bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exposure-response relations among laboratory animal workers exposed to rats
Authors: Nieuwenhuijsen M J , Putcha V , Gordon S , Heederik D , Venables K M , Cullinan P , Newman-Taylor A J 
Published: January 2003

Aim:To explore exposure-response relations in a cohort of laboratory animal workers.Methods:Exposure-response modelling was carried out in a cohort of 342 laboratory animal workers. Three exposure indices, divided into different exposure categories, were used in the analyses: intensity of exposure to rat urinary aeroallergen (RUA, the main allergen workers were exposed to), weekly duration of exposure to rats, and the product of the intensity and weekly duration of exposure. Outcomes studied were work related chest, eyes and nose, and skin symptoms that had started after employment at the sites, specific sensitisation, and a combination of symptoms and sensitisation. Cox proportional hazard modelling was used to explore exposure-response relations. Smoking, atopic status, age, and gender were taken into account.Results:We observed the clearest exposure-response relations for the intensity of exposure to RUA and the various endpoints. No clear exposure-response relations were observed for the weekly duration of exposure or the product of the intensity and weekly duration of exposure. The strongest and clearest exposure-response relations for symptoms were observed among rat sensitised workers, while the non-sensitised workers only showed small increased risks of developing symptoms without clear exposure-response relations. Sensitised workers were almost four times more likely to go on to develop chest symptoms compared to non-sensitised workers.
A longitudinal observation of early pulmonary responses to cotton dust
Authors: Wang X-R , Pan L-D , Zhang H-X , Sun B-X , Dai H-L , Christiani D C 
Published: January 2003

Aims:To examine early adverse pulmonary effects of exposure to cotton dust, and to identify potential risk factors, including atopy for pulmonary responses to cotton dust.Methods:Spirometry, methacholine challenge testing, and questionnaire; performed among 101 non-smoking newly hired textile workers at baseline (prior to starting work), and at 3, 12, and 18 months after starting work. Concentrations of airborne cotton dust in various work areas were measured at each follow up survey using vertical elutriators.Results:The incidence of non-specific respiratory symptoms was 8% at three months, then diminished afterwards. Substantial acute cross shift drops in FEV1at each follow up survey, and longitudinal declines in FVC and FEV1after 12 months of exposure were observed. Airway responsiveness to methacholine increased with follow up time, and was more pronounced among atopics. Increasing airway responsiveness was strongly correlated with cross shift drops in FEV1. In addition, one or more respiratory symptoms at three months was significantly, and pre-existing atopy marginally significantly, associated with cross shift drops in FEV1after adjusting for other covariates and confounders.Conclusion:Results suggest that non-specific respiratory symptoms, decreasing lung function, and increasing airway responsiveness are early pulmonary responses to cotton dust. In addition, the occurrence of respiratory symptoms and increasing airway responsiveness, as well as atopy, may be important predictors for acute changes in lung function among cotton textile workers.
Occupational silica exposure and risk of various diseases: an analysis using death certificates from 27 states of the United States
Authors: Calvert G M , Rice F L , Boiano J M , Sheehy J W , Sanderson W T 
Published: January 2003

