Current Evaluation and Management of Plastic Bronchitis in the Pediatric Population

Abstract

Objective:

To describe a multidisciplinary approach for the treatment of plastic bronchitis (PB) in children.

Methods:

Retrospective chart review of children with PB between 1997 and 2017. Data regarding clinical presentation, diagnosis, management, and outcomes were analyzed.

Results:

Of 34 patients presenting with PB, 24 had single ventricle (SV) heart disease, 9 had pulmonary disease, and one had no underlying disease. Median (IQR: interquartile range) age at the time of PB diagnosis was 5.5 years (IQR: 9.0). Presenting symptoms included cough productive of casts (n=27, 79%), wheezing (n=5, 15%), dyspnea (n=18, 53%), hypoxia (n=31, 91%), and respiratory failure (n=9, 26%). Diagnosis was made based on clinical evaluation, bronchoscopy findings, and/or pathology of casts. Treatment methods included bronchoscopy for cast removal (25% of SV patients, 91% of non-SV patients), chest physiotherapy (SV: 92%, non-SV: 45%), albuterol (SV: 79%, non-SV: 73%), inhaled steroids (SV: 75%, non-SV: 18%), nebulized hypertonic saline (SV: 29%, non-SV: 9%), nebulized heparin (SV: 8%, non-SV: 55%), nebulized tissue plasminogen activator (tPA; SV: 33%, non-SV: 9%), inhaled Dornase Alfa (SV: 54%, non-SV: 9%), antibiotics (SV: 46%, non-SV: 45%), systemic steroids (SV: 13%, non-SV: 45%), and lymphatic embolization (SV: 8%, non-SV: 45%). Of SV patients, 11 had no recurrence, 5 underwent heart transplantation, one awaits transplant, and 3 died due to cardiac disease. Three patients with respiratory disease had recurrent PB and one died from MRSA pneumonia.

Conclusion:

PB is a highly morbid disease with limited treatment options. Bronchoscopy and chest physiotherapy for airway clearance are among the most-utilized therapies.

Introduction

Plastic bronchitis (PB) is a rare pulmonary disorder characterized by the production of cohesive, branching casts filling the airways.¹ With variable presentations, patients with PB may present with dyspnea, wheezing, pleuritic chest pain, or fever,¹ and the size of casts produced may range from small segmental casts of one bronchus to large casts filling the airways of an entire lung.²

The histology of PB was formally classified in 1997 by Seear et al.³ who described two types of casts: type 1 inflammatory casts composed of fibrin and acute-phase inflammatory cell infiltrates, and type 2 noninflammatory acellular casts composed of mucin. Because a subset of casts did not fit into Seear’s described types, Brogan et al.⁴ proposed a new classification scheme based on the associated disease state (allergic/asthmatic, cardiac, and idiopathic) in 2002. In 2005, yet another classification system based first on the associated disease (a genetic component or predisposition) and then on cast histology (inflammatory insult leading to abnormal accumulation of mucin, fibrin, or chyle in the airways) was proposed.¹ The continuously changing classifications of PB pathogenesis suggest a generally poor understanding of the disease process. This has resulted in variability in treatment with no standard therapy. The wide range of therapies reported is a testament to the fact that none are reliably efficacious.

While PB may be associated with allergic/asthmatic or idiopathic comorbidities, in children the disease occurs as a rare complication of single-ventricle palliation of patients with single ventricle heart disease (SVHD).¹ Of children affected with PB, approximately 40% have SVHD.⁴ Lymphatic abnormalities, such as retrograde lymphatic flow from the thoracic duct (TD) toward lung parenchyma, have been postulated to play a role in the disease process. Noncardiac associations of PB include cystic fibrosis, sickle cell anemia, asthma, and lymphangiomatosis.^5,3

Plastic bronchitis is a serious condition, which can cause asphyxiation and death if left untreated.¹ Proper treatment of children with this disease is essential, but it remains poorly understood by many clinicians due to its rarity.⁶ The purpose of this study is to review the presentation, characteristics, and management strategies used at Boston Children’s Hospital in a uniquely large set of patients with PB over a 20-year period.

Methods

An institutional review board-approved retrospective review was performed of patients with a plastic bronchitis diagnosis at Boston Children’s Hospital from January 1997 to July 2017. Medical records were reviewed for data regarding demographics, clinical presentation, diagnosis, management, and outcomes.

