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Nocturnal asthma indicates poor overall control of asthma and adversely affects the quality of life of the patient. The purpose of the present study was to compare the objective measurement of nocturnal wheeze with clinical state, recall of symptoms, and changes in lung function. Nine asthmatic children aged 9 to 16 years were followed with an asthma diary and diurnal measurement of peak flow for a week before the nocturnal study; all but two were apparently well controlled. Breath sounds were recorded and analyzed continuously overnight to quantify wheeze using a phonopneumography sensor attached over the trachea. The analytical system (PulmoTrack) utilized an algorithm to detect wheeze and reject interference. The wheeze rate (Tw/Ttot = duration of wheeze/duration of recording) was calculated minute by minute throughout the night. Recordings lasted over 8 hours and all but two children had wheeze lasting for a total time of between 11 and 87 minutes. The pattern of wheezing was very variable during sleep, with episodes of wheeze separated by periods of quiet breathing. There was no relationship between subjective perception of nocturnal asthma, forced expiratory volume in 1 s (FEV(1)) next morning, and the objective measurement of wheeze. Total overnight wheeze was significantly related to the total diary symptom score and to the (small) diurnal variability of peak expiratory flow (PEF). Four of the seven children with asthma who were apparently well controlled had considerable amounts of wheeze during the night that was episodic in nature and unrelated to conventional measures of lung function or nocturnal symptoms.

Wheezing and respiratory symptoms are very common in preschool children, and the ability to diagnose asthma correctly is important. This review describes an approach to the diagnosis of asthma in preschool children by means of an inhalation bronchial challenge. The child is exposed to increasing doses of challenge agent until wheezing is detected at a dose below that at which normal subjects respond, thus indicating bronchial hyperreactivity. The technique was originally developed using simple stethoscope auscultation of the lungs together with recording of respiratory rate and oxygen saturation (by pulse oximetry). Extensive studies have confirmed the safety and practicability of the technique and the specificity for asthma when the challenge agent is adenosine 5'-monophosphate (AMP). Subsequently, acoustic recordings have been used to detect and analyse breath sounds and to quantify the wheeze; these show excellent correlation between the clinical detection of wheeze and the wheeze rate (duration of wheeze/duration of recording) during bronchial challenges in children. Equipment is now becoming available that can perform the acoustic quantification of wheeze automatically and facilitate bronchial challenges in young children.

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: deltaFEV1 > or = 10% (sensitivity 57.9%, specificity 100%); PC20-MCH: < or = 3 mg/ml (sensitivity 87.5%, specificity 86.7%); and PC20-AMP: < or = 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.

Bronchial reactivity to inhaled agents in preschool children can be undertaken by auscultating the lungs to detect wheezing, but there is a lack of information on when wheeze first appears at the endpoint of the challenge and on the acoustic characteristics of the wheeze. We recorded breath sounds continuously during tidal breathing inhalation challenges with adenosine 5'-monophosphate, using sensors attached over each upper lobe in 80 preschool children. In 35 children, the challenge was considered positive by a pediatrician who determined the endpoint by detecting wheeze on auscultation after an inhalation. Using acoustic analysis, we determined that the first wheeze appeared during the 2-min period of nebulization in 31% of positive challenges; it was unilateral in 37%, and only inspiratory in 46%. A running window of 6 sec was used to detect at least two wheezes without reference to phase of breathing, and this index had a sensitivity of 97.6% and specificity of 99.7% for determining the endpoint of a challenge. Detecting wheeze acoustically adds safety to the technique by enabling the challenge to be stopped earlier, while the lack of a need to document the phase of breathing simplifies the technique.

