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.

Exhaled nitric oxide and spirometry in respiratory health surveillance.

BACKGROUND: Exposure to pollutants in bakeries and hairdressing salons can cause airway syndromes varying from bronchial irritation to asthma. Workplace respiratory health surveillance aims to identify possible cases requiring further investigation. AIMS: To compare the performance of fractional exhaled nitric oxide (FE(NO)) and spirometry for health surveillance of apprentice bakers (ABs) and apprentice hairdressers (AHDs). Determinants of FE(NO) were also identified. METHODS: Symptoms and physician-diagnosed asthma were evaluated by questionnaire. FE(NO) was measured and spirometry was carried out. Subjects with elevated FE(NO) (FE(NO) > upper limit normal), airway obstruction [forced expiratory volume in 1 s (FEV(1))/forced vital capacity (FVC) < 95th percentile] and atopy (history of allergies) were identified. RESULTS: A total of 126 apprentices (59 ABs and 67 AHDs) participated. Twenty-nine (23%) apprentices had abnormal tests: 4 had associated high FE(NO) and airway obstruction, while 25 had either high FE(NO) (n = 15) or airway obstruction (n = 10) alone. Compared with ABs (n = 16), AHDs (n = 13) had more asthma (38 versus 0%; P < 0.05) and atopy (62 versus 6%; P < 0.05). There was no difference in symptoms, smoking FE(NO) or airways obstruction. Among 97 subjects with normal tests, no differences existed between ABs (n = 53) and AHDs (n = 44). Average FE(NO) was increased in atopic non-smokers compared with atopic smokers and non-atopic subjects (P < 0.05). Smoking, a history of allergies, FEV(1)/FVC % observed and respiratory symptoms were the main determinants of FE(NO). CONCLUSIONS: FE(NO) and spirometry were not overlapping dimensions in ABs and hairdressers, each test contributing unique information on the physiological status of the respiratory system. FE(NO) may provide added information on airway inflammation not provided by spirometry.

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.

Correlation between acoustic rhinometry and subjective nasal patency during nasal challenge test in subjects with suspected occupational rhinitis; a prospective controlled study.

OBJECTIVES: To assess the correlation between acoustic rhinometry and visual analogue scale endpoints in the context of nasal challenge with occupational agents. DESIGN: Prospective controlled study. SETTING: University teaching hospital. PARTICIPANTS: Sixty-seven subjects with a history of work-related rhinitis and asthma symptoms. MAIN OUTCOMES MEASURES: Subjects underwent nasal challenge with control and specific agent on consecutive days. Nasal congestive response to challenge was monitored by acoustic rhinometry and visual analogue scale. RESULTS: Results showed no correlation between visual analogue scale and acoustic rhinometry measurements at baseline on the control (r=-0.13, P=0.3) and active (r=0.14, P=0.2) challenge days. No correlation was found between acoustic rhinometry and visual analogue scale when analysing all measurements obtained at all times after challenge with the control and active agent (control: r=0.09, P=0.04; active: r=0.001, P=0.9). The correlation between acoustic rhinometry and visual analogue scale was good and significant (r=-0.62, P=<0.01) when the analysis was restricted to cases showing a decrease in nasal volume>40% from baseline values. CONCLUSIONS: We showed that the correlation between acoustic rhinometry and subjective nasal patency was poor on steady conditions. However, a significant correlation was observed in those cases showing a greater nasal congestive response after challenge measured by acoustic rhinometry.

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.

Risks for the development of outcomes related to occupational allergies: an application of the asthma-specific job exposure matrix compared with self-reports and investigator scores on job-training-related exposure.

