More Letters to the AAAAI

[Guest guest]

KC requested that I post some more of the letters that the AAAAI received in

response to their new position statement in regard their " Art of the State "

understanding mold and mycotoxin induced illnesses. The follow was sent on

your behalf from Jeff May.

" Mr. Kruger "

Subject: Comments on AAAAI Position Paper

Date: Wed, 01 Mar 2006 07:34:22 -0500

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Mr. Kruger,

The AAAAI position paper “The Medical Effects of Mold Exposure†by Bush et

al. claims to “review the state of the science of mold-related diseases and

provide interpretation as to what is and what is not supported by scientific

evidence.†With respect to hypersensitivity pneumonitis (HP), the position

paper states that “exposure to domestic specific fungal spores is an

extremely unlikely cause of HP, except in highly unusual circumstances, such

as workplace exposure†and concludes that “HP is an uncommon but important

disease that can occur as a result of mold exposure, particularly in

occupational settings with high levels of exposure.†These statements are

incorrect.

I have investigated several cases in which physician-diagnosed HP was the

result of home exposure to mold:

#1: A 27 year-old female living in a 2 ½ year-old house with a recently

finished and carpeted basement (where the laundry was located), was

hospitalized twice with shortness of breath and was referred by her

pulmonologist who diagnosed HP. She had and weakly positive serum

reactivity to Aspergillus, Candida, Cladosporium, Mucor, Rhodotorula and

pigeon but not to her dog or cat. The concentration of spores (NV air

sample) in the basement, where she exercised, was about 50,000 /m3 (majority

Pen/Asp), but the result of culturable sampling was only about 154 total

CFU/ m3 (less than 100 Penicillium CFU/ m3, but still about twice the

culturable exterior concentration). Dust in basement tape samples from the

carpet, and mildew from the baseboard contained Penicillium, Cladosporium,

Aureobasidium pullulans and Aspergillus nidulans. Microscopy of dust and

non-viable (NV) air samples were indicative of active mold growth (hyphae

and Aspergillus conidiophores) in the basement carpet. During NV air

sampling in the living room, a child jumped on the couch and an airborne

dust mite was trapped in the sample. The woman avoided entering her basement

and her HP symptoms abated within months.

#2: A 60+ year-old partially disabled female, forced to spend a significant

portion of each day in bed (due to an unrelated illness), was referred by

her pulmonologist who had diagnosed HP. The home had forced hot air heat

(with a dirty blower and mold growing in the dust on the return grilles) and

a finished basement (no carpeting) that had flooded several times. A furnace

humidifier contained no mold growth, though bacteria and unidentified,

flagellate unicellular organisms were present. The concentration of Pen/Asp

spores was over 1000 / m3 at a heat register (over 100 times the exterior

concentration and almost 8 times greater than the indoor ambient level

before operation of the blower, all NV samples) but the culturable sample

from the vent (reported by J. Fink) grew only “a few Penicillium†colonies

(less than 50 CFU/ m3). Tape samples from the blower contained numerous

Penicillium and yeast, as determined by microscopy and culturing. The

woman’s blood serum did not react to a commercial Penicillium antigen and

reacted only “weakly positive†to Aspergillus in the HP panel of antigens,

but was, from a culture of the tape sample, “highly positive†(IgG) to the

Aspergillus and Penicillium from the blower (yet negative in IgE reactivity

to both). In addition to significant exposures from the heating system, the

woman also had bioaerosol exposures while in bed due to the mites and mold

colonizing the feather bedding, most probably due to the body moisture she

supplied while bedridden. The heating system was professionally cleaned and

a media filter installed and the woman’s symptoms diminished, but were

exacerbated about two years later. Despite previous recommendations, the

woman did not eliminate her feather pillow or encase the mattress in

allergen control covers. Upon subsequent testing, a dust sample from the

bedding contained entire Aspergillus and Penicillium conidiophores,

suggesting active growth, and her serum IgG reactivity to Penicillium was

“strongly positive.â€

#3: A 70+ year old female, referred by her pulmonologist and diagnosed with

HP, had suffered from chronic cough, and for three years had not slept

through the night without experiencing disruptive coughing fits (one of

which resulted in a hernia). She and her retired husband had lived in the

house, which had a dirt basement floor and a steam boiler, for over 50

years, but a few years previously had moved their bedroom into a converted

porch above a dirt crawl space. The couple had a dog and had used both an

evaporative and a cool mist humidifier, and burned soot-producing jar

candles. Dust from the living room furniture contained numerous dog dander

particulates as well as many dust mite fecal pellets. There was visible

mildew on the walls of the carpeted and cluttered bedroom. Air (NV) samples

in all the rooms contained dog dander particulates, elevated numbers of

Pen/Asp spores and skin scale fragments (possibly due to bacterial

degradation caused by annual carpet washing) in a range of 2-12 microns.

