(Chest. 2001;120:1085-1093.)
© 2001
American College of Chest Physicians
Hypersensitivity Pneumonitis Induced by Spores of Lyophyllum aggregatum*
Kenji Tsushima, MD;
Keisaku Fujimoto, MD;
Yoshitaka Yamazaki, MD;
Akemi Takamizawa, MD;
Toshiya Amari, MD;
Tomonobu Koizumi, MD and
Keishi Kubo, MD
*
From the First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Correspondence to: Keishi Kubo, MD, First Department of Internal Medicine, Shinshu University School of Medicine, 3–1-1 Asahi, Matsumoto, 390-8621, Japan; e-mail: Keishik{at}hsp.md.shinshu-u.ac.jp
 |
Abstract
|
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Objectives: Lyophyllum aggregatum (LA)
is called Shimeji in Japanese and is eaten commonly as a
mushroom. Shimeji mushrooms are cultivated in an indoor
environment all year round. This study aimed to clarify the clinical
features of hypersensitivity pneumonitis (HP) induced by LA.
Patients and setting: Ten patients showed mild respiratory
symptoms including dry cough, sputum, and low-grade fever. We tried to
characterize the clinical features and the findings using chest
high-resolution CT (HRCT), pulmonary function tests (PFTs), and BAL
fluid (BALF) tests in patients with HP induced by LA. HP was diagnosed
from clinical features, HRCT findings, BALF findings, lung histology,
and lymphocyte stimulation tests (LSTs) for LA.
Results: Laboratory findings showed mean (± SD) elevated
levels of C-reactive protein (0.78 ± 1.3 mg/dL), erythrocyte
sedimentation rate (48 ± 23 mm/h), and 
-globulin
(26.9 ± 7.6%). PFTs revealed a slight decrease in the percentage
diffusing capacity of the lung for carbon monoxide, possibly due to the
presence of epithelial granulomas in the alveoli. Although 4 of 10
patients showed normal findings on the chest radiograph (CXR), chest
HRCT findings of all patients showed centrilobular small nodules and
diffuse ground-glass opacities. The BALF testing revealed an increase
in total cell counts, showing predominantly activated T lymphocytes.
The CD4/CD8 cell ratio was significantly decreased (0.5 ± 0.3). The
results of the LSTs were positive in seven of seven cases.
Conclusions: Since patients with HP induced by LA typically
have mild respiratory symptoms and sometimes normal CXR findings, their
conditions might remain undiagnosed. However, the chest HRCT images
showed the typical subacute phase of
HP.
Key Words: BAL fluid • chest high-resolution CT findings • hypersensitivity pneumonitis • Lyophyllum aggregatum
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Introduction
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Hypersensitivity
pneumonitis (HP) is an immunologically mediated inflammation of the
pulmonary parenchyma and is related to the repeated inhalation of
sensitizing agents such as organic dusts and simple
chemicals.1
The etiologic mechanism of HP is related to
the precipitating antibody of a type III allergic reaction or the
cell-mediated immunity of a type IV allergic reaction.1
Although mushroom workers’ lungs generally show the onset of HP during
the first few months of employment, it sometimes takes many
years until onset of the disease.2
Lyophyllum aggregatum (LA) is called Shimeji in
Japanese and is a common and popular mushroom throughout Asia, including Japan. In Japan, Shimeji
have recently been cultivated in an indoor environment in order to
produce a large quantity all year round. Therefore, the spores of LA
are scattered continuously in the working environment. The workers in
the indoor environment are mainly middle-aged women.
The presenting symptoms of HP commonly include a nonproductive cough,
shortness of breath (SOB), fever, chills, myalgia, and malaise. The
initial symptoms begin 4 to 8 h after exposure in the occupational
environment and persist for several hours. However, recovery is usually
spontaneous with abstinence from further exposure.
To our knowledge, there have been no studies reporting on HP induced by
LA. Recently, we treated patients with HP caused by long-term
inhalation of the spores of LA. To clarify the clinical features of
this type of HP, we examined the patients using chest CT, pulmonary
function tests (PFTs), and BAL testing.