For those who underwent cardiac catheterization, invasive hemodynamic data from the procedure closest to the PB episode were reviewed. Hemodynamic data collection parameters are shown in Table 2.

Table 2.

Catheterization data closest to 1^st plastic bronchitis episode in 23 patients with single ventricle heart disease.

Hemodynamic study	n	Median (IQR)
CI, L·min−1·m−2	21	3.05 (1.16)
Mean SVC, mmHg	17	16.00 (6.50)
Mean IVC, mmHg	10	16.00 (6.50)
Mean Fontan pressure, mmHg	18	16.00 (6.00)
Mean pulmonary artery pressure, mmHg	16	15.00 (6.36)
Pulmonary capillary wedge pressure, mmHg	18	9.00 (5.00)
Transpulmonary gradient, mmHg	18	5.50 (3.75)
Indexed pulmonary vascular resistance, WUm2	17	2.40 (0.85)
Systemic Ventricular end diastolic pressure, mmHg	17	9.00 (5.50)

Note: Data are expressed as number or medians (interquartile range, IQR)

Abbreviations: CI, cardiac index; SVC, superior vena cava blood; IVC, inferior vena cava blood; Mpap, mean pulmonary artery pressure; PCWP, pulmonary capillary wedge pressure; TPG, transpulmonary gradient; PVRi, pulmonary arterial vascular resistance index EDP, end-diastolic pressure.

Results

A total of 34 patients with PB were included.

Patients with SVHD

Twenty-four patients (14 [58.3%] male) with PB and SVHD underwent staged single ventricle palliation. Median age (interquartile range, IQR) at the time of first PB onset was 5.5 (9.0) years. PB arose 3 days to 15 years after Fontan in 18 patients with a lateral tunnel Fontan and 4 patients with an extra-cardiac conduit. Plastic bronchitis arose in 1 patient 2 years after hemi-Fontan and in 1 patient several days after Fontan takedown to a superior cavopulmonary anastomosis. Congenital heart disease diagnoses are described in Table 1. Five patients had heterotaxy syndrome including 4 with asplenia. Fifteen patients had a history of chylous effusions and 3 had protein-losing enteropathy (PLE).

Table 1.

24 cases of plastic bronchitis with single ventricle heart disease (SVHD).

