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.     

Steroid-Naive Adolescents with Mild Intermittent Allergic Asthma Have Airway Hyperresponsiveness and Elevated Exhaled Nitric Oxide Levels

Although atopic asthma symptoms often seem to disappear around puberty, subjects in this age group may experience unexpected, often severe, asthma attacks. This may be related to persistence of untreated airway hyperresponsiveness/inflammation in a life period characterized by low perceptiveness of disease-related symptoms. This study was designed to evaluate the prevalence and the severity of bronchial hyperreactivity and the exhaled nitric oxide (FE_NO) levels in a group of steroid-naive asthmatic adolescents. Fifty-two patients with mild-intermittent asthma were studied, ages 12 to 16, sensitized to house dust mites; 22 age-matched controls, were also studied. Asthma patients showed FEV₁, FEF_25–75%, and FVC values not significantly different from controls, (p>0.05, each comparison). By contrast, although none of the control subjects showed bronchial hyperreactivity, increased airway responsiveness to methacholine (MCh) was demonstrated in the majority of the patients and found to be severe in 36.5% (MCh PD₂₀ ≥ 400 µg or accumulative dose ≤1220 µg) and moderate in 32.7% (MCh PD₂₀ 400–1400 µg or accumulative dose 1220–4620 µg). In addition, FE_NO concentrations were significantly higher in asthmatics, as compared with controls (20.4 ± 5.3 ppb and 4.4 ± 0.7 ppb, respectively; p<0.01) and 83% of the patients had FE_NO levels higher than 8.9 ppb (i.e., >2 standard deviations of the mean in control subjects). A positive, statistically significant correlation was found between FEF_25–75% values and MCh PD₂₀ (r = 0.358; p<0.01) or MCh accumulative dose (r = 0.355; p<0.05). No correlations were demonstrated between MCh responsiveness and FVC or FEV₁ values or FE_NO levels and between FE_NO levels and pulmonary function parameters (p>0.05). The high incidence of bronchial hyperresponsiveness to MCh and of airway inflammation (as demonstrated by the elevated FE_NO levels) in adolescents with mild asthma suggests the need for more accurate evaluation and, possibly, for early intervention with antiinflammatory drugs in a significant proportion of patients in this age group.     

Measurement of Exhaled Nitric Oxide in a General Population Sample: A Comparison of the Medisoft HypAir FENO and Aerocrine NIOX Analyzers

Background and objective. Measuring the fraction of nitric oxide in exhaled breath (FE_NO) is increasingly utilized to assess airway inflammation in asthma. The primary aim of this study was to compare exhaled nitric oxide measurements obtained using two devices from different manufacturers, that is, the recently marketed portable and electrochemical-based Medisoft HypAir FE_NO and the well-established chemiluminescence-based Aerocrine NIOX analyzer, in an unselected population. Methods. FE_NO measurements were conducted in 106 subjects (86 healthy; 20 asthmatic; 56.6% atopic). Atopy and health status were assessed by skin prick tests and questionnaire, respectively. Results. The two instruments showed strong correlation over a wide range of FE_NO measurements (8–261.3 ppb with the HypAir, 5.6–156.8 ppb with the NIOX; r = 0.98; p < .0001). This correlation was observed in the population as a whole, as well as in healthy non-atopics, healthy atopics, and atopic asthmatics when considered separately. The measurements on the HypAir FE_NO were consistently 1.6 times (95% CI 1.11–2.05) higher than those obtained with the NIOX. Conclusions. FE_NO measurements obtained with the HypAir FE_NO correlated well with the NIOX, but were approximately 1.6 times higher. Therefore, a conversion factor is required if results are to be compared with the NIOX instrument.     

