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Article ; Online: Machine Learning Approaches to Predict Asthma Exacerbations: A Narrative Review.

Molfino, Nestor A / Turcatel, Gianluca / Riskin, Daniel

2023 Volume 41, Issue 2, Page(s) 534–552

Abstract: The implementation of artificial intelligence (AI) and machine learning (ML) techniques in healthcare has garnered significant attention in recent years, especially as a result of their potential to revolutionize personalized medicine. Despite advances ... ...

Abstract	The implementation of artificial intelligence (AI) and machine learning (ML) techniques in healthcare has garnered significant attention in recent years, especially as a result of their potential to revolutionize personalized medicine. Despite advances in the treatment and management of asthma, a significant proportion of patients continue to suffer acute exacerbations, irrespective of disease severity and therapeutic regimen. The situation is further complicated by the constellation of factors that influence disease activity in a patient with asthma, such as medical history, biomarker phenotype, pulmonary function, level of healthcare access, treatment compliance, comorbidities, personal habits, and environmental conditions. A growing body of work has demonstrated the potential for AI and ML to accurately predict asthma exacerbations while also capturing the entirety of the patient experience. However, application in the clinical setting remains mostly unexplored, and important questions on the strengths and limitations of this technology remain. This review presents an overview of the rapidly evolving landscape of AI and ML integration into asthma management by providing a snapshot of the existing scientific evidence and proposing potential avenues for future applications.
MeSH term(s)	Humans ; Artificial Intelligence ; Machine Learning ; Asthma/diagnosis ; Asthma/drug therapy ; Precision Medicine ; Patient Acuity
Language	English
Publishing date	2023-12-19
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	632651-1
ISSN	1865-8652 ; 0741-238X
ISSN (online)	1865-8652
ISSN	0741-238X
DOI	10.1007/s12325-023-02743-3
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Article ; Online: Toward a Predict and Prevent Approach in Obstructive Airway Diseases.

Couillard, Simon / Petousi, Nayia / Smigiel, Kate S / Molfino, Nestor A

The journal of allergy and clinical immunology. In practice

2023 Volume 11, Issue 3, Page(s) 704–712

Abstract: Asthma and chronic obstructive pulmonary disease are currently diagnosed and treated after the demonstration of variable airflow limitation and symptoms. Under this framework, undiagnosed and unchecked airway inflammation is associated with recurrent ... ...

Abstract	Asthma and chronic obstructive pulmonary disease are currently diagnosed and treated after the demonstration of variable airflow limitation and symptoms. Under this framework, undiagnosed and unchecked airway inflammation is associated with recurrent acute attacks, airway remodeling, airflow limitation, adverse effects of corticosteroids, and impaired quality of life, ultimately leading to the collection of side effects termed "people remodeling." This one-size-fits-all damage control approach aims to control symptoms and treat exacerbations rather than modify the underlying disease process. The advent of highly effective therapies targeting proximal drivers of airway inflammation calls for a paradigm shift; upstream-acting therapies offer potential to alter the disease course and achieve clinical remission. We propose moving away from downstream firefighting and toward a "predict and prevent" model, measuring inflammation and providing anti-inflammatory therapy early, without waiting for further clinical deterioration. Much in the same way that high blood pressure and cholesterol are used to predict and prevent heart attacks, in asthma, elevated blood eosinophils and/or exhaled nitric oxide can be used to predict and prevent asthma attacks. We also advocate moving research further upstream by identifying patients with subclinical airway inflammation or disease who may be at risk of progressing to airflow limitation and associated morbidities and intervening early to prevent them. In summary, we call for a predict and prevent approach in obstructive airway disease.
MeSH term(s)	Humans ; Quality of Life ; Asthma/diagnosis ; Asthma/drug therapy ; Asthma/prevention & control ; Pulmonary Disease, Chronic Obstructive/diagnosis ; Pulmonary Disease, Chronic Obstructive/drug therapy ; Lung ; Nitric Oxide ; Eosinophils ; Inflammation/diagnosis
Chemical Substances	Nitric Oxide (31C4KY9ESH)
Language	English
Publishing date	2023-01-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2843237-X
ISSN	2213-2201 ; 2213-2198
ISSN (online)	2213-2201
ISSN	2213-2198
DOI	10.1016/j.jaip.2023.01.008
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Article: Targeting TSLP in Asthma.

