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Volume 4 | Issue 1

Hello hello,

I hope 2006 is off to a good start for you. I hope you'll find the attached articles relating to hypersensitivity pneumonitis by Dr. Harriet Burge and Histoplasma capsulatum by Agner Martinez interesting and helpful.

 

With best wishes,

Dave Gallup

 



HYPERSENSITIVITY PNEUMONITIS

By: Dr. Harriet Burge

Hypersensitivity pneumonitis (HP), also called allergic alveolitis, is a lung disease that results from intense exposure to small particles of biological materials or a few highly reactive chemicals.  It is an allergic disease in the same general class as hay fever and asthma.  Unlike these very common diseases, HP is uncommon, and the pathogenesis of the disease is different.  Like the more familiar allergies, a series of steps are required before the disease actually begins.  Figure 1 outlines these steps.

Figure 1

What kinds of environmental exposures lead to the disease?

Antigens

HP is caused by inhalation of small particles that contain antigens (reactive proteins) that are able to stimulate an allergic response.  Some of the types of biological particles that carry these types of proteins are listed in Table 1, along with the name of the disease, and the source for exposure.

Biological source of allergen

Common name of disease

Source of organism

Thermophilic actinomycetes  (filamentous bacteria)

  • Farmer’s lung
  • Bagassosis (sugar cane worker’s disease)
  • Humidifier lung
  • Mushroom workers lung
  • Moldy hay
  • Processed sugar cane
  • Cool mist humidifier water
  • Mushroom compost

Bacillus species

  • Humidifier lung
  • Cool mist humidifier water

Mycobacterium species

  • Metalworking fluids HP (machinist’s lung)
  • Hot tub lung
  • Metalworking fluids
  • Hot tub water

Alternaria

  • Wood pulp worker’s lung
  • Moldy wood pulp

Aspergillus species

  • Malt worker’s lung
  • Farmer’s lung
  • Composter’s lung
  • Moldy barley
  • Moldy hay
  • Moldy compost (yard waste, sewage)

Aureobasidium

  • Humidifier lung
  • Sequoiosis
  • Mist from cool mist humidifiers
  • Moldy redwood bark

Cryptostroma

  • Maple bark stripper’s lung
  • Moldy wood bark

Graphium

  • Sequoiosis
  • Moldy redwood dust

Monocillium

  • Peat moss worker’s lung
  • Moldy peat moss

Penicillium

  • Peat moss worker’s lung
  • Suberosis (cork worker’s lung)
  • Cheese worker’s lung
  • Moldy peat moss
  • Moldy cork
  • Moldy cheese casings

Rhizopus

  • Wood trimmer’s disease
  • Moldy wood trimmings

Trichosporon

  • Japanese summer HP
  • Moldy wood and mats

Bird droppings

  • Bird breeders lung
  • Droppings, feathers

Table 1

In fact, it appears that almost any biological particle that is presented in an appropriate particle size and concentration may cause HP in susceptible people.

Sensitization exposure conditions

It appears that exposure to concentrated small-particle aerosols over some period of time is necessary for sensitization.  Concentration and length of exposure probably depends on the specific antigen, and co-exposures with substances that stimulate the immune system (e.g., Endotoxin, reactive chemicals, glucans, etc.).  Measured exposure concentrations of thermophilic actinomycete spores in farmer’s lung disease have been in the millions of spores per cubic meters of air, and spore clouds are visible.  Similarly, Aspergillus concentrations in composting studies have been high enough so that clouds of spores were visible. 

Risk factors

Generally, only a few exposed people actually develop HP, although all may develop specific antibodies or cells specifically sensitized against the antigen.  The host factors that control risk for the development of HP remain unknown.  HP is more common in men than in women, which may reflect gender-specific job categories.  Genetic factors may also be involved.  It may be that risk factors vary depending on the actual composition of exposure aerosols.

The sensitization process

HP is caused by an immunological response of cells in the lower airway to antigen exposure.  Initially, lymphocytes (white blood cells) become sensitized.  Other white cells then are stimulated to produce specific antibodies that participate in tissue damage.  Another set of white blood cells participate in inflammation that results from exposures that follow sensitization.  If exposure continues, this inflammation becomes chronic so that exposure is no longer necessary to support the disease process.  During the chronic phase, irreversible fibrosis occurs in the lung.  Production of specific IgG antibodies occurs in all exposed people whether or not they subsequently develop disease.  This is a superficial summary of the complicated cascade of events, many details of which remain unknown.

