Pneumonectomy; Bronchoscopy; Pulmonary Emphysema; Lung; Dyspnea
PubMed: 37353329
DOI: 10.4187/respcare.10825 -
Frontiers in Pharmacology 2023We aimed to systematically evaluate the prevalence and clinical characteristics of adverse events associated with the adaptogens and antidepressant drug interactions in...
We aimed to systematically evaluate the prevalence and clinical characteristics of adverse events associated with the adaptogens and antidepressant drug interactions in a retrospective chart review. A total of 1,816 reports of adverse events were evaluated. Cases were included in the analysis if the pharmacoepidemiological analysis showed the presence of a high probability of a causal relationship between an adaptogen and antidepressant interaction and the occurrence of adverse events. The following data were extracted from the reports: age, sex, antidepressant, plant products containing adaptogens, other concomitant medications, and clinical consequences of the interactions and their possible mechanisms. Adaptogens were involved in 9% of adverse events associated with the concomitant use of antidepressants and other preparations. We identified 30 reports in which side effects presented a causal relationship with the use of antidepressants and adaptogens. Here, we present the list of adaptogens with the corresponding antidepressants and the side effects caused by their interactions: : reboxetine (testicle pain and ejaculatory dysfunctions), sertraline (severe diarrhea), escitalopram (myalgia, epigastric pain, nausea, vomiting, restless legs syndrome, and severe cough), and paroxetine (generalized myalgia, ophthalmalgia, and ocular hypertension); : duloxetine (upper gastrointestinal bleeding), paroxetine (epistaxis), sertraline (vaginal hemorrhage), and agomelatine (irritability, agitation, headache, and dizziness); : bupropion (arthralgia and thrombocytopenia), amitriptyline (delirium), and fluoxetine (dysuria); : citalopram (generalized pruritus), escitalopram (galactorrhea), and trazodone (psoriasis relapse); : mianserin (arrhythmias), mirtazapine (edema of lower limbs and myalgia), and fluoxetine (gynecomastia); : mianserin (restless legs syndrome), paroxetine (gynecomastia and mastalgia), and venlafaxine (hyponatremia); : agomelatine (back pain and hyperhidrosis) and moclobemide (myocardial infarction); : duloxetine (back pain); : sertraline (upper gastrointestinal bleeding); : mianserin (restless legs syndrome); and : bupropion (seizures). Clinicians should monitor the adverse events associated with the concomitant use of adaptogens and antidepressant drugs in patients with mental disorders. Aggregation of side effects and pharmacokinetic interactions (inhibition of CYP and p-glycoprotein) between those medicines may result in clinically significant adverse events.
PubMed: 37829299
DOI: 10.3389/fphar.2023.1271776