The effect of exercise on exhaled nitric oxide depends on allergic rhinoconjunctivitis in children

Objective: Fractional exhaled nitric oxide (FE_NO) and exercise testing are widely used for the evaluation of pediatric asthma. The evidence relating to the effects of strenuous exercise on FE_NO in children is conflicting. Little information is available on the association between exercise and FE_NO in relation to allergic rhinoconjunctivitis (AR). We aimed to investigate the effects of AR on children's FE_NO in response to a standardized treadmill exercise test. Methods: A total of 124 children with current asthma and 124 non-asthmatic children aged 8–16 years were studied. FE_NO was measured at baseline, at 1 and 30?min after an exercise challenge test using the single breath technique with EcoMedics Exhalyzer®. A structured parental interview, spirometry, serum allergen-specific IgE and skin prick tests were performed. Results: Baseline FE_NO was higher in both asthmatics and non-asthmatics with AR than without AR (both p?<?0.001). The FE_NO time trend was dependent on AR (p?=?0.039), irrespective of asthma (p?=?0.876). In children with AR, FE_NO had declined at 1?min by a mean of 6.1 ppb with a 95% confidence level of 5.1–7.5 ppb; at 30?min, the reduction was 2.8 (2.5–3.3) ppb. In children without AR, at 1?min the decline in FE_NO was 2.7 (2.1–3.5) ppb and by 30?min post-exercise it was 1.6 (1.3–2.0) ppb. Conclusions: The impact of exercise on FE_NO was dependent on the allergic phenotype, regardless of asthma status. FE_NO decreased immediately after exercise, and did not return to baseline level within 30?min.     

Persistent elevation of exhaled nitric oxide and modification of corticosteroid therapy in asthma

BackgroundPersistent airway inflammation, detected by fractional exhaled nitric oxide (FE_NO), is occasionally observed in asthmatic patients, even in those treated with inhaled corticosteroids (ICS). However, improvement in residual airway inflammation and pulmonary function through modification of corticosteroid therapy has not been proven.MethodsThirteen asthmatic patients whose FE_NO levels were over 40 parts per billion (ppb), despite dry-powder ICS therapy, were enrolled. A 3-step change in steroid treatment was undertaken until FE_NO was less than 40 ppb. In the first step, the powder formula was changed to an ultra-fine particle compound as an equipotent ICS dose. In the second step, the ICS dose was doubled. In the third step, oral corticosteroids were added. We measured pulmonary function and FE_NO and alveolar NO concentrations (CAlvNO).ResultsDoubling the ICS dose and changing the ICS formula significantly improved FVC (p<0.001), FEV1 (p<0.05), the slope of the single nitrogen washout curve (dN₂) (p<0.01), FE_NO (p<0.001), and CAlvNO (p<0.05), relative to baseline. The reductions in FE_NO were significantly associated with the improvement in airflow limitation assessed by dN₂ (r=0.73, p=0.007). The remaining FE_NO elevation, even after doubling the ICS dose, did not decrease after oral corticosteroid administration.ConclusionsThese results suggest that modification of ICS therapy can suppress residual FE_NO elevation, and that reduction in FE_NO levels is associated with improvement in airflow limitation. However, steroid-resistance mechanisms may exist in some asthmatic patients with sustained FE_NO elevations.     

Exhaled Nitric Oxide in Pregnant Healthy and Asthmatic Women

Background. Measurement of fractioned exhaled nitric oxide (FE_NO) is useful for monitoring airway inflammation in asthma. Asthma is one of the most common diseases complicating pregnancy, and FE_NO may be helpful for monitoring asthma in pregnancy. However, some physiological alterations of FE_NO may be expected during healthy pregnancy due to vascular nitric oxide production. Until now no study assessed the level of FE_NO in asthmatic pregnant patients. Objective. We aimed to assess the possible use and reproducibility of FE_NO measurements in pregnant asthmatic women. We compared FE_NO concentrations between four groups of subjects: healthy nonpregnant and pregnant females and asthmatic nonpregnant and pregnant patients. We also investigated the relationship between FE_NO values and the level of asthma control in pregnant asthmatic patients. Methods. A total of 102 female subjects (35 healthy nonpregnant and 27 healthy pregnant females; 20 nonpregnant and 20 pregnant asthmatic women) were included in this cross-sectional study. Two FE_NO measurements were performed in each subject using an electrochemical sensor based device (NIOX MINO, Aerocrine, Solna, Sweden). Data are given as median with range. Results. The repeatability of FE_NO measurement was similar in pregnant and nonpregnant subjects. FE_NO levels did not differ significantly between healthy pregnant versus nonpregnant subjects (16.0 [8, 31] vs. 16.0 [9, 35] ppb). FE_NO levels were significantly increased in asthmatic women compared to healthy females (nonpregnant asthmatics: 38 [9, 54] ppb, p < 0.001 vs. healthy nonpregnant; pregnant asthmatic patients: 28 [10, 56] ppb; p < 0.05 vs. healthy pregnant). Conclusions. FE_NO level is not influenced by healthy pregnancy. In pregnant asthmatic patients FE_NO level is elevated compared to healthy pregnant subjects and correlates with the level of asthma control. Further studies are required to assess the use of FE_NO measurement to monitor asthma in this patient group.     