No.	Sex	Weight at 1st PB	Body surface (kg/m2) at 1st PB	Type of heart disease	Other medical history	Asthma	Age at Fontan (years)	Systemic ventricular systolic function	Systemic AVVR	Staged palliation at diagnosis of PB/Patent Fenestration	Time from Fontan to 1st PB	Chylous effusion/PLE#	Frequency of PB episode	Duration of PB episodes
C1	M	11.7	0.53	{S,D,S}*, HLHS(MS/AS)	FFT, medical NEC, left vocal cord paralysis, reflux	No	2.7	Normal	Moderate	LT fenestrated Fontan/NA	0.88 yrs	+/NA	10 per year	3 yrs
C2	F	45.4	1.27	{S,D,S}, HLHS	Tunner syndrome, portal HTN, esophageal varices, PPM	No	3.0	Mildly depressed	Moderate	LT fenestrated Fontan/NA	15.0 yrs	−/NA	Unclear	Unclear
C3	M	17.0	NA	{S,D,S}, HLHS(MS/AS)	No	No	1.7	Normal	Mild	EC fenestrated Fontan/No	0.89 yrs	+/NA	NA (developed from fenestration closure; resolved after OHT)	1 yrs
C4	M	66.1	1.69	{S,D,D}, DORV	SND, PPM, Atrial flutter	No	2.4	Normal	Mild	LT fenestrated Fontan/NA	9.63 yrs	−/NA	Unclear (resolved after Fontan takedown to Biventricle repair)	3 yrs
C5	M	30.2	1.08	{S,D,S}, HLHS(MS/AS)	No	No	2.6	Unknown	Unknown	LT fenestrated Fontan/NA	10.08 yrs	−/NA	1	Unclear
C6	M	19.1	0.91	{S,D,S}, HLHS(MA/AA)	No	No	1.8	Normal	Mild	LT fenestrated Fontan/NA	4.28 yrs	+/NA	Intermittent episodes	5 ms
C7	F	14.0	0.55	{S,L,A}, DILV, TGA	Heterotaxy with polysplenia; PPM; ECMO and Berlin Heart bridge to OHT	No	0.6	Severely depressed	Mild	Bilateral bidirectional Glenn	1.86 yrs	−/NA	Only noted on first bronchoscopy (resolved after OHT)	No further episodes
C8	F	63.1	1.56	{S,D,D}, DILV, D-TGA, IAA	L mainstem bronchial compression due to LPA stent, mild liver cirrhosis, cardioembolic stroke	Yes	1.5 (1st); 6.9 (2nd)	Normal	Mild	LT fenestrated Fontan (2nd)/NA	7.60 yrs	+/PLE	Unclear	4 yrs
C9	F	12.4	0.49	{S,D,S}, HLHS(MS/AS)	Fontan failure, ascites, hepatomegaly	No	3.0	Unknown	Unknown	LT fenestrated Fontan/NA	Unknown	+/NA	Unclear	2 yrs
C10	F	12.0	0.52	{S,D,S}, HLHS	SND s/p PPM, CVA	No	2.6	Unknown	Unknown	BDG	Unknown	+/NA	3 (resolved after LPA stenting placed)	1 yrs
C11	M	36.8	1.21	{I,D,S}, single LV	seizure, DD, heterotaxy syndrome with asplenia	No	6.9	Normal	Mild	EC fenestrated Fontan/Yes	4.34 yrs	−/−	10 casts per day	6 ms
C12	M	23.8	0.88	{S,D,D}, TGA, VSD, PS, hypoplastic LV	chronic effusions s/p pleurodesis, constrictive pericarditis	No	3.5	Normal	Mild	EC fenestrated Fontan/Yes	6.41 yrs	+/−	Only noted on first bronchoscopy	3 ms
C13	M	30.0	1.08	{S,D,D}, DORV, hypoplastic MV/LV	Sinus dysfunction, PPM	No	2.2	Normal	Mild	LT fenestrated Fontan/No	9.87 yrs	−/−	Unclear	5 yrs
C14	F	17.8	0.71	{S,D,S}, HLHS (MS/AS)		No	2.7	Normal	Mild	LT fenestrated Fontan/No	2.36 yrs	−/−	6 (developed following fenestration closure; improvement after refenestration	6 ms
C15	M	12.8	0.58	{S,D,S}, HLHS (MS/AA)	Recurrent pleural effusions, FTT	Yes	3.5	Normal	Good	LT fenestrated Fontan/No	1.86 yrs	+/−	1 (lasted for 1 ms)	1 ms
C16	F	16.0	0.67	{S,D,S}, HLHS (MS/AA)		NA	2.3	Unknown	Unknown	LT fenestrated Fontan/Yes	3.25 yrs	+/No	Unclear	10ms
C17	M	21.1	0.83	{S,D,S}, HLHS (MS/AA)	Recurrent pleural effusions; LPA stenosis s/p stent	No	3.7	Normal	Mild	LT fenestrated Fontan/Yes	1.72 yrs	+/No	Only noted expectoration of cast in clinic	No further episodes after thoracic duct ligation
C18	M	12.6	0.59	{S,D,S}, PAIVS, pulmonary vein stenosis, single RV	Highly sensitized	No	4.1	Normal	None	LT fenestrated Fontan/Yes	0.06 yrs	+/No	2 episodes	3 wks., lost follow-up
C19	F	10.2	0.47	{S,D,D} RdAVC, pulmonary vein stenosis, single RV	Heterotaxy syndrome with asplenia, FFT,	No	2.7	Unknown	Unknown	BGD+LBTS (Fontan takedown 6 ms after LT fenestrated Fontan/No	0.01 yrs	+/No	Unclear	6 ms (improvement of Fontan takedown)
C20	M	15.2	0.58	{S,D,S}, HLHS (MS/AA)	HIE	No	2.3	Normal	Good	LT fenestrated Fontan/Yes	0.01 yrs	−/−	1	During Fontan hospitalization
C21	F	NA		{A,D,D}, DORV, CAVC,PS, Single RV	Heterotaxy syndrome with asplenia; Recurrent pleural effusions; (7 mo, left sided BDG and TAPVC repair; 1 y revised TAVPVC)	No	4.0	Unknown	Unknown	BDG	Unknown	+/+	Single episode after revised TAPVC repair (prior to Fontan) (resolved with tPA)	No further episodes
C22	F	14.5	0.61	{A,D,D}, RdAVC, Hypoplastic LV	Heterotaxy syndrome with asplenia; arrhythmia	No	2.64 yrs	Moderately depressed	Moderate	LT fenestrated Fontan/No	1.48 yrs	NA/−	Unclear	2–3 ms
C23	M	NA		DORV, hypoplastic LV, PS		No	6.57 yrs	Unknown	Unknown	Fontan	8.33 yrs	NA/−	Daily	Lost to follow-up after discharge
C24	M	47.5	1.42	HLHS (MS/AS)	Recurrent pleural effusions	No	3.91 yrs	Normal	Mild	Fontan	8.29 yrs	NA/−	Daily	Resolved 2–3 wks. post thoracic duct embolization, then recurred 2 mo post embolization; Lost to follow-up