BACKGROUND AND AIM: Risks for development of occupational sensitisation, bronchial hyper-responsiveness, rhinoconjunctival and chest symptoms at work associated with continued exposure to high molecular weight (HMW) allergens were estimated with three exposure assessment methods. METHODS: A Cox regression analysis with adjustment for atopy and smoking habit was carried out in 408 apprentices in animal health technology, pastry making, and dental hygiene technology with an 8-year follow-up after training. The risk of continued exposure after training, estimated by the asthma-specific job exposure matrix (JEM), was compared with self-reports and investigator scores on job-training-related exposure. Associations between outcomes and work duration in job(s) related to training were also evaluated. RESULTS: Exposure to animal-derived HMW allergens, subsequent to the apprenticeship period, as estimated by the JEM, was associated with a significantly increased risk for occupational sensitisation (hazard ratio (HR) 6.4; 95% CI 2.3 to 18.2) and rhinoconjunctival symptoms at work (HR 2.6; 95% CI 1.1 to 6.2). Exposure to low molecular weight (LMW) agents significantly increased the risk of developing bronchial hyper-responsiveness (HR 2.3; 95% CI 1.1 to 5.4). Exposure verification appeared to be important to optimise the sensitivity and the specificity, as well as HRs produced by the JEM. Self-reports and investigator scores also indicated that further exposure to HMW allergens increased the risk of developing occupational allergies. The agreement between self-reports, investigator scores, and the JEM were moderate to good. There was no significant association between respiratory outcomes and work duration in jobs related to training. CONCLUSION: The asthma-specific JEM could estimate the risk of various outcomes of occupational allergies associated with exposure to HMW and LMW allergens, but it is relatively labour intensive. Exposure verification is an important integrated step in the JEM that optimised the performance of the matrix.

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.

Specific antibodies to diisocyanate and work-related respiratory symptoms in apprentice car-painters.

BACKGROUND: Isocyanates are the main cause of occupational asthma in most countries. Study of immunological markers of diisocyanate asthma may identify individuals at risk. OBJECTIVES: (1) To study changes in specific antibodies to hexamethylene diisocyanates (HDI); (2) to describe the incidence of work-related respiratory symptoms in relation to changes in specific antibody levels. METHODS: Prospective study in 385 apprentice car-painters during their 18 months of training. Participants were assessed on entering and completing their training using questionnaires, methacholine challenges and measurements of HDI-specific immunoglobulin E (IgE), immunoglobulin G (IgG) and subclass 4 of IgG (IgG4) antibodies. RESULTS: Complete data are available for 298 subjects. 13 subjects (4.4%) reported >or=1 new work-related lower respiratory symptoms and 19 (6.4%), >or=1 new work-related nasal symptoms. Increases in levels of specific IgE and IgG above the 97th and 95th percentiles were significantly associated with duration of exposure. Increase in specific IgG was inversely related to incidence of work-related lower respiratory symptoms (OR = 0.001, 95% CI 0.000 to 0.09) after adjusting for relevant covariates. The rise in specific IgG4 was significantly greater in those who did not develop work-related nasal symptoms (OR = 0.09, 95% CI 0.01 to 0.7). CONCLUSION: In this cohort of apprentice car-painters, a small proportion show increases in HDI-specific IgG and IgE after few months of exposure. Increases in specific IgG and IgG4 appear to have a protective effect on the incidence of work-related lower and upper respiratory symptoms, respectively. Assessment of specific antibodies to isocyanates may help identify subjects at risk of developing symptoms.

Comparison of lung morphology in COPD secondary to cigarette and biomass smoke.

OBJECTIVE: To compare lung morphology in chronic obstructive pulmonary disease (COPD) secondary to cigarette smoke (CS) and biomass smoke (BS). METHODS: Necropsies of women with COPD diagnosis by lung pathology and unique exposure to BS (n = 27) or CS (n = 21) matched by age and place of origin. Lungs were macroscopically and microscopically examined to evaluate the extent of emphysema, pigment deposition, and abnormalities in pulmonary arteries, large airways (including the Reid index) and small airways (SAWs) by a semiquantitative method. RESULTS: Both groups had variable degrees of emphysema and SAWs disease. Patients exposed to BS had more lung fibrosis and pigment deposition and thicker pulmonary arterial intima than smokers, who had more emphysema and epithelial damage (goblet cell metaplasia). The Reid index was similar in both groups. CONCLUSION: Lengthy exposure to BS can produce emphysema and other lesions typically observed in cigarette smokers, but with a slightly different distribution. Whether the differences observed are the consequence of severity of exposure or smoke composition, or both, remains to be clarified.

