Comparison of peak expiratory flow variability between workers with work-exacerbated asthma and occupational asthma

BACKGROUND: Peak expiratory flow (PEF) monitoring is frequently used to diagnose occupational asthma (OA). The variability of PEF between periods at work and away from work has not been described in workers with work-exacerbated asthma (WEA). We sought to assess and compare the diurnal variability of PEF during periods at and away from work between subjects with OA and WEA. METHODS: Workers referred for work-related asthma underwent PEF monitoring for 2 weeks at and away from work. The diagnostic of OA or WEA was subsequently made according to the respective positivity or negativity of the specific inhalation challenges. PEF mean diurnal variability was calculated during periods at and away from work. PEF graphs were also interpreted using direct visual analysis by five observers and using a computer program (Oasys-2, Expert System ) [available at: http://www.occupationalasthma.com]. RESULTS: Thirty-four subjects were investigated (WEA, n = 15; OA, n = 19). There was a greater variability of PEF at work than away from work in both OA (19.8 +/- 8.7% vs 10.7 +/- 6.3%, p < 0.001) and WEA (14.2 +/- 4.8% vs 10.6 +/- 5.6%, p = 0.02). However, the magnitude of the variability was higher in OA than in WEA (p = 0.02). The visual interpretation of PEF or the Oasys-2 program failed to distinguish WEA from OA. CONCLUSION: Although workers with OA showed a higher PEF variability than workers with WEA when at work, clinicians were unable to reliably differentiate OA from WEA using the visual interpretation of PEF graphs or the computerized analysis.     

Substance P-immunoreactive nerves in endobronchial biopsies in cough-variant asthma and classic asthma

BACKGROUND: Unlike classic asthma, cough-variant asthma does not show any evidence of airway obstruction. The main symptom is a dry cough with little known pathophysiology. Hypersensitivity of the cough receptors in cough-variant asthma and an increase in the sensory nerve density of the airway epithelium in persistent dry cough patients have been reported. Therefore, it is possible that there is a higher sensory nerve density in cough-variant asthma patients than in classic asthma patients. OBJECTIVES: This study was undertaken to compare the substance P (SP)-immunoreactive nerve density in mucosal biopsies of cough-variant asthma patients, classic asthma patients, and in control subjects. METHODS: Bronchoscopic biopsies were performed in 6 cough-variant asthma patients, 14 classic asthma patients, and 5 normal controls. The tissues obtained were stained immunohistochemically. The SP-immunoreactive nerve density was measured in the bronchial epithelium using a light microscope at 400 x magnification. RESULTS: SP- immunoreactive nerve density for the cough-variant asthma group was significantly higher than that of the classic asthma group (p = 0.001), and of the normal control group (p = 0.006). CONCLUSIONS: It is possible that a sensory nerve abnormality within the airway may be related to hypersensitivity of the cough receptor, and that this may be one of the pathophysiologies of cough-variant asthma.     

Use of peak flow variability and methacholine responsiveness in predicting changes from pre-test diagnosis of asthma.

Asthma is usually diagnosed clinically. This study investigated how methacholine challenge and peak expiratory flow monitoring influenced change from a pretest clinical diagnosis. Records of 132 patients referred with respiratory symptoms, who subsequently had reliable measurements of both airway responsiveness (provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1 (PC20)) and peak expiratory flow variability (PEFV) were reviewed. Initial and final diagnoses for each patient were classified as: a) definite asthma; b) possible asthma; and c) definitely not asthma. The predictive value of PEFV and PC20 regarding overall change from pre- to post-test diagnosis, change from initial diagnosis of possible or definitely not asthma, and change from initial diagnosis of definite asthma, were tested by multiple logistic regression analysis. Odds ratios for PC20 were expressed per doubling dose, and for PEFV per 5% variability. Clinical diagnosis of definite asthma and definitely not asthma were confirmed in 70% and 79% respectively. PC20, but not PEFV, predicted an overall change between pre- and post-test diagnosis. Both PC20 and PEFV independently predicted change to definite asthma. PEFV and interaction between PC20 and PEFV predicted a change in those whose initial diagnosis was definite asthma. Although both measurements showed a significant correlation, there was poor agreement between positive tests. Both peak expiratory flow variability and provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second influence diagnostic decision-making in patients with a high pre-test probability of asthma.     

