Peak Expiratory Flow Data Research Articles

Impact of Procedural Variation in Endoscopic Dilation for Idiopathic Subglottic Stenosis.

A small number of Idiopathic subglottic stenosis (iSGS) patients are treated at institutions across the country. Divergence in operative techniques for endoscopic dilation (ED) of iSGS has been anecdotally recognized but not formally characterized. Additionally, the relationship between procedural variation and clinical outcome has not been studied. Secondary analysis of the NoAAC iSGS1000 cohort investigated variation in procedural techniques and treatment outcomes in patients treated with ED across high-enrolling treatment centers (enrolled >10 patients in PR-02 trial). Thirteen NoAAC centers each enrolled >10 patients treated with ED for a total of 281 subjects. There was significant variation in procedural details and rate of recurrence among institutions. Hierarchal cluster analysis revealed significant heterogeneity among institutions and clusters in all procedural variables. However, analysis demonstrated a transient delay in disease recurrence in cluster 2 which disappeared with longer longitudinal follow-up. Patient-reported outcome and peak expiratory flow data supported the potential benefit of the technical variation in Cluster 2. Distinct to cluster 2, however, was routine use of adjuvant triple medical therapy (proton pump inhibitor (PPI), antibacterial agent, and steroid inhaler). Both outcome and procedural technique vary among centers employing ED to treat iSGS. A transient delay in recurrence was observed among centers that routinely prescribed adjuvant medical therapy (antibiotic, inhaled corticosteroid, and PPI) to iSGS patients after endoscopic dilation, which was further supported by patient-reported data and peak expiratory flow data. Prospective studies are needed to understand the effects of adjuvant medical therapy on recurrence after endoscopic dilation. 4 Laryngoscope, 134:3260-3266, 2024.

A stochastic mixed effects model to assess treatment effects and fluctuations in home‐measured peak expiratory flow and the association with exacerbation risk in asthma

Home‐based measures of lung function, inflammation, symptoms, and medication use are frequently collected in respiratory clinical trials. However, new statistical approaches are needed to make better use of the information contained in these data‐rich variables. In this work, we use data from two phase III asthma clinical trials demonstrating the benefit of benralizumab treatment to develop a novel longitudinal mixed effects model of peak expiratory flow (PEF), a lung function measure easily captured at home using a hand‐held device. The model is based on an extension of the mixed effects modeling framework to incorporate stochastic differential equations and allows for quantification of several statistical properties of a patient's PEF data: the longitudinal trend, long‐term fluctuations, and day‐to‐day variability. These properties are compared between treatment groups and related to a patient's exacerbation risk using a repeated time‐to‐event model. The mixed effects model adequately described the observed data from the two clinical trials, and model parameters were accurately estimated. Benralizumab treatment was shown to improve a patient's average PEF level and reduce long‐term fluctuations. Both of these effects were shown to be associated with a lower exacerbation risk. The day‐to‐day variability was neither significantly affected by treatment nor associated with exacerbation risk. Our work shows the potential of a stochastic model‐based analysis of home‐based lung function measures to support better estimation and understanding of treatment effects and disease stability. The proposed analysis can serve as a complement to descriptive statistics of home‐based measures in the reporting of respiratory clinical trials.

Modeling Recurrence in Idiopathic Subglottic Stenosis With Mobile Peak Expiratory Flow.

