Mild improvement in symptoms and pulmonary function in a long-term follow-up of patients with toluene diisocyanate-induced asthma.

BACKGROUND: Long-term follow-up of diisocyanate-induced occupational asthma has been occasionally reported. METHODS: We studied the outcome of toluene diisocyanate (TDI)-induced asthma in 46 patients at diagnosis and after a follow-up of 11 ± 3.6 years. Symptoms, anti-asthma therapy, forced expiratory volume in 1 s (FEV1) and bronchial hyperresponsiveness to methacholine were assessed. RESULTS: A significant improvement in FEV1 (% predicted) and PD20FEV1 methacholine was observed at follow-up in comparison with diagnosis. Anti-asthma treatment was performed by 42% of patients at diagnosis and by 70% at follow-up. At the time of follow-up, 32 subjects had been removed from exposure for 6.0 ± 6.9 years, whereas 14 subjects continued to work with reduced exposure to TDI. There was a significant reduction in the prevalence of attacks of shortness of breath and dyspnoea at follow-up, but only in unexposed patients. PD20FEV1 was significantly improved only in patients with a lower FEV1 at diagnosis and in those who have ceased work. Logistic regression analysis, using different models with some independent variables, showed that there were no significant determinants of improvement in FEV1 at follow-up, while a shorter duration of symptoms before diagnosis was a significant predictor of improvement in PD20FEV1 at follow-up. CONCLUSIONS: Asthma-like symptoms, bronchial hyperresponsiveness and airway obstruction improved, but did not normalize, after a long-term follow-up with cessation or reduction in TDI exposure, mainly in subjects with an early diagnosis of occupational asthma and in patients with a lower baseline FEV1 no longer exposed to TDI.

May the reduction of exposure to specific sensitizers be an alternative to work cessation in occupational asthma? Results from a follow-up study.

BACKGROUND: Few data are reported on the effects of a reduction of exposure to specific sensitizers in occupational asthma (OA). The objective of this study was to evaluate the clinical outcome of subjects with OA, comparing the effect of a reduction with that of the persistence or cessation of occupational exposure to the specific sensitizer. SUBJECTS AND METHODS: Forty-one subjects with OA due to different sensitizers were diagnosed via a specific inhalation challenge. After a follow-up interval of 3.5 years, subjects were reexamined by clinical assessment, bronchial hyperresponsiveness (BH) and induced sputum. RESULTS: At follow-up, subjects who had reduced occupational exposure (n = 22) showed a significant improvement in BH and a nonsignificant improvement in sputum eosinophilia (from 5.3 to 1.1%, n.s.), while subjects still exposed (n = 10) showed a significant decrease in FEV(1). Subjects who ceased work (n = 9) showed a trend of improvement in BH and sputum eosinophilia. Logistic analysis showed that the major determinant of improvement in BH at follow-up was the severity of BH at diagnosis, with a minimal contribution from the duration of exposure and treatment with inhaled corticosteroids during follow-up; reduction of work exposure did not enter into any model. CONCLUSION: The reduction of occupational exposure could not be considered to be as effective as work cessation, which remained the best treatment for OA. However, it was not associated with a deterioration of FEV(1) as observed in subjects with persistent exposure.

[Burden of disease of occupational asthma in Tuscany: methodological aspects and preliminary results]. / Il calcolo del Burden of disease dell'asma da lavoro in Toscana: aspetti metodologici e risultati preliminari.

In Italy, unlike in other European countries, the public health burden of work-related asthma (WRA) has not yet be defined by means of a standardized validated epidemiological metric. The aim of the present study is to describe the methodology for the calculation of the Burden of Disease of WRA in Tuscany on the grounds of available healthcare and health survey data. The paper is particularly intended to illustrate the methodological approach to estimate the prevalence of the disease.

[The occupational and active research, diagnosis and reporting of occupational diseases]. / Il Medico Competente e la ricerca attiva, diagnosi e denuncia delle malattie professionali.

