Changes In Peak Expiratory Flow Research Articles

Randomised, dose-ranging, placebo-controlled study of chimeric antibody to CD4 (keliximab) in chronic severe asthma

There is substantial circumstantial evidence that CD4 lymphocytes have a role in the pathogenesis of chronic asthma. We investigated the efficacy and safety in severe corticosteroid-dependent asthma of a single intravenous infusion of keliximab (IDEC CE9.1), a chimeric monoclonal antibody to CD4. 22 patients were recruited from two asthma clinics. In an ascending-dose design, the first eight patients were assigned 0.5 mg/kg keliximab (six) or placebo (two); the next seven were assigned 1.5 mg/kg (five) or placebo (two); and the last seven were assigned 3.0 mg/kg (five) or placebo (two). Masked data on safety for each dose group were assessed before progression to the next dose. Patients kept a daily symptom diary and measured morning and evening peak expiratory flow (PEF) at home. PEF and forced expiratory volume in 1 s (FEV1) were measured at follow-up clinic visits. Patients given 0.5 mg/kg or 1.5 mg/kg keliximab and placebo recipients did not differ in change from baseline of PEF, FEV1, or symptom score. Those given 3.0 mg/kg keliximab differed significantly from placebo recipients in change in morning PEF (median area under curve [AUC] 445 vs -82.5, p=0.005) and evening PEF (median AUC 548 vs -85, p=0.014). Symptom score showed the same pattern (though differences did not achieve significance), but there was no difference in clinic FEV1. There were no serious adverse effects related to treatment. Two patients had mild exacerbations of eczema and one developed a transient maculopapular rash. All doses of keliximab were associated with a reduction from baseline in CD4 count. Our findings raise the possibility that T-cell-directed treatment may be an alternative approach to the treatment of severe asthma.

Timing of recovery of lung function after severe hypoxemic respiratory failure in children.

To describe the timing of recovery of lung function after severe acute hypoxemic respiratory failure (AHRF) in children. A serial observational follow-up study of clinical and lung function measurements up to 53 months after acute illness. University pediatric intensive care unit in a national children's hospital. Five critically ill children aged 5-14 years. None Clinical recovery: each patient required a 3-5 month convalescence before being able to attend full-time school because of lethargy and dyspnea. All patients developed wheeze 3-12 months after illness and four received long-term bronchodilator therapy. Lung function recovery: for both the forced vital capacity (FVC) and forced vital capacity in the first second (FEV1) four patients had abnormally low values, regaining only 60-70% of predicted values for their height and sex, and all of this improvement had occurred by 6-12 months after illness. Beyond this interval, patients remained on their same FVC and FEV1 centile. FEV1/FVC ratios were consistently within the normal range, indicating a predominantly restrictive defect. Changes in peak expiratory flow exhibited a time course of improvement similar to the other lung function tests. In children, pulmonary recovery after severe AHRF may occur for 6-12 months. A 1-year follow-up could offer a rational single point for assessment of outcome and long-term counselling of child and parents.

Work-related changes in peak expiratory flow among laboratory animal workers.

Laboratory animal workers are at risk of developing allergic symptoms, of which asthmatic symptoms are the most severe. The aim was to study the relationship between allergic symptoms due to working with rats and variability and changes in peak expiratory flow (PEF). Several indices were used on the basis of the amplitude of the PEF or the differences in PEF between days with and without exposure to rat aeroallergens. Of the 398 rat workers, 73% completed PEF readings on at least 9 days, of whom 208 had PEF readings on working days with and without contact with animals. The overall prevalence rate of allergic symptoms (asthmatic, eye, nose and/or skin) among rat workers during the handling of rats was 17.3%. Asthmatic symptoms were reported by 6.7%. The PEF of the workers who reported asthmatic symptoms due to working with rats decreased significantly on days working with the animals (difference between the minimum PEF averaged over working days with animals and over days without animals (deltaPEFmin-min) = -73 L x min(-1)), compared to the workers without symptoms (2.2 L x min(-1)). This effect was more pronounced among workers with a late asthmatic response, i.e. the presence of asthmatic symptoms several hours after working with rats (deltaPEFmin-min = -11.6 L x min(-1)). Multiple regression analyses showed that only those with asthmatic symptoms several hours after working with rats and those with allergic symptoms had an increased deltaPEFmin-min. In addition, workers with asthmatic symptoms were also more likely to have a higher PEF variability than workers without asthmatic symptoms. However, no difference in PEF variability between days with and without animals contact was observed. This study shows that the peak expiratory flow of workers who reported asthmatic symptoms due to working with rats decreased significantly on days working with laboratory animals.

