Peak Expiratory Flow Variability Research Articles

Factors affecting peak expiratory flow variability and bronchial reactivity in a random population sample.

Bronchial reactivity measurements are widely used in epidemiological studies to provide an objective marker of asthma. There are, however, several potential advantages of measuring peak expiratory flow (PEF) variability instead, particularly in large studies. PEF variability and bronchial reactivity were compared in a population sample to assess the relationships of the two measurements to factors known to be associated with airways disease, and to compare their response rates. Subjects aged 18-65 were randomly selected from the electoral register of an administrative area in eastern England and randomised to attend either for a bronchial challenge test measuring the provocative dose of methacholine producing a 20% fall in FEV1 (PD20), or to measure PEF at two hourly intervals during waking hours for one week. Skin tests with common allergens were performed and a smoking history obtained. PEF variability was expressed as the amplitude % mean (highest - lowest x 100/mean). A total of 273 subjects (69%) collected a PEF meter but a completed record sheet was returned by only 247 (62%); this was still significantly more than the 202 subjects (54%) who attended for and successfully completed a challenge test. Amplitude % mean was higher in women than in men (9.7% v 8.5%). In multiple regression analysis amplitude % mean increased significantly with age, mean skin weal diameter, and with current smoking. The odds of having a PD20 below 24.5 mumol increased with mean skin weal diameter and were greater in current smokers. Neither age nor sex had a significant effect on bronchial reactivity but there were significant interactions between age and the effects of both smoking and atopy. The higher response rate associated with the use of PEF variability measurement, and the association with factors implicated in the pathogenesis of airways disease, suggest that PEF variability would be a useful measurement to employ in epidemiological studies.

Dietary Fish Oil Effects on Seasonal Hay Fever and Asthma in Pollen-sensitive Subjects

The effects of taking 18 capsules a day of Max-EPA (3.2 g/day eicosapentaenoic acid) on clinical symptoms and bronchial hyperresponsiveness were studied in pollen-sensitive subjects over a pollen season in a parallel, double-blind, placebo-controlled (olive oil) fashion. The study was conducted over the 1990 and 1991 pollen seasons in London, England. A total of 37 nonsmoking pollen-sensitive asthmatic subjects were entered into the trial, and 25 completed the 6-month study period over the 2 yr. The preseasonal geometric mean PD35 SGaw of histamine for the fish oil (n = 12) and placebo (n = 9) groups were 0.62 and 0.42 mumol, respectively. During the middle of the pollen season, histamine PD35 SGaw fell significantly for both the fish oil (0.11 mumol, p < 0.0001) and placebo groups (0.10 mumol, p < 0.007), indicating increased bronchial reactivity compared with preseasonal values, but there was no significant difference between the groups. Similarly, morning and evening peak expiratory flow (PEF), diurnal variability in PEF, nocturnal cough and wheeze, daytime wheeze, and activity, as well as nasal symptoms and increased usage of medication, were not significantly different between the groups. Compliance was confirmed by neutrophil and plasma phospholipid analysis, which showed significant rises in eicosapentaenoic acid content in the fish oil group but not in the placebo group. We conclude that dietary fish oil supplementation does not prevent seasonal hay fever and asthma in pollen-sensitive subjects during the pollen season.

Pulmonary function in adolescents with childhood asthma.

The aim of this study was to determine the pulmonary function in former and present asthmatics. We examined 77 persons aged 12-24 years, classified into four groups: 1) healthy subjects (controls) (n = 19), 2) former asthmatics (n = 19), 3) present mild asthmatics (n = 20), and 4) present severe asthmatics (n = 19). Although exhibiting no respiratory symptoms, former asthmatics had reduced airflow values measured by FEV1 (median (range) 89.7 (83-99) vs 101.4 (91-110)) and MEF25 (76.5 (68-94) vs 103.0 (97-124)), as compared with controls. Furthermore, former asthmatics had significantly increased PEF variability, as compared with controls, whereas no significant differences were found in static lung parameters, i.e. total lung capacity and residual volume, as compared with controls. In conclusion, former asthmatics, although now exhibiting no respiratory symptoms, were found to have obstructive airflow limitation, increased bronchial responsiveness, and normal lung volumes.

Relation between response to exercise and diurnal variability of peak expiratory flow in primary school children.

