Grain dust and the lungs.

Grain dust is composed of a large number of materials, including various types of grain and their disintegration products, silica, fungi, insects and mites. The clinical syndromes described in relation to exposure to grain dust are chronic bronchitis, grain dust asthma, extrinsic allergic alveolitis, grain fever and silo-filler''s lung. Rhinitis and conjunctivitis are also common in grain workers. While the concentration and the quality of dust influence the frequency and the type of clinical syndrome in grain workers, host factors are also important. Of the latter, smoking is the most important factor influencing the frequency of chronic bronchitis. The role of atopy and of bronchial hyperreactivity in grain dust asthma has yet to be assessed. Several well designed studies are currently being carried out in North America not only to delineate the frequency of the respiratory abnormalities, the pathogenetic mechanisms and the host factors, but also to establish a meaningful threshold limit concentration for grain dust.     

Pulmonary intravascular macrophages as proinflammatory cells in heaves, an asthma-like equine disease

Heaves, an obstructive neutrophilic airway inflammation of horses, is triggered by dust components such as endotoxin and has similarities to human asthma. Pulmonary intravascular macrophages (PIMs) increase horses' sensitivity to endotoxin-induced lung inflammation; however, their role in an airborne pathology remains unknown. Therefore, we investigated the role of PIMs in the development of heaves in horses. Clinical and inflammatory responses were evaluated following induction of heaves by moldy hay exposure and PIM depletion with gadolinium chloride (GC). Mares (N = 9) were exposed to four treatments: alfalfa cubes (Cb), alfalfa cubes + GC (Cb-GC), moldy hay (MH), and moldy hay + GC (MH-GC). Clinical scores and neutrophil concentrations in bronchoalveolar lavage (BAL) fluid were higher when mares received MH compared with MH-GC. BAL cells from MH-GC-treated mares had significantly lower IL-8 and TLR4 mRNA expression compared with MH-treated mares. In vitro LPS challenge significantly increased IL-8 but not TLR4 mRNA expression in BAL cells recovered from horses fed with MH, but not from the MH-GC treatment. In summary, PIM depletion attenuated clinical scores, reduced the alveolar migration of neutrophils, and decreased the expression of proinflammatory molecules in BAL cells of heaves horses, suggesting a proinflammatory role of PIMs in the development of airborne pathology.     

Prevalence of Farmer's Lung in Scotland: A Pilot Survey

In a survey of the farming population of Orkney, Ayrshire, and East Lothian the prevalence of farmer''s lung was estimated at 86 per 1,000 in both Orkney and Ayrshire and 23 per 1,000 in East Lothian. If cases with a negative farmer''s lung hay (F.L.H.) precipitin test are excluded these figures are reduced to 43, 36, and nil respectively, but those for Orkney and Ayrshire are still about 20 times higher than any figure previously reported for the prevalence of farmer''s lung in Britain.Regional variations in prevalence are probably related both to climatic conditions and to differences in agricultural methods, the latter often being dictated by economic circumstances. Nevertheless the prevalence of farmer''s lung could be reduced considerably by the energetic application of preventive measures, backed by financial incentives. The most important of these are efficient drying of hay and cereals before storage, more extensive use of silage, better ventilation of farm buildings, and the introduction of mechanical feeding systems. Individual farmworkers could be taught how to recognize the early symptoms of the disease and encouraged to wear respirators when handling mouldy fodder.     

Radiological progression and lung function in silicosis: a ten year follow up study.

Chest radiographs and spirometric tests were performed on 81 patients who had silicosis from two granite quarries in 1975, 73 of whom were followed up for two to 10 (mean 7.2) years. Each patient''s initial and most recent chest radiographs were assessed independently by three experienced readers, and the yearly declines in forced expiratory volume in one second and forced vital capacity were estimated from two to four (mean 3.45) serial spirometric readings. Estimates of individual dust exposure were based on extensive historical data on hygiene. All but 11 patients were no longer exposed to dust by the start of follow up, but 24 (45%) of 53 patients who had simple silicosis and 11 (55%) of 20 who had the complicated disease showed radiological evidence of disease progression. In patients who had simple silicosis and showed no radiological progression the yearly declines in forced expiratory volume in one second and forced vital capacity were modest (64 ml/year and 59 ml/year, respectively), whereas significantly greater declines in lung function were seen in those who showed radiological evidence of progression (97 ml/year and 95 ml/year, respectively). In addition to radiological progression the previous average dust concentration to which patients had been exposed also influenced declines in both forced expiratory volume in one second and forced vital capacity after allowing for the effects of age, smoking, duration of exposure, history of tuberculosis, initial state of disease, and baseline lung function. The probability of radiological progression was most strongly influenced by the average dust concentration previously exposed to. The progression of simple silicosis is thus accompanied by appreciable declines in lung function and is strongly affected by previous levels of exposure to dust.     

