Evaluation of the Diagnostic Accuracy of Non-Specific Bronchial Provocation Tests in the Diagnosis of Asthma: A Randomized Cross-Over Study

IntroductionThe role of bronchial provocation tests in the diagnosis of asthma remains to be fully explored. We aimed to evaluate methacholine and mannitol challenge testing, and explore the factors associated with this broncoprovocation response.MethodsObservational, cross-over, randomized trial evaluating adult cases with suspected asthma, naïve to treatment, with normal pre-bronchodilator spirometry, and negative bronchodilator test. Patients were randomized to start with methacholine or mannitol. The diagnosis of bronchial asthma was confirmed if there was a good functional and clinical response to one month with twice daily formoterol/budesonide 9/320. The diagnostic profile and the concordance were calculated. Factors associated with a positive provocation test were entered into a multivariate binomial logistic regression analysis, and classification trees were created for both tests.ResultsThe study included 108 cases (50.0% diagnosed with asthma and 51.9% cases starting with methacholine). The percentage of cases positive to methacholine and mannitol were 30.6% and 25.0% respectively. Kappa values were 0.40 (p < 0.001). The diagnostic profile for methacholine was sensitivity 59.3% and specificity 98.1%, while for mannitol it was sensitivity 48.1% and specificity 98.1%. Variables associated with a positive methacholine response included sex, atopy, FEV₁, FEV₁/FVC and FENO, whereas they were FEV₁/FVC and FENO for mannitol. A FENO value > 26 ppb, FEV1 ≤ 103.3% and female sex correctly classified 78.7% of methacholine responders. FENO value > 26 ppb was enough to correctly classify 81.5% of mannitol responders.ConclusionsOur study confirms the diagnostic profile of methacholine and mannitol challenge tests and describes the variable associated to their positivity with new proposed cutoff values.     

Acute bronchodilator responsiveness in subjects with and without airflow obstruction in five Latin American cities: The PLATINO study

BackgroundAcute bronchodilator responsiveness is an area of discussion in COPD. No information exists regarding this aspect of the disease from an unselected COPD population. We assessed acute bronchodilator responsiveness and factors influencing it in subjects with and without airway obstruction in an epidemiologic sample.MethodsCOPD was defined by GOLD criteria (post-bronchodilator FEV₁/FVC < 0.70). In this analysis, subjects with pre-bronchodilator FEV₁/FVC <0.70 but ≥0.70 post-bronchodilator were considered to have reversible obstruction. Bronchodilator responsiveness after albuterol 200 μg was assessed using three definitions: a) FVC and/or FEV₁ increment ≥12% plus ≥200 mL over baseline; b) FEV₁ ≥ 15% increase over baseline; and c) FEV₁ increase ≥10% of predicted value.ResultsThere were 756 healthy respiratory subjects, 481 subjects with reversible obstruction and 759 COPD subjects. Depending on the criterion used the proportion of person with acute bronchodilator responsiveness ranged between 15.0–28.2% in COPD, 11.4–21.6% in reversible obstructed and 2.7–7.2% in respiratory healthy. FEV₁ changes were lower (110.6 ± 7.40 vs. 164.7 ± 11.8 mL) and FVC higher (146.5 ± 14.2 mL vs. ?131.0 ± 19.6 mL) in COPD subjects compared with reversible obstructed. Substantial overlap in FEV₁ and FVC changes was observed among the groups. Acute bronchodilator responsiveness in COPD persons was associated with less obstruction and never smoking.ConclusionsOver two-thirds of persons with COPD did not demonstrate acute bronchodilator responsiveness. The overall response was small and less than that considered as significant by ATS criteria. The overlap in FEV₁ and FVC changes after bronchodilator among the groups makes it difficult to determine a threshold for separating them.     

