Effect of GR32191, a potent thromboxane receptor antagonist, on exercise induced bronchoconstriction in asthma.

Previous work suggests a role for mast cell derived mediators in exercise induced asthma. The contribution of newly generated contractile prostaglandins to exercise induced asthma was assessed by using a potent and orally active thromboxane (TP1) receptor antagonist, GR32191. The effect of 120 mg GR32191 on exercise induced asthma was observed in 12 asthmatic subjects. For the exercise challenge the subjects performed six minutes of treadmill exercise, breathing dry air at a work load that had previously been shown to induce a fall in FEV1 of 25% or more from the pre-exercise baseline. No effect of GR32191 on pre-exercise baseline airway calibre was evident. There was no significant difference in the mean maximum percentage fall in FEV1 from baseline after exercise between drug and placebo (placebo 30.2%, GR32191 day 31.6%). It is concluded that the thromboxane antagonist GR32191 has no effect on exercise induced asthma. This suggests that prostaglandins, including PGD2, that act via the thromboxane receptor do not have an important role in exercise induced asthma.     

A mask to modify inspired air temperature and humidity and its effect on exercise induced asthma.

BACKGROUND: Heat and moisture loss from the respiratory tract during exercise are important triggers of exercise induced asthma. METHODS: A new heat and moisture exchange mask has been developed which both recovers exhaled heat and water and has a sufficiently low resistance for use during exercise. The effect of the mask on inspired air temperature was studied in four normal subjects. Eight asthmatic subjects performed identical exercise protocols on three separate days, breathing room air through a conventional mouthpiece, a dummy mask, and the new heat and moisture exchange mask. Seven different asthmatic subjects exercised while breathing cold air at -13 degrees C through a dummy or active mask. RESULTS: All subjects found the new mask comfortable to wear. The mean inspired temperature when the mask was used rose to 32.5 (1.4) degrees C when normal subjects breathed room air at 24 degrees C and to 19.1 (2.7) degrees C when they inhaled subfreezing air at -13 degrees C. The heat and moisture exchange mask significantly reduced the median fall in forced expiratory volume in one second (FEV1) after exercise to 13% (range 0-49%) when asthmatic subjects breathed room air compared with 33% (10-65%) with the dummy mask and 28% (21-70%) with the mouthpiece. The fall in FEV1 when the asthmatic subjects breathed cold air was 10% (0-26%) with the heat and moisture exchange mask compared with 22% (13-51%) with the dummy mask. CONCLUSION: Use of a heat and moisture exchange mask can raise the inspired temperature and humidity and ameliorate the severity of exercise induced asthma. The mask may be of practical value in non-contact sport or for people working in subzero temperatures.     

Airway response to methacholine during exercise induced refractoriness in asthma.

To investigate the mechanisms contributing to refractoriness in exercise induced asthma a methacholine challenge test was performed 30 minutes before and 30 minutes after two exercise tests 45 minutes apart. Exercise was performed by 12 asthmatic patients while they were breathing cold air. There was a smaller airway response to the second exercise test than to the first, though there was wide variation between subjects. The response to the second methacholine challenge was reduced in some patients but showed no significant change overall. Refractoriness to exercise induced asthma positively correlated with a reduced response to methacholine. These data suggest that mediator depletion does not fully explain refractoriness.     

Attenuation of exercise induced asthma by local hyperthermia.

