Occupational Medicine Advance Access originally published online on January 22, 2007
Occupational Medicine 2007 57(3):221-224; doi:10.1093/occmed/kql162
© The Author 2007. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Pulmonary alveolar proteinosis induced by silica dust?
Riitta Sauni1,
R Järvenpää2,
E Iivonen3,
S Nevalainen4 and
J Uitti1
1 Finnish Institute of Occupational Health, Tampere, Finland and Clinic of Occupational Medicine, Tampere University Hospital, Tampere, Finland
2 Department of Diagnostic Radiology, Tampere University Hospital, Tampere, Finland
3 Department of Pulmonary Diseases, Tampere University Hospital, Tampere, Finland
4 Suomen Terveystalo Group, Lahti, Finland
Correspondence to: Riitta Sauni, Finnish Institute of Occupational Health, PO Box 486, 33101 Tampere, Finland. Tel: +358 30 474 8650; fax: +358 30 474 8605; e-mail: riitta.sauni{at}ttl.fi
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Abstract
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Abstract Pulmonary alveolar proteinosis (PAP) is a rare disease,
with several aetiologies. This study reports the first Finnish
case of PAP with possible induction by silica dust. A 58-year-old
male patient had a documented history of heavy exposure to silica
dust over a long period, although he himself considered the
exposure to be low. The patient's cumulative exposure to silica
dust was
10 mg m
–3 years according to the workplace measurements.
The patient developed classical symptoms and signs of PAP that
closely mimicked those of acute silicosis, but he did not have
any signs of classic silicosis. We conclude that significant
chronic exposure to silica favours the diagnosis of PAP rather
than acute silicosis in this case. PAP should be taken into
account when patients exposed to silica dust complain of respiratory
symptoms. A patient's assessment of his/her exposure to silica
may not always be reliable.
Keywords Acute silicosis; exposure; lung disease; occupational disease; pulmonary alveolar proteinosis; silica
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Introduction
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Pulmonary alveolar proteinosis (PAP) is an uncommon disease
that was first described in 1958 [
1]. Typical symptoms are shortness
of breath and dry cough. Histologically, there is granular eosinophilic
material in the alveoli that stains intensively with periodic
acid Schiff. A primary (idiopathic) PAP can be distinguished
from a secondary PAP. The latter has been related to infections
[
2], malignant haematological diseases [
3], immunodeficiency
disorders [
4,
5] and exposure to chemicals and inorganic dusts
like silica or cement dust, cellulose fibres, combustion products
of plastics [
6], aluminium and titanium oxide [
7–
10].
The rareness of PAP makes it impossible to study it in depth
with epidemiologic methods, and no dose–response estimates
are available in relation to, for example, silica exposure.
The clinical picture of PAP closely resembles that of acute
silicosis, but so far the two have been considered separate
diseases [
11,
12]. Acute silicosis develops after exposure to
high concentrations of respirable crystalline silica within
5 years. It seems that, in the scientific literature, the distinction
between PAP and acute silicosis has not always been clear. Previous
cases of PAP in association with silica exposure have been described
as silicoproteinosis, a feature that has also been shown to
be related to acute silicosis [
13–
15]. This study reports
a case of a drilling machine technician whose unusually long-lasting
exposure to silica dust without peaks of exposure supports the
diagnosis of PAP rather than acute silicosis, and it also presents
estimations of the exposure.
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Clinical history
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The patient was a 58-year-old man who had suffered from arterial
hypertension and ulcerative colitis. He neither had previous
history of any lung disease nor had ever smoked. He had worked
as a drilling machine technician in mines for 35 years. In the
spring of 2005, he started to experience shortness of breath
on exertion. The chest radiograph was abnormal and suggestive
of lung fibrosis (
Figure 1). High-resolution computed tomography
(HRCT) showed both ground-glass opacification and abundant reticular
interstitial infiltrate (
Figure 2). The lung function measurements
indicated mild restriction: forced vital capacity (FVC) 3.40
l (72% of predicted), forced expiratory volume in 1 s (FEV
1)
2.89 l (76% of predicted) and FEV% 80 (85% of predicted). The
diffusing capacity of the lungs was significantly reduced, diffusing
capacity (DL, CO) being 31% and transfer coefficient of the
lung (KCO) being 50% of the predicted value. The blood gas analysis
showed hypoxia (PaO
2 6.9, PaCO
2 3.9, pH 7.44). The haemoglobin
concentration was 20.3 g dl
–1, but the infection parameters
were normal. The antibodies to HIV were negative. The general
status of the patient was good. Inspiratory crackles were heard
in both lungs. Bronchoalveolar lavage (BAL) was performed through
bronchoscopy. The macroscopic appearance of the lavage fluid
was milk-like. The microscopic analysis revealed abundant amorphous
material with crystalline structures. The total cell count was
elevated, as was the lymphocyte count. Among the amorphous material
were rounded particles that stained positively with periodic
acid Schiff. A therapeutic lavage was performed for both lungs.
Thereafter, the symptoms improved to some extent, and the patient
could manage without oxygen therapy. No other predisposing factors
for PAP than silica dust exposure could be determined.