Increased sputum levels of thymus and activation-regulated chemokine in children with asthma not eosinophilic bronchitis

BackgroundThymus and activation-regulated chemokine (TARC), a member of the CC chemokine family, plays a crucial role in Th2-specific inflammation. We aimed to determine the concentration of sputum TARC in children with asthma and eosinophilic bronchitis (EB) and its relation with eosinophilic inflammation, pulmonary function, and bronchial hyper-responsiveness.MethodsIn total, 90 children with asthma, 38 with EB, and 45 control subjects were enrolled. TARC levels were measured in sputum supernatants using an ELISA. We performed pulmonary function tests and measured exhaled fractional nitric oxide, eosinophil counts in blood, and sputum and serum levels of total IgE in all children.ResultsSputum TARC levels were significantly higher in children with asthma than in either children with EB (p = 0.004) or the control subjects (p = 0.014). Among patients with asthma, sputum TARC concentration was higher in children with sputum eosinophilia than in those without sputum eosinophilia (p = 0.035). Sputum TARC levels positively correlated with eosinophil counts in sputum, serum total IgE levels, exhaled fractional nitric, and the bronchodilator response. Negative significant correlations were found between sputum TARC and FEV1/FVC (the ratio of forced expiratory volume in one second and forced expiratory vital capacity) or PC₂₀ (the provocative concentration of methacholine causing a 20% decrease in the FEV₁).ConclusionElevated TARC levels in sputum were detected in children with asthma but not in children with EB. Sputum TARC could be a supportive marker for discrimination of asthma from EB in children showing characteristics of eosinophilic airway inflammation.     

Diagnostic value of a pattern of exhaled breath condensate biomarkers in asthmatic children

BackgroundDiagnosing asthma in children is a challenge and using a single biomarker from exhaled breath condensate (EBC) showed the lack of improvement in it.ObjectiveThe aim of this study was to assess the diagnostic potential of a pattern of simple chemical biomarkers from EBC in diagnosing asthma in children in a real-life setting, its association with lung function and gastroesophageal reflux disease (GERD).MethodsIn 75 consecutive children aged 5–7 years with asthma-like symptoms the following tests were performed: skin prick tests, spirometry, impulse oscillometry (IOS), exhaled NO (F_ENO), 24-hour oesophageal pH monitoring and EBC collection with subsequent analysis of pH, carbon dioxide tension, oxygen tension, and concentrations of magnesium, calcium, iron and urates.ResultsNo significant differences were found for individual EBC biomarkers between asthmatics and non-asthmatics (p > 0.05 for all). A pattern of six EBC biomarkers showed a statistically significant (p = 0.046) predictive model for asthma (AUC = 0.698, PPV = 84.2%, NPV = 38.9%). None to moderate association (R² up to 0.43) between EBC biomarkers and lung function measures and F_ENO was found, with IOS parameters showing the best association with EBC biomarkers. A significantly higher EBC Fe was found in children with asthma and GERD compared to asthmatics without GERD (p = 0.049).ConclusionsAn approach that involves a pattern of EBC biomarkers had a better diagnostic accuracy for asthma in children in real-life settings compared to a single one. Poor to moderate association of EBC biomarkers with lung function suggests a complementary value of EBC analysis for asthma diagnosis in children.     

Efficacy and safety of ciclesonide once daily and fluticasone propionate twice daily in children with asthma

BackgroundCiclesonide is a new inhaled corticosteroid (ICS). Information about its clinical efficacy and safety in relation to other ICS in children is needed for clinical positioning.ObjectiveThis 12-week, randomized, double-blind, double-dummy, three-arm, parallel-group study compared the efficacy and safety of ciclesonide with fluticasone propionate in children with mainly moderate and severe persistent asthma.MethodsSeven hundred and forty-four patients (aged 6–11 years) were randomized to ciclesonide (80 or 160 μg once daily) or fluticasone propionate (88 μg twice daily), following a 2–4-week run-in. Efficacy measurements included forced expiratory flow in 1 s (FEV₁), morning peak expiratory flow (PEF), asthma symptom scores, rescue medication use and quality of life. Systemic effect was assessed by 24-hour urine free cortisol adjusted for creatinine.ResultsFEV₁ and morning PEF increased from baseline in all groups (p < 0.0001). Ciclesonide 160 μg was not inferior to fluticasone propionate 176 μg for FEV₁ (p = 0.0030, one-sided). In all groups, asthma symptom score sums and rescue medication use significantly improved (p < 0.0001). The percentages of asthma symptom-, rescue medication- and nocturnal awakening-free days were high, with no significant differences between treatments. Quality of life scores improved with all treatments (p < 0.0001). A significant dose–response occurred between low and higher doses of ciclesonide for exacerbations and asthma control definitions. The incidences of adverse events were comparable across treatments. Urine free cortisol levels decreased significantly with fluticasone propionate (p = 0.0103), but not with ciclesonide.ConclusionOnce-daily ciclesonide has a clinical effect similar to that of fluticasone propionate, but does not suppress cortisol excretion, in children with moderate and severe asthma.     

