André Cartier

Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations

One important goal of asthma treatment is to reduce exacerbations. The current authors investigated if the use of sputum cell counts to guide treatment would achieve this goal. A total of 117 adults with asthma were entered into a multicentre, randomised, parallel group-effectiveness study for two treatment strategies over a 2-yr period. In one strategy (the clinical strategy: CS) treatment was based on symptoms and spirometry. In the other (the sputum strategy: SS) sputum cell counts were used to guide corticosteroid therapy to keep eosinophils ≤2%; symptoms and spirometry were used to identify clinical control, exacerbations and other treatments. Patients were blind to sputum cell counts in both strategies and physicians were blind in the CS, thus removing bias. First, the minimum treatment to maintain control was identified in 107 patients (Phase 1) and then this treatment was continued (Phase 2) for the remaining of the 2 yrs. The primary outcomes were the relative risk reduction for the occurrence of the first exacerbation in Phase 2 and the length of time without exacerbation. The current authors also examined the type and severity of exacerbations and the cumulative dose of inhaled steroid needed. The duration and number of exacerbations in Phase 1 were similar in both groups. In Phase 2 there were a 126 exacerbations of which 79 occurred in the CS (62.7%) and 47 (37.3%) in the SS groups. The majority of the 126 exacerbations (101; 80.1%) were mild. The majority of the 102 exacerbations, where sputum examination was performed before any treatment (n = 70), were noneosinophilic. In the SS patients, the time to the first exacerbation was longer (by 213 days) especially in those considered to need treatment with a long acting β2-agonist (by 490 days), the relative risk ratio was lower (by 49%), and the number of exacerbations needing prednisone was reduced (5 versus 15). This benefit was seen mainly in patients needing treatment with inhaled steroid in a daily dose equivalent to fluticasone >250 μg, and was due to fewer eosinophilic exacerbations. The cumulative dose of corticosteroid during the trial was similar in both groups. Monitoring sputum cell counts was found to benefit patients with moderate-to-severe asthma by reducing the number of eosinophilic exacerbations and by reducing the severity of both eosinophilic and noneosinophilic exacerbations without increasing the total corticosteroid dose. It had no influence on the frequency of noneosinophilic exacerbations, which were the most common exacerbations.

Prevalence and intensity of rhinoconjunctivitis in subjects with occupational asthma.

Subjects with occupational asthma may also report symptoms of rhinoconjunctivitis. The aims of this study were: 1) to assess the prevalence of rhinoconjunctivitis in association with occupational asthma, and the severity of rhinoconjunctivitis according to the type of agent (high (HMW) and low (LMW) molecular weight agents) causing occupational asthma; and 2) to evaluate the timing of occurrence of symptoms of rhinoconjunctivitis in relation to those of occupational asthma. A questionnaire on symptoms of rhinoconjunctivitis and its timing in relation to the development of chest symptoms was prospectively addressed to 143 subjects consecutively referred to an occupational asthma clinic. Objective testing through specific inhalation challenges confirmed the diagnosis of occupational asthma in 40 subjects. Symptoms of rhinitis were reported at some time by 37 of the 40 subjects (92%), and of conjunctivitis by 29 of the 40 subjects (72%). The prevalence of symptoms was not different for HMW and LMW agents, although rhinitis was more intense for HMW (19 out of 24 subjects with three or more of the following symptoms: runny nose, itchy nose, nasal blockage, and sneezing) than for LMW (5 out of 14 subjects) (p<0.01). There were significantly fewer subjects with occupational asthma due to LMW agents, with rhinitis appearing before asthma (p=0.03). Figures for conjunctivitis showed a similar trend, but did not reach statistical significance. In conclusion, symptoms of rhinoconjunctivitis are often associated with occupational asthma. Rhinitis is less pronounced in the case of low molecular weight agents, but more often appears before occupational asthma in the case of high molecular weight agents.

Specific serum antibodies against isocyanates: association with occupational asthma.

Although increased levels of specific IgE and/or IgG antibodies have been documented in individual cases of occupational asthma caused by common types of isocyanates (hexamethylene diisocyanate [HDI] and diphenylmethane diisocyanate [MDI]), the frequency among workers with occupational asthma is still unknown. The sera of 62/65 workers referred for specific inhalation challenges with isocyanates were analyzed for the presence of specific antibodies to the relevant isocyanate. Most workers (39, 63%) were exposed to HDI, some to MDI (17, 27%), and a few to toluene diisocyanate (six, 10%). Specific inhalation challenges were positive in 29 subjects, eliciting either immediate (seven), early late (two), late (13), or dual (seven) reactions. Specific inhalation challenges were more often positive in those subjects with increased nonspecific bronchial responsiveness. Twenty-nine subjects demonstrated increased levels of specific IgE and/or IgG antibodies to isocyanates in the absence of antibodies against human serum albumin (increased IgE only, no subject; IgG only, 20; both IgE and IgG, nine subjects). Although there was a loose association between the results of specific inhalation challenges and levels of specific IgE, the association was much better with the level of specific IgG. Indeed, 21 of the 29 subjects (72%) with positive challenges had increased levels of specific IgG, whereas 25 of the 33 subjects (76%) with negative challenges had normal levels of antibodies. The association was significant with both HDI and MDI. The levels of antibodies were not significantly associated with the type of temporal reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Occupational asthma in snow crab-processing workers

The prevalence of occupational asthma was studied in two snow crab-processing industries in operation since 1980. Before the 1982 season, all except 10 of the 313 employees were investigated by a questionnaire, prick skin tests with common allergens, crab n and crab-boiling water extracts, and spirometry. The diagnosis was confirmed in 46 (15.6%) workers (including 33 of 64 subjects with a history highly suggestive of occupational asthma in the previous seasons) by (1) specific inhalation challenges in 33 subjects (one immediate, nine dual, and 23 late asthmatic responses) and/or (2) a combination of monitoring of peak expiratory flow rates (n = 12) and significant changes in bronchial responsiveness to histamine (n = 16) as well as in spirometry (n = 18) after reappearance of symptoms on return to work. Positive skin tests to crab (p less than 0.001) and, to a lesser degree, smoking history (p = 0.03) but not atopy (p greater than 0.05) were related to the presence of occupational asthma. A high prevalence of rhinoconjunctivitis (35 of 46) and urticaria (16 of 46) was also documented in the affected individuals.

