Eosinophilic plastic bronchitis: Case series and review of the literature

Abstract

Plastic bronchitis is a term used to describe group of life-threatening disorders characterized by the presence of large obstructing casts in the airways. Eosinophilic plastic bronchitis is a subtype of plastic bronchitis that occurs mainly in children and has not been well-described in the literature. Patients may have a history of asthma or atopy, but many do not. They often present with cough and wheezing, and frequently have complete collapse of one lung seen on imaging. The severity of presentation varies depending on the location of the casts, ranging from mild symptoms to severe airway obstruction and death. Bronchoscopy is often required to both diagnose and treat this condition. A variety of medical therapies have been used, although no formal studies have evaluated their efficacy. Symptoms may resolve after initial cast removal, but in some patients, cast formation recurs. Here, we report a case series of nine patients with eosinophilic plastic bronchitis and review the existing literature of this condition.

1 |. INTRODUCTION

Plastic bronchitis is a general term that refers to a group of likely different disorders that are characterized by the presence of large casts occupying one or more airways. This phenomenon was first recognized hundreds of years ago and has been described by different names since that time, including cast bronchitis, fibrinous bronchitis, and Hoffman’s bronchitis.¹ Several classification schemes have been proposed for plastic bronchitis. In 1997, based on nine cases of plastic bronchitis, Seear et al.² suggested separating bronchial casts into two groups: Type I inflammatory casts, composed of fibrin and eosinophils, and Type II acellular casts composed of mucin in children with congenital heart disease (CHD). A more detailed classification was provided by Madsen et al. in 2005, based on both the underlying disorder and histology of the bronchial casts.¹ Based on advancements in lymphatic imaging, plastic bronchitis can now be classified as either lymphatic or eosinophilic.³ For a comprehensive overview of the different types of plastic bronchitis, the reader is referred to the paper by Madsen et al. In children, the most common form of plastic bronchitis is associated with CHD, particularly in those with a surgically-created shunt connecting systemic and pulmonary blood flow.^1,4 Eosinophilic plastic bronchitis has only been described in case reports and small case series,’ and our understanding of this rare condition is limited. Here, we report nine cases of eosinophilic plastic bronchitis and review the existing literature regarding presentation, diagnosis, and management.

2 |. METHODS

This is a retrospective chart review of nine pediatric cases with eosinophilic plastic bronchitis. Eight patients were seen at the Children’s Hospital of Philadelphia (CHOP) and one patient was seen at Cincinnati Children’s Hospital. This case series was submitted to the CHOP Institutional Review Board and was determined to meet exemption criteria.

2.1 |. Case series

Patient characteristics are summarized in Table 1.

TABLE 1.

Demographics, clinical characteristics, evaluation, and treatment information for the patient cohort.

Patientcharacteristics	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5	Patient 6	Patient 7	Patient 8	Patient 9
Age at diagnosis	4 years	8 months	12 years	22 months	6 years	16 months	8 years	8 years	11 years
Sex	Female	Female	Male	Male	Male	Female	Male	Female	Female
Past medical history
Asthma/wheezing	+	−	−	+	−	+	−	+	+
Allergic rhinitis	+	−	−	−	−	−	+	+	+
Eczema	+	−	−	+	−	−	+	+	−
Signs and symptoms
Cough	+	+	+	+	+	+	+	+	+
Fever	−	−	−	−	+	−	−	+	+
Dyspnea	−	−	−	−	+	−	+	+	+
Decreased breath sounds	+	−	+	+	−	+	+	+	+
Serum studiesa
WBC (K/μL)	6.1	35.0	11.2	17.4	11.6	9.8	-	15.0	7.2
Neutrophils (%)	14.8	91.4	68.1	31.3	-	73.6	-	69.5	53.0
Lymphocytes (%)	64.3	5.3	22.9	57.4	-	17.4	-	17.4	28.5
Eosinophils (%)	8.7	0.9	1.8	6.1	-	0.2	-	3.1	7.4
IgE (IU/mL)	9.0	33	42	1570	-	-	-	177	275
BAL studies
WBC, BF (/μL)	200	1350	275	-	244	1975	-	1590	725
RBC, BF (/μL)	125	14,400	1775	-	19,750	400	-	-	7325
Neutrophils, BF (%)	6	80	5	-	53	38	-	69	71
Lymphocytes, BF (%)	12	6	41	-	14	6	-	1	6
Eosinophils, BF (%)	63	0	12	-	19	32	-	6	2
Macrophages, BF (%)	8	5	39	-	7	-	-	7	18
Endobronchial biopsy	Yes	No	Yes	No	Yes	No	No	No	No
Treatment
Inhaled steroid	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Systemic steroid	No	No	No	Yes	Yes	Yes	Yes	Yes	Yes
Outcome at last follow‐up	Resolution of symptoms	Lost to follow‐up	Symptom recurrence	Resolution of symptoms	Symptom recurrence	Resolution of symptoms	Resolution of symptoms	Symptom recurrence	Symptom recurrence

