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Article ; Online: Phenotype overlap in the natural history of asthma.

Ricciardolo, Fabio L M / Guida, Giuseppe / Bertolini, Francesca / Di Stefano, Antonino / Carriero, Vitina

European respiratory review : an official journal of the European Respiratory Society

2023 Volume 32, Issue 168

Abstract: The heterogeneity of asthma makes it challenging to unravel the pathophysiologic mechanisms of the disease. Despite the wealth of research identifying diverse phenotypes, many gaps still remain in our knowledge of the disease's complexity. A crucial ... ...

Abstract	The heterogeneity of asthma makes it challenging to unravel the pathophysiologic mechanisms of the disease. Despite the wealth of research identifying diverse phenotypes, many gaps still remain in our knowledge of the disease's complexity. A crucial aspect is the impact of airborne factors over a lifetime, which often results in a complex overlap of phenotypes associated with type 2 (T2), non-T2 and mixed inflammation. Evidence now shows overlaps between the phenotypes associated with T2, non-T2 and mixed T2/non-T2 inflammation. These interconnections could be induced by different determinants such as recurrent infections, environmental factors, T-helper plasticity and comorbidities, collectively resulting in a complex network of distinct pathways generally considered as mutually exclusive. In this scenario, we need to abandon the concept of asthma as a disease characterised by distinct traits grouped into static segregated categories. It is now evident that there are multiple interplays between the various physiologic, cellular and molecular features of asthma, and the overlap of phenotypes cannot be ignored.
MeSH term(s)	Humans ; Asthma/diagnosis ; Asthma/genetics ; Phenotype ; Comorbidity ; Inflammation
Language	English
Publishing date	2023-05-17
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1077620-5
ISSN	1600-0617 ; 0905-9180
ISSN (online)	1600-0617
ISSN	0905-9180
DOI	10.1183/16000617.0201-2022
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Article: Which Therapy for Non-Type(T)2/T2-Low Asthma.

Ricciardolo, Fabio L M / Carriero, Vitina / Bertolini, Francesca

Journal of personalized medicine

2021 Volume 12, Issue 1

Abstract: Currently, the asthmatic population is divided into Type 2-high and non-Type 2/Type 2-low asthmatics, with 50% of patients belonging to one of the two groups. Differently from T2-high, T2-low asthma has not been clearly defined yet, and the T2-low ... ...

Abstract	Currently, the asthmatic population is divided into Type 2-high and non-Type 2/Type 2-low asthmatics, with 50% of patients belonging to one of the two groups. Differently from T2-high, T2-low asthma has not been clearly defined yet, and the T2-low patients are identified on the basis of the absence or non-predominant expression of T2-high biomarkers. The information about the molecular mechanisms underpinning T2-low asthma is scarce, but researchers have recognized as T2-low endotypes type 1 and type 3 immune response, and remodeling events occurring without inflammatory processes. In addition, the lack of agreed biomarkers reprents a challenge for the research of an effective therapy. The first-choice medication is represented by inhaled corticosteroids despite a low efficacy is reported for/in T2-low patients. However, macrolides and long-acting anti-muscarinic drugs have been recognized as efficacious. In recent years, clinical trials targeting biomarkers playing key roles in T3 and T1 immune pathways, alarmins, and molecules involved in neutrophil recruitment have provided conflicting results probably misleading (or biased) in patients' selection. However, further studies are warranted to achieve a precise characterization of T2-low asthma with the aim of defining a tailored therapy for each single asthmatic patient.
Language	English
Publishing date	2021-12-23
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662248-8
ISSN	2075-4426
ISSN	2075-4426
DOI	10.3390/jpm12010010
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Article ; Online: MicroRNAs as Biomarkers in Corticosteroid-Resistant/Neutrophilic Asthma: Still a Long Way to Go!

Ricciardolo, Fabio L M / Carriero, Vitina / Bullone, Michela

American journal of respiratory and critical care medicine

2020 Volume 202, Issue 1, Page(s) 4–6

MeSH term(s)	Adrenal Cortex Hormones ; Asthma ; Biomarkers ; Humans ; Inflammation ; MicroRNAs ; Sputum
Chemical Substances	Adrenal Cortex Hormones ; Biomarkers ; MicroRNAs
Keywords	covid19
Language	English
Publishing date	2020-05-14
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.202004-1216ED
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Article ; Online: The Practical Role of FEF

Cirillo, Ignazio / Schiavetti, Irene / Ricciardolo, Fabio L M / Miraglia Del Giudice, Michele / Tosca, Maria Angela / Ciprandi, Giorgio

American journal of rhinology & allergy

2023 Volume 37, Issue 5, Page(s) 571–574

Abstract: Allergic rhinitis (AR) is a relevant risk factor asthma as it may frequently precede asthma onset. There is evidence that lung function may be early impaired in AR patients. In this regard, the forced expiratory flow at 25%-75% of vital capacity ( ... ...

