Exhaled nitric oxide and exercise-induced bronchospasm assessed by FEV1, FEF25-75% in childhood asthma.

The relationship between exhaled nitric oxide (eNO) and bronchial hyperresponsiveness (BHR) should be clarified. The aim of this study was to determine the relationship between eNO and exercise-induced bronchospasm (EIB) by estimation of the each lung parameter in asthmatic children who performed a bicycle ergometer exercise test. Twenty children with asthma were recruited. eNO concentration was examined by the recommended online method. To evaluate BHR, an exercise stress test was performed on a bicycle ergometer. The mean baseline eNO value was significantly correlated with the mean maximum % fall in forced expiratory volume in 1 second (FEV1), forced expiratory flow between 25% and 75% (FEF25-75%) after exercise (r=0.53, r=0.65, respectively). eNO in the EIB-positive group was significantly higher than that in the EIB-negative group by assessing FEV1, FEF25-75% (p<0.005, p=0.005). We demonstrated that the most important lung parameter assessed the occurrence of EIB by a bicycle ergometer exercise test was not only FEV1 but FEF25-75%, which significantly correlated with eNO. This suggests that not only FEV1 but FEF25-75% can be used to evaluate the correlations between BHR (EIB) and airway inflammation (eNO) in asthmatic children. A low eNO is useful for a negative predictor for EIB.     

3-min step test and treadmill exercise for evaluating exercise-induced asthma.

A simple exercise test would be useful for detecting exercise-induced asthma, a common problem in asthmatic children. The current study compared the 3-min step test with treadmill exercise for evaluating exercise-induced asthma in asthmatic children and assessed whether responses to both tests are influenced by baseline lung function and habitual physical activity. A series of 154 asthmatic children (84 male children; mean age 12.9 +/- 0.9 yrs) underwent a 3-min step-test and treadmill testing on different days within a week at least 24 h apart. Before both tests each subject did spirometry to obtain the baseline forced expiratory volume in one second (FEV1). After both exercise challenges all subjects did serial spirometry and the lowest FEV1 recorded over time was used to calculate the fall in FEV1 expressed as a percentage of the measured pre-exercise (baseline) value (% fall in FEV1) and the area above the FEV1 curve (AAC0-30 min) expressed as a percentage of the pre-exercise value. Changes in both exercise variables were also analysed in percentile subgroups defined by questionnaire answers on habitual physical activity in hours. The mean % fall in FEV1 was significantly higher for treadmill exercise than for the step test (15.0 +/- 7.5 versus 11.7 +/- 5.9); and the AAC0-30 min was larger for treadmill than for the step test (-261.6 +/- 139.9% versus -197.3 +/- 105.0% min). In all subgroups defined by habitual physical activity the mean % fall in FEV1 decreased more after treadmill exercise than after the step test. After step test and treadmill exercise no significant correlation was found between % fall in FEV1 and baseline lung function, or between % fall in FEV1 among groups defined by habitual physical activity. Although the 3-min step test yields a lower % fall in forced expiratory volume in one second (FEV1) and a lower value of the area above the FEV1 curve than treadmill testing, it is a quick, economical, reproducible and portable alternative procedure for identifying exercise-induced asthma in outpatients and epidemiological studies. Baseline lung function and habitual physical activity have no influence on the amount or duration of exercise-induced asthma.     

Eosinophils play a major role in the severity of exercise-induced bronchoconstriction in children with asthma