BACKGROUND: Prior treatment with local hyperthermia has been shown to prevent mast cell degranulation and leucocyte histamine release, and to reduce mortality and cellular infiltrates in a model of acute lung injury. Local hyperthermia is effective in reducing the symptoms of the common cold and perennial and seasonal allergic rhinitis, nasal patency also being improved in rhinitis. It is possible that these effects are mediated by common anti-inflammatory mechanisms, and that this treatment may be effective in the treatment of asthma. The effect of prior local hyperthermia on the response to exercise challenge and histamine bronchoprovocation was therefore examined. METHODS: In a randomised, double blind, placebo controlled, crossover study, 10 asthmatic subjects with exercise induced asthma used machines delivering 40 1/minute of fully humidified air at either 42 degrees C (active treatment) or 31 degrees C (placebo treatment) for 30 minutes' tidal breathing. For each pretreatment, at two week intervals they underwent exercise challenges starting one and 24 hours after starting the inhalations. After a further two weeks the protocol was repeated with histamine substituted for the exercise challenges. RESULTS: The mean (SE) maximum percentage fall in forced expiratory volume in one second (FEV1) was significantly lower one hour after treatment with air at 42 degrees C (30.8% (3.1%)) than after treatment with air at 31 degrees C (22.3% (2.9%)). There was no significant effect on exercise challenge at 24 hours, or on histamine challenge at either time point, though there were nonsignificant trends towards protection with exercise at 24 hours and with histamine at one hour. CONCLUSION: In asthmatic subjects the response to exercise challenge is significantly attenuated one hour after treatment with local hyperthermia. This treatment warrants further investigation in the treatment of clinical asthma and other inflammatory disorders.     

Respiratory heat loss in exercise-induced asthma. Measurement and clinical application

The theoretical considerations of conditioning inspired air and the application of the respiratory heat loss (RHL) formula are discussed. An on-line method for measuring RHL is described together with the apparatus for generating frigid dry and warm humid air. Exercise-induced asthma (EIA) was studied using these methods. Thirteen asthmatic and 6 normal children and adolescents participated in the study. Each subject undertook two submaximal exercise tests consisting of 6 minutes' ergometric cycling against a fixed load. One test was done while breathing cold dry air (mean temperature -22 degrees C and 0% relative humidity) and the other while breathing warm humid air (mean temperature 36 degrees C and 100% relative humidity). All the other exercise parameters (e.g. heart rate, minute ventilation, oxygen uptake) were carefully matched between the two tests. In the cold dry air tests with a mean RHL of 1,43 kcal/min, all asthmatic subjects developed EIA with a mean fall in forced expiratory volume in the 1st second (FEV1) of 48% from baseline. In the warm humid air tests with negligible RHL (0,02 kcal/min) none of the asthmatics developed EIA (mean fall in FEV1 5%). The difference between the two tests was highly significant (P less than 0,001). Neither air condition caused bronchospasm in the normal subjects. A dose-response relationship was obtained between the degree of RHL and corresponding fall in FEV1.     

Effect of nebulised salbutamol on maximal exercise performance in men with mild asthma.

The effect of 5 mg nebulised salbutamol on the cardiorespiratory responses to a progressive maximal exercise test was investigated in eight asthmatic (mean forced expiratory volume in one second (FEV1) 3.48 (1.0) litres) and eight non-asthmatic men. Exercise tests were performed on a bicycle ergometer after administration of nebulised salbutamol or matched saline placebo. In the asthmatic subjects salbutamol increased the resting FEV1 by 11%. The mean (SD) percentage fall in FEV1 after exercise did not change significantly (salbutamol 9.4 (12.8); placebo 15.0 (8.0], but because the FEV1 before exercise was increased the lowest FEV1 after exercise was also significantly higher after salbutamol than placebo (3.60 (1.13) v 2.85 (0.80) litres). Despite the improvement in FEV1 before exercise there was no significant difference in maximal workload, oxygen uptake, heart rate, or ventilation during exercise after salbutamol compared with placebo in the asthmatic patients. Tidal volume was higher at maximal exercise after salbutamol but there was no change in perception of breathlessness or exertion in the asthmatic subjects. During submaximal progressive exercise the perceived rate of exertion was reduced in the asthmatic patients and oxygen pulse was reduced in both groups owing to a small and non-significant increase in heart rate. The FEV1 and cardiorespiratory response to the progressive maximal exercise test in the non-asthmatic subjects were otherwise unchanged after salbutamol. The results suggest that 5 mg nebulised salbutamol has little effect on the cardiorespiratory responses to progressive maximal exercise in patients with mild asthma and in non-asthmatic subjects. Salbutamol in this dose may reduce the severity of exercise induced asthma, but no ergogenic effect on maximal exercise performance was shown.     

Effectiveness of a heat and moisture exchanger in preventing hyperpnoea induced bronchoconstriction in subjects with asthma.