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Materials and Methods
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Patients
We studied 10 patients with HP caused by LA. The 10 patients who
were admitted to our hospital with complaints of dyspnea on effort, dry
cough, and low-grade fever were Japanese LA workers in the indoor
environment. We diagnosed HP caused by LA from clinical symptoms,
laboratory findings, pathologic findings, lymphocyte-stimulating tests
by spores of LA, the positive occupational provocation test, the
characteristic manifestation in high-resolution CT (HRCT) findings, and
the typical BAL fluid (BALF) findings. The HP group consisted of nine
nonsmoking women and one man who had smoked 10 cigarettes a day for 10
years. Their ages ranged from 30 to 69 years (mean, 50.9 years). We
could not examine the precipitation test against spores of LA because
we could not refine antigens that caused precipitins.
The six healthy subjects were nonsmokers, were all women, and ranged in
age from 48 to 56 years (mean, 52 years). They had never suffered from
allergic diseases.
Clinical Features
Data were collected on each patient, including symptoms,
physical examination results, routine laboratory test results, and
tuberculin skin test results. The screenings for allergic disease were
measured by IgE using peripheral blood samples from the patients. We
performed a home and an occupational provocation test. The patients
left their jobs for about 2 weeks and then returned to their
occupational environment for occupational provocation test.
Chest Radiograph and CT/HRCT Scans
Chest radiographs (CXRs) and chest CT scans were obtained from
all patients. We used a helical CT scanner (HiSpeed Advantages; GE
Medical Systems; Milwaukee, WI) for the analysis of 10 patients. After
standard 10-mm-thick contiguous scanning for the screening of chest
abnormalities, scanning with 1-mm or 2-mm collimation was performed for
the affected lesions. CXRs, CT scans, and HRCT scans were reviewed by
two chest radiologists who had no knowledge of the patients’ clinical
findings. Several features, described below, were noted. The presence
of small nodules (< 5 mm) and macronodules (> 5 mm), ground-glass
opacity (GGO), and other findings were evaluated in each lobe.
PFTs
PFTs were performed by our routine method.3
Briefly, spirometry was performed using a water spirometer
(Chestac-65V; Chest Co Ltd; Tokyo, Japan). The vital capacity (VC) and
the FEV1 were measured. The percent predicted of
VC and the FEV1%
([FEV1/VC] x 100) were calculated. The
diffusing capacity of the lung for carbon monoxide (DLCO)
was measured by the single-breath method (Pulmocorder, model R1551S;
Anima; Tokyo, Japan). The predicted values for VC, residual volume, and
DLCO were determined by the formulas of
Baldwin,4
Bergland,5
and
Nishida,6
respectively. The peak expiratory flow
and the flow at 50% of FVC (V50) and at 25% of
FVC (V25) were calculated from the maximum
expiratory flow-volume curve. An arterial blood sample was drawn from
the brachial artery while the subject breathed room air to measure
PaO2,
PaCO2, and pH using a blood gas
analyzer (ABL-3; Radiometer; Copenhagen, Denmark). All measurements
were performed with subjects in the seated position.
BALF
The BAL was performed in all patients, following our laboratory
method.2
A bronchofiberscope was wedged into a subsegment
of the right middle lobe or left lingula, which was carefully lavaged
by instillation, and three 50-mL boluses of 0.9% saline solution were
withdrawn immediately using hand suction. The recovered BALF was
filtered through gauze, and the total cell numbers from the
unfractionated BALF were counted using a hemocytometer counting
chamber. Cell spreads prepared by cytocentrifugation were stained with
May-Giemsa stain. The BALF samples were divided into cell segments and
supernatant fluids, and were stored at -70°C until biochemical
analysis. The BALF pellet was analyzed for lymphocyte subsets by flow
cytometry using CD4 and CD8 monoclonal antibodies (Becton Dickinson Co;
Mountain View, CA).
