Distinct temporal patterns of immediate asthmatic reactions due to high- and low-molecular-weight agents.

BACKGROUND: Exposure to occupational agents can cause immediate asthmatic reactions. OBJECTIVE: It can be hypothesized that the pattern of immediate reactions is different for high (HMW)- and low-molecular-weight (LMW) agents. To test this, we studied the temporal features of reactions in workers who underwent specific inhalation challenges for possible occupational asthma. METHODS: We examined 467 immediate reactions due to HMW (n = 248, 53%) and LWW (n = 219, 47%) agents in regards to timing of the maximum reaction and recovery. RESULTS: The median duration of exposure to elicit significant immediate reactions was comparable for HMW and LMW agents (15 min). The median maximum fall in FEV (1) occurred after 20 min for LMW by comparison with 10 min for HMW agents (P < 0.001). The median timing of recovery of FEV (1) to 10% baseline was shorter for HMW (60 min) than for LMW (90 min) agents (P < 0.01), and significantly more subjects recovered to 10% baseline (89.5%) for HMW than for LMW agents (72.6%) (P < 0.001). Confounding variables such as age, atopy, baseline airway calibre and the maximum fall in FEV (1) at the time of the immediate reaction did not alter the significant effect of the nature of the agent per se. Immediate reactions were followed by a late asthmatic reaction more often in the case of LMW (37.3%) than HMW (26.2%) agents (P < 0.05). Significant changes in non-specific bronchial responsiveness were significantly (P = 0.02) more frequent after reactions to LMW (31.9%) than to HMW (21.4%) agents. We found similar trends by comparing reactions to flour (n = 113), the principal cause of reactions to HMW agents, and diisocyanates (n = 111), the principal LMW agent. CONCLUSIONS AND CLINICAL RELEVANCE: This study shows distinct patterns for immediate reactions due to occupational agents. These results can provide useful guidelines for performing specific inhalation challenges and improve the safety of the procedure.

Association of bronchial reactivity to occupational agents with methacholine reactivity, sputum cells and immunoglobulin E-mediated reactivity.

BACKGROUND: Bronchial responsiveness and IgE-mediated reactivity are associated with specific bronchial reactivity to allergens. OBJECTIVE: Our aim was to examine whether airway inflammation also plays a role. METHODS: Retrospective analysis of all subjects who underwent specific inhalation challenges in the investigation of occupational asthma (OA) since 2000. Responsiveness to methacholine (PC(20) ) and levels of eosinophils and neutrophils in induced sputum on the control day were associated with the presence of OA (positive-specific inhalation challenge). In a sample of subjects exposed to wheat flour, we also examined the role of specific IgE- mediated reactivity (skin reactivity, specific IgE). RESULTS: PC(20) level was significantly more often normal in subjects with OA (35 of 129, 27% instances) by comparison with non-OA (15 of 189, 8% instances), but the positive predictive value of responsiveness to methacholine for OA was low (35%). Coupling information on the level of eosinophils to responsiveness to methacholine increased positive predictive values for OA from 39% to 69% depending on the thresholds used. The best balance of positive (69%) and negative (60%) predictive values was obtained in the case of normal PC(20) and eosinophils ≥3%. In a multivariate analysis carried out in 34 subjects exposed to wheat flour, responsiveness to methacholine, sputum eosinophils, skin weal size and levels of specific IgE were all significantly associated with OA to wheat flour. CONCLUSION AND CLINICAL RELEVANCE: Information on the level of sputum eosinophils in addition to PC(20) provides a better association with OA vs. non-OA when PC(20) is normal. Levels of sputum eosinophils in addition to PC(20) and IgE-mediated reactivity increase the likelihood of OA due to wheat flour.

Factors influencing duration of exposure with symptoms and costs of occupational asthma.

The most important factor for the prognosis of occupational asthma is the length of exposure with symptoms prior to removal from exposure. We wanted to identify factors, including socioeconomic status, that can influence the delay in submitting a claim to a medicolegal agency after the onset of asthmatic symptoms, and to confirm that this delay is associated with worse respiratory prognosis and higher direct costs. This is a cross-sectional study of subjects who claimed compensation for occupational asthma at the Workers' Compensation Board of Quebec, Canada. Data were collected at re-evaluation ∼2.5 yrs after diagnosis. Information on the number of years with symptoms and removal from exposure was obtained from the medicolegal file. 60 subjects were included in the study. Being older, having a revenue of >30,000 Canadian dollars and having occupational asthma due to high molecular weight agents were all positively associated with the number of years of exposure with symptoms before removal from exposure. Subjects with persistent airway hyperresponsiveness at follow-up had a higher number of years with symptoms. Experiencing symptoms in the workplace for <1 yr generated lower direct costs. These findings might help in surveillance programmes that could be preferentially targeted for these subgroups of workers.

