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Plastic Bronchitis: An Old Disease Revisited

      Expectoration of bronchial casts (plastic bronchitis) is an uncommon but ancient problem. Herein we describe a 40-year-old man, with no prior lung disease, who had dyspnea, cough, and expectoration of long branching bronchial casts. No specific cause was delineated, although special stains for eosinophilic granule major basic protein demonstrated occasional foci of eosinophils and small amounts of extracellular major basic protein in the bronchial casts. Various diseases, such as allergic bronchopulmonary aspergillosis, bronchiectasis, and cystic fibrosis, have been associated with the formation of bronchial casts and should be considered in the differential diagnosis. Although most previously reported cases have been associated with some type of pulmonary disease, our patient had no evidence of an underlying pulmonary disorder.
      Plastic bronchitis, also known as fibrinous bronchitis or pseudomembranous bronchitis, is an uncommon entity that reportedly occurs in children and adults.
      • Bettmann M
      Report of a case of fibrinous bronchitis, with a review of all cases in the literature.
      • Woolley PB
      Massive atelectasis due to fibrinous bronchitis.
      • Leggat PO
      Plastic bronchitis.
      • Johnson RS
      • Sita-Lumsden EG
      Plastic bronchitis.
      • Sanerkin NG
      • Seal RME
      • Leopold JG
      Plastic bronchitis, mucoid impaction of the bronchi and allergic broncho-pulmonary aspergillosis, and their relationship to bronchial asthma.
      • Morgan AD
      • Bogomoletz W
      Mucoid impaction of the bronchi in relation to asthma and plastic bronchitis.
      • Fairshter RD
      • Riley CA
      • Hewlett RI
      Large bronchial casts.
      • Bowen A
      • Oudjhane K
      • Odagiri K
      • Liston SL
      • Cumming WA
      • Oh KS
      Plastic bronchitis: large, branching, mucoid bronchial casts in children.
      • Liston SL
      • Proto D
      • Siegel LG
      Plastic bronchitis.
      • Müller W
      • von der Hardt H
      • Rieger CHL
      Idiopathic and symptomatic plastic bronchitis in childhood: a report of three cases and review of the literature.
      It is characterized by the presence of large inspissated bronchial casts that are expectorated, discovered at the time of bronchoscopy, or occasionally identified in lung specimens obtained at operation or autopsy.
      • Woolley PB
      Massive atelectasis due to fibrinous bronchitis.
      • Leggat PO
      Plastic bronchitis.
      • Johnson RS
      • Sita-Lumsden EG
      Plastic bronchitis.
      • Sanerkin NG
      • Seal RME
      • Leopold JG
      Plastic bronchitis, mucoid impaction of the bronchi and allergic broncho-pulmonary aspergillosis, and their relationship to bronchial asthma.
      Typically, the initial manifestations are dyspnea with or without wheezing, cough, fever, and, occasionally, hemoptysis. Most patients have underlying pulmonary disease.
      • Sanerkin NG
      • Seal RME
      • Leopold JG
      Plastic bronchitis, mucoid impaction of the bronchi and allergic broncho-pulmonary aspergillosis, and their relationship to bronchial asthma.
      • Fairshter RD
      • Riley CA
      • Hewlett RI
      Large bronchial casts.
      The chest roentgenogram reveals a segmental or lobar infiltrate or occasionally whole-lung atelectasis. In children, the differential diagnosis includes pneumonia or aspiration of a foreign object, whereas in adults it is most commonly confused with an endobronchial lesion such as bronchogenic carcinoma. Herein we report a case of a middle-aged man, with no prior history of asthma or lung disease, who had plastic bronchitis.