The Occupational Doctor plays a key role on the protection of workers safety and prevention of occupational and work-related disease. His training and his need of updating, due to the constant transformation of work, the evolution of technology and the medical progress, set him in the center of all activities carried out to protect health in workplaces. The Occupational Doctor should devote special attention to the working anamnesis as well as to the pathological anamnesis both close and remote. He should also pay attention to semeiotics. Another important element is the relationship between the Occupational Doctor and the Doctor of General Medicine (MMG); this synergy is of vital importance in protecting health and in investigating diseases whether occupational or not. D.Lgs. 81/08 emphasizes this synergy, in fact name and phone number of Doctor of General Medicine is compulsory in Case History. Major source of information for all form of prevention is the survey of occupational disease which is a tool for epidemiological control. The use of a systematic collection of data, of protocols, of guidelines and of scientific evidence is the basis for identifying occupational diseases, their diagnosis and subsequent denunciations. This is the line suggested in MAL PROF informative system, made for registration of work-related diseases, and which is important, with other instruments, in realizing an integrated informative system for prevention in workplace. The Covenant for the Protection of Health and Prevention in Workplaces (DPCM 17/12/2007) indicates the strategic objectives of the National Health System for the consolidation and development of the existing system and of the programs promoting health and safety. These include the growth of the culture of prevention and of the epidemiological control of occupational diseases. The Occupational Doctor has an important role because he can identify the early onset of diseases during the working age and start all forms of prevention and health promotion. In the case of diagnosis of a suspected professional disease the Occupational Doctor has three distinct obligations. The first is to report to the legal authority (C.P.P. art. 365). The second requirement is the declaration of the occupational disease (D.P.R. 1124/65 art. 139) and the third is to issue the first certificate of occupational disease for compensation insurance (D.P.R. 1124/65 artt. 53, 251).

[Silica risk in construction industry: an investigation on raw materials]. / Il rischio silice nel settore edilizia: esperienza di un'indagine sulle materie prime.

Typical construction activities like demolition, excavation and sanding can expose workers to silica, but there are few investigations carried out with the aim of evaluating the silica content in raw materials used for these activities (mortars, plasters, cement...). Our intervention has been directed in looking for free crystalline silica in samples of raw materials. We have measured the silica content in these materials comparing declared and real composition found in the products. Our intent was to obtain more information about the working activities which expose workers to free crystalline silica in construction industry and to highlight the silica presence in raw materials also when the companies don't declare it, against labeling rules based on Italian law D.lgs 65/03.

[Epidemiologic surveillance in occupational bladder cancer: a Tuscan experience]. / Intervento di ricerca attiva delle neoplasie vescicali di origine professionale: una esperienza toscana.

The percentage of bladder cancer as occupational disease in West-Europe is of 5/10%, but only a few amount of them are recognized as occupational disease from INAIL. The above mentioned research project is realized in order to decrease the gap between expected and claimed cases of occupational disease and it is conducted with the collaboration of ASL of Pisa, ASL of Empoli, Azienda Ospedaliera Universitaria Pisana and INAIL. 677 patients with bladder cancer were interviewed by phone, among them 64 subjects had a working experience compatible with neoplastic risks because had a previous occupational exposure to aromatic amines and metal working fluids. These cases were discussed into a Medical Staff and 40 cases were considered "probable" for occupational disease, 18 "possible", 3 cases are suspended for more research, 3 cases are considered "no professional disease". The research allows finding out a great number of bladder cancer, increasing the total amount of workers with occupational disease. The integrated approach with the collaboration among different institutions is surely the best way to allow and guarantee a suitable and right protection of workers with occupational disease.

Bronchoalveolar lavage and morphology of the airways after cessation of exposure in asthmatic subjects sensitized to toluene diisocyanate.

To evaluate the morphologic basis of the different outcomes of toluene diisocyanate (TDI) asthma after quitting occupational exposure, we examined ten patients with TDI asthma who showed, at diagnosis, a positive TDI challenge test and nonspecific bronchial hyperresponsiveness (NSBH) to methacholine. After diagnosis, all patients ceased work and a 4- to 40-month follow-up was obtained with three to eight determinations of the cumulative dose producing a 15 percent fall in FEV1 (PD15FEV1) methacholine in each patient. Bronchoalveolar lavage (BAL) and biopsy of bronchial muscosa were performed 3 to 39 months after cessation of work, in the absence of acute exacerbations of the disease. Total cell count in BAL fluid was moderately increased in four of ten patients, eosinophils were increased in five of ten patients, and neutrophils were increased in eight of ten patients. Mucosal biopsy specimens of main or lobar bronchi were available in eight of ten patients; epithelial damage and thickening of basement membrane was observed in almost all patients, as well as a mild-to-moderate inflammatory reaction in the submucosa, mainly represented by lymphocytes, eosinophils, and neutrophils. No relationship was observed between the cellularity of BAL and the degree of NSBH at the time of BAL; mean values of total cells and differential count were not different between patients with presence or absence of the different histologic findings. Mucosal biopsy and BAL were performed also in four subjects exposed to dusts without respiratory symptoms or NSBH; similar findings were obtained except for the absence of eosinophils in BAL and a lesser degree of basement membrane thickening and inflammatory reaction in the submucosa. The study of the changes in NSBH after quitting exposure showed that five of ten patients had a significant improvement in NSBH to methacholine, as evaluated by a positive significant linear regression between months of work cessation and PD15FEV1 methacholine; only one of these five patients had an increased number of eosinophils in BAL fluid. By contrast, four of the five patients with persistent NSBH after quitting exposure had an increased number of eosinophils in BAL. We suggest that persistent NSBH in TDI asthma after cessation of work may be related to an inflammatory reaction in which eosinophil infiltration seems to be a major determinant.

