Plastic Bronchitis

Many terms have been used to describe PB, including pseudomembranous bronchitis, mucoid impaction, cast bronchitis, fibrinous bronchitis, bronchitis fibroplastica, and Hoffman bronchitis.^{19, 20} PB is a rare disorder that usually occurs in children (average age, 6 years; range, 1-17 years), but it has been described in adults as well. The exact incidence of PB remains unclear because it is a rare condition, so the diagnosis is likely missed in some patients.²¹ It is characterized by branching mucoid bronchial casts that obstruct the tracheobronchial tree, causing respiratory distress.²⁰ The casts have been classified into two groups based on the presumed underlying pathophysiology. Type I casts (inflammatory) consist predominantly of eosinophil-rich cellular infiltrates and occur primarily in children with asthma or cystic fibrosis. Type II casts (acellular) are hypocellular and are encountered in patients with a history of surgically corrected cyanotic congenital heart disease.²² Acellular casts have also been associated with chyle leakage from the endobronchial lymphatic system.²³ Broadly speaking, the pathology and pathogenesis of type I casts overlap with asthma and ABPA, whereas type II casts appear to represent a more distinct entity.

Clinically, patients with PB present with wheezing, low-grade fever, upper respiratory tract infection, dyspnea, expectoration of tree-like casts, and frequent hemoptysis.²² The condition can mimic foreign body aspiration or status asthmaticus, and urgent bronchoscopy may be required for diagnosis and treatment.²⁴ Imaging studies typically reveal atelectasis, lung infiltrates, hyperinflation of the contralateral lung, or bronchial cutoff. In advanced cases, the imaging characteristics may resemble those of bronchiectasis.²⁵ For patients in respiratory distress in whom PB is suspected, emergent bronchoscopy is recommended. The mucus plugs of PB are described as bronchial casts; that is, they take the shape of the bronchi that they fill. Although the tree-like gross appearance can be striking, the histologic appearance is underwhelming. The casts in the more distinctive form of PB (type II) usually contain mucin, fibrin, and a few lymphocytes and macrophages (Fig 7). Figure 8 shows a bronchoscopic view of complete obstruction of the right main bronchus by a bronchial cast in a patient with PB.

Open in a separate window

Figure 7

Low magnification of mucus plug in plastic bronchitis containing mucin (short black arrow), fibrin (long black arrow), macrophages (short white arrow), and a few lymphocytes (long white arrow) (magnification, 200×).

Open in a separate window

Figure 8

Bronchoscopic view of complete obstruction of the right main bronchus with a large cast in a patient with plastic bronchitis.

(Image courtesy of Dr Daniel Sterman.)

Removal of these large, rubbery mucus plugs presents a unique therapeutic challenge because they are usually too soft to grasp with forceps and too thick to suction. After removal, the plug is immersed in saline or formalin to help demonstrate its characteristic branching pattern, which forms a perfect cast of the bronchus from which it was removed. The presence of blood in the gross specimen should not alter the differential diagnosis (Fig 9).²⁴ Previous publications have described the use of other therapies for mucus clearance, including mucolytics, chest physiotherapy, intratracheal recombinant human deoxyribonuclease, hydration, and aerosolized acetylcysteine.²⁶ The use of anti-inflammatory therapy with corticosteroids and macrolides has also been reported, with varying degrees of success.²⁷ In cases of PB in which lymphatic abnormalities are causative, a low-fat, medium-chain triglyceride diet or thoracic duct ligation may be helpful.²⁸ These patients must be closely followed to allow for early bronchoscopic intervention and prevention of further morbidity.

Open in a separate window

Figure 9

A, Left-sided airway cast removed via rigid bronchoscopy from a patient with plastic bronchitis. B, Airway cast resembling the entire bronchial tree, removed via rigid bronchoscopy from a patient with plastic bronchitis.