Rising trends in the prevalence of asthma and allergic diseases among school children in the north-west coastal part of Croatia

Background. Due to the multiple factors affecting exhaled nitric oxide (NO) value, physicians are often puzzled by the result of a single measurement in asthmatic patients. Objective. The aim of this prospective transversal study was to evaluate the relative contributions to exhaled NO fraction (FE_NO) of the commonly considered major NO determinants, i.e., recent symptoms (upper and lower respiratory tract), atopy (prick skin tests and degree of allergic exposure), and treatment (dose of inhaled corticosteroid [ICS]) to know what information gives a single measure. Methods. FE_NO at 50 mL/s expiratory flow was measured in 199 asthmatic children (141 boys, age: 11.2 years ± 2.5 years). The allergic risk due to pollen exposure (ARPE index) was independently evaluated by the “Réseau National de Surveillance Aérobiologique.” Results. A multivariate analysis of FE_NO as dependent variable showed that explanatory variables explained 23% of total FE_NO variance (symptoms > atopy > ICS). In the children without recent symptoms (n = 118), a FE_NO > 23 ppb predicted atopy (sensitivity 47%, specificity 85%, p = 0.0006). Multiple regression only showed a trend to significance between FE_NO and the dose of ICS (p = 0.057, r = ? 0.19). Incidentally, despite similar dose of ICS, children under fluticasone (mean ± SD, 259 ± 149 μg/day) had lower FE_NO than those under budesonide (299 ± 195 μg/day) (median [interquartile], 21 ppb [14–42], n = 55 versus 35 ppb [19–47], n = 104; p = 0.007), which may be due to a higher potency of fluticasone. A relationship between FE_NO and ARPE index was significant in children with exclusive seasonal sensitisation (n = 31, r = 0.48, p = 0.008). Conclusion. Common exhaled NO determinants weakly explain a single value of FE_NO, which only can confidently predict atopy.     

Predictors for Identifying the Efficacy of Systemic Steroids on Sustained Exhaled Nitric Oxide Elevation in Severe Asthma

BackgroundSome patients with asthma have high levels of exhaled nitric oxide fraction (FE_NO) despite inhaled corticosteroids (ICS) therapy. Early studies suggested that this might be explained by the presence of heterogeneous airway inflammation. We aimed to assess the predictors for identifying the efficacy of systemic corticosteroids on residual FEno elevations in severe asthma.MethodsTwenty severe asthmatics with persistent FE_NO elevation (≥ 40 ppb) despite maintenance therapy including high-daily-dose ICS were enrolled. Asthma Control Questionnaire (ACQ), lung function, blood eosinophils, and FE_NO were assessed before and after 14 days treatment with 0.5 mg/kg oral prednisolone/day.ResultsACQ, blood eosinophils, FE_NO level, FVC, FEV1, FEV1/FVC ratio and the slope of the single nitrogen washout curve (?N₂) were significantly improved by treatment with prednisolone. 70% of the subjects showed ≥ 20% reductions in the FENo levels. The reduction in FENo levels was significantly correlated with the improvements in ACQ p < 0.0001), FVC (p < 0.01), FEV1 (p < 0.0001), and ?N₂ p < 0.05). Among the measurements at baseline, the FE_NO levels and blood eosinophil numbers were identified as significant predictors of ≥ 20% reductions in the FEFE_NO levels by systemic steroid therapy.ConclusionsSystemic corticosteroids could suppress the residual FE_NO elevations in more than half of the patients with severe asthma and the reduction in FE_NO levels was associated with improvements in asthma control and airflow limitation. The FE_NO levels and blood eosinophil numbers were the predictors of improved residual airway inflammation by systemic steroid therapy in severe asthma.     

