ArticleThe Journal of infectious diseases2018
Repetitive Aerosol Exposure Promotes Cavitary Tuberculosis and Enables Screening for Targeted Inhibitors of Extensive Lung Destruction.
Article in The Journal of infectious diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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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
26 citing papers in PubMed, 34 citations in OpenAlex.
- Doxycycline host-directed therapy in human pulmonary tuberculosis.The Journal of clinical investigation · 2021Trial
- Analysis of Drug Resistance Characteristics and Risk Factors of Cavitary Tuberculosis Based on Whole Genome Sequencing and Machine Learning.Open forum infectious diseases · 2026Article
- Factors associated with post-treatment resorption of lung cavities in individuals with first episodes of drug-sensitive cavitary pulmonary tuberculosis in China.BMC infectious diseases · 2025Article
- Host-Directed Therapies Based on Protease Inhibitors to ControlMicroorganisms · 2025Review
- Pathogenesis of Post-Tuberculosis Lung Disease: Defining Knowledge Gaps and Research Priorities at the Second International Post-Tuberculosis Symposium.American journal of respiratory and critical care medicine · 2024Review
- Article
- Immune evasion and provocation by Mycobacterium tuberculosis.Nature reviews. Microbiology · 2022Review
- Antibiotic-Derived Radiotracers for Positron Emission Tomography: Nuclear or "Unclear" Infection Imaging?Angewandte Chemie (International ed. in English) · 2022Review
- Understanding the tuberculosis granuloma: the matrix revolutions.Trends in molecular medicine · 2022Review
- A Ginger Root or Plum Model for the Tuberculosis "Granuloma"?American journal of respiratory and critical care medicine · 2021Article
- Integrated transcriptomic analysis of human tuberculosis granulomas and a biomimetic model identifies therapeutic targets.The Journal of clinical investigation · 2021Article
- Visualizing the dynamics of tuberculosis pathology using molecular imaging.The Journal of clinical investigation · 2021Review
- Host-Directed Therapies: Modulating Inflammation to Treat Tuberculosis.Frontiers in immunology · 2021Review
- Comprehensive plasma proteomic profiling reveals biomarkers for active tuberculosis.JCI insight · 2020Article
- Demystifying the mist: Sources of microbial bioload in dental aerosols.Journal of periodontology · 2020Review
- Cavitary tuberculosis: the gateway of disease transmission.The Lancet. Infectious diseases · 2020Review
- Radiosynthesis and Biodistribution ofACS infectious diseases · 2020Article
- Dynamic imaging in patients with tuberculosis reveals heterogeneous drug exposures in pulmonary lesions.Nature medicine · 2020Article
- A systematic approach to simultaneously evaluate safety, immunogenicity, and efficacy of novel tuberculosis vaccination strategies.Science advances · 2020Article
- Matrix Metalloproteinases in Pulmonary and Central Nervous System Tuberculosis-A Review.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Background: Cavitation is a serious consequence of tuberculosis. We tested the hypothesis that repetitive exposure to the same total bacterial burden of Mycobacterium tuberculosis drives greater lung destruction than a single exposure. We also tested whether inhibition of endogenous matrix metalloproteinase-1 (MMP-1) may inhibit cavitation during tuberculosis. Methods: Over a 3-week interval, we infected rabbits with either 5 aerosols of 500 colony-forming units (CFU) of M. tuberculosis or a single aerosol of 2500 CFU plus 4 sham aerosols. We administered the MMP-1 inhibitor cipemastat (100 mg/kg daily) during weeks 5-10 to a subset of the animals. Results: Repetitive aerosol infection produced greater lung inflammation and more cavities than a single aerosol infection of the same bacterial burden (75% of animals vs 25%). Necropsies confirmed greater lung pathology in repetitively exposed animals. For cipemastat-treated animals, there was no significant difference in cavity counts, cavity volume, or disease severity compared to controls. Conclusions: Our data show that repetitive aerosol exposure with M. tuberculosis drives greater lung damage and cavitation than a single exposure. This suggests that human lung destruction due to tuberculosis may be exacerbated in settings where individuals are repeatedly exposed. MMP-1 inhibition with cipemastat did not prevent the development of cavitation in our model.
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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.