The present study was designed to compare the clinical finding of wheeze by auscultation with an objective evaluation by acoustic means at the endpoint of a bronchial challenge in preschool children. Challenges were undertaken using a tidal breathing method in 51 preschool children as part of the investigation of possible asthma. An electronic stethoscope was used for auscultation of each lung and for the simultaneous recording of the acoustic sonogram for analysis. In 24 children, the pediatrician determined that the challenge was positive, and in 22 of these, he heard wheezing at the endpoint of the challenge. In 2 children the challenge was considered positive, based on a modest fall in saturation. The acoustic record was scanned manually for presence of wheeze defined in terms of duration, and power spectrum without reference to auscultatory findings. In positive challenges, the mean wheeze rate was 28.1% (95% CI, 19.5-36.8%), while no wheeze was detected acoustically in negative challenges. Using a cutoff wheeze rate (duration of wheeze/duration of breath phase x100) of 10% for the whole group, clinical wheezing detected by the pediatrician had a sensitivity of 100% (no false negatives) and a specificity of 91%. In conclusion, the clinical observation of wheeze agrees very well with its detection by acoustic measurement at the endpoint of a bronchial challenge in preschool children., (Copyright 2004 Wiley-Liss, Inc.)

We determined whether the exhaled nitric oxide (eNO) level in asthmatics is age-dependent. Eighty-seven asthmatic patients aged 2-41 years were studied. Hyperreactivity to adenosine 5'-monophosphate (AMP) was used to confirm asthma (

Background: Leukotriene antagonist therapy in asthmatic patients alleviates symptoms and improves exercise tolerance, however the effect of these drugs on bronchial provocation tests and exhaled nitric oxide levels are less clearly established., Objective: To determine the effect of montelukast treatment on airway hyperresponsiveness to exercise, methacholine and adenosine-5'-monophosphate and on exhaled nitric oxide levels in steroid-naive asthmatics., Methods: Following a 2 week run-in period, 20 mild to moderate asthmatics were enrolled in an open label 6 week trial of oral montelukast-sodium therapy. Bronchial hyperreactivity (exercise, methacholine and adenosine-5'-monophosphate challenges) and exhaled nitric oxide levels were measured before and after the 6 week period., Results: Montelukast treatment resulted in a significant improvement in exercise tolerance: median delta FEV1 20.0% (range 0-50) prior to treatment vs. 15.0% (range 0-50) post-treatment (P = 0.029). A significant difference was also observed for exhaled NO following therapy: median NO 16.0 ppb (range 7-41) vs. 13.0 (range 4.8-26) (P = 0.016). No change was seen in baseline lung function tests (FEV1, MEF50) or in the bronchial responsiveness (PC20) for methacholine and adenosine-5'-monophosphate., Conclusions: This study demonstrates that the leukotriene antagonist montelukast-sodium reduces bronchial hyperreactivity in response to exercise and reduces exhaled nitric oxide levels but has little effect on bronchial responsiveness to methacholine and adenosine challenges.

Exhaled nitric oxide (eNO) has been used to diagnose asthma in adults and children using either the slow vital capacity method (SVCm) or, in younger children, the tidal breathing method (TBm). Adenosine 5'-monophosphate (AMP) challenge also has been found to be a sensitive and specific test for the diagnosis of asthma. In the present study, we used the AMP provocation concentration that caused wheezing (PCW) to confirm the diagnosis of asthma (PCW < or = 200 mg/mL). We studied 36 children (2-7 years) with mild intermittent asthma, 13 children (3-7 years) with moderate persistent asthma treated with inhaled steroids, 20 nonasthmatic children (2-7 years) with chronic cough and recurrent pneumonia, and 15 healthy children (4-6 years). Expired gas was collected in collection bags by the TBm, and eNO was measured. We evaluated the efficacy of eNO values in diagnosing asthma. The mean eNO level of the mild intermittent asthmatic children (5.6 +/- 0.4 ppb) not receiving inhaled corticosteroids was significantly higher (ANOVA P < 0.0001) than that of the moderate persistent asthmatics who were treated with inhaled steroids, the nonasthmatic children with chronic cough, and the group of healthy children (3.7 +/- 0.6 ppb, P < 0.05; 3.2 +/- 0.3 ppb, P < 0.001; 2.2 +/- 0.2 ppb, P < 0.001, respectively). The points of intersection for sensitivity and specificity curves of eNO to differentiate mild intermittent asthmatics from nonasthmatic children with chronic cough and from healthy children were 77% and 88% for eNO values of 3.8 ppb and 2.9 ppb, respectively. We conclude that eNO collected by the TBm can differentiate steroid-naive young children with intermittent asthma from healthy children, from nonasthmatic children with chronic cough, and from asthmatic children treated with inhaled steroids., (Copyright 2001 Wiley-Liss, Inc.)

