Mangiferin attenuates cigarette smoke-induced chronic obstructive pulmonary disease in male albino rats.

We analyzed the ability of mangiferin to suppress cigarette smoke-induced chronic obstructive pulmonary disease. Control rats showed a marked decrease in the ratio of the forced expiratory volume at 0.1 s to forced vital capacity. The decreases in the peak expiratory flow and maximal mid-expiratory flow indicated airway remodeling and enlargement. The expression levels of superoxide dismutase (SOD), heme oxygenase-1 (HO-1), γ-glutamylcysteine synthetase, nuclear factor erythroid 2-related factor 2, and activating transcription factor 4 were increased in the control rats. The levels of oxidative stress, malondialdehyde, and reactive oxygen species peaked after 24 weeks, whereas the SOD and HO-1 levels and the total antioxidant capacity were reduced in control rats. Mangiferin restored the levels of reactive oxygen species, malondialdehyde, SOD, HO-1, and T-AOC to near normal. Increased numbers of infiltrating inflammatory cells were observed in control rats but were significantly reduced by mangiferin. In addition, edema and airway inflammation were reduced by mangiferin.

Bronchodilatory effects of B-type natriuretic peptide in acute asthma attacks: a randomized controlled clinical trial.

INTRODUCTION: B-type natriuretic peptide (BNP) regulates different physiological processes such as blood pressure, cardiac growth, and neural and skeletal development. Thus, the aim of this study w as to evaluate the effect of BNP in the treatment of acute asthma attacks. MATERIAL AND METHODS: In this randomized clinical trial, patients with acute asthma attacks were enrolled. The patients were divided randomly into two groups. Patients in the interventional group received BNP via intravenous infusion. Two µg/kg of BNP was injected as a bolus in 60 seconds. Then, infusion of BNP immediately began and was given in 0.01, 0.02, and 0.03 µg/kg/min doses every 30 minutes for the first 1.5 hours. The patients in the control group received nebulized salbutamol. Afterwards, peak flow meter findings, hemodynamic parameters, and estimation of the clinical severity of asthma in both groups were checked every 30 minutes. RESULTS: In total, 40 patients were included in this study. The values of PEFR in the 60th and 90th minutes in the control group were lower than those in the interventional group. In the 60th minute, the mean of PEFR was 377.3 in the BNP group but 335.95 in the control group (P = 0.049). Moreover, this difference remained significant in the 90th minute (P = 0.021). However, forced expiratory volume in one second (FEV1) did not differ between the groups at any time (p > 0.05). CONCLUSION: Although a large experimental study is needed to verify our hypothesis, it seems that BNP might be a therapeutic option in asthma exacerbations, particularly in those with b2 agonist receptor polymorphism.

Treatment response according to small airways disease status: The effects of high-strength extrafine pMDI beclomethasone dipropionate/formoterol fumarate in fixed dose combination in moderate uncontrolled asthmatic patients.

BACKGROUND: Inflammation in small airways is particularly clinically active in severe asthma but they still continue to be ignored as considered silent. Recently, the Atlantis study reports small airways involvement in 91% of the asthma population. Therefore in the era of phenotype driven therapy, the aim of this study was to verify if high-strength extrafine ICS/LABA in fixed dose increases clinical efficacy in moderate asthmatic patients with small airways dysfunction and it could be proposed as phenotype driven therapy. METHODS: In this prospective, non-interventional, real-life pilot study we enrolled 37 consecutive patients with moderate asthma who were uncontrolled despite GINA step 3 treatment. All subjects at enrollment were divided in two groups according to the presence of small airways dysfunction:1) small airways phenotype (SAP) group: smokers (≥10 packs/die), ex-smokers (>20 packs/year) with air trapping (FVC <80% - VR >100% - FEF 25-75%<60%); 2) non-small airways phenotype (NSAP) group: non-smokers, without air trapping (FVC ≥80% - VR ≤ 100% - FEF 25-75%≥60%). We later proceeded in both groups with a step up in therapy with high-strength extrafine pMDI beclomethasone dipropionate/formoterol fumarate (BDP/FF) (200/6 µg) in fixed dose to achieve a better control and followed patients for 6 months. RESULTS: Treatment with extrafine BDP/FF(200/6 µg) in SAP group showed a more significant improvement of FEF25-75%, FVC, RV, and a reduction of alveolar inflammatory markers such as FENO350 and alveolar exhaled pH compared with NSAP patients. CONCLUSIONS: Our preliminary results support the use of high-strength extrafine pMDI BDP/FF (200/6 µg) as phenotype driven treatment directed to small airways dysfunction demonstrating an increase of clinical efficacy in moderate asthmatics with SAP.