Relationships Between Airway Hyperresponsiveness,Inflammation, and Calibre in Asthma

Background  

Previous studies have focused upon the relationship between airway inflammation and hyperresponsiveness with different conclusions. We re-examined the relationship between airway inflammation (FE_NO), hyperresponsiveness to methacholine (AHR), and calibre (FEV₁ % predicted) in mild-to-moderate asthmatics.     

Exhaled Nitric Oxide Measurements in Hospitalized Children with Asthma

Background. The reproducibility of exhaled nitric oxide (FE_NO) measurements performed in pediatric hospitalized asthmatics has not been previously evaluated. Objective. To evaluate the reproducibility of FE_NO measurements in the hospital; to look for differences between those who were and were not able to perform FE_NO measurements; and to assess any factors correlated with FE_NO measurements. Methods. 89 hospitalized pediatric asthmatics performed FE_NO, FEV1, and peak expiratory flow rate (PEFR) maneuvers in triplicate at the time of discharge. Reproducibility was assessed using the intraclass correlation coefficient (ICC) and coefficient of variation (CV). Demographic and measured variables were compared between those who were and were not able to perform FE_NO measurements. Correlation of FE_NO with other variables was investigated. Results. FE_NO measurements showed clinically acceptable ICC and CV values (0.973 and 5.59%, respectively). These values were superior to the values obtained for FEV1 and PEFR. Subjects who successfully performed the FE_NO measurements were older, had higher PEFR readings, and had a lower asthma dyspnea score. No correlation was found between FE_NO and traditional asthma factors, though multiple factors did trend towards significance. Conclusion. FE_NO measurements can be obtained in hospitalized pediatric patients with good reproducibility. While the majority of children will be able to provide such readings, those who are younger and with a more severe exacerbation may be unsuccessful in doing so. Further research is needed to determine how best to incorporate FE_NO values into the hospital setting.     

Airway Responsiveness to Beta‐Adrenergic Agonist (Salbutamol) in Asthma

Despite the controversy of airway responsiveness to β₂‐agonist drugs in asthma, in a previous study we showed increased responsiveness of asthmatic airways to isoprenaline. Therefore, in the present study of airway sensitivity to other β₂‐agonists, salbutamol and its relationship to histamine responsiveness was reexamined. The threshold bronchodilator concentrations of inhaled salbutamol required for a 20% increase in forced expiratory flow in 1 sec (FEV₁), (PC₂₀) was measured in 20 normal and 19 asthmatic adults. Airway responsiveness to histamine, as the concentration that caused a 20% decrease in FEV₁, was also measured in 11 normal and 12 asthmatic subjects; and the correlation between PC₂₀ salbutamol and PC₂₀ histamine was evaluated. Sensitivity to salbutamol was greater in asthmatics (PC₂₀ = 7.24 mg/L) than in non‐asthmatics (PC₂₀ = 124.25 mg/L, p < 0.001). Airway responsiveness to histamine in asthmatics (PC₂₀ = 0.18 g/L) was also significantly greater than in normal subjects (PC₂₀ = 19.46 g/L, p < 0.001). There was a significant correlation between PC₂₀ salbutamol and histamine (Rs = 0.6052, p < 0.005). Maximum response to both salbutamol and histamine and slope of concentration‐response curves of both agents were significantly greater in patients with asthma than in normal subjects (p < 0.001 and p < 0.005 for maximum response and slope, respectively). The increased sensitivity of asthmatics to inhaled salbutamol suggests that they also may be more sensitive to their endogenous adrenaline, which may thus dilate and stabilize their airways.     