Parnes, Jane R / Molfino, Nestor A / Colice, Gene / Martin, Ubaldo / Corren, Jonathan / Menzies-Gow, Andrew

Journal of asthma and allergy

2022 Volume 15, Page(s) 749–765

Abstract: Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine implicated in the initiation and persistence of inflammatory pathways in asthma. Released in response to a range of epithelial insults (eg, allergens, viruses, bacteria, ... ...

Abstract	Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine implicated in the initiation and persistence of inflammatory pathways in asthma. Released in response to a range of epithelial insults (eg, allergens, viruses, bacteria, pollutants, and smoke), TSLP initiates multiple downstream innate and adaptive immune responses involved in asthma inflammation. Inhibition of TSLP is postulated to represent a novel approach to treating the diverse phenotypes and endotypes of asthma. Tezepelumab, the TSLP inhibitor farthest along in clinical development, is a human monoclonal antibody (IgG2λ) that binds specifically to TSLP, preventing interactions with its heterodimeric receptor. Results of recently published phase 2 and 3 studies, reviewed in this article, provide evidence of the safety and efficacy of tezepelumab that builds on initial findings. Tezepelumab is safe, well tolerated, and provides clinically meaningful improvements in asthma control, including reduced incidence of exacerbations and hospitalizations in patients with severe asthma. Clinical benefits were associated with reductions in levels of a broad spectrum of cytokines (eg, interleukin [IL]-5, IL-13) and baseline biomarkers (eg, blood eosinophils, immunoglobulin [Ig]E, fractional exhaled nitric oxide [FeNO]) and were observed across a range of severe asthma phenotypes (ie, eosinophilic and non-eosinophilic). These data strengthen the notion that anti-TSLP elicits broad inhibitory effects on pathways that are key to asthma inflammation rather than on narrower inhibition of individual downstream factors. This review presents the rationale for targeting TSLP to treat asthma, as well as the clinical effects of TSLP blockade on asthma outcomes, biomarkers of disease activity, airway inflammation, lung physiology, and patient symptoms.
Language	English
Publishing date	2022-06-03
Publishing country	New Zealand
Document type	Journal Article ; Review
ZDB-ID	2494877-9
ISSN	1178-6965
ISSN	1178-6965
DOI	10.2147/JAA.S275039
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Article ; Online: Effect of Tezepelumab on Lung Function in Patients With Severe, Uncontrolled Asthma in the Phase 3 NAVIGATOR Study.

Menzies-Gow, Andrew / Ambrose, Christopher S / Colice, Gene / Hunter, Gillian / Cook, Bill / Molfino, Nestor A / Llanos, Jean-Pierre / Israel, Elliot

Advances in therapy

2023 Volume 40, Issue 11, Page(s) 4957–4971

Abstract: Introduction: Severe asthma is associated with airway inflammation and airway obstruction. In the phase 3 NAVIGATOR study, tezepelumab treatment significantly improved pre-bronchodilator forced expiratory volume in 1 s (FEV: Methods: NAVIGATOR was a ... ...

