Value of bronchial reversibility to salbutamol, exhaled nitric oxide and responsiveness to methacholine to corroborate the diagnosis of asthma in children.

INTRODUCTION AND OBJECTIVES: Functional and inflammatory measures have been recommended to corroborate asthma diagnosis in schoolchildren, but the evidence in this regard is conflicting. We aimed to determine, in real-life clinical situation, the value of spirometry, spirometric bronchial reversibility to salbutamol (BDR), bronchial responsiveness to methacholine (MCT) and fractional exhaled nitric oxide (FENO), to corroborate the diagnosis of asthma in children on regular inhaled corticosteroids (ICS) referred from primary care. METHODS: One hundred and seventy-seven schoolchildren with mild-moderate persistent asthma, on treatment with regular ICS, participated in the study. Abnormal tests were defined as FENO ≥ 27 ppb, BDR (FEV1 ≥ 12%) and methacholine PC20 ≤ 4 mg/mL. RESULTS: The proportions of positive BDR, FENO and MCT, were 16.4%, 33.3%, and 87.0%, respectively. MCT was associated with FENO (p < 0.03) and BDR (p = 0.001); FENO was associated with BDR (p = 0.045), family history of asthma (p = 0.003) and use of asthma medication in the first two years of life (p = 0.004). BDR was significantly related with passive tobacco exposure (p = 0.003). CONCLUSIONS: Spirometry, BDR and BDR had a poor performance for corroborating diagnosis in our asthmatic children on ICS treatment; on the contrary, MCT was positive in most of them, which agrees with previous reports. Although asthma tests are useful to corroborate asthma when positive, clinical diagnosis remains the best current approach for asthma diagnosis, at least while better objective and feasible measurements at the daily practice are available. At present, these tests may have a better role for assessing the management and progression of the condition.

Improvement in upright and supine lung mechanics with bariatric surgery affects bronchodilator responsiveness and sleep quality.

Obesity and weight loss have complex effects on respiratory physiology, but these have been insufficiently studied, particularly at early time points following weight loss surgery and in the supine position. We evaluated 15 female participants with severe obesity before and 5 wk and 6 mo after bariatric surgery using the Pittsburgh Sleep Quality Index (PSQI), spirometry, plethysmography, and oscillometry to measure respiratory system mechanics. Oscillometry and spirometry were conducted in the upright and supine position and before and after bronchodilation with 200 µg of salbutamol. At 5 wk postsurgery, weight loss was 11.9 kg (SD 2.7) with no effect on spirometric outcomes and a slight effect on oscillometric outcomes. However, at 6 mo weight loss was 21.4 kg (SD 7.1) with a 14.1% (SD 6.1) and 17.8 (5.4)% reduction in upright and supine respiratory system resistance (Rrs),6, respectively. Respiratory system elastance also decreased by 25.7% (SD 9.4) and 20.2 (SD 7.2)% in the upright and supine positions. No changes were observed in spirometry, but sleep quality improved from PSQI of 8.4 (SD 3.5) to 4.1 (SD 2.9). Bronchodilator responsiveness was low at baseline but increased significantly after surgery, and this response was comparable to the improvement in Rrs produced by weight loss. Modeling the impedance spectra with a two-compartment model demonstrated that improvements in lung mechanics with weight loss begin in the upper or central compartment of the lungs and progress to include the peripheral compartment. Respiratory mechanics are impaired in individuals with severe obesity and is associated with poor sleep quality, but these improved substantially with weight loss. Our data provide new evidence that individuals with severe obesity may have poor sleep quality because of abnormal respiratory mechanics that weight loss improves.NEW & NOTEWORTHY This is the first study to quantify the degree of weight loss-induced improvements in respiratory system mechanics in both upright and supine positions, and its association with bronchodilator responsiveness and sleep quality at multiple time points. Weight loss induced large improvements in upright and supine respiratory system mechanics with corresponding improvements in bronchodilator responsiveness and sleep quality. Using mathematical modeling, we demonstrate that these improvements begin in the central airways and progress to include the lung periphery.

Changes in the breath sound spectrum with bronchodilation in children with asthma.