Exercise-induced bronchoconstriction (EIB) was associated with eosinophilic airway inflammation, bronchial hyperresponsiveness (BHR), atopy and airway obstruction. To understand the pathogenesis of EIB, we determine whether eosinophil is more related to the mechanism of EIB than atopy, BHR and airway obstruction. This study comprised 268 asthmatic children who underwent lung function test, methacholine challenge test, exercise challenge test, and blood tests for total IgE levels and total eosinophil counts (TEC). Urine eosinophil protein X (EPX) levels after exercise were measured by using ELISA method. EIB was observed in 195 of 268 asthmatics (72.8%). Asthmatics with EIB showed significantly increased TEC (P < 0.01) and decreased log PC(20) as compared with asthmatics without EIB. Maximal percent fall in FEV(1) after exercise was significantly correlated with TEC, log IgE, FEF(25-75%), log PC(20) (P < 0.001, respectively) and FEV(1) (P = 0.013). When the same study was carried out in nonatopic asthmatics, those with EIB showed significantly increased TEC (P = 0.01) compared with those without EIB; however, log PC(20), FEV(1), and FEF(25-75%) showed no significant differences between the two groups of nonatopic asthmatics. In addition, there was a significant correlation between the severity of EIB and TEC in nonatopic asthmatics. Urine EPX/Cr levels after exercise were correlated with the severity of EIB (r = 0.238, P = 0.014). Blood eosinophils and urine EPX/Cr after exercise correlate significantly with the maximal percent fall in FEV(1) after exercise, therefore EIB may reflect a state of eosinophilic inflammation in the airway of asthmatic children.     

The effect of montelukast on bronchial hyperreactivity in preschool children

INTRODUCTION: The effect of montelukast therapy on bronchial hyperreactivity (BHR) as measured by the methacholine challenge test in preschool children has not yet been reported. OBJECTIVE: To determine the effect of montelukast (4 mg/d) on BHR as evaluated by a provocative concentration of a substance causing a 20% fall in FEV(1) (PC(20)) values in preschool asthmatic children. PATIENTS: A total of 26 preschool children (8 girls) aged 3.3 to 6.0 years (mean [+/- SD] age, 4.7 +/- 0.8 years) with mild asthma. DESIGN: Double-blind randomized, placebo controlled, crossover study. Each child received 4 weeks of treatment with 4 mg of either montelukast or placebo separated by a 2-week washout period. Primary outcomes were PC(20) values and the stage number (triple dose) at which FEV(1) values dropped by 20%(.) Post-montelukast therapy PC(20) was compared to those for the post-placebo period. RESULTS: Following 4 weeks of montelukast treatment, the mean PC(20) was 4.79 +/- 4.69 mg/mL, while after 4 weeks of placebo the mean PC(20) was 2.07 +/- 2.37 mg/mL (p = 0.001). The montelukast/placebo ratio for PC(20) was 2.56 with a 95% confidence interval (CI) of 1.71 to 3.99. The median difference in stage was one triple dose with a 95% CI of 0.5 to 1.5. CONCLUSIONS: Four weeks of treatment with montelukast resulted in a decreased BHR compared with placebo.     

Orally administered nifedipine in chronic stable asthma. Comparison with an orally administered sympathomimetic

Calcium channel blockers have been shown to attenuate bronchoconstriction when given prior to bronchoprovocation challenge testing. However, they have not been found to induce bronchodilation when administered to asthmatic subjects with normal baseline lung function. In vitro data, on the other hand, suggest that preconstricted tracheal strips can be made to relax by the addition of calcium channel blockers. Therefore, we compared the effects of orally administered nifedipine (20 mg), albuterol (4 mg), and placebo on airway function in 10 asthmatic subjects with chronic stable asthma and baseline bronchoconstriction in a double-blinded, randomized, cross-over trial. Nifedipine caused a significant increase in FEV1 (0.21 +/- 0.08 SEM L) at 40 min after administration of the drug. The mean of the change in FEV1 throughout the 2-h observation period after nifedipine (0.19 +/- 0.08 L) was significant when compared with baseline (p less than 0.05) and placebo control values (p less than 0.005) but tended to be less than the bronchodilation observed after albuterol. Only 3 subjects had an increase in FEV1 greater than 10% of their baseline value after nifedipine compared with 7 subjects after albuterol and 2 subjects after placebo. These results are at least consistent with the hypothesis of a direct action of calcium channel blockers on bronchial smooth muscle and indicate that orally administered nifedipine has a weak bronchodilating effect in subjects with chronic stable asthma who have abnormal lung function.     

