Mucolytics for COPD: negotiating a slippery slope towards proof of efficacy

Aaron, Shawn D.

doi:10.1183/13993003.01465-2017

Cited by 8 publications

(4 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…With preclinical data demonstrating a role for proteases in multiple stages of the MCC mechanism, they represent an interesting alternative to currently available mucoactive drugs. Mucolytic drugs, such as dornase alfa and hypertonic saline have demonstrated efficacy in CF, however, studies in other muco-obstructive lung conditions including COPD and non-CF bronchiectasis have shown mixed results [ 211 , 212 , 213 , 214 , 215 ]. Heterogeneity in these conditions may be an issue; stratification or recruitment of specific disease sub-phenotypes that suffer from chronic cough and sputum production may help to uncover efficacy in these conditions.…”

Section: Targeting Proteases In Muco-obstructive Lung Diseasementioning

confidence: 99%

Proteases, Mucus, and Mucosal Immunity in Chronic Lung Disease

McKelvey

Brown

Ryan

et al. 2021

IJMS

View full text Add to dashboard Cite

Dysregulated protease activity has long been implicated in the pathogenesis of chronic lung diseases and especially in conditions that display mucus obstruction, such as chronic obstructive pulmonary disease, cystic fibrosis, and non-cystic fibrosis bronchiectasis. However, our appreciation of the roles of proteases in various aspects of such diseases continues to grow. Patients with muco-obstructive lung disease experience progressive spirals of inflammation, mucostasis, airway infection and lung function decline. Some therapies exist for the treatment of these symptoms, but they are unable to halt disease progression and patients may benefit from novel adjunct therapies. In this review, we highlight how proteases act as multifunctional enzymes that are vital for normal airway homeostasis but, when their activity becomes immoderate, also directly contribute to airway dysfunction, and impair the processes that could resolve disease. We focus on how proteases regulate the state of mucus at the airway surface, impair mucociliary clearance and ultimately, promote mucostasis. We discuss how, in parallel, proteases are able to promote an inflammatory environment in the airways by mediating proinflammatory signalling, compromising host defence mechanisms and perpetuating their own proteolytic activity causing structural lung damage. Finally, we discuss some possible reasons for the clinical inefficacy of protease inhibitors to date and propose that, especially in a combination therapy approach, proteases represent attractive therapeutic targets for muco-obstructive lung diseases.

show abstract

Section: Targeting Proteases In Muco-obstructive Lung Diseasementioning

confidence: 99%

Proteases, Mucus, and Mucosal Immunity in Chronic Lung Disease

McKelvey

Brown

Ryan

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…In previous studies, improvement in functional parameters due to the use of mucolytic drugs, including carbocysteine, was not always observed in COPD patients. This is justified by the fact that these studies were not limited to specific COPD phenotypes that may most benefit from the use of mucolytics, such as patients with chronic cough and sputum [28]. Although the present study assessed a small sample size of COPD patients, it has the merit to assess the clinical and molecular effects of carbocysteine in a well-selected COPD patient population with mucus hypersecretion and frequent exacerbations.…”

Section: Discussionmentioning

confidence: 99%

Carbocysteine Modifies Circulating miR-21, IL-8, sRAGE, and fAGEs Levels in Mild Acute Exacerbated COPD Patients: A Pilot Study

et al. 2022

View full text Add to dashboard Cite

Patients with Chronic Obstructive Pulmonary Disease (COPD) periodically experience acute exacerbation (AECOPD). Carbocysteine represents a valid add on therapy in COPD by exerting antioxidant and anti-inflammatory activities. The in vivo effects of carbocysteine on inflammatory markers are not yet fully understood. The aims of this study were to assess: (i) miR-21, IL-8, soluble Receptor for Advanced Glycation End Products (sRAGE), and fluorescent Advanced Glycation End Products (fAGEs) in control subjects (n = 9), stable (n = 9), and AECOPD patients (n = 24); and (ii) whether carbocysteine modifies these markers and the functional parameters in mild AECOPD patients. Mild AECOPD patients received or not carbocysteine along with background inhalation therapy for 20 days. At the onset and at the end of the observation period, the following parameters were evaluated: FEV1, FEF25–75%, CAT questionnaire; miR-21 by Real Time PCR; IL-8 and sRAGE by ELISA; and fAGEs by spectro-fluorescence method. COPD patients showed higher levels of miR-21, IL-8, fAGEs and lower levels of sRAGE compared to that of controls. miR-21 inversely correlated with FEV1. IL-8 and fAGEs were significantly different in stable and exacerbated COPD patients. Carbocysteine improved symptoms, FEV1 and FEF25–75%, increased sRAGE, and reduced miR-21, IL-8, and fAGEs in mild AECOPD patients. The present study provides compelling evidence that carbocysteine may help to manage mild AECOPD by downregulating some parameters of systemic inflammation.

