Tailored interventions based on exhaled nitric oxide versus clinical symptoms for asthma in children and adults

 

Abstract

Background

The measurement of severity and control of asthma in both children and adults can be based on subjective or objective measures. It has been advocated that fractional exhaled nitric oxide (FeNO) can be used to monitor airway inflammation as it correlates with some markers of asthma. Interventions for asthma therapies have been traditionally based on symptoms and/or spirometry.

Objectives

To evaluate the efficacy of tailoring asthma interventions based on exhaled nitric oxide in comparison to clinical symptoms (with or without spirometry/peak flow) for asthma related outcomes in children and adults.

Search methods

We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and reference lists of articles. The last search was completed in February 2009.

Selection criteria

All randomised controlled comparisons of adjustment of asthma therapy based on exhaled nitric oxide compared to traditional methods (primarily clinical symptoms and spirometry/peak flow).

Data collection and analysis

Results of searches were reviewed against pre-determined criteria for inclusion. Relevant studies were independently selected in duplicate. Two authors independently assessed trial quality and extracted data. Authors were contacted for further information with response from one.

Main results

Two studies have been added for this update, which now includes six (2 adults and 4 children/adolescent) studies; these studies differed in a variety of ways including definition of asthma exacerbations, FeNO cut off levels, the way in which FeNO was used to adjust therapy and duration of study. Of 1053 participants randomised, 1010 completed the trials. In the meta-analysis, there was no significant difference between groups for the primary outcome of asthma exacerbations or for other outcomes (clinical symptoms, FeNO level and spirometry). In post-hoc analysis, a significant reduction in mean final daily dose inhaled corticosteroid per adult was found in the group where treatment was based on FeNO in comparison to clinical symptoms, (mean difference -450 mcg; 95% CI -677 to -223 mcg budesonide equivalent/day). However, the total amount of inhaled corticosteroid used in one of the adult studies was 11% greater in the FeNO arm. In contrast, in the paediatric studies, there was a significant increase in inhaled corticosteroid dose in the FeNO strategy arm (mean difference of 140 mcg; 95% CI 29 to 251, mcg budesonide equivalent/day).

Authors' conclusions

Tailoring the dose of inhaled corticosteroids based on exhaled nitric oxide in comparison to clinical symptoms was carried out in different ways in the six studies and found only modest benefit at best and potentially higher doses of inhaled corticosteroids in children. The role of utilising exhaled nitric oxide to tailor the dose of inhaled corticosteroids cannot be routinely recommended for clinical practice at this stage and remains uncertain.

 

Plain language summary

Tailoring asthma interventions based on exhaled nitric oxide

In this review involving 1010 adults and children with asthma, we found that tailoring the dose of inhaled corticosteroids based on exhaled nitric oxide (compared to clinical symptoms with or without spirometry/peak flow) was beneficial in reducing the final (but not the overall) daily inhaled corticosteroid doses in adults. However in children inhaled corticosteroid dose was increased when exhaled nitric oxide guided strategy was used. There was no difference between groups in other asthma outcomes (exacerbations, spirometry, FeNO or symptom control). Thus tailoring the dose of inhaled corticosteroids based on exhaled nitric oxide cannot be routinely advocated.

 

摘要

背景

根據吐出一氧化氮濃度或臨床症狀為氣喘的成人及幼童量身定做治療策略

藉由各種主觀和客觀的測量可以對於幼童和成人的氣喘的嚴重性和控制結果加以評量。目前有人主張可以利用呼氣一氧化氮(fractional exhaled nitric oxide，FeNO)的濃度來監控呼吸道發炎症狀，因為FeNO和某些氣喘的徵狀有所相關。傳統上對於氣喘進行的介入性治療都是根據患者所表現出的症狀和/或肺功能量計來決定。

目標

評估以吐出一氧化氮或是臨床症狀(使用肺功能量計/尖峰吐氣流量)量身訂作的氣喘介入方法對於幼童或成人氣喘結果的療效。

搜尋策略

我們檢索了Cochrane Airways Group Specialised Register of Trials、Cochrane Central Register of Controlled Trials(CENTRAL)、MEDLINE和EMBASE資料庫，和文獻的參考文獻清單，最後檢索日期為2 009年2月。

選擇標準

納入根據吐出一氧化氮或是臨床症狀(使用肺功能量計/尖峰吐氣流量)為患者量身訂做氣喘介入治療法進行效果比較的隨機對照試驗。

資料收集與分析

檢索的結果會利用先前預定的條件進行篩選以確認是否將試驗納入。相關的試驗分別會被以重複的方式篩選。有2位作者會獨立評估試驗品質及摘錄數據，也會聯繫研究作者來取得更多的研究結果的資訊。

主要結論

有2個試驗被新增至本次更新當中，因此本研究納入了6個試驗(其中2個是針對成人、4個是針對幼童或青少年進行的試驗)，這些研究在許多方面皆有所不同，其中包括了對於氣喘症狀惡化的定義、FeNO中斷程度、將FeNO使用於調整治療方式的方法和研究的持續期間。在1053個隨機挑選出的患者中，有1010位患者完成試驗。在行統合分析中，這兩個組別在主要氣喘惡化成果或是其他試驗成果(例如臨床症狀、FeNO的濃度和肺功能量計讀值)上並沒有明顯的差異。在事後分析(posthoc analysis)結果中可以發現，相較於根據臨床症狀決定進行治療策略而言，根據FeNO決定治療策略可以明顯降低每位成人患者平均每日最後吸入ICS的劑量(平均差異為−450微克，95％的CI 介於−677至−233 微克budesonide equivalent/day)，然而，一個針對成人進行的研究中，在FeNO組別使用ICS總量高了11％。相較之下，在對幼童進行的試驗中，接受FeNO治療的組別明顯增加了ICS的使用劑量(平均差異為140微克，95％的CI 介於29至25微克budesonide equivalent/day)

作者結論

在6個試驗分別以不同方式藉由測量一氧化氮吐出量和臨床症狀檢視的結果，分別為患者量身決定所需ICS劑量，而研究結果發現當幼童使用最佳和可能為較高劑量的ICS時可以得到些微好處。在這個階段，在有些部分無法確認的狀況下，使用吐出性一氧化氮來調整ICS用量並無法被建議常規使用在臨床實務上。

翻譯人

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

用吐出一氧化氮濃度來調整ICS根據吐出一氧化氮濃度來調整氣喘介入治療的策略。在本研究中共納入了1010個患有氣喘的幼童及成人作為受試者，我們發現根據吐出的一氧化氮濃度(相對於利用或不利用肺功能量計/尖峰吐氣流量進行的臨床症狀判斷結果)來調整患者使用的ICS劑量對於降低成人最終(但不是整體性)每日使用ICS的劑量是有幫助的，但是對於幼童患者來說，使用吐出一氧化氮濃度的調整策略時，卻會提升了幼童的ICS使用劑量，對於其他的氣喘成果(例如症狀惡化、肺功能計、FeNO或是症狀控制等)來說，兩組的數據並沒有明顯差異。因此想要利的使用量並不能普遍使用於每個患者。