Variability in peak expiratory flow (PEF) has been proposed as a simple method of screening for asthma in epidemiological studies. This study was designed to assess whether the bronchial response to exercise and the diurnal variation in PEF identified the same subjects. Bronchial response to a free running exercise test was assessed in a cohort of 918 seven year old children and was compared with variability of PEF as assessed by twice daily recordings for a one week period. Mini Wright peak flow meters were used throughout the study. Baseline PEFs of both tests were highly correlated but there was no significant correlation between a response to exercise and variability of PEF. Of 33 children with a physician's diagnosis of asthma, 18 had at least one abnormal test, but only five children were abnormal in both tests, showing that the tests did not identify the same subjects. Increased variability of PEF, as well as a response to exercise, was associated with respiratory symptoms, but only a response to exercise was closely associated with atopy (defined as a positive skin test to any of seven aero-allergens).

Day-night variation of airways status in sympathomimetic- and theophylline-treated asthma patients

Eleven diurnally active asthma patients having a history of nocturnal asthma and treated regularly with albuterol or metaproterenol alone or with twice-daily sustained-release theophylline were evaluated for day-night pattern in peak expiratory flow (PEF) and use of supplemental beta-agonist aerosol for relief of acute asthma. Overall, significant day-night variation was observed in the supplemental use of beta-agonist medication and in airway patency. The patients managed by albuterol or metaproterenol alone used supplemental beta-agonist medication significantly more between 4 AM and 8 AM and also 8 PM and midnight in comparison to 4 PM to 8 PM; this was not true for those treated with both theophylline and beta-agonist aerosol. In patients taking a beta-agonist bronchodilator, the 24-hour mean PEF was greater than in those who also took theophylline, but the day-night variation in PEF was comparable. Supplemental isoproterenol use was significantly correlated with circadian amplitude of the PEF rhythm, but not with the 24-hour mean PEF. The greater the day-night variation in PEF, the greater the reliance on a supplemental beta-agonist bronchodilator.

Diary keeping in asthma: comparison of written and electronic methods.

To determine the extent to which symptom diaries of asthmatic patients are inaccurate or based on retrospective recall. Comparison of electronic and pencil and paper diaries. Both forms were completed twice daily at home for 14 days. Outpatient clinic. 24 asthmatic outpatients also tested for severity of asthma and for anxiety. More sessions were missed in the evening than in the morning for both types of diaries. Significantly more retrospective entries were made in the evening (26 entries, 14 patients) than in the morning (6 entries, 3 patients). Discrepant entries of peak expiratory flow accounted for 15% of those made on the appropriate day, and three quarters of patients made at least one discrepant entry. Variation in peak expiratory flow was significantly related to number of discrepancies and number of missing days, and anxiety score was significantly related to number of missing days. About a fifth of written entries may have errors. Poor diary completion may result from having unreasonable expectations of patients and giving incomplete instructions. Electronic, time coded diaries could ensure better quality of records.

Quantitative versus qualitative analysis of peak expiratory flow in occupational asthma.

Peak expiratory flow rates (PEF) are often used to confirm the diagnosis of occupational asthma. The records are usually analysed qualitatively, and this may lead to interobserver disagreement. In this study the diagnostic value of a qualitative assessment of change in PEF was compared with objective measures of change in PEF and the results of a specific inhalation challenge test with plicatic acid. Twenty five patients with possible red cedar asthma recorded PEF six times a day for three weeks at work and for two weeks away from work and underwent a challenge test with plicatic acid at the end of the recording period. Patients were considered to have cedar asthma if the FEV1 after inhalation of plicatic acid was 15% or more below that on the control day. PEF was plotted against time and assessed qualitatively by three physicians. The graph was considered positive for cedar asthma if two of the three physicians agreed that PEF was lower at work than away from work. The 95% confidence interval for variation in PEF between periods at work and away from work was also obtained from 15 asthmatic patients without occupational asthma. Differences in PEF between periods at work and away from work were considered positive for occupational asthma in the patients exposed to cedar when they were outside the 95% confidence interval for variations in PEF in the 15 patients whose asthma was nonoccupational. Of the 25 men studied, 15 had a positive response to plicatic acid. The qualitative PEF analysis had a sensitivity of 87% and a specificity of 90% in confirming red cedar asthma as diagnosed by the specific challenge test. Among the objective methods tested, only the difference in mean PEF between the maximum PEF at weekends and the minimum PEF on working days had a sensitivity (93%) greater than that of the qualitative method and a similar specificity. The qualitative assessment of PEF is a good diagnostic test for cedar asthma. Only one objective method of PEF analysis proved to be slightly more sensitive than the qualitative method and similar in specificity.

