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Biomarkers and Diagnostics in Respiratory Diseases
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Biomarkers and Diagnostics in Respiratory Diseases

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Pulmonology".

Deadline for manuscript submissions: closed (30 June 2024) | Viewed by 8709

Special Issue Editors

Dr. Silvano Dragonieri

E-Mail Website
Guest Editor
Respiratory Diseases, University of Bari, Piazza Giulio Cesare 11, 70121 Bari, Italy
Interests: obstructive lung diseases; airway obstruction; chronic obstructive pulmonary disease (COPD); obstructive sleep apnea; pulmonary medicine; respiration disorders; spirometry; allergic asthma; asthma; allergic diseases
Special Issues, Collections and Topics in MDPI journals
Dr. Andras Bikov

E-Mail Website
Guest Editor
1. Division of Infection, Immunity & Respiratory Medicine, Faculty of Biology, Medicine and Health, School of Biological Sciences, The University of Manchester, Manchester, UK
2. North West Lung Centre, Manchester University NHS Foundation Trust, Manchester, UK
Interests: respiratory physiology; respiratory mechanics; asthma; lung; pulmonary medicine; airway obstruction; chronic obstructive pulmonary disease; OSA; pulmonary function test; pneumology; sputum; respiratory immunology; exhaled biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Recent progresses in scientific knowledge have made new diagnostic biomarkers available. This could pave the way for ground-breaking therapeutic and diagnostic tools, which might improve and ease the management of respiratory diseases.

In this Special Issue, we pursue original research studies and reviews that advance the knowledge of clinicians on diagnostic biomarkers for any respiratory disease.

Furthermore, we are particularly interested in studies about novel non-invasive diagnostic biomarkers, e.g., in exhaled breath and/or in sputum. In addition, aspirant authors are encouraged to submit the results of human studies and clinical trials.

Dr. Silvano Dragonieri
Dr. Andras Bikov
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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-blind 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.

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.

Keywords

  • bespiratory diseases
  • biomarkers
  • non-invasive approaches
  • novel diagnostic tests

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Published Papers (6 papers)

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Editorial

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2 pages, 152 KiB  
Editorial
Innovating Respiratory Diagnostics: The Game-Changing Role of Biomarkers
by Silvano Dragonieri and Andras Bikov
J. Clin. Med. 2024, 13(19), 5850; https://doi.org/10.3390/jcm13195850 - 30 Sep 2024
Viewed by 409
Abstract
The field of respiratory disease diagnostics has been propelled forward by recent innovations in biomarker research [...] Full article
(This article belongs to the Special Issue Biomarkers and Diagnostics in Respiratory Diseases)