Second-order Texture Measurements of (3)He Ventilation MRI: Proof-of-concept Evaluation of Asthma Bronchodilator Response.

RATIONALE AND OBJECTIVES: (3)He magnetic resonance imaging (MRI) can be used to quantify functional responses to asthma therapy and provocation. Ventilation imaging offers quantitative information beyond ventilation defects that have not yet been exploited. Therefore, our objective was to evaluate hyperpolarized (3)He MRI ventilation defect percent (VDP) and compare this and pulmonary function measurements to ventilation image texture features and their changes post-bronchodilator administration in patients with asthma. MATERIALS AND METHODS: Volunteers with a diagnosis of asthma provided written informed consent to an ethics board-approved protocol and underwent pulmonary function tests and MRI before and after salbutamol inhalation. MR images were analyzed using VDP, and their texture was evaluated via gray-level run-length matrices. These texture classifiers were compared to VDP in responders to bronchodilation based on VDP (VDP responders) and forced expiratory volume in 1 s (FEV1) (FEV1 responders). RESULTS: In total, 47 patients with asthma (18 males 39 ± 13 years, FEV1 = 79 ± 21%) reported significantly improved FEV1, FEV1/forced vital capacity (FVC), residual volume (RV)/total lung capacity (TLC) (all P = .0001) and VDP (P = .01) post-salbutamol. Post-salbutamol, VDP responders and nonresponders to salbutamol were significantly different for coarse-texture features including long-run emphasis (LRE) and long-run, low gray-level emphasis (LRLGE, both P < .05) and for FEV1 responders to salbutamol, there was significantly different long-run, high gray-level emphasis (LRHGE, P = .04). There were significant relationships for VDP with LRE (R = .50, P = .0003), LRLGE (R = .34, P = .02), and LRHGE (R = .56, P = .0001). Receiver operating characteristic curves showed VDP with the strongest performance (AUC = .92), followed by coarse-texture classifier LRHGE (AUC = .83), FEV1 (AUC = .80), LRE (AUC = .66), FVC (AUC = .58), and LRLGE (AUC = .42). CONCLUSIONS: In patients with asthma, differences in ventilation patchiness post-salbutamol can be quantified using coarse-texture classifiers that are significantly different in bronchodilator responders.

Short-term effects of a nicotine-free e-cigarette compared to a traditional cigarette in smokers and non-smokers.