Abbreviations: BAL, bronchoalveolar lavage; BF, body fluid; HGB, hemoglobin; IgE, immunoglobulin E; RBC, red blood cell; WBC, white blood cell.

^aSerum studies listed were those obtained at the time of initial presentation. If none were performed at that time, studies that were obtained afterwards are listed. Several patients had received systemic corticosteroids before blood was drawn for these labs.

2.2 |. Patient 1

A 4-year-old female with a history of allergic rhinitis and wheezing presented with a chronic, wet cough for 9 months. She had decreased left-sided breath sounds on physical examination. Treatment with antibiotics resulted in modest improvement in symptoms that recurred following antibiotic completion. She expectorated a bronchial cast which resulted in symptomatic improvement. Histopathology of the cast showed fibrinoid material with patchy eosinophils and Charcot–Leyden crystals. Flexible bronchoscopy revealed no visible bronchial casts, although there was pulmonary eosinophilia (25%). Endobronchial biopsy demonstrated eosinophilic infiltration of the epithelium and subjacent stroma (Figure 1). The patient was subsequently treated with high-dose inhaled corticosteroids (ICS). Her symptoms have not recurred.

FIGURE 1.

Endobronchial biopsy from Patient 1. Pathology reveals subepithelial eosinophils (*) and few scattered eosinophils in the overlying epithelium (arrow).

2.3 |. Patient 2

An 8-month-old previously healthy female presented in cardiorespiratory arrest of unknown etiology. She was asymptomatic before the event. Cardiopulmonary resuscitation was performed for 15 min, and she was admitted to the intensive care unit. Due to persistent difficulties with ventilation, rigid bronchoscopy was performed which revealed a large mucus cast in the distal trachea with improved ventilation following removal. Chest computed tomography (CT) demonstrated hazy ground glass opacities throughout the right upper lobe with more focal consolidation in the right lower lobe. Flexible bronchoscopy revealed large, soft bronchial casts in the right lower lobe bronchi, which were removed. Histopathology review of a cast showed necrotic cells, eosinophils, fibrinoid material, and Charcot–Leyden crystals. She gradually improved and was discharged home with a prescription for low-dose ICS, which were discontinued 1 month later at her follow-up appointment. A follow-up chest X-ray was normal. The patient was lost to follow-up.

2.4 |. Patient 3

A 12-year-old previously healthy male presented with a productive cough of 3 months duration. He had previously been treated with ICS and several courses of antibiotics by his pediatrician without improvement. Physical exam was significant for decreased left-sided breath sounds. Pulmonary function testing showed a moderate obstructive defect. A chest CT demonstrated a left hilar density with mass effect on the left lower lobe bronchus. The patient underwent flexible bronchoscopy, and a large occlusive cast was removed from the left lower lobe with subsequent resolution of his symptoms and radiographic abnormalities. Histopathology revealed necro-inflammatory tissue fragments with eosinophilic Charcot–Leyden crystals in a fibrinoid background. Lung function testing continued to show an obstructive defect with no bronchodilator response. Low-dose ICS were prescribed. Methacholine challenge was negative for bronchial hyperreactivity. Due to symptom recurrence, repeat bronchoscopy was performed and several casts were removed from the left upper and lower lobes, and endobronchial biopsies were taken. Surgical pathology showed a mixed inflammatory infiltrate of lymphocytes with admixed eosinophils and neutrophils. His symptoms improved and his lung function stabilized, and ICS were discontinued 1 year after their initiation. One year after ICS discontinuation, the patient’s cough recurred, and two bronchoscopies were required to remove more eosinophilic casts. Since then, lung function has improved, and ICS have been continued on an as-needed basis.