Relationship Between Lung Function and Asthma Symptoms in Patients with Difficult to Control Asthma

Several studies have demonstrated a poor relationship between measures of asthma control and lung function in patients with asthma. We sought to examine this relationship in a cohort of difficult to control asthmatics attending a hospital outpatient clinic. FEV₁% and asthma control scores (ACSs) were measured at the first clinic visit and at a follow-up visit. A total of 59 patients took part in the study. At the initial visit, FEV₁% correlated with limitation of activity (p = 0.002), shortness of breath (p = 0.02), wheezing (p = 0.029), and ACS (p = 0.014). However, at follow-up, there was no correlation between FEV₁% and any measured index of asthma control. When patients with severe fixed airflow obstruction were excluded from the analysis (n = 16), FEV₁% at follow-up became significantly correlated with night waking (p = 0.02), wheezing (p = 0.05), and ACS (p = 0.036). The improvement in asthma control score at follow-up was significantly and strongly associated (r = 0.51 for total asthma control, p < 0.001) with the improvement in lung function in patients without severe fixed airflow obstruction. Lung function was not associated with any measure of asthma control in patients with severe fixed airflow obstruction. FEV₁% correlates well with asthma symptoms in difficult asthma patients with poor control but not when control improves. This loss of relationship is due to subjects with severe fixed airflow obstruction where good subjective control does not exclude the presence of significant obstruction. How severe fixed airflow obstruction should be prevented, delayed, or managed in asthma requires further research.     

Serum Levels of Interleukins (IL)-4, IL-5, IL-13, and Interferon-γ in Acute Asthma

T-cell activation and alteration of cytokine levels are involved in the pathogenesis of bronchial asthma. However, the profile of circulating T-lymphocyte subsets and related cytokines during acute asthmatic attacks is still unclear. We hypothesized that serum levels of interleukin (IL)-4, IL-5, and IL-13 would be increased, whereas IFN-γ would be decreased in acute asthma. The subjects enrolled in this study included 58 acute asthmatics, 22 asymptomatic asthmatics, and 10 healthy controls. Serum levels of IL-4, IL-5, IL-13, and IFN-γ were measured using a sandwich enzyme-linked immunosorbent assay. We correlated serum levels of IL-4, IL-5, IL-13, and IFN-γ with initial forced expiratory volume in 1 sec (FEV₁). Compared with control subjects, acute asthmatics had significantly increased levels of circulating IL-4 (p < 0.001), IL-5 (p < 0.001), and IL-13 (p < 0.001), although the differences were of borderline significance in serum IFN-γ (p = 0.069). There were also significant differences in the circulating levels of IL-4, IL-5, and IL-13 between acute asthmatics and asymptomatic asthmatics. There was no significant association between initial FEV₁ and serum levels of IL-4 or IL-13, however, among acute asthmatics, a lower initial FEV₁ was associated with higher IL-5 and/or lower IFN-γ levels. Our results suggest that serum levels of IL-4, IL-5, and IL-13 may be elevated in acute asthma, and that higher levels of IL-5 and/or lower levels of IFN-γ are associated with severe airway obstruction.     

The Strategy for Predicting Future Exacerbation of Asthma Using a Combination of the Asthma Control Test and Lung Function Test

Background. Various factors have been reported to be useful for predicting future exacerbations. Objective. This study was intended to determine a usefulness of a combination of a patient-based questionnaire, such as the Asthma Control Test (ACT) score with objective assessments, such as forced expiratory volume in 1 second (FEV₁) and/or exhaled nitric oxide (FE_NO), for predicting future exacerbations in adult asthmatics. Methods. We therefore enrolled 78 subjects with mild to moderate asthma, who were clinically stable for 3 months who all had been regularly receiving inhaled steroid treatment. All subjects underwent a routine assessment of asthma control including the ACT score, spirometry, and FE_NO, and then were followed up until a severe exacerbation occurred. The predictors of an increased risk of severe exacerbation were identified and validated using decision trees based on a classification and regression tree (CART) analysis. The properties of the developed models were the evaluated with the area under the ROC curve (AUC) (95% confidence interval [CI]). Results. The CART analysis automatically selected the variables and cut-off points, the ACT score ≤23 and FEV₁ ≤ 91.8%, with the greatest capacity for discriminating future exacerbations within one year or not. When the probalility was calculated by the likelihood ratio of a positive test (LP), the ACT score ≤23 was identified with a 60.3% probability, calculated by 1.82 of LP, whereas the combined ACT score ≤23 and the percentage of predicted FEV₁ ≤ 91.8% were identified with an 85.0% probability, calculated by an LP score of 5.43, for predicting future exacerbation. Conclusion. These results demonstrated that combining the ACT score and percentage of predicted FEV₁, but not FE_NO, can sufficiently stratify the risk for future exacerbations within one year.     