Perception of Natural Fluctuations in Peak Flow in Asthma: Clinical Severity and Psychological Correlates

Two methods of defining perception of asthma-related changes in airflow were compared, and relationships to clinical opinions of severity and assessments of psychological functioning were investigated. Perceived breathlessness (VAB) and peak expiratory flow (PEF) were recorded by 100 subjects for 28 days. Perception was defined by correlation of the two values and by the ratio of maximum change in PEF and related change in VAB. The latter method defined 24 poor perceivers (PP) and 13 exaggerated perceivers (EP), in whom presence of a psychological disorder was high (30% of PP, 54% of EP, compared to 8% of the remainder). Clinical severity in EP was assessed as greater than appeared warranted.

Do dairy products induce bronchoconstriction in adults with asthma?

Background: Dairy products have often been implicated as a cause of exacerbation of asthma, but there is little scientific evidence to support this hypothesis. Objective: We sought to determine whether dairy products induce bronchoconstriction in a group of adults with asthma. Methods: Twenty subjects with asthma (13 women and 7 men) were recruited from respondents who had previously completed a food and asthma questionnaire. Ten subjects perceived that their asthma became worse with ingestion of dairy products (positive perceivers), whereas ten were negative perceivers. None of the subjects had positive skin prick test results with cow's milk. The study was a randomized, cross-over, double-blind, placebo-controlled trial. Subjects complied with a dairy-free diet throughout the study. The active challenge was a single-dose drink equivalent to 300 ml of cow's milk. A positive reaction was defined as a 15% reduction in both FEV 1 and peak expiratory flow (PEF) on the active challenge day compared with results obtained at the same time on the placebo day. Results: For both FEV 1 and PEF there were no statistically significantly differences in group means between active challenge and placebo challenge, between sequence of administration, or between perceptions. Nine subjects showed FEV 1 or PEF changes that were greater than 15% of baseline values: four patients showed changes after both active and placebo treatment; two after treatment with placebo only; and three after active treatment alone. Of the latter group, two subjects showed changes only in PEF, and when one of these subjects underwent a further detailed study, no asthmatic reaction could be demonstrated. Conclusion: It is unlikely that dairy products have a specific bronchoconstrictor effect in most patients with asthma, regardless of their perception. (J Allergy Clin Immunol 1998;101:45-50.)

Inaccuracy of portable peak flow meters: correction is not needed. Dutch CNSLD Study Group.

This study examined whether correction of peak expiratory flow (PEF) values for the inaccuracy of the meter would affect asthma management in 102 children (7-14 y old). PEF was recorded with a mini Wright meter twice daily for 2 weeks. As expected, measured PEF overestimated PEF level and asthma control in these children on many diary days. The actual numerical differences between measured and corrected PEF on these days were very small (>5% in only five patients, maximum 10%). It is unlikely that such small changes in PEF justify changes in asthma management, even if these changes cause PEF levels to cross arbitrary borders between various levels of asthma control used in self-management plans. The clinical importance of the inaccuracy of portable PEF meters is negligible.

Hypoxia, hypocapnia and spirometry at altitude.