Abstract	Allergic rhinitis (AR) is a relevant risk factor asthma as it may frequently precede asthma onset. There is evidence that lung function may be early impaired in AR patients. In this regard, the forced expiratory flow at 25%-75% of vital capacity (FEF
MeSH term(s)	Male ; Female ; Humans ; Adolescent ; Adult ; Cross-Sectional Studies ; Nitric Oxide ; Rhinitis, Allergic/diagnosis ; Rhinitis, Allergic/epidemiology ; Asthma/diagnosis ; Asthma/epidemiology ; Bronchial Hyperreactivity
Chemical Substances	Nitric Oxide (31C4KY9ESH)
Language	English
Publishing date	2023-06-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	2482804-X
ISSN	1945-8932 ; 1945-8924
ISSN (online)	1945-8932
ISSN	1945-8924
DOI	10.1177/19458924231182272
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Article ; Online: Revisiting the role of exhaled nitric oxide in asthma.

Ricciardolo, Fabio L M

Current opinion in pulmonary medicine

2014 Volume 20, Issue 1, Page(s) 53–59

Abstract: Purpose of review: This review focuses on the most recent studies investigating fractional nitric oxide concentration in exhaled breath (FeNO) as a useful biomarker for identifying specific phenotypes in asthma and as a tool for asthma diagnosis, ... ...

Abstract	Purpose of review: This review focuses on the most recent studies investigating fractional nitric oxide concentration in exhaled breath (FeNO) as a useful biomarker for identifying specific phenotypes in asthma and as a tool for asthma diagnosis, monitoring and clinical decision-making. Recent findings: On the basis of the current literature, it has been highlighted that FeNO is a clinically relevant marker in various clinical aspects of asthma: FeNO is a predictor for developing asthma in persistent rhinitis or in infants with respiratory symptoms; FeNO contributes to identification of asthma phenotypes in both children and adults, also in relation to severity; FeNO is useful in monitoring the effectiveness of inhaled corticosteroids (including compliance) and biologic treatments like omalizumab; FeNO, in conjunction with symptom registration and lung function measurements, contributes to asthma diagnosis and optimizes asthma management. Summary: FeNO provides further information in distinguishing different phenotypes in asthma, allowing a much more appropriate control of the disease, especially in patients with difficult/severe asthma. In the future, it would be interesting to shed light on the hidden biological mechanisms responsible for low or normal FeNO values in symptomatic asthmatic patients.
MeSH term(s)	Adrenal Cortex Hormones/therapeutic use ; Asthma/diagnosis ; Asthma/drug therapy ; Asthma/metabolism ; Biomarkers/metabolism ; Breath Tests ; Exhalation ; Humans ; Nitric Oxide/metabolism ; Phenotype ; Severity of Illness Index ; Treatment Outcome
Chemical Substances	Adrenal Cortex Hormones ; Biomarkers ; Nitric Oxide (31C4KY9ESH)
Language	English
Publishing date	2014-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1285505-4
ISSN	1531-6971 ; 1070-5287 ; 1078-1641
ISSN (online)	1531-6971
ISSN	1070-5287 ; 1078-1641
DOI	10.1097/MCP.0000000000000006
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Article ; Online: Oxidative and Nitrosative Stress in the Pathogenesis of Obstructive Lung Diseases of Increasing Severity.

Di Stefano, Antonino / Maniscalco, Mauro / Balbi, Bruno / Ricciardolo, Fabio L M

Current medicinal chemistry

2020 Volume 27, Issue 42, Page(s) 7149–7158

Abstract: The imbalance between increased oxidative agents and antioxidant defence mechanisms is central in the pathogenesis of obstructive lung diseases such as asthma and COPD. In these patients, there are increased levels of reactive oxygen species. Superoxide ... ...

