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Postgraduate Education Corner: Pulmonary, Critical Care, and Sleep Pearls |

A Man in His 40s With Frequent Bronchitis, Localized Wheezes, and HemoptysisMan With Bronchitis, Wheezes, and Hemoptysis FREE TO VIEW

Shaji D. Skaria, MD; Bryan Harmon, MD; Alpa G. Desai, MD, FCCP
Author and Funding Information

From the Division of Pulmonary, Critical Care and Sleep Medicine (Drs Skaria and Desai), Department of Medicine, and Department of Pathology (Dr Harmon), Stony Brook University School of Medicine, Stony Brook, NY.

Correspondence to: Shaji D. Skaria, MD, Division of Pulmonary, Critical Care and Sleep Medicine, Stony Brook University School of Medicine, 101 Nicolls Rd, HSC T-17 Rm 040, Stony Brook, NY 11794-8172; e-mail: shaji.skaria@stonybrookmedicine.edu


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;145(6):1426-1429. doi:10.1378/chest.13-1914
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A man in his 40s presented with a 2-year history of progressive dyspnea, dry cough, and intermittent blood-streaked sputum. He also complained of dyspnea with exercise tolerance of walking one to two street blocks, wheezing, recurrent upper respiratory tract infections, and frequent bouts of bronchitis. He denied frank hemoptysis, fever, rashes, or chest pain. Review of systems revealed recent weight gain and snoring. No syncopal events or choking with meals were reported.

The patient’s past medical history included childhood asthma, allergic rhinitis, gastroesophageal reflux disease, spinal stenosis, mitral valve prolapse, atrial fibrillation, and bipolar disorder. He had multiple spinal fusion surgeries due to prior back injury. He was an ironworker for 20 years, with exposures to iron, asbestos, and silica. The patient’s medications included fluticasone/salmeterol diskus, diltiazem, esomeprazole, and albuterol hydrofluoroalkane, with diazepam and acetaminophen/oxycodone as needed. He was not taking warfarin, due to alcohol abuse and noncompliance with physician appointments.

The patient lived in New York and denied recent travel. He is an active 30-pack-year smoker with a history of alcohol, opioid, and marijuana abuse.

Physical Examination Findings

Vital signs revealed that the patient was afebrile, with normal BP, no tachycardia, and oxygen saturation of 100% on room air. He did not appear dyspneic with speaking. Head and neck examination noted no abnormalities in dentition and normal oral mucosa. He had a Malampatti class 4 airway and no macroglossia or stridor. Heart examination was normal with no murmurs or rubs appreciated. Pulmonary examination demonstrated isolated expiratory wheezes over the right lower lung field. The patient’s abdomen was nontender, with no organomegaly. There was no digital clubbing or peripheral edema. His skin was intact without nodules or rashes.

Diagnostic Studies

Pulmonary function testing demonstrated a mild obstructive pattern with FEV1/FVC of 68%; FEV1, 3.4 L (84% predicted); FVC, 5.0 L (102% predicted); total lung capacity, 7.3 L (104% predicted); residual volume, 2.2 L (105% predicted); and diffusing capacity of lung for carbon monoxide, 29.12 mL/min/mm Hg (89% predicted). Chest CT imaging was performed; abnormalities are shown in Figures 1 and 2. No lymphadenopathy or parenchymal abnormalities were noted in other CT scan sections. Results of a basic metabolic panel, liver function tests, and CBC counts with differential were all within normal limits. Transthoracic echocardiogram revealed a normal ejection fraction at 55% to 60%, slight enlargement of the right ventricle, and abnormal diastolic function of the left ventricle, but no significant thickening of chamber walls.

Figure Jump LinkFigure 1. Coronal view of chest CT scan at level of the carina.Grahic Jump Location
Figure Jump LinkFigure 2. Axial image of the chest in lung window just below the level of the secondary carina.Grahic Jump Location

The patient underwent bronchoscopy, with airway examination revealing multiple pale, friable, nodular lesions in the bronchus intermedius, left upper and right lower lobe bronchi, with associated airway narrowing in right lower lobe and left upper lobe (Fig 3). Right lower lobe and left upper lobe endobronchial biopsies were performed (Fig 3).

Figure Jump LinkFigure 3. Bronchoscopy images. A, Narrowed right upper lobe with multiple pale nodular lesions. B, Narrowed left upper lobe bronchus. C, Left upper lobe endobronchial biopsy specimen (hematoxylin and eosin stain, original magnification × 100).Grahic Jump Location
What is the diagnosis?
Diagnosis: Tracheobronchial amyloidosis

Amyloidosis is a group of diseases that result from the abnormal deposition of amyloid in various tissues of the body. Amyloid types include primary and secondary. Primary amyloidosis can involve almost any organ (including lung) and may be seen with multiple myeloma and Waldenstrom macroglobulinemia. Secondary amyloidosis is associated with chronic infections (eg, TB) or chronic inflammatory disease.