(Adapted with permission from Sriratanaviriyakul et al.⁷⁹)

Hyper-IgE Syndromes

Hyper-IgE syndromes (HIES) are a group of primary immunodeficiency syndromes associated with significantly elevated levels of IgE (usually > 2,000 International Unit/mL), recurrent skin infections, eczema, and pulmonary infections. Two distinct clinical forms have been described: autosomal-dominant HIES and autosomal-recessive HIES.⁵¹ Several mutations have been associated with HIES; mutations of signal transducer and activator of transcription 3 and DOCK8 are the most common.

The clinical manifestations of HIES vary depending on the underlying mutation, but recurrent pulmonary and cutaneous infections are the most common clinical manifestations.⁵² Staphylococcus aureus and Streptococcus pneumoniae are the most commonly isolated bacteria associated with HIES. Recurrent pneumonia may lead to long-term sequelae, such as pneumatoceles and bronchiectasis.^{53, 54} Pneumatoceles are not seen in autosomal-recessive HIES; however, recurrent pneumonia is common.⁵¹ Patients with pneumatoceles or bronchiectasis are also prone to secondary infection with Aspergillus and gram-negative bacteria, and opportunistic infections such as Pneumocystis pneumonia have also been reported. Mucus plugging of the airways is often seen in these recurrent secondary infections. Bronchoscopy is indicated for microbiologic diagnosis and for airway clearance.

Pulmonary complications are the most common cause of death in patients with HIES. In a postmortem study of six patients with autosomal-dominant HIES, all had pneumonia at the time of death, with Aspergillus and Pseudomonas being the predominant causes of infection (66% and 33%, respectively).⁵⁵ Mucus plugs obstructing the airway with resultant pneumonia is a common clinical presentation of HIES (Fig 15).

Open in a separate window

Figure 15

A-D, CT scan of the chest shows mucus plugging resulting in obstruction of multiple airways and distal consolidation in a patient with hyper-IgE syndrome.

Treatment of HIES is primarily supportive. Antibiotic prophylaxis against S. aureus with sulfamethoxazole and secondary antifungal prophylaxis is recommended and has been shown to decrease the incidence of recurrent infection.^{53, 56} Immunomodulatory therapy with intravenous immunoglobulin has been tried with variable success. Surgical intervention is often required; in a recent analysis, 22% of patients required lobectomy.⁵³ Surgical intervention should be pursued with caution, however, because it carries a high risk of complications, such as bronchopleural fistulae and impaired lung expansion.

Lipoid Pneumonia

Two clinically and pathologically distinct processes are characterized by accumulation of lipid or lipid-like material within the lungs. Exogenous lipoid pneumonia is a rare but well-characterized disorder caused by aspiration of exogenous oily material (ie, mineral, vegetable, or animal oil) into the lungs.⁵⁷ The most commonly implicated materials are liquid paraffin and mineral oil, both of which are used for treatment of constipation.⁵⁸ However, a wide variety of other oily substances have been reported to cause the disease, including petroleum-based lubricants (eg, Vaseline), oily nose drops, laxatives, spray lubricants, and lip gloss.⁵⁹ Risk factors that predispose to aspiration include gastroesophageal reflux disease and neurologic or psychiatric illness. In one case, exogenous lipoid pneumonia was reported in a commercial abalone diver who presumably aspirated aerosolized mineral oil contained in the unfiltered air generated from his surface air compressor.^{57, 60, 61}

The word exogenous refers to the fact that the lipid-like (lipoid) material in this condition is derived from materials extraneous to the human body. In contrast, so-called endogenous lipoid pneumonia is a common but nonspecific consequence of airway obstruction or narrowing by a wide variety of causes, including neoplasms, infection, inflammation, and other etiologies.⁶² The lipid in endogenous lipoid pneumonia is derived from cell membranes of macrophages, whose egress from the lung is impeded by narrowed airways. The accumulated macrophages eventually disintegrate, and the lipid from their cell membranes is ingested by other macrophages, which then take on what has been described as a foamy appearance. Accumulation of large numbers of foamy macrophages within the alveoli imparts the characteristic golden hue to the lung that has prompted terms such as golden pneumonia and cholesterol pneumonia. A similar golden material may fill the airways.

