Advances in Theranostic Biomarkers in Lung Diseases

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 16478

Special Issue Editors


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Guest Editor
Respiratory Diseases and Lung Transplant Unit, Department of Medical and Surgical Sciences and Neurosciences, University of Siena, 53100 Siena, Italy
Interests: severe asthma; biological therapy; immunology; biomarkers; lung transplantation
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Respiratory Diseases and Lung Transplant Unit, Department of Medical and Surgical Sciences and Neurosciences, University of Siena, 53100 Siena, Italy
Interests: immunology; flow cytometry; allergy; biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Theranostics is an emerging field in which diagnosis and specific targeted therapy are combined to achieve a personalized treatment approach. The selection of theranostic markers allows a promising therapeutic paradigm involving diagnosis, drug delivery, and monitoring of treatment response. The detection of numerous theranostic markers is necessary to administer effective therapy to patients with different pathological conditions, including lung diseases. Theranostic approaches in respiratory medicine are an important research topic with the aim of phenotyping different patients. Theranostics is appreciated in multiple fields, with special consideration in restrictive and obstructive lung diseases and in lung cancer. This Special Issue of Life calls for original research articles, brief reports, and review articles focusing on new diagnostic approaches and theranostic biomarkers in the field of lung disorders.

Dr. Laura Bergantini
Dr. Miriana d'Alessandro
Guest Editors

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Keywords

  • immune system
  • inflammation
  • therapy
  • biomarkers
  • oxidative stress

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Published Papers (5 papers)

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Research

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11 pages, 961 KiB  
Article
Eosinophil Cationic Protein Variation in Patients with Asthma and CRSwNP Treated with Dupilumab
by Andrea Giovanni Ledda, Giulia Costanzo, Giada Sambugaro, Cristiano Caruso, Martina Bullita, Maria Luisa Di Martino, Paolo Serra, Davide Firinu and Stefano Del Giacco
Life 2023, 13(9), 1884; https://doi.org/10.3390/life13091884 - 8 Sep 2023
Cited by 1 | Viewed by 2344
Abstract
Background: Asthma is a clinical syndrome characterized by recurrent episodes of airway obstruction, bronchial hyperresponsiveness and airway inflammation. Most patients with asthma present a “type 2” (TH2) inflammation. ILC2 and TH2 cells release cytokines IL4, IL-13 and IL-5. CRSwNP is a condition characterized [...] Read more.
Background: Asthma is a clinical syndrome characterized by recurrent episodes of airway obstruction, bronchial hyperresponsiveness and airway inflammation. Most patients with asthma present a “type 2” (TH2) inflammation. ILC2 and TH2 cells release cytokines IL4, IL-13 and IL-5. CRSwNP is a condition characterized by hyposmia or anosmia, nasal congestion, nasal discharge, and face pain or pressure that last for at least 12 weeks in a row without relief. Both asthma and CRSwNP are often characterized by a type 2 inflammation endotype and are often present in the same patient. Dupilumab is a fully human monoclonal antibody targeting the interleukin-4 receptor α (IL-4Rα) subunit, blocking IL4/IL-4Rα binding and IL13. It has been labelled for the treatment of moderate to severe asthma in patients from the age of 12 years with an eosinophilic phenotype, and it has demonstrated efficacy and acceptable safety. Our study aims to investigate the effects of dupilumab on type 2 inflammatory biomarkers, such as eosinophils and eosinophil cationic protein (ECP). ECP is an eosinophil-derived substance contained in granules that are released during inflammation and causes various biological effects, including tissue damage in asthmatic airways. Methods: ECP, Eosinophil counts (EOS), and total immunoglobulin E (IgE) levels were longitudinally measured using immunoassays in the serum of 21 patients affected by CRSwNP, of which 17 had asthma as a comorbidity, receiving 300 mg dupilumab every two weeks. Results: The EOS and ECP, after a first phase of significant increase due to the intrinsic characteristic of the block of IL-4 and IL-13, returned to the baseline 10 months after the initial administration of dupilumab. Fractional exhaled nitric oxide (FeNO) and serum total IgE decreased significantly after 9 months. Asthma Control Test (ACT) scores improved after dupilumab treatment. FEV1% and FEV1 absolute registered a significant improvement at 10 months. Conclusions: Patients who received 300 milligrams of dupilumab every two weeks first experienced a temporary increase in eosinophils (EOS) and eosinophil cationic protein (ECP), then exhibited a gradual decline in these variables with a subsequent return to the initial baseline levels. When compared to the baseline, we observed that the levels of IgE and FeNO decreased over time, while there was an increase in both FEV1 and FEV1%. Full article
(This article belongs to the Special Issue Advances in Theranostic Biomarkers in Lung Diseases)
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9 pages, 498 KiB  
Article
Using Machine Learning to Detect Theranostic Biomarkers Predicting Respiratory Treatment Response
by Vasilis Nikolaou, Sebastiano Massaro, Masoud Fakhimi and Wolfgang Garn
Life 2022, 12(6), 775; https://doi.org/10.3390/life12060775 - 24 May 2022
Cited by 2 | Viewed by 2036
Abstract
Background: Theranostic approaches—the use of diagnostics for developing targeted therapies—are gaining popularity in the field of precision medicine. They are predominately used in cancer research, whereas there is little evidence of their use in respiratory medicine. This study aims to detect theranostic biomarkers [...] Read more.
Background: Theranostic approaches—the use of diagnostics for developing targeted therapies—are gaining popularity in the field of precision medicine. They are predominately used in cancer research, whereas there is little evidence of their use in respiratory medicine. This study aims to detect theranostic biomarkers associated with respiratory-treatment responses. This will advance theory and practice on the use of biomarkers in the diagnosis of respiratory diseases and contribute to developing targeted treatments. Methods: We performed a cross-sectional analysis on a sample of 13,102 adults from the UK household longitudinal study ‘Understanding Society’. We used recursive feature selection to identify 16 biomarkers associated with respiratory treatment responses. We then implemented several machine learning algorithms using the identified biomarkers as well as age, sex, body mass index, and lung function to predict treatment response. Results: Our analysis shows that subjects with increased levels of alkaline phosphatase, glycated haemoglobin, high-density lipoprotein cholesterol, c-reactive protein, triglycerides, hemoglobin, and Clauss fibrinogen are more likely to receive respiratory treatments, adjusting for age, sex, body mass index, and lung function. Conclusions: These findings offer a valuable blueprint on why and how the use of biomarkers as diagnostic tools can prove beneficial in guiding treatment management in respiratory diseases. Full article
(This article belongs to the Special Issue Advances in Theranostic Biomarkers in Lung Diseases)
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Review