Role of add-on zileuton on total exhaled, large airway, and small airway/alveolar nitric oxide in moderate-severe persistent adult asthmatics on fluticasone 250 μg/Salmeterol 50 μg

BackgroundMeasuring non-invasive exhaled biomarkers of inflammation may be important in monitoring asthma therapy.ObjectiveEvaluate exhaled nitric oxide with add-on leukotriene synthesis inhibitor in moderate-severe persistent asthmatics on combination controllers.MethodsIn a non-randomized, non-placebo, single-blind, fixed sequence, pilot study, we evaluated 22 non-smoking, stable, moderate-severe adult asthmatics on maintenance inhaled fluticasone 250 μg/salmeterol 50 μg (F/S) via MDI bid ≥ 1 yr, with add-on oral zileuton 600 mg qid. Exhaled fractional nitric oxide (FENO) gas exchange, large airway NO, small airway/alveolar NO concentration (CANO), Juniper score and lung function were measured. Asthmatics were studied at baseline only on F/S bid (visit 1), on F/S bid pre and 2 h post first dose zileuton 600 mg (visit 2), and post 4 weeks (visit 3) F/S bid plus zileuton 600 mg qid. Values were compared at each visit and to healthy non-smoking age matched healthy controls with normal lung function.ResultsThree asthmatics stopped zileuton prematurely (headache and/or nausea) and 19 (12F) age 55 ± 17 yr (mean ± SD) completed the 4-week study. Baseline forced expiratory lung volume in 1 sec (FEV₁) was 1.6 ± 0.7L (53 ± 19% pred) (mean ± SD), FEV₁ over FVC ratio was 64 ± 11% and post 180 μg albuterol FEV₁ was 1.8 ± 0.7 L (56 ± 21% pred), and FEV₁ over FVC ratio was 67 ± 12%. Baseline Juniper scores were mild (10 ± 10) and similar (p = ns) at all visits. Baseline FENO@50 mL/s was 48 ± 27 ppb (mean ± SD), and FENO@100 mL/s was 29 ± 16 ppb, and were similar (p = ns) at all visits. Large airway NO flux was 2.0 ± 1.3 nL/s (52% asthmatics abnormal) and small airway/alveolar NO was 8.0 ± 4.0 ppb (79% asthmatics abnormal) and were similar (p = ns) at all visits. Compared to baseline, post 26 ± 6 days Zileuton, mean FEV₁ (L)% predicted increased 3.3% predicted (p = 0.03), and FEV₁ over FVC ratio increased 2.2% (p = 0.03).ConclusionIn stable, moderate-severe persistent adult asthmatics, large airway NO flux, small airway/alveolar CANO, and Juniper airway scores, were not significantly different on F/S bid vs F/S bid plus Zileuton for 4 weeks, despite significant small increase in FEV₁ over FVC ratio and FEV₁% predicted.     

Risk factors for asthma severity among emergency rooms attendees,Palestine

SettingEmergency Room of Alia Governmental hospital in Hebron district, south of West Bank, Palestine.ObjectiveTo determine the factors associated with chronic asthma severity among asthma patients attending the emergency rooms in Palestine.DesignA cross-sectional study using previously validated questionnaires.ResultsAmong the 121 patients, 45.5% had moderate/severe asthma. Most days' regular intake of oral theophylline, and using ≥5 courses/year of oral steroids were more likely to be associated with moderate/severe asthmatics (p < 0.05). Moderate/severe asthmatics compared with mild asthmatics were more likely to use inhaled short B₂-agonists more frequently (most days, 50% vs. 17%; p < 0.05) and in higher concentrations (≥1 cannister/month, 78% vs. 29%; p < 0.05). They were also more likely to get regular treatment (p < 0.05) and to report their inability to afford/obtain asthma medicines (p > 0.05).ConclusionsAccess to health services doesn't necessarily ensure a good quality of care for asthmatics. The effectiveness of oral theophyline in controlling the more severe asthma symptoms should be reconsidered. We recommend a training program for health professionals and an educational one on self-management for the asthma patients.     