      REPORT OF CASE

      A 40-year-old man was referred to the Mayo Clinic for evaluation of right lower lobe pneumonitis and cough productive of large bronchial casts. The patient's health had been normal until 2 months earlier, when a cough productive of thick white sputum had developed. Fever (to 38°C), night sweats, and progressive dyspnea subsequently developed, and expectoration of large bronchial casts prompted admission to his local hospital 6 weeks before the current referral. A chest roentgenogram disclosed a right lower lobe infiltrate. A skin test for tuberculosis was negative. The absolute blood eosinophil count was 560 cells/mm3. A differential count of the cellular elements in the sputum revealed 5% eosinophils. Serum IgE was 18 U/ml (normal, 20 to 367). A radioallergosorbent test for Aspergillus was negative.
      A 10-day oral course of prednisone, tapered from 20 mg twice daily, diminished the coughing but resulted in serum glucose levels that exceeded 400 mg/dl. Subsequent bronchoscopic examination revealed copious secretions in the right lower lobe bronchus. The right lung was lavaged with 4,000 ml of isotonic saline. A transbronchial biopsy specimen of the right lower lobe demonstrated a fibrinous intra-alveolar exudate and foamy histiocytes, consistent with proximal obstruction. The intra-alveolar material was periodic acid-Schiff negative. Silver stains for fungi and Pneumocystis were negative.
      Pulmonary function tests demonstrated a restrictive ventilatory defect: total lung capacity, 5.09 liters (70% of the predicted value); ratio of residual volume to total lung capacity, 26%; forced vital capacity, 3.64 liters (71% of predicted); forced expiratory volume in 1 second, 3.33 liters (82% of predicted); ratio of forced expiratory volume in 1 second to forced vital capacity, 91%; and diffusing capacity of the lungs for carbon monoxide, 18.8 ml/min per mm Hg (60% of predicted). No benefit was noted after administration of a β-agonist bronchodilator. A sample of arterial blood, obtained while the patient was breathing room air, revealed a partial pressure of oxygen of 52 mm Hg, a partial pressure of carbon dioxide of 33 mm Hg, and a pH of 7.47. The patient's symptoms diminished somewhat after lavage, and he was transferred for further assessment.
      The patient had a 2-year history of diabetes mellitus treated with glyburide, 10 mg twice daily. Essential hypertension of 6 years' duration was treated with atenolol, 50 mg twice daily, and clonidine hydrochloride, 0.2 mg twice daily. He had smoked 1 pack of cigarettes a day for 15 years but had discontinued smoking 4 years before admission. He consumed 2 to 6 ounces of distilled spirits daily. During the month preceding the current admission, he had lost 5.5 kg in weight. He lived in a city and was employed as a convenience store manager. The patient had no history of atopy, asthma, or other respiratory disorder.
      On examination, the temperature was 37°C, the pulse was 100/min, and the respirations were 24/min. The blood pressure was 120/80 mm Hg. The patient was in no distress. No lymphadenopathy was noted. Breath sounds were decreased over both lung fields. High-pitched inspiratory and expiratory wheezes were heard over the right lung. Inspiratory crackles were detected at the base of the left lung. The results of the rest of the physical examination were unremarkable.
      The urine contained 2 g of glucose per 100 ml but was otherwise normal. The hematocrit was 41.2%; the leukocyte count was 5,900/mm3, with 60% neutrophils, 26% lymphocytes, 7% monocytes, 4% band forms, and 3% eosinophils. The platelet count was 295,000/mm3. The blood urea nitrogen was 29 mg/dl, the creatinine was 0.9 mg/dl, and the glucose was 204 mg/dl. The serum concentrations of sodium and potassium were 136 and 4.5 meq/liter, respectively. Microscopic examination of a specimen of sputum showed many neutrophils and no organisms; sputum stains for fungi and acid-fast organisms were negative. Sputum cultures were obtained for bacteria, fungi, and acid-fast organisms. An arterial blood gas analysis (room air) revealed a partial pressure of oxygen of 62 mm Hg, a partial pressure of carbon dioxide of 32 mm Hg, and a pH of 7.44. A chest roentgenogram disclosed consolidation of the right lower lobe of the lung, with loss of volume and blunting of the right costophrenic angle (Fig. 1); the remaining lung fields were clear. No lymphadenopathy was present, and the heart appeared normal.
      Figure thumbnail gr1
      Fig. 1Chest roentgenogram obtained at time of admission of 40-year-old man to hospital for evaluation of cough productive of large bronchial casts. Note consolidation of right lower lobe and loss of volume.
