October 4, 2001

Artificial Butter Suspected in Lung Disease

By PHILIP J. HILTS[Image]

Workers in two states have come down with a severe lung disease that is apparently linked to their work with vats of artificial butter flavoring, doctors have reported.

The National Institute for Occupational Safety and Health issued a report in August that described the cases of nine workers in a small Missouri factory who developed a rare and disabling lung disorder, bronchiolitis obliterans, and an additional seven workers who had other lung problems after being exposed to artificial flavoring while mixing and packaging microwave popcorn.

The lung damage from bronchiolitis obliterans appears to be permanent, and four of the workers are so ill that they are on the waiting list for lung transplants.

Today, in a telephone interview, a doctor in Nebraska described a similar case of the lung disorder in another patient, who is also a worker handling artificial butter flavoring for popcorn. Doctors who investigated for the federal agency said that the problem appeared to be limited to workers who inhaled large amounts of the liquid flavoring and that there was no danger to anyone eating the flavoring on popcorn or in other foods.

Dr. Talmadge E. King, chief of medicine at the San Francisco General Hospital and an expert on bronchiolitis obliterans, said these cases were the first time he had heard of an outbreak of the disease, which usually occurs in individual patients. He said it sometime occurred in transplant patients whose immune systems are compromised and historically has been seen in people who had heavy exposure to chemicals in accidents like the explosion of chlorine tanks, or when farmers have opened corn silos and inhaled large amounts of nitrogen oxides at once.

Dr. Kathleen Kreiss, who led the investigation, said that the finding was a surprise and that two important questions are now being pursued by government scientists: are there cases that have not been reported, and what ingredient in the flavoring may have triggered the disease?

The cases were first reported in The Wall Street Journal on Wednesday.

The illnesses occurred in workers at a Gilster-Mary Lee Corporation plant in Jasper, Mo., where microwave popcorn was mixed with salt, oil and flavoring, then packaged.

Government investigators and the doctor in Nebraska, Dr. Susanna Von Essen at the University of Nebraska Medical Center, who treated a worker at a Nebraska company, declined to identify that company. But the government has begun to work with the Nebraska company to investigate the case, and investigators said the worker contracted the disease after working with vats of a different brand of butter flavoring from the one used in Missouri.

In Missouri, 16 current and former employees have filed a workers' compensation claim against the Gilster-Mary Lee Corporation, and a class-action lawsuit against International Flavors and Fragrances, based in New York and New Jersey, which makes the flavoring. Seven plaintiffs are still employed at the Gilster-Mary Lee factory, though some are on disability leave.

The plaintiffs are seeking an undefined amount in damages to cover medical costs.

"Some of these people can't even help out with household chores like mowing the lawn because they're so out of breath, and things like playing with their kids are hard for them," said Amy Powell, a lawyer with Humphrey,

Farrington, McClain & Edgar, a firm in Independence, Mo., that is representing the plaintiffs.

Gilster-Mary Lee has denied liability and until recently also denied benefits, Ms. Powell said. She said International Flavors and Fragrances had not yet responded to the class-action lawsuit filing

Calls to Gilster-Mary Lee and to International Flavors and Fragrances were not returned.

The workers in Missouri were young, averaging 36 years old, and that "is part of the reason this is so alarming," Ms. Powell said.

One of the Gilster workers was Angela Nally, 48, who began working on the production line in October 1993. Until then, she had been a homemaker, and

she decided to take her first job outside the home only because her husband had lost his.

Mrs. Nally drove 11 miles from her home in Carthage to the factory on the outskirts of Jasper. She worked the late shift, from midafternoon until midnight, making $5.50 an hour.

About four months after Mrs. Nally started working at the factory, she developed a persistent cough. She did not think anything of it at first. "It was kind of like a cold or a flu-type thing," she said in an interview. "I'd get to feeling better after the doctors gave me something for the cough, but it gradually kept getting worse and worse. I thought I was going to get over it, but I didn't."

Breathing became more difficult and she started coughing so hard that she broke a rib. She consulted doctors in Carthage, Joplin, Springfield and St. Louis, and soon was so weak and short of breath that her doctors advised her to quit working. So in June 1994, she did.

In October 1994, Mrs. Nally went to a hospital in Denver for a lung biopsy.

Her lungs were so inflamed and damaged that doctors warned she might have only a year to live, and she was put on a waiting list for a double-lung transplant.