Background:Although crystalline silica exposure is associated with silicosis, lung cancer, pulmonary tuberculosis, and chronic obstructive pulmonary disease (COPD), there is less support for an association with autoimmune disease, and renal disease.Methods:Using data from the US National Occupational Mortality Surveillance (NOMS) system, a matched case-control design was employed to examine each of several diseases (including silicosis, lung cancer, stomach cancer, oesophageal cancer, COPD, pulmonary tuberculosis, sarcoidosis, systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis, and various types of renal disease). Cases were subjects whose death certificate mentioned the disease of interest. A separate control group for each of the diseases of interest was selected from among subjects whose death certificate did not mention the disease of interest or any of several diseases reported to be associated with crystalline silica exposure. Subjects were assigned into a qualitative crystalline silica exposure category based on the industry/occupation pairing found on their death certificate. We also investigated whether silicotics had a higher risk of disease compared to those without silicosis.Results:Those postulated to have had detectable crystalline silica exposure had a significantly increased risk for silicosis, COPD, pulmonary tuberculosis, and rheumatoid arthritis. In addition, a significant trend of increasing risk with increasing silica exposure was observed for these same conditions and for lung cancer. Those postulated to have had the greatest crystalline silica exposure had a significantly increased risk for silicosis, lung cancer, COPD, and pulmonary tuberculosis only. Finally, those with silicosis had a significantly increased risk for COPD, pulmonary tuberculosis, and rheumatoid arthritis.Conclusions:This study corroborates the association between crystalline silica exposure and silicosis, lung cancer, COPD, and pulmonary tuberculosis. In addition, support is provided for an association between crystalline silica exposure and rheumatoid arthritis.
Reported incidence of occupational asthma in France, 1996–99: the ONAP programme
Authors: Ameille J , Pauli G , Calastreng-Crinquand A , Vervloët D , Iwatsubo Y , Popin E , Bayeux-Dunglas M C , Kopferschmitt-Kubler M C 
Published: January 2003

Aims:To estimate the general and specific incidence of occupational asthma in France in 1996–99; and to describe the distribution of cases by age, sex, suspected causal agents, and occupation.Methods:New cases of occupational asthma were collected by a national surveillance programme, based on voluntary reporting, named Observatoire National des Asthmes Professionnels (ONAP), involving a network of occupational and chest physicians. For each case, the reporting form included information on age, sex, location of workplace, occupation, suspected causal agent, and methods of diagnosis. Estimates of the working population, used to calculate incidence rates by age, sex, region, and occupation, were obtained from the Institut National de la Statistique et des Etudes Economiques (INSEE) and from the French Securite Sociale statistics.Results:In 1996–99, 2178 cases of occupational asthma were reported to the ONAP, giving a mean annual rate of 24/million. Rates in men were higher than rates in women (27/million versus 19/million). The highest rate was observed in the 15–29 years age group (30/million). The most frequently incriminated agents were flour (20.3%), isocyanates (14.1%), latex (7.2%), aldehyde (5.9%), persulphate salts (5.8%), and wood dusts (3.7%). The highest risks of occupational asthma were found in bakers and pastry makers (683/million), car painters (326/million), hairdressers (308/million), and wood workers (218/million).Conclusion:Despite likely underreporting, the number of cases of occupational asthma reported to the ONAP was approximately twice the number of compensated cases over the same period. The relevance of the programme is confirmed by the reproducibility of the results year after year, and its consistency with other surveillance programmes. The ONAP programme is useful for the identification of targets for primary prevention.
Fluid losses and hydration status of industrial workers under thermal stress working extended shifts
Authors: Brake D J , Bates G P 
Published: January 2003