We sought to establish normative peak expiratory flow (PEF) data for patients with idiopathic subglottic stenosis (iSGS), evaluate whether immediate changes in PEF after a procedure predict long-term treatment response, and test if a decline in longitudinal PEF is associated with disease recurrence. International, prospective, 3-year multicenter cohort study of 810 patients with untreated, newly diagnosed, or previously treated iSGS. iSGS patients consented and enrolled in the North American Airway Collaborative (NoAAC) iSGS1000 cohort recorded PEF data on a mobile smartphone app. Cox regression tested the associations between the magnitude of postoperative PEF improvement and longitudinal 90-day PEF decline with the risk of disease recurrence. Within the NoAAC iSGS1000 cohort, 810 patients participated in a 3-year prospective study comparing surgical treatment efficacy and 385 had appropriate PEF measurements and follow-up data. Of those patients, 42% (161/385) required at least one operation during study follow-up. The mean PEF preceding operative intervention was 241 L/min (95% confidence interval [CI]: 120-380) corresponding to a predicted PEF of 52%. The mean increase in PEF following a procedure was 111 L/min (95% CI: 96-125 L/min). Interestingly, the magnitude of immediate PEF improvement was not predictive of disease recurrence (hazard ratio [HR] for 100 L/min increase=0.90, 95% CI: 0.60-1.00). However, recurrence was associated with the magnitude of PEF decline over 90 days (30% vs. 10% decline, HR=2.2, 95% CI: 1.5-3.0). We provide normative PEF data on a large iSGS patient cohort. The degree of PEF improvement immediately after surgery was not associated with a longer procedure-free interval. However, a 30% decline in PEF over 90 days was associated with elevated risk of disease recurrence. 2 Laryngoscope, 131:E2841-E2848, 2021.

Comparison of Pulmonary Function Decline in Steroid-Treated and Steroid-Naïve Patients with Duchenne Muscular Dystrophy

To describe and compare the lung function decline in patients with Duchenne muscular dystrophy on glucocorticoid therapy in contrast with glucocorticoid-naïve patients, and to define the deciles of pulmonary decline in glucocorticoid-treated patients. This retrospective study examined lung function of patients with Duchenne muscular dystrophy over 6years of age followed between 2001 and 2015 at 2 centers-glucocorticoid-treated patients in Cincinnati, Ohio, and glucocorticoid-naïve patients in Paris, France. Forced vital capacity (FVC, FVC%), forced expiratory volume in 1second, maximal inspiratory pressure, maximal expiratory pressure, and peak expiratory flow data were analyzed. Only FVC data were available for the French cohort. There were 170 glucocorticoid-treated patients (92%), 5 patients (2.7%) with past glucocorticoid use, and 50 French glucocorticoid-naïve patients. The peak absolute FVC was higher and was achieved at earlier ages in glucocorticoid-treated compared with glucocorticoid-naïve patients (peak FVC, 2.4±0.6L vs 1.9±0.7L; P<.0001; ages 13.5±3.0years vs 14.3±2.8years; P=.03). The peak FVC% was also higher and was achieved at earlier ages in glucocorticoid-treated patients (peak FVC%, 105.1±25.1% vs 56±20.9%; P<.0001; ages 11.9±2.9years vs 13.6±3.2years; P=.002). Rates of decline for both groups varied with age. Maximal rates of decline were 5.0±0.26% per year (12-20years) for glucocorticoid-treated and 5.1±0.39% per year for glucocorticoid-naïve patients (11-20years; P=.2). Deciles of FVC% decline in glucocorticoid-treated patients show that patients experience accelerated decline at variable ages. These data describe nonlinear rates of decline of pulmonary function in patients with Duchenne muscular dystrophy, with improved function in glucocorticoid-treated patients. FVC% deciles may be a useful tool for clinical and research use.

Fluctuation Analysis of Peak Expiratory Flow and Its Association with Treatment Failure in Asthma.

Temporal fluctuations have been demonstrated in lung function and asthma control, but the effect of controller therapy on these fluctuations is unknown. To determine if fluctuations in peak expiratory flow (PEF) are predictive of subsequent treatment failure and may be modified by controller therapy. We applied detrended fluctuation analysis to once-daily PEF data from 493 participants in the LOCCS (Leukotriene Modifier Corticosteroid or Corticosteroid-Salmeterol) trial of the American Lung Association Airways Clinical Research Centers. We evaluated the coefficient of variation of PEF (CVpef) and the scaling exponent α, reflecting self-similarity of PEF, in relation to treatment failure from the run-in period of open-label inhaled fluticasone, and the treatment periods for subjects randomized to (1) continued twice daily fluticasone (F), (2) once daily fluticasone plus salmeterol (F + S), or (3) once daily oral montelukast (M). The CVpef was higher in those with treatment failure in the F and F + S groups in the run-in phase, and all three groups in the treatment phase. α was similar between those with and without treatment failure in all three groups during the run-in phase but was higher among those with treatment failure in the F and F + S groups during the treatment phase. Participants in all three groups showed variable patterns of change in α leading up to treatment failure. We conclude that increased temporal self-similarity (α) of more variable lung function (CVpef) is associated with treatment failure, but the pattern of change in self-similarity leading up to treatment failure is variable across individuals.