Abbreviations: PB, plastic bronchitis; AVVR, systemic atrioventricular valve regurgitation; PLE, protein-losing enteropathy; HLHS, hypoplastic left heart syndrome; MS, mitral stenosis; MA, mitral stenosis; FFT, failure of thrive; NEC, necrotizing enterocolitis; HTN, hypertension; PPM, permanent pacemaker; LT, lateral tunnel fenestrated; EC, extracardiac conduit; SND, sinus node dysfunction; DILV, double inlet left ventricle; TGA, transposition of the great arteries; OHT, orthotropic heart transplantation; IAA, interrupted aortic arch; CVA, cerebrovascular disease; DD, developmental disability; LV, left ventricle; VSD, ventricular septal defect; PS, pulmonary stenosis; PAVIS, pulmonary atresia with intact ventricular septum; RdAVC, right descending artery venous connection; BGD, bidirectional Glenn; LBTS, left Blalock-Taussig shunt; HIE, hypoxic-ischemic encephalopathy; DORV, double outlet right ventricle; CAVC, complete atrioventricular canal; NA, not applicable; wks, weeks; ms, months; yrs, years.

^*: Anatomic classification in Van Praagh’s 1976 classification.

^#: Patients with chylous effusion or PLE(+);Patients without chylous effusion or PLE(−);

Echocardiograms from initial PB hospitalization were available in 17 patients. Most patients (n=14, 82%) had good systemic ventricular function, 1 patient each had severe, moderate, and mild systemic ventricular dysfunction. Eleven patients (55%) had mild systemic atrioventricular valve regurgitation (AVVR), 5 (25%) had no AVVR, and 4 (20%) had moderate AVVR. One patient had comorbid asthma. Fourteen (58.3%) patients had a history of chylous effusion and 2 (8.3%) had PLE (Table 1). 20 patients had a cardiac catheterization procedure performed a median of 4 days (IQR: 44.25) from their first PB episode. Hemodynamic data from those catheterization procedures are shown in Table 2.

Among SVHD patients, signs/symptoms at the time of PB presentation were desaturation or hypoxia (n=24, 100%), cough productive of casts (n=21, 88%), respiratory distress or dyspnea (n=12, 50%), wheezing (n=1, 4%), and respiratory failure or mechanical ventilation (n=3, 13%) or tracheostomy (n=1, 4%) requirement. Life-threatening respiratory problems were encountered in 6 patients (25%). Additionally, PB presented with increased work of breathing (WOB) in 2 patients (8%), a finding of casts on bronchoscopy for pulmonary hemorrhage while being treated with extracorporeal membrane oxygenation (ECMO) in 1 patient (4%), upper respiratory infection in 5 patients (25%), and recurrent pneumonia (PNA) in 2 patients (8%).

Nineteen SVHD patients had chest computed tomography (CT) scans or X-ray available. Findings included atelectasis (unilateral [n=6, 31.6%], bibasilar subsegment [n=1, 5.3%] and both side lobes [n=2, 10.5%]), segmental opacification (unilateral [n=2, 10.5%], the lung bases [n=1, 5.3%]), pulmonary edema (n=3, 15.8%), lung collapse (n=2, 10.5%), or an absence of atelectasis or collapse (n=2, 10.5%). These variable radiologic findings were detected without diagnostic significance specific to PB. Lymphoscintigraphy was performed in 3 patients who showed abnormality of lymphatic drainage in the mid-chest region in 1 patient and an occluded TD in 2 patients.

