Simon Godfrey

Exercise-induced asthma.

A review of exercise-induced asthma is presented which describes work that has been carried out by the authors and by other investigators over recent years. The effect of exericse on lung function in asthmatic and normal subjects is compared. The influence of the type and severity of exercise on the response of the asthmatic is noted and the importance this has for interpretation of results. The effects of various drugs on exercise-induced asthma are considered in some detail. The clinical implications of the results of exercise tests in asthmatics, their relatives, and other subjects are considered in terms of the diagnosis and prognosis of asthma and its mode of inheritance. It is concluded that there is as yet no explantation for the mechanism of exercise-induced asthma, but it is a tool of potentially great value for research into the physiology and treatment of clinical asthma.

Exercise but not methacholine differentiates asthma from chronic lung disease in children.

Bronchial provocation challenges with exercise and methacholine were performed on the same day or within a short interval in 52 children with asthma, 22 with other types of chronic lung disease (including cystic fibrosis), and 19 control subjects with no evidence of chronic lung disease. There were no significant differences in the baseline lung function before the two types of challenge in the individual groups and differences between the patients with asthma and with chronic lung disease were minor. When the mean -2 SD of the methacholine response of the control group was taken as the lower limit of normal, 49/52 (94%) patients with asthma and 18/22 (82%) with chronic lung disease responded abnormally. In contrast, with the mean +2 SD of the exercise response of the control group as the upper limit of normal, 41/52 (79%) asthmatic patients responded but none of those with chronic lung disease. Thus the response to the two types of challenge helps to distinguish asthma from other types of chronic lung disease in children.

Exhaled nitric oxide in the diagnosis of asthma: comparison with bronchial provocation tests.

Background: Bronchial provocation tests such as exercise, methacholine (MCH), and adenosine-5′-monophosphate (AMP) challenges are used extensively in the diagnosis of asthma. A study was undertaken to determine whether exhaled nitric oxide (eNO) can be used to diagnose asthma in patients with non-specific respiratory symptoms and to compare this test with conventional provocation tests. Methods: Patients with non-specific respiratory symptoms and normal spirometric parameters were included in the study. eNO was measured and exercise, MCH and AMP challenges performed in all subjects. Patients were defined as asthmatic based on clinical follow up 24 months after testing. Results: Forty patients were considered asthmatic and 45 were not. The area under receiver operating characteristic curves gave values of 0.896 for eNO, 0.781 for exercise, 0.924 for MCH, and 0.939 for AMP (p = 0.033, 0.575 and 0.085 for eNO v exercise, MCH and AMP respectively). From our data, a cut off value of NO >7 ppb at a flow rate of 250 ml/s best differentiates between asthmatics and non-asthmatics (sensitivity 82.5%, specificity 88.9%). Optimal cut off values for other tests were exercise: ΔFEV1 ⩾10% (sensitivity 57.9%, specificity 100%); PC20-MCH: ⩽3 mg/ml (sensitivity 87.5%, specificity 86.7%); and PC20-AMP: ⩽150 mg/ml (sensitivity 89.5%, specificity 95.6%). Conclusions: Measurement of eNO can be used as a safe, simple and rapid test for the diagnosis of asthma and is as good as bronchial provocation tests.

Treatment of severe steroid dependent preschool asthma with nebulised budesonide suspension.

The steroid sparing effect of nebulised budesonide suspension was assessed in a double blind placebo controlled parallel group study of 36 preschool children with severe asthma who were dependent on treatment with oral steroids. Nebulised budesonide suspension significantly reduced the requirement for treatment with oral steroids, and produced a marked improvement in overall health as scored on a visual analogue scale during the clinic visits. This study shows a significant step forward in the prophylactic treatment of asthma in children under the age of 3 years, in whom the efficacy of many other nebulised treatments has been questioned.

Problems of interpreting exercise-induced asthma

Abstract Factors affecting exercise-induced asthma are reviewed based on studies in large numbers of children and young adults. Evidence is presented to show that running is a more potent and reproducible stimulus than cycling and that walking and swimming have a small and variable effect. The greatest amount of exercise-induced asthma is found after 6 to 8 minutes of steady-state running at a work rate equivalent to about two thirds of the working capacity of the subject. Exercise may be repeated every 2 hours throughout the day without any diminution of its effect in causing postexercise bronchoconstriction. The use of exercise in assessing drugs used to treat asthma is discussed, and the importance of the type of exercise test and the use of placebo preparations is emphasized. Serial exercise tests may be used to study the duration of protection from exercise-induced asthma afforded by drugs such as cromolyn sodium.

