DOI:10.2214/AJR.05.0835
AJR 2007; 188:W412-W414
© American Roentgen Ray Society
Respiratory Bronchiolitis-Associated Interstitial Lung Disease in a Nonsmoker: Radiologic and Pathologic Findings
Ok Hee Woo1,
Hwan Seok Yong1,
Yu-Whan Oh1,
Sung Yong Lee2,
Han Kyeom Kim3 and
Eun-Young Kang1
1 Department of Radiology, College of Medicine, Korea University, Korea
University Guro Hospital, 97 Guro-dong, Guro-ku, Seoul 152-703, Korea.
2 Department of Internal Medicine, College of Medicine, Korea University, Korea
University Guro Hospital, Seoul 152-703, Korea.
3 Department of Pathology, College of Medicine, Korea University, Korea
University Guro Hospital, Seoul 152-703, Korea.
Received May 17, 2005;
accepted after revision June 28, 2005.
Address correspondence to E.-Y. Kang
(keyrad{at}korea.ac.kr).
WEB This is a Web exclusive article.
Keywords: chest imaging • high-resolution CT • lung diseases • radiologic-pathologic correlation
Introduction
Respiratory bronchiolitis is a common inflammatory lesion of the
respiratory bronchioles that occurs mainly in cigarette smokers. It was first
described in 1974 by Niewoehner et al.
[1] in an autopsy study of 39
patients who died of nonpulmonary causes. Its histologic appearance is
characterized by the accumulation of pigmented macrophages within the
respiratory bronchioles and the surrounding airspaces, with minimal associated
mural inflammation [1]. In some
patients, the extent of alveolar accumulation and bronchiolar inflammation is
severe enough to produce clinical, physiologic, and imaging features of
interstitial lung disease [2,
3].
This clinicopathologic syndrome, called respiratory
bronchiolitis-associated interstitial lung disease (RB-ILD), occurs almost
exclusively in heavy cigarette smokers. A small number of cases of
cigarette-smoking-associated RB-ILD with positive imaging findings have been
reported in the existing literature, but the radiologic findings have not yet
been described regarding the occurrence of RB-ILD in nonsmokers. This article
reports a case in which radiologic features have a clinical and pathologic
correlation to histologically proven RB-ILD in a nonsmoker who was heavily
exposed to second-hand smoke.
Case Report
A 54-year-old woman presented to the thoracic outpatient department
complaining of a nonproductive cough with dyspnea. She was a nonsmoker but was
exposed to heavy cigarette smoke because she had been working as a waitress in
a pub for 8 years. She had no other medical history of note and was not on any
medication. She had no exposure to environmental agents that are known to
cause lung disease.
The patient was mildly febrile on clinical examination, and auscultation of
her chest revealed expiratory wheezing. The arterial blood gases in the room
air, however, were normal. The patient was initially treated with
broad-spectrum antibiotics and was nebulized with bronchodilators. The test
for HIV (after patient consent), the atypical serology, and the autoimmune
profile all showed negative results, and the immunoglobulins were normal; the
erythrocyte sedimentation rate was 15 mm/h. Pulmonary function tests showed
that the patient's pulmonary function was normal.
The chest radiograph showed diffusely scattered fine micronodules spread
throughout both lungs (Fig.
1A). A high-resolution CT scan showed evenly distributed,
ill-defined centrilobular nodules, and ground-glass opacities without
branching densities also spread throughout both lungs (Figs.
1B and
1C). The thoracic radiologist
suggested a diagnosis of the subacute stage of hypersensitivity pneumonitis,
but the differential diagnosis included RB-ILD. The histopathologic specimen
obtained from the lingular segment of the left upper lobe through
video-assisted thoracoscopic surgical lung biopsy showed a respiratory
bronchiolitis pattern with the accumulation of pigment-laden macrophages
within the alveolar spaces. There was also mild chronic inflammation of the
bronchioles, fibrous thickening of the wall of the bronchioles, and cuboidal
cell hyperplasia of the alveolar ducts and alveoli adjacent to the bronchioles
(Fig. 1D).
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Fig. 1A —54-year-old nonsmoking woman with pathologically proven respiratory
bronchiolitis-associated interstitial lung disease. Chest radiograph shows
diffusely scattered fine micronodules spread throughout both lungs.
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Fig. 1B —54-year-old nonsmoking woman with pathologically proven respiratory
bronchiolitis-associated interstitial lung disease. High-resolution CT scans
in axial (B) and coronal (C) planes show evenly distributed,
ill-defined centrilobular nodules and ground-glass opacities without branching
densities.
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Fig. 1C —54-year-old nonsmoking woman with pathologically proven respiratory
bronchiolitis-associated interstitial lung disease. High-resolution CT scans
in axial (B) and coronal (C) planes show evenly distributed,
ill-defined centrilobular nodules and ground-glass opacities without branching
densities.
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Fig. 1D —54-year-old nonsmoking woman with pathologically proven respiratory
bronchiolitis-associated interstitial lung disease. Photomicrograph of biopsy
specimen obtained from lingular segment of left upper lobe shows accumulation
of pigmented macrophages within alveolar spaces, with mild chronic
inflammation of bronchioles and fibrous thickening of wall of bronchioles. (H
and E, x100)
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These findings were consistent with a diagnosis of RB-ILD. The patient was
therefore diagnosed as having RB-ILD because all of the other differential
causes of her abnormal CT findings and symptoms had been excluded. The patient
was placed on high-dose corticosteroids. She was subsequently discharged when
she had improved. Follow-up high-resolution CT after 6 months showed much more
improvement in the findings (Fig.