BACKGROUND: Breath sound parameters have been suggested to be new biomarkers of airway function in patients with asthma. METHODS: We investigated the effect of bronchodilation on breath sound parameters in sixty-four children (mean age, 8.9 years; range, 6-16 years) using a breath sound analyzer. The breath sound parameters included frequency limiting 50% and 99% of the power spectrum (F50 and F99), roll-off from 600-1200 Hz (slope), and spectrum curve indices such as the ratios of the third and fourth power area to the total area of the power spectrum (P3/PT and P4/PT), total area under the curve (A3/AT and B4/AT), and the ratio of power and frequency at 50% and 75% of the highest frequency of the power spectrum (RPF75 and RPF50). Lung function was assessed using spirometry and the forced oscillation technique (FOT). All variables were assessed before and after inhalation of a ß2-agonist. RESULTS: The spectrum curve indices, A3/AT, B4/AT, RPF75, and RPF50, showed statistically significant increase following ß2-agonist inhalation. The increase in RPF50 was correlated with the decrease in the difference between resistance at 5 Hz and 20 Hz, R5-R20, measured by FOT. In the multiple regression analysis adjusted for the effect of ΔRPF75, the changes in A3/AT and B4/AT were positively correlated with that in the forced expiratory volume in one second. CONCLUSIONS: The spectrum curve indices indicated bronchodilation, and may be useful for the assessment of bronchial reversibility in children with asthma.

Association between fractional exhaled nitric oxide, sputum induction and peripheral blood eosinophil in uncontrolled asthma.

BACKGROUND: The fractional exhaled nitric oxide (FeNO) and blood eosinophils are biomarkers of eosinophilic airway inflammation used in the diagnosis and management of asthma, although induced sputum is the gold standard test for phenotypic asthma. Nevertheless, the clinical application of the correlation between sputum eosinophils, FeNO and blood eosinophils is controversial. OBJECTIVE: To investigate the clinical application of the correlation between sputum eosinophils, FeNO and blood eosinophils with uncontrolled asthmatic patients. It also examined the relationships between these biomarkers in bronchial reversibility and bronchial hyper-responsiveness (BHR). METHODS: This study evaluated 75 uncontrolled asthmatic patients (symptom control and future risk of adverse outcomes). All patients underwent the following on the same day: FeNO, spirometry, BHR or bronchodilator reversibility, sputum induction and blood collection. Eosinophilic airway inflammation was defined as sputum eosinophils ≥ 2.5% or FeNO levels ≥ 32 parts per billion (ppb). RESULTS: A significant positive relationship was between percentage of sputum eosinophils and FeNO (r = 0.4556; p < 0.0001) and percentage of blood eosinophils (r = 0.3647; p = 0.0013), and a significant negative correlation was between percentage of sputum neutrophils and FeNO (r = - 0.3653; p = 0.0013). No relationship between FeNO and percentage of blood eosinophils (p = 0.5801). ROC curve analysis identified FeNO was predictive of sputum eosinophilia [area under the curve (AUC) 0.707, p = 0.004] at a cutoff point of 35.5 ppb (sensitivity = 67.3%, specificity = 73.9%). Percentage of blood eosinophils was also highly predictive with an AUC of 0.73 (p = 0.002) at a cut-off point of 1.5%, sensitivity and specificity were 61.5 and 78.3%, respectively. Although the sputum neutrophil percentage was correlated with FeNO, ROC curve of these parameters did not show useful values (AUC = 0.297, p = 0.003; AUC = 0.295, p = 0.021). CONCLUSIONS AND CLINICAL RELEVANCE: Blood eosinophils and FeNO can accurately predict eosinophilic airway inflammation in uncontrolled asthmatic patients. FeNO is poor surrogates for sputum neutrophils and blood eosinophils. The FeNO level and blood eosinophils, which determine an optimal cutoff for sputum eosinophilia, need more studies.

Both fractional exhaled nitric oxide and sputum eosinophil were associated with uncontrolled asthma.

