The Use of Exhaled Nitric Oxide in the Management of Asthma

It has recently become clear that airways disease associated with eosinophilic airway inflammation, but not other patterns of inflammation, is closely associated with favourable short-and long-term responses to corticosteroid therapy, irrespective of the clinical context in which it occurs. Moreover, a raised exhaled nitric oxide (FE_NO) is a reasonable marker of eosinophilic airway inflammation, which has a number of advantages as a diagnostic and monitoring tool. In this review we outline essential background information on the use of FE_NO in clinical practice and discuss some recent work evaluating the clinical value of this technique.     

Exhaled Nitric Oxide in Evaluation of Young Adults with Chronic Cough

Background. Bronchial asthma (A) is frequently diagnosed in patients with chronic cough. The study was conducted to determine whether an evaluation of fractional exhaled nitric oxide (FeNO) concentration can be used as a screening test for asthma in young adults with chronic cough (CCP). Methods. The study was performed on 540 (mean age 26.5; range 18–45 years), nonsmoking young CCP. All patients had resting spirometry within normal limits and no abnormalities on chest radiographs. Skin prick tests with common aeroallergens, bronchial provocation challenge with histamine, and evaluation of FeNO concentration were performed in all patients. One hundred healthy, nonsmoking, nonatopic subjects were used as control subjects (HC). Results. Asthma (A) was diagnosed in 178 CCP (32.96%). Other frequent diagnoses included rhinitis/sinusitis (R) and gastroesophageal reflux (GERD). The median FeNO concentration in A (86 ppb; 95% CI 72 to 94,5 ppb) was significantly greater than in R (37 ppb; 95% CI 35,6 to 42,9 ppb; p < 0.0001), GERD (14,8 ppb; 95%CI 13.3 to 16.2 ppb; p < 0.0001), or in HC (13 ppb; 95%CI 11 to 15 ppb; p < 0.0001). Significant correlation was found between log_FeNO and bronchial reactivity expressed as log_PC20 (r = ?0.529; 95%CI ?0.616 to ?0.429; p < 0.0001), but even stronger correlation was demonstrated between log_FeNO and peripheral blood eosinophilia (r = 0.757; 95%CI 0.717 to 0.792). Receiver Operator Characteristic (ROC) curve analysis revealed that CCP can be screened for A by measuring FeNO concentration. Using 40 ppb as a cut-off value for the FeNO concentration, the specificity 82.6% and sensitivity 88.3% can be achieved. Conclusion. In clinical practice, assessment of FeNO concentration can be used as a screening test for asthma in young adults who have chronic cough.     

Usefulness of Exhaled Nitric Oxide for Diagnosing Asthma

Rationale. A standard asthma diagnosis is made based on clinical history, reversibility of airway obstruction, and bronchial hyperresponsiveness. Fractional exhaled nitric oxide (FeNO) is a noninvasive airway inflammatory marker that has been suggested as a diagnostic tool for asthma. The aim of this study was to establish a FeNO cut-off value for asthma diagnosis. Methods. One hundred and fourteen consecutive adult patients (mean age 34 ± 13 years) reporting symptoms consistent with asthma, with normal spirometric parameters and a negative bronchodilator test, were included in the study. All underwent a methacholine challenge test following the five-breath dosimeter protocol. FeNO was measured with a portable device (NioxMino, Aerocrine AB, Sweden) just before the methacholine challenge. The sensitivity, specificity, and diagnostic performance of FeNO measurement were calculated. Results. Thirty-five out of the 114 patients (30.7%) were diagnosed with asthma. A positive methacholine challenge was associated with higher FeNO levels and with lower forced expiratory volume in one second (FEV₁) at baseline. No correlation was found between methacholine provocative concentration causing a decrease of 20% in FEV₁ (PC₂₀) and FeNO levels. A receiver-operating characteristic curve was constructed for FeNO levels (area under the curve [AUC]: 0.762; 95% confidence interval [CI]: 0.667-0.857; p < .001). The FeNO cut-off point with maximal specificity and sensitivity for asthma diagnosis was 40 ppb. Conclusions. Patients with confirmed asthma showed higher FeNO levels. A cut-off value of 40 ppb was calculated as the most efficient for asthma diagnosis in our population. The use of FeNO measurement may be a helpful tool to rule out a diagnosis of asthma, especially in patients in whom a methacholine challenge is not feasible or available.     