Relationship between exhaled nitric oxide and IgE sensitisation in patients with asthma: influence of steroid treatment

Introduction: The influence of the degree of immunoglobulin E (IgE) sensitisation on the fraction of expired nitric oxide (FE_NO) in asthma patients being treated with inhaled corticosteroids (ICS) is not well known. Objectives: To investigate the relationship between IgE sensitisation and FE_NO, and the effect of a step‐up in ICS treatment on this relationship, in patients with allergic asthma. Methods: A primary health care centre recruited 20 non‐smoking patients with perennial allergic asthma (18 years–50 years, six male) outside the pollen season. At every visit (0, 2, 4, 8 weeks), FE_NO was measured and an exposure questionnaire was completed. ICS dose was adjusted according to FE_NO (≥22 ppb prescribed increase in ICS). Quantitative analyses of serum IgE (eight common aeroallergens) confirmed allergy. Results: At baseline, FE_NO and the sum of IgE antibody titres for perennial allergens correlated significantly (r = 0.47, P = 0.04). After a step‐up in ICS treatment, this correlation had disappeared. Nine patients had persistently elevated FE_NO at last visit (mean 35 ppb vs 16 ppb). This group was more frequently exposed to relevant allergens or colds (89% vs 27% of patients, P < 0.05) and had higher IgE antibody titres (perennial allergens) compared with the normalised group (mean 28.9 kU/L vs 10.7 kU/L, P < 0.05). Conclusion: Serum IgE against perennial allergens and FE_NO correlate in patients with allergic asthma. However, this relationship disappears after a high‐dose ICS regimen, suggesting that FE_NO relates to bronchial inflammation and not IgE levels per se. High degree of IgE sensitisation together with allergen exposure may lead to ICS‐resistant airways inflammation. Please cite this paper as: Syk J, Undén AL and Alving K. Relationship between exhaled nitric oxide and IgE sensitisation in patients with asthma: influence of steroid treatment. The Clinical Respiratory Journal 2009; 3: 143–151.     

Airway Distensibility by HRCT in Asthmatics and COPD with Comparable Airway Obstruction

Abstract

Introduction: Decreased airway distensibility (AD) in response to deep inspirations, as assessed by HRCT, has been associated with the severity of asthma and COPD. Aims: The current study was designed to compare the magnitude of AD by HRCT in individuals with asthma and COPD with comparable degrees of bronchial obstruction, and to explore factors that may influence it. Results: We enrolled a total of 12 asthmatics (M/F:7/5) and 8 COPD (7/1) with comparable degree of bronchial obstruction (FEV₁% predicted mean±SEM: 69.1 ± 5.2% and 61.2 ± 5.0%, respectively; p = 0.31). Each subject underwent chest HRCT at FRC and at TLC. A total of 701 airways (range 20 to 38 airway per subject; 2.0 to 23.1 mm in diameter) were analyzed. AD did not differ between asthmatics and COPD (mean ± SEM: 14 ± 3.5% and 17 ± 4.3%, respectively; p = 0.58). In asthmatics, AD was significantly associated with FEV₁% predicted (r² = 0.45, p = 0.018). We found a significant correlation between the change in lung volume and the change in AD by HRCT (r² = 0.64, p = 0.002). In COPD, we found significant correlations between AD and the RV% predicted (r² = 0.51, p = 0.046) and the RV/TLC (r² = 0.68, p = 0.01). Conclusions: AD was primarily affected by the dynamic ability to change lung volumes in asthmatics, and by static lung volumes in COPD.     