Effect of corticosteroids on bronchial responsiveness to methacholine in asthmatic children

To elucidate the effects of corticosteroids on nonspecific bronchial reactivity in asthmatic children, inhaled challenges with methacholine were conducted in 10 atopic asthmatic subjects (9 to 15 yr of age) before and after consecutive week-long trials of daily orally administered placebo and prednisone (60 mg/day). Pharmacologic bronchial sensitivity was evaluated as the log dose of methacholine producing a 20% fall in FEV1 (PD20-FEV1). The week-long trial of placebo had no effect on either baseline lung function or PD20-FEV1. On the other hand, after the 1-wk course of prednisone: (1) both baseline FEV1 and FEF25-75 systematically improved in the patients who initially had (i.e., before prednisone) lower values, and (2) PD20-FEV1 significantly increased (p less than 0.001) in all the subjects studied. The magnitude of increase in PD20-FEV1 after prednisone was significantly inversely related (i.e., inverse hyperbola) to the initial degree of airway obstruction (i.e., FEV1) obtained prior to prednisone treatment. Moreover, whereas 6 of 10 patients only minimally changed their baseline FEV1 after prednisone, collectively for all the subjects, the percent increase in PD20-FEV1 after prednisone was directly related (correlation coefficient, 0.70; p less than 0.05) to the corresponding percent increase in baseline FEV1 after prednisone. These findings demonstrate that after a week-long course of high-dose prednisone therapy: (1) a significant reduction occurs in bronchial sensitivity to inhaled methacholine in the asthmatic child, and (2) the degree of diminution in airway sensitivity to methacholine is inversely related to the patient's baseline status of airway obstruction.     

Comparison of percentage fall in FVC at the provocative concentration of methacholine causing a 20% fall in FEV(1) between patients with asymptomatic bronchial hyperresponsiveness and mild asthma

BACKGROUND: A significant proportion of individuals who have no symptoms of asthma or other respiratory diseases show bronchial hyperresponsiveness (BHR). BHR is usually assessed by measuring the provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)). The percentage fall in FVC at the PC(20) (DeltaFVC) has been suggested to reflect maximal airway response and to be a more useful index of disease severity in asthma than PC(20). The aim of this study was to investigate whether asymptomatic BHR would differ from symptomatic BHR with regard to DeltaFVC. METHODS: Methacholine bronchial challenge tests were conducted in children with no past or current symptoms of asthma, allergic rhinitis, or other respiratory diseases, who were identified among siblings of children with asthma. Forty-three children with asymptomatic BHR (PC(20) < 16 mg/mL) were recruited, and 43 children with mild asthma who were matched for age, sex, and PC(20) were selected (mild asthma group). The DeltaFVC on methacholine concentration-response curves was retrospectively analyzed in the two groups. RESULTS: There were no differences in the frequency of atopy, blood eosinophil counts, serum IgE levels, and spirometric values between the asymptomatic BHR and mild asthma groups. Mean (+/- SD) DeltaFVC was significantly (p = 0.005) lower in the asymptomatic BHR group (14.5 +/- 3.6%) than in the mild asthma group (16.9 +/- 4.3%). CONCLUSIONS: Our results suggest that children with asymptomatic BHR have a lower level of maximal airway response than mild asthmatics with a similar degree of BHR. This may be a possible explanation for the lack of symptoms in subjects with asymptomatic BHR.     

