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Clinical Challenges and Future Directions of Interstitial Lung Disease
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Clinical Challenges and Future Directions of Interstitial Lung Disease

A Special Issue of Journal of Clinical Medicine (ISSN 2077-0383) belonging to the section "Respiratory Medicine".

Deadline for manuscript submissions: 20 September 2026 | Viewed by 1414

Editor

Dr. Yoshiaki Zaizen

E-Mail Website
Guest Editor
Division of Respirology, Neurology and Rheumatology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan
Interests: lung pathology; pulmonary pathology; interstitial pneumonia; tuberculosis; interstitial lung disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Interstitial lung diseases (ILDs) represent a heterogeneous group of disorders characterized by varying degrees of inflammation and fibrosis in the lung parenchyma. Despite advancements in our understanding, several key clinical challenges remain. Early and accurate diagnosis is often difficult due to non-specific symptoms and overlapping radiologic and histopathologic features. In this context, multidisciplinary discussion (MDD) involving pulmonologists, radiologists, and pathologists plays a pivotal role in achieving diagnostic consensus. Optimizing treatment strategies—particularly for progressive pulmonary fibrosis (PPF)—continues to be a major challenge. Furthermore, non-pharmacological interventions such as pulmonary rehabilitation and long-term oxygen therapy are recognized as vital components of care, yet their implementation and standardization are inconsistent across clinical settings. Additionally, end-of-life care and the timely integration of palliative approaches are essential but often underutilized aspects of ILD management.

This Special Issue welcomes original research and review articles that provide solid evidence on the diagnosis, treatment, and patient-centered management of ILDs. Submissions focusing on efforts to promote early detection, improve diagnostic processes, refine therapeutic decision making, and enhance supportive and palliative care are particularly encouraged. Through this Special Issue, we aim to contribute to more effective and compassionate care for patients with ILDs.

Dr. Yoshiaki Zaizen
Guest Editor

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • interstitial lung disease
  • progressive pulmonary fibrosis
  • early detection
  • clinical diagnosis
  • multidisciplinary discussion
  • treatment
  • non-pharmacological therapy
  • end-of-life care
  • patient-centered management

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Published Papers (2 papers)

