Byssinosis

To the Editor:

Tanaka and colleagues (September 2002) (1) reported that most of the mushroom workers in their study group had experienced chronic cough, which they further characterized as organic dust toxic syndrome, hypersensitivity pneumonitis, runny nose (ie, postnasal drip syndrome), cough-variant asthma, and eosinophilic bronchitis.

These diseases (except for two cases of hypersensitivity pneumonitis) were not defined on an etiologic basis. Some cases of asthma or rhinitis could be due to an immunologic mechanism, but the authors did not measure IgE against Hypsizigus marmoreus (commonly called, Jade Gill mushrooms) spores. The remaining cases could be an irritant effect from airborne fungal spores, mycotoxin, organic dust, or endotoxin.

We suggest that the mushroom workers' chronic cough is the same (or a variant) disease as that reported in cotton textile workers, byssinosis. (2) The following points form the basis for thinking that endotoxin is the agent of chronic cough in mushroom workers.

First, symptoms reported by those with chronic cough were observed "to improve or disappear after weekend holidays." This is similar to the reported Monday-morning effect experienced by those in the cotton textile industry, which has identified endotoxin as the causative agent. (2)

Second, the rapid occurrence of chronic cough in this population of workers is similar to that in cotton textile workers, among whom Wang et al (3) reported a rapid decline in FE[V.sub.1] for newly hired, nonsmoking, female cotton dust workers after 3 months of exposure.

Third, since 71.4% of workers reporting chronic cough developed symptoms within 3 months after starting employment, sensitization to fungal spores is an unlikely responsible factor.

Endotoxin (lipopolysaccharide [LPS]) air concentrations in the harvesting room (three samples) and packing room (three samples) were reported (Table 1) to be well above the suggested no-observed-effect level for airway inflammation (ie, 10 ng/[m.sup.3]),4 although a range from 9 to 170 ng/[m.sup.3] has been reported. (5) In the cultivating room, the LPS concentration was below the no-observed-effect level but was above the level observed to cause an acute decrease in airway function (ie, 53 endotoxin units [EU]/[m.sup.3], or approximately 5 ng/[m.sup.3]), (6) to reduce lung function (ie, 4 ng/[m.sup.3]), (7) and to elicit a physiologic response (ie, 2 ng/[m.sub.3]). (8,9)

Since airborne endotoxins are highly variable, the relatively low levels of LPS reported by Tanaka et al require confirmation before these findings can be fully accepted. LPS concentrations should be expressed as EU per cubic meter and not as nanograms per cubic meter. (5,10) Reporting endotoxin values as nanograms per cubic meter does not allow an accurate comparison with other measurements. (10)

Additional data might be useful in the establishment of an occupational exposure limit (OEL) for endotoxin that minimizes the incidence of occupational disease. (5) It is proposed here that the OEL (time weighted average, 8 h) be established between the concentration reported for reducing lung function and the physiologic response (ie, 20 to 50 EU/[m.sup.3]). This will provide some margin of safety in protecting the majority of people. This proposed value is similar to the suggested OEL (50 EU/[m.sup.3]/8 h, or about 4.5 ng/[m.sup.3]) initially proposed by the National Health Council in the Netherlands, (5,10) which was a health-based standard, (11) although a higher value was finally adopted (200 EU/[m.sup.3]). (11)

The study by Tanaka et al illustrates the diversity of industries (5,6,10-14) in which workers are exposed to levels of endotoxin that are sufficient to cause respiratory diseases. Endotoxin may even be one of the major causes of health effects from outdoor pollutant particulates (15) It should be mentioned that beneficial effects of LPS resulting from occupational exposure have been suggested (notably, reduced lung cancer rates). (16,17) Thus, occupational exposure may be a two-edged sword. It has been suggested (18) that the beneficial effects of occupational exposure also be reported in studies rather than dismissing these results as bias or as some form of the healthy-worker effect.

John H. Lange

Envirosafe Training and Consultants, Inc

Pittsburgh, PA

Ugo Fedeli, MD

Giuseppe Mastrangelo, MD

Department of Environmental Medicine and Public Health, University of Padova

Padova, Italy

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: permissions@chestnet.org).

Correspondence to: John H. Lange, Envirosafe Training and Consultants, Inc, PO Box 114022, Pittsburgh, PA 15239; e-mail: john.pam.lange@worldnet.att.net

REFERENCES

(1) Tanaka H, Saikai T, Sugawara H, et al. Workplace-related chronic cough on a mushroom farm. Chest 2002; 122:1080-1085

(2) Musgrave KJ, McCawley MA. Respiratory health risks in agriculture. In: Cordasco EM, Demeter SL, Zenz C, eds. Environmental respiratory diseases. New York, NY: Van Nostrand Reinhold, 1995; 263-294

(3) Wang X-R, Pan LD, Zhang H-X, et al. Follow-up study of respiratory health of newly-hired female cotton textile workers. Am J Ind Med 2002; 41:111-118

(4) Rylander R, ed. Endotoxins in the environment: a criteria document. Int J Occup Environ Med 1997; 3:S1-S48

(5) Heederik D, Douwes J. Towards an occupational exposure limit for endotoxins? Ann Agric Environ Med 1997; 4:17-19

(6) Zock JP, Hollander A, Heederik D, et al. Acute lung function changes and low endotoxin exposures in the potato processing industry. Am J Ind Med 1998; 33:384-391