BACKGROUND: Sputum eosinophil and fractional exhaled nitric oxide (FeNO), noninvasive biomarkers of local eosinophilic airway inflammation, can be used to assess asthma outcome. Nevertheless, the clinical application of the association between FeNO and sputum eosinophil is controversial. The aim of the study was to investigate the predictive relationship between FeNO and sputum eosinophil in uncontrolled asthmatic patients and the correlation between sputum eosinophil and FeNO in bronchial reversibility and bronchial hyperresponsiveness (BHR). METHODS: A total of 69 uncontrolled asthmatic patients were included in the study. All patients underwent a clinical assessment on the same day as follows: FeNO, spirometry with BHR or bronchodilator reversibility test and induced sputum in turn. Eosinophilic airway inflammation was defined as sputum eosinophil percentage (≥2.5%)/FeNO level (≥32 parts per billion [ppb]). RESULTS: FeNO level and sputum neutrophilic percentage were higher in the sputum eosinophilia group compared to those without (49 versus 27, p=0.011; 71.12 versus 87.67, p=0.012, respectively). Sputum eosinophil percentage was higher with raised FeNO level compared to those without (10.3% versus 2.75%, p=0.03). A significant correlation was observed between sputum eosinophil percentage and FeNO level (r=0.4016; p=0.0006). There were no significant relationships between sputum eosinophilic percentage and provocative dose (PD20)/ΔFEV1 (improvement in a forced expiratory volume in 1 second [FEV1] after 400µg of salbutamol), FeNO levels and PD20/ΔFEV1. The FeNO level of 35.5 ppb was effective in assessing sputum eosinophilia, with a receiver operating characteristic area under curve (AUC) of 0.707 (p=0.011; 95% confidence interval [CI] 0.573-0.841), and 4.36% was the best diagnostic cutoff value of sputum eosinophil percentage for the FeNO level of 32 ppb (AUC 0.721; 95% CI 0.59-0.852). CONCLUSION: FeNO level can accurately detect eosinophilic asthma but has limited value to assess noneosinophilic asthma in uncontrolled stage. Further studies are required to validate the use of FeNO level to determine an optimal cutoff for sputum eosinophilia that could be used in clinical practice.

Metabolic Syndrome as a Factor Affecting Systemic Inflammation in Patients with Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a systemic disease which may be associated with other comorbidities. The aim of the study was to estimate the incidence of metabolic syndrome (MS) in COPD patients and to assess its impact on systemic inflammation and lung function. MS was diagnosed in accordance with the recommendations of the Polish Forum for the Prevention of Cardiovascular Diseases. The study group consisted of 267 patients with stable COPD in all stages of severity. All patients underwent spirometry with bronchial reversibility testing and 6 min walk test (6MWT). The following blood tests were evaluated: lipid profile, glucose and C-reactive protein as well as serum concentration of IL-6, leptin, adiponectin, and endothelin. MS was diagnosed in 93 patients (35.8%). No differences were observed in the incidence of MS in relation to airflow limitation severity (mild; moderate; severe and very severe: 38.9; 36.3; 35.2 and 25.0%, respectively). FEV1 (% predicted), FVC (% predicted), 6MWT distance (6MWD), age, and the number of pack-years were similar in patients with and without MS. MS was more frequent in males than females (38.7 vs. 28.4%, p > 0.05). Serum concentrations of IL-6, endothelin, leptin, and CRP were higher in the MS group, contrary to adiponectin concentration which was lower (p < 0.01). MS was more frequent in male COPD patients, but there were no differences in its frequency between patients with different severity of airflow limitation. We conclude that MS, as a comorbidity, occurs in all COPD stages and affects systemic inflammation. MS incidence does not depend on COPD severity.

A clinical method for detecting bronchial reversibility using a breath sound spectrum analysis in infants.

BACKGROUND: Using a breath sound analyzer, we investigated clinical parameters for detecting bronchial reversibility in infants. METHODS: A total of 59 infants (4-39 months, mean age 7.8 months) were included. In Study 1, the intra- and inter-observer variability was measured in 23 of 59 infants. Breath sound parameters, the frequency at 99% of the maximum frequency (F99), frequency at 25%, 50%, and 75% of the power spectrum (Q25, Q50, and Q75), and highest frequency of inspiratory breath sounds (HFI), and parameters obtained using the ratio of parameters, i.e. spectrum curve indices, the ratio of the third and fourth area to total area (A3/AT and B4/AT, respectively) and ratio of power and frequency at F75 and F50 (RPF75 and RPF50), were calculated. In Study 2, the relationship between parameters of breath sounds and age and stature were studied. In Study 3, breath sounds were studied before and after ß2 agonist inhalation. RESULTS: In Study 1, the data showed statistical intra- and inter-observer reliability in A3/AT (p=0.042 and 0.034, respectively) and RPF50 (p=0.001 and 0.001, respectively). In Study 2, there were no significant relationships between age, height, weight, and BMI. In Study 3, A3/AT and RPF50 significantly changed after ß2 agonist inhalation (p=0.001 and p<0.001, respectively). CONCLUSIONS: Breath sound analysis can be performed in infants, as in older children, and the spectrum curve indices are not significantly affected by age-related factors. These sound parameters may play a role in the assessment of bronchial reversibility in infants.