We performed the BAL study with six healthy volunteers as control
subjects. They were all nonsmoking women with a mean (± SD) age of
53.2 ± 8.2 years. We then compared the cell counts and populations
between the two groups.
Transbronchial Lung Biopsy
A transbronchial lung biopsy (TBLB) also was performed in all
patients. Flexible biopsy forceps were passed distally to within 1 to 2
cm of the visceral pleura, and the biopsy specimens were obtained under
fluoroscopic guidance. Several specimens were obtained from lobes
within a single lung.
The patients and healthy subjects gave written informed consent to
undergo BAL and other studies. The BAL study for healthy subjects was
approved by the Research Committee of the Shinshu University School of
Medicine. No complications occurred during or after the BAL study.
Lymphocyte Stimulation Test
A lymphocyte stimulation test (LST)7
8
was
performed in seven cases. The LST was performed at a laboratory
(Special Reference Laboratory Inc; Tokyo, Japan) without information
about the clinical history. Peripheral blood lymphoid (PBL) cells were
isolated from venous blood samples by a Ficoll-Conray gradient and were
suspended at a concentration of 1 x 106 in 1
mL RPMI 1640 medium containing 20% autologous plasma. To obtain
lymphoid cells from BALF (LCBs), the cells were cultured in glass
dishes at 37°C in a humidified atmosphere of 5%
CO2 in RPMI 1640 medium supplemented with 10%
fetal calf serum for 1 h, and the nonadherent cells were gently
collected. Almost all of the nonadherent cells were
CD3+ as determined and were considered to be T
lymphocytes. The 200 µL of PBL and LCB suspensions were
distributed into the wells of microtiter plates, and 10 µL per well
of diluted LA solution was added. Diluted LA solution was prepared as
follows. One Shimeji mushroom was suspended in 5
mL RPMI 1640 medium containing 20% human blood group AB serum and then
was sonicated (20,000 cycles, 30 s). The supernatants were
centrifuged at 3,000 rotations per minute for 5 min and were diluted
100-fold or 100,000-fold with RPMI 1640 medium solution (ie,
the diluted LA solution). The PBL and LA solutions in each of
three wells were incubated for 72 h at 37°C in a humidified
atmosphere containing 5% CO2. The LCB and LA
solutions in each of three wells were incubated using the same methods.
Then the lymphocytes were pulsed with 0.25 µCi
3H-thymidine per well for 16 h, were
harvested using a multiple automated sample harvester, and were
counted. The stimulation index (SI) was calculated using the following
formula (an SI exceeding 180% was considered to be positive):
 |
 |
Control subjects underwent testing using only the PBL or LCB
solution, which were incubated following the same method used in
patients with HP, without adding the LA solution.
We used the water from an air conditioner that had been used in the
occupational environment as a control solution for the LST study. The
water of the air conditioner and the PBL solution were incubated for
the LST study.
We also performed LST in five healthy nonsmoking women (mean age, 50.3
years; range, 44 to 57 years) who had never experienced allergic
diseases.
Statistical Analysis
The values given in the text and tables are expressed as the
mean ± SD. One-way analysis of variance and Student’s unpaired
t tests were used for comparisons between the groups. A p
value of < 0.05 was considered to be significant.
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Results
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Nine of the 10 patients were middle-aged women. The only worker
who smoked was a man, and he had never had an allergic disease. The
workers producing LA had been engaged year-round in an indoor
environment that was equipped with air-conditioning and
moisture-conditioning systems. All patients were involved with the
growing, picking, and packing of the mushrooms in the indoor
environment. The 10 patients had been engaged in this work for 1 to 25
years (mean, 11.5 years).
Symptoms
The duration of symptoms was several years, except for the
male patient, and
ranged
from 7 months to 19 years (mean, 9.8 years) (Table 1)
. The onset
of symptoms was characterized typically by the episodic occurrence
of several mild symptoms in the late afternoon and evening after work.
With continued employment, episodes became progressively more frequent.