[Sensitization to Aspergillus fumigatus and functional outcome of asthma]. / Sensibilisation à Aspergillus fumigatus et devenir fonctionnel de l'asthme.

INTRODUCTION: Despite a high prevalence in the asthmatic population, sensitization to Aspergillus has not benefited from the same research interest as the other mould species. This study aims at investigating the role of the presence or the absence of Aspergillus sensitization in the deterioration of airway caliber in asthmatics over a five-year follow-up. MATERIAL AND METHODS: One hundred and thirty-three asthmatic subjects aged 18 to 40 years were separated into two groups: those sensitized (cases) and those not sensitized (controls) to Aspergillus were matched according to the following criteria: age, gender and FEV1 (% pred). Clinical, functional, allergic and therapeutic parameters were studied. RESULTS: The FEV1 slope was less pronounced in the group sensitized to Aspergillus (-17 mL/year) in comparison to the controls (27 mL/year). There was also a less noticeable slope of forced vital capacity in the sensitized subjects (-25 mL/year) as compared to the controls (28 mL/year). All of these differences were not statistically significant. CONCLUSION: We did not find any increase in the decline in FEV1 or FVC associated with sensitization to Aspergillus.

Paper stamp checklist tool enhances asthma guidelines knowledge and implementation by primary care physicians.

BACKGROUND: The Canadian Clinical Practice Guidelines (CPGs) for the management of asthmatic patients were last published in 1999, with updates in 2001 and June 2004. Large disparities exist in the implementation of these guidelines into clinical practice. OBJECTIVE: The present study evaluated the knowledge of Quebec-based primary care physicians regarding the CPGs, as well as patient outcomes before and after introducing physicians to a new clinical tool--a memory aid in the form of a self-inking paper stamp checklist summarizing CPG criteria and guidelines for assessing asthmatic patient control and therapy. The primary objective of the present study was to assess whether the stamp would improve physicians' knowledge of the CPGs, and as a secondary objective, to assess whether it would decrease patient emergency room visits and hospitalizations. METHODS: A prospective, randomized, controlled study of 104 primary care physicians located in four Quebec regions was conducted. Each physician initially responded to questions on their knowledge of the CPGs, and was then randomly assigned to one of four groups that received information about the CPGs while implementing an intervention (the stamp tool) aimed at supporting their decision-making process at the point of care. Six months later, the physicians were retested, and patient outcomes for approximately one year were obtained from the Régie de l'assurance maladie du Québec. RESULTS: The stamp significantly improved physicians' knowledge of the CPGs in all Quebec regions tested, and reduced emergency room visits and hospitalizations in patients who were followed for at least one year. CONCLUSION: A paper stamp summarizing CPGs for asthma can be used effectively to increase the knowledge of physicians and to positively affect patient outcomes.

Interaction of body weight and ethnicity on risk of gestational diabetes mellitus.

BACKGROUND: The James Bay Cree of Canada have one of the highest recorded rates of gestational diabetes mellitus (GDM) among aboriginal people worldwide; the reasons for this elevated risk remain to be documented. OBJECTIVE: Our objective was to compare predictors and risk of GDM between the James Bay Cree and non-Native Canadians. DESIGN: Risk for GDM was compared between Cree and non-Native women by 1) adjusting statistically for differences in age, parity, pregravid weight, and smoking status (n = 402 Cree, 7718 non-Natives), and 2) matching Cree women with non-Native women for age and pregravid weight (n = 394 Cree, 788 non-Natives). Dietary and physical activity information was available for a subset of Cree women (n = 152). RESULTS: Age and pregravid weight were independent predictors of GDM in both Cree and non-Native women. After these predictors were controlled for, normal-weight (

Occurrence and risk factors of oral candidiasis treated with oral antifungals in seniors using inhaled steroids.

