Inhalation, endotoxin

Endotoxin inhalation has been proposed to explain symptoms of the acute byssinotic reaction ( ) and implicated as the causative... 

Pauwels R, Kips J, Peleman R, Straeten MVD. The effect of endotoxin inhalation on airway responsiveness and cellular influx in rats. Am Rev Respir Dis 1990 141 540-545. 

In favor of the endotoxin theory is the demonstration that endotoxins are active if administered by aerosol (62,64), as is the agent of byssinosis. In a rabbit model, inhalation of either endotoxin or cotton dust extract produces histological patterns consistent with chronic bronchitis (65). Also, in a variety of animal species, fever and dyspnea occur after short periods of inhalation of endotoxins, but when endotoxin solutions are Inhaled on two consecutive days, the second Inhalation is without effect. This suggests tolerance to endotoxins, and parallels the Monday syndrome, characteristic of byssinosis (62). 

Provocative Inhalation challenge has been used in an attempt to identify byssinogenic agents (52-54, 83-86). Results of these studies have been Inconclusive, but most positive reactions appear to be due to endotoxin contamination of the dust, or to a toxic or irritant factor (52,53). 

Small airway constriction and recruitment of leukocytes on pulmonary surfaces are prominent, documented responses to the inhalation of cotton dust. Currently, one or both of these effects are generally ascribed to endotoxin (8-10), to antigen-antibody reactions (11), to lacinilene C-7 methyl ether (1, 13), to a low molecular weight ( 1000 daltons), neutral, highly water soluble substance that is stable in boiling water and found in cotton bracts (14), to chemotaxins present in cotton mill dust extracts (15, 16) or to histamine releasing substances (17). 

Cavagna et al. (35) in 1969 described the level of airborne endotoxins in cotton cardrooms (7.2 yg/m ) and in hemp cardrooms (8.7 yg/m ). Four out of fifteen volunteers showed a drop in FEV with inhalation of 40-80 yg E. coll endotoxin. Rabbits exposed to 20 yg E. coli endotoxin/day or 2 mgm cotton extract/day responded with increased pulmonary resistance to a dose five times stronger after 20 weeks. They estimated that a textile worker breathes 40-50 yg endotoxin/8 hour shift, and pointed out the constant presence of endotoxin in cotton dusts. 

This leads to the hypothesis that byssinosis is the longterm (chronic) result of repeated acute episodes of lung injury. One factor in this injury may be inhalation of endotoxin. Endotoxins may act by triggering histamine release and subsequent bronchoconstrictlon. 

Injectables, Inhalation solutions a. Sterility test, b. CCI, AET. c. Bacterial endotoxin test Test all batches on stability with the exception of the first three batches for AE a. b. c. 0 only 0, 12, 24, 36 months 0 and expiry only... 

Lung Injury. - A POBN adduct, believed to be that of a lipid-derived radical, has been detected the lungs of rats following the instillation of endotoxin. No radicals were detected in NADPH oxidase knockout mice.339 The effects inhaled N02 have been investigated by Elsayed and colleagues. The direct, low-temperature examination of lung tissue from rats showed that N02 expo-... 

Rylander R, Holt PG (1—>3) Beta-D-glucan and endotoxin modulate immune response to inhaled allergen. Mediators Inflamm 1998 7 105-110. 

BAKE, B., RYLANDER, R. FISCHER, J. (1987) Airway hyperreactivity and bronchoconstriction after inhalation of cell-bound endotoxin, in JACOBS, R.R. WAKELYN, PJ. (Eds) Proceedings of the Eleventh Cotton Dust Research Conference, pp. 12-14. Memphis, TN National Cotton Council. 