Bimosiamose, an inhaled small-molecule pan-selectin antagonist, attenuates late asthmatic reactions following allergen challenge in mild asthmatics: a randomized, double-blind, placebo-controlled clinical cross-over-trial

BACKGROUND: Asthma is characterized by increased recruitment of inflammatory cells from the circulation into the airways. As selectins mediate tethering and rolling of leukocytes on the vascular endothelium, they constitute a promising target for the therapeutic modulation of inflammation. We evaluated the effect of inhaled bimosiamose (TBC1269), a synthetic pan-selectin antagonist, on allergen-induced late asthmatic reactions (LAR) in mild asthmatics. METHODS: Twelve male subjects with mild allergic asthma (only beta-agonists prn) with demonstrable LAR (fall of FEV1 3-8h after allergen inhalation >15% of baseline) at screening completed a randomized, double-blind, placebo-controlled clinical cross-over-trial. Subjects were treated with inhaled bimosiamose 70 mg bid or matching placebo on days 1-3 and 70 mg once on the morning of day 4. On day 4 following the last inhalation of study drug, an allergen challenge was performed. The primary endpoint was the maximum fall in FEV1 between 3 and 8h after allergen inhalation on active treatment vs. placebo. Secondary endpoints included early asthmatic response, exhaled nitric oxide, and airway hyperresponsiveness to methacholine 24h post allergen. RESULTS: Bimosiamose significantly attenuated the maximum LAR compared to placebo by 50.2% (placebo mean+/-SEM fall -13.10+/-2.30%, bimosiamose -6.52+/-3.86%, treatment effect p=0.045; linear mixed-effects model). There was no effect of active treatment on early asthmatic response, post allergen airway hyperresponsiveness or exhaled nitric oxide, and peripheral blood cells. CONCLUSIONS: Administration of the pan-selectin antagonist bimosiamose is effective in a human allergen challenge model of asthma. The result of this proof-of-concept exploratory trial is the first study that demonstrates clinical efficacy of selectin-antagonists as novel therapeutic strategy in asthma.     

Effects of single-dose fluticasone on exercise-induced asthma in asthmatic children: a pilot study

A single high dose of inhaled corticosteroid (ICS) can increase airway caliber in children with asthma attacks and laryngitis subglottica. Presumably the effect is due to the vasoconstrictive and antiedematous properties of topical steroids. Enlarged vessels have been suggested to play a role in the pathophysiology of exercise-induced bronchial obstruction (EIB). To investigate this, we evaluated the effect of a single high dose of fluticasone propionate (FP) on EIB in asthmatic children. Nine children aged 8-16 years with mild to moderate asthma were included. All children had a history of EIB, which was confirmed by an exercise test. None was taking ICS maintenance therapy. The children inhaled either a single dose of 1 mg FP or placebo on 2 separate days within 7-14 days. After inhalation, airway caliber (FEV(1)) was assessed for 4 hr before exercise. Then an exercise challenge was performed on a treadmill to assess EIB (% fall FEV(1)). A significant increase in FEV(1) was observed 1 hr after inhalation of FP compared to placebo. Response to exercise was expressed as maximal % fall in FEV(1) from baseline (% fall) and as area under the curve (AUC) of the 30-min time/response curve. The % fall FEV(1) after exercise and the AUC were significantly reduced when FP was inhaled compared to placebo inhalation (% fall 9.7% vs. 19.2%, respectively, P = 0.038 and AUC 92.0%.min vs. 205.7%.min, respectively, P = 0.03). There was considerable individual variability in reduction of EIB, with 5 out of 9 children having a clinically significant response. We conclude that a single high dose of inhaled FP has an acute protective effect on the bronchial response to exercise in a substantial proportion of asthmatic children.     

