Ont Health Technol Assess Ser. 2024 Jul 31;24(5):1-225. eCollection 2024.
Asthma is a common respiratory disease characterized by airflow obstruction caused by inflammation and narrowing of the airways. Nitric oxide is a gas that is present at low levels in the lungs, but that is elevated in the presence of airway inflammation. Fractional exhaled nitric oxide (FeNO) testing may help in the diagnosis and management of asthma by measuring the amount of nitric oxide in the breath. We conducted a health technology assessment of FeNO testing for the diagnosis and management of asthma in children and adults, which included an evaluation of the accuracy, effectiveness, cost-effectiveness, the budget impact of publicly funding FeNO testing, and patient preferences and values.
We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included study using the Quality Assessment of Diagnostic Accuracy Studies tool, version 2 (QUADAS-2) and of each systematic review using the Risk of Bias Assessment Tool for Systematic Reviews (ROBIS). We evaluated the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic economic literature search and conducted cost-utility analyses with a 20-year time horizon from a public payer perspective. We also analyzed the budget impact of publicly funding FeNO testing in children and adults in Ontario. To contextualize the potential value of FeNO testing, we spoke with people with asthma and their care partners.
We included 48 primary studies assessing the diagnostic accuracy of FeNO testing and 2 reviews evaluating the effectiveness of FeNO testing for asthma management in the clinical evidence review. The use of FeNO testing for the diagnosis of asthma reported variable (30% to 90%) sensitivities (GRADE: Very low) and consistently high (70% to 100%) specificities (GRADE: Low) in children and adults. FeNO testing for asthma management likely reduced exacerbations in children (GRADE: Moderate) and adults (GRADE: Moderate), lowered oral corticosteroid use in children (GRADE: Moderate), and slightly improved lung function in a mixed population (GRADE: Moderate), but little to no improvement was seen in other outcomes. We found that, for asthma diagnosis, FeNO testing in addition to standard testing is cost-effective in children, with an incremental cost-effectiveness ratio (ICER) of $6,192 per quality-adjusted life-year (QALY) gained. FeNO testing is not cost-effective for asthma diagnosis in adults except when a higher FeNO cut-off is applied. For asthma management, the ICER of FeNO testing compared with standard care alone is $103,893 per QALY gained in children and $200,135 per QALY gained in adults. Publicly funding FeNO testing as an adjunct to standard testing for asthma diagnosis over the next 5 years would cost about $0.10 million to $0.22 million for children and $1.19 million to $1.61 million for adults over the next 5 years, and for asthma management would cost about $22.37 million for children and $195.99 million for adults over the next 5 years. Participants were unaware if they had experience with FeNO testing because of its similarity to other types of asthma testing, but they reported valuing the potential of FeNO testing to provide more information about their condition as well as aid in the diagnosis and management. Barriers to access include lack of awareness and the limited availability of FeNO testing across the province.
We found that FeNO testing had good diagnostic specificity (i.e., low false positive rate), supporting its use as an adjunct to standard testing to help rule-in an asthma diagnosis in both children and adults. FeNO testing to monitor and manage asthma likely resulted in a reduction in the number of people who experienced exacerbations and used oral corticosteroids, but may make little to no difference in improving other health outcomes. FeNO testing is likely cost-effective as an additional test to support the diagnosis of asthma in children, as well as in adults when a higher FeNO cut-off is applied, but is likely not cost-effective as an additional test to monitor and manage asthma in both children and adults. We estimate that publicly funding FeNO testing as an adjunct to standard testing for asthma diagnosis in Ontario would result in additional costs of $0.10 million to $0.22 million for children and $1.19 million to $1.61 million for adults over the next 5 years. For monitoring and managing asthma, FeNO testing would result in additional costs of $22.37 million for children and $195.99 million for adults over the next 5 years. People we spoke with were unaware if they had experience with FeNO testing because of its similarity to other types of asthma testing, but they reported valuing the potential of FeNO testing to provide more information about their condition as well as aid in the diagnosis and management of asthma.