The effect of a heat and moisture exchanger, a device with hygroscopic material for conditioning inspired air, on hyperpnoea induced bronchoconstriction was studied in nine non-smoking volunteers with asthma, aged 19-32 years. Each had previously shown an increase of at least 100% in specific airways resistance (sRaw) to isocapnic hyperpnoea with dry air. On two separate days the subject performed isocapnic hyperpnoea with dry air at 60-70 l min-1 for five minutes. Before, immediately after, and five minutes after completion of a test sRaw measurements were made. Heat and moisture exchangers were placed in the breathing circuit on one of the two days. All subjects had an increase in sRaw of 100% or more without the heat and moisture exchangers (average increase 300%) but were protected from bronchoconstriction with the devices in place (average increase 7%) (p less than 0.005). The exchanger's resistance to airflow was less than 1 cm H2O for flow rates of 100 l min-1. A heat and moisture exchanger designed as a facemask or mouthpiece may allow a person with asthma to exercise without the need for prophylactic drugs.     

Effect of regular inhaled salbutamol on airway responsiveness and airway inflammation in rhinitic non-asthmatic subjects

BACKGROUND: Regular, inhaled beta 2 agonists may increase airway responsiveness in asthmatic subjects. The mechanism is not known but may be via an increase in airway inflammation. A study was undertaken to examine the effect of regular inhaled salbutamol on airway responsiveness to methacholine and hypertonic saline, on the maximal response plateau to methacholine, and on inflammatory cells in induced sputum in rhinitic non-asthmatic subjects. METHODS: Thirty subjects with a baseline maximal response plateau of > 15% fall in forced expiratory volume in one second (FEV1) entered a randomised, placebo controlled, parallel trial consisting of two weeks run in, four weeks of treatment, and two weeks washout. Methacholine challenges were performed at the beginning of the run in period, before treatment, after treatment, and after washout. Hypertonic saline challenges were performed before and after treatment and induced sputum samples were collected for differential cell counting. RESULTS: There was no change in airway responsiveness, maximal response plateau to methacholine, or in induced sputum eosinophils or mast cells. The maximum fall in FEV1 after hypertonic saline increased in the salbutamol group (median change 6.0%, interquartile range (IQR) 11.0) but did not change in the placebo group (median change 1.3%, IQR 5.5). CONCLUSIONS: Regular inhaled salbutamol for four weeks increases airway responsiveness to hypertonic saline but does not alter airway responsiveness to methacholine or cells in induced sputum in non-asthmatic individuals with rhinitis. The relevance of these findings to asthmatic subjects has not been established.


     

Abolition of methacholine induced bronchoconstriction by the hyperventilation of exercise or volition.

Total pulmonary resistance was measured from continuous records of flow and oesophageal pressure in five normal subjects on three separate days before and after inhalation of methacholine. The dose of methacholine produced, on average, a fivefold increase in airway resistance. Immediately after methacholine inhalation the subjects underwent a progressive exercise test on a cycle ergometer (day 1) or voluntary hyperventilation (day 2) or remained resting (day 3). On the first day during exercise pulmonary resistance fell rapidly to baseline levels within two to three minutes and remained there for the 10 minute duration of the exercise. On day 2 voluntary reproduction of the same level and pattern of ventilation as during exercise resulted in a similar fall of resistance. On the third day, when the subjects remained at rest, pulmonary resistance remained raised for 10 minutes. It is concluded that the bronchodilator effects of exercise can be explained by the increased ventilation rather than the exercise itself, but with much smaller tidal volumes than have previously been thought necessary to reduce drug induced bronchoconstriction.     

