Upper airway symptoms among workers with work-related respiratory complaints.

BACKGROUND: Work-related rhinitis and asthma symptoms frequently co-exist. AIMS: To determine the prevalence and nature of nasal, pharyngeal, laryngeal and sinus symptoms among individuals with work-related respiratory symptoms. METHODS: Individuals referred to a tertiary occupational asthma clinic for investigations with specific inhalation challenges were evaluated using the RHINASTHMA quality of life questionnaire and a questionnaire that assessed the nature and frequency of upper airway symptoms, their relationship to the workplace and their temporal relationship with the onset of asthma symptoms. RESULTS: There were 83 study participants. At least one upper airway symptom was reported by all of these individuals: nasal in 92%; pharyngeal in 82%; laryngeal in 65% and sinus in 53% of participants. Overall, there were no significant differences in the frequencies of nasal, pharyngeal, laryngeal and sinus symptoms when comparing these with occupational asthma (OA), work-exacerbated asthma (WEA) and work-related respiratory symptoms (WRS), except that nasal bleeding was most frequent among those with WRS. The presence of laryngeal symptoms was significantly associated with rhinitis-specific quality of life impairment. Individuals with workplace exposures to high molecular weight agents had greater impaired quality of life than those who were exposed to low molecular weight agents (RHINASTMA Upper Airway sub-scores: 24.0±10.4 versus 19.8±6.8; P < 0.05). CONCLUSIONS: Individuals who were referred for work-related respiratory symptoms experienced high rates of work-related nasal, pharyngeal, laryngeal and sinus symptoms, regardless of having OA, WEA or WRS.

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.

Occupational asthma and allergy in snow crab processing in Newfoundland and Labrador.

BACKGROUND: Risk factors and prevalence of occupational asthma (OA) and occupational allergy (OAl) in the snow crab-processing industry have been poorly studied. OBJECTIVE: To estimate the prevalence of OA and OAl in snow crab-processing workers and determine their relationship with exposure to snow crab allergens and other potential risk factors. METHODS: A total of 215 workers (120 female/95 male) were recruited from four plants in Newfoundland and Labrador, Canada in 2001-2002. Results from questionnaires, skin-prick tests to snow crab meat and cooking water, specific IgEs against the latter, spirometry and peak flow monitoring were used to develop a diagnostic algorithm. An index based on work history and exposure measurements of snow crab aeroallergens was developed to estimate the cumulative exposure for each worker. RESULTS: The prevalences of almost certain or highly probable OA and OAl were 15.8% and 14.9%, respectively. A high cumulative exposure to crab allergens, in jobs mostly held by women, was associated with OA (odds ratio (OR) = 14.0, 95% CI 3.0 to 65.8) (highest vs lowest Cumulative Exposure Index) and with OAl (OR = 7.1, 95% CI 1.9 to 29.0); job held when symptoms started (cleaning, packing, freezing) also predicted OA (OR = 3.9, 95% CI 1.6 to 8.7) and OAl (OR = 3.2, 95% CI 1.4 to 7.5). Atopy (OR = 2.8, 95% CI 1.2 to 6.8), female gender (OR = 10.7, 95% CI 3.6 to 32.1) and smoking were significant determinants for OA (OR = 3.1, 95% CI 1.3 to 7.4). CONCLUSIONS: The prevalences of OA and OAl are high in snow crab-processing workers of Canada's East Coast. Cumulative exposure to snow crab allergens was related to the prevalences of OA and OAl in a dose-response manner taking into account atopy, gender and smoking.

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.

Occupational rhinitis.

The present document is the result of a consensus reached by a panel of experts from European and nonEuropean countries on Occupational Rhinitis (OR), a disease of emerging relevance, which has received little attention in comparison to occupational asthma. The document covers the main items of OR including epidemiology, diagnosis, management, socio-economic impact, preventive strategies and medicolegal issues. An operational definition and classification of OR tailored to that of occupational asthma, as well as a diagnostic algorithm based on steps allowing different levels of diagnostic evidence, are proposed. The needs for future research are pointed out. Key messages are issued for each item.

Is metal fume fever a determinant of welding related respiratory symptoms and/or increased bronchial responsiveness? A longitudinal study.

