Carole Trudeau

Compliance with and accuracy of daily self-assessment of peak expiratory flows (PEF) in asthmatic subjects over a three month period

Serial peak expiratory flow (PEF) assessment has been proposed in the clinical evaluation of asthma. In subjects attending the asthma clinic of a tertiary care hospital, we wanted to assess: 1) compliance in performing PEF; and 2) accuracy of a PEF-diary. Twenty adult asthmatic subjects, all using inhaled steroids, were asked to assess their PEF in the morning and evening with a VMX instrument (Clement Clarke Int., Colombus, OH, USA). This instrument, which incorporates a standard mini-Wright peak flow meter, stores PEF data on a computer chip. Subjects were not informed that the values were being stored. The mean duration of PEF monitoring was 89 days (range 44-131 days). For the total of 20 subjects, it was estimated that 3,482 values should have been written down and stored on the VMX computer chip. Whilst 1,897 values (54%) were written down, only 1,533 (44%) were stored, 425 values being invented. Morning and evening values were stored on 34% of days; and values were stored at least once a day on 55% of days. The values written down corresponded precisely to stored values 90% of the time, and were within +/- 20 L 94% of the time. We conclude that: 1) compliance with daily peak expiratory flow assessments is generally poor in chronic stable asthmatic subjects assessed on two visits separated by a 3 month period; and 2) a substantial percentage of values (22%) is invented. The unsatisfactory compliance with peak expiratory flow monitoring in this group of asthmatics on inhaled steroids underlines the need for similar studies on peak expiratory flow monitoring as part of an action treatment plan, and in more severe and brittle asthmatics.

Should we monitor peak expiratory flow rates or record symptoms with a simple diary in the management of asthma

BACKGROUND Various means of monitoring asthma severity have been proposed to reduce morbidity and mortality rates. We compared two means of assessing asthma flare-ups: monitoring peak expiratory flow rate (PEFR) and keeping a symptom diary. METHODS This was a crossover randomized study. After a 2-week baseline period during which spirometry and PC20 methacholine were assessed, subjects were asked to record either PEFRs or to keep a symptom diary morning and evening for 6 months; a second baseline assessment separated the two periods. Subjects were asked to contact the study coordinator if the following occurred: (1) in the period of PEFR monitoring, daily fluctuations in PEFR were > 20% or the absolute value fell to < 80% of baseline or both occurred; (2) in the period of symptom diary monitoring there were nocturnal symptoms or a persistence of morning dyspnea after inhaled bronchodilator or a reduction in the duration of effect of the bronchodilator or it was impossible to go to work or school or all occurred. In that case they were asked to come to the hospital to confirm the flare-up through investigation for significant changes in FEV1 or PC20 or both. Forty subjects completed a 6-month symptom diary or PEFR recording period respectively, and 20 completed both. RESULTS A total of 31 exacerbations were reported in 28 different subjects; three subjects had two flare-ups. Thirteen of 19 (69%) flare-ups were confirmed during the symptom diary period and 9 of 12 (75%) during PEFR monitoring. Nocturnal awakenings and morning falls in PEFR > or = 20% were the most frequent occurrences. CONCLUSIONS We conclude that a simple symptom diary may be as useful as serial PEFR monitoring in documenting asthmatic flare-ups.

Salmeterol, a new inhaled beta2-adrenergic agonist, has a longer blocking effect than albuterol on hyperventilation-induced bronchoconstriction☆

The duration of the blocking effect of salmeterol (50 micrograms), albuterol (200 micrograms), and a placebo were compared in a double-blind study in 12 adult subjects with asthma who underwent hyperventilation tests with cold dry air (-20 degrees C) on 4 study days. On the first day, the hyperventilation test was performed at various time intervals (baseline, 1, 4, 6, 8, 12, and 24 hours) with spontaneous functional recovery between each test to determine the within-day within-subject variability of the response. The response was assessed by interpolating the dose of cold dry air causing a 20% fall in FEV1. On the 3 remaining days, separated by an interval of at least 5 days, the active or placebo medication was administered after spontaneous recovery from the first hyperventilation test. Spirometry was assessed 15 minutes and 1 hour later. The hyperventilation test was then performed and repeated 4 hours after administration of the drug. The test was repeated 6, 8, 12, and 24 hours later to detect any significant blocking effect. The improvement in FEV1 15 minutes and 1 hour after the drug was administered was 19.8% and 20.4%, as compared to baseline for albuterol, and 16.3% and 16.8% for salmeterol (not significant). The mean duration of the blocking effect was 0.25 hour for the placebo, 3.5 hours for albuterol, and 15.9 hours for salmeterol (F = 24.5; p less than 0.001; Newman-Keuls test was significant for every contrast). Eight of the 12 subjects still demonstrated some blocking effect 8 hours after taking salmeterol; this was true for only one subject receiving albuterol.(ABSTRACT TRUNCATED AT 250 WORDS)