Research

Jump to: Editorial

16 pages, 1449 KiB  
Article
Eosinophilic Bronchiectasis: Prevalence, Severity, and Associated Features—A Cohort Study
by Raffaele Campisi, Santi Nolasco, Manuel Mancuso, Miriam Spinella, Fabio Vignera, Nunzio Crimi, Carlo Vancheri and Claudia Crimi
J. Clin. Med. 2024, 13(16), 4932; https://doi.org/10.3390/jcm13164932 - 21 Aug 2024
Cited by 1 | Viewed by 852
Abstract
Background: Bronchiectasis (BE) has been traditionally associated with neutrophilic inflammation, but eosinophilic bronchiectasis (EB) has recently emerged. Data about prevalence, clinical features, and disease severity are lacking. This study aimed to assess the EB prevalence, compare EB with non-EB, evaluate the Type-2 (T2) [...] Read more.
Background: Bronchiectasis (BE) has been traditionally associated with neutrophilic inflammation, but eosinophilic bronchiectasis (EB) has recently emerged. Data about prevalence, clinical features, and disease severity are lacking. This study aimed to assess the EB prevalence, compare EB with non-EB, evaluate the Type-2 (T2) high endotype in BE (T2-high EB) versus non-T2-high EB, and identify EB predictors. Methods: We conducted a prospective study involving 153 BE patients. The data collected included clinical, radiological, and microbiological findings. BE severity was assessed using the bronchiectasis severity index (BSI), FACED and E-FACED scores, and the bronchiectasis etiology and comorbidity index (BACI). EB was defined as a blood eosinophil count (BEC) ≥ 300 cells/μL, and T2-high EB as BEC ≥ 300 cells/μL with fractional exhaled nitric oxide (FeNO) ≥ 25 ppb. Results: Prevalence was 27% for EB and 20% for T2-high EB. EB patients exhibited poorer lung function and more severe radiologic features, with significantly higher severity scores [BSI, FACED, E-FACED, BACI (p < 0.05)], and a higher median exacerbation rate [4 (2–5) in EB vs. 2 (1–4) in non-EB, p = 0.0002], compared with non-EB patients. T2-high EB patients showed higher severity scores [BSI, FACED, E-FACED (p < 0.05)], as well as worse lung function parameters [FEV1%, FVC%, FEF 25–75% (p < 0.05)] compared with non-T2-high EB patients. In our study, patients with EB exhibited notably worsened lung function and higher BE severity scores compared with their non-EB counterparts, with exacerbations playing a major role in these differences. We found statistically significant positive correlations between BEC and disease severity scores, such as BSI, FACED, and mMRC, as well as an inverse relationship with pulmonary function. The likelihood of EB being present was significantly higher in association with mMRC ≥ 1 (OR = 2.53; 95% CI, 1.26–5.64), exacerbations/year ≥ 1 (OR = 1.27; 95% CI, 1.0–1.63), and chronic PA colonization (OR = 3.9; 95% CI, 1.08–15.8). Conclusions: EB is a distinct endotype. Dyspnea, exacerbations, and PA colonization may be predictive of EB, emphasizing the importance of early detection for improved outcomes. BEC could serve as a useful biomarker of disease severity to consider when diagnosing EB. Full article
(This article belongs to the Special Issue Biomarkers and Diagnostics in Respiratory Diseases)
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13 pages, 2641 KiB  
Article
Managing Small Airway Disease in Patients with Severe Asthma: Transitioning from the “Silent Zone” to Achieving “Quiet Asthma”
by Giovanna Elisiana Carpagnano, Andrea Portacci, Silvano Dragonieri, Francesca Montagnolo, Ilaria Iorillo, Ernesto Lulaj, Leonardo Maselli, Enrico Buonamico and Vitaliano Nicola Quaranta
J. Clin. Med. 2024, 13(8), 2320; https://doi.org/10.3390/jcm13082320 - 17 Apr 2024
Cited by 2 | Viewed by 1784
Abstract
Background/Objectives: Several studies have demonstrated the positive clinical and functional impact of adding Long-Acting Muscarinic Antagonist (LAMA) to Inhaled Corticosteroids (ICS) and Long-Acting Beta-Agonists (LABA) therapy in the treatment of severe asthma. Aim and objectives: To demonstrate that treating Small Airways Disease (SAD) [...] Read more.