Background: Asthma is characterized in part by small airways dysfunction. Peak expiratory flow (PEF) measurement has been suggested by all international guidelines as an important tool in asthma management. The correlation between PEF and FEV(1) but not with forced expired flow at 50% of vital capacity (FEF(50)) is well-established., Study Objective: To determine the value of PEF measurement as a predictor of small airways status as expressed by FEF(50)., Design: Analysis of the association between PEF and FEF(50) in single and multiple determinations., Patients: One hundred eleven asthmatic children (mean age, 11.8 years), grouped in the following way according to FEV(1) values: within normal range (n = 46); mildly reduced FEV(1) (n = 44); and moderately/severely reduced FEV(1) (n = 21)., Results: Overall, FEF(50) and PEF were significantly correlated (r = 0.49; p < 0.0001). However, in 41.6% of the patients, the actual FEF(50) differed by > 20% from the calculated FEF(50). PEF has a high specificity (82.4%) but a poor sensitivity (51.7%) to detect FEF(50) status. PEF was better able to reflect abnormal FEF(50) in the patients with more severe asthma and to reflect normal FEF(50) values in the healthier patients. In patients with multiple measurements (n = 40), the correlation between FEF(50) and PEF was significantly better than that derived from a single determination (multiple measurements r = 0.77; single measurement, r = 0.49)., Conclusions: Although PEF is an important tool in the management of asthmatic patients, it does not yield a complete picture because it is not sensitive in detecting small airways function. It is best used at home along with regular spirometry measurements at the clinic. PEF may serve as a better index of changes in small airways function once an individual regression is determined.

Guidelines for the management of asthma rely on various methods of assessing severity and how it changes in order to select the appropriate treatment. These methods have been developed from the basic clinical skills of history taking and physical examination to which attempts at improving objectivity have been added, such as the use of asthma diaries, the home recording of peak expiratory flow (PEF) or measurements of bronchial reactivity. The present review was an attempt to determine to what extent monitoring asthma by various techniques is justified. Unfortunately, diaries and home recording of PEF are easily faked and generally unreliable while objective tests, such as the measurement of bronchial reactivity or studies of induced sputum cannot be undertaken often enough for monitoring, and there is certainly the need for prospective longitudinal controlled studies., (Copyright 2001 S. Karger AG, Basel)

Bronchial hyperreactivity is a characteristic feature of asthma and can be evaluated by different challenges. The aim of this study was to compare exercise, methacholine (MCH), and adenosine 5'-monophosphate (AMP) challenges in 135 children and young adults (mean age +/- SD, 12.4+/-3.9 years) with asthma, and to examine the utility of the different challenges in predicting those children with asthma likely to require prophylactic antiinflammatory treatment. The sensitivity of MCH challenge in detecting bronchial hyperreactivity (at or below 8 mg/mL) was 98%, that of AMP challenge (at or below 200 mg/mL) 95.5%, and that of exercise (more than 8.2% fall in FEV(1)) was 65%. There was a significant difference between mild asthmatic children (85 patients, intermittent asthma, step 1 of NIH guidelines) and moderate asthmatics (50 patients, steps 2 and 3 of guidelines) in relation to the logarithmic mean provocation concentration to elicit a 20% fall in FEV(1) (PC(20)) to MCH (0.49 mg/mL vs. 0.15 mg/mL, P<0.00001), that to AMP (7.67 mg/mL vs. 3.60 mg/mL, P = 0.001), and in relation to the mean percent fall in FEV(1) after exercise (13.9% vs. 22.0%, P = 0.001). Sensitivity and specificity curves between the two severity groups of asthma were constructed, and the intersection point of the two curves for each type of challenge was determined. When mild asthmatics were compared to moderate asthmatics, the intersection points for MCH, AMP, and exercise were 66%, 63%, and 61%, respectively. Logistic regression analysis and receiver operating characteristic (ROC) curves of the three challenges for the two severity groups of asthma showed that methacholine was a better discriminating challenge between the severity groups than the other two challenges. We conclude that the sensitivities of AMP and MCH challenges in the detection of bronchial hyperreactivity in children and young adults with asthma are very similar and higher than that of exercise. There is a significant difference between mild and moderate asthmatics within the three bronchial challenges, with MCH discriminating better than AMP or exercise between groups., (Copyright 2000 Wiley-Liss, Inc.)