Faster onset of action of formoterol versus salmeterol in patients with chronic obstructive pulmonary disease: A multicenter,randomized study

BackgroundChronic obstructive pulmonary disease (COPD) is a growing public health problem that has increased in recent years. It similarly affects men and women, especially those who smoke. The goals of COPD pharmacotherapy are to improve lung function, reduce symptoms, prevent exacerbations, and improve patients' health status. Bronchodilators are the foundation of treatment for COPD, and the long-acting β₂-agonists formoterol and salmeterol are both indicated for regular use by patients with stable COPD.ObjectiveA clinical study was conducted to compare the onset of bronchodilator effects following treatment with formoterol 12 μg administered twice-daily (BID) or salmeterol 50 μg BID. The trial also assessed whether the bronchodilator effects of treatment resulted in significant differences in clinical response.MethodsThis was a randomized, multicenter, open-label, parallel-group study of formoterol 12 μg BID versus salmeterol 50 μg BID, both administered for 28 days. Patients were current or previous smokers aged ≥40 years, with a diagnosis of stable COPD. The primary efficacy variable was change from baseline in forced expiratory volume in 1 s (FEV₁) 5 min after drug administration on day 28. Secondary efficacy variables included changes from baseline in the 6-min walk test (6MWT) and rescue medication use. The primary variable was assessed by analysis of covariance, with baseline FEV₁ as the covariate.ResultsA total of 270 patients were randomized to formoterol 12 μg BID (n = 137) or salmeterol 50 μg BID (n = 133). In the intent-to-treat population the least square (LS) mean change from baseline in FEV₁ at 5 min postdose on day 28 was 0.13 L in the formoterol group compared with 0.07 L in the salmeterol group (P = 0.022). At 30 min postdose on day 28, the LS mean change from baseline in FEV₁ was 0.17 L in the formoterol group compared with 0.07 L in the salmeterol group (P < 0.001). Similar changes were reported at 60 min postdose (0.19 L for the formoterol group versus 0.13 L for the salmeterol group, P = 0.069). Patients in the formoterol group walked longer distances in the 6MWT and used less rescue medication compared with patients in the salmeterol group, although the differences were not statistically significant.ConclusionsSignificantly greater improvements from baseline in FEV₁ were observed at 5 and 30 min postdose with formoterol 12 μg compared with salmeterol 50 μg after 28 days of treatment. Numeric improvements in the 6MWT and rescue medication use were also observed with formoterol.     

Perception of bronchodilation assessed by Visual Analogue Scale in children with asthma

BackgroundVisual Analogue Scale (VAS) has been proposed as a useful tool for assessing the perception of asthma symptoms, a cornerstone in disease management. While airway flow limitation and its reversibility are thought to be a useful marker of disease severity, there are very few studies that evaluated the response to bronchodilation (BD) testing perception by VAS. To investigate whether VAS assessment of breathlessness perception could provide a useful tool to assess the response to BD testing in asthmatic children.MethodsThis cross-sectional study included a total of 150 children (96 males, mean age 11.05 years) with asthma, 50 had bronchial obstruction (i.e. FEV₁ <80% of predicted). Perception of breathlessness was assessed by VAS; lung function was measured by spirometry. BD testing was performed in all children.ResultsIn children with bronchial obstruction, VAS at baseline was 4.7 and significantly increased to 6.9 (p < 0.001) after BD. In children without bronchial obstruction, VAS at baseline was 7.4, but further significantly increased to 8.4 after BD testing (p < 0.01). There was a significant difference in Δ VAS between children with bronchial reversibility and children without it (p < 0.0001).ConclusionsThe present study demonstrates that VAS might be considered an initial tool to assess the BD response in children with asthma, mainly with overt bronchial obstruction.     

Airway tone dysfunction among pre-schoolers with positive asthma predictive index: A case–control study

ObjectiveTo measure lung function by impulse oscillometry (IOS) and spirometry in recurrent wheezer pre-schoolers according to their asthma predictive index (API) condition.MethodsWe performed a case–control study enrolling all pre-schoolers with recurrent wheezing episodes (>3 episodes confirmed by physician) who presented at a paediatric pulmonology clinic. The population was divided according to stringent API criteria into positive or negative.ResultsIn the nine-month period, 109 pre-schoolers were enrolled. After excluding one patient (due to lung function technique problems) 108 pre-schoolers (56 males, age range from 24 to 72 months) completed the study; 50 belong to positive API and 58 to negative API group. There were no differences in demographics between groups. More use of ICS was found in those with positive API than with negative API (62% vs. 12%, respectively, p = 0.001). No differences in basal lung function and post-bronchodilator response to salbutamol (by IOS or spirometry) were found between positive and negative API pre-schoolers. However, those positive API pre-schoolers with ICS had significantly higher central basal airway resistance (RA at 20 Hz) and higher post-BD response (% change in FEF_25–75 and in FEV_0.5) than those positive API without ICS.ConclusionRecurrent wheezer pre-schoolers with positive API and ICS used may have airway dysfunction. More studies are needed to confirm this finding.     

