Bacterial Endotoxin Is an Active Component of Cigarette Smoke

Exposure to airborne endotoxin in infancy may protect against asthma by promoting enhanced TH1 response and tolerance to allergens. On the other hand, later in life, it adversely affects patients with asthma. Endotoxin binding to receptors on macrophages and other cells generates IL-12, which inhibits IgE responses. It also generates cytokines like IL-1, TNF-α, and IL-8, which cause inflammation. These signal transduction pathways resemble those leading to the generation of cytokines, such as IL-4, IL-13, and IL-5, which are responsible for the inflammation of IgE-mediated allergic disease. The main difference seems to be that endotoxin recruits neutrophils, but IgE recruits eosinophils, and the details of the tissue injury from these granulocytes differ. Sources of airborne endotoxin include many agricultural dusts, aerosols from con-taminated water in many industrial plants, contaminated heating and air-conditioning systems, mist-generating humidifiers, and damp or water-damaged homes. Acute inhalation of high concentrations of endotoxin can cause fever, cough, and dyspnea. Chronic inhalation of lesser amounts causes chronic bronchitis and emphysema and is associated with airway hyperresponsiveness. Airborne endotoxin adversely affects patients with asthma in 3 ways: (1) by increasing the severity of the airway inflammation; (2) by increasing the susceptibility to rhinovirus-induced colds; and (3) by causing chronic bronchitis and emphysema with development of irreversible airway obstruction after chronic exposure of adults. The most effective management is mitigating exposure. The potential of drug treatments requires further clinical investigation. (J Allergy Clin Immunol 2001;108:157-66.)

https://www.jacionline.org/article/S0091-6749(01)32579-4/pdf

Endotoxin-stimulated innate immunity: A contributing factor for asthma.

Context.— Although many mesotheliomas are related to asbestos exposure, not all are, and there is increasing information on other causes of mesothelioma. Objective.— To provide a review of non-asbestos causes for malignant mesothelioma. Data Sources.— Review of relevant published literature via PubMed and other search engines. Conclusions.— Currently, most pleural mesotheliomas (70% to 90%) in men in Europe and North America are attributable to asbestos exposure; for peritoneal mesothelioma the proportion is lower. In North America few mesotheliomas in women at any site are attributable to asbestos exposure, but in Europe the proportion is higher and varies considerably by locale. In certain geographic locations other types of mineral fibers (erionite, fluoro-edenite, and probably balangeroite) can induce mesothelioma. Therapeutic radiation for other malignancies is a well-established cause of mesothelioma, with relative risks as high as 30. Carbon nanotubes can also induce mesotheliomas in animals but th...

Malignant Mesothelioma and Its Non-Asbestos Causes

OBJECTIVES: The aims of this study were to document the prevalence of work related upper and lower respiratory tract symptoms in workers exposed to organic dusts and to identify variables predictive of their occurrence. METHODS: A cross sectional survey with an administered questionnaire (a previously validated adaptation of the Medical Research Council (MRC) respiratory questionnaire) was performed. Symptoms were classified as work related by their periodicity. Demographic data, smoking habits, and occupational histories were recorded. Personal exposures to dust and endotoxin were measured and individual subjects ascribed an exposure value specific to occupation, site and industry. Cox's regression techniques were used to identify variables predictive of work related upper and lower respiratory tract symptoms. Information was stored using Dbase 3 and analysed with SPSS. RESULTS: 1032 Workers (93% of the target population) were studied in nine different industries. The highest prevalences of work related lower respiratory tract symptoms (38.1%), upper respiratory tract symptoms (45.2%), and chronic bronchitis (15.5%) were found among poultry handlers. White workers were significantly more likely to complain of upper and lower respiratory tract symptoms. An individual in the swine confinement industry had a symptom complex compatible with byssinosis. Increasing current personal exposures to dust or endotoxin were found to be predictive of upper and lower respiratory tract symptoms, chronic bronchitis, and byssinosis. In a univariate analysis a relation between current exposures and the organic dust toxic syndrome was found. Present smoking and previously documented respiratory tract illness were significantly predictive of work related lower respiratory tract symptoms. Women were more likely to report work related upper respiratory tract symptoms. CONCLUSIONS: People exposed to organic dusts may have a high prevalence of work related respiratory tract symptoms which are related to dust exposures and smoking habits. Action should be taken to reduce exposures to dust and endotoxin and stopping smoking should be promoted among workers exposed to organic dusts to reduce morbidity.

https://oem.bmj.com/content/oemed/55/10/668.full.pdf

Prevalence and predictors of work related respiratory symptoms in workers exposed to organic dusts.