1. Both hypoxia and hypocapnia can cause broncho-constriction in humans, and this could have a bearing on performance at high altitude or contribute to altitude sickness. We studied the relationship between spirometry, arterial oxygen saturation and end-tidal carbon dioxide (ETCO2) concentration in a group of healthy lowland adults during a stay at high altitude, and then evaluated the response to supplementary oxygen and administration of a beta 2 agonist. 2. We collected spirometric data from 51 members of the 1994 British Mount Everest Medical Expedition at sea level (barometric pressure 101.2-101.6 kPa) and at Mount Everest Base Camp in Nepal (altitude 5300 m, barometric pressure 53-54.7 kPa) using a pocket turbine spirometer. A total of 205 spirometric measurements were made on the 51 subjects during the first 6 days after arrival at Base Camp. Further measurements were made before and after inhalation of oxygen (n = 47) or a beta 2 agonist (n = 39). ETCO2 tensions were measured on the same day as spirometric measurements in 30 of these subjects. 3. In the first 6 days after arrival at 5300 m, lower oxygen saturations were associated with lower forced expiratory volume in 1 s (FEV1; P < 0.02) and forced vital capacity (FVC; P < 0.01), but not with peak expiratory flow (PEF). Administration of supplementary oxygen for 5 min increased oxygen saturation from a mean of 81%-94%, but there was no significant change in FEV1 or FVC, whilst PEF fell by 2.3% [P < 0.001; 95% confidence intervals (CI) -4 to -0.7%]. After salbutamol administration, there was no significant change in PEF, FEV1 or FVC in 35 non-asthmatic subjects. Mean ETCO2 at Everest Base Camp was 26 mmHg, and a low ETCO2 was weakly associated with a larger drop in FVC at altitude compared with sea level (r = 0.38, P < 0.05). There was no correlation between either ETCO2 or oxygen saturation and changes in FEV1 or PEF compared with sea-level values. 4. In this study, in normal subjects who were acclimatized to hypobaric hypoxia at an altitude of 5300 m, we found no evidence of hypoxic broncho-constriction. Individuals did not have lower PEF when they were more hypoxic, and neither PEF nor FEV1 were increased by either supplementary oxygen or salbutamol. FVC fell at altitude, and there was a greater fall in FVC for subjects with lower oxygen saturations and probably lower ETCO2.

Development of OASYS-2: a system for the analysis of serial measurement of peak expiratory flow in workers with suspected occupational asthma.

Serial peak expiratory flow (PEF) measurement is usually the most appropriate first step in the confirmation of occupational asthma. Visual assessment of the plotted record is more sensitive and specific than statistical methods so far reported. The use of visual analysis is limited by lack of widespread expertise in the methods. A computer assisted diagnostic aid (OASYS-2) has been developed which is based on a scoring system developed from visual analysis. This removes the requirement for an experienced interpreter and should lead to the more widespread use of the technique. PEF records were collected from workers attending an occupational lung disease clinic for investigation of suspected occupational asthma and from workers participating in a study of respiratory symptoms in a postal sorting office. PEF records were divided into two development sets and two gold standard sets. The latter consisted of records from workers in which a final diagnosis had been reached by a method other than PEF recording. An experienced observer scored individual work and rest periods for the two development set PEF records; linear discriminant analysis was used to compare measurements taken from development set 1 records with visual scores. Two equations were produced which allowed prediction of scores for individual work or rest periods. The development set 2 was used to determine how these scores should be used to produce a whole record score. The first gold standard set was used to determine the whole record score which best separated those with and without occupational asthma. The second set determined the sensitivity and specificity of the chosen score. Two hundred and sixty eight PEF records were collected from 169 workers and divided into two development sets (81 and 60 records) and two gold standard sets (60 and 67 records). Linear discriminant analysis produced equations predicting the score for work periods incorporating five indices of PEF change and one for rest periods using seven indices. These equations correctly predicted the score for development set 1 work and rest periods on 61% of occasions (kappa = 0.47). The whole record score for development set 2 records, after weighting for definite or definitely no occupational effect, correlated with the visual score (correlation coefficient 0.86). Comparison with gold standard set 1 identified a cut off which proved to have a sensitivity of 75% and a specificity of 94% for an independent diagnosis of occupational asthma when applied to gold standard set 2. These results suggest that the sensitivity and specificity of analysing PEF records for occupational asthma using OASYS-2 approaches that of visual analysis, but it should be absolutely reproducible. The performance of OASYS-2 is more specific and approaches the sensitivity of other statistical methods of analysis. The evaluation of a large number of PEF records from workers exposed to different sensitising agents suggests that these results should be robust and should be repeatable in clinical practice.

