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.

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.

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.

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.

Airway hyperresponsiveness and risk of chest symptoms in an occupational model.

BACKGROUND: The clinical outcome of asymptomatic airway hyperresponsiveness (AHR) remains unclear. A study was undertaken to evaluate the incidence of respiratory symptoms in a cohort of asymptomatic subjects with AHR at baseline. METHODS: A 3 year prospective study involving methacholine challenge tests and serially administered questionnaires was undertaken in 769 apprentices exposed to high molecular weight allergens. Analyses were performed on 428 initially asymptomatic subjects. RESULTS: Thirty eight subjects (8.9%) were airway hyperresponsive (PC(20) < or =8 mg/ml) and asymptomatic at the start of the study. Forty four apprentices (10.3%) developed two or more respiratory symptoms unrelated to work, 13 (34.2%) in the AHR group and 31 (7.9%) in the non-AHR group (risk ratio (RR) 7.88 (95% CI 2.53 to 24.55) among subjects with AHR). The RR of developing two or more respiratory symptoms increased as the degree of PC(20) decreased with a significant trend (p<0.001). In a multivariate analysis, AHR (RR 8.33, 95% CI 2.65 to 26.16) and self-reported rhinitis on exposure to pollen through an interaction with a family history of asthma (RR 6.3, 95% CI 1.29 to 31.89) were associated with the incidence of two or more respiratory symptoms; atopy was not a significant covariate. CONCLUSION: AHR in asymptomatic subjects is an important determinant for the development of respiratory symptoms outside the workplace among apprentices exposed to high molecular weight allergens in their training environment.

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.

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.

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.

Rhinoconjunctivitis, bronchial responsiveness, and atopy as determinants for incident non-work-related asthma symptoms in apprentices exposed to high-molecular-weight allergens.

OBJECTIVE: The aim of this study was to explore the role of rhinoconjunctivitis (RC), taking into account atopy and the level of bronchial responsiveness to methacholine, on the incidence of respiratory symptoms and in the development and/or worsening of asthma. METHODS: We examined data from a prospective study in 769 students starting exposure to high-molecular-weight occupational allergens and who were serially followed for up to 44 months. RESULTS: The presence of RC symptoms at baseline was significantly associated with an increased risk of developing shortness of breath and wheezing in atopic subjects regardless of PC20 level and in subjects with a PC20

Risk factors for bronchial hyperresponsiveness in late childhood and early adolescence.

The prevalence of asthma and bronchial hyperresponsiveness (BHR) tends to decrease in male children but increase in female children in the transition from childhood to adolescence. Hormonal factors may be involved in the natural history of asthma during this period. In a prospective study of Montreal school children, the authors examined the determinants of BHR according to the child's pubertal status; 156 male children and 168 female children without a prior diagnosis of asthma were followed for an average of 4.6 yrs. Average age at follow-up was 13.4 yrs and 59% had reached puberty. The prevalence of BHR at follow-up was similar among pre- and postpubertal male children (25.0% versus 29.2%),while BHR was more common among post- compared with prepubertal female children (33.1% versus 14.2%). There were no differences in the determinants (measured in childhood) of BHR at follow-up according to pubertal status. The major determinant of BHR was a positive skin test to dust-mite antigen. BHR was also linked to exposure to gas cooking and the presence of exercise-induced bronchospasm. In conclusion, the results of this study do not support a change in asthma phenotype with the onset of puberty. Pre- and postpuberty, the major determinant of bronchial hyperresponsiveness was skin sensitivity to mite allergen.

Incidence and host determinants of work-related rhinoconjunctivitis in apprentice pastry-makers.