Abstract	Introduction: Severe asthma is associated with airway inflammation and airway obstruction. In the phase 3 NAVIGATOR study, tezepelumab treatment significantly improved pre-bronchodilator forced expiratory volume in 1 s (FEV Methods: NAVIGATOR was a multicenter, randomized, double-blind, placebo-controlled study. Patients (12-80 years old) receiving medium- or high-dose inhaled corticosteroids and at least one additional controller medication, with or without oral corticosteroids, were randomized 1:1 to tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Changes from baseline to week 52 in pre-bronchodilator FEV Results: Tezepelumab treatment improved all evaluated lung function parameters over 52 weeks compared with placebo [least-squares mean difference (95% confidence interval): pre-bronchodilator FEV Conclusion: These findings further support the benefits of tezepelumab treatment in improving airflow limitation in patients with severe, uncontrolled asthma. Clinical trial registration: NAVIGATOR (NCT03347279).
MeSH term(s)	Humans ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Bronchodilator Agents/therapeutic use ; Asthma/drug therapy ; Adrenal Cortex Hormones/therapeutic use ; Lung ; Double-Blind Method ; Forced Expiratory Volume
Chemical Substances	Bronchodilator Agents ; tezepelumab (RJ1IW3B4QX) ; Adrenal Cortex Hormones
Language	English
Publishing date	2023-09-19
Publishing country	United States
Document type	Randomized Controlled Trial ; Multicenter Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632651-1
ISSN	1865-8652 ; 0741-238X
ISSN (online)	1865-8652
ISSN	0741-238X
DOI	10.1007/s12325-023-02659-y
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Article ; Online: Recent therapeutic breakthroughs in respiratory medicine.

Molfino, Nestor A

Expert review of respiratory medicine

2013 Volume 7, Issue 4, Page(s) 331–333

MeSH term(s)	Aminophenols/therapeutic use ; Animals ; Antineoplastic Agents/therapeutic use ; Antitubercular Agents/therapeutic use ; Diarylquinolines/therapeutic use ; Humans ; Molecular Targeted Therapy/trends ; Protein Kinase Inhibitors/therapeutic use ; Pulmonary Medicine/trends ; Pyrazoles/therapeutic use ; Pyridines/therapeutic use ; Quinolones/therapeutic use ; Respiratory System Agents/adverse effects ; Respiratory System Agents/therapeutic use
Chemical Substances	Aminophenols ; Antineoplastic Agents ; Antitubercular Agents ; Diarylquinolines ; Protein Kinase Inhibitors ; Pyrazoles ; Pyridines ; Quinolones ; Respiratory System Agents ; ivacaftor (1Y740ILL1Z) ; crizotinib (53AH36668S) ; bedaquiline (78846I289Y)
Language	English
Publishing date	2013-08
Publishing country	England
Document type	Editorial
ZDB-ID	2479146-5
ISSN	1747-6356 ; 1747-6348
ISSN (online)	1747-6356
ISSN	1747-6348
DOI	10.1586/17476348.2013.814388
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Article ; Online: Reply to Lipworth and Chan.

Ambrose, Christopher S / Israel, Elliot / Bowen, Karin / Llanos, Jean-Pierre / Martin, Neil / Cook, Bill / Hellqvist, Åsa / Korn, Stephanie / Menzies-Gow, Andrew / Roseti, Stephanie L / Molfino, Nestor A / Griffiths, Janet M / Parnes, Jane R

American journal of respiratory and critical care medicine

2023 Volume 208, Issue 2, Page(s) 212–213

Language	English
Publishing date	2023-06-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.202305-0843LE
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Article ; Online: Targeting of eosinophils in asthma.

Molfino, Nestor A

Expert opinion on biological therapy

2012 Volume 12, Issue 7, Page(s) 807–809

Abstract: Severe asthma continues to be an important source of morbidity despite the availability of bronchodilators and corticosteroids. Although new treatments are needed, better identification of asthma phenotypes may improve treatment effectiveness. One ... ...