show abstract

“…Asimismo, se ha demostrado que producen mayor beneficio en los pacientes que están recibiendo corticosteroides inhalados. [91][92][93][94] Pregunta clínica 20 ¿Cuál es la eficacia y seguridad de los inhibidores de la fosfodiesterasa 4 (IPDE4) para el manejo de los pacientes con EPOC?…”

Section: Evidencia 1++unclassified

Guía de Práctica Clínica Mexicana para el diagnóstico y tratamiento de la Enfermedad Pulmonar Obstructiva Crónica <br>GUÍA MEXICANA DE EPOC, 2020

Vázquez-García¹,

Hernández-Zenteno²,

Pérez-Padilla³

et al. 2019

NCT Neumología Y Cirugía De Tórax

View full text Add to dashboard Cite

www.medigraphic.org.mx RESUMEN. Introducción: La enfermedad pulmonar obstructiva crónica (EPOC) es una de las principales causas de muerte en México y en el mundo. Pese a que en los últimos años se ha alcanzado un gran progreso en su manejo y tratamiento, esto también ha conllevado una mayor complejidad. En México, es fundamental el desarrollo de guías de práctica clínica (GPC) que estén basadas en estándares internacionales para establecer recomendaciones a todos los niveles de atención. Objetivos: El objetivo fue desarrollar una GPC con recomendaciones clínicas desarrolladas de forma sistematizada para asistir a la toma de decisiones, tanto de médicos de todos los niveles de atención, como de pacientes, cuidadores de pacientes y todos los elaboradores de políticas públicas involucrados en el manejo de pacientes con enfermedad pulmonar obstructiva crónica. Material y métodos: Este documento fue desarrollado por parte de la Sociedad Mexicana de Neumología y Cirugía de Tórax en cumplimiento con los estándares internacionales como los descritos por el Instituto de Medicina de los Estados Unidos (IOM, por sus siglas en inglés). Se integró un Grupo de Desarrollo de la Guía (GDG) de manera interdisciplinaria, considerando la participación de neumólogos y metodólogos con experiencia en revisiones sistemáticas de la literatura y el desarrollo de GPC. De forma sistematizada, se consensuaron los alcances, las preguntas clínicas y se evaluaron otras Guías Internacionales sobre el tema. Se evaluó críticamente la calidad metodológica de esas GPC. A través del abordaje ADAPTE, se transculturizó la GPC a nuestro país y, finalmente, utilizando metodología de consenso formal de expertos, se desarrollaron las recomendaciones clínicas. Resultados: Se consensuaron 40 preguntas estructuradas clínicamente relevantes para el diagnóstico y tratamiento, así como las recomendaciones clínicas pertinentes y su texto de soporte. Las recomendaciones abarcan preguntas sobre diagnóstico y tratamiento. Conclusión: Esta GPC pretende proveer recomendaciones clínicas para el diagnóstico y manejo terapéutico de los distintos estadios de la EPOC basadas en evidencia científica, que asisten en el proceso de toma de decisiones compartidas y que esperamos contribuyan a mejorar la calidad de la atención clínica en las pacientes con EPOC. Palabras clave: Guías de Práctica Clínica, medicina basada en evidencia, enfermedad pulmonar obstructiva crónica. ABSTRACT. Introduction: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of the death in Mexico and worldwide. In recent years, great progress has been achieved in its management and treatment, which also entails greater complexity. In Mexico, the development of clinical practice guidelines (CPG) under international standards is essential to stablish recommendations at all levels of care. Objectives: This Clinical Practice Guideline provides systematically developed clinical recommendations to assist clinical decision makers involved in the management of patients with COPD. Material ...

show abstract

Mucolytics for COPD: negotiating a slippery slope towards proof of efficacy

Cited by 8 publications

References 14 publications

Proteases, Mucus, and Mucosal Immunity in Chronic Lung Disease

Proteases, Mucus, and Mucosal Immunity in Chronic Lung Disease

Carbocysteine Modifies Circulating miR-21, IL-8, sRAGE, and fAGEs Levels in Mild Acute Exacerbated COPD Patients: A Pilot Study

Guía de Práctica Clínica Mexicana para el diagnóstico y tratamiento de la Enfermedad Pulmonar Obstructiva Crónica <br>GUÍA MEXICANA DE EPOC, 2020

Contact Info

Product

Resources

About