Symptoms

During the acute phase, HP patients experience flu-like symptoms with one or more of the following:

  • CoughShortness of breath (difficulty taking deep breaths)FeverMalaise (aches as occur with the flu)
  • As the disease progresses, cough, fever,shortness of breath and malaise continue, with a gradual loss of appetite and weight loss (unintentional).

Symptoms may appear after only a few weeks of exposure, or years may be required.  Once sensitization has occurred, symptoms usually develop within 4 to 12 hours following exposure.  In the acute form, symptoms disappear within days following the end of exposure.  If exposure continues, the disease may progress to the chronic form with irreversible lung damage and, possibly, death.

Diagnosis

Diagnosis of HP involves chest x-rays, listening to chest sounds, measurement of specific antibodies, and pulmonary function tests.  Abnormal chest X-rays are present in most patients, while characteristic chest sounds and specific antibodies occur only in some cases. 

HP may be confused with other lung diseases such as viral pneumonia, asthma, dust toxic syndromes, and inhalation fevers such as are caused by endotoxin exposure. 

Prevalence

A few reports of prevalence for HP in the US are listed in Table 2.  Obviously, prevalence rates vary widely from case to case.  These rates are likely to be underestimates because of confusion in diagnosing the disease

Occupation

HP Prevalence

Farmers

0.008-0.540%; 0.4-7%

Pigeon breeders

6-21%; 0.02-20%

Office workers (contaminated humidifier)

52%

Polyurethane workers

27%

Table 2

How does one measure these exposure conditions?

Nature of the aerosols

The nature of the sensitization process for HP requires small particle aerosols that can penetrate into the fine chambers of the lungs.  Sensitization also requires exposure that lasts weeks or months, although the exposure need not be continuous.  Thus, the sporadic aerosols caused by periodic handling of moldy hay may lead to HP as does the more or less continuous concentrated aerosols present during compost handling.  In residences, ultrasonic humidifiers are the most frequent culprit because they use sound waves to produce a very fine aerosol from a water reservoir that is inevitably contaminated with microorganisms.

Sampler characteristics

Because aerosol particles are so small, it is essential that the sampler used be efficient to a particle size down to at least 2mm.  In addition, the sampling method must be able to capture the concentrated aerosols generally present.  For these reasons, filtration devices are often used.  These can be analyzed either by culture or by direct counting, and provide the best estimate of actual concentration.  Culture plate devices such as the BioCassetteTM and Andersen samplers may also be used if a qualitative estimate of concentration is sufficient.  Even at 1 minute, these devices will overload.  However, the aerosol is usually of only one particle type, and if every impaction point is filled, one can assume that concentrations are sufficiently high to be of concern.

Sampling strategies

It is important to remember that, although the aerosols may be concentrated, they may not always be continuous.  Another important factor is that there is always an aerosolization mechanism associated with reservoirs for HP agents.  It is essential that an effort be made to identify possible reservoirs, and to develop a sampling plan that includes samples both before and during the activation of the suspected aerosolization trigger.  For possible ventilation system contamination, one can sample at the end of a period when the system is off (for large buildings this is usually very early Monday morning), and then during the first few minutes of operation. 

What about remediation and re-occupancy?

Protecting the patient

Given the seriousness of HP, it is wise to remove all symptomatic people from the space as soon as possible (unless the reservoir can be immediately identified and removed.  Reoccupancy for patients with symptoms should be approached carefully, with the patient spending only short times in the space until it is clear that the problem has been solved.

Removal of reservoirs

In some cases the reservoir and agent are obvious, and simple removal without even sampling may be appropriate.  This is the case for humidifiers (for example).  On the other hand, the reservoir may never be found.  In this case, it may be possible to discover aerosol generators that are likely causes.  Good example here are outbreaks of HP related to enclosed swimming pools with spray water features.  For residential ventilation system contamination, very thorough cleaning is necessary.  This is one case where I would even recommend considering duct cleaning.  Remember, although sensitization requires concentrated aerosol exposures, continuing symptoms may be triggered by relatively low aerosol concentrations.