BACKGROUND: A few studies have assessed the short-term effects of low-dose nicotine e-cigarettes, while data about nicotine-free e-cigarettes (NF e-cigarettes) are scanty. Concerns have been expressed about the use of NF e-cigarettes, because of the high concentrations of propylene glycol and other compounds in the e-cigarette vapor. METHODS: This laboratory-based study was aimed to compare the effects of ad libitum use of a NF e-cigarette or and a traditional cigarette for 5 min in healthy adult smokers (n = 10) and non-smokers (n = 10). The main outcome measures were pulmonary function tests, fraction of exhaled nitric oxide (FeNO) and fractional concentration of carbon monoxide (FeCO) in exhaled breath. RESULTS: The traditional cigarette induced statistically significant increases in FeCO in both smokers and non-smokers, while no significant changes were observed in FeNO. In non-smokers, the traditional cigarette induced a significant decrease from baseline in FEF75 (81 % ± 35 % vs 70.2 % ± 28.2 %, P = 0.013), while in smokers significant decreases were observed in FEF25 (101.3 % ± 16.4 % vs 93.5 % ± 31.7 %, P = 0.037), FEV1 (102.2 % ± 9.5 % vs 98.3 % ± 10 %, P = 0.037) and PEF (109.5 % ± 14.6 % vs 99.2 % ± 17.5 %, P = 0.009). In contrast, the only statistically significant effects induced by the NF e-cigarette in smokers were reductions in FEV1 (102.2 % ± 9.5 % vs 99.5 ± 7.6 %, P = 0.041) and FEF25 (103.4 % ± 16.4 % vs 94.2 % ± 16.2 %, P = .014). DISCUSSION: The present study demonstrated that the specific brand of NF e-cigarette utilized did not induce any majoracute effects. In contrast, several studies have shown that both traditional cigarettes and nicotine-containing e-cigarettes have acute effects on lung function. Our study expands on previous observations on the effects of NF e-cigarettes, but also for the first time describes the changes induced by smoking one traditional cigarette in a group of never smokers. CONCLUSIONS: The short-term use of the specific brand of NF e-cigarette assessed in this study had no immediate adverse effects on non-smokers and only small effects on FEV1 and FEF25 in smokers. The long-term health effects of NF e-cigarette use are unknown but worthy of further investigations. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02102191.

Forced expiratory decay in asthmatic preschool children--is it adult type?

BACKGROUND: The forced expiratory decay in healthy preschool children portrays a convex shape that differs from the linear decay in the older healthy population. The "adult-type" expiratory decay during airway obstruction is concave. The study objective was to determine if the expiratory decay in young asthmatic children is "adult-type". METHODS: Among 245 children (age 3-7 yrs), 178 had asthma (asthmatics) and 67 were non-asthmatic (controls). The expiratory flow decay was inspected by FEF25-75/FVC ratio (=1.0 when linear). Values were compared to those of our formerly studied (n = 108) healthy children. A meaningful obstruction in FEF25-75/FVC ratio was defined as 2-zScores from healthy. A meaningful response to bronchodilators was related to non-asthmatics. RESULTS: In healthy subjects FEF25-75/FVC ratio declined with age from 1.73 ± 0.17 to 1.28 ± 0.11. Non-asthmatics portrayed ratio values similar to those of healthy subjects. In asthmatics, 118/178 displayed a convex to linear expiratory decay (FEF25-75/FVC = 1.33 ± 0.22). Sixty/178 asthmatics portrayed concavity (FEF25-75/FVC-0.79 ± 0.16) that appeared when FEF50 was 43.4 ± 12%healthy. Concavity appearance was also age-dependent (30.4% of 3-4 y old and 59.1% of 6-7 y). Vital-Capacity decreased in either decays, forming a visually petit curve. Most asthmatic children respond to bronchodilators by a meaningful elevation in FEF25-75/FVC values and by a visual change in the shape of the curve. Other common spirometry indices also increased meaningfully. CONCLUSION: Most asthmatic preschool children portray convex to linear expiratory decay with diminished vital-capacity, resulting in a visually smaller than healthy curve, with seemingly normal expiratory decay. These curves may be misinterpreted as "normal" or as "no-cooperation" and may lead to misinterpretation. In response to bronchodilators, FEF25-75/FVC value increases in asthmatics and the curve changes from concave to linear or from linear to convex contour.

Better adherence to a transdermal tulobuterol patch than inhaled salmeterol in elderly chronic obstructive pulmonary disease patients.