The accuracy of portable peak flow meters.

The variability of peak expiratory flow (PEF) is now commonly used in the diagnosis and management of asthma. It is essential for PEF meters to have a linear response in order to obtain an unbiased measurement of PEF variability. As the accuracy and linearity of portable PEF meters have not been rigorously tested in recent years this aspect of their performance has been investigated. The response of several portable PEF meters was tested with absolute standards of flow generated by a computer driven, servo controlled pump and their response was compared with that of a pneumotachograph. For each device tested the readings were highly repeatable to within the limits of accuracy with which the pointer position can be assessed by eye. The between instrument variation in reading for six identical devices expressed as a 95% confidence limit was, on average across the range of flows, +/- 8.5 l/min for the Mini-Wright, +/- 7.9 l/min for the Vitalograph, and +/- 6.4 l/min for the Ferraris. PEF meters based on the Wright meter all had similar error profiles with overreading of up to 80 l/min in the mid flow range from 300 to 500 l/min. This overreading was greatest for the Mini-Wright and Ferraris devices, and less so for the original Wright and Vitalograph meters. A Micro-Medical Turbine meter was accurate up to 400 l/min and then began to underread by up to 60 l/min at 720 l/min. For the low range devices the Vitalograph device was accurate to within 10 l/min up to 200 l/min, with the Mini-Wright overreading by up to 30 l/min above 150 l/min. Although the Mini-Wright, Ferraris, and Vitalograph meters gave remarkably repeatable results their error profiles for the full range meters will lead to important errors in recording PEF variability. This may lead to incorrect diagnosis and bias in implementing strategies of asthma treatment based on PEF measurement.

Blood eosinophil numbers and activity during 24 hours: Effects of treatment with budesonide and bambuterol

The effects of the inhaled corticosteroid budesonide and the oral long-acting β-agonist bambuterol on circadian variation of blood eosinophil numbers, serum levels of eosinophil cationic protein (ECP), serum eosinophil chemotactic activity (ECA), and serum neutrophil chemotactic activity (NCA) were studied in two groups of patients with allergic asthma. Group 1 ( n = 8) had a circadian variation of peak expiratory flow (PEF) 15% or greater, and group 2 ( n = 9) had a circadian PEF variation less than 15%. Both groups were randomized and crossover treated for 4 weeks with (A) 0.4 mg budesonide at 8 am and 8 pm, (B) 20 mg bambuterol at 8 pm, and (C) placebo. At the end of each period blood eosinophil numbers, ECP, ECA, and NCA were measured during 24 hours at 4-hour intervals. No significant differences in the inflammatory parameters could be observed between the groups, although eosinophil numbers tended to be higher in group 1 than in group 2. Highest eosinophil numbers were observed at night. Budesonide reduced both eosinophil numbers and ECP levels, especially at night; bambuterol had no effect on both variables. No circadian variation or treatment effects were observed for ECA and NCA. This study suggests a role for the eosinophil in the nocturnal worsening of asthma, and it demonstrates that budesonide produces, in contrast to bambuterol, a reduction of (nocturnal) eosinophil numbers and activity.

Effects of budesonide and bambuterol on circadian variation of airway responsiveness and nocturnal symptoms of asthma

