Other Pneumoconioses - Aluminum Lung, Popcorn Lung and Flock Lung
Armando E. Fraire
University of Massachusetts Medical School
The skin and the lung are, by far (given their extensive surface area and constant contact with
ambient air), the most vulnerable organs of the body when dusts, gases, vapors and fumes are present in
the workplace. In the US alone, there are over 60 million workers whose primary work locations are at
construction sites or commercial offices or buildings where dusts, fumes and chemical exposures may
Pneumoconiosis, literally "dusty lungs", refers to the fibrotic reaction of the lung that results
from inhalation of mineral or inorganic dusts. By extension, pathologic lung reactions to non mineral
agents have been termed vegetable (organic) pneumoconiosis. The 3 main types of inorganic pneumoconioses
are silicosis, asbestosis and coal worker's pneumoconiosis. The pathologic changes from these different
diseases are quite varied and depend on the nature of the toxic exposure, host response, and major site
of respiratory system injury (upper airways vs. lower airways vs. alveoli vs. interstitial tissue vs.
Pneumoconiosis unrelated to asbestos, silica and coal dust are much less common. They include
berylliosis, siderosis, stannosis aluminosis, thesaurosis and baritosis as well as pulmonary lesions
resulting from exposure to a variety of agents such as zirconium, antimony, fiberglass, vinyl chloride
and others. As is the case with mineral pneumoconiosis the pathologic changes resulting from these (less
common) exposures are quite varied. This session focuses on three less common and less well known types
of non asbestos pneumoconiosis, namely aluminosis (for convenience herein referred to as aluminum lung)
and two recently described lung lesions that are colloquially known as popcorn lung and flock lung.
A 56 year old woman presented with a history of chronic troublesome unproductive cough. Physical
examination was normal as were pulmonary function tests. The chest radiograph showed diffuse
reticulonodular infiltrates in both lungs. The CT scan showed a larger nodule with eccentric
calcification in the right upper lobe. An open thorascopic lung biopsy showed multiple discrete non
necrotizing granulomas. Many of the granulomas contained globular birefringent particles. Energy
X ray elemental analysis (EDXEA) conducted on tiny particles carved directly out of the granulomas
showed major peaks of aluminum and silicon. She had been employed for several years at a New England
Plant manufacturing deodorants and toothpaste. Powder bags of "aluminum sulfate" and "sodium aluminum
lactate" were usually in her immediate surrounding areas at work. High dose prednisone therapy and later
low dose methotrexate therapy, along with departure from her job provided symptomatic relief.
Metalloconiosis (aluminum lung,
Aluminum is a durable, light weight metal used extensively
in industrial processes. Exposure to aluminum may occur during aluminum smelting, manufacturing of
aluminum abrasives, aluminum polishing and aluminum arc-welding.
Clinically, asthma and chronic obstructive lung disease have been described in individuals exposed to
aluminum. At the tissue level, diffuse fibrosis (with an upper lobe distribution) is a major
manifestation of exposure (Roggli). Granulomatous inflammation mimicking sarcoid (perhaps on basis of
hypersensitivity), alveolar proteinosis and DIP-like reactions are other forms of tissue response to
aluminum. Macrophages can be numerous in cases of aluminosis and found to contain fine gray to brown
cytoplasmic dust. The aluminum particles themselves appear as electron dense spheres 0.1 um to 1 um in
diameter, by electron microscopy (Roggli). An illustrative case of aluminosis characterized by
granulomatous interstitial lung disease in a 32 year old chemist was reported by De Vuyst. The disease
developed after working 8 years in a dusty atmosphere containing aluminum powders. Bronchoalveolar
lavage disclosed a helper T-lymphocyte alveolitis and a transbronchial biopsy showed sarcoid-like
epithelioid granulomas. Peripheral blood lymphocytes showed blastic transformation in the presence of
soluble aluminum (De Vuyst).
How is the diagnosis made ? Documentation of exposure to aluminum is
important but actual diagnosis can only be made with the use of ancillary techniques in combination with
one or more of the histopathologic changes (such as sarcoid like granulomas or interstitial fibrosis)
that are known to occur in aluminosis. An important diagnostic tool, particularly in patients showing
sarcoid or beryllium like granulomatosis is the helper T-cell lymphocytosis test in BAL fluid. An
alternate way is to perform in-vitro blastogenic response of peripheral
blood lymphocytes to soluble aluminum compounds (Roggli). Confirmation can also be achieved by electron
microscopy and/or demonstration of elemental aluminum in lung tissue sections by EDXEA. In the absence
of these specialized tests, the Irwin's aluminum stain may be a helpful alternate diagnostic tool. With
this technique, aluminum will appear as globules and mulberry like aggregates of dark red material lying
in the center of fibrous nodules or granulomas, after treatment of tissues with a 2% aurine tricarboxylic
acid solution (Lillie).