BACKGROUND: Inhaled long-acting ß2-agonists (LABA) are often poorly adhered to by elderly patients with chronic obstructive pulmonary disease (COPD). We hypothesized that older age and compromised cognitive function might contribute to poor adherence to inhaled medications among COPD patients, and that transdermally delivered medications could improve adherence, exercise tolerance and quality of life (QOL). OBJECTIVE: To compare adherence and effects on health outcomes between transdermal and inhaled LABA. METHODS: A total of 44 treatment-naïve, elderly Japanese patients with moderate-to-severe COPD were treated with a transdermal tulobuterol patch (TP; 2 mg, once a day) or inhaled salmeterol (50 µg, twice a day) in a randomized crossover manner. The primary outcomes were adherence to the LABA medications and changes in QOL measured by the St George's Respiratory Questionnaire. Secondary outcomes were changes in 6-min walk distance (6MWD) and spirometric values. RESULTS: The overall adherence rate was 90.3 ± 1.6% for TP and 75.5 ± 2.9% for salmeterol (P < 0.001). Adherence to salmeterol was correlated with age and Mini-Mental State Examination (MMSE) score (P < 0.05 and P < 0.01, respectively), although that to TP was relatively constant regardless of age and MMSE score. 6MWD and QOL were significantly improved from baseline after TP, but not after salmeterol treatment (P < 0.05). Similar degrees of increase in spirometric values occurred after treatment with TP and salmeterol. CONCLUSIONS: Adherence levels were higher overall with TP than with inhaled salmeterol, and more stable across age groups and MMSE levels. TP might be a favorable treatment option for COPD patients with poor adherence to an inhaled LABA.

Traffic-related air pollution and acute changes in heart rate variability and respiratory function in urban cyclists.

BACKGROUND: Few studies have examined the acute health effects of air pollution exposures experienced while cycling in traffic. OBJECTIVES: We conducted a crossover study to examine the relationship between traffic pollution and acute changes in heart rate variability. We also collected spirometry and exhaled nitric oxide measures. METHODS: Forty-two healthy adults cycled for 1 hr on high- and low-traffic routes as well as indoors. Health measures were collected before cycling and 1-4 hr after the start of cycling. Ultrafine particles (UFPs; ≤ 0.1 µm in aerodynamic diameter), particulate matter ≤ 2.5 µm in aerodynamic diameter (PM2.5), black carbon, and volatile organic compounds were measured along each cycling route, and ambient nitrogen dioxide (NO2) and ozone (O3) levels were recorded from a fixed-site monitor. Mixed-effects models were used to estimate associations between air pollutants and changes in health outcome measures relative to precycling baseline values. RESULTS: An interquartile range increase in UFP levels (18,200/cm3) was associated with a significant decrease in high-frequency power 4 hr after the start of cycling [ß = -224 msec2; 95% confidence interval (CI), -386 to -63 msec2]. Ambient NO2 levels were inversely associated with the standard deviation of normal-to-normal (NN) intervals (ß = -10 msec; 95% CI, -20 to -0.34 msec) and positively associated with the ratio of low-frequency to high-frequency power (ß = 1.4; 95% CI, 0.35 to 2.5) 2 hr after the start of cycling. We also observed significant inverse associations between ambient O3 levels and the root mean square of successive differences in adjacent NN intervals 3 hr after the start of cycling. CONCLUSIONS: Short-term exposures to traffic pollution may contribute to altered autonomic modulation of the heart in the hours immediately after cycling.

Effect of ciclesonide on bronchial asthma in athletes.

BACKGROUND: Although it is well established that the incidence of bronchial asthma is higher in the athlete population than in the general population, little information exists about the efficacy of treatment of bronchial asthma in the athlete population. OBJECTIVES: We conducted this study with the objective of determining the efficacy of treatment of bronchial asthma in an athlete population living in Niigata Prefecture, Japan. METHODS: We conducted a retrospective study of bronchial asthma in an athlete population. Athletes diagnosed as having asthma, based on the Global Initiatives for Asthma (GINA) guidelines, who visited the Niigata Institute for Health and Sports Medicine between January 2007 and June 2008 were enrolled in this study. We compared two groups of patients, a group treated with ciclesonide (CIC) alone and another treated with montelukast alone, with the treatment duration lasting at least 3 months in both groups. The CIC or montelukast groups were compared in terms of the clinical symptoms, pulmonary function parameters, and fraction of exhaled nitric oxide (FENO). RESULTS: There were no significant differences in the sex distribution, age, frequency of symptoms, pulmonary function parameters, or other examination data before treatment between the CIC and montelukast groups. The CIC group tended to show better symptom control and to need fewer changes of treatment than the montelukast group. While improvements of the pulmonary function parameters and FENO values were observed in the CIC group, no significant changes of these parameters were observed in the montelukast group. CONCLUSIONS: These data suggest that CIC offers greater promise for the control of asthma than montelukast in the athlete population, although further investigation is required.