Isolated respiratory involvement (no systemic findings) is usually due to localized primary amyloidosis and can manifest as parenchymal nodules, diffuse alveolar septal infiltration, or tracheobronchial disease. It is rare and occurs predominantly in men in the fifth to sixth decade of life.

Tracheobronchial amyloidosis is an idiopathic disease characterized by the deposition of fibrillar proteins in the submucosa of the trachea and bronchi. Pathogenesis involves the release of excess, amyloidogenic, monoclonal immunoglobulin light-chain fragments by alveolar macrophages that are incorporated into the submucosa of the tracheobronchial tree. This suggests an abnormal immune response of the bronchial lymphoid tissue rather than a systemic response.

Presenting symptoms are nonspecific and include cough, dyspnea, and, occasionally, hemoptysis. Patients are often treated for recurrent pneumonia, tracheobronchitis, or asthma prior to diagnosis. Respiratory symptoms result from progressive airway narrowing. Tracheobronchial amyloidosis may be confused with bronchial asthma, airways neoplasm, and, rarely, relapsing polychrondritis, and can result in atelectasis or postobstructive pneumonia. In addition, calcified or cartilaginous submucosal nodules may be seen during bronchoscopy, which can be similar to findings of tracheobronchiopathia osteoplastica. Prognosis is variable, as individuals may have stable lung function for years or develop extensive airway compromise resulting in death from respiratory failure, including pulmonary hemorrhage and pneumonia.

Pulmonary function abnormalities depend on the location of amyloid deposition. Proximal deposition typically causes obstructive physiology and mid-distal disease results in normal airflow rates and air trapping. Pulmonary function deterioration is an important marker of disease progression.

Diagnosis requires histologic confirmation via pulmonary biopsy, as well as workup to rule out systemic involvement. Such a workup may include abdominal fat, bone marrow, rectal, or gum biopsy, along with serum protein electrophoresis/urine protein electrophoresis and immunohistochemical staining for κ and λ light-chain proteins and for amyloid A.

There is no known effective cure for tracheobronchial amyloid. Unlike systemic amyloidosis, which may be associated with pulmonary parenchymal disease, intermittent chemotherapy with melphalan and prednisolone does not have a clear role in localized tracheobronchial amyloidosis. However, several options for airway management exist, including mechanical debulking with balloon dilatation or endobronchial stent placement, local aggressive radiotherapy, Nd-YAG laser ablation therapy, and external beam radiation therapy. For patients with milder symptoms, continued observation and clinical radiologic follow-up may be appropriate.

Nd-YAG laser ablation therapy and mechanical debulking can result in significant symptomatic and lung function improvement. However, both techniques can result in complications of bleeding due to the friable nature of these lesions. In addition, given the possibility of disease recurrence, multiple procedures may be necessary.

External beam radiation therapy may have potential as a longer-term therapy, with improvement in the radiated fields several months to years after treatment. It is often preferred for patients with bulky or distal disease not amenable to simpler bronchoscopic techniques, particularly when associated with symptom or lung function decline. Its benefits may be due to radiation effect on local plasma cells, effect on local vasculature, or the induction of immune responses against deposits by inducing local inflammation. Reported side effects include esophagitis and pneumonitis.

There are a few reports of lung transplantation for isolated pulmonary amyloidosis, though risk of amyloid recurrence in the allograft exists. Although spontaneous resolution has been reported, most cases of tracheobronchial amyloidosis recur and require multiple therapeutic interventions to control progressive respiratory symptoms.

Clinical Course

This patient presented with dyspnea, hemoptysis, and focal wheezing. CT scans of the chest demonstrated right lower lobe and left upper lobe airways narrowing, which was also seen on bronchoscopy. Endobronchial biopsy specimens confirmed the diagnosis of tracheobronchial amyloidosis, with specimens positive for both Congo red staining and apple-green birefringence on polarized microscopy (Fig 4). Results of immunohistochemical stains, serum protein electrophoresis, and urine protein electrophoresis were all negative, eliminating systemic amyloid as a diagnosis.

Figure Jump LinkFigure 4. Left upper lobe endobronchial biopsy specimen. A, Congo red stain (original magnification × 40). B, Polarized microscopy with apple-green birefringence (original magnification × 100).Grahic Jump Location

The patient subsequently underwent balloon dilatation of the left upper lobe with marked reduction in his dyspnea and resolution of wheezing and hemoptysis. Pulmonary function testing performed after this intervention revealed significant improvement in FEV1 from 3.4 L (84% predicted) to 3.85 L (94% predicted) and FEV1/FVC from 68% to 74%. Follow-up CT scans of the chest at 6 months demonstrated improvement in airway narrowing. He continues to be monitored for clinical stability.

  • 1. Differential diagnosis of tracheobronchial amyloidosis includes bronchial asthma, airways neoplasm, tracheobronchiopathia osteoplastica, and relapsing polychrondritis, and can result in atelectasis or postobstructive pneumonia.