Patrones inflamatorios en niños asmáticos basados en la determinación de óxido nítrico alveolar

IntroductionNitric oxide (NO) levels can be measured at proximal (maximum airway NO flux [J’_awNO]) and distal (alveolar NO concentration [C_ANO]) levels. Four inflammatory patterns have been described in asthmatic individuals, although their relevance has not been well established. The objective was to determine J’_awNO and C_ANO in order to establish four inflammatory categories in asthmatics.Material and methodsCross-sectional study of a sample consisting of healthy and asthmatic children. Exhaled NO was determined at multiple flows. J’_awNO and C_ANO were obtained according to the two-compartment model. The asthma control questionnaire (ACQ) and spirometry were administered to asthmatic children. Patients were categorized as type i (normal J’_awNO and C_ANO), type ii (elevated J’_awNO and normal C_ANO), type iii (elevated J’_awNO and C_ANO) and type iv (normal J’_awNO and elevated C_ANO). Correlation between FE_NO,50, J’_awNO and C_ANO was analyzed using Spearman's R Correlation Test. Analysis of variance and paired comparisons were performed using the Bonferroni correction.ResultsOne hundred sixty-two children were studied, of whom 49 (32.23%) were healthy controls and 103 (67.76%) asthmatics. In the control subjects, FE_NO,50 (ppb)(median and range) was 11.5 (1.6 to 27.3), J’_awNO (pl/s) was 516 (98.3 to 1470) and C_ANO (ppb) was 2.2 (0.1 to 4.5). Forty-four (42.7%) of the asthmatic participants were categorized as type i, 41 (39.8%) as type ii, 14 (13.5%) as type iii and 4 (3.88%) as type iv. Good correlation was observed between J’_awNO and FE_NO,50 (r = 0.97). There was no association between J’_awNO and C_ANO. FEV₁/FVC decreased significantly in type iii (mean 79.8 ± 7.5). Morbidity was significantly higher in types iii and iv.ConclusionsNormal values obtained are similar to those previously reported. Asthmatics with high C_ANO showed higher morbidity. No correlation was found between proximal and distal inflammation.     

Safety and tolerability of NVA237, a once-daily long-acting muscarinic antagonist,in COPD patients

NVA237 is a novel once-daily inhaled long-acting muscarinic antagonist administered via a dry powder inhaler. This randomized, double-blind, placebo-controlled study evaluated the safety, tolerability and bronchodilator efficacy of two doses of NVA237 (100 and 200 μg), versus placebo, in patients with moderate-to-severe COPD (forced expiratory volume in 1 s [FEV₁] ≥ 30% and <80% predicted and FEV₁/forced vital capacity [FVC] < 0.7, 30 min after inhalation of 80 μg ipratropium bromide). After appropriate washout periods, patients were randomized to treatment with NVA237 100 μg (n = 92), NVA237 200 μg (n = 98) or placebo (n = 91) for 28 days. The primary objective was evaluation of safety, with efficacy measures included as secondary objectives. NVA237 was generally well tolerated and associated with a frequency and distribution of adverse events similar to placebo. Serious adverse events were uncommon and there was no evidence of adverse cardiovascular effects or unexpected events. Trough FEV₁ was significantly higher in those receiving NVA237 compared with placebo. For NVA237 100 μg the differences were 131 and 161 mL on Days 1 and 28, respectively (p < 0.05), and for NVA237 200 μg the differences were 146 and 151 mL on Days 1 and 28, respectively (p < 0.05). Peak FEV₁, FEV₁ at all timepoints up to 24 h after dosing, and FEV₁ area under the curve during 5 min–5 h post-dosing were also significantly higher in both NVA237 groups, compared with placebo. Patients receiving NVA237 required fewer daily puffs of rescue medication and had a higher percentage of days on which rescue medication was not required. Overall, the present study provides further evidence of the safety, tolerability and bronchodilator efficacy of once-daily treatment with NVA237 100 and 200 μg in patients with moderate-to-severe COPD.     