Diagnosis was made based on clinical presentation (n=20, 83.3%), bronchoscopy (n=7, 29.2%), and pathology of casts (n=13, 54.2%). Pathologic assessment of bronchoscopy specimens or expectorated casts demonstrated that the cases were composed of fibrin and/or mucin and occasionally mixed inflammatory cells (mainly lymphocytes). Twenty-two patients (91.7%) required at least one hospital admission for treatment of their PB episodes. Treatment methods are described in Table 3.

Table 3.

Treatment methods for SVHD and non-SVHD PB patients.

Treatment Modality	Percentage of SVHD Patients Treated	Percentage of Non-SVHD Patients Treated
Bronchoscopy for cast removal	25%	91%
Chest physiotherapy	92%	45%
Albuterol	79%	73%
Inhaled steroids	75%	18%
Nebulized hypertonic saline	29%	9%
Nebulized heparin	8%	55%
Nebulized tPA	33%	9%
Inhaled Dornase Alfa	54%	9%
Antibiotics	46%	45%
Systemic steroids	13%	45%
Lymphatic embolization	8%	45%

Four patients underwent catheter-based or surgical interventions to relieve hemodynamically significant or otherwise significant lesions that could explain the PB. PB resolved in 1 patient (C4) after Fontan takedown to biventricular repair, in 1 patient (C10) after left pulmonary artery stent was placed, and in 1 patient (C21) after revision of total anomalous pulmonary venous connection (TAPVC) repair and tPA treatment. One patient (C14) had significant improvement after creation of a new fenestration between the Fontan baffle and systemic atrium. Frequency and duration of PB episodes ranged from a single episode to 10 times per year for 3 years. The median (IQR) length of follow-up was 3 years (4.2) in SVHD patients. Eleven patients (45.8%) had no further episodes of casts after treatment. Four patients underwent orthotopic heart transplantation (OHT) between 2 and 10 months after development of first PB symptoms. Of these, 1 patient died 4 weeks after OHT. Eight patients are primarily followed at an outside hospital (n=8, 28.6%) and 6 (21.4%) were lost to follow-up.

Patients associated with respiratory disorders

Nine patients (5 [55.6%] male, median [IQR] 6.0 [4.4] years) presented with PB in association with respiratory disorders (Table 4). Of these, 4 patients had asthma (1 patient also had eosinophilic esophagitis, G6PD deficiency, and adrenal insufficiency), 2 patients had both asthma and PNA, 2 patients had PNA alone, and 1 patient had Sickle cell acute chest syndrome (SCACS). Presenting signs/symptoms included cough productive of casts (n=6, 66.7%), wheezing (n=4, 44.4%), respiratory distress or dyspnea (n=6, 66.7%), desaturation or hypoxia (n=6, 66.7%), and need for mechanical ventilation (n=3, 33.3%). Additionally, 1 patient had eosinophilic PNA and 1 had acute respiratory distress syndrome (ARDS) requiring ECMO. Another patient developed methicillin-resistant Staphylococcus aureus (MRSA) PNA and required ECMO during hospitalization. Two-thirds (n=6) patients had a chest CT/X-ray, and imaging revealed atelectasis (unilateral [n=4 44.4%], bibasilar multifocal lung [n=1, 11.1%]), segmental opacification (unilateral [n=1, 11.1%]), and/or hyperinflation of the right lung (n=1, 15.8%) were observed in these patients.

Table 4.

Patient demographics 10 patients with plastic bronchitis related to pulmonary disease or other diseases.