Purpose of reviewThis review provides an update on the role of bacterial endotoxin in occupational airway disease, a problem of importance from diagnostic and preventive points of view.Recent findingsData from human inhalation studies have increased our understanding of the cell mechanisms underlyin

Endotoxin and occupational airway disease.

All the 303 full time day workers in a carpet weaving factory were submitted to a physical examination, chest radiography, and vitalograph test, and answered a respiratory questionnaire. Fifty four healthy non-exposed subjects served as controls. Dust concentrations and concentrations of bacterial endotoxin were measured. Of the 303 workers, 259 (85.5%) had airway symptoms and 62 (20.5%) had maximum mid-expiratory flow (MMF) values of less than 60% compared with 9.2% of the controls. The symptoms in 68 workers (22%) were compatible with byssinosis and 36 of these workers underwent vitalography before starting work and after four hours work on Mondays when significant reductions of their FEV1 and MMF were found. Twenty one of these 36 workers were tested on Tuesday and no differences in these measurements were found between measurements before work started and four hours later. The airborne dust concentrations in the factory were high and bacterial endotoxin was found. These findings suggest that a large number of workers in this carpet weaving factory suffer from a disease indistinguishable from byssinosis even though wool is used almost exclusively, the only cotton being the warp. The finding of endotoxin together with the absence of cotton confirms the theory that "byssinosis" is due to bacterial endotoxin rather than to cotton per se.

https://oem.bmj.com/content/oemed/44/7/479.full.pdf

Byssinosis in carpet weavers exposed to wool contaminated with endotoxin.

Dust from the village of Karain containing the fibrous zeolite erionite, talc, and physiological saline were tested by intraperitoneal injection in 486 Swiss albino mice. Malignant tumours were found in 84 (41 mesotheliomas, 31 lymphomas, 1 peripheral epidermoid carcinoma, and 11 lymphomas and mesotheliomas together) of the 321 animals which died spontaneously within nine to 32 months after injection of Karain dust (26.1%). Three mesotheliomas and no lymphomas were found among 24 animals injected in the same way with talc during the same time (12.5%). In 46 control animals injected with physiological saline three mesotheliomas and one lymphoma were seen (8.7%). Thus Karain dust appears to be a potent carcinogen, causing both mesotheliomas and malignant lymphomas.

https://oem.bmj.com/content/oemed/42/11/746.full.pdf

Peritoneal mesothelioma and malignant lymphoma in mice caused by fibrous zeolite.

Allthe303full time dayworkers inacarpet weaving factory weresubmitted toaphysical examination, chest radiography, andvitalograph test, andanswered arespiratory questionnaire. Fifty four healthy non-exposed subjects served ascontrols. Dustconcentrations andconcentrations ofbacterial endotoxin weremeasured. Ofthe303workers, 259(85-5%) hadairway symptoms and 62(20-5%) hadmaximummid-expiratory flow(MMF)values ofless than60%compared with 9*2%ofthecontrols. Thesymptoms in68workers (22%)werecompatible withbyssinosis and36 ofthese workers underwent vitalography before starting workandafter four hours workonMon- dayswhensignificant reductions oftheir FEV1andMMF werefound. Twentyoneofthese 36 workers weretested onTuesday andnodifferences inthese measurements werefoundbetween nmeasurements before workstarted andfourhours later. Theairborne dustconcentrations inthe factory werehighandbacterial endotoxin wasfound. These findings suggest that alarge numberof workers inthis carpet weaving factory suffer fromadisease indistinguishable frombyssinosis even though woolisusedalmost exclusively, theonlycotton being thewarp. Thefinding ofendotoxin together withtheabsence ofcotton confirms thetheory that "byssinosis" isduetobacterial endo- toxin rather thantocotton perse. Theknotting ofwoolcarpets isacommonindustry in Kayseri inMiddle Anatolia, Turkey. Onlyafewstud- iesonwoolcarpet factories orwoollen mills have beenpublished inEnglish andthese report anexcess ofrespiratory symptoms.12 Obstructive airway disease inworkers intextile fac- tories hasbeenrecognised since theeighteenth cen- tury, whenitwasdescribed byRamazzini. The disease hasbeentermed byssinosis andoccurs when working withsuchmaterials ascotton andflax. The classic symptoms aresubjective tightness inthechest andoften anindependent decrease oflungfunction onthefirst dayafter theweekend oraprolonged ab- sence. Thesesymptoms areoften accompanied by coughing andwheezing.` Thespecific aetiological agent inbyssinosis isun- known. Previously, ithasbeensuggested that some

M Ozesmi

Papers

Byssinosis in carpet weavers exposed to wool contaminated with endotoxin.

Peritoneal mesothelioma and malignant lymphoma in mice caused by fibrous zeolite.

Byssinosis incarpet weavers exposed towool contaminated withendotoxin