BACKGROUND: The authors recently assessed the incidence and determinants of immunologic sensitization to flour in apprentice pastry-makers. The aim of this work was to determine the incidence of work-related rhinoconjunctivitis (RC) symptoms and their determinants. METHODS: For this 188/230 entrants (81.7%) were evaluated before starting exposure to flour, and again 10.8 and 16.8 months after. Questionnaires and skin prick testing to common and work-related allergens were administered at each visit. Bronchial responsiveness to methacholine was assessed at baseline in all subjects and in a subgroup at follow-up. RESULTS: Thirty subjects (16.1%) reported new work-related RC symptoms (13.1 per 100 person-years); in three subjects (1.6%), these were accompanied by incident skin prick test reactivity to flour-derived allergens. Skin prick test reactivity to grass pollens (OR = 3.0, 95% CI, 1.3-6.7) and to pets (OR = 2.5, 95% CI, 1.1-5.9), persistent rhinitis (OR = 3.1, 95% CI, 1.1-8.4), seasonal RC (OR = 2.5, 95% CI, 1.1-5.5), RC on contact with pets (OR = 2.3, 95% CI, 1.03-5.0) and skin prick test reactivity to wheat flour (OR = 10.5, 95% CI, 2.3-46.8), assessed at baseline, were significantly associated with the incidence of work-related RC symptoms. Multivariate logistic regression analysis yielded significant OR of skin prick test reactivity to wheat flour at baseline (OR = 7.1, 95% CI, 1.7-35.1) and persistent rhinitis (OR = 3.9, 95% CI, 1.01-9.6) for the incidence of work-related RC symptoms. Increased bronchial hyperresponsiveness at follow-up was more frequent, although not significantly, in subjects positive to skin prick test to flour on entry and reporting new work-related symptoms (3/5), than in other subjects (4/17). CONCLUSIONS: The incidence of work-related RC symptoms among apprentice pastry-makers was high (16.1% 30/186), while a minority (3/30) also developed skin prick test reactivity to flour. Skin prick test reactivity to wheat flour and persistent allergic rhinitis on starting exposure to flour are significant determinants for the development of work-related RC symptoms.

Tidal expiratory flow limitation and chronic dyspnoea in patients with cystic fibrosis.

Cystic fibrosis (CF) eventually leads to hyperinflation linked to tidal expiratory flow limitation (FL) and ventilatory failure. Presence of FL was assessed at rest in 22 seated children and adults with CF (forced expiratory volume in one second (FEV1) range: 16-92% predicted), using both the negative expiratory pressure (NEP) technique and the "conventional" method based on comparison of tidal and maximal expiratory flow/volume curves. In addition, chronic dyspnoea was scored with the modified Medical Research Council (MRC) scale. Measurements were made before and 15 min after inhalation of salbutamol. With NEP, FL was present in only three malnourished patients, who had the lowest FEV1 values (16-27% pred) and claimed very severe dyspnoea (MRC score 5). By contrast, an additional seven patients were classified as FL with the conventional method. Six of these patients had little or no dyspnoea (MRC scores 0-1). Salbutamol administration had no effect on the extent of FL, and the concomitant decrease in functional residual capacity (FRC) was too small to play any clinically significant role. This study concluded that in seated patients with cystic fibrosis, expiratory flow limitation is absent at rest, unless the forced expiratory volume in one second is <30% predicted. If present, expiratory flow limitation is associated with severe chronic dyspnoea. The conventional method for assessing expiratory flow limitation is not reliable and bronchodilator administration has little effect on expiratory flow limitation.

Host determinants for the development of allergy in apprentices exposed to laboratory animals.

The aim of this study was to evaluate whether determinants of work-related symptoms, skin sensitization and diseases differ between atopic and nonatopic subjects starting a career with exposure to laboratory animals (LA). A cohort of 417 apprentices in animal-health technology was prospectively followed during 32 or 44 months. The effect on the study outcomes of variables derived from questionnaire, skin reactivity, and lung function assessments at baseline were compared in atopic (n=212) and nonatopic (n=183) subjects. Eighty-five incident cases of sensitization to a LA-derived allergen were identified, 67 among atopic and 18 among nonatopic subjects. Baseline rhinitis symptoms in contact with pets and skin sensitization to pets were associated with the development of work-related rhinoconjunctivitis (RC) symptoms in atopic subjects, whereas perannual rhinitis symptoms and having a PC20 (provocative concentration causing a 20% fall in forced expiratory volume in one second) < or = 32 mg x mL(-1) were associated in nonatopic subjects. Baseline rhinitis symptoms on contact with pets and a PC20 value < or = 32 mg x mL(-1) were significant determinants for developing sensitization to a specific allergen in atopic subjects only. Finally, baseline rhinitis symptoms in contact with pets and perannual rhinitis symptoms were associated with the development of occupational RC in atopic subjects, whereas in nonatopic subjects this was associated with having a PC20 value < or = 32 mg x mL(-1). In conclusion, the determinants for the development of specific skin sensitization, symptoms and disease are different between atopic and nonatopic apprentices starting occupational exposure to laboratory-animal-derived allergens.