No.	Gender	Age at PB diagnosis, years	Significant medical history with diagnosis of PB	Other medical history
P1	F	4.47	Asthma exacerbation	Eczema
P2	M	7.84	Severe persistent asthma and RSV infection	Allergy to eggs; EE; seasonal allergic rhinitis; GERD; G6PD deficiency anemia; adrenal insufficiency.
P3	M	2.54	Asthma/Reactive airway disease	NA
P4	M	1.45	Asthma exacerbation	Eczema; food allergies.
P5	F	5.95	Asthma or allergies	Ehlers-Danlos syndromes; Constipation and nausea; possible fibromyalgia; Status post appendectomy 3 months prior to PB; A probable diagnosis of hypermobility
P6	M	13.57	Mild asthma, acute respiratory failure	AS, autism, no CHD
P7	F	4.94	Acute onset of respiratory, MRSA necrotizing pneumonia	Speech delay; No history of previous of pneumonias; no recurrent infections.
P8	M	7.89	Streptococcus and staphylococcus viridians pneumonia; H influenza	Stevens-Johnson syndrome; bronchiectasis; no allergies except for macrolides
P9	F	7.53	Sickle cell anemia, acute chest syndrome, acute crisis	Sickle cell anemia; no asthma; no CHD
P10	M	7.91	1st:asthma exacerbation, PPS; 2nd:respiratory distress secondary to an H1N1 pneumonia, PPS; 3rd: PPS, half systemic pressures in pulmonary arteries, branch PAS, absent RSVC with LSVC feeding into CS	Alagille syndrome; PPS; CHD; Chronic cholestasis; AS with environmental exposure; Lung transplantation

Abbreviations: PB, plastic bronchitis; RSV, respiratory syncytial virus; EE, eosinophilic esophagitis; CHD, congenital heart disease; MRSA, methicillin-resistant staphylococcus aureus; PPS, peripheral pulmonary stenosis; PAS, pulmonary atresia stenosis; RSVC, right superior vena cava; LSVC, left superior vena cava; CS, coronary sinus; NA, not applicable.

Patients were diagnosed with PB based on clinical presentation (n=7, 77.8%), bronchoscopy findings (n=7, 77.8%), and pathology of casts (n=3, 33.3%). Eosinophilic casts with degradation products (Charcot-Leyden crystals) were observed in 2 patients associated with asthma only, and an inflammatory cast composed of predominately eosinophils, neutrophils, and lymphocytes was observed in 1 patient with both asthma and PNA. Eight (88.9%) patients required hospital admission for their treatment.

Treatment is described in Table 3. The median (IQR) length of follow-up was 6.1 (5.3) years in patients with asthma. Five patients with severe asthma had no subsequent episodes of PB and were discharged home on asthma therapy. One patient with PNA was discharged home on a steroid taper and did not have any subsequent episodes of PB. One patient with PNA (P8) maintained a chronic cough with signs of exacerbations within 8.4 months of follow-up. One patient (P7) with MRSA-necrotizing PNA and PB failed weaning from ECMO and died from profuse pulmonary hemorrhage, bilateral lung necrosis, and renal failure. One patient with SCACS was weaned from mechanical ventilation and had no further production of casts in 4.4 years of follow-up.

A patient with no underlying disease

A one-year-old male with PB without significant medical history developed increased WOB and respiratory distress with desaturation (Table 4). An X-ray was obtained which revealed a pneumomediastinum and collapse of the left lung. A large left bronchial tree cast and a left mainstem bronchus laceration were observed under rigid bronchoscopy. The patient remained intubated for ten days to allow the laceration to heal. Numerous eosinophils and fibrin encasing necroinflammatory debris were reported in two pathologic assessments of his casts. A course of antibiotics (Ampicillin/Sulbactam, Azithromycin, and Vancomycin) and oral steroids was completed and inhaled corticosteroids (Flovent) were continued through the winter given the remote possibility of asthma. He was also prescribed an albuterol inhaler to use if symptoms of wheezing, shortness of breath, or cough arose. The patient was followed up for 2.8 years without recurrence.

Discussion

The true prevalence of PB is unknown, as it is likely that many patients with mild forms of the disease are undiagnosed.^7,8 Many clinicians are unfamiliar with the disease and may fail to recognize milder forms of the syndrome. Much of the literature regarding PB and cast types consists of case reports or small case series.^6–12 To our knowledge, the present study includes the largest number of patients with PB.

The literature reports a slight male predominance in all categories except asthma and other allergic causes,^7,13 where females predominate in one report.¹⁴ However, we found a slight male predominance in single ventricle patients and an equal number of males and females in patients with respiratory diseases.

