Nasal nitric oxide is a useful biomarker for acute unilateral maxillary sinusitis in pediatric allergic rhinitis: A prospective observational cohort study

Abstract

Background: Nasal nitric oxide (nNO) could be a biomarker for nasal passage inflammation and sinus ostial patency. We have aimed to investigate the nNO concentration and the effect of antibiotic therapy in children with perennial allergic rhinitis (PAR) children with/without acute bacterial sinusitis.

Methods: We enrolled a cohort of 90 and 31 children with PAR, without and with acute unilateral maxillary sinusitis, and 79 normal children. Acute bacterial maxillary sinusitis was diagnosed based on clinical signs and symptoms, radiographic examination and nasal fibroendoscopy. Rhinitis control assessment test (RCAT), rhinomanometry, nNO and fractional exhaled NO (FENO) measurements were performed before and 2 weeks after antibiotic therapy.

Results: We found significantly higher mean nNO levels, FENO values, and total nasal resistance in children with PAR than in normal children (p ​< ​0.05). Acute unilateral maxillary sinusitis was associated with lower lesion-side nNO levels, higher FENO values, total nasal resistance, and poor RCAT scores (p ​< ​0.05). In multivariate analysis, age, IgE, and acute maxillary sinusitis were significant factors influencing nNO levels in children with PAR. The lesion-side nNO levels, FENO values, total nasal resistance, and RCAT scores were reversed after antibiotic therapy (p ​< ​0.05). The lesion-side nNO levels were significantly correlated to nasal obstructive scores (r ​= ​0.59, p ​< ​0.05) and expiratory nasal resistance (r ​= ​-0.54, p ​< ​0.05) in the acute maxillary sinusitis. A cut-off nNO value of 538 ​ppb showed 100% sensitivity and 94.9% specificity, to predict PAR from normal children. An nNO value of 462 ​ppb showed 100% sensitivity and 100% specificity to discriminate between the lesion-side and the unaffected sinus-side in PAR children with acute unilateral maxillary sinusitis.

Conclusions: We conclude that the obstruction of NO from the sinus into the nasal passage is the likely explanation for the decreased lesion-side nNO levels in acute unilateral maxillary sinusitis. nNO is a non-invasive biomarker with high sensitivity to diagnose and monitor treatment responses of PAR patients with acute rhinosinusitis. Both nNO and FENO levels return to baseline following antibiotic therapy, supporting the "one airway one disease" concept.

Keywords: ARIA, Allergic rhinitis and its impact on asthma; Der f, Dermatophagoides farinae; Der p, Dermatophagoides pteronyssinus; FENO, Fractional Exhaled NO; NO, Nitric oxide; RCAT, Rhinitis control assessment test; nNO, Nasal nitric oxide.

Fig. 1

The differences in nasal nitric oxide (nNO) levels in acute unilateral bacterial maxillary sinusitis patients, with comparisons between (A) allergic rhinitis patients and control subjects and (B) the non-affected side in these patients. Expiratory nasal resistance (C) and bronchial exhaled nitric oxide (FENO) levels (D) in the study groups. *Mean P ​< ​0.05 for comparisons among study groups. #mean P ​< ​0.05 when compared to baseline after antibiotic therapy.

Fig. 2

Pearson's correlation test for nasal nitric oxide (nNO) values, severity of nasal obstruction, and expiratory nasal resistance in perennial allergic rhinitis patients with acute unilateral maxillary sinusitis.

Fig. 3

Cutoff values of nasal nitric oxide (nNO) for differentiating (A) perennial allergic rhinitis and (B) acute unilateral maxillary sinusitis in comparison with normal healthy children and (C) lesion-side vs non-lesion side in unilateral acute sinusitis children by receiver operating characteristic curves. (D) Cutoff-values of increased nNO levels (over 45 ​ppb) after antibiotic treatment with 83.9% sensitivity and 62.2% specificity values to diagnose acute unilateral maxillary sinusitis in PAR children.