The measurement of bronchial reactivity is an important aid in the diagnosis of asthma, but the technique using spirometry is not feasible in young children. The aim of the present study was to determine the efficacy and safety of a modification of the chest auscultation method in the assessment of bronchial reactivity to inhaled methacholine in young asthmatic children. One hundred forty-six young children with asthma (mean age, 4.3 yr) underwent bronchial challenges with nebulized methacholine using the auscultation method (PCW). The end point was defined as the appearance of wheezing, oxygen desaturation, or tachypnea. For comparison, 30 children and young adults with asthma underwent bronchial provocation with methacholine using spirometry (PC(20)). A positive response using the auscultation method was observed in 95.9% of the younger children, and wheezes alone or in combination with other signs appeared in 80.8% of them. The mean desaturation at the end point was 4.6% (PCW) and 5.0% (PC(20)), with a similar pattern in the two groups. Cough was not helpful in determining the end point. We conclude that the modified auscultation method is effective and safe, with wheeze appearing at the end point in the large majority of the children.

Bronchial hyper-responsiveness is a cardinal feature of asthma in children, but is also present in children with some other types of chronic lung disease. Techniques are now available that enable bronchial reactivity to be measured in children of almost all ages. The responses of normal and asthmatic children to standardized challenges have been measured and the optimal cut-off values separating the normal and asthmatic response have been established statistically. All types of challenge can distinguish between the child who is normal and one with lung disease within the limits of the sensitivity and specificity of the test. However, only indirect challenges, such as those by exercise or the inhalation of adenosine 5'-monophosphate, distinguish between asthma and other types of lung disease.

An analysis was undertaken to determine the optimal cut-off separating an asthmatic from a normal response to a bronchial provocation challenge by exercise and the inhalation of methacholine or histamine in children and young adults. Data were extracted, after appropriate correction, from published studies available in Medline of large random populations that complied with preset criteria of suitability for analysis, and the distribution of bronchial reactivity in the healthy population for exercise and inhalation challenges were derived. Studies on the response to exercise and methacholine inhalation in 232 young asthmatics of varying severity were carried out by the authors and the distribution of bronchial reactivity of a young asthmatic population obtained. Comparisons of the sensitivity and specificity of the challenges were aided by the construction of receiver operating characteristic curves. The optimal cut-off point of the fall in forced expiratory volume in one second (FEV1) after exercise was 13%, with a sensitivity (power) of 63% and specificity of 94%. For inhalation challenges, the optimal cut-off point for the dose of methacholine or histamine causing a 20% fall in FEV1 was 6.6 micromol, with a sensitivity of 92% and a specificity of 89%. The cut-off values were not materially affected by the severity of the asthma and provide objective data with which to evaluate the results of bronchial provocation challenges in children and young adults.

The value of home monitoring of peak expiratory flow (PEF) as part of an action plan for asthma management in children and young adults is uncertain. We sought to determine whether home recording of PEF benefited asthma management and whether any contribution was affected by the severity of the asthma. Twenty-eight children and young adults with asthma of different severity (mean age 14 yrs; 95% confidence interval (95% CI) 12-16 yrs) recorded their symptoms, drug consumption and PEF twice daily for a mean of 82 days over a 12 week period, and attended the laboratory every 2 weeks for measurement of lung function. The number of individual patients with significant correlations for laboratory lung function tests compared with ambulatory PEF and diary scores averaged over the preceeding 2 weeks was low in all severity groups. When measured in the laboratory, PEF meter readings correlated poorly with PEF measured by spirometry. The proportion of patients with significant correlations for PEF, symptoms and rescue bronchodilator use on a day-to-day basis was 70-80% in the group of severe asthmatics and significantly less in the mild asthmatics. In a subgroup of 14 patients who were sick on a mean of 19 days, the mean difference in PEF between well and sick days was 14% of predicted. Diurnal PEF variation correlated poorly with other parameters in all groups. It is concluded that PEF monitoring adds little to daily recording of symptoms and bronchodilator use in the management of young patients with severe asthma, and it is too insensitive to register meaningful clinical changes in those with milder asthma.