Abstract	Severe asthma continues to be an important source of morbidity despite the availability of bronchodilators and corticosteroids. Although new treatments are needed, better identification of asthma phenotypes may improve treatment effectiveness. One phenotype that has emerged is eosinophilic asthma. Eosinophils in asthma have been studied for many years, and the evidence suggests they play a major role in some forms of asthma. Eosinophilic asthma can be diagnosed using peripheral blood, sputum eosinophil count or exhaled nitric oxide. Depletion of eosinophils can be achieved by corticosteroids, specific anti-interleukin 5 (IL-5) or anti-IL-5-receptor-alpha therapies, or anti-immunoglobulin E approaches. This editorial refers to the approaches that are being taken in eosinophilic asthma with emphasis on the new investigational anti-IL-5-receptor-alpha antibody, benralizumab.
MeSH term(s)	Anti-Asthmatic Agents/pharmacology ; Anti-Asthmatic Agents/therapeutic use ; Apoptosis/drug effects ; Asthma/drug therapy ; Asthma/pathology ; Eosinophils/drug effects ; Eosinophils/pathology ; Humans
Chemical Substances	Anti-Asthmatic Agents
Language	English
Publishing date	2012-07
Publishing country	England
Document type	Editorial
ZDB-ID	2052501-1
ISSN	1744-7682 ; 1471-2598
ISSN (online)	1744-7682
ISSN	1471-2598
DOI	10.1517/14712598.2012.674938
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Article ; Online: Increased vagal airway tone in fatal asthma.

Molfino, Nestor A

Medical hypotheses

2010 Volume 74, Issue 3, Page(s) 521–523

Abstract: Slow-onset asthma deaths are characterized by eosinophilic airway infiltrates and thickening of the basal membrane, while rapid-onset asthma deaths are associated with fewer airway inflammatory changes, suggesting that bronchospasm may be responsible for ...

Abstract	Slow-onset asthma deaths are characterized by eosinophilic airway infiltrates and thickening of the basal membrane, while rapid-onset asthma deaths are associated with fewer airway inflammatory changes, suggesting that bronchospasm may be responsible for the latter events. Airway tone is primarily controlled by the autonomous nervous system and can be pharmacologically modified. Therapies that stimulate the sympathetic beta(2) adrenoreceptor or inhibit the muscarinic receptor signal transduction induce bronchodilation. Parasympathetic (vagal) airway tone is enhanced in some asthmatics due to a number of stimuli, while in others it is constitutively heightened. Mainstream asthma therapy, however, only consists of corticosteroids and beta(2) agonists, not addressing this aspect. In this publication, I propose that increased vagal airway tone resulting in overwhelming bronchoconstriction and mucus plugging could be responsible for the near-fatal or fatal events observed in a number of asthmatics, in spite of their adequate treatment with standard therapies. On the basis of this hypothesis, I recommend that vagal airway tone be assessed in all patients with asthma, particularly in those with a history of near-fatal events. If the airway tone is increased, individuals should be treated with a triple combination of long-acting beta(2) agonists, inhaled steroids, and inhaled anticholinergics to prevent vagally mediated fatal events.
MeSH term(s)	Asthma/etiology ; Asthma/mortality ; Asthma/physiopathology ; Bronchi/innervation ; Bronchi/physiopathology ; Bronchial Diseases/complications ; Bronchial Diseases/mortality ; Bronchial Diseases/physiopathology ; Comorbidity ; Constriction, Pathologic/complications ; Constriction, Pathologic/mortality ; Constriction, Pathologic/physiopathology ; Humans ; Incidence ; Models, Biological ; Vagus Nerve/physiopathology
Language	English
Publishing date	2010-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	193145-3
ISSN	1532-2777 ; 0306-9877
ISSN (online)	1532-2777
ISSN	0306-9877
DOI	10.1016/j.mehy.2009.10.002
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Article ; Online: Efficacy of Tezepelumab in Severe, Uncontrolled Asthma: Pooled Analysis of the PATHWAY and NAVIGATOR Clinical Trials.