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Research

15 pages, 1044 KB  
Article
Beyond Diffusion Capacity: Continuous Exercise Oximetry Reveals Phenotype-Related Cardiopulmonary Signals in Idiopathic Pulmonary Fibrosis and Progressive Pulmonary Fibrosis—A eurILDreg Pilot Study
by Silke Tello, Anita C. Windhorst, Nadia Hamadi, Andreas Guenther and Ekaterina Krauss
J. Clin. Med. 2026, 15(14), 5572; https://doi.org/10.3390/jcm15145572 - 16 Jul 2026
Viewed by 371
Abstract
Background: Idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) are defined and monitored without definite exercise-based criterion, despite exertional desaturation being among the earliest functional signs of disease and an established independent predictor of mortality in IPF. The 6 min walk [...] Read more.
Background: Idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) are defined and monitored without definite exercise-based criterion, despite exertional desaturation being among the earliest functional signs of disease and an established independent predictor of mortality in IPF. The 6 min walk test (6MWT) provides robust prognostic information in IPF, yet whether it can kinetically distinguish IPF from PPF under sustained submaximal loading has not been systematically examined. We hypothesised that second-by-second oximetry during the 6MWT and the 1 min (min) sit-to-stand test (1STST) would expose phenotype-specific kinetic signatures invisible to static endpoints, and that test modality would matter. Methods: Fifty-one patients with IPF, 12 with PPF, and 100 with non-IPF/non-PPF ILD (reference cohort) from the European ILD Registry (eurILDreg) participated in this pilot study and completed both tests with continuous 1 Hz SpO2 and pulse-rate recording. Phenotype-specific desaturation and recovery slopes were derived from random-effects panel regression models. Multivariable linear regression tested whether IPF and PPF phenotypes carried kinetic and static-endpoint signatures independent of DLCO, age, sex, and BMI. Results: Despite substantially lower DLCO in fibrosing phenotypes (IPF 45 ± 17%, PPF 38 ± 11%, reference 55 ± 19%; p < 0.001), conventional exercise performance metrics did not differ significantly between groups (6MWD p = 0.099; 1STST repetitions p = 0.351). The 6MWT produced statistically indistinguishable per-second desaturation slopes in IPF and PPF (both ≈ −0.016%/s versus −0.011%/s in the reference), whereas the 1STST exposed a clear phenotype gradient (PPF −0.044%/s, IPF −0.027%/s, reference −0.016%/s; a 2.75-fold spread). PPF additionally showed a blunted chronotropic response during the 6MWT (PR slope +0.014 vs. +0.032 and +0.033 bpm/s in IPF and reference). Likelihood-ratio tests confirmed significant phenotype effects on seven of eight time-resolved trajectories (all p < 0.001). IPF was independently associated with greater cumulative oxygenation deficit during the 1STST (SpO2 AUC β = +669, p = 0.022), indicating excess dynamic burden beyond what diffusion capacity predicts. Conclusions: In this pilot analysis, continuous high-resolution oximetry identified two phenotype-related signals that were robust to the principal confounders. IPF was independently associated with a greater cumulative oxygenation impairment during the 1STST after DLCO adjustment, and PPF showed a blunted chronotropic response during sustained walking that, being pulse-rate based, was unaffected by supplemental oxygen and was not attributable to pulmonary hypertension. A phenotype gradient in per-second desaturation measurements during the 1STST was also observed but should be interpreted as hypothesis-generating, as the small PPF subgroup (n = 12), its greater disease severity, and supplemental oxygen use in half of its patients preclude firm attribution to phenotype. Taken as exploratory, these observations support the prospective evaluation of kinetic exercise parameters as candidate monitoring components for PPF. Full article
(This article belongs to the Special Issue Clinical Challenges and Future Directions of Interstitial Lung Disease)
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11 pages, 1291 KB  
Article
Combined HDL–BMI Phenotyping Provides Incremental Prognostic Value in Idiopathic Pulmonary Fibrosis
by Qinxue Shen, Xiaoli Ouyang, Yuexin Tan, Qing Zhang, Feng Hu, Shengyang He and Hong Peng
J. Clin. Med. 2026, 15(7), 2525; https://doi.org/10.3390/jcm15072525 - 26 Mar 2026
Viewed by 606
Abstract
Background/Objectives: Risk stratification in idiopathic pulmonary fibrosis (IPF) remains primarily based on physiological indices, yet increasing evidence suggests that systemic metabolic and nutritional vulnerability may influence outcomes in chronic interstitial lung disease. Methods: In this longitudinal, single-center cohort, 211 patients with [...] Read more.
Background/Objectives: Risk stratification in idiopathic pulmonary fibrosis (IPF) remains primarily based on physiological indices, yet increasing evidence suggests that systemic metabolic and nutritional vulnerability may influence outcomes in chronic interstitial lung disease. Methods: In this longitudinal, single-center cohort, 211 patients with IPF were followed from diagnosis until death or last follow-up. Baseline lipid profiles and body mass index (BMI) were assessed. A metabolic–nutritional phenotype was constructed using high-density lipoprotein cholesterol (HDL) and BMI. Survival was analyzed using Kaplan–Meier and multivariable Cox models adjusted for GAP stage. Incremental prognostic value beyond the GAP index was evaluated using Harrell’s C-index and time-dependent ROC analysis. Results: During a median follow-up of 29 months, 134 patients (63.5%) died. Lower HDL levels were associated with increased mortality in unadjusted analysis (HR = 1.45, 95% CI 1.03–2.04) but were not independently predictive after adjustment. In contrast, the combined HDL–BMI phenotype independently stratified mortality risk. Compared with HDL ≤ 1.0 mmol/L and BMI ≤ 24 kg/m2, patients with HDL > 1.0 mmol/L and BMI > 24 kg/m2 had significantly lower mortality (adjusted HR = 0.48, 95% CI 0.29–0.80), with stronger associations among those aged ≥ 65 years (adjusted HR = 0.37, 95% CI 0.18–0.74). The addition of HDL–BMI improved discrimination beyond GAP (C-index: 0.585 vs. 0.618; 36-month AUC: 0.633 vs. 0.675; NRI: 0.243). Conclusions: The coexistence of HDL ≤ 1.0 mmol/L and BMI ≤ 24 kg/m2 identified a subgroup with poorer survival in IPF. This combined metabolic–nutritional phenotype improved mortality risk stratification beyond the GAP stage. Full article
(This article belongs to the Special Issue Clinical Challenges and Future Directions of Interstitial Lung Disease)
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