Prolonged effect of montelukast in asthmatic children with exercise-induced bronchoconstriction

Accumulating evidence shows that cysteinyl leukotrienes are the most important mediators in exercise-induced bronchoconstriction (EIB). In contrast to several studies in adults, there are few long-term studies of leukotriene receptor antagonists (LTRAs) in children with EIB. The aim of this study was to assess the prolonged clinical and bronchoprotective effects of montelukast in asthmatic children with EIB. We randomly assigned 64 asthmatic children with EIB. Forty subjects received montelukast (5 mg/day), and 24 subjects received placebo once daily for 8 weeks. Exercise challenge was performed before and after 8 weeks of treatment. Of the 40 patients in the montelukast group, 28 patients crossed over after 8 weeks. The response was measured as asthma symptom score, maximum percent fall in forced expiratory volume in 1 sec (FEV(1)) from pre-exercise baseline, and time to recovery of FEV(1) to within 10% of pre-exercise baseline (time to recovery). Following 8 weeks of treatment with montelukast, the montelukast group compared with placebo showed significant improvements in all endpoints, including asthma symptom score, maximum percent fall in FEV(1) after exercise, and time to recovery. In the cross-over group, even 8 weeks after stopping montelukast treatment, all endpoints were significantly and persistently improved. These results indicate that montelukast provides clinical protection from airway hyperresponsiveness in asthmatic children with EIB, and suggest that LTRAs may be useful for the long-term management of asthmatic children with EIB.     

Bronchial responsiveness to adenosine 5'-monophosphate (AMP) and methacholine differ in their relationship with airway allergy and baseline FEV(1)

Bronchial hyperresponsiveness (BHR) and inflammation are central hallmarks of asthma. Studies in patients with asthma suggest that BHR to adenosine 5'-monophosphate (AMP) is a better marker of bronchial inflammation than BHR to methacholine. The association between markers of airway inflammation and BHR to methacholine and AMP in a population of young adults, with mild symptoms if any, was evaluated. A total of 230 subjects who participated in a follow-up study on occupational allergy were included. Before exposure to occupational allergens, subjects completed a questionnaire on respiratory symptoms and were tested for atopy, blood eosinophilia (> or =275/mm(3)), and BHR to methacholine and AMP (> or =15% fall in FEV(1)). Risk estimates were expressed as prevalence ratios (PR) and 95% confidence intervals (95% CI). Dose-response slopes (DRS) for methacholine and AMP were compared between healthy control subjects, self-reported allergic rhinitis, and allergic asthma. BHR to AMP was associated with allergic rhinitis (PR 2.51, 95% CI: 1.22;5.17), allergic asthma (PR 4.38, 95% CI: 1.98;9.66), with atopy (PR 3.87, 95% CI: 1.76;8.52), and blood eosinophilia (PR 3.57, 95% CI: 1.48;8.77), but not with baseline FEV(1). BHR to methacholine was inversely related to prechallenge FEV(1) (PR 0.97, 95% CI: 0.96;0.99). For both methacholine and AMP the geometric mean DRS increased along the axis asymptomatic-allergic rhinitis-allergic asthma, but for AMP the increase was the strongest. In this population study among young adults, BHR to AMP refers to allergic background of airway lability and BHR to methacholine is related to a diminished airway caliber.     

Respiratory impedance response to a deep inhalation in asthmatic children with spontaneous airway obstruction.

The aim of the study was to determine whether the bronchomotor effect of a deep inhalation (DI) may be detected during tidal breathing in asthmatic children with spontaneous airway obstruction (AO). Two groups of children aged 5-15 yrs were studied. AO was mild in group 1 (n=12, forced expiratory volume in one second (FEV1) > or = 75% predicted) and moderate-to-severe in group 2 (n=9, FEV1 > or = 70% pred). The forced oscillation technique at 12 Hz using a head generator allowed the determination of respiratory resistance in inspiration (Rrsi) and expiration (Rrse) before and after DI, at baseline and after salbutamol. At baseline, Rrsi but not Rrse was found to decrease significantly after DI in group 1 but not in group 2. The change induced by DI was significantly different in group 1 (-1.5+/-0.5 hPa x s x L(-1)) compared to group 2 (0.5+/-0.5 hPa x s x L(-1)) and exhibited significant negative correlation to FEV1 % pred. After salbutamol, DI had no effect. In conclusion, asthmatic children show a bronchomotor response to deep inhalation that depends on the degree of airway obstruction. The effect is more readily demonstrated in inspiration than in expiration.     