2.5 |. Patient 4

A 22-month-old male with a history of eczema presented with 2 months of wet cough and wheezing. Chest CT showed a mass-like opacity occluding the left lower lobe bronchus. Flexible bronchoscopy identified an occluding cast in the left mainstem bronchus, which was removed, but an additional cast in the same lobe was unable to be removed. After treatment with intravenous antibiotics, corticosteroids, and airway clearance, the patient was subsequently transferred to our center. Two flexible bronchoscopies were performed to successfully remove the cast from the left lower lobe bronchus using a combination of a snare basket, cryoprobe, and alligator forceps. Histopathology of the cast showed fibrinoid material with degenerated inflammatory cells, consisting mainly of eosinophils and numerous Charcot–Leyden crystals. High-dose ICS were prescribed but never used. At follow-up 2 months following hospital discharge, symptoms had resolved, and a chest radiograph was normal.

2.6 |. Patient 5

A previously healthy 6-year-old male presented to an outside hospital with fever, abdominal pain, and respiratory distress. A chest radiograph exhibited left lung atelectasis with mediastinal shift and chest CT demonstrated low-density material occluding the left mainstem bronchus. The patient was diagnosed with pneumonia and treated with antibiotics. Due to clinical worsening, he was referred for flexible bronchoscopy during which soft, white casts were identified in the left mainstem bronchus. The casts were composed of fibrinoid material with mixed inflammatory cells including lymphocytes, neutrophils, and eosinophils. The respiratory culture from the BAL was positive for Moraxella catarrhalis. He was prescribed azithromycin, nebulized hypertonic saline, and high-dose ICS. Repeat bronchoscopy was performed 2 months later with additional cast removal. Six months later, magnetic resonance lymphangiogram was completed in conjunction with flexible bronchoscopy and endobronchial biopsy. A large bronchial cast was evacuated from the left lower lobe and lymphangiography was normal. The patient was treated with a short course of oral corticosteroids and instructed to restart ICS. Subsequently, the patient followed up with an outside pulmonologist closer to his home.

2.7 |. Patient 6

A 16-month-old female with a history of wheezing presented to the ED with 1 day of cough and wheezing that did not improve with bronchodilator administration. A chest radiograph demonstrated hyperinflation of the left lung, prompting clinical concern for foreign body aspiration, and she was transferred to our center. Flexible bronchoscopy was performed and revealed several large casts in the left lower lobe and right middle lobe bronchi, which were subsequently removed. BAL fluid was positive for rhinovirus via polymerase chain reaction analysis. Histologic examination of the casts showed proteinaceous and fibrinoid material containing a mixed, predominantly eosinophilic, inflammatory infiltrate with Charcot–Leyden crystals. She was treated with systemic corticosteroids, albuterol, and antibiotics for presumed pneumonia. Before discharge, she was prescribed low-dose ICS. At her most recent follow-up 1.5 years following her initial presentation, she was doing well with no symptom recurrence.

2.8 |. Patient 7

An 8-year-old male with allergic rhinitis and eczema presented with 3 weeks of non-productive cough, chest pain, and dyspnea. On physical exam, there were decreased lung sounds on the left. Chest radiograph showed near complete opacification of the left hemithorax, and chest CT revealed mucus plugging of the left bronchial tree with left lung collapse. Flexible bronchoscopy identified a large white mass in the proximal left mainstem bronchus and similar casts distally. The mass was unable to be removed by either flexible or rigid bronchoscopy; therefore, a biopsy specimen of the mass was obtained and was composed of eosinophils, mucus, fibrinoid material, and Charcot–Leyden crystals. The patient was treated with antibiotics, oral corticosteroids, and low-dose ICS. At follow-up 1 month later, symptoms had resolved. Repeat flexible bronchoscopy 2 months later showed residual casts in the left distal bronchi. Six months later, chest radiograph and lung function testing were normal.