A 46 year old woman employed for 18 months at a US microwave popcorn production plant developed
shortness of breath and cough. Her FEV1, varied from 20 – 25% of predicted. A CT scan of the
chest showed pulmonary interstitial changes. A thoracoscopic lung biopsy showed focal bronchiolar
fibrosis and fibroblastic proliferation compressing bronchiolar lumina. There was no intersitial
pneumonia. She did not respond to steroids but showed partial (symptomatic) relief to a 3 month course
of cyclophosphamide. Later, she was accepted for a lung transplant and needed up to 3 L of oxygen per
minute (Kreiss) (Parmet).
Popcorn lung (Popcorn workers lung)
In May 2000, the above cited index patient and seven other
former workers at the microwave popcorn production plant were recognized as having clinical evidence of
severe bronchiolitis obliterans (Kreiss). All but one of the eight workers were non-smokers. The
suspected offending agent appeared to be a work place toxin.
The histopathologic changes reported in the index patient are those of constrictive bronchiolitis.
Two forms of bronchiolitis have been described, bronchiolitis obliterans (BO) and constrictive
bronchiolitis (CB). Non idiopathic BO may result from infectious agents, connective tissue disease and
complications form heart, lung or bone transplants. BO also occurs after inhalation of chemical agents
such nitrogen dioxide, and sulfur dioxide. Constrictive bronchiolitis (CB) refers to syndrome of airflow
limitation due to bronchiolar and peribronchiolar inflammation and fibrosis. Clinical syndromes
associated with CB include allograft recipients (bone marrow, heart and lung); collagen vascular diseases
(rheumatoid arthritis, systemic lupus erythematosus); post infectious conditions (RSV, adenovirus);
inhaled toxins (nitrogen dioxide, sulfur dioxide), drugs (penicillamine) and ulcerative colitis. Vapors
of butter flavoring may now be added to this list.
What is the responsible agent(s) for the airway damage seen in popcorn factory
workers ? Obvious suspected agent or agents are the vapors of butter flavoring. To test the
hypothesis that vapors of butter flavoring are noxious agents to the lung, Hubbs and associates exposed
rats to heated butter flavorings. Rats were exposed for 6 hours by inhalation and autopsied a day
later. By gas chromatography, the vapors consisted of a complex of various organic gases with major
peaks corresponding to diacetyl (2,3 butanedione), acetic acid, acetone and butyric acid, among others.
DIACETYL was used as a marker of exposure concentration. In the lung,
vapors containing containing 285-370 ppm diacetyl caused multifocal necrotizing
bronchiolitis. In the nasal passages vapors containing 200-270 ppm diaceytl caused necrotizing rhinitis.
How is the diagnosis made ? Clearly, history of current or past
exposure to vapors of butter flavoring is critical. Most cases reported thus far have been diagnosed as
bronchiolitis on basis of clinical, spirometric and radiographic findings. Histopathologic responses
described thus far include 1) non necrotizing granulomas, 2) constrictive bronchiolitis and 3) focal
bronchiolar fibrosis and fibroblastic proliferation compressing bronchiolar lumina". The case
illustrated in this session (contributed by Bill Travis) showed findings of constrictive bronchiolitis.
A 26 year old man first presented with increasing shortness of breath associated with
exercise and minimal but persistent dry cough. His O2 saturation at rest was 97% but
decreased to 93% upon walking 1200 ft in 5 minutes. The chest X ray showed patchy densities bilaterally
in the upper lung fields. The high resolution CT of the chest showed a pattern consistent with
bronchiolitis, most prominent in the upper lobes. The clinical differential diagnoses included
hypersensitivity pneumonitis, bronchial asthma, idiopathic interstitial pneumonitis and an infectious
He was a machine operator at a Massachusetts synthetic flock factory and was primarily
responsible for mixing and loading machines with raw flock material. He denied smoking or family history
of tuberculosis or other chronic respiratory diseases. Therapy with a short course of prednisone
provided only temporary relief of his symptoms. An open, video assisted open lung biopsy was performed.