Occupational rhinitis in workers investigated for occupational asthma

Background: The links between asthma and rhinitis are now referred to as united airways disease (UAD). Current evidence shows that the UAD model seems to be applicable to occupational rhinitis (OR) and occupational asthma (OA). A study was undertaken to objectively assess, in the context of specific inhalation challenge (SIC) testing, the concomitance of bronchial and nasal reaction in the investigation of OR and OA. Methods: 43 subjects with a history of work-related asthma symptoms underwent SIC for confirmation of OA and investigation of OR. Changes in bronchial calibre were measured by spirometry and nasal patency and airway inflammation were assessed by acoustic rhinometry and nasal lavage. Results: A positive nasal challenge was observed in 25 SIC tests and a positive bronchial challenge was observed in 17 SIC tests. A concomitant positive nasal and bronchial challenge was observed in 13 instances. This association was significant (risk ratio = 1.7; 95% CI 1.0 to 2.4; p = 0.04) and more frequent in subjects challenged with high molecular weight agents (n = 11/22) than with low molecular weight agents (n = 2/21). In subjects with a positive nasal challenge, nasal lavage showed a significant increase in eosinophils 30 min after exposure which correlated with changes in nasal patency. Conclusion: The results of this study provide objective evidence to support the concept of UAD using OR and OA as a model to demonstrate a significant concomitant physiological reaction of the nose and lungs after challenge. This study shows that OR can be assessed by objective means; it often coexists with OA but can be present without OA.

Allergenic exposure, IgE-mediated sensitization, and related symptoms in lawn cutters

AIMS The aims of the study conducted on lawn cutters were: (1) to evaluate exposure to pollens and molds; and (2) to assess the prevalence rate of IgE sensitization and symptoms in relation to exposure to pollens and molds. METHODS Environmental assessment was done with the use of personal samplers on eight workers. Our population consisted of 181 municipal park workers, including 128 lawn cutters and 67 control subjects (blue-collar workers in the hospital). A questionnaire was administered, as well as skin prick tests with seven common inhalants including pollens and eight grass molds. The main outcome variables were grass or mold sensitization (at least one of eight molds) and work-related rhinitis, conjunctivitis, and rhinoconjunctivitis. Atopy and exposure to park-related allergens, as well as sensitization to grass pollens, were considered as explanatory factors. Smoking was taken into consideration as a covariant. Both presence and duration of occupational exposure to park-related allergens were considered as parameters of exposure. Duration of exposure (months x years of exposure as lawn cutters) was used as a continuous or as a categorical variable. RESULTS Environmental monitoring showed that the concentration of pollens and molds decreased in magnitude from samples collected close to lawn cutters faces, short distance away in parks, and in the general environment. There was no difference in the prevalence rates for atopy between lawn cutters (32%) and control subjects (37%). Sensitization rates to grass pollen were also similar in lawn cutters (18%) and in control subjects (22%). However, there was a tendency for prevalence rates of sensitization to molds to be greater among lawn cutters (12% to Alternaria) compared with control subjects (5%). In the logistic model atopy was significantly related to grass sensitization (odds ratio [OR] = 7.2), mold sensitization (OR = 9.3), and sensitization to Alternaria (OR = 5.8). Grass sensitization was a significant risk factor for park-related rhinitis (OR = 5.8), conjunctivitis (OR = 5.0), and rhinoconjunctivitis (OR = 9.4). Exposure for 12 years or more was associated with rhinoconjunctivitis with an OR of 4.1 (95% confidence interval, 1.0-16.7). Smoking was not significantly related to any outcome. CONCLUSION We conclude that among lawn cutters exposure to pollens and molds is higher than in the general population, atopy is the main determinant of sensitization to these aeroallergens, and sensitization and, to a much lesser extent, exposure to grass are determinants of symptoms.

Proinflammatory mediators in nasal lavage of subjects with occupational rhinitis

We sought to investigate the type and kinetics of late-phase nasal inflammatory response after nasal challenge with occupational allergens. Participants were 10 subjects experiencing work-related rhinitis symptoms who underwent specific inhalation challenge and tested positive for occupational rhinitis. During challenge, we monitored changes in inflammatory cells, eosinophil cationic protein, myeloperoxidase, and interleukin-8 in nasal lavage samples. The challenge with the active agent induced a significant increase in the percentage of eosinophils at 30 minutes as compared with prechallenge values (P = 0.04). A significant increase in eosinophil cationic protein levels after challenge with the control (P = 0.01) and active agent (P = 0.02) was observed in the late phase after challenge. No significant changes in nasal levels of neutrophils, myeloperoxidase, and interleukin-8 were observed on both control and active challenge days. Our results suggest a predominant nasal eosinophilic inflammatory response after occupational allergen challenge.