Correlation of Exhaled Nitric Oxide, Spirometry and Asthma Symptoms

Asthma is the most common chronic disease of childhood. Asthma severity is monitored by spirometry. However, this does not directly measure airway inflammation. Exhaled nitric oxide (FeNO) is a proposed method to measure airway inflammation non-invasively. Previous studies have shown that FeNO correlates with endobronchial biopsies and symptoms in patients with asthma. We monitored daily asthma symptoms compared to monthly spirometry and FeNO. Total monthly symptom scores correlated with both forced expiratory volume at 1 sec (FEV₁) and FeNO. FeNO had a strong correlation than FEV₁. FeNO and FEV₁ were not correlated. We propose that FeNO should be used as an additional monitoring tool for asthma.     

Correlation of Exhaled Nitric Oxide,Spirometry and Asthma Symptoms

Asthma is the most common chronic disease of childhood. Asthma severity is monitored by spirometry. However, this does not directly measure airway inflammation. Exhaled nitric oxide (FeNO) is a proposed method to measure airway inflammation non-invasively. Previous studies have shown that FeNO correlates with endobronchial biopsies and symptoms in patients with asthma. We monitored daily asthma symptoms compared to monthly spirometry and FeNO. Total monthly symptom scores correlated with both forced expiratory volume at 1 sec (FEV₁) and FeNO. FeNO had a strong correlation than FEV₁. FeNO and FEV₁ were not correlated. We propose that FeNO should be used as an additional monitoring tool for asthma.     

Exhaled Nitric Oxide Decreases in Association with Attendance at an Asthma Summer Camp

Attendance at a summer asthma camp has been associated with improved outcomes in children with asthma. We hypothesized that one mechanism involved in improved asthma outcomes is reduction in airway inflammation. To investigate this, we measured the fractional concentration of exhaled nitric oxide (FeNO), lung function (forced expiratory volume in 1 sec, FEV₁) and asthma control (Juniper Asthma Control Questionnaire, ACQ) from children at the beginning and end of a 1-week asthma summer camp. We also obtained a symptoms-only ACQ at 1 and 6 months after the end of camp. We enrolled 10 girls, 17 boys, mean (± SD) age = 9.6 ± 1.3 years. At baseline, FeNO (ppb), median (25–75 IQR) = 11.4 (7.2–21.3); ACQ = 0.86 (0.43–1.21); FEV₁ (%pred, mean ± SD) = 87 ± 10. At the end of camp, FeNO = 6.2 (4.4–8.4), a change of ?45%, p < 0.0001; ACQ = 0.71 (0.43–1.14), a fall of 14%, p = 0.72; and mean FEV₁% predicted remained unchanged. There were no significant changes in the follow-up symptoms-only ACQ at 1 and 6 months. We conclude that airway inflammation, as measured by FeNO, improved during 1 week of asthma camp, but there were no significant changes in lung function or asthma control. Since no child had a change in anti-inflammatory therapy during camp, these findings suggest that airway inflammation was reduced because of improved adherence to therapy and/or reduced exposure to pro-inflammatory stimuli in the home environment. The finding of reduced inflammation following attendance at an asthma summer camp should motivate the child, the parents and the clinician to focus their efforts on improving adherence to therapy and reducing exposures at home.     

Asthma Control Test Is Correlated to FEV1 and Nitric Oxide in Greek Asthmatic Patients: Influence of Treatment

Background. Asthma is a common chronic disease affecting patients’ health status and quality of life. Although recent guidelines focus on asthma control, asthma remains poorly controlled in many patients even under specialist care. Asthma Control Test? (ACT) is a short, simple, patient-based tool that provides consistent assessment of asthma. Objective. The aim of this study was to estimate the relationship of ACT with objective measures of lung function and inflammation such as forced expiratory volume in 1st second (FEV₁) and exhaled nitric oxide (FeNO) in outpatients admitted for initial diagnosis of asthma and at follow-up. Methods. One hundred and sixty (104 women and 56 men, mean age 39.7 ± 16.6 years) asthmatic patients with newly diagnosed asthma were included in the study. Patients completed the ACT questionnaire and underwent a detailed clinical examination, FeNO measurement, and prebronchodilator spirometry before (visit 1) and 4–12 weeks after initiation of treatment (visit 2). Results. At visit 1, the mean ACT score was 21.27 ± 3.74. According to ACT score, 37 patients (23.1%) were completely controlled, 85 patients (53.1%) were partly controlled, and 38 patients (23.8%) were uncontrolled. Patients with uncontrolled asthma had statistically higher FeNO values than patients with partly controlled (p = .038) and completely controlled asthma (p = .016). ACT score was found to have a positive correlation with prebronchodilator %FEV₁ (r = 0.177, p = .025) and negative correlation with FeNO ( r = ?0.211, p = .007). At visit 2, the mean ACT score was 23.00 ± 2.19. The change in ACT score between the two visits was significantly correlated to changes in FEV₁ (r = 0.538, p < .001) and in FeNO (r = ?0.466, p < .001). Patients treated with inhaled corticosteroids (ICSs) showed significant improvement in FEV₁ and in ACT score and a decrease in FeNO compared with patients without ICS treatment. Conclusion. Although FEV₁ remains the main objective parameter for evaluating asthma, ACT score was found to reflect lung function and inflammation in a Greek asthmatic population.     