Usefulness of inhaled magnesium sulfate in the coadjuvant management of severe asthma crisis in an emergency department

RationaleTreatment of severe asthma may be difficult despite the use of several medications including parenteral corticosteroids. Intravenous magnesium sulfate (MgSO₄) is one ancillary drug for severe crisis; its inhaled use is controversial.ObjectivesTo evaluate the usefulness of inhaled MgSO₄ compared to placebo in improving lung function, oxygen saturation, and reducing hospital admission as an adjunct to standard treatment in severe asthma crisis.Patients and methodsWe conducted a placebo-controlled, double-blind clinical trial with asthmatic patients >18 years of age with asthmatic crisis and FEV₁ < 60% of predicted (%p). All subjects received 125 mg of IV methylprednisolone followed by nebulization with the combination of albuterol (7.5 mg) and ipratropium bromide (1.5 mg) diluted in 3 ml of isotonic saline solution (as placebo) or 3 ml (333 mg) of MgSO₄. After 90 min, subjects with FEV₁ < 60%p or SpO₂ < 88% or persistent symptoms were admitted to the emergency department (ED).ResultsWe included 30 patients per group who were similar at baseline. The MgSO₄ group showed higher post-bronchodilator (post-BD) FEV₁%p (69 ± 13 vs. 61 ± 12, p < 0.014) and SpO₂ (92 ± 4 vs. 88 ± 5%, p < 0.006) than the placebo group. Fewer treated patients were admitted to the ED (5 vs. 13) (p < 0.047), with relative risk (RR) of 0.26 (95% CI 0.079–0.870).ConclusionsAdding inhaled MgSO₄ treatment to standard therapy in severe asthma crisis improves FEV₁%p and SpO₂ post-BD and reduces the rate of ED admissions.     

Relationship between exhaled leukotriene and 8-isoprostane levels and asthma severity,asthma control level,and asthma control test score

ObjectiveExhaled breath condensate (EBC) is a completely non-invasive method for the collection of airway secretions to measure intense inflammation in the airways of asthmatics. It has been shown that the childhood asthma control test (c-ACT) is a good tool for use in the evaluation of asthmatics. Whether the c-ACT score and asthma control level correlate with the airway inflammation is not well known. We aimed to evaluate the relationship between exhaled cysteinyl leukotrienes (Cys-LTs) and 8-isoprostane levels and asthma severity, asthma control level and c-ACT score in asthmatic children.MethodsThirty asthmatic children were evaluated with c-ACT score and pulmonary function tests. Asthma severity and asthma control level were assessed according to GINA. EBC was collected and Cys-LTs and 8-isoprostane concentrations were determined using a specific immunoassay kit.ResultsExhaled 8-isoprostane level in patients with moderate persistent asthma [114 (55–146) pg/ml] was higher than in the mild persistent group [52 (21–91) pg/ml] (p = 0.05, Mann–Whitney U [MWU]). EBC 8-isoprostane in children with 1–4 asthma exacerbations/year [52 (16–80) pg/ml] was significantly lower than in children with >4 asthma exacerbations/year [114 (57–129) pg/ml] (p < 0.05, MWU). No significant relation was determined between exhaled 8-isoprostane and Cys-LTs levels and c-ACT score and asthma control level. Exhaled 8-isoprostane correlated negatively with bronchodilator response (p = 0.015, r = −0.45).ConclusionsExhaled 8-isoprostane, as an oxidative stress specifier, was found to be increased in relation with asthma exacerbation frequency and oxidative stress increases with the severity of asthma. In contrast to asthma severity level, c-ACT score and asthma control level may not reflect airway inflammation.     