Effect of negative ionisation of inspired air on the response of asthmatic children to exercise and inhaled histamine

To evaluate the effect of negative ionisation of inspired air on bronchial reactivity, 11 asthmatic children were challenged twice by exercise and 10 were challenged twice by histamine inhalation. The children breathed negatively ionised air (4 X 10(5) - 10 X 10(5) ions/cm3) or control room air in random order in a double-blind fashion. All challenges were matched in terms of basal lung function and the exercise tests were matched in terms of ventilation and respiratory heat loss. Exercise-induced asthma was significantly attenuated by exposure to negatively ionised air, the mean postexercise fall in one-second forced expiratory volume (FEV1) being 29% (SE 5%) of the initial value after the control and 21% (3%) after the ionised air test (p less than 0.02). Ten of the 11 subjects developed less exercise-induced asthma while breathing ionised air. Although the median dose of histamine (cumulative breath units) which caused a constant fall in FEV1 for each individual was higher with the ionised air challenge than with the control challenge the difference was not significant. Five of the 10 subjects were less sensitive to histamine and the other five more sensitive when breathing ionised air. It is concluded that negative ionisation of inspired air can modulate the bronchial response to exercise but the effect on the response to histamine is much more variable.     

Comparison of airway reactivity induced by histamine, methacholine, and isocapnic hyperventilation in normal and asthmatic subjects

In an investigation of a rapid screening test for airway reactivity using isocapnic hyperventilation with room air and cold air the results of this test were compared with the airway response to histamine and methacholine challenge. Twelve non-atopic, non-smoking normal subjects and 11 subjects with stable asthma who had an FEV1 above 74% of the predicted value were studied. In the normal subjects isocapnic hyperventilation with room air (75 l/min; 22 degrees C (SEM 0.2 degrees); 10 mg H2O/l air) and isocapnic hyperventilation with cold air (77 l/min; -10 degrees C (0.9 degrees); 2.4 mg H2O/l air) produced no significant change in FEV1. In the asthmatic subjects, hyperventilation with room air (71 l/min; 22 degrees C (0.8 degrees); 10 mg H2O/l air) caused a mean fall in FEV1 of 11.7%; cold air hyperventilation (70 l/min; -10 degrees C (0.9 degrees); 2.4 mg H2O/l air) caused a mean fall in FEV1 of 20.4%. Cold air hyperventilation produced greater separation between normal and asthmatic subjects than room air. The provocative concentration of histamine required to reduce the FEV1 by 20% (PC20) correlated closely with the PC20 for methacholine (r = 0.95; p less than 0.001). Both tests separated normal from asthmatic subjects. PC20 for both histamine and methacholine correlated with the fall in FEV1 after cold air hyperventilation (r = 0.93, p less than 0.001; r = 0.87, p less than 0.001 respectively). We conclude that the results of a rapid screening test based on hyperventilation with cold air correlate well with a standard pharmacological challenge.     

Exercise-induced change of nasal resistance in asthmatic children

Exercise-induced change of nasal resistance and forced expiratory volume in 1 second (FEV1.0) were studied in 30 asthmatic children and seven normal children. Exercise-induced asthma (EIA) was diagnosed in 19 (63%) of the 30 asthmatic patients. Unilateral complete nasal blockage after exercise (exercise-induced nasal obstruction [EINO]) was found in nine (30%) of the 30 asthmatic patients. A marked decrease in nasal resistance took place immediately or 4 minutes after exercise in all cases. EIA is most severe 5 minutes after exercise, and EINO took place 14 or 19 minutes after exercise. The seven normal children had neither EIA nor EINO. The pathophysiologic relationship between EIA and EINO is discussed.     

Response of the nose to exercise in healthy subjects and in patients with rhinitis and asthma.