Aims:To assess whether workers under significant thermal stress necessarily dehydrated during their exposure and whether “involuntary dehydration” was inevitable, as supported by ISO 9866 and other authorities. Other objectives were to quantify sweat rates against recommended occupational limits, to develop a dehydration protocol to assist with managing heat exposures, and to understand the role of meal breaks on extended shifts in terms of fluid replacement.Methods:A field investigation to examine the fluid consumption, sweat rates, and changes in the hydration state of industrial workers on extended (10, 12, and 12.5 hour) shifts under significant levels of thermal stress (wet bulb globe temperature (WBGT) >28°C) was conducted on 39 male underground miners. Urinary specific gravity was measured before, during, and at the completion of the working shift. Environmental conditions were measured hourly during the shift. Fluid replacement was measured during the working periods and during the meal breaks.Results:Average environmental conditions were severe (WBGT 30.9°C (SD 2.0°C), range 25.7–35.2°C). Fluid intake averaged 0.8 l/h during exposure (SD 0.3 l/h, range 0.3–1.5 l/h). Average urinary specific gravity at start, mid, and end of shift was 1.0251, 1.0248, and 1.0254 respectively; the differences between start and mid shift, mid and end shift, and start and end shift were not significant. However, a majority of workers were coming to work in a moderately hypohydrated state (average urinary specific gravity 1.024 (SD 0.0059)). A combined dehydration and heat illness protocol was developed. Urinary specific gravity limits of 1.022 for start of shift and 1.030 for end of shift were selected; workers exceeding these values were not allowed into the workplace (if the start of shift limit was exceeded) or were retested prior to their next working shift (if the end of shift limit was exceeded). A target of 1.015 as a euhydrated state for start of shift was adopted for workforce education.Conclusions:This study found that “involuntary dehydration” did not occur in well informed workers, which has implications for heat stress standards that do not make provision for full fluid replacement during heat exposure. Fluid replacement during meal breaks was not significantly increased above fluid replacement rates during work time, with implications for the duration and spacing of meal breaks on long shifts. Testing of urinary specific gravity was found to be a good indication of hydration status and a practical method of improving workforce awareness and understanding of this important risk factor. Approximately 10 000 dehydration tests have been conducted under the dehydration protocol in a workforce of 2000 persons exposed to thermal stress and has proved practical and reliable.
Exposure related mutagens in urine of rubber workers associated with inhalable particulate and dermal exposure
Authors: Vermeulen R , Bos R P , Pertijs J , Kromhout H 
Published: January 2003

Aims:To determine the relation of the inhalation and dermal exposure routes and mutagenic activity in the urine of rubber workers (n = 105).Methods:Mutagenic activity of ambient total suspended particulate matter (TSPM), surface contamination wipes, and Sunday and weekday urine samples was assessed withS typhimuriumYG1041 in the presence of a metabolic activation system. Each subject was grouped into one of two exposure categories for dermal exposure (high (≥25 revertants/cm2), low (<25 revertants/cm2)) based on the mutagenic activity detected on likely skin contact surfaces and into two airborne mutagenic exposure categories (high (≥210 revertants/m3), low (<210 revertants/m3)). The potential influence of skin aberrations and acetylation status (NAT2) on urinary mutagenicity levels was also evaluated.Results:A non-significant increase of +1605 revertants/g creatinine in urinary mutagenicity during the workweek relative to levels observed on Sunday was observed for the total population. Subsequent multivariate regression analyses, with the subjects’ weekday urinary mutagenicity levels as the dependent variable, revealed associations with environmental and mainstream tobacco smoke exposure, with the level of mutagenic contamination on surfaces with which the subjects had likely contact, with the subjects’ inhalable particulate exposure level, with observed mild skin aberrations, and when the subjects had a slow acetylation phenotype. Similar associations, although weaker were observed with Sunday urinary mutagenicity levels as well, except for the association with slow acetylation phenotype. Based on measured exposure levels it could be estimated that a high potential for exposure to surface contamination with mutagenic activity increased weekday urinary mutagenicity by about 62% when compared to low exposed workers, while high inhalable particulate exposure levels increased weekday urinary mutagenicity levels by about 21%. Subjects with mild skin aberrations had an additional, non-significant, increase in weekday urinary mutagenic activity compared to subjects without any skin aberrations.Discussion:Results suggest that the dermal exposure route may contribute more to the level of genotoxic compounds in urine of rubber workers than the inhalation route. Although the study was limited in size, the results warrant further investigation in the importance of and ways to effectively control the dermal exposure route in the rubber industry.
Airway pathology in asthma: Fig. 1.—
Authors: Saetta M. , Turato G. 
Published: January 2003