Lipid profiles in children with and without asthma: Interaction of asthma and obesity on hyperlipidemia

AimsThe joint effect of obesity and asthma on hyperlipidemia has never been explored. We aim to examine (1) the association of dyslipidemia and asthma, (2) the interaction effect of asthma and obesity on hyperlipidemia, and (3) whether a gender difference existed in the above relationships.MethodsBetween 2009 and 2010, 10- to 15-year-old children were recruited from 7 schools and 2 hospitals in Northern Taiwan. The population consisted of 237 asthmatic children and 225 non-asthmatic controls, and was further divided into four groups: non-obese controls, obese controls, non-obese asthmatics, and obese asthmatics. Measurements included anthropometric measures and blood samples for analysis of metabolic factors. The Cook's criteria were used to define childhood metabolic syndrome. General linear models were used to analyze how lipid profiles were associated with obesity and asthma.ResultsTotal cholesterol and low density lipoprotein cholesterol levels increased progressively in the group order obese asthmatics > non-obese asthmatics > obese controls > non-obese controls. In boys, low density lipoprotein cholesterol levels were significantly higher in obese asthmatics compared to obese non-asthmatics, with a mean difference of 6.2 mmol/L in the general linear model. We also discovered a significant interactive effect of obesity and asthma on hyperlipidemia in boys (p for interaction = 0.03).ConclusionsAsthma was associated with higher low density lipoprotein cholesterol levels and this association was amplified in overweight and obese subjects. A gender difference was observed in the joint effect of obesity and asthma on hyperlipidemia.     

Prevalence of asthma and associated factors in adolescents living in Belem (Amazon region), Para,Brazil

BackgroundThe prevalence of asthma in the Brazilian Amazon region is unknown. We studied the prevalence of asthma and associated factors in adolescents (13–14 years old) living in Belem, a large urban centre in this region.Methods3725 adolescents were evaluated according to the International Study of Asthma and Allergies in Childhood (ISAAC) protocol and a random sample of them (126 asthmatics and 254 non-asthmatics) were assessed for possible risk factors by a supplementary questionnaire (ISAAC Phase II) and skin prick tests with aeroallergens. The association between asthma and associated factors was determined by logistic regression analysis.Results3708 adolescents were enrolled, 48% were male. The prevalence of asthma in the last 12 months (identified as asthmatics) and the medical diagnosis of asthma were 20.7% and 29.3%, respectively. Risk factors significantly associated with asthma were: previous diagnosis of tuberculosis (odds ratio [OR] = 38.9; 95% confidence interval [95% CI]: 4.6–328.0) and measles (OR = 4.7; 95% CI: 2.3–9.8), breastfeeding for any length of time (OR = 4.2; 95% CI: 1.1–15.2), current rhinitis (OR = 3.2; 95% CI: 1.8–5.9), exposure to smokers (OR = 2.4; 95% CI: 1.2–4.5), moisture in home (OR = 1.8; 95% CI: 1.1–3.2) and rhinitis diagnosed by physician (OR = 1.7; 95% CI: 1.2–2.9). Sensitisation to at least one aeroallergen was significantly higher among asthmatic adolescents (86.5% vs. 32.4%; p < 0.0001).ConclusionsThe prevalence of asthma was similar to that observed in other Brazilian centres. Physician-diagnosed asthma was more frequent than the presence of symptoms suggestive of asthma. Infectious diseases, nutritional and environmental factors, as well as concomitant allergic rhinitis, were the main risk factors associated with the development of asthma in these adolescents.     

A literature review of the evidence that a 12% improvement in FEV1 is an appropriate cut-off for children

Introduction: A well-performed spirometry, using a change in forced expiratory volume in one second (FEV₁) after albuterol, is commonly used to support the likelihood of an asthma diagnosis. The current standard, accepted by the 2007 National Heart Lung and Blood Institute Asthma Expert Panel Report-3 (EPR-3) guidelines, is a 12% improvement in the FEV₁ after a bronchodilator. Objective: We sought to determine whether existing studies support or refute using a 12% improvement as a significant change in FEV₁ in children and adolescents. Data sources: We reviewed the literature of children and adolescents using Medline searches to discover pertinent population studies and comparative studies that included FEV₁ measurements. Result: The majority of the discovered studies suggest a less stringent improvement in FEV₁ in children might be applicable. Conclusion: Supported by the published literature, we suggest an alternative interpretive strategy of expressing the results of a spirometry measurement when a diagnosis of asthma in a child is being considered using a bronchodilator response.     