Adult Asthma Consensus Guidelines Update 2003

BACKGROUND Several sets of Canadian guidelines for the diagnosis and management of asthma have been published over the past 15 years. Since the last revision of the 1999 Canadian Asthma Consensus Report, important new studies have highlighted the need to incorporate new information into the asthma guidelines. OBJECTIVES To review the literature on adult asthma management published between January 2000 and June 2003; to evaluate the influence of the new evidence on the recommendations made in the 1999 Canadian Asthma Consensus Guidelines and its 2001 update; and to report new recommendations on adult asthma management. METHODS Three specific topics for which new evidence affected the previous recommendations were selected for review: initial treatment of asthma, add-on therapies in the treatment of asthma and asthma education. The resultant reviews were discussed in June 2003 at a meeting under the auspices of the Canadian Thoracic Society, and recommendations for adult asthma management were reviewed. RESULTS The present report emphasises the importance of the early introduction of inhaled corticosteroids in symptomatic patients with mild asthma; stresses the benefit of adding additional therapy, preferably long-acting beta2-agonists, to patients incompletely controlled on low doses of inhaled corticosteroids; and documents the essential role of asthma education. CONCLUSION The present report generally supports many of the previous recommendations published in the 1999 Canadian Asthma Consensus Report and provides higher levels of evidence for a number of those recommendations.

Urinary leukotriene E4 levels during early and late asthmatic responses

The sulphidopeptide leukotrienes C4 and D4 (LTC4, LTD4) are potent bronchoconstrictor mediators, released from human lung fragments after challenge with specific allergens in vitro. The purpose of this study was to measure urinary LTE4 (metabolite of LTC4 and LTD4) in subjects undergoing inhalation challenges with allergens or occupational sensitizing agents in the laboratory. Eighteen subjects with previously documented isolated early asthmatic responses (EARs), isolated late asthmatic responses (LARs), or dual (both early and late) asthmatic responses were studied. Urinary LTE4 levels increased in subjects who developed either isolated EARs (mean fall in FEV1, 27.98%) or early responses preceding LARs (mean fall in FEV1, 15.01%). The baseline levels of LTE4 were 150.26 (SEM, 49.5) pg/mg of creatinine in the isolated responders and 66.60 (SEM, 13.5) pg/mg of creatinine in the dual responders. These levels increased to 1816 (SEM, 606.1) pg/mg of creatinine (p = 0.041) and 174.80 (SEM, 40.1) pg/mg of creatinine (p = 0.025), respectively, after the EAR. The degree of maximal bronchoconstriction during the EAR correlated with the levels of LTE4 (r = 0.68; p = 0.001). No significant increase in urinary LTE4 levels occurred during the LAR. These results suggest that the LTE4 precursors, LTC4 and LTD4, are important bronchoconstrictor mediators causing EARs after allergen inhalation.

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.

Guidelines for bronchoprovocation on the investigation of occupational asthma: Report of the Subcommittee on Bronchoprovocation for Occupational Asthma

Asthma can be induced or exacerbated at work by several means. Four work-related disorders, characterized by airflow obstruction and airway hyperresponsivene ss, have been described. These include: occupational asthma, byssinosis, the reactive airways dysfunction syndrome, and variable airflow obstruction caused by irritant substances. This committee has elected to focus only on the topic of occupational asthma, which is defined as asthma that is either induced or exacerbated by exposure to a specific (as opposed to an irritant) agent found at work. The Committee has decided to exclude discussion of other causes of asthmatic exacerbations at work, which does not mean that these conditions are not important. It may also, as discussed in other sections of this report, be quite difficult to distinguish an irritant effect from a specific bronchospastic response. A preexisting history of asthma before exposure to the offending agent does not preclude the diagnosis of occupational asthma.

Follow-up of occupational asthma caused by crab and various agents

Sixty-three subjects with occupational asthma caused by crab (n = 31) and various other agents (n = 32) were studied after cessation of exposure at work for mean +/- SD intervals of 12.3 +/- 5.5 and 24.5 +/- 18.7 months (greater than 6 months in every subject), respectively. Nineteen of the subjects with asthma caused by crab and 30 of the subjects with asthma caused by various agents were still symptomatic of asthma, nine subjects of the latter group requiring bronchodilators (with inhaled beclomethasone in five) regularly. No significant changes in baseline spirometry were observed at the time of follow-up as compared with initial assessment, nine subjects (all in the asthma group caused by various agents) demonstrating significant bronchial obstruction. Improvement in bronchial responsiveness to histamine was significant (p less than 0.01) in the group with asthma caused by crab but not in the other group. Forty-eight of 52 subjects still had significant airway hyperexcitability. Subjects with asthma caused by crab who were asymptomatic and those subjects with asthma caused by various agents who used bronchodilators only if they were needed had worked for shorter intervals after onset of symptoms (p less than 0.01 and p less than 0.05, respectively). It is concluded that subjects with occupational asthma caused by various agents can remain symptomatic of asthma and demonstrate a persistence of bronchial obstruction and hyperexcitability for prolonged intervals after cessation of exposure.

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.