Relationship of non-specific airway hyper-responsiveness (AHR) to measures of peak expiratory flow (PEF) variability

Background: The relationship between airway hyper-responsiveness (AHR) and clinical asthma remains controversial and unclear. Aims: To test the hypothesis that serial measures of variability of peak expiratory flow rate (PEF) correlate with serial measures of AHR, and to determine which mathematical expression of variability provides the best correlation. Methods: A longitudinal study over 180 days of 20 atopic, moderately severe asthmatics was undertaken. A diary of medication use and morning and evening PEFR before and after (3 agonist was kept and AHR (PD₂₀ histamine) was measured at three-weekly intervals. Using group data (128 sets) In PD₂₀ was correlated with various measures of PEF variability over 9 days. Results: Within the group there was a weak but highly statistically significant correlation between AHR and measures of PEF variability - the strongest correlation being with mean morning PEF. Within individual subjects, however, the correlation was not a consistent finding and only four patients had a statistically significant relationship (p<0.05) between AHR and mean morning PEF. Conclusions: These results suggest that while PEF variability may reflect AHR for the purposes of epidemiologic studies, it is unlikely to be useful as a simple ‘non-invasive’ means of assessing AHR in individual patients. More complex measures of PEF variability do not have an advantage over simpler measures such as mean morning PEF.     

Normal airway responsiveness to methacholine in cardiac asthma

Cardiac asthma has been used as a synonym for episodes of cough, dyspnea, and wheezing caused by left ventricular dysfunction. The similarity of the terms bronchial asthma and cardiac asthma, and the observed symptoms of each disease implies a common pathophysiology. Bronchial asthma is characterized pathologically by airway narrowing, inflammation, edema, and obstruction by mucus. Bronchial asthma is defined as increased responsiveness of the tracheobronchial tree, which is manifested clinically as reversible expiratory airflow obstruction. The classic symptoms of bronchial asthma are cough, dyspnea, and wheezing. Cardiac asthma produces the same symptoms, but the pathophysiology producing these symptoms is not well described. We describe two patients with cardiac asthma who failed to demonstrate airway hyperresponsiveness to nonspecific bronchoprovocation testing and we postulate that these patients' symptoms were produced exclusively by left ventricular failure.     

A comparison of the individual best versus the predicted peak expiratory flow in patients with chronic asthma.

In the management of patients with asthma, peak expiratory flow (PEF) monitoring is used and based on the individual best PEF or the predicted PEE Recent international guidelines have recommended the use of the best PEF rather than the predicted PEF as an index, although there is little evidence to support which index is more appropriate. Therefore, we investigated the relationship between the best PEF and the predicted PEF in 166 consecutive asthmatic patients to see which value would be the better basis for their PEF monitoring. All eligible patients had undergone treatment for their asthma for over 6 months and were asked to measure their PEF four times a day. The best PEF was defined as the maximal PEF achieved at any time from all previous measurements. The predicted PEF was calculated based on a report on the standard PEF in normal Japanese subjects. The mean best PEF was significantly higher than the mean predicted PEF (p < 0.001). There was a strong correlation between the best PEF and the predicted PEF (r = 0.77, p < 0.001). However, in 72 patients (43%) the ratio of the best PEF to the predicted PEF was over 110%, and in 20 patients (12%) the ratio was lower than 90%. The best PEF was higher than the predicted PEF in 76 patients (46%) and lower in 22 patients (13%) by more than 50 L/min. These results suggest that when the predicted PEF was used as the index, pulmonary function was either underestimated or overestimated in over half of these patients. Therefore, the best PEF may be the better index for the management of patients with 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.     

Effects of inactivated influenza virus vaccination on bronchial reactivity symptom scores and peak expiratory flow variability in patients with asthma.

Even though annual influenza vaccinations are recommended by many authorities, some doctors may be reluctant to vaccinate asthmatic patients because of the risk of inducing bronchial reactivity and exacerbating the asthma. In this study we investigated the effect of inactivated trivalent influenza vaccine on airway reactivity symptom scores and peak expiratory flow (PEF) variability in 24 patients with mild stable asthma. Baseline spirometry and methacholine challenge tests were performed on all patients. Patients were then asked to record their peak expiratory flow every morning and evening, complete daily symptom score charts (morning tightness, daytime asthma, cough, and night asthma), and note bronchodilator usage for 1 week. After baseline measurements, the patients were allocated to inactivated vaccine and placebo in a random and single-blind manner. The lung function measurements and methacholine challenge tests were repeated 1 week after vaccination and placebo administration at the same time of day. PD20 (mg/mL) methacholine doses were 3.06+/-3.0 mg/mL before vaccination, 2.96+/-3.2 mg/mL after vaccination, and 2.76+/-2.91 mg/mL after placebo administration. There were no significant changes in PD20 methacholine after influenza vaccination (p>0.05). There were also no significant changes in symptom scores, bronchodilator usage, and PEFR after vaccination (p>0.05). None of the patients experienced significant local or systemic side effects after vaccination. Immunization with inactivated influenza vaccine does not induce clinical exacerbations of asthma or airway hyperreactivity in patients with mild 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.     