Coeliac disease with farmers' lung.

Two patients with allergic alveolitis due to mouldy hay antigens (farmer''s lung) were shown to have malabsorption due to coeliac disease. As similar associations have been found with other alveolar diseases, this association is probably not fortuitous and further population screening should be done.     

Increased hypoxia-inducible factor 1alpha expression in lung cells of horses with recurrent airway obstruction

ABSTRACT: BACKGROUND: Recurrent airway obstruction (RAO, also known as equine heaves) is an inflammatory condition caused by exposure of susceptible horses to organic dusts in hay. The immunological processes responsible for the development and the persistence of airway inflammation are still largely unknown. Hypoxia-inducible factor (Hif) is mainly known as a major regulator of energy homeostasis and cellular adaptation to hypoxia. More recently however, Hif also emerged as an essential regulator of innate immune responses. Here, we aimed at investigating the potential involvement of Hif1-alpha in myeloid cells in horse with recurrent airway obstruction. RESULTS: In vitro, we observed that Hif is expressed in equine myeloid cells after hay dust stimulation and regulates genes such as tumor necrosis factor alpha (TNF-alpha), interleukin-8 (IL-8) and vascular endothelial growth factor A (VEGF-A). We further showed in vivo that airway challenge with hay dust upregulated Hif1-alpha mRNA expression in myeloid cells from the bronchoalveolar lavage fluid (BALF) of healthy and RAO-affected horses, with a more pronounced effect in cells from RAO-affected horses. Finally, Hif1-alpha mRNA expression in BALF cells from challenged horses correlated positively with lung dysfunction. CONCLUSION: Taken together, our results suggest an important role for Hif1-alpha in myeloid cells during hay dust-induced inflammation in horses with RAO. We therefore propose that future research aiming at functional inactivation of Hif1 in lung myeloid cells could open new therapeutic perspectives for RAO.     

A high docosahexaenoic acid diet alters lung inflammation and recovery following repetitive exposure to aqueous organic dust extracts

Agricultural workers, especially those who work in swine confinement facilities, are at increased risk for developing pulmonary diseases including asthma, chronic obstructive pulmonary disease, and chronic bronchitis due to exposures to fumes, vapors, and organic dust. Repetitive exposure to agricultural dust leads to unresolved inflammation, a common underlying mechanism that worsens lung disease. Besides occupational exposure to dusts, diet also significantly contributes to inflammation and disease progression. Since DHA (docosahexaenoic acid), a polyunsaturated omega-3 fatty acid and its bioactive metabolites have key roles in inflammation resolution, we rationalized that individuals chronically exposed to organic dusts can benefit from dietary modifications. Here, we evaluated the role of DHA in modifying airway inflammation in a murine model of repetitive exposure to an aqueous extract of agricultural dust (three-week exposure to swine confinement dust extract, HDE) and after a one-week resolution/recovery period. We found that mice fed a high DHA diet had significantly increased bronchoalveolar lavage fluid (BALF) levels of DHA-derived resolvins and lower TNFα along with altered plasma levels of endocannabinoids and related lipid mediators. Following the one-week recovery we identified significantly reduced BALF cellularity and cytokine/chemokine release along with increased BALF amphiregulin and resolvins in DHA diet-fed versus control diet-fed mice challenged with HDE. We further report observations on the effects of repetitive HDE exposure on lung Ym1+ and Arg-1+ macrophages. Overall, our findings support a protective role for DHA and identify DHA-derived resolvins and endocannabinoids among the potential mediators of DHA in altering airway inflammation in chronic agricultural dust exposure.     

Respiratory profiles of grain handlers and sedentary workers.

