Conflict of Interest Statement: None of the authors has a financial relationship
with a commercial entity that has an interest in the subject of this manuscript.
INGEL K. DEMEDTS
GUY F. JOOS
GUY G. BRUSSELLE
Ghent University Hospital
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Is Giant Cell Interstitial Pneumonitis Synonymous
with Hard Metal Lung Disease?
To the Editor:
The large caseseriesof hard metal diseasedescribed by Moriyami
and colleagues in their article provides an important source of
clinico-pathologic data pertaining to a rare, but important inter-
stitial lung disease (1). The implications of the authors’ reported
observations from an immunologicalperspective werehighlighted
inthe erudite editorial byNemeryandAbraham in the sameissue
(2). There were, however, important epidemiologic inferences to
be drawn from this report that are also worthy of comment.
The authors used electron probe microanalysis to assess the
elemental content in lung biopsy material from 85 patients with
interstitial lung disease ‘‘suspected to be of environmental or
occupational origin.’’ Although 23 of the 85 biopsies studied
(27%) manifest pathologic findings of giant cell interstitial
pneumonitis (GIP), the basis for study inclusion (i.e., etiological
suspicion of an occupational disease) is not elucidated and may
very well have included such histology as one criterion. This
would be a reasonable approach, given that GIP has come to be
treated as a pathologic finding wholly attributable to hard metal
or related cobalt-containing exposures. Indeed, this was the
stated rationale for ‘‘delisting’’ GIP as an ‘‘idiopathic’’ pneumo-
nia in the 2002 American Thoracic Society/European Respira-
tory Society (ATS/ERS) statement on the classification of
idiopathic interstitial pneumonias (3).
In that light, the further epidemiologic observation of Mor-
iyama and colleagues is all the more intriguing: of the 23 patients
with GIP, 2 (8.7%) had no occupational history of exposure (one
was a schoolteacher) and no tungsten or cobalt detectable by
probe analysis. A recent case report from India of an office
sweeper with GIP but no suspect history also raises the question
equated with hard metal lung disease (4). There certainly have
been cases of GIP in which an occupational history was atypical,
but where metals analysis indicated likely occult cobalt exposure
(5). Conversely, a thorough metal analysis can be negative, but
nonetheless the occupational or environmental history may be
highly suspect, as in the case of a 15-year-old with GIP both of
whose parents had occupational exposure to hard metal (6).
Nemery and Abraham argue cogently that we need to fill in our
it may have been premature to banish GIP from the schema of
‘‘idiopathic interstitial pneumonias,’’ as was done in the ATS/
ERS statement (3).
Conflict of Interest Statement: P.D.B. has no financial relationship with a com-
mercial entity that has an interest in the subject of this manuscript.
PAUL D. BLANC
University of California, San Francisco
San Francisco, California
1. Moriyama H, Kobayashi M, Takada T, Shimizu T, Terada M, Narita J-I,
Maruyuma M, Watanabe K, Suzuki E, Gejyo F. Two-dimensional
analysis of elements and mononuclear cells in hard metal lung disease.
Am J Respir Crit Care Med 2007;176:70–77.
2. Nemery B, Abraham JL. Hard metal lung disease: still hard to under-
stand. Am J Respir Crit Care Med 2007;176:2–3.
3. American Thoracic Society. American Thoracic Society/European Res-
piratory Society international multidisciplinary consensus classification
of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med
4. Menon B, Sharma A, Kripalani J, Jain S. Giant cell interstitial pneumonia
in a 60-year-old female without hard metal disease. Respiration
5. Choi JW, Lee KS, Chung MP, Han J, Chung MJ, Park JS. Giant cell
interstitial pneumonia: high-resolution CT and pathologic findings in
four adult patients. Am J Radiol 2005;184:268–272.
6. Kakugawa T, Mukae H, Nagata T, Ishii H, Kaida H, Hayashi T, Suematsu
T, Kadota J-I, Kohno S. Giant cell interstitial pneumonia in a 15-year-
old boy. Intern Med 2002;41:1007–1012.
From the Authors:
We appreciate Dr. Blanc’s comments on our article (1). We
screened 85 biopsies; tungsten was detected in surgical biopsies
from 17 patients and in transbronchial biopsies (TBBs) from
three additional patients. Three TBBs were excluded from our
study because the pathologists could not make an accurate
pathologic diagnosis due to the small size of the TBB. A TBB
from an office sweeper without an exposure history was patho-
logically diagnosed as giant cell interstitial pneumonia (GIP)
(2), but we did not include TBB cases. Even though pathologists
find giant cells when screening biopsies, they should be careful
in making a final diagnosis of GIP, because giant cells are found
in other diseases such as viral pneumonia, especially pneumonia
due to measles, and sarcoidosis.
We applied an improved technique for element analysis of
tissue sections using an electron probe microanalyzer (EPMA)
with a wavelength dispersive spectrometer (WDS) (1). This
technique has about 10 times higher sensitivity than EPMA with
an energy dispersive spectrometer and enabled us to detect
tungsten in lung tissue in which the element was not found by the
other method (unpublished data; Reference 3). We found two
the hard metal industry. Finally, 2 (10.5%) of 19 surgical lung
biopsies were thought to be ‘‘idiopathic’’ GIP in our case series.
Inaddition toEPMA,atomic absorption spectrometry, plasma
optical emission mass spectrometry, and ionic coupled plasma
emission spectrometry have been used to detect tungsten and
detect elements in dissolved tissue solution. Using these methods,
one cannot see the relationship between elements and the charac-
accumulation within alveolar space; thus, some GIP diagnosed as
hard metal lung disease might actually be ‘‘idiopathic’’ GIP.
834AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINEVOL 1762007