A large proportion of patients with exogenous lipoid pneumonia are asymptomatic at presentation. In symptomatic individuals, the clinical presentation is usually insidious; persistent cough, dyspnea, fever, and weight loss are the most common symptoms. Airspace disease is the most prevalent findings on chest CT scan. Other patterns include ground glass nodules, solid nodules, and crazy paving. Lung involvement is usually bilateral and multilobar, with a predilection for the lower lobes.^{60, 63} A density measurement between −30 and −150 Hounsfield units suggests the presence of fat in the lesion and may point toward this diagnosis.⁶⁰

As reported by Gondouin et al,⁶⁰ BAL and transbronchial biopsy help confirm the diagnosis in most patients with exogenous lipoid pneumonia. BAL fluid in exogenous lipoid pneumonia is often milky or oily (Fig 16)^{60, 64} and contains foamy macrophages with large (coarse) vacuoles. The pathologic appearance in transbronchial or surgical lung biopsies is confirmatory. It is characterized by the presence of foamy macrophages within the airspaces (alveolar lumens) and/or interstitium, containing variably sized coarse vacuoles within their cytoplasm (Fig 17). In contrast, the foamy macrophages seen in endogenous lipoid pneumonia contain fine vacuoles of uniform size that are present exclusively within airspaces (Fig 18). Although the vacuoles of exogenous lipoid pneumonia are remnants of lipid-like substances, the lipid itself is removed by processing in formalin-fixed paraffin-embedded sections.^{60, 64} Varying degrees of interstitial fibrosis are often present in exogenous lipoid pneumonia, and a giant cell reaction to the lipoid material in the interstitium is common. Cytologic profiles are nonspecific; lymphocytic, neutrophilic, and mixed profiles have been reported. In contrast with formalin-fixed paraffin-embedded transbronchial lung biopsies, BAL fluid samples can be subjected to fat stains, such as oil red O, which should be requested if the diagnosis is suspected clinically. Bronchoscopy may show plugs within the airways (Fig 19), occasionally associated with aspirated food particles.

Open in a separate window

Figure 16

Gross appearance of BAL fluid in exogenous lipoid pneumonia in a patient taking Lorenzo’s oil.

(Adapted with permission from Majori et al.⁸²)

Open in a separate window

Figure 17

Microscopic appearance of exogenous lipoid pneumonia. Macrophages containing coarse vacuoles of varying sizes fill the airspaces (short arrows). Similar macrophages are focally present within the interstitium (long arrow). This appearance is pathognomonic (magnification, 200×).

Open in a separate window

Figure 18

Microscopic appearance of endogenous lipoid pneumonia. Macrophages containing fine uniform vacuoles fill the airspaces (arrows). This is a common and nonspecific pathologic finding in lung specimens (magnification, 200×).

Open in a separate window

Figure 19

A, Bronchoscopic view of exogenous lipoid pneumonia with airway plugs. B, Photograph of airway plugs removed from a patient with exogenous lipoid pneumonia.

Identifying and discontinuing use of the causative agent is the cornerstone of therapy.⁵⁸ There are anecdotal reports of successful treatment of exogenous lipoid pneumonia with corticosteroids and whole lung lavage.⁶⁵

Pulmonary Alveolar Proteinosis

Pulmonary alveolar proteinosis (PAP) is caused by the abnormal accumulation of surfactant phospholipoprotein within alveoli. This accumulation is thought to be caused by failure of alveolar macrophages to clear surfactant from the lungs. PAP presents as one of three distinct forms: congenital, secondary, or acquired.⁶⁶ The congenital form is characterized by an acute onset of rapidly progressive respiratory distress immediately after birth.⁶⁷ Secondary PAP is secondary to conditions that reduce the number of alveolar macrophages or inhibit their function, such as some hematologic malignancies and infections.⁶⁶ Acquired PAP (commonly known as autoimmune PAP) is by far the most common form of PAP in adulthood. It usually affects middle-aged individuals; 90% of cases have an autoimmune etiology and are associated with antibodies directed against granulocyte-macrophage colony-stimulating factor (GM-CSF). PAP is more prevalent in men and has a strong association with cigarette smoking.^{68, 69}