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32 pages, 957 KiB  
Review
Diagnosis of Fibrotic Hypersensitivity Pneumonitis: Is There a Role for Biomarkers?
by João O. Pereira, Vânia Fernandes, Tiago M. Alfaro, Sara Freitas and Carlos Robalo Cordeiro
Life 2023, 13(2), 565; https://doi.org/10.3390/life13020565 - 17 Feb 2023
Cited by 4 | Viewed by 3610
Abstract
Hypersensitivity pneumonitis is a complex interstitial lung syndrome and is associated with significant morbimortality, particularly for fibrotic disease. This condition is characterized by sensitization to a specific antigen, whose early identification is associated with improved outcomes. Biomarkers measure objectively biologic processes and may [...] Read more.
Hypersensitivity pneumonitis is a complex interstitial lung syndrome and is associated with significant morbimortality, particularly for fibrotic disease. This condition is characterized by sensitization to a specific antigen, whose early identification is associated with improved outcomes. Biomarkers measure objectively biologic processes and may support clinical decisions. These tools evolved to play a crucial role in the diagnosis and management of a wide range of human diseases. This is not the case, however, with hypersensitivity pneumonitis, where there is still great room for research in the path to find consensual diagnostic biomarkers. Gaps in the current evidence include lack of validation, validation against healthy controls alone, small sampling and heterogeneity in diagnostic and classification criteria. Furthermore, discriminatory accuracy is currently limited by overlapping mechanisms of inflammation, damage and fibrogenesis between ILDs. Still, biomarkers such as BAL lymphocyte counts and specific serum IgGs made their way into clinical guidelines, while others including KL-6, SP-D, YKL-40 and apolipoproteins have shown promising results in leading centers and have potential to translate into daily practice. As research proceeds, it is expected that the emergence of novel categories of biomarkers will offer new and thriving tools that could complement those currently available. Full article
(This article belongs to the Special Issue Advances in Theranostic Biomarkers in Lung Diseases)
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Other