BACKGROUND--Although the nose and the bronchi are both involved in the process of regulating respiratory heat exchange, thermal changes may precipitate airway obstruction during exercise but rarely cause nasal obstruction in patients with rhinitis. The cause of the different response of the nose and bronchial tree has hardly been investigated. This study was performed to assess the response of the nose during exercise in the presence of rhinitis, asthma, and in normal controls. METHODS--Ten healthy subjects (group 1), 15 patients with asthma and rhinitis (group 2), 10 with rhinitis only (group 3), and 11 with asthma only (group 4) were included in the study. Exercise was performed on a bicycle ergometer for six minutes, reaching a heart rate of 80% of predicted. Bronchial and nasal responses were measured by forced expiratory volume in one second (FEV1) and posterior rhinomanometry, respectively. A drop in the FEV1 of 20% or more was considered a positive exercise induced asthma challenge test. RESULTS--Heart rate and ventilation increased by a similar proportion in the four groups. The FEV1 significantly decreased in asthmatic patients (groups 2 and 4) but it did not change in healthy subjects (group 1) or in those with rhinitis (group 3). Thirteen asthmatic patients developed exercise induced asthma. Nasal patency increased with exercise by a similar proportion in all groups, and no differences were detected between those with rhinitis (groups 2 and 3) and those without (groups 1 and 4). Nasal patency had returned to basal values at 25 minutes after completion of exercise in the four groups. The nose of patients with exercise induced asthma, however, remained significantly more patent than in patients without exercise induced asthma between 10 and 30 minutes after exercise. CONCLUSIONS--These results suggest that the nose responds differently from the bronchi during exercise induced airway obstruction: whereas the bronchial tree responds by becoming narrowed, the nose becomes more patent. These findings suggest that the mechanisms regulating the response of the nose to exercise are different from those involved in the response of the bronchial tree.     

Involvement of vascular endothelial growth factor in exercise induced bronchoconstriction in asthmatic patients

BACKGROUND: There is evidence that the bronchial microcirculation has the potential to contribute to the pathophysiological mechanisms of exercise induced bronchoconstriction (EIB) in asthmatic subjects. Vascular endothelial growth factor (VEGF), which is highly expressed in asthmatic airways, increases vascular permeability. The relationship between VEGF levels in induced sputum and the severity of EIB in asthmatic subjects was studied. METHODS: The concentration of VEGF in induced sputum was examined in 23 asthmatic subjects and 11 normal controls. The asthmatic subjects performed an exercise test and the % maximal fall in forced expiratory volume in 1 second (FEV(1)) was measured. Beclomethasone dipropionate (BDP) 400 micro g twice daily was administered to the asthmatic subjects for 8 weeks and the exercise test and sputum induction were repeated. RESULTS: The concentration of VEGF in induced sputum was significantly higher in asthmatic subjects than in normal controls. There was a significant correlation between the concentration of VEGF and the % maximal fall in FEV(1) (r=0.826, p=0.0001) and between the concentration of VEGF and airway vascular permeability index (r=0.621, p=0.0037). After treatment with inhaled BDP there was a significant decrease in the concentration of VEGF in the asthmatic subjects (before treatment: 7051 (2361) pg/ml, after treatment: 4498 (2135) pg/ml, p<0.0001). The change in the concentration of VEGF was significantly correlated with the change in the % maximal fall in FEV(1) (r=0.463, p=0.031). CONCLUSIONS: Excessive production of VEGF in asthmatic airways may contribute to the pathogenesis of EIB via increased airway vascular permeability.     

Effect of inhaled piriprost (U-60, 257) a novel leukotriene inhibitor, on allergen and exercise induced bronchoconstriction in asthma.

The leukotrienes, a group of oxidative metabolites of arachidonic acid, have potent pharmacological actions on human airways. We have investigated the effects of a leukotriene synthesis inhibitor, piriprost (U-60, 257) administered by inhalation on allergen and exercise induced bronchoconstriction in 12 subjects with allergic asthma. Subjects underwent diagnostic challenges with allergen and treadmill exercise to define the strengths of the stimuli required to reduce the FEV1 to about 25% of baseline (PS25). On separate study days subjects inhaled either piriprost 1 mg or vehicle placebo, followed 15 minutes later by the PS25 allergen or exercise. The FEV1 was measured at regular intervals before and after challenge up to 60 minutes. After allergen challenge in six subjects peak expiratory flow (PEF) was measured for the following 20 hours. When compared with placebo, inhalation of piriprost had no significant protective effect on the fall in FEV1 at any time point within 60 minutes of allergen or exercise challenge. In the four subjects with a documented late asthmatic reaction 2-12 hours after allergen challenge piriprost had no protective effect when compared with placebo. In the subjects who recorded PEF over 20 hours after allergen challenge there was no significant difference between piriprost and placebo. Piriprost was appreciably more irritant to the respiratory tract than was placebo. On the assumption that inhaled piriprost was bioavailable in the airways, this study casts doubt on any theory of a pivotal role for leukotrienes in the pathogenesis of acute exercise and allergen induced airway bronchoconstriction in asthma.     

