Plastic Bronchitis: An Unusual Complication Associated With Sickle Cell Disease and the Acute Chest Syndrome

Plastic bronchitis is reported as a rare entity characterized by the formation of branching mucoid bronchial casts.12 These endobronchial casts of rubber-like consistency are organized aggregates of mucofibrinous substrate mixed with inflammatory cells. They may become firmly wedged and occlude the tracheobronchial tree at many levels.3 Obstruction involving both main stem bronchi is rare.4 Bowen et al2 reported that before 1985 there had been approximately 40 known cases of plastic bronchitis in children. Subsequently, in 1989, Perez-Soler5 reported an additional 72 cases of plastic bronchitis collected from his own personal experience.Galen described a similar condition in the second century AD.136 Although the condition is usually a sign of an underlying bronchopulmonary disorder such as asthma1-46-8 or allergy,1-3 the cause of cast formation remains an enigma in other cases. Respiratory infections with Corynebacterium diphtheria, Haemophilus influenzae, Klebsiella pneumoniae, Mycobacterium tuberculosis, and viral illnesses have been associated with the formation of bronchial casts.8 Other processes associated with bronchial cast formation include bronchiectasis,38cystic fibrosis,3468 and as a complication after the Fontan procedure.9To our knowledge this entity has not been described in pediatric patients with sickle cell disease. In this report, we describe three patients with acute chest syndrome (ACS) and a protracted clinical course due to plastic bronchitis.The cases of three children with sickle cell disease and ACS unresponsive to traditional medical management, who required bronchoscopy for the removal of fibromucinous casts are reported. The three patients varied in age and symptomatology at presentation (Table 1). Significant past medical history included previous episodes of ACS in all three patients and asthma in two of the patients. Each patient had continued exacerbation of their ACS and ultimately progressed to respiratory failure requiring intubation and mechanical ventilation. One patient required high-frequency oscillatory ventilation to maintain adequate oxygenation.Medical management consisted of fluid administration, and broad spectrum antibiotics including vancomycin, ceftriaxone, and erythromycin. A double-volume red blood cell exchange transfusion was performed in all three patients. Management of the pulmonary process initially consisted of aggressive pulmonary hygiene with frequent aerosolized β-agonists, N-acetylcysteine, DNase, intravenous methylprednisolone, and chest physiotherapy.Chest radiographs were done in all three for initial evaluation and after acute exacerbations (Table 2). Ultrasonography of the chest revealed significant pleural effusions in all three. Diagnostic and therapeutic thoracenteses were performed, revealing transudative fluid. Culture and Gram stains were all negative.Flexible fiberoptic bronchoscopy (FFB) was performed when the patients failed to improve with medical management. FFB revealed mucus casts causing obstruction (Fig 1). In two patients rigid bronchoscopy was required to remove the cast when FFB failed. In all cases the patients were successfully extubated and discharged home without residual pulmonary disease related to ACS or plastic bronchitis.All of the patients in our series presented with clinical characteristics consistent with ACS. ACS as described in sickle cell patients refers to any acute pathology having in common chest pain, fever, cough, and dyspnea with abnormal radiologic chest findings. In our review of the literature, plastic bronchitis has not been described in patients with sickle cell disease and ACS. Continued significant respiratory compromise and persistent radiographic abnormality, despite conventional management of ACS, necessitated the use of bronchoscopy for further evaluation of our patients. Bronchoscopic removal of mucoid branching and tubular casts was followed by significant improvement in clinical and radiographic findings in these patients. In one of the patients the need for multiple bronchoscopies for cast removal may have been secondary to impaired mucociliary clearance from the use of high-frequency ventilation.10-13Pulmonary complications in ACS include pneumonia, infarction, pulmonary edema, acute pulmonary sequestration, and bone marrow/fat embolism.14 The ACS is the most common of the pulmonary complications associated with sickle cell disease, occurring in approximately one third of individuals.1516 The syndrome is radiographically characterized by the findings of a new pulmonary infiltrate, usually accompanied by fever, chest pain, hypoxemia, and leukocytosis.1416 In patients with ACS, the chest radiograph often depicts complete opacification of a lung field.1517 One third of patients will present with a normal or unremarkable chest radiograph during a sickle cell crisis and go on to develop a radiographic abnormality hours to several days later.14 Pleural effusions occur in 25% to 35% of cases.14 In contrast to the reported incidence of pleural effusion in ACS, all of our patients developed pleural effusions.Therapy in ACS is geared toward maintenance of adequate oxygenation,16 treating underlying cause, relief of pain,16 repletion of intravascular volume, and reduction of sickle cell hemoglobin concentration.14Serjeant18 has