Surfactant nebulization does not alter airflow obstruction and bronchial responsiveness to histamine in asthmatic children.

To test the hypothesis that surfactant nebulization improves pulmonary function and reduces bronchial responsiveness to histamine, we studied 12 children with asthma. We measured before and after inhalation of 100 mg nebulized natural-derived bovine surfactant (Alveofact (registered)) and after nebulization of 0.9% NaCl the change in peak expiratory flow, vital VC, FEV1, and forced expiratory flows at 50 and 75% of the flow-volume curve. In addition, we performed a histamine inhalation challenge. We did not find any significant changes in these parameters after nebulization of surfactant. These findings indicate that the inhalation of nebulized surfactant does not alter airflow obstruction and does not alter bronchial responsiveness to histamine in asthmatic children with airflow obstruction.

Associations of PM10 and airborne iron with respiratory health of adults living near a steel factory.

The association between daily PM10 (particles with a median aerodynamic diameter of < or = 10 microns) and iron particle concentrations and respiratory health was studied in a population of adults selected for current or recent bronchodilator use. Acute changes in respiratory health were measured as changes in peak expiratory flow (PEF), and daily prevalence of respiratory symptoms and medication use as recorded in a diary. The study period was October 11 through December 22, 1993. The study population included 32 adults living near a large steel industry in Wijk aan Zee, the Netherlands. During the study period, 24-h average PM10 concentrations in Wijk aan Zee ranged from 36 to 137 micrograms/m3 while the 24-h average concentrations of iron, silicon, sodium, and manganese ranged from approximately zero to 6.95, 1.84, 12.02, and 0.37 micrograms/m3 respectively. The steel industry was found to contribute significantly to the PM10 concentrations, and especially to the iron and manganese concentrations in the air. The association of changes in respiratory health with changes in PM10, iron, sodium, and silicon was evaluated using a time series approach. A statistically significant decrease in PEF was found to be associated with increasing PM10 concentrations. Stronger associations were found for smokers than for nonsmokers, and for subjects reporting many chronic respiratory symptoms than for subjects reporting few such symptoms. Increased concentrations of iron tended to be associated with a decline in PEF, with a lag of 2 to 3 d, although the association did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

High dose fluticasone propionate, 1 mg daily, versus fluticasone propionate, 2 mg daily, or budesonide, 1.6 mg daily, in patients with chronic severe asthma. International Study Group

Airway inflammation is now regarded as fundamental in the pathogenesis of asthma and treatment with inhaled corticosteroids has proved effective. There is a need for drugs in this category with higher topical potency but fewer side-effects than those presently available. A double-blind, parallel group study was conducted in 671 patients with severe asthma (already taking between 0.8-2.0 mg of inhaled corticosteroid daily) to compare the safety and efficacy of 6 weeks of treatment with inhaled fluticasone propionate (FP), 1 mg daily, to fluticasone propionate, 2 mg daily, and budesonide (BUD), 1.6 mg daily, delivered via a metered-dose inhaler. Peak expiratory flow (PEF), asthma symptoms, and usage of rescue medication were recorded daily by the patient. At each clinic visit (-2, 0, 3 and 6 weeks) morning serum cortisol levels, bone markers and spirometry were assessed. The changes in mean morning PEF from baseline (weeks 1-6) were: FP 2 mg daily +24 l.min-1; FP 1 mg daily +21 l.min-1; BUD 1.6 mg daily +13 l.min-1. A similar rank order for the three treatments was seen for evening PEF, clinic spirometry, reduction of diurnal PEF variation, symptom scores, and requirement for rescue bronchodilators. The mean serum cortisol levels remained well within the normal range in all three groups. Analysis of the geometric mean cortisol ratio (treatment/baseline ratio after 6 weeks treatment) showed a changed rank order, the values being: FP 1 mg daily 1.04; BUD 1.6 mg daily 0.97; FP 2 mg daily 0.88.(ABSTRACT TRUNCATED AT 250 WORDS)