Influence of diltiazem on bronchoconstriction induced by cold air breathing during exercise.

Since the calcium antagonists nifedipine and verapamil have been shown to diminish exercise induced asthma, the effect of oral diltiazem, a calcium channel blocker not previously investigated in this context, was studied. Ten patients with bronchial asthma were given 60 mg diltiazem or placebo four hours before the challenge in a double blind, randomised, crossover fashion. Exercise was performed on a cycle ergometer while the subjects were breathing cold air, resulting in a respiratory heat exchange which was similar at the two study sessions. FEV1 and specific conductance (sGaw) were recorded before and three, 10, 15, and 30 minutes after the challenge. No significant differences were found between placebo and diltiazem days in the fall of FEV1 or sGaw after exercise. Thus unlike other calcium antagonists diltiazem, in a dose of 60 mg given orally four hours before exercise, failed to protect against exercise induced asthma.     

Mid-expiratory flow versus FEV1 measurements in the diagnosis of exercise induced asthma in elite athletes

BACKGROUND: A fall in FEV(1) of > or =10% following bronchoprovocation (eucapnic voluntary hyperventilation (EVH) or exercise) is regarded as the gold standard criterion for diagnosing exercise induced asthma (EIA) in athletes. Previous studies have suggested that mid-expiratory flow (FEF(50)) might be used to supplement FEV(1) to improve the sensitivity and specificity of the diagnosis. A study was undertaken to investigate the response of FEF(50) following EVH or exercise challenges in elite athletes as an adjunct to FEV(1). METHODS: Sixty six male (36 asthmatic, 30 non-asthmatic) and 50 female (24 asthmatic, 26 non-asthmatic) elite athletes volunteered for the study. Maximal voluntary flow-volume loops were measured before and 3, 5, 10, and 15 minutes after stopping EVH or exercise. A fall in FEV(1) of > or =10% and a fall in FEF(50) of > or =26% were used as the cut off criteria for identification of EIA. RESULTS: There was a strong correlation between DeltaFEV(1) and DeltaFEF(50) following bronchoprovocation (r = 0.94, p = 0.000). Sixty athletes had a fall in FEV(1) of > or =10% leading to the diagnosis of EIA. Using the FEF(50) criterion alone led to 21 (35%) of these asthmatic athletes receiving a false negative diagnosis. The lowest fall in FEF(50) in an athlete with a > or =10% fall in FEV(1) was 14.3%. Reducing the FEF(50) criteria to > or =14% led to 13 athletes receiving a false positive diagnosis. Only one athlete had a fall in FEF(50) of > or =26% in the absence of a fall in FEV(1) of > or =10% (DeltaFEV(1) = 8.9%). CONCLUSION: The inclusion of FEF(50) in the diagnosis of EIA in elite athletes reduces the sensitivity and does not enhance the sensitivity or specificity of the diagnosis. The use of FEF(50) alone is insufficiently sensitive to diagnose EIA reliably in elite athletes.     

Airway response to salbutamol: effect of regular salbutamol inhalations in normal, atopic, and asthmatic subjects.

This study was designed to determine whether resistance to the airway effects of the beta-agonist, salbutamol, would develop in three groups of subjects while taking large doses of inhaled salbutamol. Six normal non-atopic, six atopic non-asthmatic, and eight atopic asthmatic subjects were studied by an identical technique. The development of resistance was assessed from salbutamol dose-response studies in which the airway response was measured as specific airway conductance (sGaw). Further evidence was sought in the atopic and asthmatic subjects by measuring the airway response to a standard histamine inhalation challenge and the protective effect of 100 micrograms salbutamol on this challenge, and by six-hourly peak flow recordings. Subjects were assessed before and during four weeks in which they took inhaled salbutamol regularly in doses increasing to 500 microgram quid in week 4. Normal subjects showed a progressive reduction in the bronchodilator (sGaw) response to salbutamol during the four weeks, indicating the progressive development of resistance. The atopic subjects, both asthmatic and non-asthmatic, showed no reduction in the response to salbutamol during the four weeks, nor any change in the response to histamine challenge or in regular peak flow readings. These results demonstrate that asthmatic patients do not develop bronchial beta-adrenoceptor resistance easily and suggests that they and atopic non-asthmatic subjects are less susceptible to its development than normal subjects.     