Comparison of bronchoconstriction induced by cycling and running

Bicycle ergometer, treadmill, and free range running exercise have been used to induce bronchoconstriction in 10 asthmatic subjects who were relatively well and free from symptoms at the time of study. Comparisons have been made with normal subjects under similar laboratory conditions. Bronchoconstriction was measured by peak expiratory flow rate before, during, and after each test. Ventilation, pulse rate, and gas exchange were also measured. The work involved in the different types of exercise was matched to produce similar ventilation and pulse rates for any one subject. Exercise-induced bronchoconstriction was significantly less on the bicycle ergometer than on running (treadmill or free range). The normal subjects showed less than one quarter the bronchial lability of the asthmatic subjects in any one test. All subjects had lower respiratory exchange ratios during running compared with cycling and this appeared to correlate with the bronchial lability in the asthmatics, who also had rather higher pulse rates during running. Running involves a proportion of high-efficiency negative work which might partly account for the observed differences.

Treatment of childhood asthma for 13 months and longer with beclomethasone dipropionate aerosol

Twenty-six children with asthma were treated with beclomethasone dipropionate aerosol in a dose adjusted to their symptoms for 13 to 20 months. 18 children in the group had been taking systemic steroids at the start of the trial and all were successfully weaned off them, mostly within 2 months. All but 1 of the children were satisfactorily controlled by beclomethasone, but 15 children needed short courses of oral steroids at times of severe exacerbations. There was no evidence of either suppression or acceleration of growth, nor was there any adrenal suppression as assessed at intervals by the estimation of the resting level of plasma cortisol and the response to tetracosactrin. No other side effects were encountered apart from exacerbations of eczema or rhinitis in some children previously on systemic steroids.

Long-term Trial of Disodium Cromoglycate and Isoprenaline in Children with Asthma

A year-long double-blind trial was carried out in 53 asthmatic children with severe perennial symptoms who were not receiving corticosteroids or corticotrophin. The treatment group were given disodium cromoglycate with isoprenaline (Intal Co.) while the placebo group were given lactose with isoprenaline four times daily. The groups were closely matched for clinical, physiological, and immunological features. Evaluation was based on the use of a diary and clinical and physiological investigations, including exercise tests. After one year 71% of the treatment group were still well controlled while 76% of the placebo group had dropped out because of inadequate control of symptoms. There was no rise in the rate of failure towards the end of the trial period and there were no seasonal variations in the failure rate. No important toxic effects were noted. It was impossible to predict the outcome of the trial in any given patient from his clinical, physiological, or immunological status at the beginning. However, the prevention of exercise-induced asthma by premedication with disodium cromoglycate in a laboratory exercise test did correlate well with the satisfactory clinical response to the drug.

Yield from flexible bronchoscopy in children

Flexible fiberoptic (FO) bronchoscopy can now be undertaken readily in children using topical anesthesia and light sedation and has largely supplanted rigid open tube (OT) bronchoscopy for diagnostic purposes. The present study examined the contribution of the FO bronchoscope to clinical management in children presenting with specific types of problems. We examined the first 200 consecutive flexible bronchoscopies performed in 1995 in children under 18 years of age (median age, 2.27 years). Indications for bronchoscopy were noisy breathing (26.5%), recurrent pneumonia (21.0%), suspected pneumonia in an immunocompromised patient (10.5%), atelectasis or bronchial toilet (12.5%), possible foreign body aspiration (13.0%), and miscellaneous other reasons (16.5%). Inspection of the airway was abnormal in 67.0% of all investigations and made a clinically meaningful contribution to management in 67.5%, especially in those with noisy breathing (98.1%), possible foreign body aspiration (100%), and atelectasis (76.0%). Bronchoalveolar lavage (BAL) cytology was abnormal in 80.4% of the 107 lavages, but contributed little to management except in those with recurrent pneumonia (73.8%). Bacteria were isolated in 26.6% of the 109 specimens cultured, but this finding rarely affected management. Fungi were isolated in 47.4% of the 19 lavages in the immunocomprised group. Together, inspection, BAL and microbiology contributed to management in a mean of 90.5% (range, 76.2–100%) of patients in the various groups. We concluded that a high yield of clinically meaningful information can be expected from FO bronchoscopy in children when coupled with BAL and microbiological studies of lavage fluid. Pediatr. Pulmonol. 1997; 23:261–269

Bronchial provocation determined by breath sounds compared with lung function.

Bronchial provocation testing with methacholine was undertaken in 15 children aged 5 to 8 years with obstructive lung disease, mostly asthma (13/15). The methacholine was inhaled during two minutes of tidal breathing in increasing concentrations. After each inhalation, lung function was measured and clinical signs recorded independently by two observers unaware of each others results. The logarithm of the concentration of methacholine which caused wheezing over the trachea correlated closely with the logarithm of the concentration of methacholine causing a 20% fall in the forced expiratory volume in one second (FEV1) but was 52% greater on average. At the end of the test there was a mean (SD) fall in FEV1 of 33.3 (7.4)% and a fall in oxygen saturation of 5.2 (3.1)%. Bronchial provocation testing by listening for wheeze over the trachea is a safe technique, which correlates with objective measures of lung function in young children.