Transient changes in the pulmonary function of welders: a cross sectional study of Monday peak expiratory flow.

The aim was to compare the peak expiratory flow (PEF) of welders and non-welders over a 12 hour period from the start of work on Monday. The two study groups consisted of 20 welders and 20 non-welders, all men who had essentially never smoked, with no significant difference in age, height, ethnicity, or baseline spirometry between the groups. The PEF was measured for each welder before the start of work and 15 minutes, 30 minutes, and 1, 2, 4, 7, and 12 hours after the start of welding. The same method was applied to the non-welders, for whom a proxy time for the start of welding was used. The percentage change in baseline PEF was calculated for each subject at each of the recording times. The welder and non-welder group means for these results were significantly different at 15 minutes (p = 0.028). Also, the group mean for maximum fall in PEF (at any of the recording times during the 12 hour period) was significantly greater for the welders (p = 0.011). 50% of the welders (10/20), but only 5% of the non-welders (1/20), experienced a fall in PEF in excess of 5% (p = 0.0046). 25% of the welders (5/20) experienced drops of greater than 5% within the first 15 minutes. The results are suggestive of an immediate type reaction in welders, similar to that seen in some cases of occupational asthma, although not so severe. Studies to determine if these reactions reflect non-specific bronchial hyper-responsiveness would be useful. It is recommended that future studies also undertake breathing zone measurements to relate the response to particular constituents of the welding plume, especially the gases ozone and nitrogen dioxide.

Bronchoconstriction occurring during exercise in asthmatic subjects.

To demonstrate physiologic changes associated with asthma symptoms that many patients with asthma develop during exercise, we used sustained constant-load and interval exercise protocols with subjects breathing dry room temperature air. In constant-load exercise, subjects pedaled a stationary bicycle at 50% of their maximal power capacity for 36 min. In interval protocols, subjects pedaled at 60% of maximal capacity for 6 min and then 40% of maximal for 6 min; the 12-min cycle was repeated three times for a total exercise time of 36 min. Maximal expiratory flow versus volume maneuvers (MEFV) were obtained before, at 6-min intervals during, and at 5-min intervals after exercise. Changes in peak expiratory flow (PEF), forced expiratory volume in 1 s (FEV1), and forced expiratory flow at 50% of pre-exercise vital capacity (FEF50) were compared with pre-exercise values. Within 15 min after a maximal 1-min incremental exercise protocol, mean flows decreased compared with pre-exercise (PEF, mean -22%, range -46 to 5%; FEV1, mean -21%, range -42 to -3%; FEF50, mean -41%, range -80 to 3%; all p < 0.05). There were no significant changes in MEFV flows until 18 min of constant-load exercise, when FEV1 and FEF50 fell (FEV1, mean -6%, range -15 to 2%; FEF50, mean -14%, range -32 to 6%; both p < 0.05), although changes in PEF were minimal and were not significantly different compared with pre-exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Arterial Oxygen Saturation in Acute Childhood Asthma: Interpretation of Change Following Salbutamol Nebulization