Background/Objectives: Several studies have demonstrated the positive clinical and functional impact of adding Long-Acting Muscarinic Antagonist (LAMA) to Inhaled Corticosteroids (ICS) and Long-Acting Beta-Agonists (LABA) therapy in the treatment of severe asthma. Aim and objectives: To demonstrate that treating Small Airways Disease (SAD) in severe asthma patients who are candidates for biologics can improve respiratory symptoms, lung function, and airways inflammation, potentially avoiding or delaying the use of biological therapy. Methods: Thirty-two severe asthma patients with SAD were transitioned from separate inhalers for ICS/LABA and LAMA to extrafine single-inhaler beclomethasone, formoterol, and glycopyrronium. None of these patients underwent biological therapy before the study. Follow-up evaluations were conducted at baseline (T0) and three months after initiation (T3). Assessments included clinical evaluations, spirometry, oscillometry, and inflammation markers. Results: Transitioning to single-inhaler triple therapy from T0 to T3 resulted in significant improvements in Asthma Control Test (ACT) and SAD parameters, including increased Forced Expiratory Volume in the mid-range of lung capacity and improved airway resistance and reactance measurements using impulse oscillometry. A significant reduction in airway inflammation was evidenced by lower levels of Fractional Exhaled Nitric Oxide 350 (FeNO 350) (p < 0.001 for all). Conclusions: Adopting a single-inhaler triple therapy notably enhanced clinical control and small airway function in patients with severe asthma and SAD, supporting the positive impact of target-therapy for the achievement of a stable state termed “Quiet Asthma”. Full article
(This article belongs to the Special Issue Biomarkers and Diagnostics in Respiratory Diseases)
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12 pages, 1151 KiB  
Article
A Serological Neoepitope Biomarker of Neutrophil Elastase-Degraded Calprotectin, Associated with Neutrophil Activity, Identifies Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease More Effectively Than Total Calprotectin
by Annika Hummersgaard Hansen, Joachim Høg Mortensen, Sarah Rank Rønnow, Morten Asser Karsdal, Diana Julie Leeming and Jannie Marie Bülow Sand
J. Clin. Med. 2023, 12(24), 7589; https://doi.org/10.3390/jcm12247589 - 8 Dec 2023
Cited by 1 | Viewed by 1472
Abstract
Neutrophil activation can release neutrophil extracellular traps (NETs) in acute inflammation. NETs result in the release of human neutrophil elastase (HNE) and calprotectin, where the former can degrade the latter and generate protein fragments associated with neutrophil activity. We investigated this in chronic [...] Read more.
Neutrophil activation can release neutrophil extracellular traps (NETs) in acute inflammation. NETs result in the release of human neutrophil elastase (HNE) and calprotectin, where the former can degrade the latter and generate protein fragments associated with neutrophil activity. We investigated this in chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) using the novel neoepitope biomarker CPa9-HNE, quantifying a specific HNE-mediated fragment of calprotectin in serum. CPa9-HNE was compared to total calprotectin. Initially, CPa9-HNE was measured in healthy (n = 39), COPD (n = 67), and IPF (n = 16) serum using a neoepitope-specific competitive enzyme-linked immunosorbent assay. Then, a head-to-head comparison of CPa9-HNE and total calprotectin, a non-neoepitope, was conducted in healthy (n = 19), COPD (n = 25), and IPF (n = 19) participants. CPa9-HNE levels were significantly increased in COPD (p < 0.0001) and IPF subjects (p = 0.0001) when compared to healthy participants. Additionally, CPa9-HNE distinguished IPF (p < 0.0001) and COPD (p < 0.0001) from healthy participants more effectively than total calprotectin for IPF (p = 0.0051) and COPD (p = 0.0069). Here, CPa9-HNE also distinguished IPF from COPD (p = 0.045) participants, which was not observed for total calprotectin (p = 0.98). Neutrophil activity was significantly higher, as assessed via serum CPa9-HNE, for COPD and IPF compared to healthy participants. Additionally, CPa9-HNE exceeded the ability of non-neoepitope calprotectin serum measurements to separate healthy from lung disease and even COPD from IPF participants, indicating that neutrophil activity is essential for both COPD and IPF. Full article
(This article belongs to the Special Issue Biomarkers and Diagnostics in Respiratory Diseases)
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13 pages, 925 KiB  
Article
Biomarkers of the L-Arginine/Dimethylarginine/Nitric Oxide Pathway in People with Chronic Airflow Obstruction and Obstructive Sleep Apnoea
by Juliane Hannemann, Elin H. Thorarinnsdottir, André F. S. Amaral, Edzard Schwedhelm, Lena Schmidt-Hutten, Heike Stang, Bryndis Benediktsdottir, Ingibjörg Gunnarsdóttir, Thórarinn Gislason and Rainer Böger