Asthma from childhood to adulthood: course and outcome of lung function

Lung function (FEV1 before and after bronchodilatation) was studied prospectively over five visits in 55 asthmatic children (28 boys) from childhood to adulthood (age 30). At the last follow-up recordings were made at rest, after cold air challenge (CACh), and after bronchodilatation. Results were related to clinical asthma scoring and to sensitization to furred animals, as described in a companion paper. Lung function outcome was shown to be influenced by initial FEV1 (% predicted) and gender, but not by initial asthma severity or sensitization. FEV1 (% predicted) was higher in females than in males over the first two follow-ups, but the reverse was found over the subsequent visits. It deteriorated from childhood to adulthood in the females but improved in the males. In adulthood the females (for height 170 cm) had a steeper normalized annual fall in post-bronchodilator FEV1 than the males (55 +/- 38 vs. 25 +/- 36 ml; P = 0.006). The degree of bronchial hyperresponsiveness was associated significantly with asthma severity and the extent of sensitization to furred animals, but not with gender. The results indicate a better lung function outcome for asthmatic boys than for girls, confirming trends seen in clinical asthma severity. In adulthood the extent of sensitization to relevant perennial inhaled allergens significantly influences airway responsiveness and asthma severity, but not lung function.     

Ascorbic acid supplementation attenuates exercise-induced bronchoconstriction in patients with asthma

BACKGROUND: Previous research has shown that diet can modify the bronchoconstrictor response to exercise in asthmatic subjects. OBJECTIVE: Determine the effect of ascorbic acid supplementation on pulmonary function and several urinary markers of airway inflammation in asthmatic subjects with exercise-induced bronchoconstriction (EIB). METHODS: Eight asthmatic subjects with documented EIB participated in a randomized, placebo controlled double-blind crossover trial. Subjects entered the study on their usual diet and were placed on either 2 weeks of ascorbic acid supplementation (1500 mg/day) or placebo, followed by a 1-week washout period, before crossing over to the alternative diet. Pre- and post-exercise pulmonary function, asthma symptom scores, fraction of exhaled nitric oxide (FENO), and urinary leukotriene (LT) C4-E4 and 9alpha, 11beta-prostagladin (PG) F2] were assessed at the beginning of the trial (usual diet) and at the end of each treatment period. Results: The ascorbic acid diet significantly reduced (p < 0.05) the maximum fall in post-exercise FEV1 (-6.4 +/- 2.4%) compared to usual (-14.3 +/- 1.6%) and placebo diet (-12.9 +/- 2.4%). Asthma symptoms scores significantly improved (p<0.05) on the ascorbic acid diet compared to the placebo and usual diet. Post-exercise FENO, LTC4-E4 and 9alpha, 11beta-PGF2 concentration was significantly lower (p<0.05) on the ascorbic acid diet compared to the placebo and usual diet. CONCLUSION: Ascorbic acid supplementation provides a protective effect against exercise-induced airway narrowing in asthmatic subjects.     

Adenosine level in exhaled breath increases during exercise-induced bronchoconstriction.

In asthmatic patients, airway obstruction provoked by exercise challenge is accompanied by an increase in plasma adenosine level. In this study, the current authors investigated if exercise-induced bronchoconstriction was associated with local changes of adenosine concentration in the airways. Oral exhaled breath condensate (EBC) collection (5-min duration) and forced expiratory volume in one second (FEV1) measurements were performed at rest (baseline) and 4-8 times after treadmill exercise challenge in healthy and asthmatic subjects. Adenosine concentration in EBC was determined by HPLC. Observations indicated that physical exercise results in bronchoconstriction together with a significant increase of adenosine level in EBC in asthmatic patients (mean+/-sd maximal fall in FEV1 27+/-13%; associated increase in adenosine 110+/-76% as compared to baseline), but not in healthy control subjects. Exercise-induced changes in adenosine concentration correlated significantly with the fall in FEV1 values in asthmatic patients. In conclusion, the observed increase in adenosine concentration of oral exhaled breath condensate most probably reflects changes in the airways during exercise-induced bronchoconstriction. Due to its known bronchoconstrictor property in asthma, adenosine may contribute to the development of bronchospasm.     