Matrix metalloproteinases, IL-8 and glutathione in the prognosis of workers exposed to chlorine.

BACKGROUND: Workers exposed to chlorine may be at risk of deterioration in FEV1. METHODS: A prospective study of 72 workers examined over a 5.8 +/- 1.9 year period. A sample of induced sputum for cells and mediators was obtained in 69 subjects at baseline (Vb) and in 36 both at Vb and at follow-up (Vf). RESULTS: Sixty-four workers (89%) experienced at least one accidental inhalation of chlorine in the interval. The mean decrease in FEV1 was 30 ml/year and thus was within normal limits. Among the analysed remodelling markers, the level of the MMP-9-TIMP-1 complex, but not of free MMP-9 and TIMP-1, significantly diminished from Vb to Vf. We found significant correlations between neutrophils, IL-8, MMP-9 and MMP9-TIMP-1 complex at Vb and Vf. While levels of total glutathione, IL-8, MMP9, TIMP-1 and MMP9-TIMP-1 complex were highly correlated with each other at Vb, this was inconstant at Vf. Levels of MMP9-TIMP1 complex and of TIMP1 at Vf were significantly lower in workers reporting chlorine puffs with mild acute respiratory symptoms between visits compared to those who had no, or asymptomatic inhalations (P = 0.03 and 0.02, respectively). The fall in FEV1 from Vb to Vf was significantly correlated with levels of glutathione at Vb. Cough between visits was associated with a decrease in FEV1 (P = 0.06). CONCLUSION: Although no accelerated loss in FEV1 was documented in these workers exposed to chlorine, subjects with a greater fall in FEV1 were more likely to report cough and have higher levels of total glutathione at Vb.

Which tools best predict the incidence of work-related sensitisation and symptoms.

BACKGROUND/AIM: This study used information from the questionnaire alone or in conjunction with clinical tests, such as skin-prick testing (SPT) and bronchial responsiveness (BR) testing at entry, to develop models for estimating the probability of the occurrence of specific IgE-sensitisation to and respiratory symptoms in contact with laboratory animal (LA) allergens after 32 months' training in an animal health technology programme. METHODS: Four multivariable logistic regression models were developed for each endpoint, consisting of: (1) questionnaire; (2) questionnaire and SPT; (3) questionnaire and BR testing; and (4) questionnaire, SPT and BR testing. The prognostic models were derived from a cohort of Canadian animal health technology apprentices. The models' internal validity and diagnostic accuracy were evaluated and compared. RESULTS: Symptoms indicative of asthma and allergic symptoms at baseline composed the final questionnaire model for the occurrence of occupational sensitisation and symptoms. Both questionnaire models showed a good discrimination (area under the receiver operating characteristics curve were 0.73 and 0.78, respectively) and calibration (Hosmer-Lemeshow test p value >0.10). Addition of SPT and/or BR testing increased the specificity of the questionnaire model for LA sensitisation, but not for symptoms at work. To facilitate their application in practice, the final questionnaire models were converted to easy-to-use scoring system. CONCLUSIONS: Questionnaire is an easy tool that can give accurate prediction of the incidence of occupational sensitisation and symptoms.

Workplace-specific challenges as a contribution to the diagnosis of occupational asthma.

The diagnosis of occupational asthma can be made by exposing workers to the relevant agent either in a hospital laboratory through specific inhalation challenges (SICs) or in the workplace. As suggested by several authors, workers with negative laboratory SIC can be monitored at the workplace under supervision. The present study aims to assess the frequency of, and identify factors associated with, a positive workplace reaction in workers with negative SIC in the laboratory. The results of workplace challenges were examined in 99 workers who underwent negative SIC between 1994 and 2004. A positive reaction either in the SIC or in the workplace was defined as a sustained fall in forced expiratory volume in one second of > or =20%. In total, 22 (22.2%) workers showed positive responses at the workplace. These subjects more often had increased baseline methacholine responsiveness (90.5 versus 67.6%). They also underwent more days of SIC testing (4.9 versus 3.3 days) and were exposed more often to two or more agents (56 versus 28.4%) and for a longer period of time (363.3 versus 220.4 min) in the laboratory. The present study illustrates the usefulness of workplace monitoring of airway function in the investigation of occupational asthma and identifies factors that are more often associated with a positive reaction.