Determining the time to maximal bronchodilator response in asthmatic children.

BACKGROUND: The interval between bronchodilator administration and post-bronchodilator lung function testing is critical for accurate interpretation of the bronchodilator response. The time course of this response in children is not well documented. We aimed to document the time taken to achieve maximal lung function following salbutamol inhalation. METHODS: Eighteen asthmatic children between 7 and 18 years of age with a history of bronchodilator responsiveness were recruited. Spirometry was performed before and at 0, 10, 15, 20, 40, 60, and 90 minutes after salbutamol inhalation 600 microg (Ventolin; GlaxoSmithKline) via a spacer (Volumatic; GlaxoSmithKline). RESULTS: Spirometric indices significantly increased after salbutamol inhalation (p < 0.001). The group median time to maximal response in forced expiratory volume in 1 second (FEV(1)) was 17.5 (10-60: 10th-90th centiles) minutes after salbutamol. The magnitude of group response in FEV(1) was significantly higher at 15 and 20 minutes than at 0 and 10 minutes post-salbutamol inhalation (repeat measures analysis of variance [ANOVA] on ranks; p < 0.05). CONCLUSION: We conclude that a minimal interval of 20 minutes, before re-testing spirometry, is required to document the maximal response to bronchodilators in the majority of asthmatic children.

Comparison of single 2000-microg dose treatment vs. sequential repeated-dose 500-microg treatments with nebulized budesonide in acute asthma exacerbations.

BACKGROUND: High repeated doses of inhaled corticosteroids (ICSs) are recognized as having a more rapid improvement of outcomes than a single dose of ICS in severe acute asthma. However, to our knowledge, there has been no direct comparison of the early effects of single or repeated administration of the same total dosage of ICS in children with moderate to severe exacerbations of asthma. OBJECTIVE: To compare the efficacy of a single dose of 2000 microg of nebulized budesonide with 4 repeated doses of 500 microg of nebulized budesonide in 40 children with an acute asthma exacerbation. METHODS: Randomized, double-blind, parallel study that compared the efficacy of 2000 microg of nebulized budesonide, administered in a single dose, with repeated doses (4 doses of 500 microg each) during the first 90 minutes in 40 children (mean [SD] age, 10.7 [2.4] years) with an acute asthma exacerbation that required treatment with an oral corticosteroid. Forced expiratory volume in 1 second, asthma attack score, and oxygen saturation were evaluated at 20, 40, 60, 90, 120, 180, and 240 minutes after initial treatment. Oral corticosteroids were given to all patients at 90 minutes. RESULTS: There were no significant differences in forced expiratory volume in 1 second (P = .54) at any times between the groups. Also, asthma scores and oxygen saturation were not different in either group within 90 minutes (P = .51 and P = .64, respectively) and thereafter (P = .35 and P = .87, respectively). CONCLUSION: The use of a single dose of nebulized budesonide is as effective as repeated administration of the same total dosage during the first 90 minutes before giving oral corticosteroids in children with moderate to severe exacerbations of asthma.

[Effect of resveratrol on chronic obstructive pulmonary disease in rats and its mechanism].

The purpose of this study is to establish COPD animal model by intra-tracheal instillation of bleomycin (BLM) once and exposure to cigarette smoke for continuous 27 d, and to observe the effects of the inhalation on the model. At the 29th day, blood samples were taken from cervical artery for blood-gas analysis and parameters of lung function were recorded. Bronchoalveolar lavage fluid (BALF) was collected to measure intercellular adhesion molecule-1 (ICAM-1) concentration. The results showed that atomization inhaled resveratrol could alleviate rat COPD lung injury accompanied by amelioration of pathological changes, increase the ratio of forced expiratory volume in 0.3 s (FEV0.3) and forced vital capacity (FVC), and decrease the ICAM-1 level in BALF. The ultimate reduction of inflammatory factors was involved, at least in part, in the mechanism of resveratrol effects.