The significance of change in SaO2 (δSaO2) following initial bronchodilator therapy in acute childhood asthma is not clear. Increase in SaO2 following initial bronchodilator therapy has been advocated as a measure of improvement in acute asthma. We hypothesized that the initial level of SaO2 would be inversely related to δSaO2 and would change very little for most children with mild or moderate asthma. Therefore, we measured SaO2 before and 30 min after salbutamol inhalation in 135 children (age range 1-14.5 yr) presenting to an emergency room with mild/moderate (SaO2 > 91%) and severe (SaO2 ≤ 91%) asthma. δSaO2 was inversely related to initial SaO2 (p < 0.01) with the greatest rise (7%) occurring in children with the lowest initial level (84%). SaO2 increased more in the severe group than the mild to moderate group—2.3% versus 0.6% respectively (p < 0.01)—although the change in peak expiratory flow (PEF) was similar for both groups. δSaO2 expressed as a percent of potential increase increased with decreasing SaO2 indicating that a small δSaO2 at a higher initial SaO2 could not be fully explained by a "ceiling" effect. We postulate that varying contributions of bronchoconstriction and ventilation perfusion inequality could explain this observation. Thus, salbutamol usually improves hypoxia in severe asthma, but SaO2 is not a reliable guide to response to initial bronchodilator therapy in the majority of children with asthma (SaO2≥91 %) as it usually increases little and does not reflect increase in PEF.

Circadian rhythm of peak expiratory flow in children passively exposed and not exposed to cigarette smoke.

Because airway calibre shows a circadian rhythm and since exposure to passive smoking reduced lung function this study was undertaken to investigate whether passive smoking affects the circadian rhythm of peak expiratory flow (PEF) in schoolchildren. Twenty schoolchildren (12 boys and 8 girls, aged 10-11 years) exposed to passive smoking were matched for sex, age, and height with 20 children who had not been exposed to cigarette smoke. Exposure to passive smoking was assessed by questionnaire and by urinary cotinine concentrations. A portable spirometer was used to measure PEF at 16:00, 20:00, 22:00, 06:00, 08:00, and 12:00 hours on a consecutive Saturday and Sunday. The circadian changes in PEF were measured by the cosinor method. Both groups showed diurnal fluctuation in PEF values with a noticeable circadian rhythm. PEF peaks were the same in the two groups and occurred around 15:00 hours. The cosinor mean was approximately 10% lower in children exposed to passive smoking and the amplitude was approximately 60% higher than in the unexposed children. Passive smoking in children is associated with a reduction in the cosinor mean and an increase in the amplitude of the normal circadian rhythm of airway calibre. This increased PEF rhythm amplitude may be considered as an early indication of airway obstruction.

Acute health effects of PM10 pollution on symptomatic and asymptomatic children.

This study assessed the association between daily changes in respiratory health and respirable particulate pollution (PM10) in Utah Valley during the winter of 1990-1991. During the study period, 24-h PM10 concentrations ranged from 7 to 251 micrograms/m3. Participants included symptomatic and asymptomatic samples of fifth- and sixth-grade students. Relatively small but statistically significant (p less than 0.01) negative associations between peak expiratory flow (PEF) and PM10 were observed for both the symptomatic and asymptomatic samples. The association was strongest for the symptomatic children. Large associations between the incidence of respiratory symptoms, especially cough, and PM10 pollution were also observed for both samples. Again the association was strongest for the symptomatic sample. Immediate and delayed PM10 effects were observed. Respiratory symptoms and PEF changes were more closely associated with 5-day moving-average PM10 levels than with concurrent-day levels. These associations were also observed at PM10 levels below the 24-h standard of 150 micrograms/m3. This study indicates that both symptomatic and asymptomatic children may suffer acute health effects of respirable particulate pollution, with symptomatic children suffering the most.