Oral candidiasis (OC) is a frequent side effect of inhaled corticosteroids (iCSTs). This study estimated occurrence and significance of risk factors of OC treated with antifungals in users of iCSTs under conditions of normal use. This retrospective analysis used data drawn from drug insurance plan records in Quebec, Canada. The sample contained 27,000 seniors using anti-asthma medications during 1990. Three years of data (1989-1991) were searched for use of oral antifungals concurrent with exposure to iCSTs. A case-control study examined factors leading to increased probability of first incidence of OC in new users of iCSTs. Three-year occurrence for OC was 7%. Increased risk for a first occurrence of OC was significantly associated with higher doses of iCST, increased length of iCST exposure, use of antibiotics, use of oral steroids, having three or more prescribers, a history of use of both high and low strengths of iCST, and concurrent use of oral steroids and diabetes medications. The occurrence of OC is relatively high. Knowledge of factors leading to increased risk could facilitate the targetting of patients who need timely intervention, under conditions of normal use.

Orthopnea and tidal expiratory flow limitation in patients with stable COPD.

BACKGROUND: Orthopnea is a common feature in COPD patients, although its nature is poorly understood. OBJECTIVE: To study the role of tidal expiratory flow limitation (FL) in the genesis of orthopnea in patients with stable COPD. MEASUREMENTS: Tidal FL was assessed in 117 ambulatory COPD patients in sitting and supine positions using the negative expiratory pressure method. The presence or absence of orthopnea was also noted. RESULTS AND CONCLUSIONS: In patients with stable COPD with tidal expiratory FL in seated and/or supine position, there is a high prevalence of orthopnea, which probably results in part from increased inspiratory efforts due to dynamic pulmonary hyperinflation and the concomitant increase in inspiratory threshold load due to intrinsic positive end-expiratory pressure. Increased airway resistance in supine position due to lower end-expiratory lung volume probably also plays a role in the genesis of orthopnea.

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.

Single-dose effect of astemizole on bronchoconstriction induced by histamine in asthmatic subjects.

STUDY OBJECTIVE: Astemizole, administered for seven days to asthmatic subjects, had an effect of bronchoconstriction induced by inhaled histamine for a mean period of 42 days. This study evaluates whether a single dose of astemizole would have the same effect. SUBJECTS: Sixteen adult asthmatic subjects took part in the study. DESIGN: They first underwent three inhalation tests and skin prick tests with histamine on three different days. On the last day, a methacholine inhalation test was also performed. They subsequently received either a placebo or an active preparation of astemizole. The histamine inhalation test was repeated one day, two days, one week, and/or ten days after administering the drug. RESULTS: Overall, no significant change in mean PC20 or in the mean diameter of the skin reaction to histamine was observed. However, three out of the eight subjects (38 percent) receiving active and none receiving placebo medication showed significant increases in PC20 histamine (p = 0.05). This effect lasted for one to two days. CONCLUSIONS: We conclude that a single dose of 10 mg/ml of astemizole can have a significant effect on bronchial but not cutaneous reactivity to histamine. This effect is of short duration (one to two days).

Exercise limitation in obstructive lung disease.

OBJECTIVE: To study the relationship of resting pulmonary function to maximal exercise power output (Wmax) in obstructive lung disease (OLD). SETTING: University Hospital Pulmonary Function Laboratory. SUBJECTS: Twenty-five patients with OLD (6 with asthma and 19 with COPD). METHODS: Measurement of pulmonary lung function, resting arterial blood gases, and maximal symptom-limited exercise on a cycle ergometer. RESULTS AND CONCLUSIONS: In OLD, the only significant contributor to Wmax was the inspiratory capacity (r2 = 0.66; p < 0.001).