Peak expiratory flow as a surrogate for health related quality of life in chronic obstructive pulmonary disease: a preliminary cross sectional study.

Health Related Quality of Life (HRQL) measures can capture the non-respiratory effects of Chronic Obstructive Pulmonary Disease (COPD). However the relationship with Peak Expiratory Flow (PEF) is not well understood. To determine the relationship of PEF and quality of life measurements in patients with COPD. A cross section of consecutive patients in a university clinic. Stable patients with COPD defined by the Global Initiative on chronic Obstructive Lung Disease (GOLD) criteria, were recruited into the study. Spirometry was done using American Thoracic Society's standards and reference equations from African American norms of the US population. Quality of life was measured with the St George's Respiratory Questionnaire (SGRQ). Out of 50 patients recruited for the study, 48 provided complete data with acceptable spirometry and PEF data. The mean (SD) age and body mass index was 68.4 (8.9) years and 21.4 (4.6) kg/m(2) respectively and 96% of the patients were in moderate-severe stages of COPD using the GOLD criteria. Percent predicted PEF correlated with percent predicted FEV1; r= 0.559 p<0.001 and also showed a significant, though moderate correlation between PEF readings and SGRQ scores especially in the activity (r= -0.455 p< 0.01) and total scores (r=-0.415 p<0.01) for pre bronchodilator (BD) percent predicted PEF. In regression analysis, PEF was associated with SGRQ (-0.11 95% CI -0.19, -0.03) after adjusting for age, sex, height, smoking and disease severity. PEF correlates with SGRQ scores and may be a useful surrogate for HRQL in patients with COPD.

Urban Adolescents Readily Comply with a Complicated Asthma Research Protocol

PURPOSEAdolescents are often cited as having poor rates of compliance with medical regimens and research protocols. We quantified compliance in a cohort of urban adolescents participating in a complex research protocol in which measures were obtained without direct supervision by research personnel.METHODSA total of 54 early adolescents ages 10–13 were asked to wear a vest containing a personal air pollutant exposure monitor for two 24-hour periods and to perform daily peak expiratory flow (PEF) for six consecutive days. Compliance with wearing the vest was measured by comparing accelerometer data from a device within the vest to one worn continuously on the child’s wrist. Daily PEF data were recorded using an electronic meter.RESULTSA priori definition of compliance was met by 85% of the adolescents by wearing the exposure monitoring vest and 72% by performing PEF.CONCLUSIONSThese findings suggest that early adolescents can be compliant with complex research protocols that are needed to help bridge gaps in pediatric asthma research.

Detrended fluctuation analysis of peak expiratory flow and exacerbation frequency in COPD

We investigated whether exacerbation frequency in chronic obstructive pulmonary disease (COPD) was related to an exponent α which quantifies self-similarity in daily peak expiratory flow (PEF) and is calculated using detrended fluctuation analysis (DFA). We examined data from COPD patients who recorded an increase in respiratory symptoms and post-bronchodilator PEF on daily diary cards. We also investigated PEF data from a double-blind, placebo-controlled trial of the anti-cholinergic agent, tiotropium. In the observational study there were 308 patients with COPD (195 males; mean ± sd age 68.3 ± 8.4 yrs, forced expiratory volume in 1 s (FEV(1)) 1.12 ± 0.46 L, FEV(1) % predicted 44.5 ± 16.4%). The mean ± sd α over the first year was 0.944 ± 0.19 and it was positively related to the frequency of exacerbations per year (p=0.009). In the clinical trial, α was lower in COPD patients randomised to tiotropium, mean ± sd 0.87 ± 0.21 (n=48) than on placebo, mean ± sd 0.95 ± 0.19 (n=52; p=0.035). Power analysis showed that fewer patients would be required for clinical studies with α as the outcome measure than exacerbation frequency. DFA shows that daily PEF in COPD has long-term correlations which are related to exacerbation frequency. Monitoring of PEF and use of α may result in smaller COPD patient sample sizes in trials.