Difference between two exhaled nitric oxide analyzers,NIOX VERO® electrochemical hand-held analyzer and NOA280i® chemiluminescence stationary analyzer

Background: Fractional exhaled nitric oxide (FE_NO) is useful for the evaluation of eosinophilic airway inflammation, including that seen in asthma. Although a new electrochemical hand-held FE_NO analyzer, the NIOX VERO^® (Aerocrine AB, Solna, Sweden), is clinically convenient to use, it has not been fully compared with the chemiluminescence stationary electrochemical analyzer NOA280i^® (Sievers Instruments, Boulder, CO, USA) in terms of the level of measured FE_NO. The aim of this study was to determine whether there is a difference between the two analyzers. Methods: The FE_NO levels measured with both NIOX VERO^® and NOA280i^® were evaluated in 1,369 adults at Juntendo University Hospital from May 2016 to October 2016. Results: The median FE_NO level measured with the NIOX VERO^® was significantly lower than that measured with the NOA280i^® (41 ppb, range 5–368 ppb vs. 29 ppb, range 5–251 ppb; p < 0.001). There was a strong positive correlation in the measurement of FE_NO level between the NOA280i^® and the NIOX VERO^® (r = 0.942, p < 0.001). The following conversion equation was calculated: FE_NO (NOA280i^®) = 1.362 (SE, 0.661) + 1.384 (SE, 0.021) × FE_NO (NIOX VERO^®). Conclusions: To our best knowledge, we have provided the first report showing that the measured FE_NO level with the NIOX VERO^® was approximately 30% lower than that with the NOA280i^® and that there was a significant correlation between the measurements of these two devices. The correction equation that we provided may help assess the data obtained by these two analyzers. Abbreviations ATS American Thoracic Society

BMI Body mass index

ERS European Respiratory Society

FE_NO Fractional exhaled nitric oxide

GINA Global Initiative for Asthma

NO Nitric oxide

ppb Parts per billion

ROC Receiver operating characteristic

SD Standard deviation

     

Benralizumab and mepolizumab treatment outcomes in two severe asthma clinics

Background and Objective

This study compared the clinical outcomes of severe asthmatics treated with mepolizumab and benralizumab in a tertiary care severe asthma service setting.

Methods

Patient data at baseline, six and 12 months were collected prospectively at two large tertiary hospital severe asthma clinics following treatment initiation. Two hundred and four patients received treatment with mepolizumab (117) or benralizumab (87). Baseline characteristics between groups were similar in regard to age, gender, body mass index, steroid dose and blood eosinophil count. However, the mepolizumab cohort had a higher Asthma Control Questionnaire Score (ACQ) at baseline (4.0 ± 1.1 vs. 3.6 ± 0.9, p = 0.018), accompanied by more frequent reliever medication usage and lower prebronchodilator FEV₁% (56.0 ± 20.1 vs. 63.8 ± 18.9, p = 0.008).

Results

After 6 months treatment, both treatments induced significant improvements in (i) ACQ of 2.3 ± 0.1 (p < 0.001), (ii) oral steroid requiring exacerbations (incident rate ratio 0.26 (0.18–0.37), p < 0.001) and (iii) FEV₁. However, the improvement in FEV₁ was 0.18 (0.05–0.30) litres greater with benralizumab than with mepolizumab (p = 0.002) even when adjusting statistically for baseline differences between groups. These differences were even more pronounced at 12 months post-treatment initiation, when the improvement in exacerbation frequency with benralizumab was 64% greater than with mepolizumab (p = 0.01). Whilst both treatments significantly reduced the blood eosinophil count at 6 and 12 months, this reduction was substantially greater with benralizumab than mepolizumab (−260 cells/μL [−400 to −110, p = 0.001]).

Conclusion

In this large group of severe eosinophilic asthmatics, mepolizumab and benralizumab both improved disease parameters. However, benralizumab treatment appeared significantly more effective than mepolizumab in reducing exacerbations, improving FEV₁ and depleting blood eosinophils.     