2.9 |. Patient 8

A 9-year-old female with three episodes of left lower lobe pneumonia in the preceding 6 months presented to her pediatrician with fever, cough, and dyspnea. A chest radiograph demonstrated a left lower lobe opacity, and she was treated with oral antibiotics. Symptoms worsened and she presented to the emergency room. A CT chest showed complete collapse of the left lung. A bronchoscopy revealed bronchial casts occupying all large left-sided airways that were removed using cryoextraction and suctioning. Histopathology showed fibrinopurulent and necrotic debris, eosinophils, and Charcot–Leyden crystals. She was treated with oral and inhaled steroids, antibiotics for post-obstructive pneumonia, and chronic azithromycin. Following initial discharge, her symptoms recurred multiple times and more casts were removed during several bronchoscopies. Dupilumab injections were prescribed to treat a presumed underlying eosinophilic inflammatory process. She has bronchiectasis on her most recent CT chest.

2.10 |. Patient 9

An 11-year-old female with asthma and allergic rhinitis presented to the emergency department with cough, fever, chest pain, and dyspnea. She had decreased breath sounds on the left and a chest radiograph demonstrated complete opacification of her left hemithorax (Figure 2). She was treated with antibiotics, nebulized hypertonic saline, and intrapulmonary percussive ventilation for 2 days without improvement in her chest radiograph. Flexible bronchoscopy was then performed and revealed a large, friable cast completely obstructing the left mainstem bronchus (Figure 2) that was removed with cryoextraction. Countless casts were seen distally and were removed with cryoextraction, suction, and forceps. Histopathology of a cast showed fibrinoid material, eosinophils, and Curschmann spirals. Her inhaled steroid dose was increased, and she completed a course of antibiotics and oral steroids. Four months later, a repeat CT chest showed airway obstruction in multiple left-sided airways with peribronchovascular ground glass opacities in the left upper and lower lobes. She periodically expectorated small casts. Her mother reported that she had not been using her prescribed ICS. Bronchial casts were removed during three subsequent bronchoscopies using cryoextraction. An additional bronchoscopy is planned for the near future.

FIGURE 2.

Bronchial cast obstructing the left mainstem bronchus as seen on (A) chest X-ray, (B) CT scan, and (C, D) bronchoscopy.

3 |. DISCUSSION

3.1 |. Eosinophilic plastic bronchitis

Eosinophilic plastic bronchitis (Type I casts in the Seear criteria) has only been described in small case series. However, this condition is likely underestimated and, in some cases, can be fatal. Eosinophilic casts are characterized by a dense fibrinoid background, an abundance of eosinophils, and often, Charcot–Leyden crystals or Curschmann spirals (Figure 3).^1,2,5 Charcot–Leyden crystals are colorless, hexagonal crystals that were first described by Jean-Martin Charcot in 1853, and subsequently by Ernst Victor von Leyden in 1871.⁶ They are a hallmark of eosinophilic inflammation.⁷ In addition to being present in the sputum of those with asthma, Charcot–Leyden crystals are reportedly present in the casts found in eosinophilic plastic bronchitis in the majority of cases.^1,5,8–11 Curschmann spirals, described by Heinrich Curschmann in 1882, are also seen in the sputum of patients with asthma and consist of white or yellow mucus threads bound by fibrils.⁶ In our case series, the casts of one patients had Curschmann spirals, while eight had Charcot–Leyden crystals.

FIGURE 3.

Histopathology of bronchial cast with degenerating eosinophils admixed with Charcot–Leyden crystals.

Eosinophilic plastic bronchitis differs from the lymphatic plastic bronchitis seen in CHD and lymphatic disorders. Dori et al. demonstrated that many patients with single ventricle physiology who undergo palliation surgery develop lymphatic abnormalities that can be seen on MR lymphangiography and treated with percutaneous lymphatic interventional procedures.^12,13 This is primarily seen when a central shunt connecting the systemic to pulmonary vasculature is present, although it can also occur in primary pulmonary lymphatic disorders.¹³ The exact pathophysiologic mechanism by which lymphatic casts form is debated; a genetic predisposition, increased pulmonary venous pressure and low cardiac output, mucus hyper-secretion, and inflammation leading to increased alveolar capillary permeability are all factors that have been hypothesized to play a role.^1,4,14 In addition to percutaneous lymphatic interventional procedures, management may involve pleurodesis to treat chylothorax, minimizing long-chain triglyceride intake to decrease intestinal lymph production, and the use of inhaled medications such as tissue plasminogen activator (TPA), although this has not been rigorously studied in a controlled fashion.^1,13,15