BACKGROUND: The current prospective study investigated the hypothesis of metal fume fever (MFF) being a predictor for the development of respiratory symptoms and functional abnormalities. METHODS: The study consisted of a pre-exposure and two follow up assessments of 286 welding apprentices during an average period of 15 months. A respiratory and a systemic symptom questionnaire, skin prick tests to common allergens and metal salts, spirometry, and methacholine challenge tests were administered. RESULTS: Developing at least one positive skin prick test to a metallic salt solution was found in 11.8% of apprentices. Possible MFF (at least one of fever, feelings of flu, general malaise, chills, dry cough, metallic taste, or shortness of breath) was reported by 39.2% of apprentices. The presence of at least one welding related respiratory symptom (cough, wheezing, or chest tightness) suggestive of welding related asthma was reported by 13.8%. MFF was significantly associated with these respiratory symptoms (OR = 4.92, 95% CI 2.10 to 11.52), after adjusting for age, atopy, smoking, physician diagnosed asthma, and symptoms of non-welding related asthma. Apprentices with possible MFF, and no welding related respiratory symptoms suggestive of welding related asthma at the first follow up, had an increased risk of developing the latter symptoms by the second follow up visit (OR = 7.4, 95% CI 1.97 to 27.45) compared with those not having MFF. MFF was not significantly associated with an increase in bronchial responsiveness. CONCLUSION: MFF could be a predictor for the development of respiratory symptoms but not for functional abnormalities in welders.

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.

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.

Airway hyperresponsiveness and symptoms of asthma in a six-year follow-up study of childhood asthma.

BACKGROUND AND AIM: In an inception cohort study of 457 asthmatic children diagnosed at the age of 3 to 4 years, airway hyperresponsiveness (AHR) was assessed 6 years after first diagnosis in a subgroup of 84 children. Our objective was to associate the level of AHR with the symptomatic asthma status at follow-up. METHODS: Information on respiratory symptoms and medication use for the previous 6 years was obtained. Children with reported wheezing episodes during the previous year (n = 169) or for > or = 2 years at any time during the follow-up period (n = 85) were eligible for the challenge test. RESULTS: Among the 254 eligible children, 166 were randomly selected. The parents of 88 of them consented to have their child participate. At the time of assessment of AHR, 19 children (22%) were asymptomatic and 24 others (29%) had symptoms but did not use any medication. Forty-one children (49%) were symptomatic and required medication, including antiinflammatory preparations in 26 instances (31%). All but two children had significant AHR. There was no significant association between the level of AHR and graded symptomatic and medication score. Twenty-four of the 70 children (34%) with greatly enhanced AHR used no medication. CONCLUSIONS: This study shows that (1) almost all children first diagnosed with asthma 6 years ago and with persisting but not necessarily current symptoms of asthma have increased AHR, which satisfies a proposed epidemiologic definition of asthma; (2) AHR was present in 95% of the 20 currently asymptomatic children; and (3) one third of children with greatly enhanced AHR did not use any treatment.

Comparison between peak expiratory flow rates (PEFR) and FEV1 in the monitoring of asthmatic subjects at an outpatient clinic.

Peak expiratory flow rate (PEFR) monitoring is often used alone in evaluating bronchial caliber and the response to a bronchodilator in the assessment of asthmatic subjects. A 15% change in airway caliber has been proposed as the criteria for modifying treatment. Our aim was to determine if changes in PEFR from one visit to the next can adequately evaluate changes in airway caliber as assessed by FEV1, which is considered the gold standard, and to identify the characteristics of subjects whose evaluations were inadequate. This was a retrospective study of 197 asthmatic subjects seen regularly at an outpatient clinic for whom FEV1 and PEFR assessments, prebronchodilator and postbronchodilator, were available for two visits. There was a high correlation between PEFR and FEV1 (in absolute value or percent predicted) (r = 0.83 and r = 0.75). However, 24 of 56 (43%) of those who had a change in FEV1 of 15% or more between two visits (mean change [%] +/- SD, range [best-lowest/best] = 20.9 +/- 5.1%, 15 to 36%) showed changes in PEFR of less than 15% (6.7 +/- 6.5%, 8.0 to 13.9%). On the other hand, 14 of 42 (33%) subjects with changes in FEV1 of less than 15% (9.8 +/- 3.2%, 1.1 to 13.8%) had changes in PEFR of 15% or more (22.2 +/- 10.9%, 16 to 35%). This discrepancy was not related to differences in baseline FEV1, control status, or the relationship between changes in FEV1 and PEFR in response to a bronchodilator. In conclusion, assessment of airway caliber through PEFR monitoring may not be valid in some asthmatic subjects and can often lead to underestimation or overestimation of changes in FEV1. None of the explanations considered made it possible to identify these subjects.

