Stratifying a Risk for an Increased Variation of Airway Caliber among the Clinically Stable Asthma

ABSTRACTBackgroundRecently, correlations of peak expiratory flow (PEF) variation have been shown to facilitate the prediction of later asthma symptoms and exacerbations. However, it has not been fully examined whether or not any patient characteristics are associated with the residual airway lability in treated asthmatics. The objective of this study is to examine a predictive marker for increased variation of PEF in patients with clinically stable asthma.MethodsWe studied 297 asthmatic patients who were monitored for PEF twice a day. Asthma Control Questionnaire (ACQ), spirometry, and exhaled nitric oxide fraction (FENO) were measured. After the assessment of baseline values, PEF measuring was continued and associations between these clinical markers and later variation of PEF over a week (Min%Max) were investigated.Results17.5% of the subjects showed increased PEF variability (Min%Max < 80%). ACQ, forced expiratory volume in 1 s % of predicted (%FEV1), and FENO were identified as independent predictors of Min%Max < 80%. An ACQ ≥ 0.4 yielded 96% sensitivity and 59% specificity, a %FEV1 ≤ 85% yielded 62% sensitivity and 89% specificity, and a FENO ≥ 40 ppb yielded 75% sensitivity and 90% specificity for identifying the subjects with high variability in PEF. When we combine %FEV1 ≤ 85% and FENO ≥ 40 ppb, this index showed the highest specificity (98%) for increased PEF variability.ConclusionsThese results indicate that ACQ, %FEV1 and FENO can stratify the risk for increased variation in airway caliber among patients with stable asthma. This may help identify subjects in whom further monitoring of lung function fluctuations is indicated

Improvement of Airflow Limitation by Fluticasone Propionate/Salmeterol in Chronic Obstructive Pulmonary Disease: What is the Specific Marker?

Backgrounds: Inhaled corticosteroids (ICS)/inhaled long-acting beta2-agonists (LABA) combination drugs are widely used for the long-term management of chronic obstructive pulmonary disease (COPD). However, COPD is a heterogeneous condition and treatment with ICS is associated with a higher risk of pneumonia. The identification of a specific marker for predicting the efficacy of ICS/LABA on pulmonary function would be useful in the treatment of COPD. Methods: Fourteen COPD patients receiving tiotropium therapy participated consecutively. The relationship between the baseline exhaled nitric oxide (FENO) levels as well as serum markers and changes in pulmonary function by fluticasone propionate (FP)/salmeterol (SAL) were analyzed. Results: FP/SAL therapy significantly improved forced vital capacity, forced expiratory volume in 1 s (FEV1), and the third phase slope of the single nitrogen washout curve (ΔN2) as well as the FENO level. The baseline FENO levels and positive specific IgE (atopy+) were significantly associated with airway obstructive changes assessed by FEV1 and ΔN2. A baseline FENO level >35 ppb yielded 80.0% sensitivity and 66.7% specificity for identifying the subjects with significant improvement in FEV1 (greater than 200 mL). An atopy+ yielded 60.0% sensitivity and 88.9% specificity for an improvement in FEV1. When combined with FENO > 35 ppb and atopy+, it showed 40% sensitivity and 100.0% specificity for FEV1 improvement. Alternatively, COPD subjects with FENO ≤ 35 ppb and atopy− did not show significant improvement in FEV1. Conclusion: Combining FENO and specific IgE may be a useful marker for predicting the response to ICS/LABA on airflow limitation in COPD

Increase of nitrosative stress in patients with eosinophilic pneumonia

<p>Abstract</p> <p>Background</p> <p>Exhaled nitric oxide (NO) production is increased in asthma and reflects the degree of airway inflammation. The alveolar NO concentration (Calv) in interstitial pneumonia is reported to be increased. However, it remains unknown whether NO production is increased and nitrosative stress occurs in eosinophilic pneumonia (EP). We hypothesized that nitrosative stress markers including Calv, inducible type of NO synthase (iNOS), and 3-nitrotyrosine (3-NT), are upregulated in EP.</p> <p>Methods</p> <p>Exhaled NO including fractional exhaled NO (FE_NO) and Calv was measured in ten healthy subjects, 13 patients with idiopathic pulmonary fibrosis (IPF), and 13 patients with EP. iNOS expression and 3-NT formation were assessed by immunocytochemistory in BALf cells. The exhaled NO, lung function, and systemic inflammatory markers of the EP patients were investigated after corticosteroid treatment for 4 weeks.</p> <p>Results</p> <p>The Calv levels in the EP group (14.4 ± 2.0 ppb) were significantly higher than those in the healthy subjects (5.1 ± 0.6 ppb, p < 0.01) and the IPF groups (6.3 ± 0.6 ppb, p < 0.01) as well as the FE_NOand the corrected Calv levels (all p < 0.01). More iNOS and 3-NT positive cells were observed in the EP group compared to the healthy subject and IPF patient. The Calv levels had significant positive correlations with both iNOS (r = 0.858, p < 0.05) and 3-NT positive cells (r = 0.924, p < 0.01). Corticosteroid treatment significantly reduced both the FE_NO(p < 0.05) and the Calv levels (p < 0.01). The magnitude of reduction in the Calv levels had a significant positive correlation with the peripheral blood eosinophil counts (r = 0.802, p < 0.05).</p> <p>Conclusions</p> <p>These results suggested that excessive nitrosative stress occurred in EP and that Calv could be a marker of the disease activity.</p