Effects of the inhaled corticosteroid budesonide and the oral beta-agonist bambuterol on the nocturnal worsening of asthma were studied in patients with allergic asthma with a circadian peak expiratory flow variation greater than or equal to 15% (group 1, n = 8) and less than 15% (group 2, n = 9). Airflow limitation and airway responsiveness to histamine were measured during 24 hours after 4 weeks of treatment with (A) 0.4 mg budesonide at 8 AM and 8 PM, (B) 20 mg bambuterol at 8 PM, and (C) placebo, in a randomized, crossover design. Patients in group 1 had worse nocturnal symptom scores and a greater airway responsiveness than patients in group 2; in addition, patients in group 1 had a larger increase in responsiveness during the night (1.1 versus 0.6 doubling concentrations [DC]). Both budesonide and bambuterol improved responsiveness more at night than during daytime, thus decreasing circadian variation: at 4 AM, increases in PC20 were 2.0 DC after budesonide and 0.8 DC after bambuterol, compared with placebo. Bambuterol reduced circadian variation in FEV1, but in contrast to budesonide, did not improve 24-hour mean levels of FEV1 and PC20. Both drugs beneficially influenced nocturnal symptoms; the effects of budesonide were stronger than those of bambuterol. Our findings demonstrate that budesonide and bambuterol reduce nocturnal airway responsiveness and asthma symptoms and suggest a relationship between the degree of airway responsiveness and the presence of nocturnal symptoms of asthma.

Peak expiratory flow variability and bronchial responsiveness to methacholine. An epidemiologic study in 117 workers.

We studied the relationships between peak expiratory flow (PEF) variability and bronchial responsiveness to methacholine in 117 workers attending the annual compulsory examination (mean age, 38.7 yr +/- 9.5; men, 86.3%). Subjects recorded their highest PEF out of three, every 3 waking hours (i.e., five times a day) for 7 days, each using a newly purchased Vitalograph peak flow meter, and underwent methacholine challenge tests with a maximal cumulative dose of 1,200 micrograms. Those with a FEV1 fall of 15% or more were considered as reactors. The variability of PEF was expressed as the amplitude percent mean, calculated from daily amplitude (highest-lowest reading/mean reading of the day x 100), averaged over 6 days, from the second to the seventh. This index had a continuous distribution, skewed towards the greatest amplitudes, and correlated negatively with FEV1 (r = -0.25, p = 0.01). Subjects with asthma (n = 8) had greater variations. In the 109 nonasthmatics, greater variability was observed in subjects with wheeze apart from colds, breathlessness, or hay fever; the average amplitude was greater in reactors than in nonreactors to methacholine (16.9% versus 9.3%, p less than 0.001). The subjects with excessive PEF variability were all methacholine reactors, but they were only a subgroup of the reactors. These results provide evidence that excessive PEF variability is an indicator of bronchial hyperresponsiveness to methacholine in a population sample.

Blood eosinophil count as risk factor for relapse in acute asthma

In this retrospective investigation comprising 54 adult patients included in two studies of the treatment of acute asthma, the risk of relapse was studied. The set of variables that best predicted the length of time before a new asthmatic attack comprised blood eosinophil count (P less than 0.001), FEV1 on arrival (P less than 0.001) and increased medication on discharge (P less than 0.01). The set of variables that best predicted the number of new attacks during a period of 1 yr consisted of eosinophil count (P less than 0.001), FEV1 (P less than 0.001), increased medication on discharge, age and breathing rate on arrival (P less than 0.05). Patients with an eosinophil count of more than 500 x 10(6) l-1 and a FEV1 of less tha 1.0 l ran a six-fold greater risk of returning with a new attack within 1 month than patients with lower eosinophil count and higher FEV1. No significant correlation was found between post-treatment PEF variation and relapse in acute asthma.

Bronchial responsiveness, oscillations of peak flow rate and symptoms in patients with mitral stenosis

To better characterize airway hyperresponsiveness reported in cardiac patients questionnaire-recorded symptoms, bronchial responsiveness to methacholine (Mch) and to ultrasonically nebulized distilled water (UNDW), diurnal oscillations of peak expiratory flow (PEF) rate were evaluated in 32 patients with moderate mitral stenosis. Twenty patients were responsive to Mch (defined as provocative dose producing a 20% fall in forced expiratory volume in one second (PD20 FEV1) less than 3.2 mg) (geometric mean PD20 FEV1 851 +/- 154 micrograms SE). Only two patients showed a fall in FEV1 greater than 20% after UNDW challenge. Patients responsive to Mch challenge had lower FEV1 as percentage of vital capacity (FEV1/VC) (80 +/- 4.8 vs 83 +/- 3.8%, p less than 0.05), higher coefficient of variation of PEF (CV-PEF) (7.1 +/- 2.8 vs 5 +/- 2.4, p less than 0.05) and higher prevalence of wheeze (70 vs 25%, p less than 0.05) in comparison with patients non-responsive to Mch challenge. CV-PEF was significantly related to FEV1 (r = 0.347, p less than 0.05) and maximal expiratory flow at 50% expired volume (MEF50) (r = 0.405, p less than 0.05). The probability of responding to Mch bronchial challenge increased proportionally with the increase in CV-PEF and the decrease in FEV1, FEV1/VC and MEF50. Airway hyperresponsiveness of patients with mitral stenosis seems to be more similar to that reported in bronchitic than in asthmatic patients.