Duration and magnitude of action of 50 and 100 μg of inhaled salmeterol in protecting against bronchoconstriction induced by hyperventilation of dry cold air in subjects with asthma

Salmeterol is a new long-acting and highly selective &-agonist agent. Clinical studies have shown that it has a very long (at least 12 hours) duration of action in terms of its bronchodilator effect1 and that its effect on bronchial hyperresponsiveness may even be longer. In a recent study we showed that salmeterol administered in a single dose of 50 pg still had a complete blocking effect on hyperventilation-induced asthma in four of 12 subjects (one third) who were tested up to 12 hours later.’ The recommended dose of this preparation varies between 50 and 100 pg every 12 hours. The aim of this study was to expand our previous work on characterizing the magnitude and duration of action of inhaled salmetereol on hyperventilation-induced bronchoconstriction in a more detailed way, especially on the interval between 12 and 24 hours and later after its administration. We also wanted to compare the efficacy of two different doses, 50 and 100 pg. recent modification in their need for a bronchodilator) were included in the study. The project was accepted by a local ethics committee, and a written consent form was obtained from each participant.

Reproducibility of acoustic rhinometry in the investigation of occupational rhinitis.

Background To diagnose occupational rhinitis, it is mandatory to conduct an objective assessment of changes in nasal patency during specific inhalation challenge (SIC). The reproducibility of acoustic rhinometry measurements in the setting of occupational challenges has never been examined. This study assessed the reproducibility of acoustic rhinometry during SIC investigation of occupational rhinitis. Methods Twenty-four subjects underwent acoustic rhinometry measurements during SIC investigation of occupational rhinitis. Subjects attended 3–6 days of SIC within a week by means of a realistic or closed-circuit apparatus methodology Results All of the within-day intraclass correlation coefficients (ICCs) for nasal volume (2–5 cm) and minimum cross-sectional area (MCA) based on a different number of measurements (2–7) were above 0.85; all of the coefficients of variation (CVs) for the same parameters were low (below 10%). The between-day CVs based on different numbers of SIC sessions ranged from 8.0 to 8.8% and from 6.8 to 8.8% for nasal volume and MCA, respectively. The between-day ICCs ranged from 0.80 to 0.88 and from 0.83 to 0.94 for nasal volume and MCA, respectively. Conclusion Acoustic rhinometry showed good within- and between-day reproducibility and can be recommended for the objective monitoring of nasal patency during SIC investigating occupational rhinitis.

Matrix Metalloproteinase-9 Increases in the Sputum from Allergic Occupational Asthma Patients after Specific Inhalation Challenge.

Background: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play a role in the pathogenesis of asthma. MMP-9 increases in the sputum of asthmatic patients after bronchial challenge with common allergens. We sought to assess whether a high-molecular-weight occupational allergen was able to induce changes in MMP-9 as well as in other MMPs and TIMPs in subjects with occupational asthma. Methods: Ten patients underwent specific inhalation challenge (SIC) on 2 consecutive days. We monitored changes in lung function by measuring FEV1 for 7 h. Induced sputum test was performed at 6 h after sham and flour challenge. The total and differential cell counts were analyzed. Levels of MMPs (specifically MMP-2, MMP-7, MMP-9 and MMP-13) were measured using Fluorokine® MultiAnalyte Profiling kits and a Luminex® Bioanalyzer, while levels of TIMP-1 and TIMP-2 were measured by ELISA. Results: Flour challenge increased the percentage of eosinophils in sputum samples. Asthmatic reactions induced by flour were associated with a significant increase in the sputum level of MMP-9 (p = 0.05), but not in the levels of MMP-2, MMP-7, MMP-13, TIMP-1 and TIMP-2. Sputum levels of MMP-9 measured after flour challenge were nearly significantly correlated (r = 0.67; p = 0.06) with the maximal fall in FEV1 observed during the asthmatic reaction, but they did not correlate with the number of neutrophils (r = 0.18; p = 0.7) and eosinophils (r = 0.55; p = 0.2). Conclusions: This study showed that MMP-9 increases in sputum samples from sensitized occupational asthma patients after SIC with flour.

Fever and leucocytosis accompanying asthmatic reactions due to occupational agents: frequency and associated factors

Fever is sometimes associated with asthmatic reactions following specific inhalation challenges with occupational agents. Our aims were to estimate the prevalence of fever in subjects with occupational asthma confirmed by specific inhalation challenge and to examine the characteristics and clinical correlates of subjects who develop fever on specific inhalation challenge. We performed a retrospective analysis of 317 subjects who had positive specific inhalation challenge to occupational agents and a comparison of subjects who developed fever after specific inhalation challenge with a random sample of those who did not. Fifteen subjects (5%) developed fever associated with positive specific inhalation challenge. They were compared with a random sample of 60 subjects who did not develop fever. The fever group: 1) showed a larger increase in absolute number of blood neutrophils, and a larger decrease both of blood lymphocytes and forced vital capacity after specific inhalation challenge; 2) included fewer atopics; 3) had been exposed more frequently to low rather than high molecular compounds; and 4) always experienced a late reaction and had more atypical reactions. We conclude that after positive specific inhalation challenge; fever occurs infrequently, and is associated with an increase in blood neutrophils and a decrease in blood lymphocytes and forced vital capacity. Such reactions seem more likely to occur in nonatopic subjects exposed to low molecular weight agents.