During 1978, grain handlers employed at three large inland grain terminals were studied along with an equal number of office workers matched for sex, age and smoking history. Respiratory symptoms and spirometric abnormalities were no more frequent in 16 grain handlers who were non-smokers than in their controls. However, 20 grain handlers who were smokers complained significantly more (P less than 0.01) of grade 1 dyspnea and had significantly lower ratios of forced expiratory volume in the first second to forced vital capacity (P less than 0.05) than their controls. Only 3% of the grain handlers were sensitive to grain dust, and 18% were found to be atopic but to have good lung function. A family history of asthma or allergic rhinitis was no more frequent in the grain handlers than in the control subjects. We conclude that the combination of cigarette smoking and exposure to grain dust causes a deterioration in lung function.     

Respiratory disorders in Manitoba cattle farmers.

A group of 76 cattle farmers from southern Manitoba answered the National Heart, Lung, and Blood Institute questionnaire on respiratory symptoms and supplementary questions on farming and farming-related syndromes. Lung function was tested, serum was examined for precipitating antibodies, and skin testing with common allergens was performed. Analysis of the men''s answers revealed a high prevalence of chronic respiratory symptoms among the farmers in all categories of smoking history, and the presence of these symptoms was significantly associated with a history of symptoms related to handling mouldy hay or grain; 51% of the men had chronic symptoms and 55% had symptoms related to crop handling. In seven farmers (9%) the symptoms related to crop handling suggested an attack of farmer''s lung. One other farmer, with a history of illness after handling mouldy hay, had a reduced total lung capacity, and in 18 the ratio of the forced expiratory volume in the first second to the forced vital capacity was lower than predicted. Precipitating antibodies against Thermoactinomyces were absent in all farmers, but two farmers had antibodies against Aspergillus ruber. Immediate hypersensitivity was found in 16 (21%) of the farmers; sensitivity to Dermatophagoides farinae was commonest.     

支气管哮喘患者心理特征研究进展

支气管哮喘是全球范围内影响巨大的慢性气道炎症性呼吸道疾病,近年来随着空气污染的加剧和吸烟人数的增多,其发病率呈逐年上升的趋势,引起医学界越来越多的关注。支气管哮喘是由遗传因素、生物因素、心理因素等多种发病因素综合影响所致,随着研究的深入,有关心理因素对支气管哮喘的作用取得了重大的进展,其中支气管哮喘患者存在明显的人格特征和情绪障碍,并且患者特有的人格特征以及情绪障碍会对患者的病情和生活质量产生一定的影响。鉴于此,本文就支气管哮喘患者的性格特征、情绪特征以及其对疾病的影响进行简要阐述,以供临床参考。     

Pulmonary emphysema associated with the FZ alpha 1-antitrypsin phenotype.

In one family three brothers were found to have a moderate deficiency of alpha 1-antitrypsin associated with the unusual Pi (protease inhibitor) phenotype FZ. The Pi phenotypes of their six living siblings were found to be FM (in three), M (in two) and MZ (in one). The three FZ brothers all had moderate to severe obstructive airways disease, and two had at least moderately severe pulmonary emphysema. Additional risk factors included moderate cigarette smoking in two and prolonged exposure to grain dust in all three. The same risk factors applied to the six non-FZ siblings, but they had only mild symptoms and pulmonary dysfunction or no lung problems at all; one, a female smoker with the MZ phenotype, had probable early emphysema demonstrated radiologically. The three FZ men may have had reduced fertility, as they produced only 1 child among them, as compared with 39 among the other eight siblings. This family study thus suggests that individuals with the FZ phenotype are at risk for pulmonary emphysema and chronic obstructive airways disease, particularly in the presence of other risk factors, such as cigarette smoking and grain dust exposure.     

Storage mites

The interest in allergy to storage mites has increased over the past few years. Storage mites feed on a variety of substances and they can be found in many different products such as grain, flour, hay and straw, but also in house dust samples. The more common genera areLepidoglyphus, Tyrophagus, Glycyphagus, Acarus andBlomia. Several species of storage mites have been shown to cause IgE-mediated sensitization among rural workers, who to a varying extent develop asthma, rhinitis or conjunctivitis when exposed to barn dust. However, a number of studies, have reported on sensitization to storage mites also among urban people, indicating that sensitization is not restricted to individuals with occupational exposure. Regarding the allergenic relationship between storage mites and house dust mites, there appears to be a limited allergenic cross-reactivity between the two species. However, both species also possess their own unique allergens. Further research on identification and characterization of storage mite allergens and their cross-reactivity is required to understand the complexity of epitopes and allergens.     

