Membranous obliteration of bronchi is a rare finding, but has been reported in cases of chronic airway inflammation. We report a case of progressive membranous obliterative bronchitis leading to chronic respiratory failure and ultimately death.
Our patient is a 35-year-old woman with a history of uncontrolled type 1 diabetes mellitus who developed bronchiectasis and chronic hypercapnic respiratory failure after an episode of severe multilobar pneumonia and acute respiratory distress syndrome. She had no history of pulmonary disease or respiratory infections until 2 years before presentation, when she had a prolonged hospitalization for diabetic ketoacidosis and acute respiratory distress syndrome secondary to multilobar pneumonia. Respiratory cultures at that time grew methicillin-sensitive Staphylococcus aureus, and polymerase chain reaction testing of a nasal swab was positive for H1N1 influenza. She required prolonged mechanical ventilation and was hospitalized for 6 weeks. She was eventually discharged to a rehabilitation facility with supplemental oxygen.
Over the next 2 years, the patient was hospitalized 8 times with acute on chronic respiratory failure, and required endotracheal intubation during 4 of these hospitalizations. A new finding of bronchiectasis was seen on computed tomographic imaging of the chest, and her recurrent respiratory failure was initially attributed to exacerbation of postinfectious bronchiectasis. Bronchoscopy was performed on multiple admissions. One year after her initial presentation, bronchoscopy showed patent airways, but some subsegmental bronchi were noted to have mucosal projections, including in the right lower lobe (RLL): refer to Figure 1A. Three months later, bronchoscopy revealed new narrowing of some of the RLL (Fig. 1B) and right upper lobe (RUL) subsegmental bronchial orifices secondary to development of circumferential membranes occluding the airways. The bronchoscope could not be advanced through these narrowed airways.
On the current presentation, chest x-ray revealed significant volume loss of the right lung (Fig. 2). Findings on bronchoscopy helped to explain this development. There was complete occlusion of the apical segment of the RUL, and narrowing of the anterior and posterior segments of the RUL. In addition, multiple RLL subsegmental bronchi were found to be obstructed by membranes (refer to Fig. 3). An attempt was made to perforate a membrane using a combination of argon plasma coagulation, forceps, and balloon dilation. The membrane was thick and resistant to perforation (Fig. 3). Pathologic examination of the membranous tissue showed fibrosis and infiltration by macrophages and lymphocytes (Fig. 4).
Although clinically the patient did not appear to have a history of lung disease before her episode of multifocal pneumonia 2 years prior, given a concern for occult underlying disease an extensive workup for bronchiectasis was performed. Cystic fibrosis mutation analysis was negative for 32 mutations (LabCorp-Esterix). No immunodeficiency was appreciated: testing was negative for human immunodeficiency virus, and immunoglobulin levels were within normal limits. Her α-1 antitrypsin genotype was MM. Repeated acid fast cultures showed no growth. An endobronchial biopsy was performed, which showed normal ciliated respiratory epithelium. A rheumatologic workup was also negative, with the exception of a positive antinuclear antibody titer (1:320). The etiology of her bronchiectasis and membranous obliterative bronchitis was therefore thought to be a sequela of severe infection. Pulmonary function testing performed ∼16 months after her initial presentation showed a forced expiratory volume in 1 second (forced expiratory volume in 1 second) of 0.54 L (19% of the predicted). The patient was not a candidate for lung transplantation due to poor nutritional status and lack of family support. Her clinical course continued to deteriorate, with recurrent episodes of hypercapnic respiratory failure requiring ventilatory support. In the end, palliative care measures were pursued, and the patient expired at home.
Occlusion of the bronchi was initially thought to be a congenital disorder resulting from anomalous airway development, with symptomatic presentation in childhood or as late as middle age.1–3 However, later reports suggested that intense inflammation could also trigger the formation of membranous structures. Examples included a response to free crystalline silica in a patient with pneumoconiosis,4 the presence of a foreign body in the left main bronchus,5 and prolonged tracheostomy placement resulting in obstruction of the right main bronchus.6 Membranous obliteration of the bronchi has been described following a postinfluenza bacterial pneumonia, although in a pediatric, rather than adult, patient. This patient also had a progressive course, and died as a result of subsequent respiratory failure.7
A 2006 case series describing 3 adults with cystic fibrosis, one of whom was postlung transplantation, attempted to define a unifying pathophysiologic process and proposed the term “membranous obliterative bronchitis” to describe it. In one of the 3 patients they were able to break through one of the membranes, and this revealed patent distal airways. On the basis of histologic findings of granulation tissue with occasional inflammatory cells, the authors proposed that inflammation results in granulation tissue formation, protrusion of small polyp-like structures, and continued inward growth of granulation tissue resulting in obstruction.8,9 Serial bronchoscopic examination performed in our patient support this hypothesis by demonstrating the progression of disease. Initially, circumferential mucosal projections were present and encroached on the airway opening. Later, these affected airways became totally occluded by membranes.
Membranous occlusion of the airways has also been reported following lung transplantation.10–12 A single-center review of lung transplant recipients found that 2% developed symptomatic narrowing of the bronchus intermedius over 15 years and defined this as the vanishing bronchus syndrome (VBS).13 Experience from another lung transplant center showed a 0.02% rate of VBS over a 10-year period.14,15 It is hypothesized that VBS develops secondary to abnormal airway healing in the setting of poor airway perfusion.14 Other authors hypothesize that this finding could be a manifestation of chronic rejection.12 Patients with the disease have responded to serial balloon dilation, bronchoplasty, and stent placement.10
Stenosis without complete occlusion of the bronchus has been described in a number of inflammatory states. Granulomatosis with polyangiitis is associated with airway narrowing: although subglottic tracheal stenosis is more commonly seen, focal bronchial stenosis has also been well-described.16–18 Inflammatory bowel disease can cause a number of pulmonary manifestations including bronchiolitis obliterans syndrome, diffuse panbronchiolitis, and bronchiectasis. It can also cause nodular or circumferential narrowing of the lumen of the trachea and mainstem bronchi.19,20 Focal stenosis of a central bronchus has also been described in postinfectious states, including after infections with tuberculosis and histoplasmosis. Sarcoidosis can cause endobronchial cobblestoning which in some cases has led to narrowing of the airway.21 Amyloidosis has been shown to cause thickening of the mainstem bronchi.22 It is possible that these inflammatory conditions which cause narrowing of the bronchi could in time lead to complete occlusion.
The case presented here is unique because it is the first adult noncystic fibrosis, nontransplant patient in which this membranous obliterative bronchitis has been reported. In addition, it is the first to describe the progression over time of membrane formation based on serial bronchoscopies. This pathologic process resulted in worsening of her chronic respiratory failure, and eventually led to her demise. Membranous obliterative bronchitis remains poorly described, and further investigation is needed to understand the airway abnormalities predisposing to membrane development and delineate proper clinical management of patients with this potentially dangerous entity. The optimal therapeutic intervention has not been clearly defined, but proper therapy could positively affect patient care as airways distal to the obstruction can remain patent.
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