      On the second hospital day, the patient expectorated several large bronchial casts (Fig. 2 A). Sputum cultures grew normal flora. Serum immunodiffusion studies for A. fumigatus, A. niger, Micropolyspora faeni, Thermoactinomyces vulgaris, Thermomonospora viridis, and Alternaria were negative. Total serum IgE was 34 IU/ml (normal, 20 to 367). Serum IgE specific to Aspergillus was 119% of the negative control value. Antinuclear antibody, anti-dsDNA antibody, and rheumatoid factor were negative. The anti-human immunodeficiency virus antibody was negative.
      Figure thumbnail gr2
      Fig. 2A, Photograph of expectorated bronchial cast from right lower lobe. B, Representative photomicrograph of bronchial cast. Multiple microscopic sections of the cast were similar in appearance. It was composed of strands of fibrin that were covered with mucus and contained moderate numbers of lymphocytes and foamy histiocytes. Special stains for fungi were negative. (Hematoxylin-eosin; x250.) Although no eosinophils were identified on routine light microscopy, a special stain for eosinophilic granule major basic protein demonstrated occasional foci of eosinophils and extracellular deposition of major basic protein.
      • Peters MS
      • Schroeter AL
      • Kephart GM
      • Gleich GJ
      Localization of eosinophil granule major basic protein in chronic urticaria.
      Pulmonary function studies demonstrated a mild restrictive abnormality: total lung capacity, 5.30 liters (74% of predicted); vital capacity, 3.98 liters (73% of predicted); ratio of residual volume to total lung capacity, 25%; forced vital capacity, 3.96 liters (73% of predicted); forced expiratory volume in 1 second, 3.63 liters (83% of predicted); maximal voluntary ventilation, 155 liters/min (90% of predicted); and diffusing capacity of the lungs for carbon monoxide, 23.9 ml/min per mm Hg (71% of predicted). Sweat tests for sodium were 13 and 15 meq/liter (normal, 0 to 60). Serum glycosylated hemoglobin was 11.4% (normal, 4 to 7%).
      Bronchoscopy, performed on the fourth hospital day, disclosed a thick mucous plug in the right lower lobe bronchus. The mucous plug was removed with use of multiple lavages and alligator forceps. The remaining tracheobronchial tree appeared normal. Microscopic examination of bronchoalveolar lavage fluid revealed 78 × 10
      • Morgan AD
      • Bogomoletz W
      Mucoid impaction of the bronchi in relation to asthma and plastic bronchitis.
      total cells in a 60-ml specimen, with a cell differential of 87% lymphocytes, 12% macrophages, and 1% eosinophils. Typing to determine the percentage of T and B cells was technically unsatisfactory. Cultures or special stains (or both) of the bronchoalveolar lavage fluid for bacteria, acid-fast organisms, fungi, and Pneumocystis were negative.
      The patient continued to expectorate bronchial casts and to have dyspnea with minimal exertion. On the fifth hospital day, open-lung biopsy specimens were obtained from the right upper and lower lobes. At thoracotomy, no free pleural fluid was noted. The upper lobe appeared normal; however, a small nodular infiltrate was detected in the right lower lobe. Cultures for bacteria, fungi, and viral organisms were negative.
      Treatment was begun with prednisone, 40 mg orally per day; albuterol sulfate and triamcinolone acetonide were administered by metered-dose inhaler four times daily. Oxygen was administered as needed for comfort. The atenolol regimen was discontinued. Clonidine hydrochloride and insulin therapy were continued. The patient was dismissed on the 10th hospital day.
      Three weeks after dismissal, the patient was admitted to his local hospital because of hemoptysis and a temperature of 38.3°C; diffuse alveolar infiltrates were noted throughout the entire right lung. The hematocrit was 48.3%; the leukocyte count was 8,000/mm3, with 39% neutrophils, 31% lymphocytes, and 24% band forms. At bronchoscopy, extensive mucoid secretions were identified in the right lower lobe; bloody secretions emanated from the right upper and right middle lobe bronchi. Cultures of the lavage fluid for bacteria, fungi, and acid-fast organisms were negative. Acetylcysteine administered by nebulization was added to the therapeutic regimen. The patient improved symptomatically and was dismissed from the hospital. Oxygen therapy was discontinued 1 month later.
      Eight months after the onset of symptoms, the prednisone therapy was slowly being tapered. Attempts to decrease the dose to less than 30 mg/day on two occasions resulted in exacerbation of symptoms and recurrence of the cough productive of bronchial casts. The patient was no longer receiving acetylcysteine. Treatment consisted of an inhaled β-agonist bronchodilator, inhaled triamcinolone, and suppressive therapy with trimethoprim and sulfamethoxazole (Septra DS) twice a day.