哮喘是一种常见的呼吸道疾病，其特征是气流阻塞，由气道炎症和狭窄引起。一氧化氮是一种在肺部含量较低的气体，但在气道炎症存在时会升高。呼出气一氧化氮（FeNO）检测可通过测量呼吸中一氧化氮的含量，帮助诊断和管理哮喘。我们对儿童和成人哮喘的 FeNO 检测进行了卫生技术评估，其中包括对准确性、有效性、成本效益、公开资助 FeNO 检测的预算影响以及患者偏好和价值观的评估。
我们对临床证据进行了系统的文献检索。我们使用 QUADAS-2 工具评估了每个纳入研究的偏倚风险，使用 ROBIS 工具评估了每个系统评价的偏倚风险。我们根据 Grading of Recommendations Assessment, Development, and Evaluation (GRADE) 工作组的标准评估了证据体的质量。我们进行了系统的经济文献检索，并从公共支付者的角度进行了 20 年时间跨度的成本效用分析。我们还分析了在安大略省为儿童和成人公开资助 FeNO 检测的预算影响。为了使 FeNO 检测的潜在价值具体化，我们与哮喘患者及其护理伙伴进行了交谈。
我们纳入了 48 项评估 FeNO 检测诊断准确性的主要研究和 2 项评估 FeNO 检测在哮喘管理中有效性的综述。在儿童和成人中，FeNO 检测用于哮喘诊断的报告显示，其灵敏度（30%至 90%）存在差异（GRADE：非常低），而特异性（70%至 100%）一直较高（GRADE：低）。FeNO 检测用于哮喘管理可能减少儿童（GRADE：中度）和成人（GRADE：中度）的哮喘发作，减少儿童口服皮质类固醇的使用（GRADE：中度），并在混合人群中稍微改善肺功能（GRADE：中度），但其他结果未见明显改善。我们发现，对于哮喘诊断，儿童中 FeNO 检测加标准检测具有成本效益，增量成本效益比（ICER）为每获得一个质量调整生命年（QALY）增加 6192 加元。对于成人，FeNO 检测在哮喘诊断中不具有成本效益，除非应用较高的 FeNO 截断值。对于哮喘管理，与单独使用标准护理相比，FeNO 检测在儿童中的 ICER 为每获得一个 QALY 增加 103893 加元，在成人中增加 200135 加元。在未来 5 年内，为儿童哮喘诊断提供额外的 FeNO 检测，将在未来 5 年内增加约 0.10 百万至 0.22 百万加元的成本，为成人增加约 1.19 百万至 1.61 百万加元的成本。参与者不知道他们是否有过 FeNO 检测的经验，因为它与其他类型的哮喘检测相似，但他们报告说重视 FeNO 检测在提供有关病情的更多信息以及帮助诊断和管理方面的潜在价值。获取障碍包括缺乏认识和全省范围内 FeNO 检测的有限可用性。
我们发现，FeNO 检测具有良好的诊断特异性（即低假阳性率），支持其作为标准检测的辅助手段，以帮助儿童和成人哮喘诊断。FeNO 检测用于监测和管理哮喘可能会减少哮喘发作和口服皮质类固醇的人数，但在改善其他健康结果方面可能作用不大。FeNO 检测作为辅助诊断儿童哮喘的额外检测具有成本效益，在应用较高的 FeNO 截断值时也具有成本效益，但作为监测和管理哮喘的额外检测在儿童和成人中可能不具有成本效益。我们估计，在安大略省，将 FeNO 检测作为哮喘诊断的标准检测的辅助手段，在未来 5 年内，将使儿童的额外成本增加 0.10 百万至 0.22 百万加元，使成人的额外成本增加 1.19 百万至 1.61 百万加元。在未来 5 年内，将 FeNO 检测用于监测和管理哮喘，将使儿童的额外成本增加 22.37 百万加元，使成人的额外成本增加 195.99 百万加元。我们交谈过的人不知道他们是否有过 FeNO 检测的经验，因为它与其他类型的哮喘检测相似，但他们报告说重视 FeNO 检测在提供有关病情的更多信息以及帮助诊断和管理哮喘方面的潜在价值。