Abstract	The imbalance between increased oxidative agents and antioxidant defence mechanisms is central in the pathogenesis of obstructive lung diseases such as asthma and COPD. In these patients, there are increased levels of reactive oxygen species. Superoxide anions (O
MeSH term(s)	Animals ; Antioxidants ; Humans ; Hydrogen Peroxide ; Nitrosative Stress ; Oxidation-Reduction ; Oxidative Stress ; Peroxidase/metabolism ; Pulmonary Disease, Chronic Obstructive/drug therapy
Chemical Substances	Antioxidants ; Hydrogen Peroxide (BBX060AN9V) ; Peroxidase (EC 1.11.1.7)
Language	English
Publishing date	2020-06-04
Publishing country	United Arab Emirates
Document type	Journal Article
ZDB-ID	1319315-6
ISSN	1875-533X ; 0929-8673
ISSN (online)	1875-533X
ISSN	0929-8673
DOI	10.2174/0929867327666200604165451
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Article ; Online: The impact of aging on outpatients with asthma in a real-world setting.

Ciprandi, Giorgio / Schiavetti, Irene / Ricciardolo, Fabio L M

Respiratory medicine

2018 Volume 136, Page(s) 58–64

Abstract: Background: Asthma is characterized by airway inflammation and bronchial hyperreactivity. It is conceived that aging may affect asthma characteristics, but this issue is still not completely clarified in clinical practice.: Objective: The present ... ...

Abstract	Background: Asthma is characterized by airway inflammation and bronchial hyperreactivity. It is conceived that aging may affect asthma characteristics, but this issue is still not completely clarified in clinical practice. Objective: The present study investigated whether aging may affect some clinical and functional factors in outpatients with asthma visited in a real-world setting, such as clinical practice. Methods: Globally, 391 outpatients (163 males, median age 47 years) with asthma were consecutively evaluated. The following parameters were assessed: history, including, smoking, comorbidity, and inhaled corticosteroids (ICS) use, physical examination, body mass index (BMI), lung function, level of asthma control, asthma control test (ACT), and fractional exhaled NO (FeNO). Results: The elderly with asthma had: more frequently not controlled asthma, higher BMI, higher ICS dosages, more impaired lung function, including plethysmographic parameters, than adult asthmatics (p < 0.001 for all, but p = 0.002 for RV and p = 0.008 for FRC). Elderly asthmatics were also less frequently allergic (p < 0.001) and had less rhinitis comorbidity (p < 0.001) and less nasal symptoms (p < 0.05) than younger asthmatics. Conclusions: The present study conducted in a real-world setting shows that aging significantly affects asthma, mainly concerning asthma control, lung function, and steroid-sensitivity.
MeSH term(s)	Administration, Inhalation ; Adolescent ; Adrenal Cortex Hormones/administration & dosage ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Ambulatory Care ; Asthma/physiopathology ; Asthma/prevention & control ; Body Mass Index ; Breath Tests ; Female ; Forced Expiratory Volume/physiology ; Humans ; Hypersensitivity/complications ; Hypersensitivity/physiopathology ; Male ; Middle Aged ; Nitric Oxide/metabolism ; Physical Examination ; Rhinitis/complications ; Rhinitis/physiopathology ; Smoking/adverse effects ; Smoking/physiopathology ; Vital Capacity/physiology ; Young Adult
Chemical Substances	Adrenal Cortex Hormones ; Nitric Oxide (31C4KY9ESH)
Language	English
Publishing date	2018-01-31
Publishing country	England
Document type	Journal Article ; Observational Study
ZDB-ID	1003348-8
ISSN	1532-3064 ; 0954-6111
ISSN (online)	1532-3064
ISSN	0954-6111
DOI	10.1016/j.rmed.2018.01.018
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Article ; Online: Exhaled nitric oxide in asthma: from diagnosis to management.

Guida, Giuseppe / Carriero, Vitina / Bertolini, Francesca / Pizzimenti, Stefano / Heffler, Enrico / Paoletti, Giovanni / Ricciardolo, Fabio L M

Current opinion in allergy and clinical immunology

2022 Volume 23, Issue 1, Page(s) 29–35

Abstract: Purpose of review: Exhaled nitric oxide (FENO) is a noninvasive marker of eosinophilic airway inflammation, therefore, highly informative in asthma. Although FENO measurement is a potentially accessible tool to many physicians, recommendations regarding ...