Diagnosis of flour-induced occupational asthma in a cross-sectional study.

The diagnosis of occupational asthma is usually performed in epidemiology using a combination of symptoms and bronchial hyperresponsiveness, while in a clinical setting the 'gold standard' for the diagnosis of occupational asthma is the specific bronchial challenge test in the laboratory The aim of this study was to detect new cases of flour-induced occupational asthma (OA) in a group of workers exposed to grain and/or flour dust, by means of a step-by-step approach, as used in a clinical setting. In an epidemiological study, III millers and 186 bakers were examined by means of questionnaire, pulmonary function tests and skin-prick tests (SPT) to common allergens and to wheat flour dust extracts. From the whole sample, 82 subjects who showed asthma-like symptoms in the questionnaire and/or low forced expiratory volume in 1 sec (FEV1) were selected. Selected subjects underwent methacholine challenge test, and hyperreactive subjects underwent specific bronchial challenge with flour dust in the laboratory. Sixty-two of the selected subjects performed the methacholine challenge test, and 22 (33 8%) were hyperreactive (PD20 FEV1 <1 mg of methacholine). Fifteen of 22 hyperreactive subjects underwent specific bronchial challenge test (s BCT) with flour dust; a positive response was elicited in six subjects. These subjects can be diagnosed as having flour-induced occupational asthma. Atopy and skin sensitivity to flour was partially related to the response to flour bronchial challenge. Bronchial hyperreactivity can be observed in a small percentage of subjects with asthma-like symptoms and/or low FEV1, and a positive response to s BCTwas observed in a subgroup of hyperreactive subjects.Therefore, using these selection criteria, a diagnosis of flour-induced OA, as commonly performed in a clinical setting, can be performed in few previously undiagnosed subjects.This approach could be relevant for an early diagnosis ofoccupational asthma.

Salbutamol plus beclomethasone dipropionate, but not salbutamol alone, completely prevent early and late asthmatic responses to allergen.

The effect of a week treatment with inhaled salbutamol plus placebo (S+P) vs. salbutamol combined with beclomethasone dipropionate (S+BDP) on early and late asthmatic responses to inhaled allergen was studied in ten atopic patients in a randomized, double-blind, cross-over study. All patients had previously shown a dual type response to the specific bronchial provocative test (sBPT). Each patient performed two periods of treatment for a week, with a 15 day interval between them: (a) salbutamol 0.3 mg, tid + placebo; (b) salbutamol 0.3 mg+BDP 0.2 mg, tid; at the end of each treatment period, sBPT was performed and the last treatments were given 1.5-2 h before and 3-4 h after allergen challenge. S + BDP completely prevented both early and late responses to allergen, while S + P reduced but did not completely inhibit early and late responses. The difference between the two treatments was significant for early and late asthmatic responses. Non-specific bronchial hyperresponsiveness to methacholine was performed before each treatment period, after 6 days of treatment before sBPT and the day after sBPT at the end of the treatment period; there was only a mild increase in PD15FEV1 methacholine after 6 days of treatment with S + BDP in comparison with S + P treatment. These results suggest that salbutamol plus beclomethasone may be used effectively in the prophylaxis of early and late asthmatic reactions induced by allergen in sensitized subjects.

Dyspnoea is associated with pulmonary function impairment in exposed workers.