1E).
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Fig. 1E —54-year-old nonsmoking woman with pathologically proven respiratory
bronchiolitis-associated interstitial lung disease. Follow-up high-resolution
CT scan after 6 months, at same level as B, shows improvement of
ill-defined centrilobular nodules and ground-glass opacities.
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Discussion
Respiratory bronchiolitis is almost invariably present as an incidental
finding in a lung biopsy in cigarette smokers and is usually not associated
with respiratory symptoms [1].
Some heavy smokers, however, have pathologic findings of respiratory
bronchiolitis associated with clinical findings, which are similar to those of
an interstitial lung disease. This subgroup is referred to as having RB-ILD
[2,
3], which is usually discovered
on a respiratory function test. At diagnosis, most patients are asymptomatic,
already in the fourth or fifth decade of life, and have had an insidious onset
of dyspnea. The diagnosis is often made in an open or thoracoscopic lung
biopsy. The prognosis is good, and no deaths have yet been reported. The
patients improve or stabilize after smoking cessation, with or without
corticosteroid treatment
[4].
Pathologically, respiratory bronchiolitis is a distinct lesion
characterized by the accumulation of yellow-brown-pigmented macrophages within
the respiratory bronchioles and in the alveolar ducts and alveoli. The
separation of incidental respiratory bronchiolitis and RB-ILD on the basis of
their morphologic features is a controversial issue. Myers et al.
[3], in the original
description of RB-ILD, considered the histologic features of RB-ILD to be
indistinguishable from those of respiratory bronchiolitis, although they
described nonspecific fibrosis in the alveolar septa adjacent to the
respiratory bronchioles in the cases that they studied. They separated RB-ILD
from respiratory bronchiolitis on the basis of clinical, not pathologic,
evidence of an interstitial lung disease. It is important to note, as
emphasized by Yousem et al.
[2], that the lesions in
patients with RB-ILD are more pronounced than the focal clusters of
macrophages seen in the small airways of healthy cigarette smokers. The
finding of respiratory bronchiolitis is not specific to exposure to cigarette
smoke because similar abnormalities have been described in the lung biopsies
of patients with asbestos and nonasbestos mineral dust exposure
[5].
The chest radiographic findings of patients with RB-ILD show
reticulonodular interstitial opacities with a normal-appearing lung volume,
typically fine and diffuse or basally predominant
[2,
3]. In 20-28% of patients with
biopsy-proven RB-ILD, however, chest radiography has been reported as normal
[2,
3]. The CT findings of RB-ILD
include ground-glass opacities, centrilobular nodules, and interstitial
thickening with upper-lung-zone predominance
[6,
7]. In addition to respiratory
bronchiolitis, the radiologic differential diagnosis of RB-ILD includes
nonspecific interstitial pneumonitis, desquamative interstitial pneumonia, and
acute or subacute hypersensitivity pneumonitis.
The occurrence of respiratory bronchiolitis in the absence of smoking is
extremely uncommon, and its cause is unknown. In a previous study, 107 (98%)
of 109 patients with respiratory bronchiolitis were smokers, including 83
current smokers and 24 former smokers, and three of them smoked pipes. Only
two of the 109 patients with respiratory bronchiolitis were nonsmokers. One
patient, though, was exposed to diesel fumes and fiberglass and another to
second-hand smoke [8]. The
subject in our case was a nonsmoker, but she was indirectly and continuously
exposed to cigarette smoke while working as a waitress. Thus, she is
considered a second-hand smoker.
Respiratory bronchiolitis is a highly sensitive and relatively specific
morphologic marker of cigarette smoking, but few studies have quantified its
incidence in cigarette smokers or have assessed the significance of this
finding in nonsmokers. The relevance of these findings is unclear, and the
role of second-hand smoke or environmental exposure in the cause of
respiratory bronchiolitis has not been clearly described. It should be
remembered, however, that pigmented intraluminal macrophages occur in various
dust-related environmental lung diseases. By definition, the macrophages in
respiratory bronchiolitis contain yellow-brown pigments that are thought to be
derived from cigarette smoke.
In our study, pathologic findings showed a marked accumulation of pigmented
macrophages within the alveolar spaces. Fraig et al.
[8] reported that respiratory
bronchiolitis that had developed in nonsmokers was classified as variant
respiratory bronchiolitis and that pigmented macrophages were seldom observed,
unlike classical respiratory bronchiolitis. However, the results in our study
showed pigmented macrophages within the alveolar spaces, with a mild chronic
inflammation of the bronchioles and fibrous thickening of the wall of the
bronchioles, as in typical RB-ILD. Pigmented macrophages are regarded as
indicative of cigarette smoking, but their presence in our case means that
pigmented macrophages are also related to indirect exposure to cigarette
smoke.
In summary, we presented a case of RB-ILD in a nonsmoker, showing
groundglass opacities and centrilobular nodules spread throughout both lungs
on high-resolution CT images. The patient manifested the characteristics of
typical RB-ILD in histopathology, such as pigmented macrophages within the
alveolar spaces and fibrous thickening of the wall of the bronchioles. Thus,
RB-ILD could be considered when these findings of small airways disease are
detected on radiographs or CT scans, even when the patient is not a cigarette
smoker.
References
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bronchiolitis causing interstitial lung disease: a clinicopathologic study of
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features with clinical and pathologic correlation. J Comput Assist
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- Fraig M, Shreesha U, Savici D, Katzenstein AL. Respiratory
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Introduction
Case Report