Methacholine and adenosine 5'-monophosphate challenges in preschool children with cough-variant and classic asthma

Bronchial challenge with different stimuli provides different information and may be used as an adjunct to understand the pathophysiology of cough variant asthma (CVA) in young children in whom the mechanism of disease is still unresolved. This study was designed to investigate the hypothesis that airway hyperresponsiveness (AHR) to methacholine and adenosine 5'-monophosphate (AMP) is similar in preschool children with CVA and classic asthma. We examined airway response to methacholine and AMP in well-defined 3-6-year-old children with CVA (n = 18), classic persistent asthma (n = 31), and healthy controls (n = 10) by transcutaneous oxygen monitorization. The number of AMP responsive children was significantly lower in the group with CVA (38.9%) than classic persistent asthma (67.7%) (P = 0.049). Mean provocative concentration of AMP causing a 15% fall in transcutaneous oxygen tension (PC15PtcO2 AMP) in children with CVA and classic persistent asthma were 234.58 and 36.35 mg/ml, respectively (P = 0.001). None of the healthy children in the control group responded to AMP. The severity of methacholine responsiveness was found similar in CVA and classic persistent asthma groups (P = 0.738). Although both asthma groups showed a similar pattern in methacholine responsiveness, preschool children with CVA were found to differ from children with classic persistent asthma with regard to response profiles to AMP challenge which may point to different pathophysiologic mechanisms of CVA in the young age group.     

Maximal airway response in adolescents with long-term asthma remission and persisting airway hypersensitivity: its profile and the effect of inhaled corticosteroids

BACKGROUND: Many children with asthma go into long-term clinical remission at adolescence, but bronchial hyperresponsiveness (BHR) persists in some of these subjects. BHR in asthma is characterized by an increase in sensitivity and in maximal airway response to bronchoconstrictor stimuli. OBJECTIVE: The aims of this study were to compare the profiles of maximal airway response between adolescents with asthma remission and adolescents with symptomatic asthma to a similar degree of airway hypersensitivity, and to determine whether maximal airway response in adolescents with asthma remission is reduced by prolonged treatment with inhaled corticosteroids. METHODS: A high-dose methacholine inhalation test was performed in 46 adolescents with long-term asthma remission (remission group) and 44 adolescents with symptomatic asthma (symptomatic group). Subjects exhibiting a maximal response plateau in the remission group were administered inhaled budesonide (400 microg bid, budesonide/remission group, n = 15) or identical placebo (placebo/remission group, n = 15) for 6 months, and the subjects in the symptomatic group were administered the same regimen of budesonide (budesonide/symptomatic group, n = 17). The plateau level was measured after 3 months and 6 months of treatment. RESULTS: Thirty-four subjects (73.9%) in the remission group featured a maximal response plateau on the dose-response curve to methacholine, whereas 19 subjects (43.2%) in the symptomatic group had a plateau (p = 0.003). In neither the placebo/remission group nor the budesonide/remission group did the plateau level change significantly over the 6-month period, whereas budesonide markedly decreased the level in the budesonide/symptomatic group. CONCLUSION: The difference in frequency of detection of a plateau between the remission group and the symptomatic group, as well as the difference in its response to treatment with budesonide between the two groups, suggests that inflammatory changes impact the maximal airway response in symptomatic asthmatic adolescents but not in adolescents with asthma remission.     