Chronic-Duration Exposure and Cancer. Several studies have examined the relationship between chronic exposure to ammonia and respiratory effects. Studies of farmers working in enclosed livestock facilities provide evidence that ammonia may contribute to transient respiratory distress (Choudat et al. 1994 Cormier et al. 2000 Donham et al. 1995, 2000 Heederik et al. 1990, 1991 Melbostad and Eduard 2001 Reynolds et al. 1996 Vogelzang et al. 1997, 2000) however, co-exposure to total dust, respirable dust, carbon dioxide, total endotoxins, respirable endotoxins, fungi, bacteria, and/or molds complicates the interpretation of these studies. A study of workers at a fertilizer production facility found an association between respiratory effects and ammonia exposure (Ballal et al. 1998). Another study did not find respiratory effects (Holness et al. 1989). Animal studies examining the chronic toxicity of inhaled ammonia were not identified. The human data were considered adequate for derivation of an inhalation MRL (Holness et al. 1989). No chronic-duration oral or dermal data were located. Studies by these routes of exposure would provide useful information on the identification of target organs especially after low-dose exposure. 

Weitzberg, E., Rudehill, A., Alving, K., and Lundberg, J. M. (1991). Nitric oxide inhalation selectively attenuates pulmonary hypertension and arterial hypoxia in procine endotoxin shock. Acta Physiol. Scand. 143, 451-452. 

Gordon T. (1994) Role of the complement system in the acute respiratory effects of inhaled endotoxin and cotton dust. Inhal. Tox., 6, 253-66. 

Michel O., Nagy A.M., Schroeven M., Duchateau J., Neve J., Fondu P. and Sergysels R. (1997) Dose-response relationship to inhaled endotoxin in normal subjects. Am. J. Respir. Crit. Care Med., 156, 1157-64. 

Inhaled endotoxins are an important component of bioaerosols in both occupational and non-occupational settings. They may produce fever, malaise, airway obstraction and acute pulmonary inflammation. Endotoxins are integral components of the outer membrane of Gm - bacteria and are composed of lipopolysaccharides associated with proteins... 

Environmental airborne endotoxins are usually associated with dust particles or aqueous aerosol with a broad size distribution. Endotoxin exposure has been associated with a variety of pulmonary and systemic diseases in homes, office buildings and occupational environments. These diseases or conditions include chronic nose and throat irritation, humidifier fever, organic dust toxic syndrome, grain fever, byssinosis, asthma-like syndrome, exacerbation of asthma, and progressive irreversible airflow obstruction (Heederik et al., 1991 Michel et al., 1996 Muittari et al., 1980 Olenchock, 1990 Rylan-der, 1996 Rylander et al., 1978 Schenker et al., 1998 Schwartz et al., 1994 Schwartz et al., 1995). Recognition of the link between endotoxin exposures and these conditions has led to proposals to establish occupational health exposure limits. The Netherlands Health Council has recently published a criteria document for endotoxin that recommends a health-based occupational exposure limit of 50 EU/m for full shift, personal, inhalable dust sampling (Douwes and Heederik, 1998). 

Peptidoglycans have been postulated as a possible causative agent for pulmonary inflammation associated with inhalation of Gm+ bacteria. Peptidoglycans are components of the cell wall envelope of bacteria and are especially prevalent in the backbone of Gm+ bacteria. They may act as endotoxin-like molecules when inhaled. Muramic acid is an amino sugar component of peptidoglycans that does not appear elsewhere in nature and is a suitable marker for analytical assays (Black et al., 1994 Fox et al., 1993 Fox et al., 1995 Sonesson et al., 1988). Although peptidoglycans have been found in hospital and home air conditioner filters (Fox and Rosario, 1994), to date there have been no systematic dose-response studies to identify their potency. 

Rylander R. (1996) Airway responsiveness and chest symptoms after inhalation of endotoxin or (13)-P-D-glucan. Indoor Built Environ., 5, 106-111. 

Rhesus macaques (Macaca mulatta) have been used extensively as a model for lethal inhaled intoxication of SEB. Efforts to develop lethal aerosolized SEB animal models in rabbits and endotoxin-primed mice are ongoing. The following pre-... 

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