Exhaled nitric oxide, serum ECP and airway responsiveness in mild asthmatic children.

The purpose of the present study was to assess the possible relationships between exhaled nitric oxide (ENO), a circulating marker of eosinophil activation, serum eosinophil cationic protein (SECP), level of airway responsiveness to methacholine and lung function in asthmatic children, as well as to compare these markers between children with and without inhaled steroid therapy. In a cross-sectional study ENO, SECP and bronchial hyperresponsiveness to methacholine were evaluated in a group of 57 asthmatic children (21 without and 36 with regulator inhaled steroid therapy; aged 6-13 yrs). ENO was significantly lower in steroid treated children (p<0.01). No significant differences between steroid treated and untreated children were observed for the provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1; PC20), SECP and FEV1. In the whole study population significant increase correlations were observed between PC20 and SECP (r=-0.329, p=0.013) and between ENO and FEV1% of predicted (r=-0.348, p<0.01). In the group not receiving inhaled steroids the inverse relationship between PC20 and SECP was more evident (r=-0.581, p<0.001). In the steroid-treated group a significant inverse relationship was observed between ENO and FEV1 (r=-0.426, p=0.0011). The level of exhaled nitric oxide and the relationships between lung function, bronchial reactivity and markers of inflammation are different between steroid-treated and untreated asthmatic children. This has implications for the monitoring of asthma in childhood.     

An isoflow-volume technique for assessing airway dynamics in children and adults

BACKGROUND: We propose a new approach to the measurement of small airway function as an alternative to recordings of maximal expiratory flow-volume (MEFV) curves. OBJECTIVES: A newly developed technique to record isoflow-volume (IFV) curves to be tested against maximal respiratory flow curves. METHODS: An isoflow whistle (IFW; Iflopen) measures the length of a constant expiration after full inspiration. The note of the whistle enables a subject to generate an even expiration, and the isoflow maintenance times at 1 l x s(-1) (IFMT1) and 2 l x s(-1) (IFMT2) are recorded. The accuracy and reproducibility of the IFV technique were evaluated in 17 healthy adults (age 17-55 years) and in 14 asthmatic children (age 6-14 years). Comparisons with standard lung function parameters, such as forced expiratory volume in 1 s (FEV1), maximal expiratory flow at 50% (MEF50) and 25% (MEF25) vital capacity and peak expiratory flow (PEF), obtained with a Wright Peakflow Meter were undertaken in 102 healthy (aged 8-14 years) and 101 asthmatic children (aged 6-17 years). A bronchial challenge test was performed in 13 asthmatic children. RESULTS: The expired volume measured by the IFW showed an acceptable agreement with that of a pneumotachograph (mean error of 4.32% for IFMT1 and 5.93% for IFMT2). In healthy and in asthmatic children, the correlations between FEV1 and IFMT1 or IFMT2 (r = 0.92 and 0.94, respectively) were found to be greater than that between FEV1 and PEF (r = 0.68). During bronchial challenge tests in 13 asthmatic children, the FEV1 decreased to 69% of baseline and IFMT1 to 58% of baseline. CONCLUSIONS: The IFV technique accurately measured airway obstruction and closely followed changes in standard parameters of the MEFV curve.     

The effect of montelukast on lung function and exhaled nitric oxide in infants with early childhood asthma.