Nonsensitizing causes of occupational asthma.

Irritant-induced asthma and RADS are related conditions that need further study focusing on the following questions: (1) Are there differences between the pathologic and functional features that follow single or multiple exposures to an irritant material? (2) What is the time course of the changes? (3) What are the physiologic correlates in terms of onset of airway hyperresponsiveness? (4) What are the risk markers (besides exposure)? (5) Are there means of modulating the reaction by using anti-inflammatory preparations? Developing an animal model of irritant-induced asthma and conducting prospective epidemiologic surveys in high-risk workers may be most effective routes to provide satisfactory answers to these questions. Further examination of the physiopathology of such conditions as byssinosis, grain-dust-induced respiratory disease, and aluminum potroom asthma as well as of the differences from and similarities to OA is also warranted.

Alzheimer's disease: environmental factors and etiologic hypotheses.

A review of published reports on conventional and unconventional viruses, aluminum, neurotoxic metals and trace elements, neurotoxins of biological origin and immune systems, suggest that environmental factors, possibly multiple ones, play a significant role in the etiology of Alzheimer's disease. A complex interaction between genetic predisposition to this illness, natural aging processes, environmental factors over a life-time exposure and pathological alterations of the host immune system is proposed.

Parental age and birth order in Alzheimer's disease: a case-control study in the Saguenay-Lac-St-Jean area (Quebec, Canada).

Parental age at the time of birth of 133 clinically diagnosed Alzheimer patients from the Saguenay-Lac-St-Jean area (Quebec, Canada) were compared with those of 6 control groups formed out a population registry. The birth order of the Alzheimer patients was also analyzed. The results did not show any parental age or birth order effect, which is in agreement with previous reports. The importance of control selection in such studies is stressed.

Ascertainment of informative Alzheimer disease families from the IMAGE Project registry for genetic linkage analysis studies.

Genetic linkage analysis requires the identification and documentation of large families with many affected members present, preferably in more than one generation. The IMAGE Project has been establishing a population-based Alzheimer disease (AD) registry in the Saguenay - Lac-Saint-Jean region of the Province of Quebec. The population of this region has a well-documented ancestry, with reliable genealogical records (since 1842) computerized by SOREP. We have recently begun to investigate the pedigrees of selected probands (definite, probable and possible) from the IMAGE registry in order to identify informative pedigrees for genetic linkage analysis. Interviews were carried out with close relatives of the probands (at least one informant per sibship) to identify secondary AD cases. The questionnaires used pertain to the accuracy of genealogical records, to family medical history and to a retrospective diagnosis of AD for people with cognitive deficits. By these means, we have documented a large extended pedigree in which a total of 15 individuals with cognitive deficits were ascertained over three generations. Of these cases, 7 are still living and there is autopsy confirmation in another one. Computer simulations using the program SIMLINK revealed that this is a potentially informative family for linkage analysis. Horizontal extension of the pedigree to second cousins of the proband is now being carried out. This will render the family IMAGE/1 even more informative in genetic linkage analysis studies.

[Chronic hyperventilation syndrome. The role of respiratory re-training]. / Le syndrome d'hyperventilation chronique. Rôle de la rééducation respiratoire.

This study compares three non-pharmacological approaches to the chronic hyperventilation syndrome (CHS). Eighteen subjects were evaluated at the start of the study then one and 6 months after having received in a random fashion one of the following treatments: group I (teaching approach of one hour on the respiratory physiology of the CHS and on breathing techniques; n = 5); group II (same approach as in group I with breathing retraining of 8 sessions; n = 8); group III (same as group II with the addition of a modified Jacobson's progressive relaxation; n = 5). Whereas all three groups had a similar symptomatic score at the beginning of the study (although subjects of group III had in general higher scores and were symptomatic for a longer period), our results show that all subjects improved after 4 weeks, those in group II showing the greatest improvement (p < 0.05). This confirms the relevance of applied and repeated pedagogy in approaching subjects with the CHS.