ArticleAmerican journal of respiratory and critical care medicine2019
An Improved Inhaled Mucolytic to Treat Airway Muco-obstructive Diseases.
Article in American journal of respiratory and critical care medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 118 citations in OpenAlex.
- Impact of N-Acetylcysteine on Mucus Hypersecretion in the Airways: A Systematic Review.International journal of chronic obstructive pulmonary disease · 2024Pooled it
- Micro/nanoscale bubble-mediated mucolytic conditioning of the lung model of cystic fibrosis enhances nanoparticle transport through the mucus.Biomaterials · 2026Article
- Carbocisteine Reduces Airway Mucus Obstruction and Alters Inflammatory Cell Populations in a Model of Muco-Obstructive Lung Disease.Immunology and cell biology · 2026Article
- Myeloperoxidase impairs mucociliary transport on human airway epithelium.Disease models & mechanisms · 2026Article
- Cilia-independent gas-liquid transport, a third mechanism mediating airway mucus clearance.The Journal of clinical investigation · 2026Article
- Mucoactive Agents in Muco-Obstructive Lung Diseases: A Critical Reappraisal of Pharmacological Effects and Clinical Outcomes.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Review
- Inactivating conditions of therapeutic mycobacteriophages.Microbiology spectrum · 2026Article
- Airway mucus in infection.Frontiers in physiology · 2026Review
- Inhalable nanoparticle-based delivery systems for the treatment of pulmonary infections:Drug delivery · 2025Review
- High-resolution multimodal imaging reveals spatial and temporal heterogeneity of airway mucus plugging in mice with muco-obstructive lung disease.Scientific reports · 2025Article
- Revolutionizing antibiotic therapy: Polymyxin B and FeJournal of pharmaceutical analysis · 2025Article
- Inactivating conditions of therapeutic mycobacteriophages.bioRxiv : the preprint server for biology · 2025Article
- Macroheterogeneities Induced by Disulfide Bond Reduction in Native Mucus.ACS applied bio materials · 2025Article
- Mucins and Their Roles in Asthma.Immunological reviews · 2025Review
- Identification of Nicotinic Acetylcholine Receptor for N-Acetylcysteine to Rescue Nicotine-induced Injury Using Beating Cilia in Primary Tissue Derived Airway Organoids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Biopolymeric Inhalable Dry Powders for Pulmonary Drug Delivery.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Emerging cell and molecular targets for treating mucus hypersecretion in asthma.Allergology international : official journal of the Japanese Society of Allergology · 2024Review
- Functional prediction of the potential NGLY1 mutations associated with rare disease CDG.Heliyon · 2024Article
- Insights onMicroorganisms · 2024Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
rationaleAirways obstruction with thick, adherent mucus is a pathophysiologic and clinical feature of muco-obstructive respiratory diseases, including chronic obstructive pulmonary disease, asthma, and cystic fibrosis (CF). Mucins, the dominant biopolymer in mucus, organize into complex polymeric networks via the formation of covalent disulfide bonds, which govern the viscoelastic properties of the mucus gel. For decades, inhaled N-acetylcysteine (NAC) has been used as a mucolytic to reduce mucin disulfide bonds with little, if any, therapeutic effects. Improvement of mucolytic therapy requires the identification of NAC deficiencies and the development of compounds that overcome them.
objectivesElucidate the pharmacological limitations of NAC and test a novel mucin-reducing agent, P3001, in preclinical settings.
methodsThe study used biochemical (e.g., Western blotting, mass spectrometry) and biophysical assays (e.g., microrheology/macrorheology, spinnability, mucus velocity measurements) to test compound efficacy and toxicity in in vitro and in vivo models and patient sputa. MEASUREMENTS AND MAIN
resultsDithiothreitol and P3001 were directly compared with NAC in vitro and both exhibited superior reducing activities. In vivo, P3001 significantly decreased lung mucus burden in βENaC-overexpressing mice, whereas NAC did not (n = 6-24 mice per group). In NAC-treated CF subjects (n = 5), aerosolized NAC was rapidly cleared from the lungs and did not alter sputum biophysical properties. In contrast, P3001 acted faster and at lower concentrations than did NAC, and it was more effective than DNase in CF sputum ex vivo.
conclusionsThese results suggest that reducing the viscoelasticity of airway mucus is an achievable therapeutic goal with P3001 class mucolytic agents.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.