Structural changes and airway remodelling in occupational asthma at a mean interval of 14 years after cessation of exposure.

BACKGROUND: Occupational asthma (OA) may cause alterations of airways with inflammation and remodelling after cessation of exposure. Although the long-term clinical, functional and induced sputum sequelae have been examined in workers removed from exposure, the long-term pathological outcomes are unknown. OBJECTIVE: We aimed to investigate whether airway inflammation and remodelling were present in bronchial biopsies of subjects with prior OA but without evidence of persisting asthma at a mean interval of 14 years after cessation of exposure. METHODS: Ten clinically and functionally asymptomatic subjects with a prior diagnosis of OA were recruited and underwent bronchoscopy, bronchoalveolar lavage and bronchial biopsy. Comparisons were made with biopsies from normal control subjects. Epithelial detachment, epithelial metaplasia, mucous gland and airway smooth muscle (ASM) areas as well as the distance between the epithelium and ASM were measured by image analysis. The amount of collagen present was assessed by van Gieson staining. The numbers of TGF-beta1- and eosinophil cationic protein (ECP)-positive cells were evaluated by specific immunostaining. RESULTS: Statistically significant increases were found in the numbers of TGF-beta1- and ECP-positive cells and in the amount of subepithelial fibrosis present in the biopsies of subjects with prior OA compared with control biopsies. The distance between the epithelium and ASM was significantly reduced in the OA group. Increases in epithelial metaplasia, ASM mass, mucous gland numbers, collagen deposition and eosinophilia in the OA group were not statistically significant. There was no evidence of ongoing inflammation in the group with prior OA as assessed by the number of T lymphocytes present. CONCLUSION: Some aspects of airway inflammation and remodelling persist in subjects with prior OA long after cessation of exposure even in the absence of clinical, sputum and functional abnormalities. These findings are relevant to the assessment of long-term sequelae in subjects with OA when reviewed after cessation of exposure.

Assessment of impairment/disability due to occupational asthma through a multidimensional approach.

Subjects with occupational asthma (OA) are often left with permanent sequelae after removal from exposure, and assessing their impairment/disability should utilise various tools. The aim of the present study was to examine whether: 1) assessment of inflammation in induced sputum is relevant to impairment; and 2) use of questionnaires on quality of life and psychological factors can be useful for the evaluation of disability. In total, 40 subjects were prospectively assessed for permanent impairment/disability due to OA 2 yrs after cessation of exposure. Impairment was assessed as follows: 1) need for asthma medication; 2) asthma severity; 3) airway calibre and responsiveness; and 4) degree of inflammation in induced sputum. Disability was assessed according to quality of life and psychological distress. There was a significant improvement in airway responsiveness and inflammation from diagnosis to the present assessment. Sputum eosinophils > or =2% and neutrophils >60% were present in eight (20%) and 12 (30%) out of all subjects, respectively, one or the other feature being the only abnormalities in 15% of subjects. Quality of life was moderately affected and there was a prevalence of depression and anxiety close to 50%. In the assessment of subjects with occupational asthma, information on airway inflammation and psychological impacts are relevant to the assessment of impairment/disability, although these findings need further investigation.

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.

Exaggerated bronchoconstriction due to inhalation challenges with occupational agents.

Inhalation challenges with occupational agents are used to confirm the aetiology of occupational asthma. It has been proposed that using closed-circuit equipment rather than the realistic challenge method would improve the methodology of these tests. Changes in forced expiratory volume in one second (FEV1) were examined in 496 subjects with "positive specific inhalation challenges", i.e. changes in FEVI of > or = 20% after exposure to an occupational agent, including 357 subjects exposed by the realistic method, 108 using the closed-circuit method and 31 by both methods. For immediate reactions, 18 of 95 (19%) showed changes in FEV1 of > or = 30% with the closed-circuit method, whereas a significantly larger proportion, i.e. 77 of 200 (38.5%), showed such changes using the realistic method. As regards nonimmediate reactions, changes in FEV1 of > or = 30% occurred in 16 of 43 (37%) cases with the closed-circuit method as compared to a larger proportion, i.e. 87 of 180 (48%) cases, using the realistic method. This favourable effect was significantly more pronounced in workers with higher levels of bronchial hyperresponsiveness to methacholine. It is concluded that, for agents that can be generated using the closed-circuit method, use of such apparatus results in a smaller proportion of exaggerated bronchoconstriction than does the realistic method, this being particularly true for low-molecular weight agents.

