# Interstitial lung abnormalities: to treat or not to treat? The hamlet dilemma

**Authors:** Umberto Zanini, Giovanni Franco, Chiara Pirotta, Eleonora Passeri, Sofia Maria Mazzotta, Giovanni Ferrara, Marco Mura, Paola Faverio, Fabrizio Luppi

PMC · DOI: 10.3389/fmed.2026.1762243 · Frontiers in Medicine · 2026-02-13

## TL;DR

This review discusses the uncertainty around treating interstitial lung abnormalities, which are often found incidentally and may or may not progress to serious disease.

## Contribution

The paper provides a synthesis of current evidence and debates to guide clinical decisions on managing interstitial lung abnormalities.

## Key findings

- Some interstitial lung abnormalities may progress to pulmonary fibrosis, while others remain stable.
- There is no consensus on when to start treatment versus monitoring in interstitial lung abnormalities.
- Current guidelines emphasize risk stratification but lack clear criteria for intervention.

## Abstract

Interstitial lung abnormalities (ILAs) are increasingly recognized as incidental findings on chest computed tomography and may represent an early stage in the spectrum of interstitial lung disease (ILD). However, their clinical significance and optimal management remain debated. While some ILAs may progress to pulmonary fibrosis and functional impairment, many remain stable, and the criteria for initiating diagnostic evaluation, determining monitoring intensity, and starting therapeutic interventions are not clearly established. Current guidelines emphasize risk stratification and longitudinal surveillance, yet significant uncertainties persist regarding which individuals may benefit from early treatment rather than conservative follow-up. This narrative review synthesizes the existing evidence on ILA epidemiology, natural history, and proposed management approaches. We analyse data supporting both early intervention—particularly when ILAs evolve into clinically meaningful ILD—and watchful waiting strategies to avoid overtreatment in asymptomatic and stable cases. The review highlights persistent knowledge gaps, including the lack of consensus on defining progression, determining optimal follow-up intervals, and identifying clear indications for pharmacologic therapy. Overall, ILAs represent a heterogeneous and still poorly defined entity. By critically examining current evidence and ongoing debates, this review aims to guide clinicians in navigating the “to treat or not to treat” dilemma and to outline key priorities for future research.

## Linked entities

- **Diseases:** pulmonary fibrosis (MONDO:0002771), interstitial lung disease (MONDO:0015925)

## Full-text entities

- **Genes:** SFTPD (surfactant protein D) [NCBI Gene 6441] {aka COLEC7, PSP-D, SFTP4, SP-D}, RETN (resistin) [NCBI Gene 56729] {aka ADSF, FIZZ3, RENT, RETN1, RSTN, XCP1}, MUC5B (mucin 5B, oligomeric mucus/gel-forming) [NCBI Gene 727897] {aka MG1, MUC-5B, MUC5, MUC9}, SFTPC (surfactant protein C) [NCBI Gene 6440] {aka BRICD6, PSP-C, SFTP2, SMDP2, SP-C}, MMP13 (matrix metallopeptidase 13) [NCBI Gene 4322] {aka CLG3, MANDP1, MDST, MMP-13}, TERC (telomerase RNA component) [NCBI Gene 7012] {aka DKCA1, PFBMFT2, SCARNA19, TER, TR, TRC3}, MMP1 (matrix metallopeptidase 1) [NCBI Gene 4312] {aka CLG}, PARN (poly(A)-specific ribonuclease) [NCBI Gene 5073] {aka DAN, DKCB6, PFBMFT4}, ABCA3 (ATP binding cassette subfamily A member 3) [NCBI Gene 21] {aka ABC-C, ABC3, EST111653, LBM180, SMDP3}, SFTPA2 (surfactant protein A2) [NCBI Gene 729238] {aka COLEC5, ILD2, PSAP, PSP-A, PSPA, SFTP1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, TERT (telomerase reverse transcriptase) [NCBI Gene 7015] {aka CMM9, DKCA2, DKCB4, EST2, PFBMFT1, TCS1}, MMP7 (matrix metallopeptidase 7) [NCBI Gene 4316] {aka MMP-7, MPSL1, PUMP-1}, RTEL1 (regulator of telomere elongation helicase 1) [NCBI Gene 51750] {aka C20orf41, DKCA4, DKCB5, NHL, PFBMFT3, RTEL}, MUC1 (mucin 1, cell surface associated) [NCBI Gene 4582] {aka ADMCKD, ADMCKD1, ADTKD2, CA 15-3, CD227, Ca15-3}, SFTPA1 (surfactant protein A1) [NCBI Gene 653509] {aka COLEC4, ILD1, PSP-A, PSPA, SFTP1, SFTPA1B}
- **Diseases:** fibrosis (MESH:D005355), metabolic disturbances (MESH:D024821), hyperglycemia (MESH:D006943), liver disease (MESH:D008107), inflammation (MESH:D007249), gastrointestinal symptoms (MESH:D012817), systemic autoimmune disorder (MESH:D020274), respiratory bronchiolitis-ILD (MESH:D012140), radiation pneumonitis (MESH:D017564), abnormal lung function (MESH:D008171), opportunistic infections (MESH:D009894), cancer (MESH:D009369), impairment (MESH:D060825), shortness of breath (MESH:D004417), lung cancer (MESH:D008175), anxiety (MESH:D001007), lung function loss (MESH:D055370), autoimmune (MESH:D001327), nausea (MESH:D009325), hypersensitivity pneumonitis (MESH:D000542), Diarrhoea (MESH:D003967), pneumonitis (MESH:D011014), myositis (MESH:D009220), neuropsychiatric effects (MESH:D065606), reticular abnormalities (MESH:C538361), alveolar (MESH:D002282), bone fragility (MESH:C536063), alveolar epithelial injury (MESH:D009375), fibrotic abnormalities (MESH:D000014), bronchiectasis (MESH:D001987), hypertension (MESH:D006973), cytopenias (MESH:D006402), connective tissue disease (MESH:D003240), bone marrow dysfunction (MESH:D001855), sarcoidosis (MESH:D012507), interstitial abnormalities (MESH:D065167), cardiovascular and malignancy (MESH:D002318), IPF (MESH:D054990), osteoporosis (MESH:D010024), rheumatologic (MESH:D012216), cough (MESH:D003371), weight loss (MESH:D015431), PPF (MESH:D011658), short telomere syndrome (MESH:C536801), impaired gas exchange (MESH:D011007), CTD-ILD disease (MESH:D017563), dyspepsia (MESH:D004415), impaired lung function (MESH:D003072), desquamative interstitial pneumonia (MESH:C562470)
- **Chemicals:** mycophenolate mofetil (MESH:D009173), oxygen (MESH:D010100), tocilizumab (MESH:C502936), Carbon Monoxide (MESH:D002248), azathioprine (MESH:D001379), ILA (-), rituximab (MESH:D000069283), pirfenidone (MESH:C093844), nintedanib (MESH:C530716)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** rs35705950

## Full text

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## References

99 references — full list in the complete paper: https://tomesphere.com/paper/PMC12946126/full.md

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Source: https://tomesphere.com/paper/PMC12946126