Ability of Exhaled Nitric Oxide to Discriminate for Airflow Obstruction Among Frequent Exacerbators of Clinically Diagnosed Asthma.

OBJECTIVE: Fraction of exhaled nitric oxide (FENO) has been proposed as a non-invasive biomarker for allergic inflammation seen in asthma. Many asthmatics in clinical practice have never had spirometry and recent data report misdiagnoses in patients with physician diagnosed (PD) asthma. The aim of this study was to assess the ability of FENO to discriminate between those with and without airflow obstruction (AO) among patients with PD-asthma. METHODS: Frequent exacerbators of PD-asthma (with 2 or more asthma exacerbations leading to emergency room visit or hospitalization within last 12 months) were enrolled. All patients underwent diagnostic evaluations including spirometry, FENO testing and serum immunoglobulin (IgE) and eosinophils. Serial spirometry and methacholine challenge testing (MCT) were performed as indicated. AO was defined by a decreased FEV1/FVC ratio (< 70% and/or < LLN), or a positive MCT. RESULTS: Of the 222 patients with PD-asthma, AO was found in 136 (vs. 86 without AO). 81.6% of patients with AO and 66.2% without AO completed FENO testing. There was no significant difference in the mean FENO levels among patients with or without AO (40.8 vs. 30.4 ppb, P = 0.10). Likewise, there was no difference in the serum IgE levels and serum eosinophils. CONCLUSIONS: Our analyses suggest that FENO levels do not help discriminate between those with and without AO in patients with PD-asthma. Patients who experience symptoms of asthma may have elevated FENO levels above the suggested cut points of 20-25 ppb. Objective confirmation of AO should be considered in all patients with PD-asthma, irrespective of FENO levels.

Misdiagnosis Among Frequent Exacerbators of Clinically Diagnosed Asthma and COPD in Absence of Confirmation of Airflow Obstruction.

PURPOSE: Clinical diagnosis of severe asthma and chronic obstructive lung disease (COPD) remains a challenge and often flawed with lack of objective confirmation of airflow obstruction (AO). Misdiagnosis of asthma and COPD has been reported in stable disease, data are non-existent in frequent exacerbators. We investigated misdiagnosis and its predictors in frequent exacerbators. METHODS: The cohort comprised of frequent severe exacerbators (requiring ≥2 emergency room (ER) visits or hospitalizations) of physician diagnosed (PD)-asthma and PD-COPD. All patients underwent a rigorous diagnostic algorithm over a follow-up period of 10 ± 6 months. Two board-certified pulmonologists ascertained final diagnosis. Patients with persistent absence of AO were identified to have misdiagnosis. Multivariate logistic regression analyses were used to identify predictors of misdiagnoses. RESULTS: Among 333 frequent exacerbators analyzed (171 patients with PD-asthma, 162 with PD-COPD, mean annual exacerbations 3.4 ± 2.8), 24 % of patients had a baseline post-bronchodilator spirometry. Misdiagnosis was found in 26 % (87 of 333) of patients. Another 12 % (41 of 333) of patients had obstructive lung diseases other than asthma and COPD. Independent risk factors for misdiagnosis were spirometry underutilization (PD-asthma: OR = 2.8, 95 % CI 1.16-6.78, p = 0.02 and PD-COPD: OR = 10.7, 95 % CI 2.05-56.27, p = 0.005) and pack years of smoking (PD-COPD: OR = 1.05, 95 % CI 1.01-1.11, p = 0.03). CONCLUSIONS: Objective confirmation of AO is essential in preventing misdiagnosis in frequent severe exacerbators of clinically diagnosed asthma and COPD, a third of whom have neither. Spirometry utilization is strongly associated with a reduced risk of misdiagnosis. Smoking is associated with increased risk of misdiagnosis in severe COPD, but not asthma.