Combined salmeterol/fluticasone propionate versus fluticasone propionate alone in mild asthma : a placebo-controlled comparison.

BACKGROUND AND OBJECTIVE: Combined therapy with inhaled corticosteroids (ICSs) and long-acting beta(2)-adrenoceptor agonists (LABAs) is the recommended approach for the treatment of patients with asthma that is uncontrolled on ICSs alone. Additional studies are needed to assess the safety and efficacy of combination treatment with ICSs and LABAs in patients with mild asthma. The aim of this study was to compare the efficacy and tolerability of once-daily salmeterol/fluticasone propionate combination (SFC) with once-daily fluticasone propionate (FP) over a 12-week treatment period in patients with mild persistent asthma. METHODS: This was a randomized, double-blind, placebo-controlled, parallel-group, multicentre study carried out in primary care or at a hospital outpatient department and included patients 12-79 years of age with mild persistent asthma (n = 458). After a 2-week run-in period, patients were randomized to receive SFC 50 microg/100 microg (n = 149), FP 100 microg (n = 154) or placebo (n = 155) once daily in the morning for 12 weeks. The primary efficacy endpoint was patient-recorded pre-dose mean morning peak expiratory flow (PEF). Other assessments included asthma symptom scores, use of rescue medication and investigator-recorded exacerbations. Lung function was measured and assessed during clinic visits. RESULTS: For the primary efficacy endpoint of mean change in morning PEF, SFC achieved significantly greater increases from baseline than both placebo (difference in adjusted means 23 L/min; 95% CI 15.0, 30.3; p < 0.001) and FP (difference in adjusted means 14 L/min; 95% CI 6.3, 21.7; p < 0.001). Compared with those who received FP, patients in the SFC group demonstrated significantly greater improvements in mean evening PEF (95% CI 11.7, 28.1; p < 0.001), forced expiratory volume in 1 second (95% CI 0.093, 0.257; p < 0.001), forced expiratory flow between 25% and 75% of forced vital capacity (95% CI 0.242, 0.617; p < 0.001), the percentage of symptom-free days (95% CI 0.34, 0.87; p = 0.011), and the percentage of rescue medication-free days (95% CI 0.34, 0.90; p = 0.018). During weeks 5-12, 52% of patients in the SFC group achieved 'well controlled' asthma, compared with 42% and 26% of patients in the FP and placebo groups, respectively. Only one patient (receiving placebo) had a severe asthma exacerbation during the study; the frequency of adverse events was similar across the three treatment groups. CONCLUSION: Once-daily SFC 50 microg/100 microg provided significantly greater improvements in lung function and in asthma symptoms than once-daily FP 100 microg alone in patients with mild persistent asthma. However, twice-daily treatment with either SFC or ICSs plus short acting beta(2)-adrenoceptor agonists could be required to achieve guideline-defined asthma control in some patients.

Spirometry parameters in patients undergoing hemodialysis with bicarbonate and acetate dialysates.

INTRODUCTION: End-stage renal disease causes impairment of all body organs including the heart and the lung. The main problems in the afflicted patients are pulmonary edema due to increased permeability of the capillaries, intravascular and interstitial volume overload, hypertension, and congestive heart failure. These changes cause altered physiologic and mechanical function of the lungs and subsequently increase in airway resistance. We aimed to study the impact of hemodialysis on spirometry parameters. MATERIALS AND METHODS: In a cross-sectional study performed on 41 patients on maintenance hemodialysis, spirometry was done before and after the dialysis session. The patients were on either acetate or bicarbonate hemodialysis with the same method, dialysis machine, and duration of dialysis. Alterations in spirometry parameters including forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and maximal midexpiratory flow rate were determined and their relation with serum electrolytes, serum creatinine, blood urea nitrogen, and hemoglobin were analyzed. RESULTS: Twenty-nine patients undergoing dialysis with bicarbonate dialysate and 21 on dialysis with acetate were compared. Improvement in spirometry parameters was only significant in patients undergoing dialysis with bicarbonate dialysate. All spirometry parameters showed significant increases in the bicarbonate group except for the FEV1/FVC ratio. Furthermore, significant increase in these parameters was only prominent in the men. Postdialysis weight reduction and laboratory indexes had no significant correlation with improvement of spirometry parameters. CONCLUSIONS: Dialysis with bicarbonate dialysate causes significant improvement in spirometry parameters in men on maintenance dialysis. This effect might be independent of the effect of removing the volume overload by dialysis.