Reference Values and Determinants of Exhaled Nitric Oxide in Healthy Korean Adults

Background: Measuring fractional exhaled nitric oxide (FeNO) provides an indication of airway inflammation and is used as an inflammatory marker for asthma management. However, reference values and determinants of FeNO levels are not well defined in healthy Asian adults. This study aimed to establish FeNO reference values in nonsmoking, healthy Asian adults and to determine the factors related to FeNO levels. Methods. The authors measured FeNO in 166 nonsmoking, healthy Korean adults and collected data regarding factors possibly associated with FeNO, including age, height, weight, and respiratory symptoms. Lung function was measured using spirometry, and atopic status was determined based on the skin-prick test. Results. In a multivariate linear regression analysis, FeNO levels were positively associated with male gender (p = .008) and atopy (p = .044) after adjusting for age, height, weight, forced expiratory volume in one second (FEV₁), and chronic rhinitis. Reference values were presented according to gender and atopic status, and the mean FeNO value was highest in male atopic subjects (37.3 ± 12.1 ppb), followed by nonatopic males (33.9 ± 14.3 ppb), atopic females (28.6 ± 17.7 ppb), and nonatopic females (24.1 ± 10.6 ppb). In healthy Korean adults, FeNO levels showed a significant and independent association with male gender and atopy. Conclusions. We believe that the presented FeNO reference values and the determining factors could be useful for research and clinical practice in the adult Asian population.     

Association of Asthma Education with Asthma Control Evaluated by Asthma Control Test,FEV1, and Fractional Exhaled Nitric Oxide

Background. Asthma education is an important adjunct for asthma control although the way asthma education affects asthma outcomes is poorly understood. The asthma control test (ACT), forced expiratory volume in 1 s (FEV₁), and fractional exhaled nitric oxide (FeNO) have all been used as markers of asthma control. However, the use of FeNO as a surrogate marker remains controversial. Objectives. (i) To examine whether asthma education is associated with asthma control; (ii) to compare absolute levels and changes of ACT, FEV₁, and FeNO over a year; and (iii) to evaluate whether FeNO can be used as an additional marker of asthma control. Methods. Fifty asthmatics with poor adherence (12 mild, 21 moderate, and 17 severe) received asthma education at study entry. Medications were unchanged for the first 3 months, and ACT, FEV₁, and FeNO measurements were recorded at entry, 3, 6, and 12 months. Asthma control was assessed at each visit and patients were categorized as either “stable” or “unstable” asthmatics according to the global initiative for asthma (GINA) guidelines. Results. A significant decrease in FeNO and increase in ACT score were noted in the stable asthmatic group at 3 months (p < .001), and this persisted over 12 months. Significant correlations were seen between changes (Δ) in FeNO, ACT, and FEV₁ over time. However, significant correlations between the absolute levels were not maintained over 12 months. A decrease of ≥18.6% in FeNO and a ≥3-point increase in ACT score (sensitivity: 80% and 73.3% and specificity: 83.3% and 87.5%, respectively) were associated with stable asthma control although the absolute levels were not. Conclusions. Asthma education may be useful to achieve stable control. In addition, changes rather than absolute levels of FeNO and ACT may be better markers of asthma control.     

Exhaled Nitric Oxide Predicts Asthma Exacerbation

The fraction of exhaled nitric oxide (FeNO) is elevated in asthmatics compared to normal subjects. Many studies have demonstrated that FeNO correlates with other markers of airway inflammation. The purpose of this study was to assess the clinical utility of routine monitoring of FeNO in determining its ability to predict future asthma exacerbations compared with other standard clinical measures of spirometry, peak flows, quality of life score, medication usage, and symptoms. A convenience sample of 22 patients with moderate and severe‐persistent asthma in the University of New Mexico Adult Asthma Clinic were evaluated during a routine clinic visit and then noted whether they had an exacerbation within 2 weeks of the initial appointment. Those with an exacerbation had a higher mean FeNO (29.67 ppb ± 14.48) compared to those who did not (12.92 ppb ± 5.17), p = 0.002. A nominal logistic regression model to determine those variables that predict asthma exacerbation found that FeNO was the only significant predictor, p = 0.03. Thus, FeNO appears to be a clinically useful tool to assess disease control in this population.     