This review focuses on the major cellular and structural changes present in the airways and lung parenchyma in asthma in comparison with chronic obstructive pulmonary disease (COPD) in an attempt to underline the possible mechanisms contributing to airflow limitation in these two diseases.Both asthma and COPD are characterized by a thickening of the airway wall and by the presence of an inflammatory process, but the inflammatory cells infiltrating the airway wall differ between the two diseases.In asthma, the most striking feature is the eosinophilic infiltration, whereas, in COPD, it is the CD8 T‐lymphocytic infiltration of the airway wall. In the lung parenchyma, both diseases are characterized by an inflammatory process, whereas destruction and fibrosis of the alveolar walls occur in COPD but not in asthma.These cellular and structural changes may contribute to the development of airflow limitation (that characterizes both asthma and chronic obstructive pulmonary disease) by inducing either an increase in resistance or a decrease in driving pressure.
Cytokines in asthma
Authors: Kips J.C. 
Published: January 2003

The airway inflammation underlying asthma is regulated by a network of mutually interacting cytokines. The exact functional role of each individual cytokine in the pathogenesis of the disease remains to be fully established.Type 2 T‐helper cells are currently considered to play a crucial role in this process.In vivoanimal data suggest a sequential involvement of interleukin (IL)‐4 and IL‐5 in the induction of allergen-induced airway changes. The potential role of other type 2 T‐helper cell-like cytokines in asthma is increasingly being recognized. In particular, IL‐4 and -13 display a large degree of redundancy. Whereas IL‐4 seems to be crucial in the primary allergen sensitization process, IL-13 might be more important during secondary exposure to aerosolized allergen. Animal models also indicate that T‐cell-derived cytokine production, rather than eosinophil influx or immunoglobulin‐E synthesis, is causally related to altered airway behaviour.An important aspect when evaluating the functional role of cytokines in a complex disease such as asthma is the interaction with other cytokines in the microenvironment. Increased expression of pro-inflammatory cytokines such as tumour necrosis factor‐α can further enhance the inflammatory process, and is increasingly linked to disease severity. In addition, decreased expression of immunoregulatory cytokines, including interleukin-12, interleukin-18 or interferon gamma could also strengthen the type 2 T‐helper cell-driven inflammatory process.
Cytokines in chronic obstructive pulmonary disease
Authors: Chung K.F. 
Published: January 2003

Chronic obstructive pulmonary disease (COPD) is characterized by chronic obstruction of expiratory flow affecting peripheral airways, associated with chronic bronchitis (mucus hypersecretion with goblet cell and submucosal gland hyperplasia) and emphysema (destruction of airway parenchyma), together with fibrosis and tissue damage, and inflammation of the small airways. Cytokines are extracellular signalling proteins. Increased levels of interleukin (IL)‐6, IL‐1β, tumour necrosis factor‐α (TNF‐α) and IL‐8 have been measured in sputum, with further increases during exacerbations, and the bronchiolar epithelium over-expresses monocyte chemotactic protein (MCP)‐1 and IL‐8. IL‐8 can account for some chemotactic activity of sputum, and sputum IL‐8 levels correlate with airway bacterial load and blood myeloperoxidase levels. The expression of chemokines such as regulated on activation, normal T‐cell expressed and secreted (RANTES) may underlie the airway eosinophilia observed in some COPD patients. Cytokines may be involved in tissue remodelling. TNF‐α and IL‐1β stimulate macrophages to produced matrix metalloproteinase‐9 (MMP‐9), and bronchial epithelial cells to produce extracellular matrix glycoproteins such as tenascin. Increased expression of transforming growth factor‐β (TGFβ) and of epidermal growth factor (EGF) occurs in the epithelium and submucosal cells of patients with chronic bronchitis. TGFβ and EGF activate proliferation of fibroblasts, while activation of the EGF receptor leads to mucin gene expression.The cytokine profile seen in chronic obstructive pulmonary disease is different from that observed in asthma. The role of these cytokines needs to be defined and there is a potential for anticytokine therapy in chronic obstructive pulmonary disease.
Modern treatment of chronic obstructive pulmonary disease
Authors: Calverley P.M.A. 
Published: January 2003