The onset of acquired PAP is usually insidious with slowly progressive dyspnea and cough; however, acute respiratory failure has also been reported.⁷⁰ There is often a prolonged latency before diagnosis, and approximately 30% of patients are asymptomatic at presentation.⁶⁹

High-resolution CT scan is useful in the initial evaluation of patients with suspected PAP. Radiographic abnormalities are often out of proportion to symptoms (ie, they are surprisingly dramatic despite the associated mild symptomatology). The classic radiologic finding is a crazy-paving pattern on high-resolution CT scan, which manifests as bilateral ground-glass opacities superimposed on a background of smooth interlobular and intralobular septal thickening. However, the crazy-paving pattern can be seen in several other pulmonary diseases and is therefore not specific for PAP.⁷¹ Although PAP is defined by filling of the alveoli, the tracheobronchial tree may also be affected (Fig 20).⁷² Dense lipoproteinaceous material plugging the distal small airways has resulted in segmental atelectasis in some cases.

Open in a separate window

Figure 20

A-D, Bronchoscopic images show mucoid plugs within the airways in a patient with pulmonary alveolar proteinosis. Note the white-yellow, thick appearance.

(Image courtesy of Dr Abdul Hamid Alraiyes.)

Diagnosis of PAP is greatly facilitated by BAL and transbronchial lung biopsy. On gross examination, BAL fluid in PAP is milky and opaque. After it has settled, it separates into two layers: thick sediment at the bottom and a clear supernatant at top. On light microscopy, the airspaces (the lumens of the alveoli) are filled with a pathognomonic eosinophilic amorphous material (Fig 21). This material often contains acicular spaces and dense eosinophilic globules. It is usually, but not invariably, periodic acid-Schiff stain-positive and diastase-resistant.⁷¹ Alveolar septa are normal in most cases, despite what one would expect from the interstitial appearance of the disease on imaging. Anti-GM-CSF antibody titers can be measured in BAL fluid and correlate with severity of disease.⁷³

Open in a separate window

Figure 21

Microscopic findings in a patient with pulmonary alveolar proteinosis. Granular eosinophilic material fills the alveoli (black arrows). Alveolar septa (white arrows) are normal (magnification, 40×).

Therapeutic lung lavage is an established treatment modality for PAP, resulting in clinical, symptomatic, and radiographic improvement and reduced mortality. Lavage needs to be repeated in most patients (median of twice per patient).⁷¹ Exogenous GM-CSF has recently been reported as a therapy for autoimmune PAP; however, it is associated with less clinical improvement than with therapeutic lung lavage and can take up to 8 to 12 weeks to appear.⁷¹

Chronic Eosinophilic Pneumonia

Chronic eosinophilic pneumonia (CEP) is an idiopathic inflammatory disorder whose pathologic hallmark is the accumulation of large numbers of eosinophils within the alveoli. It typically affects patients in their 30s and 40s, many of whom have a history of atopy or asthma. Common symptoms include productive cough, fever, dyspnea, weight loss, and night sweats. Although uncommon, CEP can also present with bronchoconstriction and mucus plugs in the lower lung and has been reported in children and in middle-aged adults.^{74, 75} The classic radiologic pattern has been described as the “photographic negative of pulmonary edema.”⁷⁶ However, this pattern is present only in 25% of cases; therefore, its absence does not exclude CEP.⁷⁶

Mucus plugs occur in some patients with CEP. In these patients, they appear as thick, yellow-white impactions inside the airways. The most likely cause of mucus plugging in these patients is the presence of eosinophil-rich inflammatory infiltrates, conceptually similar to those seen in asthma and ABPA. The diagnosis of CEP can be confirmed by lung biopsy and BAL, both of which can demonstrate large numbers of eosinophils. CEP is exquisitely sensitive to corticosteroid therapy.

Financial/nonfinancial disclosures: None declared.