Introduction:
While mucus is a normal secretion in the respiratory tract, certain respiratory conditions lead to thickened mucus plugs within the airways, known as inspissated mucus. These plugs exhibit diverse pathologic compositions, often correlating with distinct clinical, radiologic, and bronchoscopy features. Conditions such as allergic bronchopulmonary aspergillosis, plastic bronchitis, and asthma are well-known for involving mucus plugs. Other respiratory disorders associated with airway plugs include Aspergillus tracheobronchitis, hyper-IgE syndrome, exogenous lipoid pneumonia, pulmonary alveolar proteinosis, and chronic eosinophilic pneumonia. This article reviews the pathology, diagnosis, and management of conditions involving mucus plugs.
What Is Mucus?
Mucin is a mixture of water, proteins, ions, glycoproteins, and lipids, with its structure varying based on environmental and pathophysiological factors. The clinical use of sputum appearance and odor is a longstanding practice for identifying specific lung conditions. Notable examples include currant jelly sputum in Klebsiella infections and the pungent smell often associated with Pseudomonas infections. Pathological processes can alter mucus composition, leading to thickened, obstructive mucus plugs in the airways. Factors like structural abnormalities and medications with anticholinergic properties influence mucus consistency and flow. Mucus plugs can obstruct airways, causing complications like atelectasis and recurrent infections. Bronchial casts, known as ‘mucoid pseudotumors, may form, presenting a mass-like appearance on chest imaging. In chronic airway diseases like asthma and COPD, increased mucin levels contribute to biofilm formation, fostering the presence of pathogens such as Pseudomonas aeruginosa and Klebsiella pneumonia in the affected airways.
What Diseases Are Characterized by Plugs in Air Passages?
The diseases that are characterized by plugs in air passages are as follows:
1. Allergic bronchopulmonary aspergillosis (ABPA) is a well-recognized respiratory condition caused by an allergic hypersensitivity response to Aspergillus fungi in the airways. ABPA is commonly associated with asthma but can also occur in individuals without asthma or those with cystic fibrosis. Clinical presentation often includes chronic respiratory symptoms, and mucoid impaction can lead to complications such as atelectasis. Imaging reveals central bronchiectasis and mucus plugging, with CT scans showing high-density mucus. The microscopic appearance, allergic mucin, exhibits a lamellated structure with eosinophils and Charcot-Leyden crystals. While Aspergillus fumigatus is the primary causative agent, other fungi can also contribute. Treatment involves long-term corticosteroids, with antifungal therapy considered adjunctive. Repeat bronchoscopy and therapy re-initiation may be necessary due to recurring obstructive symptoms.
2. Plastic bronchitis (PB), known by various terms such as pseudomembranous bronchitis, mucoid impaction, and cast bronchitis, is a rare disorder predominantly observed in children but also seen in adults. PB is characterized by branching mucoid bronchial casts obstructing the airways, causing respiratory distress. These casts are classified into two types based on their underlying pathophysiology: type I (inflammatory) casts, mainly in children with asthma or cystic fibrosis, and type II (acellular) casts, associated with surgically corrected cyanotic congenital heart disease. Patients with PB typically exhibit symptoms like wheezing, fever, upper respiratory tract infection, dyspnea, and expectoration of tree-like casts, resembling foreign body aspiration or severe asthma. Imaging studies reveal atelectasis, lung infiltrates, and hyperinflation, resembling bronchiectasis in advanced cases. Urgent bronchoscopy is required for diagnosis and treatment. Removal of these casts presents a challenge, and therapeutic approaches include mucolytics, chest physiotherapy, and anti-inflammatory therapies with varying success. Close follow-up is crucial for early intervention and preventing further complications.
3. Mucus plugging of the bronchi is a common autopsy in fatal status asthmaticus, with luminal occlusion primarily composed of mucus and cell debris contributing to fatal asthma cases. Mucus plugs can affect pediatric and adult patients with asthma, potentially obstructing small or large airways, with a tendency for more obstructions in the right lung. The etiology of mucus plugging in asthma is multifactorial, involving hypertrophy and hyperplasia of goblet cells, upregulation of the MUC5AC gene, and increased secretion stimulation. Mucus plugs in asthma consist of mucin, fibrin, and various inflammatory cells, lacking the lamellated appearance in conditions like ABPA. Although mucus plugs are rarely visible on radiography in asthma, chest CT scans may reveal mucus impaction, correlating with asthma severity. While mucolytic therapies have shown limited effectiveness in status asthmaticus, glucocorticoids, and anticholinergic agents may help regulate mucus hypersecretion according to current guidelines.
