Just as with the more conventional pathogenic bacteria, this containment process causes inflammation. To the lung, inflammation is inflammation, regardless of the primary inciting event. Patients with hypersensitivity pneumonia develop nonspecific symptoms often within hours of being exposed to these dusts. And these symptoms, such as fever, chills, headache, cough, and shortness of breath, can be easily misdiagnosed as flu, bronchitis, or another kind of pneumonia, or in rare circumstances, a lung cancer.
That is, unless the doctor first thinks of the diagnosis and then asks some very specific questions. Generally, a patient with hypersensitivity pneumonia has been exposed to organic dust as a result of his or her job or hobby. The prototypical form is farmer’s lung, a condition that develops when farmers working with hay inhale large amounts of spores from a group of bacteria called thermophilic actinomycetes.
The term itself is a mouthful, but anyone who has done any composting in the garden knows that these actinomycetes are really a noseful. They are an important element in composted soil, producing its characteristic earthy smell. The name actinomycete suggests a branching fungus, and in fact that’s what scientists thought they were for many years. But in reality, they belong to the realm of bacteria that branch into long filaments and that resemble fungi in appearance. “Thermophilic” means heat loving. These organisms are most active at 120 –150 degrees Fahrenheit.
Although physicians had recognized for centuries an association between exposure to dusts from farms and respiratory problems, the first and certainly one of the most colorful accounts of farmer’s lung was published in the British Medical Journal by Dr. J. Munro Campbell, a tuberculosis officer in Grange-over-Sands, England, located in Westmorland County. He wrote:
The summer of 1931 proved a very bad season for hay-making in Westmorland, owing to rain, and much of the hay was eventually taken in in an unsatisfactorily damp condition. The inevitable result was the development of a great deal of mould, especially in the lower strata, so that working with it later produced dense clouds of “white” or “hay” dust, stated by those afflicted to be the worst they had ever experienced. In the ordinary course of farm-work, transient cough and wheeziness are recognized effects of contact with “white” dust, but in five of the cases which I had the opportunity of examining, the symptoms were so severe that they seem worth recording. These cases were seen during the period April to June, 1932, which in itself is significant as being the period when the supply of last year’s hay was nearing the end.
All the patients were farmers or farm labourers, whose ages ranged from 21 to 46 years, and whose previous health records were good. . . . The onset of [symptoms] was very similar in each case: a noticeable shortness of breath for some weeks previously whilst carrying out the normal routine, including work with hay, until a climax was reached by some specific act ( for example, clearing out the remainder of the hay from a barn) and within 36 hours, the man was extremely [short of breath], a step or two being impossible, distressed, and cyanotic, and appeared almost in extremis.
It was about three weeks later that most of these cases were seen by me, when doubts arose as to the possible existence of tuberculosis infection. . . . Later, when the patients were able to attend for x-ray examination, films showed a generalized, very fine granular stippling (reminiscent of, though much finer than, silicosis). . . . Several of these patients have been examined three to four months afterwards, and except [ for one of them], have very gradually lost their shortness of breath. No other symptoms remained troublesome, and the chest signs later were practically negative. X-ray films now showed very little stippling.
This “hay” dust, when allowed to settle on a clean plate, was found to be a soft, slaty-grey powder. Samples of the sputa were examined when obtainable, and showed no tubercle bacilli; though in one case a definite fungus was found, this finding was not repeated, either in this patient’s or in any other patient’s sputum and no other clues to a possible cause were found in the sputa. Though samples of the hay dust were examined and several fungi recognized, no evidence of any correlating factor could be found.
The “fungi” that Dr. Campbell saw were very likely thermophilic actinomycetes, which have been only recently reclassified as bacteria. Why would these bacteria be in a stack of hay in the first place? Nature always has a purpose, and aside from causing disease in these farmers, what possible grander purpose could these odiferous organisms serve? The answer to this question can be summarized in two words—decay and putrefaction.