Symptoms were characterized by a cough, sputum, SOB, difficulty
breathing, and fever. The results of the physical examinations were as
follows: the heart sound was normal; and rhonchi or fine crackles were
heard in the lower lung fields in the patients who showed reticular
shadows on their CXR. Although the results of home provocation tests
were negative in all patients, an occupational provocation test was
positive in six of six patients who showed the low-grade fever, cough,
and dyspnea.
Laboratory Findings
WBC counts ranged from 5,300 to 9,580 cells/µL (mean,
7,000 ± 1,650 cells/µL), the C-reactive protein level ranged from
0.08 to 3.4 mg/dL (mean, 0.78 ± 1.3 mg/dL), and the erythrocyte
sedimentation rate ranged from 16 to 93 mm/h (mean, 48 ± 23 mm/h)
(Table 2
). However, the data showed a slight inflammation change without
leukocytosis. IgG (mean, 2,720 ± 900 mg/dL), IgA (mean, 377 ± 95
mg/dL), and gamma globulin (mean, 26.9 ± 7.6%) showed slightly
elevated levels.
PFTs
The predicted values for VCs and forced expiratory volumes were
within normal limits (Table 3
). The %DLCO showed a slight decrease (70.7 ± 11%), and
the V50/V25 ratio showed a
slightly higher level (3.10 ± 0.9). Arterial blood gas analysis
showed a decrease in PaO2 ranging
from 60.0 to 85.1 mm Hg (mean, 71.8 ± 7.3 mm Hg).
Analysis of BALF
The total cell counts of BALF ranged from
23 x 104 to
56.5 x 104 cells/mL (mean, 35.5 ± 12 x
104 cells/mL) and showed a slightly increased level. BALF
showed lymphocytosis and a decrease in the CD4/CD8 ratio (mean,
0.52 ± 0.3), except in patient 4 (Table 4
).
TBLB Findings
Five of 10 pathologic findings revealed the presence of
epithelioid noncaseating granuloma. Four of 10 pathologic findings
revealed Masson bodies. All patients showed histopathologic findings of
alveolitis that were characterized by diffuse infiltration of the
pulmonary interstitium by plasma cells
and
lymphocytes (Table 5)
. Figure 1
shows TBLB findings for cases 1, 2, 3,
and 6.
).
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Figure 1.. Specimens obtained by TBLB (hematoxylin-eosin in
all panels). Top left, A: case 1,
granulomatous alveolitis with an infiltrate of mononuclear cells and
giant cells (arrow). Bottom left, B: case
2, peribronchial alveolitis, alveolitis with an infiltrate of
mononuclear cells, and organized formation (Masson body; arrow)
[original x200]. Top right, C: case
6, bronchiolitis and alveolitis with an infiltrate of mononuclear
cells. Bottom right, D: case 3,
noncaseating granulomatous alveolitis with an infiltrate of mononuclear
cells and giant cells (arrow) [original x200].
|
|
CXR and HRCT
The CXR showed bilateral diffuse GGOs in six patients and normal
findings in four patients.
Figures
2 and
3
show a typical case, a normal CXR, and CXR revealing GGOs,
respectively. However, the chest HRCT scan revealed bilateral diffuse
GGOs and centrilobular fine small nodules in all patients. Patients 2,
3, and 10 showed fibrosis with interstitial septa thickening on the
chest HRCT scan (Table 5)
.
LSTs
The results of LSTs in peripheral blood and BALF samples performed
with LA solution were positive in seven of seven patients and in five
of five cases, respectively, although the results of the LSTs using the
water of the air conditioner as a control solution were negative in two
patients (Table 6
). The results of LSTs in peripheral blood with LA solution were
negative in all the healthy women, and the SI values ranged from 107 to
139%.