4. Aspergillus tracheobronchitis (AT) is a rare but severe form of aspergillosis affecting the tracheobronchial tree, particularly in immunocompromised or neutropenic individuals and those undergoing lung transplantation or cytotoxic chemotherapy. AT presents three histopathologic patterns: obstructive, ulcerative, and pseudomembranous, focusing on the obstructive and pseudomembranous forms associated with mucus plugging. Obstructive AT, initially identified in AIDS (acquired immunodeficiency syndrome) patients, involves the expectoration of thick mucus plugs containing Aspergillus without significant inflammation or invasive/allergic features. It can progress to invasive tracheobronchitis in immunocompromised hosts; lung transplant recipients are particularly vulnerable. Pathologically, mucus plugs are believed to be laden with Aspergillus hyphae and eosinophils, with limited invasion. Pseudomembranous AT, a form of invasive aspergillosis, is characterized by extensive pseudomembrane formation and sloughing of necrotic epithelium in the airways. More common in patients with hematologic malignancies than lung transplant recipients., it can lead to severe complications, including atelectasis and acute respiratory failure. Bronchoscopy is essential for diagnosis, and treatment involves systemic antifungals, with voriconazole being a primary recommendation. Caution is advised when attempting the bronchoscopy removal of pseudomembranes due to the high risk of severe bleeding.
5. Hyper-IgE syndromes (HIES) encompass primary immunodeficiency conditions marked by substantially elevated IgE levels, recurrent skin infections, eczema, and pulmonary infections. Clinical presentations vary based on the underlying mutation, with recurrent pulmonary and cutaneous infections being common. Pneumatoceles and bronchiectasis may result from recurrent pneumonia, leading to susceptibility to secondary infections, including Aspergillus and gram-negative bacteria. Mucus plugging in the airways is a recurrent feature, necessitating bronchoscopy for diagnosis and airway clearance. Pulmonary complications, especially pneumonia, are the primary cause of death in HIES patients.
6. Accumulation of lipid or lipid-like material in the lungs manifests in two distinct processes. Exogenous lipoid pneumonia, a rare disorder, results from aspirating external oily substances, commonly mineral oil or liquid paraffin, used for constipation treatment. Various other materials, like Vaseline, oily nose drops, and lip gloss, have also been reported as causes. Risk factors include gastroesophageal reflux disease and neurologic or psychiatric conditions. In contrast, endogenous lipoid pneumonia is a nonspecific consequence of airway obstruction by neoplasms, infection, inflammation, or other causes, where lipid is derived from macrophage cell membranes.
7. Pulmonary alveolar proteinosis (PAP) arises from the abnormal accumulation of surfactant phospholipoprotein within the alveoli, primarily due to impaired clearance by alveolar macrophages. There are three forms of PAP: congenital, secondary, and acquired (autoimmune). Acquired PAP, predominant in adults, often involves autoimmune factors with antibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF). It typically affects middle-aged men, showing a strong association with smoking. The onset of acquired PAP is usually gradual, marked by progressive dyspnea and cough, occasionally leading to acute respiratory failure.
8. Chronic eosinophilic pneumonia (CEP) is an inflammatory disorder characterized by an accumulation of eosinophils in alveoli, typically affecting individuals in their 30s and 40s, often with a history of atopy or asthma. Symptoms include cough, fever, dyspnea, weight loss, and night sweats. While a classic radiologic pattern is observed in only 25% of cases, mucus plugs can present as thick, yellow-white impactions in the airways. A lung biopsy and bronchoalveolar lavage (BAL) can confirm the diagnosis by revealing elevated eosinophils. CEP is highly responsive to corticosteroid therapy.
Mucus dysfunction is also documented in panbronchiolitis, immunodeficiencies (hypogammaglobinemia, HIV, malignancy, transplant recipients), and conditions associated with genetic markers. Recent therapeutic procedures, such as transtracheal oxygen catheter placement and bronchoscopic thermoplasty, have been linked to mucus plug formation. In infectious pneumonia, airway plugs may be present, but histopathologically, they differ from mucin-containing plugs seen in CEP and chronic aspiration. Thorough history-taking aids in diagnosis.
Management:
The initial management of mucus plugs involves proper hydration, humidification, bronchodilation, and mucolytic agents through nebulization. If these measures prove ineffective, flexible bronchoscopy may be necessary for therapeutic intervention and to gather diagnostic information. While most plugs respond to suction techniques, resilient mucus plugs can be challenging to aspirate, often requiring advanced bronchoscopic interventions. Cryoadhesion, a technique that removes thick mucus plugs adherent to the airways, provides an efficient and minimally invasive approach to tackle tenacious mucus, blood clots, and organic foreign bodies. It is crucial to send mucus specimens retrieved during bronchoscopy for culture and comprehensive pathological analysis, especially when the diagnosis is unclear.
Conclusion:
Obstruction or plugs in the air passages can significantly impede respiratory function, leading to breathing difficulties and potential health complications. Prompt identification and appropriate intervention are crucial in ensuring optimal lung function. These plugs are associated with various infectious diseases causing mucus formation, as revealed by radiological and histological features. Early detection helps better manage these diseases to avoid respiratory complications.