The effect of tiotropium on the pulmonary diffusing capacity.

To our knowledge, there is no data on the effect of tiotropium on pulmonary gas exchange in healthy subjects. The aim of this study was to assess the effects of tiotropium on pulmonary diffusing capacity. Twenty-one healthy volunteers were enrolled for a prospective, randomized, double-blind, placebo-controlled study. Spirometric measurements, including pulmonary-diffusing capacity, were obtained before and after inhalation of drug or placebo. There was a significant decrease in forced vital capacity (FVC) and, consequently, an increase in the forced expiratory volume in one second (FEV1) to FVC ratio after placebo inhalation (p < 0.05), but no changes were found for percent-predicted FVC, FEV1, percent-predicted FEV1, percent-predicted forced expiratory flow (FEF25%-75%), percent-predicted peak expiratory flow (PEF), diffusing capacity of the lung for carbon monoxide (DLCO), single-breath alveolar volume (VA) and DLCO/VA ratio when compared with the baseline. Tiotropium inhalation caused a significant increase in FVC, percent-predicted FEV1, FEV1/FVC and percent-predicted FEF25%-75%, although the decrease in DLCO was insignificant (12.4 +/- 0.9 to 11.4 +/- 0.9). In conclusion, tiotropium does not change the pulmonary-diffusing capacity in healthy volunteers.

A randomized, double-blind trial of the effect of anti-asthma treatment on lung function in children with asthma.

BACKGROUND: Pulmonary function tests (PFTs) and especially spirometry measures are useful tools in evaluating early response to treatment of asthma in children mainly due to their worldwide availability. The aim of our study was to determine the effects of anti-asthma treatment in children, equally on FEV(1), FEF25-75%, R(int) and SR(aw) values. METHODS: Children 6-18 years of age with moderate atopic asthma were randomized to 4-week, placebo-controlled, double-blind trial. Patients were randomly allocated to receive 200 microg budesonide (B) (n=29), 5 or 10 mg (according to age) montelukast (M) (n=29), 200 microg B + 5 or 10 mg M (n=29), 200 microg B + 9 microg formoterol (F) (n=29) or placebo (n=27). FEV(1,) FEF25-75%, R(int), SR(aw) were measured before and after treatment. RESULTS: R(int), SR(aw), FEV(1) improved significantly in all active treatment groups while FEF25-75% improved significantly only in BM group and M group. Combination therapy, showed significantly greater effects on R(int) than monotherapy: BM group compared to B group (P=0.01) and M group (P=0.03) and BF group compared to B group (P=0.01) and M group (P=0.04). CONCLUSION: This study shows that using single parameter for monitoring asthma can be misleading. Using combination of lung function techniques provides better assessment of treatment. Results of our study confirm this hypothesis. The best effect on large and small airways was achieved with combined anti-inflammatory therapy.

Same efficacies of ipratropium and salbutamol in reversing methacholine-induced bronchoconstriction.

