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Open research questions in Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis

799 gap statements mined from Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis papers in our 7.9M-paper local library, which holds 2,982 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • Therapeutic challenges, including the need for prompt cessation of the offending drug. The potential for irreversible lung injury if the condition is not recognized and treated early.

    Levofloxacin-Induced Eosinophilic Pneumonia with Systemic Manifestations: A Case Report and Literature Review · 2026 · DOI

  • The lack of a standardized approach for identifying progression and guiding treatment in non-IPF fibrosing ILDs. The need for a reproducible visual scoring approach on radiological criteria of the 2022 progressive pulmonary fibrosis guideline.

    Assessment of fibrosing interstitial lung disease progression: CT visual score on radiological progressive pulmonary fibrosis criteria versus 3D-CT volume-histogram analysis · 2026 · DOI

  • The gap is the lack of automated ILA assessment methods that can provide objective and accurate evaluations. The current study aims to address this gap by applying a previously developed AI model to a cohort of patients with esophageal cancer.

    Prognostic value of AI-derived probability of interstitial lung abnormalities and interstitial lung disease in patients with esophageal cancer · 2026 · DOI

  • Limited understanding of the occurrence of progressive pulmonary fibrosis in connective tissue disease-associated interstitial lung disease. Limited knowledge of the factors associated with time to progressive pulmonary fibrosis onset and survival. Need for further research on treatment patterns and outcomes in patients with progressive pulmonary fibrosis.

    Occurrence of progressive pulmonary fibrosis and its association with survival in connective tissue disease-associated interstitial lung disease: an international retrospective cohort study · 2026 · DOI

  • The lack of high-quality evidence supporting optimal screening strategies for RA-ILD. The variability in recommendations for RA-ILD across different clinical practice guidelines. The need for a comprehensive evaluation of the different clinical emphases observed in the guidelines.

    Divergent approaches to rheumatoid arthritis–associated interstitial lung disease: a comparative analysis of international clinical practice guidelines · 2026 · DOI

  • The need for more selective and effective treatments for IPF. The limited understanding of the molecular mechanisms underlying IPF. The lack of targeted therapies for IPF.

    Correction: Novara et al. A Scoping Review of Emerging Treatments in the Pipeline for Idiopathic Pulmonary Fibrosis: Future Perspectives. Biomedicines 2026, 14, 1293 · 2026 · DOI

  • Substantial unmet need remains for interventions that target mechanisms sustaining pathological remodeling in IPF. The complete donor-recipient pathway for lactate-associated fibroblast–macrophage signaling has not yet been demonstrated using matched human IPF fibroblasts and macrophages. No lactate-directed therapeutic strategy has yet demonstrated clinical efficacy in IPF.

    Lactate-associated fibroblast–macrophage signaling in idiopathic pulmonary fibrosis: evidence boundaries and immunopharmacological opportunities · 2026 · DOI

  • It highlights the need for further research into the therapeutic potential of targeting glycolysis in pulmonary fibrosis.

    Glycolysis in pulmonary fibrosis: From drivers to therapeutic opportunities (Review) · 2026 · DOI

  • The need for further research to understand the long-term effects of these antifibrotic drugs.

    Pirfenidone and Nintedanib in Pulmonary Fibrosis: Lights and Shadows · 2024 · DOI

  • However, the cell populations and transcriptional states through which mtDNA injury shapes lung damage and repair remain unclear.

    Mitochondria-Targeted OGG1 remodels Alveolar Epithelial Transitional States and Immune-Epithelial Communication after Chlorine Lung Injury · 2026 · DOI

  • Lung fibrosis progression is marked by impaired alveolar epithelial regeneration and uncontrolled myofibroblast differentiation, though the underlying mechanisms remain poorly understood.

    Atg5 deficiency alters myofibroblast accumulation and alveolar regeneration in lung fibrosis · 2026 · DOI

  • Idiopathic pulmonary fibrosis (IPF) is a fatal disease whose pathogenic mechanisms remain incompletely understood.

    PHB2 acts as a braker of progressive pulmonary fibrosis via intervention of DDR2-elicited signaling · 2026 · DOI

  • ObjectiveProton pump inhibitors (PPIs) are prescribed in the intensive care unit (ICU), but their association with outcomes in patients with pulmonary fibrosis remains unclear.

    Proton pump inhibitors use and clinical outcomes in critically ill patients with pulmonary fibrosis: A retrospective cohort study with propensity score matching · 2026 · DOI

  • Aluminum‐associated interstitial lung disease is an exposure‐related fibrotic lung disorder, but the metabolic and innate immune mechanisms underlying persistent pulmonary remodeling after aluminum exposure remain incompletely understood.

