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

Investigating nuclear shell structure in the vicinity of 78Ni: Low-lying excited states in the neutron-rich isotopes 80,82Zn

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Data Reproducibility and Effectiveness of Bronchodilators for Improving Physical Activity in COPD Patients

Increasing physical activity (PA) in patients with chronic obstructive pulmonary disease (COPD) is an important issue, however, the effect of bronchodilators on PA is still controversial. The indicators of PA, as measured by an accelerometer, can easily fluctuate based on several factors, which might cause inconsistent results. In this review, we listed the indicators of PA and the factors influencing the reproducibility of indicators of PA, and reviewed reports in which the effects of bronchodilators on PA were evaluated by an accelerometer. Then, we investigated the association between the processing of influencing factors and the effectiveness of bronchodilators for improving the PA of COPD patients. Fifteen reports were extracted using the PubMed database. In all seven reports in which adjustment was performed for at least two of four influencing factors (non-wear time, data from days with special behavior, environmental factors, and number of valid days required to obtain reproducible data), bronchodilators showed beneficial effects on PA. No adjustment was made for any of these factors in any of the four bronchodilator-ineffective reports. This suggests that the processing of influencing factors to secure reproducibility might affect the results regarding the effectiveness of bronchodilators for improving PA in COPD patients

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