Efficacy of salbutamol (S) was compared to that of ipratropium (I) or to their association, after methacholine challenge testing (MCT). MCT was performed in 4 groups of 10 patients suspected to suffer from asthma; mean changes in FEV1, maximal midexpiratory flow rate (MMFR), and airway resistance (Raw) were the same in all groups. After MCT, the group 1 patients inhaled S and then I, 10 min later; both drugs were given in the reverse order to the group 2 patients. The group 3 patients inhaled a mixture of both drugs just after MCT; the group 4 patients were not given any bronchodilator till the 20th min after MCT, when they inhaled S. Short-term (10 min) bronchodilator effects of S, I or S + I on spirometric variables were of the same magnitude and Raw returned to its baseline value. Further improvement (10-20 min) in FEV1 was mainly due to spontaneous recovery, whereas further increase in MMFR was due also to bronchodilator actions of drugs. It is concluded that ipratropium could be proposed as an alternative bronchodilator to salbutamol after MCT.

The impact of spirometry on pediatric asthma diagnosis and treatment.

Research has shown that spirometry is underutilized in the clinical setting. This study profiles the use of spirometry in an asthma management program at an inner-city community health clinic. Eligible subjects included 56 children who presented with an acute asthma exacerbation. Physicians recorded patient diagnosis before and after viewing spirometry. Bivariate and multivariate analysis was used to determine associations between symptoms and forced expiratory volume in 1 second (FEV1). Physicians changed 30.4% of patients' treatment plans after viewing spirometry results. Wheezing was significantly associated with FEV1 in bivariate analysis; however, multivariate modeling failed to identify significant relationships. The use of spirometry influenced patient diagnosis and treatment.

Eosinophilic inflammation, remodeling of lower airway, bronchial responsiveness and cough reflex sensitivity in non-asthmatic subjects with nasal allergy.

BACKGROUND: It has been reported that nasal allergy influences the lower airway inflammation and functions. We elucidated whether nasal allergy would contribute to lower airway inflammation and functions. METHODS: 266 subjects aged 21-39 years were interviewed with special emphasis on history of asthma and nasal allergies (perennial allergic rhinitis (PAR) and seasonal allergic rhinitis (Japanese cedar pollinosis; PO)). Symptomatic subject was defined when nasal symptoms were present during a 3-week study period. Pulmonary function, provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 s (PC20), capsaicin cough threshold defined as capsaicin concentration eliciting 5 or more coughs (C5) and eosinophil percentage in hypertonic saline-induced sputum were measured. RESULTS: Based on the interview, 232 subjects without asthma were divided into symptomatic (n = 25) and asymptomatic (n = 22) PAR, PO on-season (n = 15) and off-season (n = 36), and non-nasal allergy subjects (control) (n = 134). Sputum eosinophils were significantly greater in symptomatic PAR than another four groups (p < 0.01). FEV1/FVC ratio was significantly lower in PAR than control (p < 0.05). Maximum mean expiratory flow was lower in PAR than control (asymptomatic: p < 0.05, symptomatic: p = 0.06). C5 was not different among groups. PAR tended to have a lower PC20 compared to control (symptomatic: p = 0.078; asymptomatic: p = 0.086). CONCLUSIONS: These results suggest that eosinophilic inflammation occurred in symptomatic period of PAR may contribute to development of lower airway remodeling and bronchial hyperresponsiveness. Reversely, PO may not be associated with lower airway eosinophilic inflammation or abnormal bronchial functions. Nasal allergy dose not influence the cough reflex sensitivity.

Forskolin versus sodium cromoglycate for prevention of asthma attacks: a single-blinded clinical trial.

To determine the efficacy of forskolin in preventing asthma attacks, we performed a single-blinded clinical study in children and adult out-patients at a public hospital in Mexico. Forty patients of either sex with mild persistent or moderate persistent asthma were assigned randomly to 6 months of treatment with forskolin at 10 mg/day orally (capsules) or with two inhalations of sodium cromoglycate every 8 h, i.e. three times a day. The number of patients who had asthma attacks during the treatment period was significantly lower among those receiving forskolin (8/20, 40%) than among those receiving sodium cromoglycate (17/20, 85%). Values of forced expiratory volume in 1 s and forced expiratory flow, mid-phase, A similar in the two groups during the treatment period. We conclude that forskolin is more effective than sod cromoglycate in preventing asthma attacks in patients with mild persistent or moderate persistent asthma.