Jocelyne L'Archevêque

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.

Natural history of occupational asthma: Relevance of type of agent and other factors in the rate of development of symptoms in affected subjects

It is unknown whether factors such as the nature of the agent, gender, age, atopy, smoking habits, continuous or noncontinuous exposure, and pattern of asthmatic reaction can influence the rate of development of symptoms in subjects with occupational asthma. We compared several clinical and functional parameters among three groups of subjects with occupational asthma caused by Western red cedar (group 1, n = 433), isocyanates (group 2, n = 107), and high molecular weight agents acting through an IgE-mediated mechanism (group 3, n = 121). Survival analysis showed that the three curves relating years of exposure before onset of symptoms to the proportion of subjects without symptoms were significantly different in two respects: (1) almost 40% of subjects in groups 1 and 2 as compared with 20% of subjects in group 3 became symptomatic within 1 year of exposure; (2) after 5 years of exposure, the rate of sensitization was slower for subjects in groups 2 and 3 as compared with those in group 1. Having a nonimmediate reaction at the time of specific inhalation challenges, being continuously exposed and being younger slightly increased the risk at each time point on the curve of developing symptoms in subjects with occupational asthma. These data suggest that the natural history for onset of occupational asthma is different depending on the sensitizing agent. Factors such as age, type of exposure, and pattern of reaction on exposure to the agent also modulate the rate of development of this condition.

Is reactive airways dysfunction syndrome a variant of occupational asthma

BACKGROUND Reactive airways dysfunction syndrome (RADS) or irritant-induced asthma is a syndrome that leaves subjects with asthma-like symptoms after one or more exposures to a high concentration of an irritant substance. The degree of reversibility of airway obstruction in subjects with RADS is nevertheless unknown, as is the degree of associated lesions at the airway level. METHODS We compared the acute reversibility of forced expiratory volume in 1 second (FEV1) after inhalation of albuterol (200 micrograms) in 15 subjects with RADS (12 cases caused by chlorine inhalation) with that of 30 subjects with occupational asthma (OA) caused by various agents. They were paired according to baseline airway obstruction (61% and 63% of predicted value in the RADS and OA groups), requirement for medication (bronchodilator only--7 of 15 subjects with RADS and 14 of 30 subjects with OA--as compared with bronchodilator + inhaled steroids in 8 of 15 subjects with RADS and 16 of 30 subjects with OA, respectively), and interval since removal from exposure (means of 30 and 24 months in the RADS and OA groups). In addition, five nonsmokers with RADS who had not received inhaled steroids underwent bronchoscopy with lavage and bronchial biopsies less than 2 years after the exposure. RESULTS The percentage increase in FEV1 over baseline after inhalation of albuterol was 10% +/- 9% in the RADS group and 19% +/- 16% in the OA group (p = 0.005). Only 2 of 15 subjects (13%) with RADS and 12 of 30 subjects (40%) with OA showed an improvement in FEV1 of 20% or greater after inhalation of albuterol. Bronchoalveolar lavage showed an increased number of cells with a predominance of lymphocytes, and biopsy specimens showed increased basement membrane thickness in the five subjects with RADS who underwent bronchoscopy. CONCLUSION Subjects with RADS are generally left with less airway reversibility than those with OA. We suggest that this difference is secondary to distinct pathologic changes.

Quality of life of subjects with occupational asthma

BACKGROUND The aim of the study was to assess the quality of life in subjects with occupational asthma after removal from exposure to the offending agent by comparison with a group of subjects paired for clinical and functional indices in order to show the separation between the two groups of subjects with a hypothesized different quality of life and relate the impairment in quality of life to anthropometric, clinical, and functional variables. METHODS A previously described asthma quality of life questionnaire (Juniper EF, et al. Thorax 1992;47:76-83) was administered to two groups of subjects in a prospective manner. Information on the clinical and functional severity of asthma was obtained from each subject. Two groups of subjects were assessed: group 1, 134 subjects with occupational asthma who were seen more than 2 years after the diagnosis was confirmed, and group 2, 91 subjects who were seen in specialized asthma clinics of tertiary care hospitals for treatment of nonoccupational asthma and matched with 91 of the 134 subjects with occupational asthma from group 1 according to need for medication and (when available), baseline forced expiratory volume in 1 second (FEV1), and level of bronchial responsiveness. RESULTS A statistically significant difference was seen in the four domains (asthma symptoms, limitation of activities, emotional dysfunction, environmental stimuli) and in the total score of the quality of life questionnaire between the two groups of matched subjects; the mean difference in the total score was 0.6 on a scale of 1 (no limitation or none of the time) to 7 (severe limitation or all the time). A weak but statistically significant correlation between the total score and several indices (FEV1, bronchial responsiveness and asthma severity) was generally obtained. CONCLUSION The quality of life of subjects with occupational asthma is slightly less satisfactory than that of subjects paired for clinical and functional indices, although the magnitude of the difference is small; and quality of life is weakly correlated with clinical and functional indices.