Abstract	Purpose of review: Exhaled nitric oxide (FENO) is a noninvasive marker of eosinophilic airway inflammation, therefore, highly informative in asthma. Although FENO measurement is a potentially accessible tool to many physicians, recommendations regarding its clinical utility in diagnosing or tailoring treatment have not reached the expected diffusion. More recently FENO emerged as a biomarker for type-2 asthma phenotyping and a predictor of response to biologics. Recent findings: The physiological discoveries and relevant acquisitions in clinical practice regarding FENO in asthma are presented. The FENO story draw a wavy path, characterized by promising findings, exciting confirmations and periods of low visibility. FENO emerged as a tool to increase the probability of asthma diagnosis. FENO predicts response to inhaled glucocorticoids (ICS), favoring the development of tailored treatment strategies and unrevealing nonadherence to ICS in difficult-to-treat or uncontrolled asthma. Finally, FENO was associated with a more severe phenotype and became a consolidated biomarker of type-2 inflammation. Summary: FENO demonstrated to be a noninvasive and very reproducible test, encompassing many applications in the field of asthma management. Its routinely use, according to international guidelines, may improve the quality of patient assistance, from difficult-to-treat cases to biologic monitoring.
MeSH term(s)	Humans ; Nitric Oxide ; Breath Tests ; Asthma/diagnosis ; Asthma/drug therapy ; Glucocorticoids/therapeutic use ; Biomarkers ; Exhalation
Chemical Substances	Nitric Oxide (31C4KY9ESH) ; Glucocorticoids ; Biomarkers
Language	English
Publishing date	2022-11-24
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	2088710-3
ISSN	1473-6322 ; 1528-4050
ISSN (online)	1473-6322
ISSN	1528-4050
DOI	10.1097/ACI.0000000000000877
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Article ; Online: Perspectives on exhaled nitric oxide.

Ricciardolo, Fabio L M / Silkoff, Philip E

Journal of breath research

2017 Volume 11, Issue 4, Page(s) 47104

Abstract: The history of nitric oxide (NO) in the respiratory field dates back to the beginning of the 1990s with the pioneering study by Lars Gustafsson et al describing the presence of endogenous NO in the exhaled breath of human beings. Soon after, independent ... ...

Abstract	The history of nitric oxide (NO) in the respiratory field dates back to the beginning of the 1990s with the pioneering study by Lars Gustafsson et al describing the presence of endogenous NO in the exhaled breath of human beings. Soon after, independent studies showed that exhaled NO concentrations (F
Language	English
Publishing date	2017-09-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2381007-5
ISSN	1752-7163 ; 1752-7155
ISSN (online)	1752-7163
ISSN	1752-7155
DOI	10.1088/1752-7163/aa7f0e
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Article: Bone Morphogenic Proteins and Their Antagonists in the Lower Airways of Stable COPD Patients.

Di Stefano, Antonino / Rosani, Umberto / Levra, Stefano / Gnemmi, Isabella / Brun, Paola / Maniscalco, Mauro / D'Anna, Silvestro Ennio / Carriero, Vitina / Bertolini, Francesca / Ricciardolo, Fabio L M

Biology

2023 Volume 12, Issue 10

Abstract: Background: Bone morphogenic proteins (BMPs) and their antagonists are involved in the tissue development and homeostasis of various organs.: Objective: To determine transcriptomic and protein expression of BMPs and their antagonists in stable COPD.!# ...

Abstract	Background: Bone morphogenic proteins (BMPs) and their antagonists are involved in the tissue development and homeostasis of various organs. Objective: To determine transcriptomic and protein expression of BMPs and their antagonists in stable COPD. Methods: We measured the expression and localization of BMPs and some relevant antagonists in bronchial biopsies of stable mild/moderate COPD (MCOPD) (n = 18), severe/very severe COPD (SCOPD) (n = 16), control smokers (CS) (n = 13), and control non-smokers (CNS) (n = 11), and in lung parenchyma of MCOPD (n = 9), CS (n = 11), and CNS (n = 9) using immunohistochemistry and transcriptome analysis, in vitro after the stimulation of the 16HBE cells. Results: In bronchial biopsies, BMP4 antagonists CRIM1 and chordin were increased in the bronchial epithelium and lamina propria of COPD patients. BMP4 expression was decreased in the bronchial epithelium of SCOPD and MCOPD compared to CNS. Lung transcriptomic data showed non-significant changes between groups. CRIM1 and chordin were significantly decreased in the alveolar macrophages and alveolar septa in COPD patients. External 16HBE treatment with BMP4 protein reduced the bronchial epithelial cell proliferation. Conclusions: These data show an imbalance between BMP proteins and their antagonists in the lungs of stable COPD. This imbalance may play a role in the remodeling of the airways, altering the regenerative-reparative responses of the diseased bronchioles and lung parenchyma.
Language	English
Publishing date	2023-10-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology12101304
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