|
Discussion
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To our knowledge, this is the first study to report on HP induced
by LA. The disease has not been reported previously because the
patients typically have mild respiratory symptoms and doctors cannot
distinguish the abnormalities on the CXR. The characteristics of the
present patients were that they had mild respiratory symptoms that
mimicked the so-called common cold and, in some patients, normal CXR
findings. In Nagano, > 1,000 people are employed in the cultivation
of LA in an indoor environment. The workers who cultivate LA are
engaged in cultivation year round in an indoor environment that is
equipped with air-conditioning and moisture-conditioning systems. The
room temperature is maintained at approximately 15°C year round, and
the humidity is maintained at approximately 99% year round. LA is
produced in large quantities in the indoor environment, so workers are
continuously exposed to the spores of LA. The Agricultural Association
in Nagano reported that the spores of LA are dispersed in large
quantities immediately after harvesting and that the later the
harvesting period, the greater the quantities of spores. The
Agricultural Association in Nagano measured the number of spores
dropped on a glass slide after 30 min of collection and reported that
the spore size was approximately 4.0 µm. Approximately 1,480 spores
were collected during the 30-min period.
It was suggested that HP was caused by long-term inhalation of the
spores of LA, because patients had been employed for several years in
the cultivation of LA in an indoor environment and the spores were
distributed throughout the occupational environment. HP is a
granulomatous interstitial lung disease resulting from an immunologic
reaction to inhaled organic or inorganic antigens.9
10
The
immunopathologic mechanisms developing HP are believed to
involve both immune complex deposition and cell-mediated
immunity.1
Although it was suggested that the antigens of
LA are spores of LA, we attempted to develop a precipitating assay but
have so far been unsuccessful. The LST is primarily regarded as a test
of cell-mediated immunity (type IV) by
lymphocytes.7
11
Therefore, we diagnosed HP by the
LST for LA. To clarify whether HP induced by LA can be induced by other
antigens, we screened for spores of other mushrooms that are present in
a moist and damp environment that had been cultured from the
workplace. The screenings were negative in two patients.
In Japan, most HP is characterized as summer-type HP,12
but in some areas, including Nagano prefecture, different kinds of
mushrooms are cultured in an indoor environment. The patients inhale
the spores of LA long term. The HP induced by LA occurred in
workers who had worked in this indoor environment for several
years. The present study showed that there were differences between the
CD4/CD8 ratios of BALF lymphocytes and the total cell counts of BALF
among patients with HP induced by LA, patients with summer-type
HP,13
and healthy subjects (Table 7
). There are several studies14
15
16
17
on the surface
phenotypes of BALF lymphocytes in HP. In farmer’s lung, Semenzato et
al17
reported a 0.47 ratio for 16 subjects, whereas
Leatherman et al14
reported a 0.6 ratio for 6
subjects. However, Brummund et al15
reported no
decrease of the CD4/CD8 ratio in the four patients with farmer’s lung.
In addition, Ando et al13
reported a 0.6 ratio in patients
with summer-type HP. The total cell counts of BALF samples were
markedly increased in patients with summer-type HP and farmer’s lung.
In the present study, the CD4/CD8 ratio of BALF lymphocytes in patients
with HP induced by LA was 0.5, and the total cell count of BALF samples
from patients with HP induced by LA was
35.5 x 104 cells/mL. Some possible reasons for
this difference are that the phenotypes of BAL lymphocytes may be
dependent on the kind and/or dose of the inhaled causative antigens.
The causative antigens have been demonstrated to have direct complement
activation,17
mitogenic activity,18
and
adjuvant activity.19
Some studies on the phenotypes and
functions of BALF lymphocytes suggest the importance of cytotoxic T
lymphocytes in the pathogenesis of HP.20
The phenotypes of
BALF lymphocytes may be dependent on the difference in the size and
nature of the granuloma formation. The lymphocyte influx may be
polyclonal, and populations obtained by BALF therefore may be dependent
on variables other than immunologic responses with selective
chemotaxis. Patients with a low CD4/CD8 ratio in BALF samples may be
induced by the continuous exposure to low concentrations of antigens in
the indoor occupational environment.
The symptoms of most patients improved before receiving treatment.