 


 

FUNGUS OF THE MONTH: Histoplasma capsulatum

By Agner Martinez

Histoplasma capsulatum is the etiologic agent of histplasmosis, a common granulomatous disease of worldwide distribution. Inhalation of a sufficient amount of conidia can potentially cause an infection in the lungs of a healthy person. In the vast majority of cases the infection is benign, leaving only residual calcifications in the lung and sometimes the spleen. However, it can occasionally progress to a life threatening, disseminated form particularly affecting the reticuloendothelial system. There are three varieties recognized, depending on the clinical disease: Histoplasma capsulatum var. capsulatum is the most common cause of histoplasmosis; var. duboisii causes histoplasmosis duboisii, common in Africa; and var. farciminosum causes lymphangitis of horses and mules, and is endemic in Asia, Europe, and Africa.

Despite its worldwide distribution, H. capsulatum is most commonly encountered in tropical or subtropical regions, as well as in several large river basins in temperate regions. The most highly endemic areas in the United States are the central and eastern states, especially along the valleys of the Ohio, Mississippi, and St. Lawrence rivers.

Histoplasma capsulatum is a dimorphic (having two forms) fungus that grows as a white to brownish mycelia on natural substrates and in culture at temperatures below 35º C. The organism produces characteristic tuberculate (warty), round, or pyriform (pear-shaped) macroconidia (larger spores; 8-16 µm in diameter) and small (2-5 µm in diameter) round, sparse, or abundant microconidia (smaller spores). When inhaled into the alveolar spaces, it is primarily the microconidia that sprout and then transform into small budding yeasts that are 2 to 5 µm in diameter. In culture at a temperature of 37º C the organism also grows in the yeast-like form. The variety duboisii differs by the production of larger yeast cells, which are 8 to 15 µm in length with thick walls.  Because of close similarity that exists between spores of Histoplasma and the spores produced by many other fungi, identification of this fungus on spore traps is not possible and could be easily placed under Penicillium or Aspergillus type spores.. Similarly, identification of this fungus by direct microscopic examination of tapes, bulks, and swabs is problematic.  The most effective method for recovering this fungus is the bulk collection and culturing of guanos.

The saprophytic fungus Sepedonium also produces tuberculate macroconidia, but is usually distinguishable from H. capsulatum by the absence of microconidia and does not convert to the yeast form at 37º C. There are other fungi with Chrysosporium type conidia that may also resemble H. capsulatum. The full identification of the organism requires demonstration of the appropriate exoantigen and/or conversion to the yeast form at 37º C.  Selective media such as Mycobiont agar have been used to grow species of Histoplasma.  Once the plates are inoculated they are incubated for 3 to 4 weeks.

It is firmly established that H. capsulatum grows in soil with high nitrogen content, generally associated with the guano of birds and bats. The first isolation of the organism from a natural environment was from soil near a chicken house, and since that time it has been recovered on numerous occasions from bat caves, bird roosts, chicken houses, silos inhabited by pigeons, and other such environments. In avian habitats, the organism seems to grow preferentially where the guano is rooting and mixed with soil rather than in nests or fresh deposits.

Anyone working at a job or present near activities where material contaminated with H.capsulatum becomes airborne can develop histoplasmosis if enough spores are inhaled. After an exposure, how ill a person becomes varies greatly and most likely depends on the number of spores inhaled and a person’s susceptibility to the disease. Infants, young children, and older persons, in particular those with chronic lung disease, are at increased risk for developing symptomatic histoplasmosis. The disease can also appear as an opportunistic infection in persons infected with Human Immunodeficiency Virus (HIV).

Some occupations and hobbies may be at increased risk for exposure to H. capsulatum such as construction, demolition, chimney cleaning, farming, gardening, restoring of historic or abandoned buildings, roofing, bridge inspection, and cave exploration, among others. Individuals likely to come into contact with contaminated soil, bat droppings, bird manures, or similar materials should take appropriate precautions. As far as we know there are no documented cases of histoplasmosis specifically associated with indoor air quality.

 

References:

  1. Center for Disease Control, www.cdc.gov.

 


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