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Occupational history and exposure
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Exposure to fine silica dust is difficult to evaluate without
quantitative measurements at the worksite. Such measurements
had been conducted over the years in the mines where our patient
worked. The patient had worked for
70% of his working time in
mines in which the concentration of silica dust had been 0.13–0.18
mg m
–3 depending on the working site. The other 30% of
his working time had been spent doing test drillings either
in underground (one-third of the time) or in open air (two-thirds
of the time). The silica dust concentration during the underground
drilling had been 0.21 mg m
–3, and in open air it had
been 1.04 mg m
–3. The silica measurements are static samples
that reflect the minimum exposure level of all the workers in
that site. The exposure of those workers who take part in, for
example, drilling is probably remarkably higher. On the basis
of the static samples, the cumulative exposure to silica dust
can be approximated to be
10 mg m
–3 years, indicating
heavy exposure. According to the patient himself, the silica
exposure was relatively low.
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Discussion
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The gold standard for the diagnosis of PAP has been open-lung
biopsy. However, nowadays, BAL alone is sufficient to diagnose
most cases of PAP [
16]. The BAL findings of our patient were
typical of PAP, as were the radiographic findings (
Figures 1 and
2). We found no other known aetiological reason for PAP
than occupational exposure, primarily to silica dust. However,
the possibility of idiopathic PAP and concomitant exposure to
silica dust cannot be ruled out in a study of a single case
such as this.
The clinical picture of PAP resembles closely that of acute silicosis [11,12,17]. Acute silicosis develops after exposure to high concentrations of respirable crystalline silica within a period ranging from a few weeks to 5 years after the initial exposure and in its classical form it is fatal [18–20]. In our case, the exposure to silica dust had continued much longer, for 35 years before the first respiratory symptoms. Although the exposure levels of silica were considered high, to our knowledge, there were no extraordinary high peak exposures. This opinion is based on the statements of the patient and the management of the mine. There are no continuous monitoring results of silica dust levels available. The unusually long time and the even level of exposure to silica do not support the diagnosis of acute silicosis.
However, this case raises an interesting question, whether acute silicosis and silica-induced PAP can be variants of the same disease. The common symptoms of both PAP and acute silicosis include progressive dyspnoea, cough, crackles, weight loss, fever, clubbing, cyanosis and chest pain [1,11,16]. The histopathology, including the filling of alveoli with phospholipids and proteins, and radiological findings are very similar in both diseases. In chest radiographs, bilateral, symmetric alveolar filling patterns with perihilar infiltrates are commonly seen [21,22]. HRCT shows reticular, reticonodular and ground-glass opacities [22–24].
The relationship between silica dust exposure and a PAP-like disease has been documented in several studies. Exposure to silica dust has induced changes in the lungs of rats and mice that resemble the histological features of PAP in humans [25,26]. As early as the 1930s, an acute type of silicosis was described [13] that resembled PAP histologically. It was related to heavy exposure to silica over a relatively short period of time, and it was called silicoproteinosis [8,9,14]. We have found three publications about PAP due to occupational silica exposure. One of these concerned a US cement truck driver [27], one involved a US sandblaster [7] and the third discussed a French ceramics worker [28]. It is hard to deduce the model of silica exposure needed for PAP from these cases.
There is conflicting evidence as to whether silicotic nodules are present in patients with silica-induced PAP [9,14,15,28]. In a study of 13 PAP cases [29], two showed both silicosis and PAP radiologically. The chest radiograph or HRCT of our patient did not show any signs of chronic silicosis, although there was a long history of extensive silica dust exposure. It is possible that chronic silicosis and PAP have different pathogenetic mechanisms. It has been suggested that silica dust may mechanically irritate Type II pneumocytes and provoke an excessive discharge of surfactant and associated lipids without the fibrogenic effect that is essential in chronic silicosis [30].
The National Institute for Occupational Safety and Health (NIOSH) in the USA recommends an exposure limit of 0.05 mg m–3 for respirable crystalline silica as a time-weighted average for up to a 10-h workday during a 40-h workweek to reduce the health risks of silica [31]. The NIOSH hazard review of silica also mentions PAP as one possible adverse health effect of silica in addition to silicosis and lung cancer. In Finland, the exposure limit for respirable crystalline silica is 0.2 mg m–3 although this limit is under discussion. Studies show that the risk of silicosis and lung cancer is increased when the concentration of silica dust increases. The silica dust concentration of our patient's worksite varied from 0.13 mg m–3 to 1.04 mg m–3. However, the patient himself evaluated the amount of dust as being relatively low. It is possible that respirable crystalline silica, which includes particles with aerodynamic diameters of less than 10 µm, is partly invisible and may lead to an underestimation of the health risks and to a worker neglecting the use of respiratory protection.
Although PAP is a rare pulmonary disease, it should be taken into account when patients exposed to silica dust complain of chest tightness and cough and when there are typical signs of PAP radiologically. It is also noteworthy that the self-estimation of silica dust exposure of patients may not always be reliable. Exposure to silica should be controlled with industrial hygiene measures and kept as low as possible, respiratory protection being used when necessary.
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Conflicts of interest
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None declared.
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Abstract
Introduction