Additive effect of oxitropium bromide in combination with inhaled corticosteroids in the treatment of elderly patients with chronic asthma

The efficacy of the addition of inhaled oxitropium bromide in combination with inhaled corticosteroids in the treatment of elderly asthmatic patients whose asthma is not well controlled was evaluated. A randomized, open-label cross-over trial comparing 4-week treatment periods with and without regular inhalation of 200 μg of oxitropium bromide four times per day was performed. Twenty-four patients (mean age ± SD: 62 ± 7 years) completed the study. The dose of beclomethasone dipropionate in this patient group was 1300 ± 800 μg/day. Forced expiratory volume in 1 second (FEV₁) was significantly improved after treatment with regular inhalation of oxitropium bromide when compared with FEV₁ after treatment without oxitropium (1.73 ± 0.60 vs 1.63 ± 0.68). Both morning and evening peak expiratory flow rates were significantly greater during the treatment period with regular inhalation of oxitropium bromide. The score for dyspnea/chest tightness was also significantly improved during the oxitropium bromide period. There was no statistically significant improvement in forced vital capacity, scores for other symptoms or the frequency of rescue inhalation of fenoterol. The results of this study demonstrated that the addition of regular inhalation of oxitropium bromide is beneficial in elderly asthmatics whose asthma is not well controlled, even when treated with high-dose inhaled steroids.     

Changes in Exhaled Nitric Oxide Measured by Two Offline Methods Predict Improvements in Bronchial Hyperresponsiveness after Inhaled Steroid Therapy in Japanese Adults with Asthma

BackgroundThe fraction of exhaled nitric oxide (FeNO) is a useful marker of eosinophilic airway inflammation in asthmatics. No studies have examined the relationship between the change in FeNO levels measured offline and changes in bronchial hyperresponsiveness (BHR) in asthmatic patients treated with inhaled corticosteroids (ICS). The objective of this study was to investigate the relationship between the change in FeNO levels measured offline and the change in BHR to acetylcholine in asthmatic patients taking ICS.MethodsThe study population comprised 41 ICS-treated asthmatics from our outpatient clinic. We measured FeNO levels by two methods—with a Sievers kit (“FeNOs”) and with a kit from the Center for Environmental Information Science, Japan (“FeNOc”) at baseline and after 1 year of regular treatment. We also used spirometry to test BHR to acetylcholine (PC_20Ach).ResultsThe mean of duration of observation was 406 days. There were significant relationships between ?logPC_20Ach and logPC_20Ach (r = ? 0.877, P < 0.001), FeNOs (r = 0.465, P = 0.002), and FeNOc (r = 0.524, P = 0.004) at baseline, but not with age, the dose of ICS, FEV₁, or %FEV₁. Moreover, there was a significant relationship between ?logPC_20Ach and ?FeNOs (r = ? 0.386, P = 0.013) and ?FeNOc (r = ? 0.473, P = 0.004), but not with ?FEV1.ConclusionsChanges in FeNOs and FeNOc correlated with improvements in BHR to acetylcholine in adult asthmatics after ICS therapy. Our findings suggest that offline monitoring of FeNO will facilitate the management of bronchial asthma in patients treated with ICS.     

Development of Lung Function in Preterm Infants During the First Two Years of Life

IntroductionIt remains unclear if prematurity itself can influence post delivery lung development and particularly, the bronchial size.AimTo assess lung function during the first two years of life in healthy preterm infants and compare the measurements to those obtained in healthy term infants during the same time period.MethodsThis observational longitudinal study assessed lung function in 74 preterm (30 + 0 to 35 + 6 weeks’ gestational age) and 76 healthy term control infants who were recruited between 2011 and 2013. Measurements of tidal breathing, passive respiratory mechanics, tidal and raised volume forced expirations (V’maxFRC and FEF_25–75, respectively) were undertaken following administration of oral chloral hydrate sedation according to ATS/ERS recommendations at 6- and 18-months corrected age.ResultsLung function measurements were obtained from the preterm infants and full term controls initially at 6 months of age. Preterm infants had lower absolute and adjusted values (for gestational age, postnatal age, sex, body size, and confounding factors) for respiratory compliance and V’maxFRC. At 18 months corrected postnatal age, similar measurements were repeated in 57 preterm infants and 61 term controls. A catch-up in tidal volume, respiratory mechanics parameters, FEV_0.5 and forced expiratory flows was seen in preterm infants.ConclusionWhen compared with term controls, the lower forced expiratory flows observed in the healthy preterm group at 6 months was no longer evident at 18 months corrected age, suggesting a catch-up growth of airway function.