3.2 |. Prevalence

The prevalence of eosinophilic plastic bronchitis is unknown, and only a handful of cases have been reported in the literature. The largest case series consist of four patients.^2,9 In asthma, mucus plugging of airways is common. However, eosinophilic plastic bronchitis represents a different entity.^4,9 Some articles may refer to mucus plugging as “bronchial casts.” For example, Perez-Soler¹⁶ collected gastric fluid from 72 children and sputum from 2 children with “wheezing bronchitis” and reports that “structures compatible with bronchial casts were found in all cases.” These casts were 0.5–2 cm in length, and the majority (65) of these children experienced chronic cough and wheezing for more than 9 months. The author concluded that “a significant number of children classified as a chesty child may be affected by a subacute or chronic type of bronchitis characterized by the formation of bronchial casts.” It is unclear whether this phenomenon represents a milder form of eosinophilic plastic bronchitis with smaller casts, or a different process entirely. Other authors have hypothesized that some children who experience wheezing and cough with respiratory tract infections and are diagnosed with asthma may actually be suffering from small airway obstruction by eosinophilic casts.²

3.3 |. Pathophysiology

The mechanism by which eosinophilic casts form in the airways of affected individuals has not yet been elucidated. At least in some cases, it may be related to acute eosinophilic inflammation, which increases lymphatic permeability, in the setting of asthma.¹⁷ However, a significant proportion of patients with eosinophilic plastic bronchitis do not have asthma, and even aggressive asthma therapy is not helpful in many cases.^5,9,18 While only one of our patients underwent evaluation for lymphatic abnormalities, it is possible that abnormal lymphatic flow plays a role in the pathogenesis of eosinophilic plastic bronchitis. Geanacopoulos et al. analyzed 23 bronchial casts from patients with CHD who underwent percutaneous lymphatic intervention and found that most bronchial casts were composed of a proteinaceous extracellular matrix, the cellular component was predominantly lymphocytic, and the median BAL lymphocyte count was normal.¹⁴ All casts in our case series contained a proteinaceous background, and the predominant inflammatory cell type was eosinophils. The BAL lymphocyte count was less than 15% in all but one patient. Therefore, while the extracellular matrix and BAL lymphocyte counts seen in our cohort are comparable to those seen in children with CHD and lymphatic abnormalities, the predominance of eosinophils in their bronchial casts (as opposed to lymphocytes) points toward a likely different pathophysiology in eosinophilic plastic bronchitis. The degree to which the extracellular component of casts can be analyzed by light microscopy is generally limited to mucinous versus proteinaceous. Densely eosinophilic proteinaceous material forming strands is morphologically similar to fibrin in blood clots, but a distinction between fibrin and other dense proteins cannot be established.

It is unclear whether a preceding respiratory tract infection plays a role in the pathogenesis of eosinophilic casts, although antibiotics are usually not helpful.⁴ In many cases, a recognizable infection has not been reported,⁹ although there has been a described association between severe influenza infection and eosinophilic plastic bronchitis.^10,19 In our case series, likely infections were identified in two patients (rhinovirus and M. catarrhalis). Patients usually present to medical attention when the casts are significant enough to cause entire lung or lobar collapse, and it is possible that cast formation may have started weeks before presentation during a more remote respiratory infection.

According to recent research, Charcot–Leyden crystals are thought to be formed by the process of eosinophilic extracellular trap cell death (EETosis), a cell-death process distinct from apoptosis, and the crystallization of the cytoplasmic protein galectin-10.⁷ Through this process, eosinophil extracellular traps (EETs) and Charcot–Leyden crystals form.^7,20 These EETs consist of filamentous, web-like chromatin, cell debris, and eosinophilic granules, all of which contribute to increasing the thickness and viscosity of eosinophilic secretions.²¹ In one case report of eosinophilic plastic bronchitis in the setting of acute influenza A infection, abundant EETs and eosinophilic granule proteins were found in histopathologic examination of a bronchial cast.¹⁰ Authors hypothesized that that influenza infection triggered EETosis which led to the crystallization of galectin-10, formation of Charcot–Leyden crystals, and ultimately bronchial cast formation. While it is clear that in the majority of cases in which Charcot–Leyden crystals are formed (various allergic, oncologic, and infectious diseases),⁷ no bronchial cast is found, it may be that eosinophilic plastic bronchitis occurs because of an accentuated EETosis that is triggered by an unknown mechanism.

