Chronic eosinophilic pneumonia with endobronchial nodules: a case report

Abstract

Chronic eosinophilic pneumonia (CEP) is a rare, idiopathic condition characterized by pulmonary eosinophilic infiltration and peripheral opacities, typically responsive to corticosteroids. Tracheobronchial involvement is uncommon. We report a 44-year-old male patient presenting with clinical picture consistent with CEP with marked eosinophilia of 2.7 × 10⁹/L. Bronchoscopy showed diffuse endobronchial nodules, which were resolved after steroid treatment. Biopsy confirmed eosinophilic infiltration. The diagnosis of CEP with endobronchial involvement was made. The patient showed rapid clinical and radiological improvement shortly after systemic corticosteroid therapy. However, relapse occurred after steroid tapering consistent with steroid dependent disease necessitating treatment with benralizumab as steroid sparing biologic therapy. This case highlights an unusual manifestation of CEP involving the tracheobronchial mucosa, which may be associated with more symptom burden and relapsing disease course, emphasizing the importance of recognizing airway involvement in eosinophilic lung diseases.

Highlights

• •Chronic eosinophilic pneumonia may rarely present with diffuse endobronchial nodules and Tracheobronchial eosinophilic mucosal involvement.
• •Bronchoscopy with endobronchial biopsy demonstrated marked eosinophilic infiltration without evidence of vasculitis, helping differentiate CEP from other eosinophilic disorders such as EGPA.
• •Tracheobronchial mucosal involvement in CEP may be associated with a more aggressive, relapsing disease course requiring escalation to biologic therapy.

1. Introduction

CEP is characterized by abnormal accumulation of eosinophils within the lungs. In contrast to acute eosinophilic pneumonia (AEP), the onset of symptoms is usually subacute with dyspnea, wheeze and fever, asthma accompanied CEP in up to half of patients [1] CEP is a rare among diffuse parenchymal lung diseases. The incidence of CEP in the general population remains undetermined. However, registry data from patients with interstitial lung diseases (ILD) suggest that CEP accounts for approximately 2.7% of cases in a European registry and 0.5–1.2% in a United States ILD registry [2]. The typical age group is individuals in their 30s to 40s [1]. Diagnostic clues include subacute pulmonary and constitutional symptoms, eosinophilia detected either in peripheral blood of more than 0.5 × 10⁹/L or in Bronchoalveolar lavage (BAL) of more than 25%, although varying eosinophil thresholds have been reported across different studies, characteristic imaging findings and exclusion of other causes of eosinophilia. Chest radiograph shows peripheral and upper lobe infiltrate typically described as “photographic negative” of pulmonary edema. Differential diagnosis of eosinophilic pneumonia (EP) should always be considered, such as drug-induced eosinophilic pneumonia (DEP), Eosinophilic Granulomatosis with polyangiitis (EGPA) or Allergic Bronchopulmonary Aspergillosis (ABPA). Treatment response to systemic glucocorticoid is typically rapid, but relapse is common and reported in up to 61% in 6 months [3]. In this report, we describe a patient with Chronic eosinophilic pneumonia who exhibited an unusual finding of eosinophilic involvement of the tracheobronchial tree. Biopsy confirmed eosinophilic infiltration of the bronchial mucosa without evidence of vasculitis. Nodules have been described in eosinophilic diseases affecting various parts of the body. However histopathologic descriptions of airway mucosal involvement in CEP remain scarce in the literature and represent an area that warrants further study and reporting. Several case reports described endobronchial nodules in CEP [[4], [5], [6], [7]]. These reports described airway involvement with eosinophilic inflammation in the central airways, similar to the macroscopic description in our case. However, reports describing the histopathologic findings of airway lesions specifically have been scarce. Endobronchial nodules have been described in other eosinophilic pneumonia such as EGPA [8,9]. The histopathology of these lesions revealed a necrotizing bronchial inflammation as well as granulomatous eosinophilic inflammation. Seung et al. described a similar finding of tracheal inflammation without nodules associated with acute eosinophilia [10]. Endobronchial polyps that showed intense eosinophilic leukocytic infiltration was previously reported in several cases in eosinophilic asthma as well [[11], [12], [13]].

Tracheobronchial nodules in patients with eosinophilic pneumonia appear to be associated with a more symptomatic disease course. However, this phenomenon has not been extensively studied. A retrospective study conducted in Japan analyzed 36 cases of biopsy-proven EP. Tracheobronchial nodules were identified in 6.9% of patients with CEP. Among the 36 patients, only two presented with endobronchial nodules, both of whom were diagnosed with CEP. In these cases, the nodules resolved following systemic corticosteroid treatment [14], similar to the case described in this report.