Porphyrin derivatives as inhibitors for acetylcholinesterase from Drosophila melanogaster

The cure for Alzheimer''s disease (AD) is still unknown. According to Cholinergic hypothesis, Alzheimer''s disease is caused by the reduced synthesis of the neurotransmitter, Acetylcholine. Regional cerebral blood flow can be increased in patients with Alzheimer''s disease by Acetylcholinesterase (AChE) inhibitors. In this regard, Tetraphenylporphinesulfonate (TPPS), 5,10,15,20- Tetrakis (4-sulfonatophenyl) porphyrinato Iron(III) Chloride (FeTPPS) and 5,10,15,20-Tetrakis (4-sulfonatophenyl) porphyrinatoIron(III) nitrosyl Chloride (FeNOTPPS) were investigated as candidate compounds for inhibition of Acteylcholinesterase of Drosophila melanogaster (DmAChE) by use of Molecular Docking. The results show that FeNOTPPS forms the most stable complex with DmAChE.     

A major outbreak of asthma associated with a thunderstorm: experience of accident and emergency departments and patients' characteristics. Thames Regions Accident and Emergency Trainees Association.

OBJECTIVE--To investigate the time course of an epidemic of asthma after a thunderstorm, characteristics of patients affected, and the demand on emergency medical resources. DESIGN--Study of registers and records in accident and emergency departments and questionnaire to staff. SETTING--London area. SUBJECTS--All patients presenting at 12 accident and emergency departments with asthma or other airway disease. MAIN OUTCOME MEASURES--Numbers of patients, clinical features, information on shortage of resources--equipment, drugs and staff. RESULTS--The epidemic had a sudden onset on 24 June 1994; 640 patients with asthma or other airways disease attended during 30 hours from 1800 on 24 June, nearly 10 times the expected number. Over half (365) the patients were aged 21 to 40 years. A history of hay fever was recorded in 403 patients; for 283 patients this was the first known attack of asthma; a history of chronic obstructive airways disease was recorded in 12 patients. In all, 104 patients were admitted (including five to an intensive care unit). Several departments ran out of equipment or drugs, called in additional doctors, or both. CONCLUSIONS--This study supports the view that this epidemic was larger than previously reported epidemics and the hypothesis that "thunderstorm associated asthma'' is related to aeroallergens. Demands on resources were considerable; a larger proportion of patients needing intensive care would have caused greater problems.     

Diesel Exhaust Particles Induce Cysteine Oxidation and S-Glutathionylation in House Dust Mite Induced Murine Asthma

Background

Diesel exhaust particle (DEP) exposure enhances allergic inflammation and has been linked to the incidence of asthma. Oxidative stress on the thiol molecules cysteine (Cys) and glutathione (GSH) can promote inflammatory host responses. The effect of DEP on the thiol oxidation/reduction (redox) state in the asthmatic lung is unknown.

Objective

To determine if DEP exposure alters the Cys or GSH redox state in the asthmatic airway.

Methods

Bronchoalveolar lavage fluid was obtained from a house dust mite (HDM) induced murine asthma model exposed to DEP. GSH, glutathione disulfide (GSSG), Cys, cystine (CySS), and s-glutathionylated cysteine (CySSG) were determined by high pressure liquid chromatography.

Results

DEP co-administered with HDM, but not DEP or HDM alone, decreased total Cys, increased CySS, and increased CySSG without significantly altering GSH or GSSG.

Conclusions

DEP exposure promotes oxidation and S-glutathionylation of cysteine amino acids in the asthmatic airway, suggesting a novel mechanism by which DEP may enhance allergic inflammatory responses.     

Early onset airway obstruction in response to organic dust in the horse.