Effective treatment of respiratory symptoms, airway inflammation and impairment of lung function is the goal of any asthma therapy. Although montelukast has been shown to be a possible add-on therapy for anti-inflammatory treatment in older children, its efficacy in infants and young children is not well known. The aim of this study was to investigate its effect in infants and young children with early childhood asthma. In a prospective randomised double-blind placebo-controlled study, 24 young children (10-26 months) with wheeze, allergy and a positive family history of asthma consistent with the diagnosis of early childhood asthma were randomised to receive montelukast 4 mg or placebo. The forced expiratory volume in 0.5 seconds (FEV0.5) was measured using the raised volume rapid thoracic compression technique, and fractional exhaled nitric oxide (FeNO) and symptom scores were determined. No change was noted in FEV0.5, FeNO or symptom score in the placebo group following the treatment period. In contrast, significant improvements in mean+/-SD FEV0.5 (189.0+/-37.8 and 214.4+/-44.9 mL before and after treatment, respectively), FeNO (29.8+/-10.0 and 19.0+/-8.5 ppb) and median symptom score (5.5 and 1.5) were noted following treatment with montelukast. In conclusion, montelukast has a positive effect on lung function, airway inflammation and symptom scores in very young children with early childhood asthma.     

Bronchial responsiveness to exercise after human cardiopulmonary transplantation

Heart-lung transplant (HLT) recipients characteristically display marked bronchial hyperresponsiveness (BHR) to inhaled methacholine, but their bronchial responsiveness (BR) to exercise has not been reported. We measured BR to exercise in 13 stable HLT recipients, 13 normal control (NC) subjects and 13 asthmatic patients (AS). All subjects exercised for eight minutes on a bicycle ergometer at a work level designed to obtain and maintain 80 percent maximum heart rate, or to tolerance. The postexercise fall in FEV1 was equivalent in the HLT group and the NC group (0 +/- 0.2 L vs 0 +/- 0.2 L:p = NS) in contrast to the AS group (-0.6 +/- 0.5 L:p less than 0.01). Stable HLT recipients do not exhibit BHR to exercise at tolerable work loads. This observation supports the hypothesis that BHR to methacholine after HLT is due to denervation hypersensitivity of muscarinic receptors rather than other causes.     

Agreement between spirometry and tracheal auscultation in assessing bronchial responsiveness in asthmatic children.

We have recently found that changes in lung sounds correspond well with a 20% fall in the forced expiratory volume in 1 s (FEV1) after methacholine challenge in asthmatic children. Up to now, little was known about the agreement between a 20% fall in FEV1 and a change in lung sounds after repeated bronchial challenge. In this study we investigated the agreement between the total cumulative histamine dose causing a fall in FEV1 of 20% or more (PD20) and the detection of a change in lung sounds (PDlung sounds) after two bronchial challenges on different occasions in asthmatic children. Fifteen asthmatic children (nine boys), mean age 10.8 years (range 9-15), were studied. All performed two histamine challenge tests on 2 days, with a 24 h to 1 week interval. Lung sounds were recorded over the trachea for 1 min and stored on tape. Lung sounds were analysed directly and also scored from the tape-recording by a blinded second investigator. Wheeze, cough, and an increase in respiratory rate were assessed. The relationship between PD20 and PDlung sounds was calculated by Bland and Altman's measurement of agreement. Eleven children had a positive challenge test (PD20 < or = 16.0 mg ml-1) on both test days; four had a positive challenge on one test day. In 24 out of 26 positive challenges, wheeze, cough, prolonged expiration and/or increased respiratory rate were detected one dose-step before, or at the dose-step of histamine that induced a fall in FEV1 of 20% or more. In two challenges, PD20 was not detected by a change in lung sounds. In four out of four negative challenges (PD20 > 16.0 mg ml-1) no change in lung sounds could be detected. Good agreement between the logarithm of PD20 and the logarithm of PDlung sounds was found on both test days. The mean difference was 0.04 and the limits of agreement (d +/- 2 SD of the differences) were 0.04 +/- 0.41. A good agreement was found between the total cumulative histamine dose causing a fall in FEV1 of 20% or more and the detection of a change in lung sounds after two bronchial challenges on different occasions in asthmatic children.