2. Case description

A 44- year-old male arborist was referred for evaluation of non-resolving pneumonia. He has no significant past medical history. Over the past year, he has experienced recurrent episodes of worsening shortness of breath, wheeze and productive cough of thick sputum. He has been treated with multiple courses of antibiotics and prednisone, with significant symptomatic improvement following prednisone therapy. However, his symptoms, including worsening dyspnea and sputum production, frequently recurred upon discontinuation of prednisone. He has occasionally experienced fever during these episodes. He has also been prescribed inhalers including inhaled corticosteroid, Long and short Acting beta agonist with partial improvement. He also reported chronic nasal congestion. Additionally, he has had unintentional weight loss of approximately 10 pounds over the past year. In recent weeks before his encounter with us, his respiratory symptoms have progressively worsened, leading him to stop working.

His social history includes a remote five-year smoking history, having quit 20 years ago. He also occasionally smoked Cannabis but ceased use few weeks prior to his evaluation due to worsening respiratory symptoms. Occupationally, he has been working as an arborist, primarily involved in tree cutting, a job he transitioned to one year before the onset of his symptoms. He has no recent travel outside of Canada, no recent initiation of any new medications and no symptoms suggestive of neuropathy. Additionally, he denies any renal, cardiac or dermatological manifestations.

The patient's vital signs were within normal limits. On chest auscultation, bilateral wheezing was noted on expiration. Cardiovascular examination revealed normal heart sounds, with no signs of volume overload. Spirometry demonstrate FEV₁ of 3.54 L (81% predicted), an FVC of 5.48 L (100% predicted), and an FEV₁/FVC ratio of 65, consistent with mild obstruction. Total lung capacity (TLC) was measured at 8.78 L (117% predicted), and the diffusing capacity for carbon monoxide (DLCO), corrected to hemoglobin, was 93% predicted, indicating normal lung volumes and gas exchange. Although the bronchodilator response was initially negative, subsequent PFTs two months later showed a 20% improvement in FEV1 (Increase of 850 ml) following treatment with inhaled and systemic corticosteroid, confirming a diagnosis of asthma. Arterial blood gas analysis was within normal limits.

A chest radiograph revealed a right upper lobe peripheral opacity, which subsequently improved following therapy (Fig. 1). A Computed tomography (CT) of the chest was requested at that time. However, by the time the patient underwent imaging, systemic corticosteroid therapy had already been initiated. Consequently, the peripheral opacities previously observed on chest X-ray had been resolved, and the CT thorax was completely normal.

Fig. 1.

A chest radiograph revealed a right upper lobe peripheral opacity (a), which subsequently improved following therapy (b).

The patient's eosinophil count was significantly elevated with peak of 2.7 × 10⁹/L. Total leukocyte count is 10.9 x10*9/L. Autoimmune serology, including antinuclear antibody (ANA), rheumatoid factor (RF), anticyclic citrullinated peptide (Anti-CCP), perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) and cytoplasmic ANCA (c-ANCA) were negative. Total serum IgE was measured at 122 IU/ml, while specific IgE testing for aspergillus was <0.1 IU/ml, serum tryptase level was within normal limits. Renal and liver function tests were unremarkable. Serological testing for strongyloides by IgG enzyme immunoassay was negative. Routine urine analysis showed no evidence of proteinuria or hematuria.

Bronchoscopy and bronchoalveolar lavage (BAL) revealed diffuse, viscid and copious clear secretions within the airways. Multiple white nodules were observed throughout the tracheobronchial tree; these nodules were adherent to the mucosa and could not be removed by scraping or suctioning. Following treatment, repeated bronchoscopy 2 months after treatment showed complete resolution of nodules (Fig. 2). BAL fluid analysis demonstrated a marked eosinophilia of 51%. Histopathologic examination of endobronchial biopsy showed nonspecific epithelial erosion and ulceration with acute and chronic inflammation, characterized by abundant eosinophilic infiltration. There was no evidence of vasculitis (Fig. 3).

Fig. 2.

Endobronchial nodules throughout the tracheobronchial mucosa. Bronchoscopy and bronchoalveolar lavage (BAL) revealed diffuse, viscid and copious clear secretions within the airways (a). Multiple white nodules were observed throughout the tracheobronchial tree; these nodules were adherent to the mucosa (b). Two months after treatment, repeated bronchoscopy showed complete resolution of nodules (c).

Fig. 3.

Hematoxylin and eosin (H&E) stained section at 40× magnification. Histopathology showed abundant eosinophils. There is both intact and ulcerated surface epithelium.

A CT scan of the sinuses revealed polyps noted in the left maxillary antrum, with moderate diffuse inflammatory changes observed in the paranasal sinuses overall. An ear, nose and throat (ENT) consultation with flexible sinonasal endoscopy demonstrated grade 1 nasal polyposis bilaterally.