(7) Milton DK, Wypij DW, Kriebel D, et al. Endotoxin exposure-response in a fiberglass manufacturing facility. Am J Ind Med 1996; 29:3-13

(8) Wolff SM. Biological effects of bacterial endotoxins in man. In: Kass EH, Wolff SM, eds. Bacterial lipopolysaccharides. Chicago, IL: University of Chicago Press, 1973; 251-256

(9) Post W, Heederik D, Houba R. Decline in lung function related to exposure and selection processes among workers in the grain processing and animal feed industry. Occup Environ Med 1998; 55:349-355

(10) American Thoracic Society. Respiratory health hazards in agriculture. Am J Respir Crit Care Med 1998; 158:S1-S76

(11) Thorn J, Beijer L, Honsson T, et al. Measurements strategies for the determination of airborne bacterial endotoxin in sewage treatment plants. Ann Occup Hyg 2002; 46:549-554

(12) Vogel PF, van der Gulden JW, Folgering H, et al. Endotoxin exposure as a major determinant of lung function decline in pig farmers. Am J Respir Crit Care Med 1998; 157:15-18

(13) Eduard W, Douwes J, Mehl R, et al. Short term exposure to airborne microbial agents during farm work: exposure-response relations with eye and respiratory symptoms. Occup Environ Med 2001; 58:113-118

(14) Rylander R. Endotoxin in the environment: exposure and effects. J Endotoxin Res 2002; 8:241-252

(15) Becker S, Fenton MJ, Soukup JM. Involvement of microbial components and toll-like receptors 2 and 4 in cytokine responses to air pollution particles. Am J Respir Cell Mol Biol 2002; 27:611-618

(16) Mastrangelo G, Marzia V, Marcer G. Reduced lung cancer mortality in diary farmers: is endotoxin exposure the key factor? Am J Ind Med 1996; 30:601-609

(17) Enterline PE, Sykora JL, Keleti G, et al. Endotoxin, cotton dust and cancer. Lancet 1985; 2:934-935

(18) Lange JH. Reduced cancer rates in agricultural workers: a benefit of environmental and occupational endotoxin exposure. Med Hypotheses 2000; 55:383-385

To the Editor:

We thank Lange et al for their comments. They have raised an important issue about airborne endotoxin exposure in occupational chronic cough. We reported that airborne endotoxin, as well as antigens from mushroom spores, was one of the important causes of cough in mushroom workers. As Lange et al have suggested, the phenomenon occurring in the mushroom farm workers is similar to that in cotton textile workers (byssinosis). Actually, some mushroom workers noticed cough in the first 2 weeks. This seems too short a time in which to be sensitized by mushroom spore antigens, therefore, we think that the cough resulted from exposure to chemicals, for example, endotoxin. As stated in our report, the latent time period from the start of working to the onset of symptoms of organic dust toxic syndrome (average, 1.8 months) was the shortest, the second was eosinophilic bronchitis (average, 3.5 months) and the third was cough-variant asthma (average, 4.1 months). However, we recently have seen two cases of hypersensitivity pneumonitis due to another kind of mushroom spore in which the latent period was only 2 months in one patient (1) and 3 months in the other (unpublished data). Based on these cases, 3 months might be enough time to be sensitized by mushroom antigens, in which case all 71.4% of workers reporting chronic cough that developed within 3 months after the start of employment might not be the result of endotoxin inhalation alone. We speculate that a high concentration of airborne mushroom spores may shorten the sensitization period in the contemporary mushroom farm worker. Thirty percent of workers were sensitized to the spore in the first year and 93% in the second year. (2) We are now developing a system for measuring serum IgG and IgE levels in response to the spore antigens in our laboratory.

Our results on the effects of mushroom antigens on peripheral blood mononuclear cells in mushroom workers have now been published. (3) Levels of CD[14.sup.+]-positive monocytes, acting with innate immunity and contributing to a primary defense mechanism in mucosal tissue, increased in mushroom workers. CD14 is a ligand of lipopolysaceharide, and its signal acts through the toll-like receptor 4. Therefore, sensitivity to lipopolysaccharide is speculated to be enhanced in mushroom workers. We agree that airborne endotoxin plays an important role in the mechanism of chronic cough in mushroom workers, but the contribution seems to be only a part of the cause.

Hiroshi Tanaka, MD

Toyohiro Saikai, MD

Shosaku Abe, MD

Sapporo Medical University

Sapporo, Japan

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: permissions@chestnet.org).

Correspondence to: Hiroshi Tanaka, MD, Sapporo Medical University, South-1, West-16, Chuo-Ku, Sapporo, Japan 060-8543; e-malt: tanakah@sapmed.ac.jp

REFERENCES

(1) Saikai T, Tanaka H, Fuji M, et al. Hypersensitivity pneumonitis induced by the spore of Pleurotus eryngii (Eringi). Intern Med 2002; 41:571-573

(2) Tanaka H, Saikai T, Sugawara H, et al. Three-year follow-up study of allergy in workers in a mushroom factory. Respir Med 200i; 95:943-948

(3) Saikai T, Tanaka H, Matsuura A, et al. Cellular compartment of peripheral mononuclear cells and in. vivo response to spore extract in mushroom plant workers [abstract]. Am J Respir Crit Care Med 2001; 163:A153

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