Individual characteristics and quitting in apprentices exposed to high-molecular-weight agents.

To determine whether specific immunological sensitization (SIS) and symptoms of allergy are associated with quitting apprenticeships with exposure to high-molecular-weight (HMW) agents. In a cohort study of 769 apprentices starting career programs in animal health technology (AHT), pastry-making (PM), and dental hygiene technology (DHT), health status was assessed at baseline and yearly for up to 44 mo. Subjects who quit the apprenticeship were contacted and offered a last series of measurements as if they pursued. The effect of various factors-at baseline and during the career program-on quitting was examined. Eighty-nine of 769 subjects (11.6%) quit, of whom 74 participated in this study. In multivariate analysis, a history of hay fever (OR = 1.66, 95% CI = 1.0 to 2.75) and attending the pastry-making program (OR = 2.33, 95% CI = 1.11 to 4.91) were significant determinants for quitting. In the subgroup of AHT, SIS to laboratory animals, hay fever, and shortness of breath were significant determinants by univariate analysis; in PM, the only determinant was age; and in DHT, hay fever. Work-related symptoms during training were not associated with quitting. In a multivariate logistic regression analysis in AHT, including characteristics at baseline and at follow-up, baseline SIS (OR = 2.8, 95% CI = 0.94 to 8.38) and symptoms of asthma in general during follow-up (OR = 2.2, 95% CI = 0.94 to 5.38) were the main determinants for quitting, though they were of borderline significance. We conclude that health-related self-selection out of an apprenticeship with exposure to HMW agents is likely to occur and to cause an attrition bias.

Comparison of serial monitoring of peak expiratory flow and FEV1 in the diagnosis of occupational asthma.

Peak expiratory flow (PEF) monitoring is often used to establish the relationship between occupational exposure and asthma. FEV1 has been found to be a better physiologic index than PEF in the measurement of airflow obstruction. The aim of this study was to compare the accuracy of serial monitoring of PEF and FEV1 in the diagnosis of occupational asthma. Twenty consecutive subjects referred for possible occupational asthma were asked to perform serial monitoring of PEF and FEV1 using a portable ventilometer. Two sets of graphs were plotted for both PEF and FEV1: graphs with the best of all values and graphs with the best of two reproducible values. Three observers interpreted both PEF and FEV1 recordings by the visual method in a blind, randomized manner as either compatible with occupational asthma or not. Eleven of the subjects had a positive inhalation challenge test (high-molecular-weight agents, n = 6; low-molecular-weight agents, n = 5). In the case of analysis of the graphs plotted with the best of all values, the sensitivity of the PEF recording interpreted by the three observers was 82, 73, and 73%, and of the FEV1 recording as 55, 55, and 45%; specificity of PEF recording was 89, 100, and 100%, and of FEV1 was 56, 89, and 100%. When an agreement between two of the three readers was required to define occupational asthma, sensitivity and specificity were 73 and 100% for PEF and 55 and 89% for FEV1. Lower sensitivities were found when the same analyses were performed with the graphs plotted with the best of two reproducible values. It was concluded that unsupervised FEV1 is not more accurate than unsupervised PEF monitoring in the diagnosis of occupational asthma. Plotting graphs using the best value gives better diagnostic accuracy than plotting them with the best of two reproducible values.

Outcome of specific bronchial responsiveness to occupational agents after removal from exposure.