Intravenous magnesium for acute asthma: Failure to decrease emergency treatment duration or need for hospitalization

To evaluate the efficacy of routine early administration of i.v. magnesium to patients with acute asthma. Prospective, randomized clinical trial. Urban teaching hospital emergency department. One hundred twenty consecutive patients aged 18 to 65 years with acute asthma unresponsive to a single albuterol treatment. All patients received oxygen, 125 mg i.v. methylprednisolone, and hourly albuterol inhalation therapy. The study group also received 2 g i.v. magnesium sulfate infused over 20 minutes. Demographic and clinical characteristics were similar in both groups. Hospitalization was necessary in 13 of 58 patients who received magnesium (22%; 95% confidence intervals [CI], 13% to 32%) and 11 of 62 control patients (17%; 95% CI 10% to 26%; P = .523). Duration of ED treatment in discharged patients was 224 +/- 75 minutes in the magnesium group (95% CI, 208 to 240 minutes) and 228 +/- 90 minutes in the control group (95% CI, 209 to 247 minutes, P = .832). In addition, changes in peak expiratory flow were not statistically different. Routine early administration of IV magnesium in acute asthma does not alter treatment outcome.

An Epidemiologic Approach to the Study of Acute Reversible Health Effects in the Workplace

We present an epidemiologic approach for the study of the irritant effects of sodium borate exposure that can be used to study acute reversible health effects more generally. Acute irritant responses, such as symptoms of nasal irritation or cough, are subjective. They may, however, be accompanied by transient airway obstruction, which can be objectively measured by a change in peak expiratory flow (PEF) or forced expiratory volume in one second (FEV1). Because these physiologic responses are reversible and follow short-term peaks of exposure, they cannot be studied effectively using conventional epidemiologic methods of design and analysis. The proposed study design is a short-term prospective cohort study with frequently repeated measures of health effects and simultaneous measures of exposure. Because each subject passes through periods of high and low short-term exposure, the study has the form of a crossover design. This design permits each acute response to be linked to the corresponding short-term average exposure, providing the data necessary for dose-response analyses within subject. We present the results of the sodium borate study to illustrate the analysis of such data.

Budesonide and terbutaline or terbutaline alone in children with mild asthma: effects on bronchial hyperresponsiveness and diurnal variation in peak flow.

The effects of treatment with budesonide (200 micrograms twice daily) and terbutaline (500 micrograms four times daily) has been compared with the effects of placebo and terbutaline in 27 children with mild asthma, aged 7-14 years, in a double blind, randomised placebo controlled study over eight weeks. Bronchial responsiveness (PC20 histamine), lung function, the amplitude of diurnal variation in peak expiratory flow (PEF), and symptom scores were measured. Baseline FEV1 was over 70% predicted and PC20 histamine less than 8 mg/ml. Twelve children were treated with budesonide and terbutaline and 15 with placebo and terbutaline. After four and eight weeks of treatment the change in PC20 was significantly greater after budesonide and terbutaline than after terbutaline alone by 2.1 (95% CI 0.5-3.8) and 1.3 (95% CI 0.1-2.5) doubling doses respectively. Mean FEV1 did not change in either group. The change in afternoon and nocturnal PEF was significantly greater after budesonide and terbutaline than after terbutaline alone. The amplitude of diurnal variation in PEF did not change significantly in either group. Peak flow reversibility decreased in the budesonide group. There were no differences between treatments for cough and dyspnoea, but wheeze improved in the budesonide group. The children with mild asthma treated with budesonide and terbutaline showed improvement in bronchial responsiveness, afternoon and nocturnal PEF, and symptoms of wheeze and a fall in peak flow reversibility by comparison with those who received terbutaline alone.

Platelet activation in nocturnal asthma.

Platelet activation may be a factor in the bronchial hyperresponsiveness that characterises asthma. As hyperresponsiveness is increased at night, changes in platelet activation over 24 hours were related to the diurnal changes in peak expiratory flow and plasma catecholamine concentrations in five subjects with asthma and five normal subjects. The effect of muscarinic receptor blockade with intravenous atropine at 0400 hours on these measurements was also studied. Platelet activation, assessed as the ration of beta thromboglobulin to platelet factor 4, was highest when the peak expiratory flow rate was at its lowest in the asthmatic subjects. There was no correlation between platelet activation and plasma catecholamine concentrations. Intravenous atropine did not alter the ratio of beta thromboglobulin to platelet factor 4, suggesting that parasympathetic activity is not the cause of the increased platelet activation at night.