Background: Bronchial hyperreactivity to methacholine is present in children with asthma and other types of paediatric chronic obstructive pulmonary disease (COPD), while hyperreactivity to exercise is more specific for asthma. Adenosine 5'-monophosphate (AMP) is a potent bronchoconstrictor and, like exercise, may provoke asthma by activating mast cells. This study investigated the suitability of AMP as a specific challenge for asthma in children., Methods: Bronchial provocation challenges with methacholine and AMP were performed in a double blind fashion using tidal breathing in 51 children with asthma, 21 with paediatric COPD of various types, and in 19 control children. Each subject also underwent a standardised exercise challenge after inhalation challenges were completed. Sensitivity and specificity curves were constructed and the intersection point of sensitivity and specificity for each type of challenge was determined., Results: When the asthmatic patients were compared with the children with COPD, the intersection points for AMP, exercise and methacholine were 90%, 85%, and 50%, respectively. When compared with the controls the same intersection points were 98%, 84%, and 92%, and when children with paediatric COPD were compared with controls they were 55%, 50%, and 82%., Conclusions: Methacholine distinguishes both asthma and paediatric COPD from controls with a sensitivity of 82-92%, but does not distinguish between asthma and paediatric COPD; exercise and AMP distinguish asthma from controls with a sensitivity and specificity of 84-98% but they also distinguish asthma from paediatric COPD with a sensitivity and specificity of 85-90%. AMP inhalation is a practical aid for diagnosing asthma and distinguishing it from COPD in children of all ages.

The purpose of the study was to determine the age at which young asthmatic children could master the use of a new powder inhaler device (Turbuhaler). We studied 59 children with asthma between the ages of 3 and 6 years who consecutively attended the asthma clinic of the pediatric department. Efficiency of inhalation and the pharmacological effect of the terbutaline in the inhaler were measured by scores for inhalation technique and clinical response. None of the 3-year-old children used the device efficiently, but 43% of the 4-year-old, 67% of the 5-year-old, and 80% of the 6-year-old children used the inhaler correctly. Although inhaler technique was not perfect in the younger age group, 50% of the 3-year-old children demonstrated clinical improvement of asthma symptoms after inhalation. In the older age groups, 79%, 92%, and 100% of the 4, 5, and 6-year-old children demonstrated clinical improvement of asthma symptoms after inhalation. It is concluded that the new mode of dry powder delivery system (Bricanyl Turbuhaler) can be used in young asthmatic children who are 4 years of age and above.

Nine young asthmatic children aged 2-5 years underwent methacholine challenge after placebo or albuterol administered by metered dose inhaler through a spacer device (Babyhaler) with a face mask in a double-blind, cross-over, randomized study. The methacholine challenge was performed using chest auscultation to define the provocative concentration of methacholine that causes wheezing (PCW). The PCW increased from a geometric mean of 0.28 mg/mL after placebo to 3.59 mg/mL after albuterol (P < 0.0001). The protective effect of albuterol against methacholine-induced bronchospasm was 3.7 +/- 1.2 doubling doses. We conclude that administration of drugs from a metered dose inhaler through the Babyhaler with a face mask is effective. Albuterol causes a major reduction in the bronchial hyperreactivity in young wheezy children shortly after administration.

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.

