Phenotypes and Endotypes in Interstitial Lung Diseases—Second Edition

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: 31 October 2026 | Viewed by 1244

Special Issue Editor


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Guest Editor
Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Milan, Italy
Interests: interstitial lung disease; pulmonary fibrosis; orphan lung diseases; non-cystic fibrosis bronchiectasis; pneumonia/pulmonary infection; sarcoidosis
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Special Issue Information

Dear Colleagues,

Interstitial lung diseases (ILDs) are a heterogeneous group of more than 200 entities of either known or unknown etiology. The heterogeneity seen in ILDs manifests at many levels, including their symptoms, disease course, radiological and histological features, and biological underpinnings. This heterogeneity has been a substantial barrier to understanding the mechanisms of these diseases and developing effective and personalized treatments. Despite the growing interest and clinical research into ILDs, the management of patients remains sub-optimal, mainly because of the limited knowledge of the diseases’ pathogenesis, the highly variable and unpredictable behavior of the diseases, and their heterogeneous responses to treatment. Recent data suggest that different ILDs may share similar pathogenetic and biological pathways and thus be amenable to the same treatment. A paradigmatic example is the progressive pulmonary fibrosis (PPF) phenotype, in which nintedanib, a tyrosine kinase inhibitor targeting the PDGF and several other growth factors, has shown efficacy regardless of ILD etiology. A growing amount of evidence points towards the subgroup characterization of ILDs through endotypes, which are defined by specific genetic and molecular biomarkers. Thus, the future of ILDs lies in precision medicine approaches that are based on phenotypic and endotypic features. The aim of this Special Issue is to outline the status of knowledge in this field.

Dr. Francesco Amati
Guest Editor

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Keywords

  • interstitial lung diseases (ILDs)
  • heterogeneity
  • pathogenesis
  • progressive pulmonary fibrosis (PPF)
  • molecular biomarkers

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Related Special Issue

Published Papers (2 papers)

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Editorial

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3 pages, 147 KB  
Editorial
Endotypes and Phenotypes in ILD: Is It Time to Reclassify ILD by Risk Stratification?
by Francesco Amati, Anna Stainer and Stefano Aliberti
Biomedicines 2025, 13(7), 1529; https://doi.org/10.3390/biomedicines13071529 - 23 Jun 2025
Viewed by 646
Abstract
Interstitial lung diseases (ILD) comprise a heterogeneous group of disorders that present significant challenges in both diagnosis and management due to their varied nature, which encompasses different degrees of inflammation and fibrosis affecting lung tissue [...] Full article

Research

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14 pages, 2085 KB  
Article
Maintenance of Effectiveness of Pirfenidone in Elderly Patients with Progressive Functional Impairment: A Real-World Retrospective Study in IPF
by Stefano Levra, Cecilia Rivero, Fabiana Giannoccaro, Giuseppe Guida, Francesca Bertolini, Vitina Carriero, Elisa Arrigo, Maurizio Balbi, Carlo Albera and Fabio Luigi Massimo Ricciardolo
Biomedicines 2025, 13(11), 2809; https://doi.org/10.3390/biomedicines13112809 - 18 Nov 2025
Viewed by 389
Abstract
Background/Objectives: In clinical trials designed to evaluate efficacy and safety of pirfenidone in patients with idiopathic pulmonary fibrosis (IPF), inclusion criteria were age ≤ 80 years, FVC ≥ 50%pred and DLco ≥ 35%pred. The outcomes in patients progressing beyond these criteria are not [...] Read more.
Background/Objectives: In clinical trials designed to evaluate efficacy and safety of pirfenidone in patients with idiopathic pulmonary fibrosis (IPF), inclusion criteria were age ≤ 80 years, FVC ≥ 50%pred and DLco ≥ 35%pred. The outcomes in patients progressing beyond these criteria are not yet fully investigated. This study aims to evaluate the effectiveness of pirfenidone in patients who, during treatment, progress beyond the criteria adopted in clinical trials. Methods: This observational retrospective single-centre study included patients younger than 81 years and with mild-to-moderate IPF who had initiated pirfenidone from December 2011 to October 2023. We compared the monthly decline in absolute FVC and %DLco before and after the progression beyond one or more inclusion criteria used in clinical trials. Results: A total of 174 patients were included in the study, with a mean follow-up of 39.2 months (SD ± 29.7 months, range 2–152 months). Seventy-six of them remained within all criteria (control group), 72 passed one criterion, 25 two criteria and 1 all criteria. There was no difference in the trend of FVC and %DLco between the control group and the groups that passed one or two criteria. The intra-individual trend after passing one criterion was similar to that shown before, for both FVC and %DLco. The intra-individual trend also appeared to be preserved when analyzing a small group of patients who had passed any two criteria. Conclusions: Neither attaining advanced age nor the development of severe functional impairment appeared to limit the effectiveness of pirfenidone. Full article
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