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Exhaled nitric oxide (NO) production, upregulated by inflammatory cytokines and mediators in central and peripheral airways, can be easily and non-invasively detected in exhaled air in asthma and other respiratory conditions as a promising tool for disease monitoring. The American Thoracic Society and European Respiratory Society released recommendations that standardize the measurement of the fractional exhaled NO (FeNO). In asthma, increased FeNO reflects eosinophilic-mediated inflammatory pathways and, as a biomarker of T2 inflammation can be used to identify asthma T2 phenotype. In this setting its measurement has shown to be an important tool especially in the diagnostic process, in the assessment and evaluation of poor adherence or predicting positive response to inhaled corticosteroids treatment, in phenotyping severe asthma patients and as a biomarker to predict the response to biologic treatments. The discovery of the role of NO in the pathogenesis of different diseases affecting the airways and the possibility to estimate the predominant site of increased NO production has provided new insight on its regulatory role in the airways, making it suitable for a potential extended use in clinical practice for different pulmonary diseases, even though its role remains less clear than in asthma. Monitoring FeNO in pulmonary obstructive lung diseases including chronic bronchitis and emphysema, interstitial lung diseases, obstructive sleep apnea and other pulmonary diseases is still under debate but has opened up a window to the role NO may play in the management of these diseases. The use of FeNO is reliable, cost effective and recommendable in both adults and children, and should be implemented in the management of patients with asthma and other respiratory conditions., Competing Interests: Jaymin Morjaria has received honoraria for speaking and financial support to attend meetings/advisory boards from Wyeth, Chiesi, Pfizer, MSD, Boehringer Ingelheim, Teva, GSK/Allen & Hanburys, Napp, Almirall, AstraZeneca, Trudell, Cook Medical, Medela AG, Medtronics and Novartis. He has been an expert witness in a court case relating to the impact of smoking on illness severity, ITU admissions and mortality from Covid-19 in South Africa in 2020. The entire proceeds of the work were donated to multiple charities. Mario Malerba has received honoraria for speaking and financial support for attending meetings and/or serving on the advisory boards from Chiesi, Astra-Zeneca, GSK, Laboratori Guidotti, Boehringer Ingelheim, Vitalaire, Grifols, CLS Behring. All the authors have no other relevant affiliations of financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Jaymin Morjaria is also an Associate Editor of Therapeutic Advances in Chronic Disease; therefore, the peer-review process was managed by alternative members of the Board, and he had no involvement in the decision-making process. Beatrice Ragnoli and Mario Malerba are members of the Editorial Board of Therapeutic Advances in Chronic Disease and had no involvement in the peer review process., (© The Author(s), 2023.)

Bronchial asthma is a chronic inflammatory condition with increasing prevalence worldwide that may present as heterogeneous phenotypes defined by the T2-mediated pattern of airway inflammation T2-high and T2-low asthma. Severe refractory asthma includes a subset of asthmatic patients who fail to control their disease despite maximal therapy and represent a group of patients needing marked resource utilization and hence may be eligible to add-on biological therapies. Among the new biologics, we focused our attention on two monoclonal antibodies: dupilumab, exerting a dual blockade of cytokine (interleukin (IL)-4 and IL-13) signaling; and tezepelumab, acting at a higher level preventing the binding of thymic stromal lymphopoietin (TSLP) to its receptor, thus blocking TSLP, IL-25, and IL-33 signaling, hence modulating airway T2 immune responses. With their different mechanisms of action, these two biologics represent important options to provide an enhanced personalized treatment regimen. Several clinical trials have been conducted testing the efficacy and safety of dupilumab in severe refractory asthmatic patients showing improvements in lung function, asthma control, and reducing exacerbations. Similar results were reported with tezepelumab that, differently from dupilumab, acts irrespectively on eosinophilic or non-eosinophilic phenotype. In this review, we provide an overview of the most important highlights regarding dupilumab and tezepelumab characteristics and mechanism of action with a critical review of the principal results of clinical (Phase II and III) studies concluded and those still in progress., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JM has received honoraria for speaking and financial support to attend meetings or advisory boards from Wyeth, Chiesi, Pfizer, MSD, Boehringer Ingelheim, Teva, GSK/Allen & Hanburys, Napp, Almirall, AstraZeneca, Trudell, Cook Medical, Medela AG, and Novartis. He has been an expert witness in a court case relating to the impact of smoking on illness severity, ITU admissions and mortality form COVID-19 in South Africa in 2020. The entire proceeds of the work were donated to various charities. He is also an associate editor of Therapeutic Advances in Chronic Disease, therefore, the peer-review process was managed by alternative members of the Board, and he had no involvement in the decision-making process. MM has received honoraria for speaking and financial support for attending meetings and serving on the advisory boards from Chiesi, AstraZeneca, GSK, Laboratori Guidotti, and Boehringer Ingelheim. The authors have no other relevant affiliations of financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the article apart from those disclosed. The other authors declare no conflicts of interest., (© The Author(s), 2022.)