      METHODS

      Tissue was fixed in 10% buffered formalin and processed routinely for light microscopy. All sections were stained with hematoxylin-eosin. Sections of the bronchial cast were also stained with mucicarmine and periodic acid-Schiff with and without diastase for mucin, Mallory's phosphotungstic acid-hematoxylin for fibrin, and silver chromate for fungi and P. carinii. Special staining procedures were performed on the mucous plug and the open-lung biopsy specimen for eosinophilic granule major basic protein by immunofluorescence microscopy.
      • Peters MS
      • Schroeter AL
      • Kephart GM
      • Gleich GJ
      Localization of eosinophil granule major basic protein in chronic urticaria.

      PATHOLOGIC FINDINGS

      The bronchial cast (Fig. 2 A) was white and rubbery. Microscopically (Fig. 2 B), it was composed of strands of fibrin layered with mucus, as confirmed by the mucicarmine and phosphotungstic acid-hematoxylin stains. It lacked the lamel-lated appearance characteristic of the bronchial casts associated with asthma or allergic bronchopulmonary aspergillosis (mucoid impaction of bronchi). The cast contained moderate numbers of inflammatory cells, primarily lymphocytes and foamy histiocytes. Eosinophils and neutrophils were absent, as were Charcot-Leyden crystals. The fungal stain was negative. The cast was stained for the presence of eosinophilic granule major basic protein; immunofluorescence microscopy demonstrated occasional to numerous eosinophils scattered throughout. At a microscopic magnification of xl60, five small foci of extracellular deposition of major basic protein were observed. These findings suggest that eosinophilic degranulation had occurred; however, the extracellular deposition was not extensive.
      • Peters MS
      • Schroeter AL
      • Kephart GM
      • Gleich GJ
      Localization of eosinophil granule major basic protein in chronic urticaria.
      The right lower lobe specimen was grossly unremarkable, and no bronchial casts were visible. Both the transbronchial biopsy and open-lung biopsy specimens showed features of an endogenous lipoid (obstructive) pneumonia (Fig. 3). Alveolar spaces were filled with foamy histiocytes, a few lymphocytes, and proteinaceous debris. The interstitium focally contained only a few lymphocytes. Some of the airways contained the same admixture of fibrin, mucus, and inflammatory cells as that seen in the expectorated cast. A mild submucosal infiltrate of chronic inflammatory cells was present in some bronchi and bronchioles, but histologic features of asthma were not present. No evidence of underlying bronchiectasis was found. Special stains for the presence of eosinophilic granule major basic protein demonstrated only occasional eosinophils and no extracellular deposition of major basic protein in the open-lung biopsy specimen.
      Figure thumbnail gr3
      Fig. 3Biopsy specimen from right lower lobe, showing features of an endogenous (obstructive) pneumonia. Bronchiole contained inspissated fibrin and mucus, resembling pattern shown in . (Hematoxylin-eosin; × 100.)