Flock lung (lymphocytic bronchiolitis and peribronchiolitis with
multifocal lymphoid hyperplasia) (LBP-BLH)
Kern and associates first called attention (1997) to the
occurrence of chronic interstitial lung disease among workers in the nylon flocking industry. Flocking
is a process in which continuous synthetic fibers (mainly nylon) are chopped into short segments and then
applied to an adhesive-coated backing fabric to produce a plush finish such as in fabrics used to
upholster seating in the automotive industry. Although the cut fibers, or flock, are of non-respirable
size, smaller respirable nylon shards may be produced during processing Two other young men employed at
a nylon flocking plant in Rhode Island developed interstitial lung disease of unknown etiology. This led
to identification of four additional cases for a total of seven cases. In six of seven patients who had
a biopsy, a picture of non specific interstitial pneumonitis was noted. The seventh had bronchiolitis
obliterans organizing pneumonia. All seven had peribronchovascular interstitial lymphoid nodules, with
germinal centers and most had lymphocytic bronchiolitis and interstitial fibrosis. All of these patients
improved symptomatically after leaving work for variable periods of time.
To investigate the problem, the National Institute of Occupational Safety and Health
(NIOSH) of the Centers for Disease Control hosted a clinical-pathological workshop to review additional
accumulated case load of patients with interstitial lung disease associated with the flocking industry.
In all, biopsies from fifteen patients (eight open, seven transbronchial) were reviewed at the workshop
by a panel of pathologists led by Tom Colby. In this group of flock workers the main histopathologic
findings was a peribronchiolar lymphocytic interstitial inflammation with associated lymphoid
The histopathologic features in the group of 15 cases were classified as prominent,
variable and not found. Prominent features included peribronchiolar
lymphocytes interstitial (BLH); Bronchiolar mural lymphocytic inflammation and peribronchiolar alveolar
macrophages. Variable features included Type II hyperplasia;
non-lymphocytic interstitial inflammatory cells, bronchiolar mural fibrosis and organizing air space
processes such as BOOP. Features not identified included granulomas,
smooth muscle hyperplasia, honeycombing, vascular changes and severe interstitial fibrosis.
How is the diagnosis of flock lung made? In the proper
clinical setting, a diagnosis can be made in biopsy material that shows LBP-BLH, bronchiolar mural
lymphocytic infiltration and peribronchiolar accumulation of macrophages.
The rest of the story: More recent cases of workers
employed in a North Carolina nylon producing plant reported in 2000 by Kern et al had differing
histopathology, with one worker showing DIP on lung biopsy and one showing mild acute inflammation on BAL
fluid. Of two other workers one had marked acute inflammation and the other, malignant cells in his BAL
fluid. In one other recent case from Nova Scotia, a 60 year old nylon flock worker also showed a
different pattern of lung injury in his biopsy with a less prominent lymphoid hyperplasia and a rather
distinct histiocytic component to the inflammatory infiltrate (Alex Boag, personal communication, October
2003). These additional cases suggest a pathologic spectrum of disease broader than that first described
at the NIOSH conference and further support the likelihood that flock workers lung is caused by inhaled
fragments of nylon fibers (Kern).
The putative (or confirmed) work-related toxins, clinical manifestations, principal
pulmonary function abnormalities, main histopathology and key references for aluminum, popcorn and flock
lungs are summarized in the following table:
ALUMINUM LUNG, POPCORN LUNG AND FLOCK LUNG
LB = Lymphocytic bronchiolitis
|Lung Lesion ||# of cases ||Toxic agent ||Signs and symptoms ||Respiratory function ||Pathologic findings||Main refs|
|Aluminum lung ||1 ||Elemental aluminum ||Cough Dyspnea ||Normal in this case ||Diffuse fibrosis, granulomas, aggregates of histiocytes ||Hull Roggli Corrin|
|Popcorn lung ||8 ||Butter flavoring ketones. Diacetyl and other vapors ? ||Cough Dyspnea ||¯Fev1 ||Non-necrotizing granulomas, Constrictive bronchiolitis ||Kreiss Hubbs Parmet|
|Flock lung ||15 ||Respirable shard-like nylon fibers ||Cough Dyspnea ||O2 desaturation on exercise ||LB PB LH ||Boag Kern|
PB = Peribronchiolitis
LH = Lymphoid Hyperplasia
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