Background: There is evidence that the prevalence of asthma in children and young people is increasing., Methods: An examination of a total population (35,170) of 17 year old Jewish boys of one seaside urban area in Israel was undertaken during two years, 1986 and 1990, by trained respiratory physicians in a regional recruiting office of the Israel Defence Forces. All boys who had ever been diagnosed as having asthma or symptoms that could have been due to asthma underwent a further examination by respiratory physicians that included spirometry at rest. A test to evaluate exercise induced asthma was performed on a treadmill in 88% of the boys., Results: Lifetime prevalence (asthma in the past or at present) increased from 7.9% in 1986 to 9.6% in 1990. Point prevalence (current asthma) increased from 5.0% to 5.9%. The prevalence of current asthma increased in all degrees of severity (mild disease from 3.3% to 3.7%, moderate disease from 1.7% to 2.2%, and severe disease from 0.03% to 0.04%). By the age of 17, 77.4% of boys who had suffered from asthma had no or only very mild symptoms., Conclusions: It is considered that the measured increase in prevalence of asthma from 1986 to 1990 reflects a true increase among the Jewish Israeli population.

Asthma is a common disease of children the basis of which is a state of chronic immunological inflammation which causes bronchial hyperreactivity and renders the patient liable to develop widespread airways obstruction in response to a variety of stimuli. In many instances it is likely that the immunological inflammation results from ongoing antigenic stimuli with the release of chemical mediators responsible for short term bronchospasm and cytokines responsible for the ongoing inflammatory process. Other insults can apparently result in very similar immunological events in asthmatics, particularly viral infections and a similar process can be initiated in children without asthma, including those with chronic bacterial infections of the lungs. There are differences in the bronchial hyperreactivity of asthma and other diseases which suggest that in the asthmatic the mast cell is either different structurally or functionally and this renders the patient susceptible to exercise induced asthma in addition to the bronchial hyperreactivity to chemical mediators common to a number of diseases with hyperreactivity. There is good evidence of direct genetic control of atopy and the large majority of children with asthma are atopic but there is no direct genetic link between atopy and asthma and twin studies strongly suggest the existence of a 'permissive' asthma gene which will allow the disease to develop if there is an appropriate external trigger. The only drugs which have been shown to significantly reduce bronchial reactivity are the corticosteroids with a lesser effect noted for sodium cromoglycate and nedocromil. Inhaled corticosteroids can reverse the immunologic inflammatory process and reduce bronchial reactivity, sometimes to normal levels, but on stopping treatment the patient reverts back to the asthmatic state. At the present time it appears that controlled longterm inhaled corticosteroid therapy is the most rational treatment for significant perennial childhood asthma.

Twenty one children with asthma aged 1.0-10.5 years (mean (SD) 3.3 (2.5) years) were admitted to the hospital to evaluate pulmonary right middle lobe or lingular collapse lasting one to 12 months (mean (SD) 4.4 (3.8) months). Seven children had mild asthma and were treated with inhaled beta 2 agonists as needed. Nine had moderate asthma treated with either sodium cromoglycate or slow release theophylline. Five had severe asthma treated with inhaled steroids. Each child underwent fibreoptic bronchoscopy under local anaesthesia and a bronchoalveolar lavage. Differential cell counts of the lavage fluid revealed predominance of neutrophils in 12 patients (57%). In nine of these patients cultures grew pathogenic bacteria, mainly Haemophilus influenzae and Streptococcus pneumoniae. There was no correlation between the severity of asthma and a positive bacterial culture. There was also no correlation between the duration of the right middle lobe collapse and a positive culture. We conclude that longstanding right middle lobe collapse in asthmatic children is often associated with bacterial infection.

In June 1990 a meeting of Paediatric Respiratory Physicians was held near Adelaide. The guidelines for assessing and treating asthma as prepared by the Thoracic Society of Australia and New Zealand for the management of patients with asthma was considered. Although not explicitly stated, these guidelines were designed for adult asthmatics. There was complete agreement that a companion statement was needed to take into account differences between the management of children and adults. This document fulfils that role. Further recommendations are found in a statement prepared by Australian and New Zealand respiratory paediatricians following a workshop in June 1989. This present statement should be read in association with the previous documents.

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.

