Document O1QydrRKLmBRa669VdvbBk5q1

Unlocking the mysteries of respiratory diseases In a research project on brown hmg disease, or byssinoais--an ailment that afflicts many cotton mill employ bob a University of Chicago team has found toxins that may prove to be a clue to the general msdunim of numerous respiratory diseasea that affect employ ees in chemical plants and in other in dustrial settings. Among such occupa tional maladies: aabeatoaia, silicosis, black lung disease in coal miners and chronic asthma, which afflicts some workers in the chemical industry (CW, Sept 22, 1982, fk Sf). Furthermore, the study team devel oped procedures that may be used in pinpointing the agents that cause such diseases. And, of course, if those agents can be found, it may be possible to de vise measures to keep them handcuffed. In the brown lung project, the Chica go study team--headed by Associate Professor David Lynn--has not yet been able to identify a causative agent, but it has found four toxins that were formed, Lynn thinks, by the action of some such agent He says the hamii were found in the lungs of deceased cotton mill workers, and that he sad his co-workers have shown that those com pounds were absent, or present only at considerably lower levels, in the tangs from a control group that did not work with cottou. This is the first study so far to find specific toxins associated with cotton workers, but Lynn cautions that the study was "Our research was aimed at developing techniques to deter mine the cause of brown lung disease, not proving its ssinristinn with cotton work," Lynn says. "Nevertheless, our results are dramatic sad imply there is aa association." FMetigi Washington offi cials who are concerned with occupa tional health are aware of the Chicago team's work but regard Lynn's recent report to the Amercan Chemical Soci ety as a first-stage finding. Lynn has yet to show a cause and effect relation ship between brown lung disease and the four lung toxins he has iaolatod, says Robert M. OasteDan, chief of the c.hiucal section diviahiu of respiratory disease studies at the National Institute for Occupational Safety and Health (Morgantown, W. Va.). "It's early in the game," says CasteDao, who has heard Lynn present hie work. "Hie work is still preliminary." And while Lynn's work does suggest a possible mecha nism by which a variety of environmen tally induced lung diseases might devel op, in that area, Castellan says, "the csuse-and-effect relationship becomes even more tenuous." Lynn, in a cautionary note, states that his study does not provide conclu sive answers to these questions but does provide an important lead in the search for the cause and perhaps even tual prevention of byasmoeia. the Chi cago researchers say the source of the toxins in the lungs isn't certain, though they have isolated one from cotton and also have found related compounds that could serve as precursors for the other three. In addition, two of the toxins were found m tobacco leaves. As to the validity of the studies, observers say Toxfcrw found In cotton mS employees may be the toy to OVnOT avGUSTOI fTMMMS the main limitations were that the sam ple was too small and the subjects' case histories were too incomplete to make general assumptions tying the toxins to cotton mills. Only seven cotton workers and eight other persons were tested. A He? Nevertheless, Lynn, who is an associate professor of chemistry, says these results at least point to cotton dust as the cause of byasinoeiB. "All seven cotton workers had the toxins in their lungs and none of the others had any," he says. "This isn't proof, but it does strongly indicate a tink between cotton dust and byssinoais." The four toxins the Chicago group holated are all members of a family of compounds called oxidised Cu fatly ac ids. Many compounds of this family are fntiiwi in nature; in mammals, for exam ple, they serve as precursors for proste- Lynn theorises that ensymes, either m cotton or m the hugs, oxidise the Ci, fatty adds Lc., adds having 18 carbon atoms in each molecule--to the toxins. "We aren't sure if this occurs in cotton particles, or if there is something in cotton that induces tang ensymes to do the toxin-fonmng reaction," he says, adding that both may be taking {dace. If tiie latter is true, other eniyme teduc- ing agents might be involved in causing other occupational hug diseases. Besides trying to answer that ques tion, Lynn's research group is now try ing to determine why these compounds accumulate in the hugs of cotton work ers; they are found there even yean after exposure to cotton dust has ceased. If it tuns out that cotton dust contains an enzyme inducer, the com pound might permanently turn on these fatty-add oxidizing enzymes in hug cells. The enzyme might then convert naturally occurring C1S fatty adds into toxin molecules. Since the precursor compounds are found in tobacco leaves, they might be widespread throughout nature and be readOy available as sub strates for the enzyme. Another theory is that the compounds are formed only while exposure is tak ing place but that they are incorporated into the cell membranes of lung cells. The cell membranes would then be a toxin reservoir, slowly releasing the compounds over time. Outoomt. Further research will be greatly aided by techniques developed in this study, according to Lynn. `This is the most important outcome of our work," he says. "We now know how to spot the presence of toxins quickly and which four compounds to look for in dust samples and samples from affect ed subjects. We have all the tools we need to see if a dear link exists be tween damaging compounds and a his tory of work in a cotton mill. If a com plete study with more subjects reproduces our results, we'll have an answer to this question." Lynn has synthesized all four tnyina m the laboratory, and they will now be tested to see whether they induce a byssiziosie-like disease in test animals. `This," he says, "would be compelling evidence that the toxins we found in the cotton workers cause byssinoais." nrSYnr 31. ISM/Oumicil Week S6 C 2D co ccon