Exhaled Nitric Oxide Predicts Asthma Exacerbation

The fraction of exhaled nitric oxide (FeNO) is elevated in asthmatics compared to normal subjects. Many studies have demonstrated that FeNO correlates with other markers of airway inflammation. The purpose of this study was to assess the clinical utility of routine monitoring of FeNO in determining its ability to predict future asthma exacerbations compared with other standard clinical measures of spirometry, peak flows, quality of life score, medication usage, and symptoms. A convenience sample of 22 patients with moderate and severe-persistent asthma in the University of New Mexico Adult Asthma Clinic were evaluated during a routine clinic visit and then noted whether they had an exacerbation within 2 weeks of the initial appointment. Those with an exacerbation had a higher mean FeNO (29.67 ppb ± 14.48) compared to those who did not (12.92 ppb ± 5.17), p = 0.002. A nominal logistic regression model to determine those variables that predict asthma exacerbation found that FeNO was the only significant predictor, p = 0.03. Thus, FeNO appears to be a clinically useful tool to assess disease control in this population.     

Association of Exhaled Nitric Oxide to Asthma Burden in Asthmatics on Inhaled Corticosteroids

Background. Fractional exhaled nitric oxide (FENO) is a marker of airway inflammation. Its role in assessing asthma burden in clinical practice needs more study. Objective. To determine whether higher FENO levels are associated with greater asthma burden. Methods. This was a multicenter cross-sectional retrospective study of atopic 12- to 56-year-old persistent asthmatics on inhaled corticosteroids (ICS). Questionnaire and 1-year retrospective administrative data were used to analyze by unadjusted and adjusted robust Poisson regression (relative risks) and negative binomial regression [incidence rate ratios (IRRs)] the associations of masked FENO levels (NIOX MINO®) to short-acting beta-agonist (SABA) dispensings and oral corticosteroid (OCS) use in the past year independent of spirometry and an asthma control tool [Asthma Control Test (ACT)]. Results. FENO levels ranged from 7–215ppb (median 28ppb) in 325 patients. Higher FENO levels significantly correlated with more SABA dispensings and OCS courses in the past year, lower FEV₁% predicted levels, but not ACT score. FENO highest (≥48ppb) versus lowest (≤19ppb) quartile values were associated independently in the past year with ≥7 SABA canisters dispensed (relative risk=2.40, 95% CI=1.25–4.62) and total number of SABA canisters dispensed (IRR=1.46, 95% CI=1.12–1.99) and with ≥1 OCS course (relative risk=1.48, 95% CI=1.06-2.07) and total number of OCS courses (IRR=1.71, 95% CI=1.09–2.66). The significant independent relationship of higher FENO levels to increasing SABA dispensings and OCS courses was confirmed by linear trend analyses. Conclusions. Independent and clinically meaningful associations between higher FENO levels and greater asthma burden during a prior year in persistent asthmatics on ICS suggest that FENO measurement may be a complementary tool to help clinicians assess asthma burden.     

Adiposity,Adipokines, and Exhaled Nitric Oxide in Healthy Adults Without Asthma

Background. Epidemiological studies have shown that obesity/adiposity is closely associated with asthma in terms of development, severity, and control of asthma. However, effects of obesity/adiposity on airway inflammation are not well known in subjects without asthma. We assessed whether fractional exhaled nitric oxide (FeNO), a marker of eosinophilic airway inflammation, was associated with obesity/adiposity in nonasthmatic healthy adults. Methods. We measured FeNO and serum levels of adipose-derived hormones and adipokines in 117 adult subjects without a previous diagnosis of asthma or current asthmatic symptoms. Associations between FeNO and measures of obesity/adiposity [body mass index (BMI), body fat mass, and body fat percentages] were examined by correlation analyses and uni- and multivariate linear regression analyses. Results. FeNO was not significantly associated with BMI, body fat mass, or body fat percentage by a multivariate linear regression model, adjusting for age, gender, chronic rhinitis, atopy, and lung function. No significant association of FeNO with serum levels of leptin, adiponectin, tumor necrosis factor (TNF)-α, or interleukin (IL)-6 was observed. Conclusions. These findings suggest that in healthy subjects without asthma, obesity/adiposity has no significant effect on eosinophilic airway inflammation and that hormones and systemic inflammation derived from adipose tissue do not affect eosinophilic airway inflammation.     