In our case series, an endobronchial biopsy was performed in three patients and demonstrated eosinophilic inflammation (bronchitis). Non-asthmatic eosinophilic bronchitis was first described in 1989 and is defined by the presence of chronic cough with sputum eosinophilia (>2.5%) and no airway hyperresponsiveness.^22–24 This condition is effectively treated by ICS. Bronchial cast formation has not been described in association with eosinophilic bronchitis and although it is likely a different condition than eosinophilic plastic bronchitis, the underlying pathophysiology may be similar in at least a subset of patients.

3.4 |. Clinical presentation

Patients often present with cough, dyspnea, and chest pain. Fever may also be present, and wheezing and decreased breath sounds may be heard on auscultation.^2,9,10,25 In several reported cases, the child had recently failed outpatient management for presumed pneumonia with oral antibiotics.¹⁸ A more dramatic presentation including severe respiratory distress and even cyanosis has also been reported, due to large airway obstruction.⁹ In our case series, one child presented with cardiopulmonary arrest due to presumed airway obstruction, and symptoms improved after the removal of a large cast found at the carina. Some children may have a history of expectorating casts (seen in one patient in our series), that may have been mistaken to be food material by the child’s parents (noodles in one case report, chicken in another).⁹ At the time of presentation to a hospital for evaluation, imaging often shows complete collapse of an entire lung or lobe.^2,9,10,18,25 This was the case in several of our patients. Interestingly, in our case series, eight of nine cases occurred in the left lung. In cases reported in the literature, there also seems to be a predominance of left-sided cases. The left mainstem bronchus is longer and narrower than the right mainstem bronchus, which would predispose it to being obstructed by a cast. However, this would not explain why smaller casts form more distally on the left side more than on the right side. It may be that patients with only small airway casts never present to medical attention and are therefore not mentioned in the literature. In several reported cases, sweat tests were performed and were normal.^2,5,8,25

In 2005, Madsen et al. collected and described 22 cases of eosinophilic plastic bronchitis that had been reported in the literature to that point.¹ Twenty-one patients were aged 15 years or younger. Twelve of these patients had at least one atopic condition. Amongst the 10 patients without reported atopy, eight were younger than 3 years old. Madsen et al. surmise that it is possible that these children may have had an atopic condition such has asthma that had not yet been recognized. Since 2005, at least four other cases of eosinophilic plastic bronchitis (ages 4, 7, 15, and 27 years) in otherwise well patients have been reported.^8,10,11,18 Two of these patients had asthma and the other two had no recognized atopic condition. In our case series, six (67%) had a known atopic condition, and five had a diagnosis of asthma.

When bronchoscopy is performed, eosinophilic bronchial casts appear as white–yellow friable material that is often obstructing a large airway.^5,8,18 Peripheral eosinophilia is often present but may also be absent.^2,9,11,25 Pulmonary eosinophilia (BAL eosinophils >10%) was present in four of seven patients in which a BAL was performed in our case series, while only three patients had serum eosinophils >5%. However, this information is difficult to interpret because several patients had already been treated with systemic and ICS before these lab results.

Three of our patients had endobronchial biopsies performed. In the reported cases in the literature, biopsy was only rarely performed. When performed, lung biopsy has shown infiltrates of eosinophilic and plasma cells, and widespread airway occlusion by fibrin and eosinophilic casts.^2,9 Autopsy of a 17-month-old boy who died from airway obstruction showed diffuse airway occlusion by fibrin casts infiltrated with eosinophils.²

3.5 |. Treatment

There are no prospective studies assessing the efficacy of any therapy for eosinophilic plastic bronchitis. Extraction of large casts via bronchoscopy should always be the first step in management. If medical or mechanical mucus mobilization therapies are used, the physician should be aware that casts may be dislodged proximally toward larger airways, which can result in fatal airway obstruction.¹ For casts seen in the mainstem bronchi, the bronchoscopic technique used (flexible or rigid) will vary based on the experience of each specialty (otolaryngology, pulmonology, pediatric surgery) in a given location. However, in most case reports, casts are present in more distal airways as well, and therefore flexible bronchoscopy is required.^2,8,9,11,18 The specific techniques employed to remove eosinophilic casts using flexible bronchoscopy are not described in detail in most case reports of eosinophilic plastic bronchitis, although individual reports mention the use of forceps¹⁸ and cryoextraction.¹¹