What are the questionnaire items most useful in identifying subjects with occupational asthma

The present study assessed the usefulness of key items obtained from a clinical “open” questionnaire prospectively administered to 212 subjects, referred to four tertiary-care hospitals for predicting the diagnosis of occupational asthma (OA). Of these subjects, 72 (34%) were diagnosed as OA (53% with OA due to high-molecular-weight agents) according to results of specific inhalation challenges, and 90 (42%) as non-OA. Wheezing at work occurred in 88% of subjects with OA and was the most specific symptom (85%). Nasal and eye symptoms were commonly associated symptoms. Wheezing, nasal and ocular itching at work were positively, and loss of voice negatively associated with the presence of OA in the case of high-, but not low molecular-weight agents. A prediction model based on responses to nasal itching, daily symptoms over the week at work, nasal secretions, absence of loss of voice, wheezing, and sputum, correctly predicted 156 out of 212 (74%) subjects according to the presence or absence of OA by final diagnosis. In conclusion, key items, i.e. wheezing, nasal and ocular itching and loss of voice, are satisfactorily associated with the presence of occupational asthma in subjects exposed to high-molecular-weight agents. Therefore, these should be addressed with high priority by physicians. However, no questionnaire-derived item is helpful in subjects exposed to low-molecular-weight agents.

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.

How many times per day should peak expiratory flow rates be assessed when investigating occupational asthma

BACKGROUND--Serial peak expiratory flow rate (PEF) recording has been advocated as a sensitive and specific means of confirming work related asthma. The optimum number of recordings per day to achieve the best between-reader and within-reader reproducibility and sensitivity/specificity ratio compared with the final diagnosis determined by specific inhalation challenges is unknown. METHODS--PEF recording was carried out every two hours in 74 subjects referred for possible occupational asthma. Specific inhalation challenges performed in a hospital laboratory or at the workplace (positive in 33 subjects and negative in 41) were considered the gold standard. The duration of monitoring at work and away from work was at least two weeks each. Graphs of PEF recordings were generated in four different ways: every two hours, four times/day, three times/day, and every morning and evening. The graphs were assessed by three readers in three different centres in a blind manner. Furthermore, one third of each type of graph was read blind by the same reader one week after the initial interpretation. RESULTS--Agreement between the three readers was a little more frequent (82%) in the case of the every two hour readings than for the other types of readings (70% v 77%). Agreement between at least two of the three readers occurred in 73% of positive challenges (sensitivity) and in 78% of negative challenges (specificity) for every two hour readings. The figures varied from 61% to 70% for positive challenges and from 78% to 88% for negative challenges for the other types of readings. Within-subject reproducibility from one reading to the next (one week apart) was excellent (83% to 100%). CONCLUSIONS--Recording PEF every two hours results in a slightly more satisfactory agreement between readers and in concordance in terms of sensitivity/specificity than less frequent PEF readings, although the four times a day assessment is almost as satisfactory.