Predicting asthma exacerbations: Peak expiratory flow revisited

The ability to predict and prevent future exacerbations has been a consistent focus of asthma research. Although some progress has been made on identifying factors associated with an increased risk of exacerbation at the population and individual levels, no measure or instrument is available for widespread use in the asthma community. In this issue of the Journal, Thamrin et al present a statistical method used to calculate the future exacerbation risk for a patient (as defined by deterioration in percent predicted peak expiratory flow [PEF]) based on the history of fluctuations in lung function (percent predicted PEF). The authors challenge us to reframe our analytic approach to asthma. Frey et al have suggested that a patient with asthma should be thought of as a complex, nonlinear dynamic systems network; such a network exhibits fluctuations over time in physiologic and clinical variables. However, such a system also exhibits memory effects, and although changes can occur over time, the recent past will include most of the pertinent information needed to predict the short-term future risk. Viewingasthma through this framework, it follows that the single best individual parameter to predict the risk of an exacerbation over the next year is the history of an exacerbation in the prior year. The natural history of asthma in any given patient is a summation of personal characteristics (eg, demographics, inflammatory profile, and lungmechanics), genetics, both the physical (exposure to environment [environmental tobacco smoke, pollution, and allergens]) and psychosocial (access to care) environment, and therapy (including adherence). The complex interaction of these factors results in the overall clinical phenotype expressed by a patient, and this helps explain why the recent past is a strong predictor of future events. Modeling asthma as a complex, nonlinear dynamic system also fits with our increasing recognition of the heterogeneity of asthma. Patients with asthma present differently in regard to symptoms, physiologic measures, inflammatory indices, and perception of obstruction; measuring a single parameter at a single point might not

Predicting future risk of asthma exacerbations using individual conditional probabilities

Determination of future risk of exacerbations is a key issue in the management of asthma. We previously developed a method to calculate conditional probabilities (π) of future decreases in lung function by using the daily fluctuations in peak expiratory flow (PEF). We aimed to extend calculation of π values to individual patients, validated by using electronically recorded data from 2 past clinical trials. Twice-daily PEF data were analyzed from 78 patients with severe (study A) and 61 patients with poorly controlled (study B) asthma. For each patient, the π value was calculated from 5000 PEF data points simulated based on the correlation and distribution properties of observed PEF. Given an initial PEF, the π value was defined as the probability of a decrease in PEF to less than 80% of predicted value on 2 consecutive days within a month. These probabilities were then compared with actual occurrences of such events and clinically defined exacerbations within the following month. π Values were related to actual occurrences of decreases in PEF (adjusted R(2) > 0.800 for both studies). Every increase of 10% in π value was associated with an odds ratio of having a future exacerbation of 1.24 (95% CI, 1.07-1.43) for study Aand 1.13 (95% CI, 1.02-1.26) for study B, with better sensitivity and specificity than clinic-measured FEV(1). These results from 2 independent datasets with differing asthmatic populations and differing exacerbation criteria provide support that clinically relevant quantification of individual future risk of exacerbations is possible.