Perception of Bronchoconstriction in Elderly Asthmatics

The impaired perception of bronchoconstriction in asthmatic patients may increase the risk of severe exacerbation. To characterize the perception of bronchoconstriction in elderly asthma patients, we compared the perception in older patients with that of younger patients. To determine the influence of perception of long-standing diseases, we further evaluated the perception in early-onset elderly asthma patients and in late-onset elderly asthma patients. The study group consisted of 80 stable asthmatic patients. The patients were grouped according to their age (group 1, < 60 years, n = 37; group 2, ≥ 60 years, n = 43). Each group was separated into two subgroups according to the duration of symptoms (late-onset asthma 1A and 2A, < 5 years, early-onset asthma 1B and 2B, ≥ 5 years). A histamine inhalation test was performed for each patient. Dyspnea was assessed by modified Borg scale. The Borg score in forced expiratory volume in 1 sec (FEV₁) reduction by 20% was determined as perception score 20 (PS₂₀). The mean perception scores of the elderly asthmatic patients were significantly lower than those of the younger asthmatic patients (group 1, PS₂₀ = 2.35 ± 0.17; group 2, PS₂₀ = 1.37 ± 0.12; p < 0.0001). The differences of mean perception score (PS₂₀) between early- and late-onset subgroups were insignificant (1A, 2.63 ± 0.30 and IB, 2.07 ± 0.16; p = 0.101; 2A, 1.36 ± 0.19 and 2B, 1.59 ± 0.120; p = 0.91). The mean perception scores of male asthmatic patients were significantly lower than those of female patients (p = 0.03). There was a correlation between PS₂₀ and %FEV₁ in the younger group (r = 0.392, p = 0.02), but not in the elderly group (r = 139, p = 0.375). The correlation between PS₂₀ and PD₂₀ in both younger and elderly group was insignificant (p > 0.05). Elderly asthmatics perceive less intense respiratory distress for a decrease of 20% in FEV₁ than do younger asthmatics. This underperception of bronchoconstriction may result in a delay in medical care during an acute asthmatic episode. Thus, we strongly recommend that elderly asthmatic patients should be followed up more frequently and closely.     

Urates in exhaled breath condensate as a biomarker of control in childhood asthma

Objective: The aim of this study was to (1) investigate the possibility to use urates in exhaled breath condensate (EBC) as a biomarker of airway inflammation and control in childhood asthma and (2) explore their association with other biomarkers of airway inflammation and clinical indices of asthma control (Asthma Control Test [ACT], quality of life [PAQLQ], lung function, prn beta-agonist use, time from last exacerbation [TLE]. Methods: This cross-sectional study comprised 103 consecutive patients (age 6–18 years) divided in groups of uncontrolled ([NC], n?=?53) and controlled asthma ([C], n?=?50). Measured lung function and biomarkers included: spirometry, eosinophilic cationic protein (ECP), high-sensitivity C-reactive protein (hs-CRP), exhaled NO (F_ENO), pH and urates in EBC and exhaled breath temperature (EBT). Results: Statistically significant differences were found between groups for EBC urates, EBC pH and EBT (NC versus C: EBC urates, median [IQR], µmol/L; 10 [6] versus 45 [29], p?<?0.001; EBC pH, mean [SD], 7.2 [0.17] versus 7.33 [0.16], p?=?0.002; EBT mean [SD], °C; 34.26 [0.83], versus 33.90 [0.60], p?=?0.014). EBC urates showed significant association with TLE and F_ENO (r?=?0.518, p?<?0.001; r?=?0.369, p?=?0.007, respectively) in NC, and EBC pH (r?=?0.351, p?<?0.001), FEV₁ (r?=?0.222, p?=?0.024), ACT (r?=?0.654, p?<?0.001), PAQLQ (r?=?0.686, p?<?0.001) and prn salbutamol use (r?=??0.527, p?<?0.001) in all asthmatics. Conclusion: In our study, EBC urates were found to be the best single predictor of asthma control and underlying airway inflammation. Our results provide evidence supporting the potential utility to use EBC urates as an additional non-invasive biomarker of control in childhood asthma.