Decay and putrefaction are as much a part of the natural cycle of life on this planet as birth and growth. In fact, the study of these natural destructive processes occupied much of the early work of no less than Louis Pasteur. Economic needs often propel scientific work, and Pasteur had been enlisted to help the French beer industry, which was being decimated by decay and putrefaction. In a presentation that he delivered in 1863, titled “Investigation into the Role Attributed to Atmospheric Oxygen Gas in the Destruction of Animal and Vegetable Substances After Death,” he said:
Fermentation, putrefaction, and slow combustion are the three phenomena which concur in the accomplishment of this great fact of the destruction of organic substances—a condition necessary for the maintenance of life on the earth. . . .
. . . In every case, life, manifesting itself in the lowest forms of organization, appears to me to be one of the essential conditions of these phenomena, but life of a nature unknown hitherto; that is to say, without consumption of air or of free oxygen.
. . . This leads to the general conclusion that life controls the work of death in all its phases, and that the three terms of that perpetual return to the atmosphere, and to the mineral kingdom, of the elements which vegetables and animals have abstracted from them, are correlative acts of development and of the multiplication of organized beings. . . . [emphasis added]
But [it] is worthy of remark and this is precisely the principal fact to which I today wish to draw the attention of the Academy: the slow combustion of organic substances after death, however real, is barely perceptible when the air is deprived of the germs of lower organisms. It becomes rapid, considerable, not to be compared with the former situation, should the organic substances be covered by moulds . . .
Translation: living organisms are necessary for the process of decay. This was a radical departure from the status quo, and the significance of Pasteur’s discovery cannot be overstated. His experiments showed for the first time that the decay of organisms was in fact a biological and not a purely chemical process. The findings from this same series of experiments partly led to his attack on contemporary scientists who believed in the spontaneous generation of life.
Since Pasteur’s time, scientists have learned that one of the most important agents of biological decay is the group of bacteria called the thermophilic actinomycetes, which are the primary decomposers of tough plant materials like bark, leaves, and stems. In the warm environment of a compost heap, they are especially effective at attacking the components of raw plant tissues, such as cellulose, chitin, and lignin. Other types of microorganisms and insects complete the decay cycle, converting organic matter back into inorganic substances. These inorganic substances become the building blocks for the next generation of living organisms. This process is important not just for creating fertilizer. Imagine the result if the fallen leaves from tens of thousands of years of trees never decomposed. The entire earth would be buried beneath them. As Pasteur recognized, the job thermophilic actinomycetes do is essential to life itself.
Unfortunately, however, the spores from these necessary actinomycetes happen to be a perfect size for being inhaled into the lungs of humans. It has been estimated that farmers working in an area where moldy hay is disturbed could inhale approximately 750,000 actinomycete spores per minute.
Farmers are not the only ones at risk, either. The same syndrome occurs in pigeon breeders and parakeet fanciers. People who harvest sugarcane and coffee beans, or those
who cure tobacco, or anyone who works with wood dust, cheese, maple bark, mushrooms, soybean feed, and barley can get hypersensitivity pneumonia. Cases have been ascribed to exposure to moldy shower curtains and moist saxophone mouthpieces. The list continues to grow. In the absence of an obvious source of exposure, in which case the patient will often have already made the connection, a doctor needs to take a meticulously detailed occupational and environmental history to make an accurate diagnosis.
Philip Bradford, however, was not a farmer, or a pigeon breeder or a harvester of sugarcane, or anything else on that expansive list of potential causes. He was a banker.
If Rubin’s suspicion was true, then there was a missing piece of information, and he was determined to find it. “When I was a senior resident at the Peter Bent Brigham Hospital, Professor J. Pepys from the Brompton Hospital in London was a visiting professor,” says Rubin, “and I was ‘in charge’ of him for the week. He did some of the pioneering work in hypersensitivity pneumonia, and he had written a book on allergic diseases of the lung.” Rubin had read that book, and he knew that the devil (or in this case, the diagnosis) was in the details.