Effect of Hourly Concentration of Particulate Matter on Hospitalized Childrenʼs Peak Expiratory Flow

PP-29-004 Background/Aims: There is little information about the possible association between hourly short-term air pollution and peak expiratory flow in asthmatic children. We collected and analyzed hourly air pollution data and peak expiratory flow data from asthmatic children. Methods: Subjects in this study were 17 patients aged 8–15 years with severe asthma who were hospitalized during 1 October 2000 through 24 December 2000. Measurements of peak expiratory flow and particulate matter (PM) were conducted immediately prior to medication twice a day, at 7 am and 7 pm, under the guidance of trained nurses. The changes in asthmatic children were estimated according to each 10 μg/m3 increment in PM with a 50% cut-off aerodynamic diameter of ≤2.5 μm (PM2.5) adjusted for sex, age at baseline survey, height at baseline survey, and temperature. Lagged-hour exposures of up to 24 hours were examined. Results: A decline in peak expiratory flow at 7 am was associated with the hourly concentration of PM2.5 during the period from lag 15 to lag 0. The largest effect size was −3.39 L/min (95% CI: −4.31, −2.46) for 10 μg/ of hourly concentration of PM2.5 between 11 pm and 12 pm on the previous night (lag 7). Some of the significant associations remained even after adjustment for other air pollutants. Conclusion: There was an association between a decline in peak expiratory flow and increased hourly concentration of PM2.5 up to 24 hours before peak expiratory flow measurement, especially in the morning.

Variability of lung function predicts loss of asthma control following withdrawal of inhaled corticosteroid treatment

BackgroundOne aspect of a multidimensional approach to understanding asthma as a complex dynamic disease is to study how lung function varies with time. Variability measures of lung function have been...

The validation of work-related self-reported asthma exacerbation

Objective: To determine the validity of work-related self-reported exacerbation of asthma using the findings from serial peak expiratory flow (PEF) measurements as the standard. Methods: Adults with asthma treated in...

Subjective symptom perceptual accuracy in asthmatic children and their parents in India

Inaccurate symptom perception is a key factor in increased morbidity and mortality in asthmatic patients. Information is sparse on whether children and their parents can accurately perceive severity of symptoms. To determine symptom perceptual accuracy in children with asthma and either of their parents. Fifty-two asthmatic children and either of their parents recorded independently, for 2 weeks, subjective evaluation of the child's symptoms on a 100-mm visual analog scale (VAS). Peak expiratory flow (PEF) was used as an objective measurement. Both VAS and PEF data were graded into green, yellow, and red zones. The 2 sets of VAS zones (children and parents) were separately matched with PEF zones to determine perceptual accuracy. Children and parents were accurate more than half of the time (60% and 62%, respectively), but accuracy decreased when the "child was unstable" (PEF <80% of personal best), with underestimation being significant (P < .001). Among the readings obtained, underestimation of severity of symptoms was significant in children with severe asthma (125 [45%] of 278 readings), those affected by environmental tobacco smoke (130 [24%] of 532), and those in the younger age group (127 [45%] of 280). Underestimation was significantly greater when PEF readings were in the yellow zone (P < .001). Symptom perception by children was as reliable as that by their parents. However, parents and children tended to underestimate severity when the child was unstable. An early decline in PEF readings was missed by children and their parents, which could contribute to increased morbidity and mortality in this vulnerable age group.

Peak flow monitoring in clinical practice and clinical asthma trials

This review summarizes recent reports on peak expiratory flow (PEF) monitoring in clinical asthma trials and clinical practice. In clinical trials, summary measures such as average morning PEF provide only a fraction of the available information about asthma control and treatment response. New statistical models should improve the yield from PEF datasets. Improved criteria are needed for the diagnosis of exacerbations, and these may be developed from quality-control analysis of existing datasets. In clinical practice we must reduce the burden of monitoring and increase the ease of interpretation of PEF data. Electronic monitoring, with short message service or Internet communication, may assist with both. There is a need for standardized user-friendly PEF charts and simple statistically appropriate interpretative tools, which will facilitate the development of clinical algorithms and individualized written action plans. Normal values for diurnal variability should be updated to reflect twice daily monitoring. Current use of PEF data is limited by the burden of monitoring and the continuing use of interpretative tools that were originally developed for their practical feasibility rather than their clinical validity. Both of these problems may be improved by giving attention to methods for recording, displaying and analysing PEF data.