  • 2. Prognosis is variable, and pulmonary function deterioration is an important marker of disease progression and risk of death from pulmonary compromise.

  • 3. Bronchoscopic biopsies demonstrating Congo red positivity with apple-green birefringence under polarized-light microscopy are diagnostic for amyloid involvement of the lungs, but may not be sufficient to rule out systemic disease.

  • 4. While there is no cure, options for management of tracheobronchial amyloidosis range from observation with clinical radiologic follow-up to bronchoscopic debulking, balloon dilatation, Nd-YAG laser therapy, and external beam radiation therapy.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Other contributions:CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.

Utz J, Swensen S, Gertz M. Pulmonary amyloidosis. The Mayo Clinic experience from 1980 to 1993. Ann Intern Med. 1996;124(4):407-413.
 
Falk RH, Comenzo RL, Skinner M. The systemic amyloidoses. N Engl J Med. 1997;337(13):898-909.
 
Kurrus JA, Hayes JK, Hoidal JR, Menendez MM, Elstad MR. Radiation therapy for tracheobronchial amyloidosis. Chest. 1998;114(5):1489-1492.
 
Gillmore JD, Hawkins PN. Amyloidosis and the respiratory tract. Thorax. 1999;54(5):444-451.
 
Capizzi SA, Betancourt E, Prakash UB. Tracheobronchial amyloidosis. Mayo Clin Proc. 2000;75(11):1148-1152.
 
O’Regan A, Fenlon HM, Beamis JF Jr, Steele MP, Skinner M, Berk JL. Tracheobronchial amyloidosis. The Boston University experience from 1984 to 1999. Medicine (Baltimore). 2000;79(2):69-79.
 
Berk JL, O’Regan A, Skinner M. Pulmonary and tracheobronchial amyloidosis. Semin Respir Crit Care Med. 2002;23(2):155-165.
 
Da Silva L, Bellicanta J, Marques R, et al. Tracheobronchial amyloidosis. J Bras Pneumol. 2004;30(6):581-584.
 
Monroe A, Walia R, Zlotecki RA, Jantz MA. Tracheobronchial amyloidosis: a case report of successful treatment with external beam radiation therapy. Chest. 2004;125(2):784-789.
 
Neben-Wittich MA, Foote RL, Kalra S. External beam radiation therapy for tracheobronchial amyloidosis. Chest. 2007;132(1):262-267.
 

Figures

Figure Jump LinkFigure 1. Coronal view of chest CT scan at level of the carina.Grahic Jump Location
Figure Jump LinkFigure 2. Axial image of the chest in lung window just below the level of the secondary carina.Grahic Jump Location
Figure Jump LinkFigure 3. Bronchoscopy images. A, Narrowed right upper lobe with multiple pale nodular lesions. B, Narrowed left upper lobe bronchus. C, Left upper lobe endobronchial biopsy specimen (hematoxylin and eosin stain, original magnification × 100).Grahic Jump Location
Figure Jump LinkFigure 4. Left upper lobe endobronchial biopsy specimen. A, Congo red stain (original magnification × 40). B, Polarized microscopy with apple-green birefringence (original magnification × 100).Grahic Jump Location

Tables

Suggested Readings

Utz J, Swensen S, Gertz M. Pulmonary amyloidosis. The Mayo Clinic experience from 1980 to 1993. Ann Intern Med. 1996;124(4):407-413.
 
Falk RH, Comenzo RL, Skinner M. The systemic amyloidoses. N Engl J Med. 1997;337(13):898-909.
 
Kurrus JA, Hayes JK, Hoidal JR, Menendez MM, Elstad MR. Radiation therapy for tracheobronchial amyloidosis. Chest. 1998;114(5):1489-1492.
 
Gillmore JD, Hawkins PN. Amyloidosis and the respiratory tract. Thorax. 1999;54(5):444-451.
 
Capizzi SA, Betancourt E, Prakash UB. Tracheobronchial amyloidosis. Mayo Clin Proc. 2000;75(11):1148-1152.
 
O’Regan A, Fenlon HM, Beamis JF Jr, Steele MP, Skinner M, Berk JL. Tracheobronchial amyloidosis. The Boston University experience from 1984 to 1999. Medicine (Baltimore). 2000;79(2):69-79.
 
Berk JL, O’Regan A, Skinner M. Pulmonary and tracheobronchial amyloidosis. Semin Respir Crit Care Med. 2002;23(2):155-165.
 
Da Silva L, Bellicanta J, Marques R, et al. Tracheobronchial amyloidosis. J Bras Pneumol. 2004;30(6):581-584.
 
Monroe A, Walia R, Zlotecki RA, Jantz MA. Tracheobronchial amyloidosis: a case report of successful treatment with external beam radiation therapy. Chest. 2004;125(2):784-789.
 
Neben-Wittich MA, Foote RL, Kalra S. External beam radiation therapy for tracheobronchial amyloidosis. Chest. 2007;132(1):262-267.
 
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