Her condition has now stabilized, and she said she has been moved to the "inactive" waiting list. Mrs. Nally said she suspected her illness was linked to her job because she had been active and healthy before starting at the plant, and she soon noticed that other workers shared her symptoms. But no one in the company or on the production line ever talked about it, she said.

The investigation of the outbreak began more than a year ago when a doctor in Kansas City, Mo., Allen Parmet, who handles occupational health problems, noticed that several patients had the rare, disabling lung problem. Late last year, he saw six patients at the same time with the disorder, all from one small area of Missouri. That was four more than he had seen in his entire career.

He reported the cases to the Missouri Department of Health, where an investigation was begun.

Dr. Eduardo Simoes, the state epidemiologist for Missouri, said his group calculated that the odds of having that number of cases in a town as small as Jasper were less than one in 10,000. Federal investigators were asked to aid the investigation in August 2000.

The investigators have done a test on rats, and have found that when they inhale substantial amounts of butter flavoring like that used in the Missouri plant, many develop similar lung disease.

The chief ingredient in the flavoring is a chemical called diacetyl, said Dr. Greg Kullman of the federal agency, and it may be the agent that triggers the problem. Tests of the effects of diacetyl on rodents have

begun, Dr. Kullman said.

FDA Approves New Drug for Crohn's

.c The Associated Press 

WASHINGTON (AP) - Sufferers of Crohn's disease won a new treatment Wednesday that promises to decrease the intestinal inflammation that causes much of the disorder's misery.

The Food and Drug Administration approved Entocort EC, saying the capsule promises fewer side effects than other steroids, such as prednisone, that are used to treat Crohn's.

Entocort EC capsules are formulated to release the medication, known chemically as budesonide, once they reach the intestine. That means less of the steroidal drug is absorbed into the body than other Crohn's treatments allow, the FDA said.

Crohn's disease is a chronic bowel inflammation that eventually breaks down the intestinal wall. It afflicts more than 500,000 Americans, most of them under age 30. Symptoms include severe and persistent diarrhea, abdominal pain, fever, fatigue and weight loss. About half of all Crohn's patients at some point require surgery to remove intestinal obstructions or repair holes in the bowel.

The cause isn't known, although a recently discovered genetic abnormality renders some families particularly vulnerable. There is no known cure, although certain drugs can ease symptoms in some patients. The most common inflammation-reducing drugs are steroids, but long-term steroid use can cause some serious side effects.

In clinical trials of almost 1,000 patients with mild to moderate Crohn's, about half of patients taking Entocort EC experienced improvement in their symptoms after two months of therapy, said manufacturer AstraZeneca.

Entocort users experienced fewer of the typical side effects of Crohn's treatment, including facial swelling and acne, the FDA said. Typical Entocort side effects included headache, respiratory infection and nausea, the agency said.

AstraZeneca said the prescription medication would be in pharmacies later this year, and cost about $5.40 a day.

AP-NY-10-03-01 1850EDT

Pharmacies remiss in dispensing drug combinations 

CHICAGO (Reuters) - Pharmacies could be more vigilant about preventing combinations of drugs that should not be taken together from being dispensed, researchers said Tuesday.

Computerized warning systems now in use should enable pharmacists to identify prescriptions containing contraindicated drugs, or medications that regulators have warned should not be taken together, researchers for a drug safety group said.

A study of a heartburn medication that was later withdrawn from the market found that patients who received prescriptions for it and a contraindicated drug most often got both medications from the same pharmacy.

The drug, cisapride, was voluntarily withdrawn from the market last year after it was blamed for causing an irregular heartbeat in 270 patients, 70 of whom died. Most of the cases involved use of cisapride with contraindicated drugs.

Of more than 131,000 cisapride prescriptions examined between 1995 and 1999, more than 3 percent, or 4,414, were dispensed with at least one contraindicated drug. Of those, 50 percent were prescribed for patients by the same physicians and 89 percent were dispensed by the same pharmacies -- 17 percent of them on the same day.

Study authors Judith Jones and Suellen Curkendall of The Degge Group Ltd., in Arlington, Virginia, writing in the Journal of the American Medical Association, said they did not determine how often pharmacies caught the mistake in prescribing bad drug combinations, but they suggested that warning systems could be improved without resorting to complicated communications among different pharmacies.

"This suggests that the pharmacist, who is focused solely on the therapy, more often has the opportunity to apply critical information necessary to prevent contraindicated co-dispensings," the report said.