recommended the routine use of exchange transfusion in patients with ACS, claiming dramatic radiological improvement within 48 hours after transfusion in almost all cases.Allergic bronchopulmonary aspergillosis and asthma are the two most common diseases associated with the formation of bronchial casts.13468 Other processes linked to bronchial cast formation include respiratory infections with various organisms, bronchiectasis,38 cystic fibrosis,3468 and as a pulmonary complication after the Fontan procedure9 for the repair of congenital heart disease.The clinical presentation of plastic bronchitis includes wheezing, upper respiratory symptoms, and low-grade fever.6 More than 70% of patients with plastic bronchitis have a history of chronic cough with some patients describing expectoration of casts during a previous illness.6 Physical examination reveals varying degrees of tachypnea, wheezing, and rales.6 Typically, the breath sounds are decreased over the affected area with dullness to percussion. Thus, the clinical features in plastic bronchitis may be indistinguishable from ACS. A characteristic bruit de drapeau, or flapping sound, caused by a hard cast thrown against the bronchial wall on inspiration, has been described in adults.6Laboratory results and chest radiographs are nonspecific. Peripheral eosinophilia may be seen when an allergic process contributes to cast formation.6 Obstructive emphysema, air leaks, focal airspace consolidation, or atelectasis of an entire lung may be seen.2Endoscopically, the casts appear as whitish to tan masses of rubbery material, sometimes too thick to pass through the suction port of the bronchoscope but too friable to grasp with forceps (see Fig2).16 The cast material may extend to the most distal portions of the bronchi.16 The bronchial casts of our patients were examined by a pulmonary pathologist. Gross description of the specimens reported cylindrical gray-white pieces of soft tissue, with some specimens showing branching patterns. Microscopic examination of the cast specimens showed largely acellular, fibromucinous material in the specimens from cases two and three and similar material with degenerating inflammatory cells in case one (Fig3). These findings are consistent with previous descriptions of casts found in plastic bronchitis.Previously reported microscopic evaluation of the casts in plastic bronchitis show them to be composed of a variety of elements ranging from acellular fibromucinous material to the presence of cellular elements including epithelial cells, inflammatory cells, necrotic debris, and eosinophils depending on the etiology of cast formation.36 The typical features of asthmatic casts are the laminar arrangement of the mucus, fibrin and other eosinophilic material, usually in various stages of degeneration, Curschmann's spirals, Charcot-Leyden crystals, and cellular detritus from epithelial cells may also be seen.38 On occasion, one may observe a persistent lumen, trapped air bubbles, mycelia, or bacteria in the cast.3 The substrate has no consistent composition and may contain entirely fibrin, entirely mucin, or a mixture of both in nonconstant ratios.3 Mucoid impaction of the bronchi is sometimes used synonymously with plastic bronchitis; however, it differs in that it is characterized by the local accumulation of inspissated mucus within a segmental bronchus. It is composed of layers of eosinophils in the obstructing plugs and is seen more specifically in asthmatic patients.7Therapy for plastic bronchitis is individualized and consists of the removal of obstructing casts,3bronchodilators,68 hydration,28N-acetylcysteine,2368 systemic steroids,8 antibiotics for bacterial infection,38 chest physical therapy,23 and postural drainage.8 In our patients neither the direct administration of DNase or N-acetylcysteine by flexible bronchoscopy allowed for degradation or removal of the mucoid casts.The etiology of cast formation in our patients is unclear. Two of the three patients had a history of asthma, a known association with plastic bronchitis. Neither of these two patients presented with signs or symptoms of asthma, making this an unlikely causative agent. Additionally, the typical features of asthmatic casts previously described were not present in either specimen from the patients with the histories of asthma. The three cases occurred within 4 weeks of each other, within a single urban area, suggesting a common etiology. However, a single pathogen was not identified. We did not specifically perform studies for mycoplasma and chlamydia therefore these organisms cannot be ruled out as the etiology of plastic bronchitis in our patients.We conclude that plastic bronchitis can be a complicating factor in sickle cell disease and ACS. The specific cause for the cast formation in the setting of sickle cell disease and ACS is unknown. We speculate that it may be secondary either to impaired mechanical clearance of secretions from splinting of the chest during pain crisis or to ischemia of the bronchial tree in vasocclusive crisis resulting in ciliary dysfunction. Failure to respond to conventional therapy, as well as aggressive chest physiotherapy and incentive spirometry19 should prompt a more detailed evaluation regarding the etiology of ACS. Flexible bronchoscopy may be of diagnostic and therapeutic value in these patients. Rigid broncoscopy may be required for removal of large casts.