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

Background: Some patients with asthma have high levels of exhaled nitric oxide fraction (FENO) 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. Methods: Twenty severe asthmatics with persistent FENO elevation (≥40 ppb) despite maintenance therapy including high-daily-dose ICS were enrolled. Asthma Control Questionnaire (ACQ), lung function, blood eosinophils, and FENO were assessed before and after 14 days treatment with 0.5 mg/kg oral prednisolone/day. Results: ACQ, blood eosinophils, FENO 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 FENO levels and blood eosinophil numbers were identified as significant predictors of ≥20% reductions in the FEFENO levels by systemic steroid therapy. Conclusions: Systemic corticosteroids could suppress the residual FENO elevations in more than half of the patients with severe asthma and the reduction in FENO levels was associated with improvements in asthma control and airflow limitation. The FENO levels and blood eosinophil numbers were the predictors of improved residual airway inflammation by systemic steroid therapy in severe asthma

Persistently high exhaled nitric oxide and loss of lung function in controlled asthma

AbstractBackgroundsIt remains unclear whether a persistently high exhaled nitric oxide fraction (FeNO) in patients with controlled asthma is associated with the progressive loss of lung function.MethodsThis was a 3-year prospective study. We examined the changes in pre- and post-bronchodilator forced expiratory volume in 1 s (FEV1) and FeNO in 140 patients with controlled asthma. We initially determined the FeNO cut-off point for identifying patients with a rapid decline in FEV1 (>40 mL/yr). Next, a total of 122 patients who maintained high or non-high FeNO were selected, and the associations between the FeNO trend and changes in FEV1 and bronchodilator response (BDR) were investigated.ResultsA FeNO level >40.3 ppb yielded 43% sensitivity and 86% specificity for identifying patients with a rapid decline in FEV1. Patients with persistently high FeNO had higher rates of decline in FEV1 (42.7 ± 37.5 mL/yr) than patients with non-high FeNO (16.7 ± 31.5 mL/yr) (p < 0.0005). The changes in BDR from baseline to the end of the study, in patients who had high or non-high levels of FeNO were −0.8% and 0.1%, respectively (p < 0.01). In a multivariate analysis adjusted by age, body mass index, asthma control, blood eosinophil numbers, and FEV1% of predicted, a FeNO level of ≥40 ppb was independently associated with an accelerated decline in FEV1 (p < 0.05).ConclusionsThis study suggests that FeNO is potentially valuable tool for identifying individuals who are at risk of a progressive loss of lung function among patients with controlled asthma

Practical Recommendations for a Selection of Inhaled Corticosteroids in COPD: A Composite ICO Chart

The use of inhaled corticosteroids (ICS) for the maintenance of bronchodilator treatment in patients with chronic obstructive pulmonary disease (COPD) is controversial. While some patients achieve clinical benefits, such as fewer exacerbations and improved symptoms, others do not, and some experience undesired side effects, such as pneumonia. Thus, we reviewed the evidence related to predictors of ICS therapy treatment response in patients with COPD. The first priority clinical markers when considering the efficacy of ICS are type 2 inflammatory biomarkers, followed by a history of suspected asthma and recurrent exacerbations. It is also necessary to consider any potential infection risk associated with ICS, and several risk factors for pneumonia when using ICS have been clarified in recent years. In this article, based on the evidence supporting the selection of ICS for COPD, we propose an ICS composite that can be added to the COPD (ICO) chart for use in clinical practice. The chart divided the type 2 biomarkers into three ranges and provided recommendations (recommend, consider, and against) by combining the history of suspected asthma, history of exacerbations, and risk of infection

Exhaled Nitric Oxide Cutoff Values for Asthma Diagnosis According to Rhinitis and Smoking Status in Japanese Subjects

Background: Measurement of the exhaled nitric oxide fraction (FEno) has been proposed as a useful diagnostic test for asthma. However, most of the data concerning the fEno cutoff values for the diagnosis of asthma have not yet examined using standard procedures. Furthermore, there is no detailed study that investigated the cutoff values that takes into account patient factors that influence the FEno levels. Methods: FEno was measured in 142 steroid-naive asthmatics and 224 control subjects using an online electrochemical nitric oxide analyzer in accordance with the current guidelines. Subjects without respiratory symptoms and normal spirometric parameters were included in the control group. Asthma was diagnosed on the basis of the presence of significant airway reversibility and/or airway hyperresponsiveness during clinical follow up 6 months after FEno measurements. Results: FEno was significantly higher in asthmatic patients compared with control subjects (p < 0.01). Based on all study subjects, the receiver operating characteristic curves indicated that the cutoff value of FEno 22 parts per billion (ppb) was associated with the highest combination of sensitivity (90.8%) and specificity (83.9%). Multivariate analysis showed allergic rhinitis, current smoking, and asthma were significant factors influencing the FEno levels. The cutoff values of FEno to discriminate asthma from non-asthma ranged from 18 to 28 ppb depending on rhinitis and smoking status. Conclusions: The cutoff values presented may be useful for the interpretation of FEno values in the clinical practice

Sequential Biotherapy Targeting IL-5 and IL-4/13 in Patients with Eosinophilic Asthma with Sinusitis and Otitis Media

Type 2 (T2) inflammation plays an important role in the pathogenesis of allergic diseases such as asthma, eosinophilic chronic rhinosinusitis (ECRS), or eosinophilic otitis media (EOM). Currently, in severe asthma with the T2 phenotype, biologics targeting mediators of T2 inflammation dramatically improve the management of severe asthma. While treatment with a single biologic is common, little is known about cases of the sequential use of two biologics. Here, we report a case of severe asthma with refractory ECRS and EOM in which total control of these allergic diseases could not be achieved with a single biologic but could be achieved via the sequential use of the anti-IL-5 receptor antibody and human anti-IL-4/13 receptor monoclonal antibody. It is suggested that it is necessary to control multiple T2 inflammatory pathways to achieve total control of severe allergic diseases. Sequential biotherapy may help solve the clinical challenges associated with single-agent molecular-targeted therapies