As described in the written report of the case in the New England Journal of Medicine, Rubin uncovered the following potential exposures that Bradford had encountered. “Thirteen years earlier he had joined the Air Force, and during the next four years, he was stationed in Vietnam, Texas, central United States and Europe. Subsequently, he resided in New England and traveled only to Detroit and Chicago. For approximately a year and a half before admission [to the hospital], he worked in a new high-rise building in Boston. A pet dog had been recently examined by a veterinarian and reported to be normal. There was no history of allergy except for mild seasonal hay fever that began at the age of 20 years.”
Although Bradford’s job did not put him at risk for a textbook case of hypersensitivity pneumonia, Rubin knew that modern times bring modern risks. Investigators have reported people who have developed hypersensitivity pneumonia because of organisms circulated by air conditioners and humidifiers. “I questioned Bradford at length about humidifiers, his home heating system, hobbies, but I couldn’t come up with any exposures that would account for his symptoms,” Rubin explained.
Bradford recalls that Rubin took “an exhaustive personal history. I had spent a year in Vietnam in the air force, and there was some speculation that I had some exotic something-or-other that I had brought back from Southeast Asia.”
Finally, from the extensive lists of questions and the meticulous lines of inquiry, one clue emerged. The symptoms had begun shortly after Bradford’s firm moved into a new office space. The new building was similar in design to so many modern structures that punctuated the Boston skyline in the 1970s—essentially a concrete box studded with smoked-glass windows. Like most workers in modern high-rises, Bradford was entirely at the mercy of a heating, ventilation, and air-conditioning (HVAC) system for his air supply. Such buildings are effectively sealed off from the fresh air outside, and Rubin thought his patient could be reacting to something that the HVAC system had exposed him to.
But that theory had at least two glaring problems. “He went into the office every day. Why would the symptoms be intermittent? And if it was the office, why weren’t other co-workers getting sick?” Rubin wondered. Then he thought of a possible solution to the first of these difficulties with the theory.
“It became apparent that the new building was fraught with problems involving the ductwork. I asked Mr. Bradford to get copies of the maintenance records of the HVAC duct from the building managers to find out exactly when the air had been blown back and forth and when repair work had been done on the ductwork going into his office,” explained Rubin. “When he brought them back to me, sure enough, they revealed a possible explanation. The system was cleaned by forcing air through the ducts under pressure. The duct system had been blown clean twice. And it jived perfectly with the timing of the patient’s symptoms. Within the first day after major ductwork had been done during working hours, he experienced an episode of pulmonary infiltrates [nodules on the chest x-ray].”
Rubin’s next step was to send a sample of Bradford’s blood to the Harvard School of Public Health for analysis. He ordered a precipitin test, which Dr. Pepys had helped to develop. In this test, the patient’s blood is mixed with a preparation of thermophilic actinomycetes to see if antibodies in the blood will clump—or precipitate—with an antigen from the bacteria.
Although the owners of the building thought Rubin’s hypothesis was somewhat farfetched, there were precedents. Four years earlier, Dr. Edward Banaszak and his colleagues reported a cluster of hypersensitivity pneumonia cases in the New England Journal of Medicine. Their report described the travails of four office workers who had developed fever, chills, cough, and shortness of breath. They demonstrated that the airconditioning system in the office where the victims worked harbored thermophilic actinomycetes. The patients all had a positive precipitin test. After a thorough cleaning and modification of the system, all four patients were cured.
Then the results of Bradford’s blood test returned—negative. Disappointed but not discouraged, Rubin persisted. “I didn’t have much faith in the test,” he says. “I checked with an expert in the field who was of the same opinion. If it’s positive, great, but if it’s negative, that doesn’t necessarily mean anything.” Undaunted, Rubin decided to check the ducts himself. Armed with special equipment for culturing actinomycetes, he proceeded to Bradford’s building.