      DISCUSSION

      In 1902, Bettmann
      • Bettmann M
      Report of a case of fibrinous bronchitis, with a review of all cases in the literature.
      reported a case of fibrinous bronchitis in a 22-year-old woman who expectorated a 10-cm-long cast with branchings down to the seventh- or eighth-order bronchi. His review of the literature showed extensive previous reports; although several cases have subsequently been reported, it is still an uncommon process. In most reported cases, it has been associated with some type of pulmonary disease. Our case is unusual in that no underlying pulmonary disease was evident.
      Several processes can be associated with formation of bronchial casts
      • Sanerkin NG
      • Seal RME
      • Leopold JG
      Plastic bronchitis, mucoid impaction of the bronchi and allergic broncho-pulmonary aspergillosis, and their relationship to bronchial asthma.
      • Fairshter RD
      • Riley CA
      • Hewlett RI
      Large bronchial casts.
      • Waring WW
      • Brunt CH
      • Hilman BC
      Mucoid impaction of the bronchi in cystic fibrosis.
      • Hinson KFW
      • Moon AJ
      • Plummer NS
      Bronchopulmonary aspergillosis: a review and a report of eight new cases.
      and must be considered in the differential diagnosis of plastic bronchitis. Respiratory infections with diphtheria and other diseases or organisms (such as Haemophilus, Klebsiella, tuberculosis, and viral illnesses) have been associated with either concomitant or subsequent formation of bronchial casts. Rheumatic fever, rheumatic heart disease, and constrictive pericarditis are less clearly associated with bronchial casts. Bronchiectasis and cystic fibrosis have been associated with mucous plugs and formation of bronchial casts.
      • Waring WW
      • Brunt CH
      • Hilman BC
      Mucoid impaction of the bronchi in cystic fibrosis.
      Our patient had no evidence of infection or bronchiectasis, and a sweat chloride test helped to exclude the presence of cystic fibrosis.
      Allergic bronchopulmonary aspergillosis and asthma are the two most common diseases associated with formation of bronchial casts. The major differential features of allergic bronchopulmonary aspergillosis are the identification of small numbers of Aspergillus organisms in the bronchial cast,
      • Hinson KFW
      • Moon AJ
      • Plummer NS
      Bronchopulmonary aspergillosis: a review and a report of eight new cases.
      increased total IgE and Aspergillus-specific IgE (as determined by the radioallergosorbent test), and the immediate cutaneous reactivity to Aspergillus skin test antigen.
      • Greenberger PA
      Allergic bronchopulmonary aspergillosis and fungoses.
      In previous reports from the literature,
      • Sanerkin NG
      • Seal RME
      • Leopold JG
      Plastic bronchitis, mucoid impaction of the bronchi and allergic broncho-pulmonary aspergillosis, and their relationship to bronchial asthma.
      • Morgan AD
      • Bogomoletz W
      Mucoid impaction of the bronchi in relation to asthma and plastic bronchitis.
      • Fairshter RD
      • Riley CA
      • Hewlett RI
      Large bronchial casts.
      asthma has been present in most patients with formation of bronchial casts. The typical features of asthmatic casts are the laminar arrangement of the mucus, fibrin, and other eosinophilic material; the presence of eosinophils, usually in various stages of degeneration, Curschmann's spirals, and Charcot-Leyden crystals; and cellular detritus from epithelial cells.
      • Sanerkin NG
      • Seal RME
      • Leopold JG
      Plastic bronchitis, mucoid impaction of the bronchi and allergic broncho-pulmonary aspergillosis, and their relationship to bronchial asthma.
      The absence of such features in our case opposes the presence of subclinical asthma in this patient. In contrast, special stains of the cast showed the presence of eosinophilic granule major basic protein with extracellular deposition, which is suggestive of an allergic-mediated process.
      Sanerkin and Evans
      • Sanerkin NG
      • Evans DMD
      The sputum in bronchial asthma: pathognomonic patterns.