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.

Relationship of Airway Hyperresponsiveness to Respiratory Symptoms and Diurnal Peak Flow Variation in Patients with Obstructive Lung Disease

This study reports on the relationship of airway hyperresponsiveness (AH) with respiratory symptoms and diurnal peak flow expiratory (PEF) variation in 221 hyperresponsive patients with moderately severe airways obstruction. The disease was in a stable phase in all patients. Closely adhering to the American Thoracic Society criteria, patients were divided into three syndrome diagnoses based on a standardized history: asthma (n = 81), asthmatic bronchitis (AB, n = 69), and chronic obstructive pulmonary disease [( COPD] n = 44); 27 subjects could not be placed in any group. Mean (+/- SEM) log2 PC20 histamine values were significantly lower in the asthmatic group (-2.77 +/- 0.20 mg/ml) than in the COPD (-0.89 +/- 0.29 mg/ml) and AB groups (-1.37 +/- 0.25 mg/ml; one-way ANOVA, p less than 0.001). However, considerable overlap of individual responses existed. Differences between the groups could not be attributed to differences in prechallenge FEV1 levels. For every level of FEV1, asthmatic subjects were more hyperresponsive than patients with COPD. The dependence of PC20 on prechallenge FEV1 was comparable in all groups. There was a significant correlation between the degree of AH and diurnal PEF variation (rho = -0.401, p less than 0.001), which was stronger in asthma (rho = -0.409) than in COPD (rho = -0.325). Despite this obvious association, a wide range of diurnal PEF variation values existed for every level of PC20, indicating that PEF variability and AH are not interchangeable. The relationships between symptoms and both AH levels and PEF variation were weak. No significant differences were found between syndrome diagnosis groups with respect to diurnal PEF variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Atopy on the Natural History of Symptoms, Peak Expiratory Flow, and Bronchial Responsiveness in 7- and 8-Year-Old Children with Cough and Wheeze: A 12-Month Longitudinal Study

Recurrent lower respiratory tract symptoms are common and disabling in childhood, but little is known of their natural history and relationship to asthma. We report a 12-month longitudinal study designed to determine the influence of atopy on respiratory symptoms and bronchial responsiveness in 7- and 8-yr-old children. A postal questionnaire inquiring into the presence of respiratory symptoms was sent to 3,698 children aged 7 and 8 yr. Those reporting either current wheeze (14.8%) or current cough in the absence of wheeze (12.8%) were randomized, and a sample was invited to attend for skin testing. The following groups of symptomatic children entered the longitudinal study: 48 atopic children with cough, 48 atopic children with wheeze, 48 nonatopic children with cough, and 48 nonatopic children with wheeze. All children recorded twice daily the best of three peak expiratory flow (PEF) measurements and completed a 10-point symptom score card, each day for 1 yr. They also recorded all treatment taken and made a note of relevant life events. Each child was seen monthly for general assessment and for measurement of methacholine bronchial responsiveness. Despite the arduous nature of the study 183 of the 192 children (95.3%) successfully completed the 12 months of observation. Symptom groups were compared with regard to FEV1, bronchial responsiveness, symptom chronicity and severity, and diurnal and day-to-day variation in PEF. Atopy was associated with a lower FEV1, increased prevalence of bronchial hyperresponsiveness, greater within-day and between-day variation in PEF, and greater severity of respiratory symptoms compared with the absence of atopy. Wheeze was associated with lower FEV1, increased prevalence of bronchial hyperresponsiveness, greater within-day and between-day variation in PEF1 and greater severity of respiratory symptoms compared with cough [corrected].