Many cases of PB have been associated with increased systemic venous pressures resulting from SVHD and corrective surgical procedures.⁵ Patients with SVHD are at the greatest risk of PB-related death,⁴ and in roughly half of all SVHD patients with PB, PB will be a chronic disease. Corrective procedures for SVHD result in significant elevation of the central venous pressure (CVP) and subsequent anatomic changes in the lymphatic system, such as TD dilation due to lymphatic congestion.¹⁵ Formation of thrombus in the innominate vein can also impede thoracic duct drainage resulting in lymphatic changes. A break in mucosal integrity and injury to the alveolar-capillary barrier can cause abnormal perfusion of the bronchial submucosa with lymph and slow seepage of lymph proteins into the bronchial lumen,² which likely contribute to the formation of casts. Once in the airway, the proteins dry and denature, solidifying the cast. Data from catheterization closest to first PB episode (Table 2) showed some evidence of systemic venous hypertension. However, not all patients with elevated central venous pressures develop PB and discriminating risk factors have not been identified.

Previous research describes PB arising in patients with respiratory disorders, including severe asthma/allergies, viral respiratory infection, cystic fibrosis, and SCACS, which is consistent with our patient population. These comorbidities suggest that bronchial mucosal inflammation may affect lymphatic permeability and contribute to cast formation. Increase of the lymphatic flow due to elevated CVP is known as a precipitant of PB as well. The onset of the clinical symptoms can be provoked by increased pressure that results in severe respiratory infection and production of eosinophilic casts. Casts often improve after treatment for asthma or atopy. One patient in our cohort did not have an underlying disease; previous literature has suggested that this is the case in roughly one third of children with PB.⁴

The clinical presentation of PB varies, with dyspnea, wheezing, and desaturation as common manifestations. A classically reported symptom is the sound of a “flag snapping” on physical examination. This is thought to be caused by the sound of the mucus plug hitting the airway wall.¹⁶ However, it is rarely heard and a more common finding may be diminished breath sounds. In our study, chest radiographs showed atelectasis, opacification, and collapse of the involved lung segment with compensatory hyperinflation, while other studies have reported patients with bilateral patchy consolidations without evidence of volume loss.¹⁰ Radiologic findings (Figure 1) are generally nonspecific, meaning that diagnosis of PB must be confirmed by observation of casts (Figure 2).

Figure 1.

Cast of the left bronchial tree removed from the left mainstem bronchus using forceps.

Figure 2.

Computed tomography (CT) image of the chest showing complete opacification of the left bronchial tree with low-density material along the airways and distal air space, resolving pneumomediastinum, multifocal atelectasis of the right lung, and small bilateral pleural effusions. These findings suggest a diagnosis of plastic bronchitis with an air leak.

Type of casts observed vary based on the underlying disease process. The 13 casts observed in SVHD patients were described as acellular and predominantly mucin or fibrin. However, recent studies have suggested that pulmonary lymphatic disorders play a role in cast formation, as casts containing chyle have been observed alongside SVHD.¹⁷ Casts associated with asthma/atopy are usually described as ‘inflammatory’ with abundant eosinophils and Charcot–Leyden crystals in a fibrinous background, which is consistent with our findings. Pathologic assessment of the cast was not performed in the patient with SCACS. However, previous reports have described fibrinous PB casts to be associated with SCACS as surrounded by a thin, bright yellow fluid similar to bilirubin in appearance containing pigmented histiocytes.³ Thirty-seven percent of the bronchial lavage fluids from SCACS patients were positive for lipid-laden macrophages as well.¹⁸

Based on dilated lymphatic vessels observed in lung biopsies and the abnormal lung tracer intake shown by lymphoscintigraphy in patients with PB, lymphatic abnormalities are thought to play a role in the disease process. Lymph normally flows in a central direction and is regulated by the presence of valves. Incompetence of these lymphatic valves or a mechanical disruption of the TD can lead to abnormal flow patterns^19,14 This has been observed in patients with SVHD and PB who present for lymphatic imaging.²⁰ In our series, 1 patient had a lymphatic drainage abnormality in the mid-chest region and another 2 had occluded TDs based on lymphangiographic findings. Lymphatic imaging was key in delineating lymphatic anatomy, lymphatic flow, and planning for treatment.