This study aimed to evaluate the prevalence of dysponea and its predictors in studies on several working male groups in British Columbia (BC), Canada (cedar sawmill, grain elevator, pulpmill, and aluminum smelter workers), and Tuscany (T), Italy, (shoe and furniture makers, millers, bakers, and pharmaceutical workers). We performed cross-sectional health studies (interviews and pulmonary function tests) for 2498 BC and 1474 T workers exposed to air contaminants, and 1110 BC and 243 T controls. Similar questionnaires and the same definitions were used in BC and in T. Pulmonary function tests were also performed. The participation rates were >92% in BC workers and 82% in T workers. The overall prevalence of moderate dyspnoea was not different in exposed BC and T workers in comparison with controls. Slight dyspnoea was significantly more frequent in BC workers, but not in T workers, with respect to controls. After adjusting for age, body mass index (BMI), smoking, current asthma, and chronic bronchitis, forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were found to be significantly associated with slight and moderate dyspnoea in BC workers, and slight dyspnoea in T workers. Isolated dyspnoea is associated with reduction in FEV1 and FVC in working populations, after adjusting for potentially confounding variables.

Risk factors for chronic respiratory disorders in a sample of farmers in middle Italy.

OBJECTIVE: To evaluate the prevalence of respiratory symptoms in agricultural workers in a rural area of Tuscany and to relate them to some occupational risk factors. SUBJECTS AND METHODS: A cross sectional study was performed on a sample of 461 agricultural workers from two rural area of Tuscany. All subjects underwent to respiratory questionnaire, pulmonary function test and skin prick tests. Occupational risk factors were evaluated as response to questions related to 11 specific jobs, most of them related to cow-shed works. RESULTS: Subjects had high mean age and a long work duration. Smoking habit was significantly associated with symptoms of chronic bronchitis, while atopy was significantly associated with chronic cough, phlegm and dyspnea. In comparison with a control group of workers which did not report any occupational risk factors (reference group), logistic analysis showed that most symptoms were significantly associated with some specific jobs related to animal breeding, taking into account differences due to age, smoking habit, atopy and district. Mean pulmonary function tests were in the normal range, without any significant relationship with different risk factors, except smoking habit. Increased work duration was associated with significant decrease of pulmonary function. CONCLUSION: Symptoms of chronic bronchitis were frequent in this population of farmers of Middle Italy. The analysis of risk factors confirms a relevant role for some specific occupational risk factors, related to jobs in the cow-shed, in the development of respiratory disorders.

[The occupational risk in IRCCS of Neurosciences]. / Il rischio professionale negli IRCCS di Neuroscienze.

The results of meta-analysis carried out on all documents for the valuation of the risk, recorded by IRCCS of Neuroscience, has led to identify a risk matrix for the medical personnel of the Scientific Institute of Neuroscience. Such analysis allowed to tackle the day to day risk faced by hospital staff. As a general rule the IRCCS of Neurosciences distinguishes themselves as structures of mainly neurologic typology and as structures of more typical psychiatric interest. In the first case the analogy with the traditional Hospital structures are more noticeable, in the second case instead the kind of patients and the particular relations between the health worker and the patient himself may represent an important differentiation factor. This is, above all, evident on the biological risk; for it's determinism has an important rule the interpersonal relationship between the health worker and the patient. Concerning other risk factors such as the chemical and the allergic one, it is noticeable a closed analogy with the actual Hospital reality. On work organization level, manual handling of patients is often necessary and also the relatives risks. In this kind of structures the stress factor is of the greatest importance, it should therefore have a strong consideration on the valuation of risk by the IRCCS.

[Knowledge of occupational risk in IRCCS of Neurosciences]. / Conoscenza del rischio professionale negli IRCCS di Neuroscienze.

A Professional Multicentric Audit, concerning Staff knowledge level about security on workplaces, was conducted by way of a standardized questionnaire given to 1022 (26.4%) IRCCS professional staff pertaining to Neurobiology. Four were the principal tasks of the questionnaire investigating the "sensibility" and "consciousness" concerning risk prevention on workplaces. It came out that there is a great variability in the knowledge level on this field, even if the "medium value" is "pretty good".

[Phenomenon of occupational accidents of workers of IRCCS of Neurosciences]. / Il fenomeno infortunistico negli operatori degli IRCCS di Neuroscienze.

On the basis of information collected from ten IRCCS, it has emerged altogether that the accident are not much frequent. Accident statistics indices from 1994 to 1998 were respectively: frequency rate 21.36, incidence rate 3.32, severity rate 0.24. In the "Neurology" Institutes we have above all needlestick injuries and cufs to the arms and hands. The workers most exposed are doctors, trained nurses, technicians. In the "Psychic" Institutes we have falling, impact, lifting and physical contact accidents. The injuries are contusions to legs and head. The most exposed workers are therapists and rehabilitation educators.