Early detection of changes in lung mechanics with oscillometry following bariatric surgery in severe obesity.

Obesity is associated with respiratory symptoms that are reported to improve with weight loss, but this is poorly reflected in spirometry, and few studies have measured respiratory mechanics with oscillometry. We investigated whether early changes in lung mechanics following weight loss are detectable with oscillometry. Furthermore, we investigated whether the changes in lung mechanics measured in the supine position following weight loss are associated with changes in sleep quality. Nineteen severely obese female subjects (mean body mass index, 47.2 ± 6.6 kg/m(2)) were evaluated using spirometry, oscillometry, plethysmography, and the Pittsburgh Sleep Quality Index before and 5 weeks after bariatric surgery. These tests were conducted in both the upright and the supine position, and pre- and postbronchodilation with 200 µg of salbutamol. Five weeks after surgery, weight loss of 11.5 ± 2.5 kg was not associated with changes in spirometry and plethysmography, with the exception of functional residual capacity. There were also no changes in upright respiratory system resistance (Rrs) or reactance following weight loss. Importantly, however, in the supine position, weight loss caused a substantial reduction in Rrs. In addition, sleep quality improved significantly and was highly correlated with the reduction in supine Rrs. Prior to weight loss, subjects did not respond to the bronchodilator when assessed in the upright position with either spirometry or oscillometry; however, with modest weight loss, bronchodilator responsiveness returned to the normal range. Improvements in lung mechanics occur very early after weight loss, mostly in the supine position, resulting in improved sleep quality. These improvements are detectable with oscillometry but not with spirometry.

Bronchodilator response as a marker of poor asthma control.

BACKGROUND: Asthma guidelines emphasise the importance of monitoring disease control in managing asthma. OBJECTIVE: The aim of this study was to evaluate the relationship between lung function, including bronchodilator response in terms of improving in FEV1 after administration of salbutamol, and asthma control. METHODS: 246 patients with known asthma and in regular chronic treatment according to international guidelines were consecutively enrolled in a 12 month-period. All patients were evaluated by asthma control test (ACT), spirometry and bronchodilator test with salbutamol 400 mcg. RESULTS: Mean ACT value was 18.8. Patients with significant bronchial reversibility had lower ACT mean values. This finding was confirmed in both patients with airway obstruction and in those with normal spirometry. There was a significant correlation between ACT values and bronchodilator response. CONCLUSIONS: The persistence of a significant degree of bronchodilator response despite regular treatment according to guidelines was a marker of worse asthma control. CLINICAL IMPLICATIONS: Bronchodilator response, correlating with worse asthma control even in patients with normal spirometry, should be test at every visit as it may add information on asthma control.

Evaluation of airway responsiveness using colored three-dimensional analyses of a new forced oscillation technique in controlled asthmatic and nonasthmatic children.

BACKGROUND: Bronchodilator response (BDR) is routinely used in asthma management. A new forced oscillation technique (FOT) is able to quickly measure respiratory system resistance (Rrs) and reactance (Xrs) at each tidal breath phase. The present study evaluated bronchial changes by using the new FOT. METHODS: Respiratory resistance and reactance were measured using FOT in 132 children (age, 10.86±4.78 years; M:F=88:44), including asthmatic (n=98) and nonasthmatic children (n=34), pre- and post-bronchodilator inhalation in an asymptomatic state. Whole-breath or within-breath changes in Rrs and Xrs were measured and compared pre- and post-bronchodilator inhalation and between each group. All patients performed spirometry and forced expiratory nitric oxide pre- and post-bronchodilator inhalation. RESULTS: Spirometric parameters showed significant positive changes at V50 and V25 in both groups; however, these changes were not significantly different between the groups. eNO was significantly higher in the asthmatic group than in the nonasthmatic group; however, there was no significant change pre- and post-inhalation in either group. Rrs in the asthma group was significantly higher in the expiratory phase than in the inspiratory phase. Rrs and Xrs before and after bronchodilator inhalation were significantly different in the asthma group alone, except for the expiratory-inspiratory phase of each of these parameters. Changes in Rrs and Xrs at 5Hz (R5 and X5) in a whole-breath and the inspiratory phase were significantly different between the groups. CONCLUSIONS: Changes in X5 and R5 reflect bronchial reversibility. The new FOT is useful for asthmatic children.