Equine recurrent airway obstruction (RAO) has been used as a naturally occurring model of human asthma. However, it is unknown whether there is an early-phase response in RAO. The aim of this study was to determine whether exposure to organic dust induces immediate changes in lung function in RAO-affected horses, which could be mediated by airway mast cells. Six RAO-affected horses in remission and six control horses were challenged with hay-straw dust suspension by nebulization. Total respiratory resistance at 1 Hz, measured by forced oscillation, was increased from 0.62 +/- 0.09 cmH(2)O.l(-1).s (mean +/- SE) to 1.23 +/- 0.20 cmH(2)O.l(-1).s 15 min after nebulization in control horses (P = 0.023) but did not change significantly in the RAO group. Total respiratory reactance at 1 Hz (P = 0.005) was significantly lower in the control horses (-0.77 +/- 0.07 cmH(2)O.l(-1).s) than in the RAO group (-0.49 +/- 0.04 cmH(2)O.l(-1).s) 15 min after nebulization. Bronchoalveolar lavage fluid (BALF) histamine concentration was significantly elevated 10 and 20 min postnebulization in control horses but not in RAO horses. Minimum reactance at 1 Hz in the early postnebulization period significantly correlated with both prechallenge BALF mast cell numbers (r = -0.65, P = 0.02) and peak BALF histamine concentration postnebulization (r = -0.61, P = 0.04). In conclusion, RAO horses, unlike human asthmatic patients, do not exhibit an early-phase response. However, healthy control horses do demonstrate a mild but significant early (<20 min) phase response to inhaled organic dust. This response may serve to decrease the subsequent dose of dust inhaled and as such provide a protective mechanism, which may be compromised in RAO horses.     

Non-smoking wives of heavy smokers have a higher risk of lung cancer: a study from Japan.

In a study in 29 health centre districts in Japan 91 540 non-smoking wives aged 40 and above were followed up for 14 years (1966-79), and standardised mortality rates for lung cancer were assessed according to the smoking habits of their husbands. Wives of heavy smokers were found to have a higher risk of developing lung cancer and a dose-response relation was observed. The relation between the husband''s smoking and the wife''s risk of developing lung cancer showed a similar pattern when analysed by age and occupation of the husband. The risk was particularly great in agricultural families when the husbands were aged 40-59 at enrolment. The husbands'' smoking habit did not affect their wives'' risk of dying from other disease such as stomach cancer, cervical cancer, and ischaemic heart disease. The risk of developing emphysema and asthma seemed to be higher in non-smoking wives of heavy smokers but the effect was not statistically significant. The husband''s drinking habit seemed to have no effect on any causes of death in their wives, including lung cancer. These results indicate the possible importance of passive or indirect smoking as one of the causal factors of lung cancer. They also appear to explain the long-standing riddle of why many women develop lung cancer although they themselves are non-smokers. These results also cast doubt on the practice of assessing the relative risk of developing lung cancer in smokers by comparing them with non-smokers.     

B7-H3 Promotes Pathogenesis of Autoimmune Disease and Inflammation by Regulating the Activity of Different T Cell Subsets

B7-H3 is a cell surface molecule in the immunoglobulin superfamily that is frequently upregulated in response to autoantigens and pathogens during host T cell immune responses. However, B7-H3''s role in the differential regulation of T cell subsets remains largely unknown. Therefore, we constructed a new B7-H3 deficient mouse strain (B7-H3 KO) and evaluated the functions of B7-H3 in the regulation of Th1, Th2, and Th17 subsets in experimental autoimmune encephalomyelitis (EAE), experimental asthma, and collagen-induced arthritis (CIA); these mouse models were used to predict human immune responses in multiple sclerosis, asthma, and rheumatoid arthritis, respectively. Here, we demonstrate that B7-H3 KO mice have significantly less inflammation, decreased pathogenesis, and limited disease progression in both EAE and CIA mouse models when compared with littermates; these results were accompanied by a decrease in IFN-γ and IL-17 production. In sharp contrast, B7-H3 KO mice developed severe ovalbumin (OVA)-induced asthma with characteristic infiltrations of eosinophils in the lung, increased IL-5 and IL-13 in lavage fluid, and elevated IgE anti-OVA antibodies in the blood. Our results suggest B7-H3 has a costimulatory function on Th1/Th17 but a coinhibitory function on Th2 responses. Our studies reveal that B7-H3 could affect different T cell subsets which have important implications for regulating pathogenesis and disease progression in human autoimmune disease.