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12 pages, 639 KiB  
Systematic Review
Extracellular Vesicles in Pulmonary Fibrosis Models and Biological Fluids of Interstitial Lung Disease Patients: A Scoping Review
by Miriana d’Alessandro, Laura Bergantini, Elena Bargagli and Silvia Vidal
Life 2021, 11(12), 1401; https://doi.org/10.3390/life11121401 - 15 Dec 2021
Cited by 7 | Viewed by 3607
Abstract
Introduction: Interstitial lung diseases (ILDs) are a heterogeneous group of diffuse parenchymal lung disorders characterized by the pathogenetic involvement of interstitium. Therefore, an elucidation of the etiology and pathogenesis as well as the identification of diagnostic and prognostic biomarkers of such diseases is [...] Read more.
Introduction: Interstitial lung diseases (ILDs) are a heterogeneous group of diffuse parenchymal lung disorders characterized by the pathogenetic involvement of interstitium. Therefore, an elucidation of the etiology and pathogenesis as well as the identification of diagnostic and prognostic biomarkers of such diseases is more compelling than ever. It is of note that there is increasing evidence of the involvement of extracellular vesicles (EVs) in the pathogenesis of lung diseases including lung cancer, chronic obstructive pulmonary disease and pulmonary fibrosis. It has been speculated that EVs play a pivotal role as mediators of intercellular communication, as well as the highlighting of the role of EVs as co-operators in the development of lung diseases such as IPF. Methods: The present study aimed to carry out a systematic exploratory search of the literature (through the scoping review approach) to identify and systematize the main results of the pathogenetic role of EVs in pulmonary fibrosis models and biological fluids from ILD patients, including plasma, bronchoalveolar lavage (BAL) and sputum. Conclusion: Fibroblast-to-mesenchymal differentiation, collagen and extracellular matrix deposition are key mechanisms in the development and progression of IPF. EV-coupled miRNA are important modulators of biological processes in terms of intercellular communication as shown in pulmonary fibrosis models as well as biofluids. The helpfulness of EVs as diagnostic and theranostic markers is worth further investigation. The evolving potential of EVs to translate effective EV-based therapies into clinical practice is of growing interest, due to the urgent need for novel therapeutic strategies for IPF patients. Full article
(This article belongs to the Special Issue Advances in Theranostic Biomarkers in Lung Diseases)
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15 pages, 267 KiB  
Systematic Review
Molecular Targets for Biological Therapies of Severe Asthma: Focus on Benralizumab and Tezepelumab
by Shih-Lung Cheng
Life 2021, 11(8), 744; https://doi.org/10.3390/life11080744 - 26 Jul 2021
Cited by 6 | Viewed by 3553
Abstract
Asthma is a heterogeneous respiratory disease characterized by usually reversible bronchial obstruction, which is clinically expressed by different phenotypes driven by complex pathobiological mechanisms (endotypes). In recent years several molecular effectors and signaling pathways have emerged as suitable targets for biological therapies of [...] Read more.
Asthma is a heterogeneous respiratory disease characterized by usually reversible bronchial obstruction, which is clinically expressed by different phenotypes driven by complex pathobiological mechanisms (endotypes). In recent years several molecular effectors and signaling pathways have emerged as suitable targets for biological therapies of severe asthma, refractory to standard treatments. Indeed, various therapeutic mono-clonal antibodies currently allow one to intercept at different levels the chain of pathogenic events leading to type 2 (T2) airway inflammation. Pro-allergic immunoglobulin E (IgE) is the first molecule against which an anti-asthma monoclonal antibody (omalizumab) was developed; today other targets are successfully being exploited by biological treatments for severe asthma. In particular, pro-eosinophilic interleukin 5 (IL-5) can be targeted by mepolizumab or reslizumab, whereas benralizumab is a selective blocker of IL-5 receptor, and IL-4 and IL-13 can be targeted by dupilumab. Besides these drugs, which are already available in medical practice, other biologics are under clinical development such as those targeting innate cytokines, including the alarmin thymic stromal lymphopoietin (TSLP), which plays a key role in the pathogenesis of type 2 asthma. Therefore, ongoing and future biological therapies are significantly changing severe asthma management on a global level. These new therapeutic options make it possible to implement phenotype/endotype-specific treatments, which are delineating personalized approaches precisely addressing the individual traits of asthma pathobiology. The aim of the study is to review the immunopathology and treatment efficacy for severe asthma and focused on new biological agents with benralizumab (anti-IL-5) and tezepelumab (anti-TSLP). Full article
(This article belongs to the Special Issue Advances in Theranostic Biomarkers in Lung Diseases)
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