呼气相气道内负压法检测呼气流速受限应用于儿童支气管激发试验的可行性

目的 观察支气管哮喘(简称哮喘)患儿支气管组胺激发试验前、后呼气流速受限(EFL)情况,并与常规的以第1秒用力呼气容积(FEV1)作为判断指标的支气管激发试验结果进行比较,探讨EFL作为支气管激发试验判断指标的可行性.方法 非急性发作期哮喘30例患儿,采用呼气相气道内负压(NEP)法检测患儿支气管组胺激发试验前、后EFL情况.结果 30例非急性发作期哮喘息儿中,支气管组胺激发试验阳性者(BPT阳性组)19例,阴性者(BPT阴性组)11例.BPT阳性患儿激发前、后FEV1分别为(1.71±0.52)L和(1.21±0.34)L,FEV1下降率为(29.04±7.49)%,19例BPT阳性患儿激发前和激发后分别有1例和3例出现卧位EFL,坐位时均无EFL,患儿3分法EFL和5分法EFL激发前(分别为1.05±0.23和0.05±0.22)与激发后(分别为1.16±0.37和0.26±0.65)比较差异均无统计学意义(t分别为1.455和1.714,P分别为0.163和0.104).BPT阴性患儿激发前、后FEV1分别为(1.89±0.80)L和(1.79±0.78)L,FEV1下降率为(6.09±5.29)%,11例BPT阴性患儿激发前与激发后均无EFL.结论 NEP法检测EFL不能敏感反映传统支气管激发试验阳性判断标准(FEV1下降≥20%)的变化,其在支气管激发试验中的可行性和阳性判断标准尚有待进一步研究探讨.     

Assessment of diurnal variability of peak expiratory flow in stable asthmatics.

Five daily readings of peak expiratory flow (PEF) were obtained for three days on 100 patients with chronic stable asthma. The variability of PEF was calculated as the amplitude percent mean (A%M) from the readings obtained on the third day, and compared to previously reported data from 152 healthy Indian adults. Patients with severe asthma exhibited significantly higher A%M than patients with both mild and moderate asthma (p < 0.05), but there was considerable overlap across disease categories. The area under the receiver operating characteristic curve plotted to assess the performance of PEF variability as a discriminator in diagnosing asthma was 0.826, with best discrimination at a value of 12.5 (sensitivity 0.640, specificity 0.941). Using a cut-off value of 16.5 (as proposed earlier by us) improved specificity to 0.987 but reduced sensitivity to 0.510. Using a traditional cut-off of 20, specificity remained almost unchanged (0.993), but sensitivity dropped further to 0.440. Thus A%M>16.5 is a useful marker of bronchial asthma in epidemiological studies in India. However, its use in population screening, clinical diagnosis, or in the assessment of the severity of asthma in individual patients has serious limitations because of poor sensitivity.     

Timing of lowest and highest peak expiratory flow in patients with asthma: influence of anti-inflammatory treatment

We sought to determine the optimal time for measuring peak expiratory flow rate (PEF) in patients with mild to moderate asthma, before and after treatment with inhaled beclomethasone dipropionate (BDP). After 2 weeks of observation, BDP (400 microg/d) was given to 22 patients with mild to moderate asthma. The dose of BDP (800-1200 microg/d) was increased every 2 weeks until PEF varied by no more than 20% each day. PEF was measured four times daily: on awakening, around noon, in the evening and at bedtime. Significant (P < 0.05) rhythms were detected by single cosinor analysis in all patients, both during observation and during treatment. Analysis by the population mean-cosinor method showed that the mean mesor was 378.8+/-59.1 lmin(-1), the mean amplitude was 53.9+/-13.4 lmin(-1), and the mean acrophase was at 16:26+/-0:32 before treatment. After treatment, the mean mesor was 528.0+/-61.9 l min(-1), the mean amplitude was 37.6+/-12.2 lmin(-1), and the mean acrophase was at 16:35+/-0:32. The mesor increased significantly (P<0.05), and the amplitude decreased significantly (P<0.05) after treatment. The acrophase did not change. These data indicate that PEF is lowest at 04:30 and highest at 16:30 in patients with mild to moderate asthma, both during observation and during treatment. We conclude that if one needs to assess PEF twice a day, this should ideally be done at 04:30 and 16:30, not only before but also after treatment with BDP.     

Can measurement of peak expiratory flow enhance compliance in chronic asthma?

Almost all patients with chronic asthma will derive benefit from self-measurement of PEF. Unquestionably, this is of value for educating patients about their disease and treatment, leading in turn to improved compliance. It will be several years before it becomes clear what proportion of patients are willing to manage their asthma themselves and are sufficiently competent in the interpretation of their measurement of PEF to do so safely. It remains to be seen what effect greater use of PEF measurement by patients will have upon present levels of morbidity and mortality from asthma.