ASTHMA MORBIDITY IN CHILDREN AND AMBIENT AIRBORNE PARTICULATE EXPOSURE

ISEE-272 Introduction: No study has looked at fine versus coarse particle health effects on asthmatic children (PM2.5 vs. PM2.5-10). Few non-invasive biomarkers of asthma morbidity have been evaluated for their implementation into field epidemiological studies. We performed a panel study to address these scientific gaps. Aim: The purpose of this study was two-fold: 1.) to test biomarkers of asthma morbidity for their potential application in larger field epidemiological studies and 2.) to test the hypothesis that there were differences in persistent asthmatic children's responses to fine and coarse particulate air pollution. Methods: We performed a panel study of the health effects of PM<2.5 and PM2.5-10 on asthmatic children using an observation period, including peak particle season and excluding peak ozone season. From September 2003 through May 2004, we enrolled 28 persistent asthmatic children from the Chapel Hill area into a 6-week panel study. Each child was 8-18 years old and had one comprehensive clinical evaluation (2-3 hr), one panel enrollment (45 min.), and one panel completion (10 min.) visit at the US EPA's Human Studies Facility in Chapel Hill, North Carolina. The clinical evaluation included a medical history, vital signs, physical exam, spirometry, buccal swab, allergy skin test, nasal lavage, collection of exhaled breath condensates, exhaled nitric oxide measurement, urine collection, and blood draw. Children were provided with an electronic peak flow meter for twice daily peak expiratory flow assessment, and a personal digital assistant/mobile telephone for internet-based daily health diary collection, upon enrollment. Daily PM<2.5 and PM2.5-10 measurements were made concurrently using a centrally located dichotomous air sampler on the roof of the Human Studies Facility, from August 2003 through June 2004. Results: Most study children were moderate persistent asthmatics (18, 64%), with four severe persistent, five mild persistent, and only two mild intermittent. All 28 children completed the entire 6-week panel. Children were on study for an average of 42 days (+/− 1.8 days) with an 85% diary and 89% peak flow meter completion average. Eighteen of the 28 children consented to the blood draw (64%). The mean daily PM<2.5 and PM2.5-10 measurements were 11.3 (Interquartile range: 8.1) and 5.6 (Interquartile range: 4.6), respectively. A sub-group of 18 children had supplemental outdoor monitoring performed at their residence for up to five consecutive days. Particulate air pollution levels were consistently below the standards set by the USEPA. Conclusion: We successfully evaluated, enrolled, and retained persistent asthmatic children within a 6-week daily diary study with good compliance. This study demonstrates that persistent asthmatic children can provide reasonably complete daily diary and peak expiratory flow data for up to six weeks using the technology employed in our study. These findings do not necessarily represent United States Environmental Protection Agency policy.

The analysis of peak expiratory flow data using a three‐level hierarchical model

Peak expiratory flow (PEF) is a measure commonly used in clinical practice and research for respiratory diseases such as asthma. In research, PEF is usually recorded in a diary for a 2-week period with two or more measurements per day. Interest may lie in whether certain groups of individuals tend to have higher or lower PEF. In addition the variability of PEF may be of interest as, for example, asthmatics tend to have more variable airways. In this paper we develop a three-level hierarchical model that can simultaneously model the mean level and variability of PEF. The variability is broken down into three components, between-subject variability, between-day within-subject variability, and within-day within-subject variability. The latter two components are of specific clinical interest. We fit both classical and Bayesian models. The Bayesian models have the advantage of taking the uncertainty in the variance component estimates into account when estimating the standard errors of the fixed effects. In addition, the Bayesian models provide an intuitive and simple way to investigate the within-subject variance components.

Effect of peak expiratory flow data quantity on diagnostic sensitivity and specificity in occupational asthma.