However, GGOs and centrilobular small nodules (CLSNs) did not disappear
on the chest HRCT scans. The granuloma of HP that is induced by LA
appears small and immature in the alveoli similar to other types of
HP. The small diameter of the spores enables them to easily
reach the terminal airway and alveoli. Therefore, the correlation
between the decrease in %DLCO and the results of
pathohistology shows an abnormal lesion in the terminal airway and
alveoli. No patients with HP developed a severe condition due to
critical respiratory failure. However, corticosteroid treatment may be
necessary during the subacute phase of the disease, during which CLSNs
and GGOs are seen, because clinical features did not improve when
patients were only separated from the hostile environment. In addition,
the chest HRCT scans of some patients revealed interstitial thickening
and microhoneycombing changes. In four patients who underwent
corticosteroid treatment, the treatment improved blood gas analysis and
the %DLCO, and the CLSNs and GGOs disappeared. Patients
who used a facemask for the prevention of spore inhalation also showed
a loss of GGOs and CLSNs.
In Japan, there have been few studies of HP caused by the
inhalation of spores from Cortinus shiitake21
and Pholiota nameko.22
To clarify the
pathogenesis, further studies are required regarding the
occupational history of patients in whom HP induced by LA has been
diagnosed. Further studies should include research into precipitant
antigens to LA.
In summary, the present findings clarified the clinical features of HP
induced by LA. The patients had mild respiratory symptoms and sometimes
normal CXRs. However, chest HRCT scans showed images of the typical
subacute phase of HP.
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Figure 2.. The CXR made on hospital admission was normal
(left, A). The chest HRCT scan on hospital admission showed
diffuse GGOs (top right, B) and CLSNs
(bottom right, C) [case 1].
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Figure 3.. The CXR on hospital admission showed GGOs in
the bilateral lower lungs (left, A). The chest HRCT scan on
admission showed diffuse GGOs (top right,
B) and CLSNs (bottom right,
C) [case 4].
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Acknowledgements
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We thank Drs. Jiro Hirayama, Yoshiki Hirose,
Masashige Morita, and Hikaru Yagi for introducing the patients to our
hospital.
|
Footnotes
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Abbreviations:
BALF = BAL fluid; CLSN = centrilobular small nodules; CXR = chest
radiograph; DLCO = diffusing capacity of the lung for
carbon monoxide; GGO = ground-glass opacity; HP = hypersensitivity
pneumonitis; HRCT = high-resolution CT; LA = Lyophyllum
aggregatum; LCB = lymphoid cell in BAL fluid; LST = lymphocyte
stimulation test; PBL = peripheral blood lymphoid cell;
PFT = pulmonary function test; SI = stimulation index;
SOB = shortness of breath; TBLB = transbronchial lung biopsy;
VC = vital capacity; V25 = flow at 25% of
FVC; V50 = flow at 50% of FVC
Received for publication July 12, 2000.
Accepted for publication March 13, 2001.
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References
|
|---|
-
Yoshizawa, Y, Nakazawa, T, Ripani, LM, et al (1982) Development of chronic pulmonary inflammation in immunized guinea pigs by aerosol challenge with antigen-relationship of immune complex disease and cell mediated hypersensitivity. J Allergy Clin Immunol 70,114-119[CrossRef][ISI][Medline]
-
Kubo, K, Hanaoka, M, Hayano, T, et al (1998) Inflammatory cytokines in BAL fluid and pulmonary hemodynamics in high-altitude pulmonary edema. Respir Physiol 111,301-310[CrossRef][ISI][Medline]
-
Kubo, K, Yamazaki, Y, Masubuchi, T, et al (1998) Pulmonary infection with Mycobacterium avium-intracellulare leads to air trapping distal to the small airway. Am J Respir Crit Care Med 158,979-984[Abstract/Free Full Text]
-
Baldwin, ED, Cournand, A, Richards, DW, Jr (1948) Pulmonary insufficiency: I. Physiological classification, clinical methods of analysis, standard values in normal subjects. Medicine 27,243-278[Medline]
-
Berglund, E, Birath, G, Bjure, J, et al (1963) Spirometric studies in normal subjects: I. Forced expirograms in subjects between 7 and 70 years of age. Acta Med Scand 173,185-191[ISI][Medline]
-
Nishida, O, Kambe, M, Sewake, N, et al (1976) Pulmonary function in healthy subjects and its prediction: 5. Pulmonary diffusion capacity in adults. Jpn J Clin Pathol 24,941-947
-
Holland, P, Mauer, AM (1964) Drug induced in vitro stimulation of peripheral lymphocytes. Lancet 1,1368-1369[CrossRef][Medline]
-
Valentine, F (1971) Lymphocyte transformation. Bloom, BR Glade, PR eds. In vitro methods in cell mediated immunity ,443 Academic Press New York, NY.