Validation Study of Fractional Exhaled Nitric Oxide Measurements Using a Handheld Monitoring Device

We tested reproducibility of exhaled nitric oxide (FE_NO) and inter-operator handling when measured with a handheld device, NIOX MINO®. We enrolled 20 volunteers using a priori goals of acceptable reproducibility to be mean within-subject standard deviation less than 3 parts per billion (ppb) for FE_NO measurements less than 30 ppb, and mean coefficient of variation less than 10% for FE_NO measurements more than 30 ppb. Seventeen subjects with measurements less than 30 ppb displayed a mean standard deviation of 1.15, and 3 subjects with FE_NO more than 30 ppb had a mean coefficient of variation of 2.4%. We conclude that NIOX MINO demonstrates excellent reproducibility for all ranges of FE_NO.     

Validation Study of Fractional Exhaled Nitric Oxide Measurements Using a Handheld Monitoring Device

We tested reproducibility of exhaled nitric oxide (FE_NO) and inter-operator handling when measured with a handheld device, NIOX MINO®. We enrolled 20 volunteers using a priori goals of acceptable reproducibility to be mean within-subject standard deviation less than 3 parts per billion (ppb) for FE_NO measurements less than 30 ppb, and mean coefficient of variation less than 10% for FE_NO measurements more than 30 ppb. Seventeen subjects with measurements less than 30 ppb displayed a mean standard deviation of 1.15, and 3 subjects with FE_NO more than 30 ppb had a mean coefficient of variation of 2.4%. We conclude that NIOX MINO demonstrates excellent reproducibility for all ranges of FE_NO.     

Measurement of Fractional Exhaled Nitric Oxide by a New Portable Device: Comparison with the Standard Technique

Background. Fractional exhaled nitric oxide (FeNO) measurement is a reliable, noninvasive marker of airway inflammation. The use of portable FeNO analyzers may enable the assessment of airway inflammation in primary care. Objective. The authors compared FeNO values obtained by a new portable device (NObreath, Bedfont, UK) to those of the standard stationary analyzer (NIOX, Aerocrine, Sweden) in a large cohort of asthmatic patients. Methods. One hundred and fifty-four (age range: 14–83 years, forced expiratory volume in one second [FEV₁] range: 48–134% predicted, asthma control test [ACT] range: 7–25) out of 168 recruited patients completed the study. Each patient performed at least two valid FeNO measurements at a constant flow rate of 50 ml/s on each of the two analyzers. Results. A significant relationship between the FeNO values obtained by the two devices (r = .95, p < .001) was found. Altman-Bland plot confirmed this agreement. Within-patient repeatability was excellent in both devices. Intraclass correlation coefficients for NIOX and NObreath values were .925 and .967, respectively. By means of receiver operating characteristic curve analysis, the FeNO cutoff points that better identified patients with ACT ≥ 20 were 15 ppb (0.84 sensitivity and 0.42 specificity) by NIOX and 25 ppb (0.53 sensitivity and 0.69 specificity) by NObreath. Easiness to use of both devices, assessed by visual analogue scale was not different. Conclusion. FeNO measurements obtained by the new portable FeNO analyzer are reliable because they are directly comparable with those obtained by the stationary standard device. The use of portable instruments may facilitate the FeNO measurement in primary care.     

Fractional Exhaled Nitric Oxide Has a Good Correlation with Asthma Control and Lung Function in Latino Children with Asthma

