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Molecular Mechanisms of Chronic Lung Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 31 January 2027 | Viewed by 932

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Guest Editor
Pneumogenomics Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico
Interests: interstitial lung disease; HLA; genetic studies; CPFE
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Special Issue Information

Dear Colleagues,

The molecular mechanisms underlying chronic lung diseases—such as COPD, asthma, and ILDs—involve a harmful cycle of ongoing inflammation, oxidative stress, and an imbalance between proteases and antiproteases. This cycle leads to airway remodeling, including fibrosis and increased mucus production, as well as alveolar destruction seen in emphysema. Factors like genetics, smoking, pollutants, and immune responses disrupt normal lung function and repair processes. Key contributors include inflammatory cells such as neutrophils, macrophages, and T cells, along with cytokines (e.g., TNF-α, interleukins), chemokines (e.g., CXCL, CCL), reactive oxygen species (ROS), and proteases such as MMPs and elastases. These elements cause tissue damage and weaken defense mechanisms, often continuing even after the initial triggers are gone.

We welcome the submission of original research, reviews, mini-reviews, and perspective articles that cover, but are not limited to, the following topics:

  • The role of inflammaging in chronic lung diseases and its influence on the outcomes.
  • Cytokine networks modulating metalloproteinases related to chronic lung diseases.
  • Genetic/genomic and epigenetic/epigenomic ongoing studies of inflammation, oxidative stress, and imbalances between proteases and antiproteases in chronic lung diseases.
  • The role of innate alterations in the development of chronic lung diseases.
  • Alterations in the activity of inflammasomes that favor the development of degenerative lung pathologies.

Dr. Ramcés Falfán-Valencia
Guest Editor

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Keywords

  • interstitial lung diseases
  • chronic respiratory diseases
  • genetic susceptibility
  • genomic
  • cytokine networks
  • metalloproteinases
  • inflammasome
  • inflammatory cytokines
  • telomere length

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Published Papers (1 paper)

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Research

31 pages, 10750 KB  
Article
Integrative Multivariate Genomics Identifies Shared Epithelial–Immune and Cytokine-Regulatory Mechanisms Across Major Chronic Lung Diseases
by Chung-Chih Liao, Ke-Ru Liao and Jung-Miao Li
Int. J. Mol. Sci. 2026, 27(15), 6946; https://doi.org/10.3390/ijms27156946 - 2 Aug 2026
Viewed by 235
Abstract
Chronic lung diseases, including asthma, chronic obstructive pulmonary disease, bronchiectasis, and idiopathic pulmonary fibrosis, are clinically distinct but share epithelial injury, host-defense, inflammatory, and remodeling processes. We integrated European-ancestry genome-wide association study (GWAS) summary statistics for these four diseases using genomic structural equation [...] Read more.
Chronic lung diseases, including asthma, chronic obstructive pulmonary disease, bronchiectasis, and idiopathic pulmonary fibrosis, are clinically distinct but share epithelial injury, host-defense, inflammatory, and remodeling processes. We integrated European-ancestry genome-wide association study (GWAS) summary statistics for these four diseases using genomic structural equation modeling to construct a multivariate chronic lung disease (mvCLD) factor. Variant-level association testing was combined with genomic control assessment, locus annotation, GWAS-by-subtraction, fine-mapping, transcriptomic prioritization, pathway enrichment, single-cell spatial mapping, and heritability partitioning. For discovery, across 6,255,777 autosomal variants, mvCLD identified 2067 genome-wide significant variants, 30 loci, and 53 lead variants. Five lead variants were genome-wide significant for mvCLD but not for any component disease and showed high-confidence fine-mapping support. For gene prioritization, transcriptomic and gene-level analyses prioritized 21 candidate genes, including ORMDL3, GSDMB, IL18RAP, IL18R1, IL1R1, SMAD3, and CLEC16A. In exploratory functional analyses, enrichment analyses converged on interleukin, cytokine-receptor, JAK-STAT, interleukin-4/interleukin-13, thymic stromal lymphopoietin, asthma, and lung fibrosis pathways. Exploratory single-cell spatial mapping, based on a mouse embryonic atlas, showed the strongest overall enrichment in the lung annotation, although cross-dataset cell-type and tissue analyses did not reach significance after false discovery rate correction; heritability partitioning implicated conserved and active regulatory elements. These findings support a shared epithelial–immune and cytokine-regulatory genetic architecture across major chronic lung diseases and nominate biologically coherent candidate genes and pathways for future functional and translational studies. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Chronic Lung Diseases)
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