In our experience, the cryoprobe is an invaluable tool in removing eosinophilic bronchial casts. Cryoextraction is a well-described, effective technique to remove material from the tracheobronchial tree, including foreign bodies, blood clots, and mucus plugs.^26,27 This method uses a liquified gas (cryogen) under high pressure, usually nitrous oxide or carbon dioxide, which is delivered through a catheter to the tip of the cryoprobe where it freezes to temperatures as low as −40°C. The cryoprobe adheres tightly to objects that it comes in contact with, especially those with significant water content.²⁸ In the case of eosinophilic plastic bronchitis, using a cryoprobe may be more effective and less time-consuming than using a combination of other tools such as forceps and suction.

Different medical therapies reported in the literature include inhaled and/or systemic corticosteroids, bronchodilators, antibiotics, nebulized hypertonic saline, dornase alpha, nebulized acetylcysteine, inhaled TPA, and mechanical mucus mobilization therapy such as high-frequency chest-wall oscillation.^{1,8,9,11,18,25} All of the patients in our series were treated with inhaled and systemic steroids. It is important to note that none of these therapies have been rigorously studied in a prospective fashion and their evidence is therefore limited to anecdotes and case reports. Although there is some evidence (based on case reports²⁹ and ex vivo studies)³⁰ suggesting that inhaled TPA may be effective in treating lymphatic plastic bronchitis, it has not been well-studied in eosinophilic plastic bronchitis. Furthermore, its prolonged use may cause airway irritation and hemoptysis, and therefore it should be used with caution.³ Schultz et al. describe the case of a teenage boy with eosinophilic plastic bronchitis and ongoing symptoms despite treatment with inhaled steroids, oral steroids, and bronchodilators.⁵ Azithromycin (250 mg three times per week) was prescribed and his symptoms resolved completely, only to return when he became less adherent to the therapy. Symptoms once again disappeared when he restarted Azithromycin and as of the time of the article publication (5 months later), he remained symptom-free. Additionally, his spirometry results normalized. The mechanism of azithromycin’s apparent efficacy in this case is unclear, although authors speculate that its anti-inflammatory properties likely provided the benefit. Systemic steroids likely provide some benefit in certain patients, based on the observation that some patients have improved with the initiation of systemic steroids²⁵ and others have relapsed when oral steroids were weaned.² One patient in our series was prescribed dupilumab, an anti-IL-4 receptor antibody. Utilization of anti-eosinophil biologic medications such as anti-IL-5 (e.g., mepolizumab and benralizumab) and anti-IL-4 receptor (dupilumab) antibodies may be worthwhile in refractory cases of eosinophilic plastic bronchitis.

3.6 |. Prognosis

In the Madsen review of 22 patients with eosinophilic plastic bronchitis,¹ outcomes of 15 patients were reported; several of them resolved after treatment with ICS or antibiotics. However, recurrent disease was also reported, and 3 (14%) of these individuals died from acute airway obstruction. Other cases of recurrence of eosinophilic casts following initial bronchoscopic removal of have been reported.^8,18 Patients may require several bronchoscopies for cast extraction, despite therapy with ICS, antibiotics, and airway clearance therapies.¹⁸ Because casts may be occupying large airways for a long period of time before bronchoscopic removal, patients may develop bronchiectasis.^5,8,9 Two patients in our series had bronchiectasis on follow-up CT scans, although this information was not available for the other patients in our series.

4 |. CONCLUSION

Eosinophilic plastic bronchitis is a subtype of plastic bronchitis that likely differs in its pathogenesis from plastic bronchitis associated with CHD. Therefore, it should be viewed (and reported) as a distinct entity. Although an atopic history is seen in many patients, others have no history of atopy. Patients often present with cough and fever, and therefore this disorder should be considered in the differential diagnosis of unresolving pneumonia. A variety of therapies have been used, although none have been studied in a controlled fashion. The single most important management step is bronchoscopic removal of bronchial casts, and cryoextraction should be strongly considered as a first-line tool. Caution should be exercised in prescribing airway clearance therapy before bronchoscopic removal, as mobilization of casts proximally can lead to life-threatening large airway obstruction. Prognosis is variable, with some patients experiencing only one episode and others having multiple relapses of cast formation.

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.