Using Fractional Exhaled Nitric Oxide Measurement in Clinical Asthma Management

Rupani, Hitasha; Kent, Brian D.

doi:10.1016/j.chest.2021.10.015

Cited by 35 publications

(39 citation statements)

References 95 publications

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“…The patients in the analysis were regular users of inhaled steroids in the baseline phase of the clinical trial. Because FeNO levels show greater fluctuations in response to these inhaled medications than those of PBEC [ 71 , 72 ], it is possible that the low FeNO group included a relatively large number of patients not only with non-type 2 asthma, but also with type 2 asthma, which may have influenced the results.…”

Section: Discussionmentioning

confidence: 99%

Comparative Efficacy and Safety of Tezepelumab and Other Biologics in Patients with Inadequately Controlled Asthma According to Thresholds of Type 2 Inflammatory Biomarkers: A Systematic Review and Network Meta-Analysis

Andō

Fukuda

Tanaka

et al. 2022

Cells

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The anti-thymic stromal lymphopoietin antibody (tezepelumab) has therapeutical potential for inadequately controlled asthma. However, evidence comparing tezepelumab with other biologics is scarce. To address this issue, we performed a network meta-analysis to compare and rank the efficacy of five treatments (tezepelumab, dupilumab, benralizumab, mepolizumab, and placebo) in overall participants and in subgroups stratified by the thresholds of type 2 inflammatory biomarkers, including peripheral blood eosinophil count (PBEC) and fractional exhaled nitric oxide (FeNO). The primary endpoints were annualized exacerbation rate (AER) and any adverse events (AAEs). In the ranking assessment using surface under the cumulative ranking curve (SUCRA) of AER, tezepelumab ranked the highest overall and across subgroups (based on PBEC and FeNO level thresholds). A significant difference was observed between tezepelumab and dupilumab in the patient subgroup with PBEC < 150, and between tezepelumab and benralizumab in overall participants and the patient subgroup with PBEC ≥ 300 and ≥150, respectively. There was no significant difference in the incidence of AAEs in the overall participants between each pair of five treatment arms. These results provide a basis for the development of treatment strategies for asthma and may guide basic, clinical, or translational research.

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Section: Discussionmentioning

confidence: 99%

Comparative Efficacy and Safety of Tezepelumab and Other Biologics in Patients with Inadequately Controlled Asthma According to Thresholds of Type 2 Inflammatory Biomarkers: A Systematic Review and Network Meta-Analysis

Andō

Fukuda

Tanaka

et al. 2022

Cells

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“…FeNO is influenced by diet and medications such as inhaled corticosteroids, as well as demographic factors such as gender and ethnicity [14]. This has provoked concerns regarding its reliability as a clinical tool.…”

Section: Asthma Diagnosismentioning

confidence: 99%

Asthma diagnosis using patient-reported outcome measures and objective diagnostic tests: now and into the future

Nawaz

Ravindran²,

Kuruvilla

2022

Current Opinion in Pulmonary Medicine

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Purpose of reviewThe global prevalence of asthma continues to increase; however, asthma remains under-diagnosed and under-treated. This results in a significant burden on the healthcare system and preventable patient morbidity and mortality. Over-diagnosis of asthma based on clinical history alone also complicates patient management. This heightens the importance of a prompt and accurate asthma diagnosis. Therefore, a review of the literature was performed regarding both objective diagnostic testing for asthma and using patient-reported outcome measures. Recent findingsThe cornerstone of asthma diagnosis remains spirometry with testing for bronchodilator reversibility testing for pediatric and adult populations. This test may need to be repeated at multiple time points due to its low sensitivity. Peak flow measurement, fractional exhaled nitric oxide testing, and allergy testing are useful adjuncts to the diagnosis and phenotyping of asthma. Bronchoprovocation testing is reserved for people with high clinical suspicion for asthma, but negative spirometry. Novel noninvasive testing modalities may play a diagnostic role in the future. The advent of remote digital health monitoring technology has resulted in revisiting patient-reported outcome measures for the diagnosis and monitoring of asthma. SummaryOverall, improved diagnostic tools for asthma are crucial for earlier recognition and treatment of the disease and improved patient care outcomes worldwide.

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“…Our model captures the cellular effect of therapies and subsequent impact on clinical end points, including FeNO (a marker of T2 inflammation 15 ), eosinophils (which may directly contribute to asthma severity 16 ), and FEV1 (a measure of airway function), for severe, uncontrolled asthma. Calibration is verified using data from therapies targeting IL‐5, IL‐13, IL‐4Rα, TSLP, and IgE, and further validated against held‐out anti‐TSLP data.…”

Section: Introductionmentioning

confidence: 99%

Integrated systems modeling of severe asthma: Exploration of IL‐33/ST2 antagonism

Gadkar

Feigelman²,

Sukumaran

et al. 2022

CPT Pharmacom & Syst Pharma

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Asthma is a complex, heterogeneous disease with a high unmet medical need, despite therapies targeting a multitude of pathways. The ability to quantitatively integrate preclinical and clinical data on these pathways could aid in the development and testing of novel targets and therapeutics. In this work, we develop a computational model of asthma biology, including key cell types and mediators, and create a virtual population capturing clinical heterogeneity. The simulated responses to therapies targeting IL-13, IL-4Rα, IL-5, IgE, and TSLP demonstrate agreement with clinical endpoints and biomarkers of type 2 (T2) inflammation, including blood eosinophils, FEV1, IgE, and FeNO. We use the model to explore the potential benefit of targeting the IL-33 pathway with anti-IL-33 and anti-ST2. Model predictions are compared with data on blood eosinophils, FeNO, and FEV1 from recent anti-IL-33 and anti-ST2 trials and used to interpret trial results based on pathway biology and pharmacology. Results of sensitivity analyses on the contributions of IL-33 to the predicted biomarker changes suggest that anti-ST2 therapy reduces circulating blood eosinophil levels primarily through its impact on eosinophil progenitor maturation and IL-5-dependent survival, and induces changes in FeNO and FEV1 through its effect on immune cells involved in T2 cytokine production. Finally, we also investigate the impact of ST2 genetics on the conferred benefit of anti-ST2. The model includes representation of a wide array of biologic mechanisms and interventions that will provide mechanistic insight and support clinical program design for a wide range of novel therapies during drug development.

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Using Fractional Exhaled Nitric Oxide Measurement in Clinical Asthma Management

Cited by 35 publications

References 95 publications

Comparative Efficacy and Safety of Tezepelumab and Other Biologics in Patients with Inadequately Controlled Asthma According to Thresholds of Type 2 Inflammatory Biomarkers: A Systematic Review and Network Meta-Analysis

Comparative Efficacy and Safety of Tezepelumab and Other Biologics in Patients with Inadequately Controlled Asthma According to Thresholds of Type 2 Inflammatory Biomarkers: A Systematic Review and Network Meta-Analysis

Asthma diagnosis using patient-reported outcome measures and objective diagnostic tests: now and into the future

Integrated systems modeling of severe asthma: Exploration of IL‐33/ST2 antagonism

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