[Asthma in hairdressers: a report of 5 cases]. / Asma dei parrucchieri: descrizione di 5 casi.

The paper reports 5 cases of bronchial asthma in hairdressers exposed to bleaching dusts containing potassium and ammonium persulphate. All subjects complained of asthmatic symptoms at diagnosis, and underwent measurement of non-specific bronchial hyperresponsiveness to methacholine, skin prick tests for common allergens, PEF monitoring during 2 weeks at work, specific bronchial challenge (SBC) test with bleaching dust, and assessment of airway inflammation by induced sputum technique. All subjects were reassessed during a follow-up of 1 to 5 years. All subjects were negative for skin prick tests, but 3 showed an abnormal PEF variability at work (Maximal Amplitude > 10%, in at least half of the monitoring period). All subjects showed a positive airway response to SBC with bleaching dust, and 4 subjects did not react to the control tests with lactose dust. One subject only showed a high percentage of eosinophils (> 3%) in the induced sputum, while all were hyperreactive to methacholine (PD20FEV1 < 0.3 mg). During the follow-up, 2 subjects stopped working and 4 were treated by inhaled corticosteroids and bronchodilators. All subjects reported a significant improvement in asthmatic symptoms, related partly to the reduction of occupational exposure in the workplace and to the efficacy of anti-inflammatory treatment. In conclusion, similar findings were observed in these 5 cases of hairdresser asthma: absence of atopy, positive response to SBC, mild changes in PEF and variable percentages of eosinophils in induced sputum. Pharmacological treatment, associated with reduction of occupational exposure, could improve asthmatic symptoms, despite continuing the job.

[Specific bronchial provocation tests with flour in the diagnosis of occupational bronchial asthma]. / Il test di provocazione bronchiale specifico con polvere di farina nella diagnosi di asma bronchiale professionale.

The gold standard in the diagnosis of occupational asthma is the specific bronchial provocation test (sBPT), but other diagnostic criteria have been proven to have a similar sensitivity, mainly in asthma due to high molecular weight compounds. In order to assess wether some clinical findings can predict the positive response to sBPT, we studied 37 subjects (14 millers and 23 bakers) with suspected occupational asthma who underwent sBPT with wheat flour dust (dust exposure in a small cabin: geometric mean 12.1 mg/m3 for up to 30 min). A positive response to sBPT (FEV1 > 20%) was elicited in 20 subjects (11 early, 4 late, and 5 dual responses). There was no significant difference between subjects with positive or negative sBPT as regards mean age, smoking, length of employment, duration of symptoms, atopy (skin positivity to one or more common allergens) and PD20FEV1 methacholine. The percentage of subjects with work-related symptoms was significantly higher in subjects with positive sBPT with respect to subjects with negative sBPT (81% versus 41.2%, p < 0.01 by chi 2 test); furthermore, FEV1 was significantly lower in subjects with positive sBPT. The percentage of positive skin response to wheat flour extract (mean wheal diameter > or = 3 mm) was mildly but not significantly higher in subjects with positive sBPT (68.4% versus 41.2%). None of the following clinical factors (age < 35 years, asthma symptoms pre-existing occupational exposure, non smokers, atopy and bronchial hyperresponsiveness to methacholine), alone or in combination, were associated with higher prevalence of positive sBPT. We conclude that the response to sBPT in subjects with suspected occupational asthma due to flour dust can not be adequately predicted by other clinical, allergologic and functional data. Therefore, sBPT with flour dust should always be performed in subjects with suspected occupational asthma.

Comparison between Airway Responses to High versus Low Molecular Weight Compounds in Occupational Asthma.

Occupational asthma (OA) is a heterogeneous disease, and the characteristics of the sensitizer responsible for OA may induce different clinical, functional, and biological manifestations. We examined the characteristics of 74 patients with OA induced by low molecular weight compounds (LMWC) or by high molecular weight compounds (HMWC) and diagnosed by specific inhalation challenge (SIC). Patients with OA induced by LMWC had a longer occupational exposure before the beginning of symptoms, a lower sputum eosinophilia, and a higher prevalence of late airway response (LAR), in comparison with patients with OA induced by HMWC. Pulmonary function tended to be poorer and atopy tended to be less frequent in LMWC-induced OA than in HMWC-induced OA. These data confirm and extend previous observations showing that the characteristics of the specific sensitizer inducing OA may determine different clinical, functional, and biological features, probably related to the difference pathogenetic mechanisms underlying these different types of OA.