Bronchial Hyperresponsiveness and FeNO | Asthma Management

Bronchial hyperresponsiveness (BHR) is one of pathophysiological features usually associated with chronic inflammation and reversible obstruction of airways in patients with asthma. This phenomenon is also found out in the pathogenesis of chronic obstructive pulmonary disease (COPD) and known as a risk factor for the development of respiratory symptoms as well as a predictor for lung functional impairment.  Clinically, Bronchial hyperresponsiveness is defined by excessive bronchospasm responding to a specific or nonspecific stimulus.

Methacholine challenge

It is useful for diagnosis of asthma, especially in patients without clinical symptom of asthma or without abnormalities in lung function measured by spirometry or whole body plethysmography. However, until now, the use of methacholine challenge to find out Bronchial hyperresponsiveness for diagnosis of asthma is still not available in some medical centers, even though in some national hospital of respiratory diseases in developing countries. Moreover, methacholine challenge may produce severe bronchospasm in some patients and should be avoided in some clinical situations such as pregnant women or patients with severe cardiovascular diseases.

Recently, exhaled nitric oxide (NO) has been used as a biomarker of asthma because the concentration of NO in exhaled breath is significantly correlated with the level of inflammation in the airways. The measure of NO in exhaled breath (Fractional exhaled nitric oxide) is a non-invasive method for evaluating an allergic inflammation and plays an important role in the diagnosis and control of asthma. In asthma, although Fractional exhaled nitric oxide correlates significantly with other biomarkers of inflammation such as eosinophil count in sputum or total IgE in serum, the correlation between Fractional exhaled nitric oxide and Bronchial hyperresponsiveness is still controversial.

This study was planned to describe:

1) Level of exhaled NO in subjects with bronchial hyperresponsiveness (BHR) diagnosed by methacholine challenge;
2.) Correlation between the level of exhaled NO and the dose of methacholine in subjects with positive bronchial hyperresponsiveness.
3) Cute-off of exhaled NO for diagnosing bronchial hyperresponsiveness in the study population.

It was a cross-sectional and descriptive study. Subjects who had been realized a methacholine challenge for diagnosis of bronchial hyperresponsiveness at Clinical Research Unit of Lam Dong Medical College were included in the study after signing an Institutional Review Board approved consent form. These subjects had one of following symptoms with suggestive asthma were included in the study: chronic or a nocturnal cough, wheezing or chest tightness at night or during physical exercise. 

The percentage of wheezing and nocturnal coughing in subjects with positive Bronchial hyperresponsiveness was significantly higher than that in subjects with negative Bronchial hyperresponsiveness.Correlation between methacholine dose and FeNO (fractional exhaled nitric oxide) level measured at 50 mL/s in subjects with positive bronchial hyperresponsiveness.

Discussion

Currently, the relationship between fractional exhaled nitric oxide (FeNO) and Bronchial hyperresponsiveness identified by methacholine challenge is still controversial. In this study, the correlation between the dose of methacholine causing significant bronchoconstriction (PD20 - methacholine) and the concentration of NO in exhaled breath (fractional exhaled nitric oxide) measured at 50 mL/s has been demonstrated in figure.



In subjects with asthma, Bronchial hyperresponsiveness is often present and considered as one of the features of this disease. In asthma, fractional exhaled nitric oxide is also increased and similar with chronic airways inflammation and associated with hypereosinophilic. According to current recommendations,  fractional exhaled nitric oxide can be used to diagnose and monitor the treatment of asthma.

Fractional exhaled nitric oxide is also a good biomarker to diagnose asthma. Whereas, methacholine is a chemical product and not available in some areas and countries. The measure of  fractional exhaled nitric oxide may be an alternative method to screen out Bronchial hyperresponsiveness. 

Finally, methacholine challenge does not seem to be necessary to be done in subjects with the high level of fractional exhaled nitric oxide or low level of  fractional exhaled nitric oxide. However, more studies on the correlation between of fractional exhaled nitric oxide and BHR in subjects with atypical symptoms of asthma should be realized in the future to clarify the role of of  fractional exhaled nitric oxide in diagnosis of BHR.

Conclusion

Bronchial hyperresponsiveness (BHR) is one of asthma features. The present of BHR is useful for clinicians to diagnose asthma in subjects with atypical symptoms. However, the use of methacholine challenge to confirm BHR is not available in some respiratory centers and unsafe in some clinical settings. Hence, the measure of fractional exhaled nitric oxide is a relevant alternative method to screen out Bronchial hyperresponsiveness in subjects with suspected symptoms of asthma.