-
Robert, RC, Moore, VL (1977) Immunopathogenesis of hypersensitivity pneumonitis. Am Rev Respir Dis 116,1075-1090[ISI][Medline]
-
Lopez, M, Salvaggio, JE (1988) Hypersensitivity pneumonitis. Murray, JF Nadel, JA eds. Textbook of respiratory medicine ,1606 WB Saunders Philadelphia, PA.
-
Hirshhorn, K, Bach, F, Kolodny, RL, et al (1963) Immune response and mitosis of human peripheral blood lymphocytes in vitro. Science 142,1185-1187[Abstract/Free Full Text]
-
Ando, M, Arima, K, Yoneda, R, et al (1991) Japanese summer-type hypersensitivity pneumonitis-geographic distribution, home environment, and clinical characteristics of 621 cases. Am Rev Respir Dis 144,765-769[ISI][Medline]
-
Ando, M, Sakata, T, Yoshida, K, et al (1990) Serotype-related antigen of Trichosporon cutaneum in the induction of summer-type hypersensitivity pneumonitis: correlation between serotype of inhalation challenge-positive antigen and that of the isolates from patient’s homes. J Allergy Clin Immunol 85,36-44[CrossRef][ISI][Medline]
-
Leatherman, JW, Michael, AF, Schwartz, BE, et al (1984) Lung T cells in hypersensitivity pneumonitis. Ann Intern Med 100,390-392
-
Brummund, W, Kurup, VP, Resnick, A, et al (1988) Immunologic response to Faenia rectivirgula (Micropolyspora faeni) in a diary farm family. J Allergy Clin Immunol 82,190-195[CrossRef][ISI][Medline]
-
Marx, JJ, Flaherty, DK (1976) Activation of the complement sequence by extracts of bacteria and fungi associated with hypersensitivity pneumonitis. J Allergy Clin Immunol 57,328-334[CrossRef][ISI][Medline]
-
Semenzato, G, Agostini, C, Zambello, R (1986) Lung T cells in hypersensitivity pneumonitis: phenotypic and functional analyses. J Immunol 137,1164-1172[Abstract]
-
Smith, SM, Synder, IS, Burrel, R (1980) Mitogenic response to Micropolyspora faeni cell walls. J Allergy Clin Immunol 65,298-304[CrossRef][ISI][Medline]
-
Bice, DE, McCarron, K, Hoffman, EO, et al (1977) Adjuvant properties of Micropolyspora faeni. Int Arch Allergy Appl Immunol 55,267-274[ISI][Medline]
-
Semenzato, G, Trentin, L, Zambello, R, et al (1988) Different types of cytotoxic lymphocytes recovered from the lungs of patients with hypersensitivity pneumonitis. Am Rev Respir Dis 137,70-74[ISI][Medline]
-
Nakazawa, T, Kanaya, I, Umeeda, Y, et al (1981) Mushroom worker’s lung due to inhalation of spores of the Cortinus shiitake. Jpn Thorac Clin Med 11,934-938
-
Nakazawa, T, Tochigi, T (1989) Hypersensitivity pneumonitis due to mushroom (Pholiota nameko) spores. Chest 95,1149-1151[Abstract/Free Full Text]
TOP
Abstract
Introduction