Snow covered the ground at the exterior, and the indoor air yielded

(culturable samples) 92, 58 and 23 CFU/ m3 (most of which consisted of

Aspergillus and Penicillium spp.) in the master bedroom, dining room and

basement, respectively. The woman stopped coughing as soon as she put on a

NIOSH N95 disposable mask, and did not cough for three hours, but resumed as

soon as she took the mask off. She spent the night in the guest room, where

there was hardwood flooring and slept soundly to morning.

The authors have ignored a number of papers:

1-Lee YM, Kim YK, Kim SO, Kim SJ, Park HS J Korean Med Sci. 2005

Dec;20(6):1073-5.

“A case of hypersensitivity pneumonitis caused by Penicillium species in a

home environmentâ€

We report a case of hypersensitivity pneumonitis in a 30-yr-old female

housewife caused by Penicillium species found in her home environment. The

patient was diagnosed according to history, chest radiograph, spirometry,

high-resolution chest CT, and transbronchial lung biopsy. To identify the

causative agent, cultured aeromolds were collected by the open-plate method.

From the main fungi cultured, fungal antigens were prepared, and immunoblot

analysis with the patient's serum and each fungal antigen was performed. A

fungal colonies were isolated from the patient's home. Immunoblotting

analysis with the patient's sera demonstrated a IgG-binding fractions to

Penicillium species extract, while binding was not noted with control

subject. This study indicates that the patient had hypersensitivity

pneumonitis on exposure to Penicillium species in her home environment.

2. Ikeda T, Kuroda M, Ueshima K., Nihon Kokyuki Gakkai Zasshi. 2002

May;40(5):387-91.

“A case of hypersensitivity pneumonitis caused by Gyrodontium versicolorâ€

A 36-year-old woman was admitted to our hospital because of fever, dry

cough, dyspnea on exertion and body weight loss in August 2000. Chest

radiography and CT scanning showed diffuse ground glass opacity and small

centrilobular nodules in the middle and lower lung fields of both lungs.

Serum antibody against Trichosporon cutaneum was positive; and summer-type

hypersensitivity pneumonitis was therefore initially diagnosed. Treatment

with methylprednisolone and prednisolone decreased the symptoms, but the

dyspnea reappeared when the patient was at home. Inspection of her house

revealed the presence of fungi under the floor. After these were removed,

her symptoms disappeared completely. The lymphocytic stimulation test of the

peripheral blood was positive for the fungi, and it was therefore suggested

that they were the cause of her hypersensitivity pneumonitis. The fungi were

identified as Gyrodontium versicolor. This is the first report of

hypersensitivity pneumonitis caused by Gyrodontium versicolor.

3. Lee SK, Kim SS, Nahm DH, Park HS, Oh YJ, Park KJ, Kim SO, Kim SJ.

Allergy. 2000 Dec;55(12):1190-3.

“Hypersensitivity pneumonitis caused by Fusarium napiforme in a home

environmentâ€

BACKGROUND: We report a case of hypersensitivity pneumonitis (HP) in a

17-year-old male student caused by Fusarium napiforme found in his home

environment. METHODS: The patient was diagnosed according to history, chest

radiograph, spirometry, high-resolution chest CT, and transbronchial lung

biopsy. To identify the causative agent, cultured aeromolds were collected

by the open-plate method. From the main fungi cultured, fungal antigens were

prepared, and immunoblot analysis with the patient's serum and each fungal

antigen was performed. RESULTS: Five fungal species were isolated from the

patient's home. Immunoblotting analysis with the patient's serum

demonstrated more than 10 IgG-binding fractions to F. napiforme extract

only, while little binding was noted with the other fungal antigens.

CONCLUSIONS: We should be aware that HP may be caused by F. napiforme in the

home environment.

4. RS, Dyer Z, Liebhaber MI, Kell DL, Harber P., Am J Respir Crit

Care Med. 1999 Nov;160(5 Pt 1):1758-61.