    AlCl 3 Aerosol Exposure Is Associated With Pulmonary Lactate Accumulation, Neutrophil Dysfunction, and Fibrosis‐Like Remodeling · 2026 · DOI

  • We and others have shown that TGF-β-mediated activation of the Mechanistic Target of Rapamycin Complex 1 (mTORC1) and downstream upregulation of Activating Transcription Factor 4 (ATF4) promote increased expression of the enzymes required for de novo glycine synthesis; however, whether mTOR and ATF4 regulate other metabolic pathways in lung fibroblasts has not been explored.

    mTOR signaling regulates multiple metabolic pathways in human lung fibroblasts after TGF-β and in pulmonary fibrosis · 2025 · DOI

  • Identification of pathways preventing timely recovery from acute respiratory viral infection is under-studied but essential for long-term health.

    Lung basement membranes are compositionally and structurally altered following resolution of influenza infection · 2025 · DOI

  • Regulatory T (Treg) cells are well recognized for their role in immune regulation; however, their role in tissue regeneration is not fully understood.

    Regulatory T cells protect against aberrant remodeling in a mouse model of pulmonary fibrosis · 2025 · DOI

  • However, the effects of systemic miR-26a deficiency on pulmonary fibrosis have not been investigated.

    Systemic miR-26a deficiency attenuates pulmonary fibrosis via PTEN upregulation and downstream TIMP-1 suppression · 2025 · DOI

  • Several microRNAs (miRNAs) have been implicated in the pathophysiology of pulmonary fibrosis; however, the detailed mechanisms remain unclear.

    Systemic miR-26a deficiency attenuates pulmonary fibrosis via PTEN upregulation and downstream TIMP-1 suppression · 2025 · DOI

  • The pathogenesis and underlying mechanisms are poorly understood although a combination of environmental and genetic factors is implicated.

    The role of epigenetic regulation in idiopathic pulmonary fibrosis · 2025 · DOI

  • Investigation of the underlying mechanisms of HRR in IPF, - Validation of HRR in larger, multicenter cohorts, - Exploration of the prognostic value of HRR in other…

    Hemoglobin-to-RDW Ratio and All-Cause Mortality in Idiopathic Pulmonary Fibrosis: Complementary Value to Echocardiographic Right Ventricular–Pulmonary Arterial Coupling · 2026 · DOI

  • Investigating the potential use of CAL101 in IPF - Evaluating the efficacy of CAL101 in a phase II…

    Correction: Novara et al. A Scoping Review of Emerging Treatments in the Pipeline for Idiopathic Pulmonary Fibrosis: Future Perspectives. Biomedicines 2026, 14, 1293 · 2026 · DOI

  • Translating preclinical findings into clinically viable therapies for PF - Investigating the interplay and crosstalk between glycolysis and other metabolic pathways, such as glutaminolysis and lipid metabolism - Developing more effective and less toxic personalized…

    Glycolysis in pulmonary fibrosis: From drivers to therapeutic opportunities (Review) · 2026 · DOI

  • The study on RA-ILD patients was incomplete due to COVID-19 pandemic reasons, - No data are available for Sarcoidosis, - The evaluation of the effectiveness of Pirfenidone and Nintedanib is based on a limited number of clinical…

    Pirfenidone and Nintedanib in Pulmonary Fibrosis: Lights and Shadows · 2024 · DOI

  • This study fills a key gap in understanding the broader health care burden of AEx beyond idiopathic pulmonary fibrosis.

    Health care utilization and costs associated with acute exacerbation of fibrosing interstitial lung disease in the United States: A retrospective administrative claims database analysis · 2026 · DOI

Most-cited papers in Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis

Most recent work

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Open questions raised by papers listed on this page include: (1) The lack of a standardized approach for identifying progression and guiding treatment in non-IPF fibrosing ILDs (“Assessment of fibrosing interstitial lung disease progression: CT visual score…”, 2026); (2) The gap is the lack of automated ILA assessment methods that can provide objective and accurate evaluations (“Prognostic value of AI-derived probability of interstitial lung abnormalities…”, 2026); (3) The lack of high-quality evidence supporting optimal screening strategies for RA-ILD (“Divergent approaches to rheumatoid arthritis–associated interstitial lung…”, 2026); (4) The cell populations and transcriptional states through which mtDNA injury shapes lung damage and repair remain unclear (“Mitochondria-Targeted OGG1 remodels Alveolar Epithelial Transitional States and…”, 2026); (5) Lung fibrosis progression is marked by impaired alveolar epithelial regeneration and uncontrolled myofibroblast differentiation, though the underlying mechanisms remain poorly understood (“Atg5 deficiency alters myofibroblast accumulation and alveolar regeneration in…”, 2026). 799 gap statements have been mined from Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis papers in our 7.9M-paper local library, which holds 2,982 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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