A decrease in specific bronchial responsiveness (SBR) could occur after removal from exposure to an agent causing occupational asthma as a result of loss of immunologic and/or nonspecific bronchial reactivity (NSBR). We studied 15 subjects with occupational asthma (eight to a high- and seven to a low-molecular-weight agent, isocyanate in all instances), proved by specific inhalation challenges (SIC) done 2 yr or more before. Subjects were reexposed in the same way as in the initial SIC: for subjects who did not react, the exposure was increased until either an asthmatic reaction occurred or a maximum of 2 h was reached. NSBR was assessed before and after SIC. Subjects had a decrease in their SBR if the total dose of agent necessary to induce asthmatic reaction was greater by twofold compared with the initial SIC. There was a significant improvement in NSBR in seven of 15 subjects. Nine of 15 subjects (60%) had a decrease in their SBR. Only one had a complete loss of SBR. Changes in NSBR, molecular weight of the offending agent, decrease of antibody level against offending agents, or duration of exposure at work did not explain the decrease in SBR. We conclude that after removal from exposure to the offending agent a majority of subjects (60%) show a decrease but a persistence of SBR to high- and low-molecular-weight agents.

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.

Cross-sectional assessment of workers with repeated exposure to chlorine over a three year period.

Airflow obstruction has been described in workers who experienced symptoms after acute exposure to chlorine. Persistent bronchial hyperresponsiveness has also been assessed, but mainly in case studies. In this cross-sectional study, we have assessed the relationship between inhalational accidents ("puffs") involving chlorine and persistent symptoms as well as hyperresponsiveness in 239 out of 255 at-risk workers (94%). No relationship was found between persistent symptoms and the exposure variables studied. Forced vital capacity (FVC) was higher in subjects who had had no symptoms after a "puff", compared with those who had experienced mild symptoms. Forced expiratory volume in one second (FEV1) and FVC were significantly lower in subjects who experienced more than 10 puffs with mild symptoms than in subjects who reported no symptomatic puff. The presence of bronchial hyperresponsiveness was not related to exposure, but the methacholine dose-response slope showed a tendency to increased bronchial responsiveness with increased exposure. A significant difference was shown in subjects who experienced more than 10 puffs with mild symptoms. In this group of workers, repeated exposure to chlorine with acute respiratory symptoms was associated with a slight but significant reduction in expiratory flow rates, together with an increase in bronchial responsiveness, without long-term symptoms.

Do subjects investigated for occupational asthma through serial peak expiratory flow measurements falsify their results?

BACKGROUND AND AIM: Serial assessment of peak expiratory flow (PEF) rates has been advocated as a sensitive and specific means of investigating occupational asthma. The possibility that, for several reasons, subjects do not accurately report their values has been raised. The availability of portable instruments that assess PEF and store timings and values now make it possible to estimate compliance and accuracy of results. METHODS: Twenty-one subjects consecutively investigated for occupational asthma were asked to assess their PEF every 2 hours during the day, both at work and away from work, with a VMX instrument (Clement Clarke International, Columbus, Ohio) and record the times and values on a sheet of paper. The subjects were not aware that the data were also being stored on a computer chip. The diagnosis was occupational asthma in eight subjects, personal asthma in four subjects, and neither condition in nine subjects. RESULTS: The mean duration of recording was 36 days (range, 14 to 79 days). At least 6048 values should have been recorded, but only 4839 (80%) were either recorded or stored. Reported values corresponded precisely to stored values in 2533 of 4839 recordings (52%). The timing of the recording was also examined in relation to the time at which the recording was solicited; values recorded within 1 hour of the solicited time were judged as acceptable. Of the total of 3342 recordings stored, 2375 (71%) satisfied this criterion. Compliance was significantly less satisfactory in those referred by the Workers' Compensation Board (n = 11). CONCLUSION: In this survey of 21 subjects investigated for possible occupational asthma, compliance with PEF recording, as assessed by comparing recorded and stored results and the time at which the recording was solicited, was poor.

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.

The reversibility of airway obstruction to an inhaled beta 2-adrenergic agent is less satisfactory after methacholine testing in asthmatic subjects.