Corren, Jonathan / Menzies-Gow, Andrew / Chupp, Geoffrey / Israel, Elliot / Korn, Stephanie / Cook, Bill / Ambrose, Christopher S / Hellqvist, Åsa / Roseti, Stephanie L / Molfino, Nestor A / Llanos, Jean-Pierre / Martin, Neil / Bowen, Karin / Griffiths, Janet M / Parnes, Jane R / Colice, Gene

American journal of respiratory and critical care medicine

2023 Volume 208, Issue 1, Page(s) 13–24

Abstract: Rationale: ...

Abstract	Rationale:
MeSH term(s)	Adult ; Adolescent ; Humans ; Young Adult ; Middle Aged ; Aged ; Child ; Aged, 80 and over ; Anti-Asthmatic Agents/therapeutic use ; Treatment Outcome ; Asthma/drug therapy ; Antibodies, Monoclonal, Humanized/therapeutic use ; Double-Blind Method
Chemical Substances	tezepelumab (RJ1IW3B4QX) ; Anti-Asthmatic Agents ; Antibodies, Monoclonal, Humanized
Language	English
Publishing date	2023-04-05
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.202210-2005OC
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Article: Effect of Biologic Therapies on Airway Hyperresponsiveness and Allergic Response: A Systematic Literature Review.

Spahn, Joseph D / Brightling, Christopher E / O'Byrne, Paul M / Simpson, Lisa J / Molfino, Nestor A / Ambrose, Christopher S / Martin, Neil / Hallstrand, Teal S

Journal of asthma and allergy

2023 Volume 16, Page(s) 755–774

Abstract: Background: Airway hyperresponsiveness (AHR) is a key feature of asthma. Biologic therapies used to treat asthma target specific components of the inflammatory pathway, and their effects on AHR can provide valuable information about the underlying ... ...

Abstract	Background: Airway hyperresponsiveness (AHR) is a key feature of asthma. Biologic therapies used to treat asthma target specific components of the inflammatory pathway, and their effects on AHR can provide valuable information about the underlying disease pathophysiology. This review summarizes the available evidence regarding the effects of biologics on allergen-specific and non-allergen-specific airway responses in patients with asthma. Methods: We conducted a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, including risk-of-bias assessment. PubMed and Ovid were searched for studies published between January 1997 and December 2021. Eligible studies were randomized, placebo-controlled trials that assessed the effects of biologics on AHR, early allergic response (EAR) and/or late allergic response (LAR) in patients with asthma. Results: Thirty studies were identified for inclusion. Bronchoprovocation testing was allergen-specific in 18 studies and non-allergen-specific in 12 studies. Omalizumab reduced AHR to methacholine, acetylcholine or adenosine monophosphate (3/9 studies), and reduced EAR (4/5 studies) and LAR (2/3 studies). Mepolizumab had no effect on AHR (3/3 studies), EAR or LAR (1/1 study). Tezepelumab reduced AHR to methacholine or mannitol (3/3 studies), and reduced EAR and LAR (1/1 study). Pitrakinra reduced LAR, with no effect on AHR (1/1 study). Etanercept reduced AHR to methacholine (1/2 studies). No effects were observed for lebrikizumab, tocilizumab, efalizumab, IMA-638 and anti-OX40 ligand on AHR, EAR or LAR; benralizumab on LAR; tralokinumab on AHR; and Ro-24-7472 on AHR or LAR (all 1/1 study each). No dupilumab or reslizumab studies were identified. Conclusion: Omalizumab and tezepelumab reduced EAR and LAR to allergens. Tezepelumab consistently reduced AHR to methacholine or mannitol. These findings provide insights into AHR mechanisms and the precise effects of asthma biologics. Furthermore, findings suggest that tezepelumab broadly targets allergen-specific and non-allergic forms of AHR, and the underlying cells and mediators involved in asthma.
Language	English
Publishing date	2023-07-21
Publishing country	New Zealand
Document type	Journal Article ; Review
ZDB-ID	2494877-9
ISSN	1178-6965
ISSN	1178-6965
DOI	10.2147/JAA.S410592
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