Bronchial reactivity to inhaled methacholine was measured by the steady-state tidal breathing method in asthmatic children aged 1 to 17 yr. The children were divided into three clinical groups according to their minimal therapeutic requirements: mild asthma, children requiring infrequent treatment with inhaled beta-agonists (81 patients); moderate asthma, children requiring daily preventive treatment with either cromolyn sodium or slow-release theophylline (67 patients); and severe asthma, children requiring daily preventive treatment with oral or inhaled steroids (34 patients). They were also divided into three age groups: from 1 to 6 yr, tested by using bronchial provocation with tracheal auscultation (BPTA) to determine the methacholine concentration causing wheezing (PCW); and from 7 to 11 yr and 12 to 17 yr, using lung function testing to determine the concentration causing a 20% fall in FEV1 (PC20). For the whole group the mean level of bronchial reactivity to methacholine correlated inversely with the severity of bronchial asthma according to the minimal drug requirements (p less than 0.0001) and was similar over the whole age range (p less than 0.9965) for each severity grouping. In the older children the difference between moderate and severe asthma was not significant, but this may have been a result of the effect of corticosteroids in the severe group. We concluded that age has no significant effect on the methacholine response in asthmatic children over a wide age range.

Exercise-induced asthma is considered in terms of the stimulus, the intermediary pathway and the response. Various controversies about each of these components are discussed. The stimulus may be cooling of the airways, loss of water or neither of these, and there is evidence for and against the identity of exercise- and hyperventilation-induced asthma. The intermediary pathway seems certain to involve the release of chemical mediators, although other neurogenic mechanisms have been proposed. Since the response is far from uniform, it may well be that different pathways are involved in different subjects. The effector mechanism appears to be bronchospasm, but recent evidence has suggested that an inflammatory response may be involved in a late reaction to exercise. The variability of exercise-induced asthma may well be due to variations in intrinsic bronchial reactivity resulting from allergenic stimulation.

Thirty-three asthmatics were followed up for a mean of 8 1/2 years in prospective study in order to observe the clinical course of the disease. The severity of asthma was graded according to the treatment each required to keep him in reasonable health. Regular exercise tests were performed so that a comparison could be made between the degree of exercise-induced asthma and the severity of the disease. In this group of severe perennial childhood asthmatics profound exercise-induced asthma was found to exist throughout the entire clinical spectrum of the disease with no appreciable difference until the patient became symptom-free. Exercise-induced asthma then disappeared only to return if clinical asthma recurred. This study showed that exercise-induced asthma is a sensitive indicator of clinical asthma but has no prognostic significance in the symptom-free patient.

Twelve asthmatics (ages 8 to 33 yr) with proven exercise-induced asthma (EIA) and allergen-induced asthma (AIA) were investigated in an attempt to elucidate the pathways through which each type of attack develops. All patients were rendered refractory to EIA by repeated exercise at short intervals and were then immediately challenged by inhalation with an allergen known to evoke AIA. After an average of three runs all subjects were rendered refractory to EIA (post-exercise fall in FEV1 of 7 +/- 8% SEM compared with the control postexercise fall of 32 +/- 14%). In this refractory state six patients failed to respond to antigen challenge (6 +/- 4% SEM fall in FEV1 compared with the 30 +/- 3% fall in control study, p less than 0.001), suggesting a common pathway for EIA and AIA, such as the exhaustion of stored chemical mediators. Six other patients developed attacks of AIA while refractory to EIA, which were at least as severe as those in their control study (34 +/- 7% SEM fall in FEV1 compared with 29 +/- 3%). The fact that AIA could develop while EIA was blocked in this group requires an alternate pathway or mechanism for their AIA. The only significant difference between the AIA "blocked" and AIA "nonblocked" groups was a lower baseline level of lung function in all tests in the nonblocked group.

Heart rate, blood pressure, pulsus paradoxus, and cardiac output measured by means of transthoracic electrical impedance cardiography have been recorded in 29 children mean age 10 years +/- 2 SD during status asthmaticus. Changes were recorded over the first two hours of treatment during which all patients received oxygen, intravenous fluid, and hydrocortisone, and were randomly assigned to receive aminophylline, salbutamol, or both. Admission values showed significant correlation of pulsus paradoxus with PaCO2 (r = 0.66). Pulsus paradoxus was greater than 20 mmHg for all patients with PaCO2 above 5.5 kPa. Mean stroke volume and cardiac output were 89% and 131% of the resting convalescent values in the same children. Stroke volume cardiac output and heart rate did not correlate with peak expiratory flow rate or blood gas measurements. Aminophylline and salbutamol together were associated with significantly greater increase in PEF than aminophylline alone (P less than 0.05). Nebulised salbutamol was just as effective as intravenous salbutamol. Heart rate and systolic blood pressure declined significantly after nebulised salbutamol and aminophylline, but not after intravenous salbutamol and aminophylline. Stroke volume and cardiac output did not change significantly in any treatment group.

