Combined measurements of fractional exhaled nitric oxide and nasal nitric oxide levels for assessing upper airway diseases in asthmatic patients

ABSTRACT

Background: Despite the close linkage between rhinitis, chronic rhinosinusitis (CRS) and asthma, relevant biomarkers of both upper and lower airway inflammation are rare. Methods: Patients with asthma (without upper airway disease [UAD; n = 24], with rhinitis [n = 25], CRS [n = 24], and nasal polyps [n = 2]), isolated rhinitis (n = 13), isolated CRS (n = 13), and 10 healthy controls were prospectively recruited. Fractional exhaled nitric oxide (NO) levels at 50 mL/s (FeNO₅₀), nasal NO levels, Lund–Macay-scores of sinus computed tomography and an asthma control questionnaire (ACQ) were evaluated. Results: Asthma was associated with higher FeNO₅₀ levels irrespective of the UAD category. FeNO₅₀ levels were higher in asthmatics with CRS (median: 54.0 ppb) than those with rhinitis (35.2 ppb, p = 0.02) and those without UAD (34.3 ppb, p = 0.002). Nasal NO levels were higher in rhinitis patients than other UAD categories, irrespective of the asthma concomitance. Nasal NO levels were higher in asthmatics with rhinitis (112.8 ppb) than those without UAD (67.2 ppb, p = 0.001) and those with CRS (57.6 ppb, p < 0.0001). A receiver-operating-characteristic curve analysis for detecting comorbid allergic rhinitis (AR) in asthmatics showed a high area under the curve (0.87). Nasal NO levels were positively correlated with FeNO₅₀ levels (ρ = 0.56, p = 0.003) in asthmatics with rhinitis. In contrast, they were negatively correlated with the Lund–Macay (ρ = −0.46, p = 0.03) and ACQ scores (ρ = −0.52, p = 0.009) in asthmatics with CRS. Conclusions: Higher nasal NO levels reflect the presence of AR, irrespective of asthma concomitance. Higher FeNO₅₀ levels reflect the presence of CRS and asthma. These NO measurements are useful for assessing comorbid UAD in asthmatics.

KEYWORDS:

• Biomarkers
• diagnostics
• rhinitis/sinusitis

Acknowledgements

The authors thank Professor Elizabeth F. Juniper for approving the use of the Asthma Control Questionnaire.

Declaration of interest

ANi received honorarium from Astellas, AstraZeneca, Kyorin, GSK, Boehringer Ingelheim, research findings from Astellas, and donated funds from Boehlinger Ingelheim, Kyorin, Astellas, MSD, Daiichi Sankyo, Taiho, Teijin,Ono, Takeda, Maruho. TO received donated funds from Ono. MT received donated funds from MSD. Other authors have no conflicts of interest.

Additional information

Funding

This work was supported in part by research grants from MSD, Eisai, Novartis Pharma and AstraZeneca.