Treatments for PB include a combination of pharmacologic, nonpharmacologic, and surgical treatment options. Chest physiotherapy (used in 92% of SVHD patients and 45% of non-SVHD patients) and/or bronchoscopy for cast removal (25% of SVHD patients, 91% of non-SVHD patients) are among the most utilized treatment modalities. There is a notable difference in the rate of bronchoscopy between SVHD and non-SVHD patients, which can likely be attributed to the difference in illness severity between these groups. Critically ill SVHD patients with decreased pulmonary reserve may not be candidates for invasive procedures. Endoscopic removal of casts may be complicated by tenacious consistency and friability of plugs, but careful use of optical forceps with rigid suction aids effective cast removal. Due to the difficulties of curing cast formation, many patients who do not respond to medical treatment will require serial rigid bronchoscopy if they develop profound airway obstruction.

Inhaled steroids were used in 75% of SVHD patients compared to 18% of non-SVHD patients, while systemic steroids were preferred in non-SVHD patients (SVHD: 13%, non-SVHD: 45%). Half of the patients with asthma-associated PB in our cohort improved following treatment with systemic steroids and 1 patient with idiopathic PB was treated successfully with both nebulized and oral steroids. It has been postulated in existing research that effectiveness of steroids in the treatment of PB may be due to the anti-inflammatory effects of corticosteroid on infiltrating eosinophils.¹²

Previous reports suggest that tPA can improve PB through fibrin depolymerization. Thirty-three percent of SVHD patients and 9% of non-SVHD patients in our cohort received inhaled tPA. Casts dissolved best with an initial dose of 5 mg every 4 hours and subsequently every 12 hours. However, tPA may irritate the airway, result in hemoptysis or dyspnea after inhalation, and is expensive. While there are hemostasis-related concerns with the use of tPA,⁷ none of our patients had any bleeding complications. Heparin has no effect on fibrin-containing casts, but its anti-inflammatory properties may decrease mucin secretion. Over half of our asthma and/or PNA cohort was treated with nebulized heparin, compared to only 8% of SVHD patients. Heparin is less irritating to the airway and less expensive than tPA. Based on our findings, tPA may be more effective on SVHD-related fibrin casts while heparin is better for mucin casts in non-SVHD patients. Nebulized hypertonic saline was used in 29% of SVHD patients and 9% of non-SVHD patients without much success.

Pulmonary vasodilators, such as sildenafil, may increase cardiac output by decreasing pulmonary vascular resistance and augmenting ventricular filling⁹, perhaps reducing PB recurrence. In SVHD patients, 44% were treated with Sildenafil. However, this approach is empiric and cannot be recommended based on the available data.⁷ Cardiac output may also be improved with surgical attempts to optimize Fontan physiology in SVHD patients.²¹ In our study, PB symptoms improved after refenestration (n=1), Fontan takedown (n=2), and revised TAPVC repair (n=1). Three patients had resolution of PB symptoms after OHT.

In patients with lymphatic abnormalities, PB may be treated with MRI-guided selective lymphatic embolization.²⁰ Thoracic duct ligation has been performed with reports of symptomatic improvement.^22,6 In our cohort, 2 patients underwent TD ligation with initial resolution of symptoms, but PB recurred in one. Selective lymphatic collateral embolization offers some advantages over other surgical treatments, including maintenance of TD patency and treatment specific to pathologic lymphatic vessels.

While a broad variety of therapies are utilized to treat PB, none are universally employed. Optimal therapies for this disease are still being identified and developed. This study reports the use of bronchoscopy for cast removal, but different methods may be utilized at other institutions. Emerging techniques for cast removal, such as cryoadhesion and cryoextraction, have been reported to be useful in patients with tracheobronchial obstructions.^23,24 In the future of PB treatment, emerging technologies should also be considered.

This study shares many limitations of retrospective case series. Only treatments and adverse events recorded in the medical record could be reported. Risk factors for the development of PB could not be identified as an appropriate control group without PB could not be identified. That being said, our clinical experience suggests that individuals with similar filling pressures, cardiac anatomy, and other perceived risk factors may range from no PB symptoms to the development of chronic, unremitting casts.

Conclusion

Optimal therapies for PB remain limited, with treatment varying on a case-by-case basis. Airway clearance using standard chest physiotherapy and/or bronchoscopy is one of the most-utilized therapies in the treatment of PB. Selective lymphatic embolization at centers with appropriate interventional expertise offers a potential new treatment option for patients with PB.