That was not the first time Rubin had stepped outside of the ivory tower. As an epidemiology intelligence officer with the CDC, he had chased down hepatitis epidemics, and during the Biafran war in the mid1960s in Nigeria, he had treated war victims. Once, while investigating a case of rabies in Kansas for the CDC, he helped trap wild animals to track the source of the deadly virus.
So to him, there wasn’t anything unusual about shedding his shirt and tie and poking his head into the mouths of the HVAC ducts. He recalls, “We had lunch in the executive dining room first, which was much nicer than the facilities at the hospital. Then I put on work clothes and climbed up a ladder. I took samples and swabs from many areas, especially wet ones.”
Next, Rubin planted the material onto culture plates, to see if any thermophilic actinomycetes or other organisms were present. This procedure is similar to a doctor taking a culture from a patient with a possible strep throat. The swab, after being dabbed on a wet surface of a duct in the first case, or on a patient’s throat in the second, is then touched to a petri dish that contains nutrients that will support the growth of the microorganism being sought. And sure enough, several days after Rubin obtained the material, an abundant growth of thermophilic actinomycetes was thriving on the plates. Every sample, from every site tested, produced them.
Next, Rubin prepared a new antigen from the bacteria he had obtained in the ducts. He again performed the precipitin test on Bradford’s serum, but this time with the new preparation from the ducts at Bradford’s office building. Now the precipitin test was strongly positive. There was another unintentional consequence of this phase of the investigation: Bradford inadvertently inhaled another dose of the air from the ducts, and promptly developed mild symptoms again. Another set of x-rays showed a reappearance of the same ominous nodules.
“This clinched the diagnosis,” recalls Rubin.
As we continually alter our environment, we create increasing numbers of unnatural hazards. People have developed hypersensitivity pneumonia from central and room humidifiers, heating and cooling systems, moisture-damaged building materials, cool-mist vaporizers, and even automobile air conditioners. One man developed hypersensitivity pneumonia from contaminated water in his home sauna.
Other infectious agents have been transmitted via air-conditioning and ventilation sources, including the bacteria that caused the famous outbreak of Legionnaire’s disease at the American Legion convention at the Bellevue-Stratford Hotel in Philadelphia
in 1976. In fact, indoor air pollution has become an enormous problem.
The Massachusetts Environmental Protection Agency estimates that 50 percent of all illnesses are attributed to some form of pollution. It further estimates that the annual cost to society is $100 billion, if both medical expenses and worker absenteeism are included.
Some modern office buildings are so contaminated that their occupants suffer from an array of problems—collectively known as the “tight building syndrome” or the “sick building syndrome”—including nasal irritation and nosebleeds, dry throat, scratchy eyes, shortness of breath, lethargy, headache, and more.
The range of contaminants is vast and includes construction dusts, tobacco smoke, and a class of chemicals called volatile organic compounds, which are emitted by copying machines, paints and varnishes, furniture and rugs, and all the other synthetic materials in modern offices. Then there are the organic dusts, like those that caused Bradford’s symptoms.
Several studies have shown that workers in buildings with mechanical ventilation—like Bradford’s—exhibit many more symptoms than workers in buildings with natural ventilation. In one study, researchers increased the amount of fresh air pumped through a building without telling the workers. Sure enough, the researchers recorded far fewer symptoms of “tight building syndrome” after the increase in ventilation.
Proper ventilation is crucial. In the typical system, fresh outside air is drawn through an intake port. This air is then blown into the building, sometimes after being humidified. The important factor is how often the air is exchanged in these buildings. Fewer air exchanges per day uses less energy and is therefore cheaper, at least in the short run. In industrialized societies, especially in colder climates, people spend a majority of their time indoors, so there is a large potential for this indoor pollution. Proper design of these HVAC systems is important; for example, if the location of the intake port it is too close to traffic, carbon monoxide can be blown into the building.
The Deadly Dinner Party: and Other Medical Detective Stories Page 12