Running produces a greater amount of post-exercise bronchoconstriction than other forms of exercise carried out a similar metabolic rates. The treadmill can be used to provide a standardized form of exercise when studying the asthmatic child. The severity of post-exercise bronchoconstriction depends upon the rate of working on the treadmill and the duration of exercise. A maximum response is obtained by six minutes of running at an uphill slope of 10% at a speed of 5 kmph (3 mph). Even with this type of test, there is still considerable variation in the response from time to time and greatest reporducibility is obtained by repeating the test within one week. Treadmill exercise tests may be used in the diagnosis of asthma and in the assessment of its likely severity.

Thirteen asthmatic children aged 9-14 years participated in a double blind randomised trial to compare the effectiveness and duration of action of 2 formulations of sodium cromoglycate; one a 20 mg capsule of powdered sodium cromoglycate delivered by turbo inhaler (spinhaler), and the other 1 mg of aerosolised sodium cromoglycate delivered by pressurised cannister inhaler (aerosol). The children performed exercise tests on each of 3 days in a 10 day period--15 minutes, 2 hours, and 6 hours after inhalation of powder, aerosol, or a placebo. Two patients were not protected from exercise induced asthma by either formulation of sodium cromoglycate. Among the remaining patients both formulations gave good protection from exercise induced asthma 15 minutes after inhalation, and the effect of both wore off steadily over the next 6 hours. The spinhaler gave appreciably better protection than the aerosol at 15 minutes after inhalation, and was the only formulation to provide good protection at 2 hours and 6 hours. The more limited effectiveness of the aerosol may be explained by the lower dose of sodium cromoglycate and the more complicated inhalation technique required.

Nineteen asthmatic children treated with the aerosol steroid, beclomethasone dipropionate, were followed 3 to 5 yr. Good control was maintained in all but one child throughout, although 73% have needed 1 or 2 wk of supplementary oral steroids per year for exacerbations. Growth has been along the percentile on which the child entered the study. No serious side effects have been encountered among 41 children treated between 1 and 5 yr with beclomethasone dipropionate. Seventeen percent needed prolonged alternate-day oral steroids, although all but one child did eventually return to good control with beclomethasone dipropionate.

Co-administration of intravenous albuterol and theophylline resulted in increased theophylline clearance in a child with severe asthma. This required a threefold increase in theophylline dosage to maintain therapeutic serum theophylline concentrations. The possible effect of intravenous albuterol on theophylline metabolism was further supported by a 50 percent decrease in theophylline clearance upon discontinuation of albuterol and a second increase in its clearance when albuterol was readministered. To the best of our knowledge, this is the first documentation of enhanced theophylline clearance by albuterol.

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.

Thirteen children each exercised for 6 min by running on a treadmill and by tethered swimming, breathing air at room temperature and either 8% or 99% relative humidity continuously. Ventilation, gas exchange and heart rate were closely matched in all four tests in each child, with a mean oxygen consumption of 32.3 +/- 1.7 ml x min-1 x kg-1. The post-exercise fall in FEV1 expressed as a percentage of the baseline FEV1 (delta FEV1) was significantly greater after running compared with swimming breathing either humid or dry air. The delta FEV1 was also related to respiratory heat loss (RHL) calculated from measurements of inspired and expired gas temperature and humidity. At a standardised RHL, the difference between running and swimming was highly significant [delta FEV1 (%) +/- SE = 39 +/- 5 and 28 +/- 4 respectively, p less than 0.01]. These experiments suggest that the type of exercise influences the severity of exercise-induced asthma even under conditions of the same metabolic stress and respiratory heat loss.