Background. Although the measurement of fractional exhaled nitric oxide (FE_NO) has been recommended for observational studies and clinical trials of asthma, FE_NO has not been examined in studies of childhood asthma in Latin America, Objective. To examine the relationship between FE_NO and indicators of disease control or severity [asthma control test/childhood asthma control test (ACT/C-ACT), lung function, and exercise challenge test (ECT)] in Mexican children with persistent asthma, Methods. Children (6–18 years of age) with persistent asthma were consecutively recruited in a tertiary asthma clinic and divided into two groups, e.g. FE_NO < 20 parts per billion (ppb) and ≥20 ppb.Adequate FE_NO measurements were obtained in 134 (83.2%) of 161 eligible children, Results. Children with FE_NO<20 ppb had significantly higher scores on the ACT/C-ACT than those with FE_NO ≥ 20 ppb (median [interquartile range] :23 [20.8–25] vs. 21 [18–24], p = .002, respectively). Compared to children with FE_NO ≥20 ppb, those with FE_NO <20 ppb had a higher baseline predicted forced expiratory volume (FEV₁₎ [94% (92.5%–99.4%) vs. 83% (81%–89.9%), p = .001] and a lower probability of having a positive ECT (42.7% vs. 71.2%, p = .001). In addition, FE_NO was significantly inversely correlated with the participants’ ACT/C-ACT score and predicted FEV₁, and directly correlated with positive ECT, Conclusion. Among Mexican children with persistent asthma, low levels of FE_NO ( <20 ppb) are associated with better asthma control, and higher lung function.     

Comparison of two exhaled nitric oxide analyzers: the NIOX MINO hand-held electrochemical analyzer and the NOA280i stationary chemiluminescence analyzer

Background and objective: Measurement of the fraction of nitric oxide (FeNO) in exhaled air is useful in the management of asthma. A new hand‐held nitric oxide (NO) analyzer, the NIOX MINO, is simple and easy to use in clinical practice. In this study, FeNO values measured using the NIOX MINO were compared with those obtained using a stationary chemiluminescence analyzer, the Sievers NOA280i. Methods: FeNO was measured in 100 adults, using both the NIOX MINO and the NOA280i. Nine (9.0%) of these subjects had asthma. The first acceptable measurement with the NIOX MINO and the mean of two acceptable measurements with the NOA280i were compared. Results: There was a significant correlation between FeNO concentrations measured with the two devices (r = 0.876, P < 0.001). A Bland–Altman plot showed a high degree of agreement between the two devices: the mean inter‐device difference was 3.3 parts per billion (ppb), and the 95% limits of agreement were ?7.0 and 13.6 ppb. In addition, the mean relative difference was 14.5%, with the 95% limits of agreement being ?33.7 and 62.7%. The mean value (± standard error of the mean) for FeNO as measured with the NIOX MINO (18.8 ± 0.9 ppb) was significantly lower than that measured with the NOA280i (22.1 ± 1.2 ppb, P < 0.001). Conclusions: There was a significant correlation, but only moderate agreement, between FeNO values measured with the NIOX MINO and those measured with the NOA280i, with the NIOX MINO values being significantly lower than the NOA280i values. Significant differences in FeNO values obtained with these two NO analyzers should be considered when interpreting the results of FeNO measurements.     

Exhaled Nitric Oxide in Children with Allergic Rhinitis and/or Asthma: A Relationship with Bronchial Hyperreactivity

Background. Nowadays, the measure of the fractional concentration of exhaled nitric oxide (FeNO) enables to assess airway inflammation during an office visit and there is international consensus on this testing methodology. The aim of this study was to evaluate whether FeNO measurement is predictable for bronchial hyperreactivity (BHR) in children with allergic rhinitis, asthma, or both. Methods. Two hundred and eighty children with allergic rhinitis, allergic asthma, or both were evaluated. Bronchial function (FEV₁ and FEF_25–75), BHR (assessed by methacholine challenge), FeNO, and sensitizations were assessed. Results. Bronchial function, BHR, and FeNO were significantly different in the three groups (p < .001). A strong inverse correlation between FeNO and BHR was found in patients with asthma and with asthma and rhinitis (r?=??0.63 and r?=??0.61, respectively). A cutoff of 32 ppb of FeNO was a predictive factor for BHR. Conclusions. This study highlights the relevance of FeNO as possible marker for BHR in allergic children and underlines the close link between upper and lower airways.     

Exhaled Nitric Oxide and Bronchial Wall Thickening in Asthmatics During and After Acute Exacerbation: Evidence of Bronchial Wall Remodeling

To assess whether bronchial wall thickening during asthma exacerbations is due to active inflammation in severe asthmatics, we measured bronchial wall thickness and exhaled nitric oxide (FeNO) following treatment. Nine asthmatics were compared with seven controls with high-resolution computed tomography, spirometry, and FeNO measurements. The asthmatic bronchial wall area percent and FeNO was greater than controls. Following treatment, the FEV₁ markedly improved, FeNO decreased modestly, and bronchial wall area percent did not change significantly. Bronchial wall thickening persisted after treatment of acute asthma exacerbation despite improvement in spirometry and decline in FeNO, possibly due to chronic airway remodeling.