Pulmonary Function in a Hospital Population of Asthmatic Children

Traditionally, assessment of control of pediatric asthma has relied on symptoms reported by the child and his or her family, and on clinical examination at office visits. A survey of the pulmonary function of 100 clinically stable asthmatic children, recruited from the outpatient clinics of the Royal Children's Hospital, Melbourne, Australia for a clinical drug trial was performed. Correlation of baseline pulmonary function with symptom scores recorded at home and home monitoring of peak expiratory flow variability (PEFV) found that a third of these clinically stable asthmatic children had an abnormal FEV1 and half had an abnormal FEF25-75; however, there was no correlation between symptom scores and FEV1 or PEFV. Objective measurements of pulmonary function are needed to ensure good asthma control. Home monitoring of peak expiratory flow can provide a valuable aid for the management of pediatric asthma.

The distribution of peak expiratory flow variability in a population sample.

Although serial peak expiratory flow (PEF) measurements are often used to assess the variability of airflow obstruction, the range of values to be expected in the general population has never been defined, nor is there any consensus as to how PEF variability should be expressed. We have compared PEF recordings made by 121 subjects selected at random from the population of a small town (Group A) and 221 subjects selected because of wheeze in the last year (Group B). Subjects were asked to record PEF every 2 h during waking hours for 7 days using a mini-Wright peak flow meter. Seven indices of PEF variability were derived for each subject and the range for each index determined. All indices showed a positively skewed distribution in the random sample. Two variability indices, standard deviation percent mean and amplitude percent mean, provided the greatest separation between subjects with both a diagnosis of asthma and wheeze in the last year and subjects with neither feature and also provided the highest intra-class correlation coefficients. We conclude that amplitude percent mean and standard deviation percent mean provide the best means of expressing PEF variability for epidemiological purposes, but that amplitude percent mean is more easily derived and appears to be the index of choice. PEF variability has a continuous distribution in the general population and no clear-cut division between asthmatic and nonasthmatic subjects can be defined.

Fatal asthma in a young patient with severe bronchial hyperresponsiveness but stable peak flow records

We report the sudden death of a 16 yr old boy with asthma. At presentation, the patient had symptoms of active asthma, mild bronchoconstriction, severe airway hyperresponsiveness to methacholine, and increased variability of peak expiratory flow records. After the patient was placed on inhaled beclomethasone (1 mg b.i.d preceded by inhaled fenoterol 0.4 mg b.i.d) he rapidly felt better, lung function improved, but airway responsiveness remained severe. Four months later, on the day he died, he was well until a fatal attack of asthma occurred around midnight without identifiable precipitating factors. Taken to hospital, he was dead on arrival. Necroscopy and microscopy showed the characteristic features of asthma death. This case report suggests that; a) asthma death may occur suddenly and unexpectedly; b) asthma death may not be prevented by long-term treatment with high-dose inhaled beclomethasone; c) severe bronchial hyperresponsiveness, even in the presence of stable peak flow records, may identify asthmatic patients at risk of sudden death.

Nonspecific bronchial reactivity and its relationship to the clinical expression of asthma. A longitudinal study.

The contribution of nonspecific bronchial reactivity to the day-to-day clinical expression of asthma is uncertain. We have examined this relationship in a longitudinal study of eight children and 12 adults. Measurements of reactivity to methacholine were made every 2 to 3 wk over a period of 12 to 18 months, deriving the dose that caused a 20% fall in FEV1 (PD20). Throughout the study, all patients kept a daily record of symptoms and treatment and twice daily measurements of peak expiratory flow (PEF). A significant relationship was found between subjects' overall reactivity (median PD20) and both their average day-to-day variation in morning PEF (Spearman's rho = -0.53, p = 0.016) and diurnal variation in PEF (Spearman's rho = -0.60, p = 0.004). However, examining the temporal relationship between reactivity and asthma within subjects, individual PD20 measurements were not consistently related to concurrent asthma severity: in only six subjects did changes in PD20 generally reflect simultaneous trends in symptoms or PEF. In several patients, exacerbations of asthma occurred in the absence of bronchial hyperreactivity (PD20 greater than 12.8 mumol). We conclude that nonspecific bronchial reactivity is only one mechanism underlying airflow obstruction in asthma, and that its relationship to the clinical state of asthma is not sufficiently close to be of practical clinical use.