The patient was started on a course of prednisone (40 mg/day) in combination with triple inhaler therapy, including an inhaled corticosteroid (ICS), long-acting beta agonist (LABA) and long-acting muscarinic antagonist (LAMA). However, upon tapering the prednisone to 10 mg the patient's symptoms recurred with worsening shortness of breath, cough and wheezing. Additionally, hypoxia was noted, with oxygen saturation dropping to 88%. This led to a brief hospital admission for monitoring. During this period, prednisone was reintroduced initially at a higher dose with a plan for gradual tapering while monitoring symptoms through regular follow-ups.

Patient was subsequently started on biological therapy for his CEP/uncontrolled asthma with benralizumab (30 mg every 8 weeks) a monoclonal antibody that blocks the Interleukin-5 receptor (IL-5Ra) on eosinophils. Initially patient experienced clinical improvement; however. After three months, as the dosing interval was extended, symptoms recurred and systemic prednisone was reintroduced. The patient remained on biologic therapy with intermittent courses of prednisone. Inhaled therapy was escalated to include combination of budesonide, glycopyrrolate and formoterol fumarate with an addition of an extra inhaled corticosteroid inhaler (Ciclesonide). After one year of continuing biologic therapy, the patient was able to completely discontinue systemic steroid without further respiratory exacerbation.

Despite improvement in respiratory status, the patient continued to report persistent sinonasal symptoms. He was therefore referred again to ENT for consideration of surgical intervention and subsequently underwent bilateral functional endoscopic sinus surgery with good clinical response. Histopathological examination of the nasal polys demonstrated mixed inflammatory cells infiltrate, including lymphocytes, plasma cells, scattered patchy neutrophils and eosinophils.

3. Discussion

The endobronchial mucosal involvement observed in this case highlights an uncommon manifestation of CEP. While CEP classically affects the lung parenchyma, airway mucosal infiltration by eosinophils has been only rarely described. The presence of diffuse endobronchial lesions with biopsy confirmed eosinophilic infiltration, in the absence of necrotizing vasculitis, suggests that eosinophilic inflammation in CEP may extend to involve the bronchial mucosa which clinically manifest as asthma.

Extrapolating from the inflammatory mechanism observed in type 2-high asthma, eosinophilic infiltration likely represents a key driver of airway involvement in eosinophilic lung disease. Type 2 inflammation is primarily mediated by IL-5 and IL-4/IL-13 pathways, which promote eosinophilic maturation, recruitment and activation within the airway mucosa [15]. This results in eosinophilic inflammation, mucus hypersecretion and airway hyper-responsiveness as observed in this patient with a clear diagnosis of asthma. Given this shared inflammatory milieu, it is plausible that similar mechanism underlie the development of airway mucosal eosinophilic infiltration and endobronchial lesions in CEP.

Clinically AEP, CEP and EGPA may share overlapping features of pulmonary eosinophilia; However several characteristics help differentiate these entities. AEP typically presents as an acute febrile illness which could progress to hypoxic respiratory failure. Peripheral eosinophilia may initially be absent in AEP [16]. In contrast CEP and EGPA follows a more subacute to chronic course and marked peripheral eosinophilia. EGPA is a multisystem eosinophilic disorder that is distinguished by extrapulmonary manifestations such as neuropathy, renal involvement and other vasculitic features. ANCA positivity may support the diagnosis, although its present only in 30-40% of patients [17].

CEP and EGPA represent distinct entities with differing underlying histopathologic features of airway involvement. When tissue biopsy is obtained in CEP it is characterized by squamous metaplasia of the epithelium and prominent eosinophilic infiltration involving the epithelial and subepithelial layers, with extension into the alveolar walls and adjacent alveolar spaces. [14]. In contrast, EGPA is defined by necrotizing vasculitis affecting small to medium size vessels, accompanied by eosinophil-rich granulomatous inflammation [18].

Given the patient's occupation as an arborist and potential inhalational exposure to environmental allergens, occupational exposure may represent a possible inhalational trigger in a predisposed host. However, no specific antigen was identified.

The management of CEP has traditionally been based on systemic corticosteroids, which typically induce rapid clinical and radiologic improvement. However, relapse is common and many patients develop steroid dependence, necessitating prolonged therapy and exposing them cumulative side effects. Previous case reports have associated tracheobronchial nodules with more severe disease and increased symptoms burden, which may further support the need for escalation of therapy in selected patients [9,14]. In such cases, biologic therapies have emerged as potential steroid sparing options. Agent targeting IL-5 pathway suppress eosinophilic airway inflammation. Earlier initiation of biologic therapy may therefore be considered in patients with features of severe disease.

Informed consent

Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images.

Ethics approval

Ethical approval is not required for this study in accordance with local or national guidelines of King Abdulaziz University, Jeddah Saudi Arabia.

Availability of data and material

Not applicable.

Funding

None.

CRediT authorship contribution statement

Lugain Khoj: Conceptualization, Formal analysis, Methodology, Supervision, Writing – original draft, Writing – review & editing. Inderdeep Dhaliwal: Conceptualization, Data curation, Formal analysis, Writing – original draft, Writing – review & editing.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.