Chronic obstructive pulmonary disease (COPD) is a major cause of ill health and medical expenditure worldwide. Despite recent increases in the knowledge about the nature of the disease process and recognition of cytokine-mediated pathways of inflammation, current management is focussed on patient outcomes that relate to physiological measures of dysfunction.The new Global initiative in Obstructive Lung Disease (GOLD) management guidelines are evidence-based and stress both pharmacological and nonpharmacological therapy. Effective drug therapy can help smoking cessation in motivated patients (nicotine replacement, bupropion). Bronchodilator therapy is best given by inhaler, can use either beta-agonists or anticholinergics and is more effective if long acting. Health status and exercise performance can improve without parallel changes in forced expiratory volume in one second. Inhaled corticosteroids are indicated if there is a significant bronchodilator response or the patient has more severe disease with frequent exacerbations.Antioxidant therapy remains controversial but may reduce exacerbation number. Acute exacerbations require higher doses of bronchodilators and short courses of oral corticosteroids. New drug treatment is a major priority for chronic obstructive pulmonary disease research.
Cytokine modulators as novel therapies for airway disease
Authors: Barnes P.J. 
Published: January 2003

Cytokines play a critical role in orchestrating and perpetuating inflammation in asthma and chronic obstructive pulmonary disease (COPD), and several specific cytokine and chemokine inhibitors are now in development for the future therapy of these diseases.Anti-interleukin (IL)‐5 is very effective at reducing peripheral blood and airway eosinophil numbers, but does not appear to be effective against symptomatic asthma. Inhibition of IL‐4 with soluble IL‐4 receptors has shown promising early results in asthma. Inhibitory cytokines, such as IL-10, interferons and IL-12 are less promising, as systemic delivery causes side-effects. Inhibition of tumour necrosis factor‐α may be useful in severe asthma and for treating severe COPD with systemic features.Many chemokines are involved in the inflammatory response of asthma and COPD and several low-molecular-weight inhibitors of chemokine receptors are in development. CCR3 antagonists (which block eosinophil chemotaxis) and CXCR2 antagonists (which block neutrophil and monocyte chemotaxis) are in clinical development for the treatment of asthma and COPD respectively.Because so many cytokines are involved in asthma, drugs that inhibit the synthesis of multiple cytokines may prove to be more useful; several such classes of drug are now in clinical development and any risk of side-effects with these nonspecific inhibitors may be reduced by the use of inhalational route of delivery.
Disease of the airways in chronic obstructive pulmonary disease
Authors: Cosio Piqueras M.G. , Cosio M.G. 
Published: January 2003

The pathological hallmarks of chronic obstructive pulmonary disease (COPD) are inflammation of the small airways (bronchiolitis) and destruction of lung parenchyma (emphysema). The functional consequence of these abnormalities is airflow limitation.Airway abnormalities and emphysema interact in a complex fashion in the development of airflow limitation in COPD. In an attempt to improve understanding of the role of the airways in COPD, the morphological counterparts of airflow limitation, the cellular inflammatory infiltrate in the airways and the relationship between emphysema type and airway abnormalities are reviewed.Significant correlation between airway remodelling and functional measurements are found in earlier stages of COPD. In advanced COPD, airflow limitation is reflected by airway narrowing, airway deformity and extent of emphysema. The cellular inflammatory infiltrate is mainly composed of neutrophils in early stages of COPD. However, the presence of CD8+ T‐cells seems to differentiate smokers with COPD from smokers that would not develop the disease. The inflammatory changes and remodelling found in the airways and their contribution to airflow obstruction might be modulated by the type of emphysema smokers develop, with centrilobular emphysema showing more severe inflammatory changes and narrower airways than panlobular emphysema.In conclusion, the degree of airway involvement in chronic obstructive pulmonary disease can vary greatly for the same degree of airflow obstruction, depending on the type of emphysema smokers develop. If the underlying lung abnormalities in chronic obstructive pulmonary disease vary, as the evidence suggests, the study of cigarette-induced lung disease as a single entity will further delay understanding of chronic obstructive pulmonary disease.