“Hypersensitivity pneumonitis from Pezizia domiciliana. A case of El Nino

lungâ€

A previously healthy woman developed severe dyspnea and was found to have

restrictive lung disease and evidence of alveolitis. Open lung biopsy

revealed extrinsic allergic alveolitis (hypersensitivity pneumonitis). The

etiology was not initially apparent, but a home inspection showed an unusual

mushroom growing in the patient's basement. Air sampling and serum

precipitins against the fungal antigens confirmed that Pezizia domiciliana

was the cause of the patient's hypersensitivity pneumonitis. This is the

first described case of hypersensitivity pneumonitis cause by P.

domiciliana. We speculate that unprecedented rainfall and flooding of the

patient's basement as a result of El Nino rains produced ideal factors for

the growth of this fungus.

5. s RL, s CP, Coalson JJ. Ann Allergy Asthma Immunol. 2005

Aug;95(2):115-28. Ann Allergy Asthma Immunol. 2005 Aug;95(2):99.

“Hypersensitivity pneumonitis: beyond classic occupational disease-changing

concepts of diagnosis and managementâ€

OBJECTIVE: To review inhaled antigens in home environments that cause

hypersensitivity pneumonitis (HP) of varied clinical expressions and

histopathologic patterns. DATA SOURCES: Computer-assisted MEDLINE and manual

searches for articles concerning HP, interstitial lung disease (ILD),

epidemiology of HP and ILD, challenge procedures of HP, and indoor fungi.

STUDY SELECTION: Published articles concerning inhaled antigens in home

environments and HP were selected. RESULTS: Current criteria for the

diagnosis of HP are too restrictive, because most apply only to the classic

acute presentation and are of limited value in the subacute and insidious

forms. Clinical expressions vary across the gamut of respiratory tract signs

and symptoms. Patterns on lung biopsy may include all histopathologic

descriptions of idiopathic ILD. The home is the likely causative environment

rather than the workplace. Exposures may be occult and require in-depth

environmental histories and on-site investigations to detect antigens and

sources. CONCLUSIONS: Natural or environmental challenges have become an

important tool for diagnosing HP and determining effectiveness of

remediation. Early diagnosis and effective remediation of the cause lead to

a high survival rate, whereas diagnosis in advanced stages leads to

disability and/or premature death.

6. Venkatesh P, Wild L.,Paediatr Drugs. 2005;7(4):235-44.

Hypersensitivity pneumonitis in children: clinical features, diagnosis, and

treatment.

Hypersensitivity pneumonitis (HP), or extrinsic allergic alveolitis, is a

form of immune-mediated inflammatory lung disease involving the distal

portions of the lungs associated with intense or repeated exposure to a

variety of finely dispersed environmental antigens. Although once believed

to be a disease of adults because of its frequent association with the

occupational setting, HP exists in the pediatric population and often goes

unrecognized. Childhood HP is often associated with exposure to antigens in

the home environment as well as with certain hobbies. Patients present in

any one of the three disease stages: acute, subacute, and chronic, all with

unique clinical presentations. Histopathologic findings depend on the

disease stage at the time of evaluation. The immuno-pathogenesis is complex,

but immune-complex (type III hypersensitivity) and cell-mediated (type IV

hypersensitivity) immune responses appear to be the primary immune

mechanisms involved in the pathogenesis of HP. Diagnosis can be very

challenging. Although no single diagnostic or clinical laboratory test is

available to diagnose HP, the most significant diagnostic tool is a detailed

environmental exposure history. Avoidance of the inciting antigen is the

most important form of treatment. Acute HP is responsive to antigen removal

alone. However, a short course of prednisone for 2-3 weeks can be useful in

patients with severe attacks. Subacute and chronic HP may require higher

doses of corticosteroids for a longer duration (i.e. months); however, the

long-term efficacy of using corticosteroids is still not well defined. As

with most hypersensitivity diseases, early diagnosis provides the best

prognosis.

7. Moran JV, Greenberger PA, R., Allergy Asthma Proc. 2002

Jul-Aug;23(4):265-70.

“Long-term evaluation of hypersensitivity pneumonitis: a case study

follow-up and literature reviewâ€

This study reports a 3-year follow-up of a classic presentation of

hypersensitivity pneumonitis (HP), originally reported elsewhere, after

removal of the causative antigens. The literature is reviewed and this case

is compared with outcomes of series previously reported. The patient was

reevaluated by clinical, serologic, radiographic, and pulmonary function

testing 3 years after removal of her home's contaminated humidifier,

cleaning of the home, and administration of a course of prednisone. Repeat

serologic measurements revealed positive serum precipitins only for

Aspergillus flavus and Phoma herbarum, significantly fewer than her original

panel, which revealed precipitating antibodies to her humidifier water and

10 other specific antigens. Pulmonary function tests remained stable.

