Chronic Obstructive Pulmonary Disease: From Mechanisms to Personalized Therapeutic Strategies

Dear Colleagues,

Chronic obstructive pulmonary disease (COPD) remains one of the leading causes of morbidity and mortality worldwide, yet our understanding of the disease has been profoundly transformed in the last decade. Once viewed as a uniform consequence of cigarette smoking and progressive airflow limitation, COPD is now recognised as a heterogeneous syndrome arising from distinct pathobiological mechanisms—chronic type 2 and non-type 2 inflammation, oxidative stress, accelerated lung ageing, dysregulated repair, microbial dysbiosis along the gut–lung axis, and structural remodelling of small airways and alveolar tissue—that converge on overlapping but mechanistically separable clinical phenotypes. Two converging shifts are reshaping clinical practice. First, the "treatable traits" paradigm has reframed management as the systematic identification and individualised targeting of pulmonary, extrapulmonary, and behavioural traits. Second, the demonstration that a sizeable proportion of patients with COPD harbour type 2 inflammation has brought monoclonal antibodies—already established in severe asthma—into the COPD armamentarium. The recent regulatory approval of dupilumab in COPD with elevated blood eosinophils, alongside positive trials of mepolizumab and emerging programmes targeting the IL-33 and TSLP alarmin axes, signals the entry of pulmonology into the era of biologic therapy for obstructive airway disease. Yet bridging mechanism and personalised therapy in real-world practice begets the following challenges: which biomarkers reliably stratify patients; how endotypes intersect with structural and behavioural traits; how biologics are best positioned alongside optimised inhaled therapy, pulmonary rehabilitation and smoking cessation; and how imaging, oscillometry, multi-omics can refine trait identification at scale. We are pleased to invite you to contribute to a Special Issue dedicated to bringing together the mechanistic insights, methodological innovations, and clinical evidence that will shape the next generation of personalised COPD care.

This Special Issue aims to assemble a comprehensive, mechanism-to-clinic collection of original research, and authoritative reviews on the pathobiology, phenotyping and personalised treatment of COPD—with explicit emphasis on biologic therapy and the treatable-traits framework as the two main vehicles of precision care. Consistent with the scope of Biomedicines, contributions are expected to address the identification, development and clinical translation of biological agents and novel targeted strategies—including the characterisation of new therapeutic targets, biomarker-driven patient stratification, and early-phase clinical evidence—with the ultimate goal of informing precision-medicine pathways for patients with COPD. We aim to collect at least ten high-quality articles spanning mechanistic, methodological and clinical perspectives, integrating pulmonology, immunology and imaging.

In this Special Issue, original research articles, brief communications and reviews (narrative, scoping and systematic) are welcome. Research areas may include, but are not limited to, the following:

• Pathobiology of COPD: Oxidative stress, accelerated lung ageing, mitochondrial dysfunction, cellular senescence, and impaired tissue repair.
• Inflammatory and immune endotypes: Type 2, neutrophilic and pauci-granulocytic profiles; cellular and cytokine networks; the role of innate lymphoid cells and alarmins.
• Multi-omics and molecular phenotyping: Transcriptomics, proteomics, metabolomics and microbiome signatures as mechanism-anchored biomarkers.
• Type 2 inflammation in COPD: Epidemiology, mechanisms, and clinical correlates of the eosinophilic endotype.
• Biomarkers for biologic eligibility in COPD: Blood eosinophil count variability, FeNO, IgE, sputum cytology, and emerging omics-based signatures.
• Dupilumab in COPD: Pivotal trial evidence (BOREAS, NOTUS), real-world data, responder profiling, and long-term outcomes.
• Anti-IL-5/IL-5R strategies in COPD: Mepolizumab, benralizumab, and lessons from MATINEE and earlier programmes.
• Alarmin-targeted therapies (anti-IL-33, anti-TSLP, tozorakimab): Rationale, mechanism, and emerging clinical data.
• The treatable-traits paradigm: Operational definitions, assessment tools, and implementation in routine respiratory practice.
• Pulmonary treatable traits beyond inflammation: Small airway dysfunction (impulse oscillometry, multiple-breath washout), bronchiectasis, mucus hypersecretion, and chronic bronchial infection.
• Extrapulmonary and behavioural traits: Cardiovascular comorbidity, sarcopenia, anxiety/depression, smoking persistence, and adherence.
• Phenotyping and endotyping with imaging and physiology: HRCT-derived biomarkers, quantitative CT, MRI, and lung function clusters.
• Asthma–COPD overlap (ACO): Nosology, biomarker profiles, and therapeutic implications for biologic prescribing.
• The gut–lung axis in COPD: Microbiome, dysbiosis, and host–microbe interactions as therapeutic targets.
• Personalised pharmacological strategies: Positioning of biologics relative to triple inhaled therapy, oral corticosteroid sparing, and exacerbation prevention.

We look forward to receiving your contributions. 

Dr. Alberto Ricci
Dr. Michela D'Ascanio
Dr. Pier-Valerio Mari
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• COPD
• personalized therapy
• treatable traits
• biologic therapy
• dupilumab
• mepolizumab
• type 2 inflammation
• phenotyping
• small airway disease
• precision medicine