Serial peak expiratory flow records are recommended in the first-line investigation of suspected occupational asthma. The effects of sequentially reducing the numbers of working weeks, consecutive days at work and readings taken per day on diagnostic sensitivity and specificity were investigated, using good quality peak expiratory flow records from 81 workers with independently confirmed occupational asthma and 60 asthmatics without occupational exposure. Sensitivity was 81.8% for records of 4 weeks' duration and 70% for those of 2 weeks' duration (specificity 93.8 and 82.4% respectively). The sensitivity fell to 56.7% if there were only 2 consecutive workdays in each work period. Although best at 8 readings x day(-1), sensitivity and specificity were acceptable with four daily readings (82.4 and 87%). The effect of defining a record as being of adequate quality if it was of > or = 2.5 weeks' duration, with > or = 4 readings x day(-1) and > or = 3 consecutive workdays in each work period, was tested in records not used in the initial data reduction process. The sensitivity and specificity respectively of adequate records were 78.1 and 91.8 versus 63.6 and 83.3% for inadequate records. Peak expiratory flow records for the diagnosis of occupational asthma should be interpreted with caution if they do not satisfy the suggested minimum data quantity criteria.

Airway responsiveness and peak flow variability in the diagnosis of asthma for epidemiological studies.

Airway responsiveness and variability in peak expiratory flow (PEF) are widely used as objective diagnostic measures of asthma, but it is not clear how these variables should be calculated or adjusted to obtain the highest diagnostic validity for physician-diagnosed asthma in the community. Data from a community-based sample of 1,513 adults has been used. Airway responsiveness to methacholine and 7-day PEF data were obtained in 1991, asthma and respiratory symptoms were diagnosed by questionnaires in 1991 and 1999. Airway responsiveness was expressed as the provocative dose causing a 20% fall in forced expiratory volume in one second (PD20), two-point and least-squares regression slopes. PEF variability was expressed as daily amplitude, weekly standard deviation and mean of the two lowest readings. Continuous measures were adjusted for measures of baseline airway calibre by linear regression. Measures of airway responsiveness had greater sensitivity for specificity for self-reported diagnosed asthma than expressions of PEF variability, before and after adjustment for airway calibre. Diagnostic validity was substantially better in adults aged <50 yrs; PD20 provided the best sensitivity for specificity (61% for 95% at 8.3 micromol). In those aged > or =50 yrs, no measure was closely related to diagnosed asthma. In younger age groups, provocative dose causing a 20% fall in forced expiratory volume in one second provides a valuable objective measure of asthma for epidemiological studies, but is unable to distinguish between asthma and chronic obstructive pulmonary disease in older people.

Addition of leukotriene antagonists to therapy in chronic persistent asthma: a randomised double-blind placebo-controlled trial

Controlled trials suggest that leukotriene receptor antagonists can improve lung function and reduce requirement for oral or inhaled corticosteroids in patients with asthma. We aimed to assess whether montelukast, a leukotriene receptor antagonist, can improve symptoms or lung function in patients with chronic asthma with symptoms already taking corticosteroids. We did a double-blind, placebo-controlled, crossover, randomised add-on study in which 100 patients with asthma and symptoms despite treatment with inhaled corticosteroids and additional therapy were given 10 mg montelukast sodium for 14 days in an outpatient clinic setting. Outcome measures were symptoms and peak flow diaries. 72 patients had diary data for analysis. Compared with placebo, addition of montelukast did not result in any significant change in symptom scores (mean difference between the last 7 days of each treatment period 0.05; 95% CI --0.86 to 1.14), rescue inhaled beta(2) agonist use (mean difference in puffs per day 0.41; -0.29 to 0.57), or twice daily peak expiratory flow (PEF) measurements (mean difference in morning PEF 1.18 L/min; -14.29 to 17.14), and mean difference in evening peak flow (-0.50; -17.42 to 12.86). When treatment response was defined as a 15% or greater increase in mean peak flow readings, there were four responders to montelukast and seven responders to placebo. Based on PEF data from our previous studies of a similar patient group we would have expected to detect changes of more than 5%. Used as additional therapy in a hospital outpatient clinic setting, montelukast did not provide such additional benefit in patients with moderate or severe asthma.