J. Clin. Med. 2023, 12(16), 5230; https://doi.org/10.3390/jcm12165230 - 11 Aug 2023
Cited by 2 | Viewed by 1648
Abstract
Background: Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) are common chronic diseases that are associated with chronic and intermittent hypoxemia, respectively. Patients affected by the overlap of COPD and OSA have a particularly unfavourable prognosis. The L-arginine/nitric oxide (NO) pathway [...] Read more.
Background: Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) are common chronic diseases that are associated with chronic and intermittent hypoxemia, respectively. Patients affected by the overlap of COPD and OSA have a particularly unfavourable prognosis. The L-arginine/nitric oxide (NO) pathway plays an important role in regulating pulmonary vascular function. Asymmetric (ADMA) and symmetric dimethylarginine (SDMA) interfere with NO production. Methods: We analysed the serum concentrations of ADMA, SDMA, L-arginine, L-citrulline, and L-ornithine in a large sample of the Icelandic general population together with chronic airflow obstruction (CAO), a key physiological marker of COPD that was assessed by post-bronchodilator spirometry (FEV1/FVC < LLN). OSA risk was determined by the multivariable apnoea prediction (MAP) index. Results: 713 individuals were analysed, of whom 78 (10.9%) showed CAO and 215 (30%) had MAP > 0.5. SDMA was significantly higher in individuals with CAO (0.518 [0.461–0.616] vs. 0.494 [0.441–0.565] µmol/L; p = 0.005), but ADMA was not. However, ADMA was significantly associated with decreasing FEV1 percent predicted among those with CAO (p = 0.002). ADMA was 0.50 (0.44–0.56) µmol/L in MAP ≤ 0.5 versus 0.52 (0.46–0.58) µmol/L in MAP > 0.5 (p = 0.008). SDMA was 0.49 (0.44–0.56) µmol/L versus 0.51 (0.46–0.60) µmol/L, respectively (p = 0.004). The highest values for ADMA and SDMA were observed in individuals with overlap of CAO and MAP > 0.5, which was accompanied by lower L-citrulline levels. Conclusions: The plasma concentrations of ADMA and SDMA are elevated in COPD patients with concomitant intermittent hypoxaemia. This may account for impaired pulmonary NO production, enhanced pulmonary vasoconstriction, and disease progression. Full article
(This article belongs to the Special Issue Biomarkers and Diagnostics in Respiratory Diseases)
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12 pages, 605 KiB  
Article
Calcium, Phosphate, and Vitamin D Status in Patients with Sarcoidosis—Associations with Disease Activity and Symptoms
by Łukasz Gwadera, Adam J. Białas, Anna Kumor-Kisielewska, Joanna Miłkowska-Dymanowska, Sebastian Majewski and Wojciech J. Piotrowski
J. Clin. Med. 2023, 12(14), 4745; https://doi.org/10.3390/jcm12144745 - 18 Jul 2023
Cited by 3 | Viewed by 1990
Abstract
Sarcoidosis is a systemic granulomatous disease with a variety of presentations. One of the known symptoms are altered vitamin D metabolism and hypercalcemia. In our study, we aimed to assess associations between disease activity, inflammatory parameters, and vitamin D and calcium status. The [...] Read more.
Sarcoidosis is a systemic granulomatous disease with a variety of presentations. One of the known symptoms are altered vitamin D metabolism and hypercalcemia. In our study, we aimed to assess associations between disease activity, inflammatory parameters, and vitamin D and calcium status. The secondary aim was to find any dependencies between calcium and vitamin D metabolism and fatigue and quality of life in patients with sarcoidosis. We enrolled 58 patients with sarcoidosis (47 classified as active disease, 11 classified as non-active) and compared them with 25 healthy volunteers. Calcium concentration was significantly higher in the study group than in healthy controls. It correlated with some inflammatory markers but not with vitamin D status. Not calcium nor vitamin D, but phosphate concentration correlated with life quality was assessed with the use of the Sarcoidosis Health Questionnaire. An association between phosphate concentration and fatigue was also noted, but it did not reach statistical significance. Calcium concentration was higher in patients with sarcoidosis, but it was not an indicator of the disease activity, while phosphate concentration was significantly lower in patients with active sarcoidosis. Full article
(This article belongs to the Special Issue Biomarkers and Diagnostics in Respiratory Diseases)
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