Evaluation of bronchial responsiveness to exercise in children as an objective measure of asthma in epidemiological surveys.

BACKGROUND: Exercise has been proposed as a useful challenge test for the measurement of bronchial responsiveness in community surveys of the prevalence of childhood asthma. This study aimed to develop a standardised exercise challenge in which the sensitivity to detect asthma was increased by inhalation of dry air. METHODS: Sixty four children aged 12-13 years who had reported wheeze in the past 12 months and 70 control subjects were invited to participate in an exercise challenge at school. Subjects performed eight minutes of cycle exercise while breathing dry air at a workload calculated to produce a minute ventilation of 60% maximum voluntary ventilation during the final three minutes. A fall in forced expiratory volume in one second (FEV1) of 10% or more from baseline was considered a positive test. Data on recent asthma symptoms, asthma morbidity, and use of medication were collected by parent completed questionnaires in those subjects who reported wheeze in the past 12 months. Repeatability of the exercise test was determined in a further 13 children with known asthma. RESULTS: Fifty five children (88%) who reported wheeze in the previous 12 months and 54 control subjects (77%) were studied. Nine subjects in whom baseline FEV1 was less than 75% predicted did not perform the exercise test. Technically unsatisfactory tests were obtained in five subjects. Twenty six (57%) subjects who reported wheeze and three controls (6%) had a positive exercise test, giving a sensitivity of 57% (26 of 46) and specificity of 94% (47 of 50). Estimates of the repeatability of the exercise test showed a mean difference in percentage fall in FEV1 for patients with asthma of 3.08% (95% limits of agreement -7.76% to 13.92%). CONCLUSIONS: Despite attempts to maximise the stimulus to bronchoconstriction in this exercise challenge test, its sensitivity and specificity were not improved in comparison with previous epidemiological studies of the prevalence of asthma.     

Safety of fibreoptic bronchoscopy in asthmatic and control subjects and effect on asthma control over two weeks.

BACKGROUND: Concerns remain about the safety of bronchoscopy in asthma and there are few data on the effect of this procedure on asthma control in the days or weeks following bronchoscopy. METHODS: In an initial study of bronchoalveolar lavage and bronchial biopsies in asthmatic and control subjects, data on peak expiratory flow rates (PEFR) collected prospectively before and after the procedure were available from 21 of the 29 asthmatic subjects studied. These showed a median 23% fall in PEFR from baseline after bronchoscopy (range 3-58%). To determine whether this fall in PEFR following bronchoscopy reflected bronchospasm or the effect of sedation, PEFR and spirometric tests were performed during the two hours following bronchoscopy in a further study of 15 symptomatic asthmatic subjects and 20 non-asthmatic controls. To examine the effect on asthma control, asthmatic patients recorded PEFR, symptom scores, and medication use for two weeks before and after bronchoscopy. RESULTS: After bronchoscopy with bronchial biopsies there was no difference between the median maximal fall in either PEFR or arterial oxygen saturation between the 15 asthmatic patients (10.4% and 4%, respectively) and 20 controls (12% and 3%). Moreover, there were no significant changes in PEFR, symptom score, or medication use by the asthmatic subjects in the two weeks after bronchoscopy when compared with the two weeks before bronchoscopy. CONCLUSIONS: Fibreoptic bronchoscopy is well tolerated in asthmatic subjects. Falls in PEFR in both asthmatic and non-asthmatic subjects after bronchial biopsy may reflect the effects of sedation rather than bronchospasm. Additional bronchoalveolar lavage may cause bronchoconstriction. Careful monitoring is therefore essential. Peak flow monitoring up to two weeks after bronchoscopy with bronchial biopsy revealed no delayed effects on asthma control.