Physical exam revealed bibasilar rales. Computed tomography scan revealed

pulmonary fibrosis, bronchiectasis, and honeycombing that was compared with

3 years earlier. Although most of the data obtained on reevaluation suggest

remission, radiographic findings have not remitted. Long-term follow-up of

parameters of HP disease activity do not always reveal consistent findings.

This patient appears to be in a category of HP between the classic subacute

and chronic stages.

8. Yoshizawa Y, Ohtani Y, Hayakawa H, Sato A, Suga M, Ando M.,J Allergy Clin

Immunol. 1999 Feb;103(2 Pt 1):315-20.

“Chronic hypersensitivity pneumonitis in Japan: a nationwide epidemiologic

Surveyâ€

BACKGROUND: Pulmonary fibrosis inevitably develops in patients with chronic

hypersensitivity pneumonitis (HP). OBJECTIVE: We conducted a nationwide

epidemiologic study in Japan to evaluate the frequency and clinical

characteristics of chronic HP. METHODS: This report is on 36 cases of

chronic HP, including 10 patients with summer-type HP, 5 patients with

home-related HP, 7 patients with bird fancier's lung, 5 patients with

isocyanate-induced HP, 4 patients with farmer's lung, and 5 patients with

other types of chronic HP. Chronic HP was further subgrouped into 2 types:

one type of patients were first seen with chronic disease (9 patients), and

the other type became chronic with fibrosis after repeated acute episodes

(27 patients). RESULTS: The upper lung field was frequently involved in

chronic HP (17%). Ground-glass opacities were observed in 57% and air space

consolidation in 30% of the patients. Honeycombing was apparent in 37%.

Twenty-six of 28 patients had antibodies to the presumptive antigens. Five

of 8 patients with chronic HP were positive for antigen-induced lymphocyte

proliferation. In 2 cases patients did not have detectable antibodies to

causative antigens, although antigen-induced lymphocyte proliferation was

detectable. The ratio of CD4 to CD8 in BAL lymphocytes was lowest in

isocyanate-induced HP (mean 0.22) and tended to be high in farmer's lung and

bird fancier's lung. Granulomas were observed in 39% and Masson bodies in

42% of specimens on histologic examination. Administration of prednisolone

was effective in 58% of patients. CONCLUSIONS: The insidious form of chronic

HP has probably been misdiagnosed as idiopathic pulmonary fibrosis when a

good history was not taken and immunologic (especially antigen-induced

lymphocyte proliferation) and BAL testing were not counted.

Also:

Apostolakos, M.J., Rossmoore, H., Beckett, W.S. 2001, “Hypersensitivity

pneumonitis from ordinary residential exposures,†Environ. Health Perspect.,

vol. 109, no.9, pp. 979-81.

Hirakata, Y., Katoh, T., Ishii, Y., Kitamura, S., Sugiyama, Y.,2002,

“Trichosporon asahii-induced asthma in a family with Japanese summer-type

hypersensitivity pneumonitis,†Ann. Allergy Asthma Immunol., vol.88, no.3,

pp. 335-8.

Park, H.S., Jung, K.S., Kim, S.O., Kim, S.J, 1994, “Hypersensitivity

pneumonitis induced by Penicillium expansum in a home environment,†Clin.

Exp. Allerg., vol. 24, no.4, pp. 383-5.

Patel, A.M., Ryu, J.H., , C.E., 2001, “Hypersensitivity pneumonitis:

current concepts and future questions,†J. Allergy Clin. Immunol., vol.108,

no.5, pp. 661-70.

Suda, T., Sato, A., Ida, M., et. al., 1995, “Hypersensitivity pneumonitis

associated with home ultrasonic humidifiers,†Chest, vol.107, no.3, pp.

711-7.

Yoshida, K., Ando, M., Sakata, T., Araki, S., 1989, “Prevention of

summer-type hypersensitivity pneumonitis: effect of elimination of

Trichosporon cutaneum from the patients' homes,†Arch. Environ. Health,

vol.44, no.5, pp. 317-22.

HP as a result of home exposure and home exposure to mold is probably

under-diagnosed in the U.S. The illness is a serious public health concern

(no doubt with more cases than illness due to exposure to radon, for

example, for which there has been great expenditures).

The AAAAI position paper should modified to reflect importance of home

exposures to antigens.

C. May, M.A., Author

May Indoor Air Investigations LLC

Cambridge, MA

www.mayindoorair.com

www.myhouseiskillingme.com