Exhaled Nitric Oxide Using End-Tidal Concentration during Methacholine Challenge

Abstract

Increased nitric oxide in exhaled gas in patients with asthma is thought to reflect the severity of airway inflammation and perhaps airway reactivity. Several studies attempted to identify a relationship between exhaled NO levels and airway reactivity or severity of airway inflammation for the purpose of finding out if exhaled NO could be used in place of pulmonary function testing and airway provocation test. Unfortunately, the relationship is not always evident. In recent years, it has become clearer that exhaled NO becomes elevated primarily in atopic asthma patients. All previous studies have used the single vital capacity slow exhalation maneuver to measure ENO (FeNO50). This method is subject to errors because it requires patient cooperation, is flow rate dependent and adds more stress on the patient. Recently, we showed that end tidal NO concentration (NOet) is clinically relevant, is much easier to measure and is not subject to flow variation or patient cooperation. We used NOet (ppb) measurement before and during methacholine challenge in patients with symptoms of mild, persistent asthma. In addition we calculated NO production (NOpr) (nmole/ min) to correct for possible changes in ventilation. Eleven patients exhibited hyper-responsiveness to methacholine (responders) and 17 exhibited negative response (non-responders). The responders had a slightly higher NO level than the non-responders whether expressed in ppb or in nmol/min but did not reach statistical significance: NOet values were 15.1±2.4 ppb (±SE) and 11.7±2.3 ppb respectively and NOpr values were 5.83±0.86 nmol/min and 5.12±1.13 nmol/min respectively. There was no correlation between baseline NOet levels and the change in FEV1 in the responders. Furthermore, there was no consistent change in NOet or NOpr levels during broncho-constriction with methacholine. We conclude that although exhaled NO levels may serve as a helpful adjunct in treatment of asthma, its level alone does not reflect severity of the disease in mild asthmatics nor the airway responsiveness to methacholine. Exhaled NO was estimated using the average NO value at end expiration during normal tidal breathing. This method was quicker, repeatable and much easier on the patients and none of the patients objected to doing the measurement. There was no need to put patients through the complicated single full vital capacity slow exhaled maneuver to obtain this information.