AIMS: The aim of this work was to compare the response to an inhaled beta 2-adrenergic agent in two situations: (1) spontaneous airway obstruction in asthmatic subjects who had withheld treatment with the medication for more than 12 hs; and (2) after methacholine-induced airway obstruction once airway caliber had recovered to the premethacholine test value. SUBJECTS AND METHODS: Sixteen asthmatic subjects who showed a 20% or more improvement in FEV1 after inhaled beta 2-adrenergic agent (B2) (salbutamol, 200 micrograms) entered a double-blind crossover randomized trial in which the following tests were carried out: (1) FEV1 response after inhaling a placebo or active B2; (2) FEV1 response after inhaling a placebo or active B2 after a methacholine test that had induced a 20% or more reduction in FEV1, once FEV1 had recovered to the premethacholine value after inhaling salbutamol in an open fashion. RESULTS: As expected, the mean percent improvement in FEV1 in the spontaneous airway obstruction situation was 21.7 +/- 8.5% after inhaling the active B2 and 2.2 +/- 1.8% after placebo B2 (p < 0.001). Following recovery after methacholine challenge, the FEV1 was slightly superior (mean difference of 146 mL) to the premethacholine value before inhaling the active or placebo B2. In this situation, the percent improvement in FEV1 after inhaling the active B2 was only 7.5 +/- 4.4% and not significantly different from after inhaling placebo B2 (4.9 +/- 5.4%). Consequently, the end FEV1 value after inhaling active B2 was significantly higher in a situation of spontaneous airway obstruction than after methacholine-induced airway obstruction (mean difference = 110 mL; p = 0.02). CONCLUSION: After a methacholine test, the reversibility of an inhaled beta 2 agent is not significantly different from a placebo and is less satisfactory than in a situation of spontaneous airway obstruction. The mechanism for this needs to be explored but it is not secondary to persisting airway obstruction.

Prevalence of occupational asthma among workers exposed to eastern white cedar.

We assessed the prevalence of occupational asthma among current (n = 29/31, 94%) and former (n = 13/49, 27%) employees of a sawmill in which eastern white cedar has been made into shingles during the past 3 yr. All participants answered a respiratory questionnaire, and all except one underwent spirometry and methacholine inhalation tests. All those with bronchial hyperresponsiveness (PC20 methacholine < or = 19 mg/ml) were invited to undergo specific inhalation challenges. Mean duration of exposure was 13 mo (19 workers > 12 mo). Twenty-eight workers (65%) reported a history compatible with asthma, and 25 (58%) had symptoms that were suggestive of occupational asthma. Only two subjects had significant airway obstruction (FEV1 < 80% pred) (mean value = 98% pred). Eighteen subjects (42%) had a PC20 < or = 16 mg/ml. Specific inhalation tests with plicatic acid and/or western red cedar (which contains twice as much plicatic acid as eastern white cedar), were done on 12 subjects who had a PC20 < or = 16 mg/ml when they were assessed. Three subjects were considered to have positive tests (one had an isolated immediate reaction, one had a late reaction, and one had significant changes in PC20 each time he was exposed but no changes in FEV1). Environmental monitoring showed concentrations of total dusts above 2 mg/m3 in half of the samples. The prevalence of occupational asthma in this workplace was three of 42 participants (7%) or at least three of 80 (3.8%) of all current or ex-workers. This is comparable to the prevalence of occupational asthma in subjects exposed to western red cedar.

Bronchial hyperresponsiveness can improve while spirometry plateaus two to three years after repeated exposure to chlorine causing respiratory symptoms.

Repeated exposure to chlorine in pulp mills and paper can induce persistent asthma-like symptoms such as bronchial hyperresponsiveness and variable changes in airway caliber. The long-term time course of bronchial hyperresponsiveness has not been examined. We studied 20 of 29 subjects (69% participation rate) who demonstrated bronchial hyperresponsiveness to methacholine when they were first assessed, 18 to 24 mo after repeatedly inhaling "puffs" of high concentrations of chlorine in a paper mill over a 3-mo period. Each subject answered a respiratory questionnaire and underwent spirometry and a methacholine inhalation test 12 mo after the initial survey, 30 to 36 mo after the chlorine inhalations. Three subjects required inhaled steroids at the time of the initial survey and three at the time of the second, including two who carried on using these preparations. Only one subject changed smoking habits. There were no significant overall changes in FEV1 on the two occasions, nine subjects having a FEV1 < 80% on the first occasion and eight on the second. Six of the 18 subjects (33%) who underwent a methacholine inhalation test on both occasions had significantly improved PC20 results, including five for whom the PC20 value was within the normal range. All six subjects had normal FEV1 values on both assessments. Although changes in spirometry induced by repeated exposure to chlorine seem to persist, bronchial hyperresponsiveness can improve significantly in those with normal airway caliber. This suggests that less pronounced bronchial alterations induced by repeated exposures to chlorine may be reversible.