Occupational IgE-mediated sensitization and asthma caused by clam and shrimp☆☆☆★★★

BACKGROUND To confirm occupational asthma caused by clam and shrimp in a food company worker, the following investigation was planned in 60 other exposed workers (56 participants). METHODS Before the production period of clam and shrimp, a medical and occupational questionnaire was carried out and skin and RAST testing were done with common inhalants and clam, shrimp, crab, and lobster extracts. During the production period, environmental monitoring was performed with personal and general samplers; inhalation testing with methacholine was proposed to subjects with immediate skin reactivity to clam, shrimp, or both. After the production period, all subjects with an immediate skin reactivity to clam, shrimp, or both and either a history of rhinoconjunctivitis, asthma, or bronchial hyperresponsiveness were seen by a specialist. RESULTS Including the index case in whom occupational asthma to clam and shrimp had been confirmed, four (7%) subjects had a history of rhinoconjunctivitis and two (4%) had a history of asthma during the period of clam production, whereas three (5%) subjects had rhinoconjunctivitis and two (4%) had asthma during the shrimp production. Three (5%) subjects had immediate skin reactivity to clam, and nine (16%) subjects to shrimp. Four (7%) subjects had increased specific IgE antibodies (RAST binding > or = 3%) to clam and eight (14%) to shrimp. Significant associations were found between immunologic reactivity to clam and shrimp on the one hand and to crab and lobster on the other. Environmental monitoring demonstrated clam and shrimp on the air sampling filters. Occupational asthma caused by clam was confirmed by specific inhalation challenges in one subject in addition to the index case. These two subjects had skin reactivity and increased specific IgE antibodies to clam, shrimp, or both. CONCLUSION By including the initial subject, the prevalence of immediate sensitization is 5% to 7% to clam and 14% to 16% to shrimp. Two (4%) subjects had occupational asthma caused by clam, and one (2%) had occupational asthma caused by shrimp.

Long-Term Outcomes of Acute Irritant-induced Asthma

RATIONALE The long-term outcomes of acute irritant-induced asthma (IIA) are mostly unknown. OBJECTIVES To study the long-term outcomes of IIA. METHODS We reassessed 35 subjects who experienced IIA at a mean interval of 13.6 +/- 5.2 years. MEASUREMENTS AND MAIN RESULTS The causal agent was chlorine in 20 cases (57%). At diagnosis, the mean +/- SD FEV(1) was 74.5 +/- 19.5% predicted, and all subjects showed bronchial hyperresponsiveness. At reassessment, all subjects reported respiratory symptoms, and 24 (68%) were on inhaled steroids. There were no significant improvements in FEV(1) and FEV(1)/FVC values. Twenty-three subjects had a methacholine test, and only six subjects had normal levels of responsiveness. Of the remaining 12 subjects, six had improvement in FEV(1) after bronchodilator >or=10%. In samples of induced sputum obtained from 27 subjects, six had eosinophils >or=2%. Levels of inflammatory and remodeling mediators were higher than in control subjects but were no different from subjects with occupational asthma due to sensitization. Quality of life score was 4.4 +/- 1.5 on a 0 (worst) to 7 (best) scale. Twelve subjects had an abnormal depression score. CONCLUSIONS This study provides the first evidence of significant long-term impact of acute IIA on various outcomes.

Long-Term Outcomes in a Prospective Cohort of Apprentices Exposed to High-Molecular-Weight Agents

RATIONALE We conducted a long-term (8-yr) follow-up of 408 apprentices entering programs involving exposure to high-molecular-weight allergens. OBJECTIVES The objectives were to assess the frequency of new and persisting sensitization, symptoms, and bronchial hyperresponsiveness in relation with job history after ending apprenticeship and to examine characteristics significantly associated with the incidence and remission of these occupational outcomes. METHODS A respiratory symptom questionnaire, skin prick tests with work-related allergens (laboratory animals, flour, and latex), spirometry, and methacholine challenge were administered. The association between incidence or remission of these outcomes and individual characteristics at baseline and end of apprenticeship was examined. MEASUREMENTS AND MAIN RESULTS In subjects who at any time during follow-up held a job related to their training (78%), the incidence of sensitization, rhinoconjunctival and chest symptoms, and bronchial hyperresponsiveness at follow-up was 1.3, 1.7, 0.7, and 2.0 per 100 person-years, respectively. The remission of these outcomes acquired during apprenticeship was 18.5, 9.6, 9.6, and 12.4 per 100 person-years, respectively, in subjects no longer in a job related to training. Several clinical, immunological, and functional characteristics at baseline and acquired during apprenticeship were found to be significantly associated with the incidence and remission of the outcomes. CONCLUSIONS The incidence of sensitization, symptoms, and bronchial hyperresponsiveness was lower while at work than during the apprenticeship period. A high proportion of subjects in a job not related to training experienced remission of symptoms acquired during apprenticeship.