Follow-up of occupational asthma after removal from or diminution of exposure to the responsible agent: relevance of the length of the interval from cessation of exposure.

STUDY OBJECTIVE: We set the hypothesis that follow-up surveys of occupational asthma (OA) could now show better improvement in the asthmatic condition because of a more prolonged interval since removal from exposure than in previously reported studies. PATIENTS/METHODS: Ninety-nine subjects with OA were assessed and were separated into two groups according to the duration of cessation of exposure: (1) group removed for > or = 5 years: 48 subjects studied 8.9+/-2.2 years after cessation of exposure; (2) group removed for <5 years: 51 subjects with OA, comparable in terms of history and functional results at time of diagnosis, with a time lapse from last exposure of 3.1+/-1.2 years. On the follow-up visit, questionnaires including information on the current and previous use of inhaled steroids, spirometry, and methacholine tests were administered and results were compared with those obtained at the time of diagnosis. RESULTS: At the follow-up visit, no significant changes in spirometry were observed in the two groups. However, a significant improvement in provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) from a mean value of 1.5 to 3.7 mg/mL was documented (p<0.001). The proportion of subjects having normal PC20 at the follow-up visit was significantly higher in the group removed from exposure for >5 years than in the group removed for < or = 5 years (16/33 vs 8/42; p=0.01). Stepwise logistic regression showed that follow-up PC20 could be predicted from baseline PC20 (p<0.001, odds ratio [OR]=4.1, 95% confidence interval [CI]=1.8 to 9.1), duration of exposure (p=0.04, OR=0.9, 95% CI=0.8 to 1.0), the interval since removal from exposure (p=0.002, OR=1.7, 95% CI=1.2 to 2.5), and the type of agent; subjects with OA due to high-molecular-weight agent showed a less favorable outcome (p=0.04, OR=0.2, 95% CI=0.03 to 1.0). Current and past treatments with inhaled steroids were not significant predictors. CONCLUSION: Results obtained in the group of this study removed for >5 years show better prognostic figures than those reported in most previous studies. Comparison with the group removed for a shorter interval and the stepwise logistic regression analysis suggest that the longer duration of the interval from cessation of exposure appears to be a factor determining this difference.

Occupational asthma due to various agents. Absence of clinical and functional improvement at an interval of four or more years after cessation of exposure.

We have previously shown that in some subjects with occupational asthma caused by various agents, there is no improvement approximately two years after exposure ended. These results could be explained by the short interval between diagnosis and follow-up. In the current study, we saw 28 subjects with occupational asthma at two intervals, 2.3 years (range, three months to 5.7 years) and 5.8 years (range, 4.3 to 10.9 years) after the cessation of exposure. Various causes of occupational asthma were included. The diagnosis was confirmed in 26 of the cases by specific inhalation challenges in the laboratory, and in the remaining two cases by combined monitoring of peak expiratory flow rates and bronchial responsiveness. All subjects had symptoms of asthma at both follow-up assessments. There were no changes in the need for medication, spirometry, or bronchial hyperresponsiveness. Depending on the interval of the follow-up, four to six subjects required inhaled steroid agents in addition to the usual bronchodilators, 11 had FEV1 less than 80 percent of predicted, and 26 or 27 had an abnormal PC 20 histamine. Only two subjects demonstrated sustained improvement in PC 20 at the first and second follow-ups, and one other showed changes during the second follow-up assessment which were not present at the first. We conclude that except for three subjects, the need for medication did not diminish, nor did airway obstruction and hyperresponsiveness improve in this group of subjects with occupational asthma long after exposure ended. These results differ from other studies, which demonstrated that some recovery takes place in a greater proportion of individuals.