      reviewed bronchial casts from seven patients, of whom four had clinical asthma and three did not. Additionally, they reviewed sections of the casts from six patients with plastic bronchitis previously described in the literature (five of whom had clinical asthma). These investigators concluded that all casts were essentially identical to the aforementioned description of plugs expectorated by patients with asthma. They noted that the relative proportions of cast components varied considerably between cases but concluded that, on the basis of pathologic findings, all patients reviewed (those with and those without asthma) suffered from allergic bronchitis.
      • Sanerkin NG
      • Seal RME
      • Leopold JG
      Plastic bronchitis, mucoid impaction of the bronchi and allergic broncho-pulmonary aspergillosis, and their relationship to bronchial asthma.
      Others disagree with this conclusion.
      • Morgan AD
      • Bogomoletz W
      Mucoid impaction of the bronchi in relation to asthma and plastic bronchitis.
      • Fairshter RD
      • Riley CA
      • Hewlett RI
      Large bronchial casts.
      Morgan and Bogomoletz
      • Morgan AD
      • Bogomoletz W
      Mucoid impaction of the bronchi in relation to asthma and plastic bronchitis.
      believe that plastic bronchitis is a clinical rather than a pathologic entity and that allergy is only one of its causes. Although we favor the position of Morgan and Bogomoletz solely on the basis of histologic findings, the presence of eosinophilic granule major basic protein in our case is intriguing and raises the question of an allergic-mediated process.
      Therapy for plastic bronchitis consists of bron-chodilators for those with asthma, antibiotics for bacterial infection, hydration, chest physical therapy, and postural drainage. Aerosol acetylcysteine has been reported to facilitate bronchial clearance of plugs,
      • Urschel Jr, HC
      • Paulson DL
      • Shaw RR
      Mucoid impaction of the bronchi.
      but caution must be exercised because of possible induction of bron-chospasm by this agent. Bronchoscopic facilitation of drainage may be of benefit to some patients.
      • Johnson RS
      • Sita-Lumsden EG
      Plastic bronchitis.
      • Urschel Jr, HC
      • Paulson DL
      • Shaw RR
      Mucoid impaction of the bronchi.
      If flexible bronchoscopy fails,
      • Fairshter RD
      • Riley CA
      • Hewlett RI
      Large bronchial casts.
      then consideration should be given to rigid bronchoscopy or surgical intervention as a last resort. The role of corticosteroids (inhaled, orally administered, or both) is uncertain, although they are likely to be beneficial in any allergic-mediated reaction. Controlled trials substantiating the benefit of the previously mentioned therapeutic modalities are not available. In our patient, we noted a definite clinical correlation of exacerbation with attempts to taper the dosage of prednisone to less than 30 mg/day. The natural history of this entity is uncertain, but the literature suggests a high incidence of remissions after a few months. Some patients have experienced exacerbations after months or years of remission.
      • Johnson RS
      • Sita-Lumsden EG
      Plastic bronchitis.

      CONCLUSION

      Various diseases have been associated with the formation of bronchial casts. The cause is uncertain, although most cases occur in patients with asthma and the casts have pathologic characteristics consistent with those observed in asthma. Allergic bronchopulmonary aspergillosis, bronchiectasis, and cystic fibrosis should be excluded. Idiopathic plastic bronchitis is probably a nonspecific response to a variety of stimuli that results in production of extremely tenacious secretions that are difficult to clear.

      ACKNOWLEDGMENT

      We thank Gail M. Kephart and Dr. Gerald J. Gleich for special assistance in performing and interpreting the test for eosinophilic granule major basic protein. We also thank Doris J. Hegna for secretarial assistance.

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        Plastic bronchitis, mucoid impaction of the bronchi and allergic broncho-pulmonary aspergillosis, and their relationship to bronchial asthma.
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        Mucoid impaction of the bronchi in relation to asthma and plastic bronchitis.
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        Plastic bronchitis: large, branching, mucoid bronchial casts in children.
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