Mucus plugs, while a seemingly minor issue, can be a significant indicator of underlying respiratory conditions. These thick, inspissated forms of mucus accumulate in the airways and, while mucus itself is a normal product of the respiratory system, these plugs signal a problem. Understanding how to identify, manage, and ultimately get rid of mucus plugs is crucial for respiratory health. This guide, based on the latest medical understanding, will delve into the nature of mucus plugs, their causes, associated conditions, and the methods for their removal and management.
Understanding Mucus Plugs
Mucus is a complex substance, a mixture of mucin glycoproteins, water, ions, proteins, and lipids. Its composition is dynamic, changing in response to both environmental and internal bodily conditions. Clinically, the appearance and even odor of sputum have long been used to provide clues to underlying lung conditions. Think of the classic “currant jelly” sputum in Klebsiella infections or the foul odor associated with anaerobic infections.
However, when mucus becomes abnormally thick and obstructs the airways, it transforms into what we call a mucus plug. This thickening and blockage can be triggered by various pathological processes that disrupt normal flow within the tracheobronchial tree. Consistency can be influenced not just by disease, but also by external factors like medications with anticholinergic effects.
Mucus plugs can cause partial or complete blockages in airways, leading to serious consequences. These range from atelectasis (lung collapse) to recurrent infections. In some cases, impacted mucus can solidify into a bronchial cast, a semisolid occlusion that mirrors the shape of the airway where it formed. These casts can even mimic tumors on chest imaging, a condition termed “mucoid pseudotumor.”
The formation of mucus plugs often begins with the airway epithelium’s reaction to external antigens. This triggers a cascade, leading to increased secretion of mucin. Individuals with chronic airway diseases like asthma, cystic fibrosis, and COPD already have elevated baseline mucin levels. Acute flare-ups further exacerbate this, promoting biofilm formation and creating environments where pathogens like Pseudomonas aeruginosa and Klebsiella pneumoniae can thrive in compromised airways.
This article focuses on respiratory diseases where mucus plugs are a key feature, and also explores conditions where they might be present, even if not the primary characteristic. The goal is to equip you with the knowledge to understand the differential diagnosis of mucus plugs and the diagnostic and management approaches based on imaging, bronchoscopy, and pathology.
Diseases Characterized by Classic Mucin-Containing Mucus Plugs
Certain respiratory conditions are strongly associated with the formation of mucus plugs composed primarily of mucin. These conditions often have distinct characteristics that aid in diagnosis and management.
Allergic Bronchopulmonary Aspergillosis (ABPA)
Aspergillus is a common fungus, and allergic bronchopulmonary aspergillosis (ABPA) is a condition arising from an allergic reaction to its presence in the airways. This isn’t an infection in the typical sense, but a hypersensitivity response, rich in eosinophils. Pathologically, ABPA is characterized by mucus impaction in the bronchi, eosinophil-rich granulomas centered around the bronchioles, and eosinophils in the alveoli near the bronchioles.
Bronchocentric granulomatosis, once considered separate, is now largely understood as being related to ABPA or granulomatous inflammation in infections like tuberculosis or fungal infections. Mucoid impaction, however, can occur independently of ABPA, and eosinophilic pneumonia features can also be present in various conditions unrelated to ABPA.
While Aspergillus fumigatus is the most common culprit in ABPA, other fungi can also be involved, such as Pseudallescheria boydii, Curvularia species, and others. ABPA is most frequently seen in patients with asthma, but also occurs in those with cystic fibrosis and even individuals without pre-existing asthma.
Diagnosis of ABPA is usually based on clinical findings. It typically manifests as a chronic respiratory illness, rarely as acute respiratory failure. Mucus impaction in ABPA can obstruct major bronchi, leading to atelectasis or consolidation, severely impacting respiratory function. In asthmatics, this impaction combined with airway inflammation can cause symptoms like hemoptysis (coughing up blood), systemic symptoms like weight loss and fatigue, and lung infiltrates that can mimic malignancy or tuberculosis. Clues to ABPA include a history of asthma, expectoration of mucus plugs, and eosinophilia (high eosinophil count) in the blood.
Imaging in ABPA reveals central bronchiectasis (widening of the bronchi) and mucus plugging around the hilum (center of the lung). CT scans often show mucus impaction that is denser than muscle tissue. This high density is thought to be due to calcium and metal salts within the mucus. The distribution of these plugs is different from plastic bronchitis; in ABPA, they are more common in the upper lobes and segmental bronchi, while plastic bronchitis affects lower lobes and central airways more often. Obstruction of lobar bronchi can create the “finger-in-glove” sign on chest X-rays and cause lobar collapse. Bronchoscopy can visualize these bronchial casts. Rigid bronchoscopy or cryoprobes may be needed to remove tenacious secretions that don’t respond to standard suction or forceps. In cystic fibrosis patients, recombinant human deoxyribonuclease can aid in mucus plug removal.
Figure 1. High Attenuation Mucus in ABPA
Figure 1: High attenuation mucus (arrows) seen on CT scan of the chest in (A) mediastinal and (B) lung windows in a patient with Allergic Bronchopulmonary Aspergillosis. The density of the mucus plugs in ABPA is often higher than surrounding tissues, a key imaging characteristic.
The mucus plugs in ABPA, known as allergic mucin, have distinctive microscopic features. Unlike normal mucus or mucus in uncomplicated asthma, allergic mucin has a lamellated appearance under low magnification, due to alternating layers of mucin and fibrin. These layers contain numerous eosinophils (both living and degenerating) and Charcot-Leyden crystals. Charcot-Leyden crystals are rhomboid or bipyramidal structures made of lysophospholipase, an enzyme from eosinophils, and indicate eosinophil-rich inflammation. Histopathology or cultures may reveal small numbers of degenerating fungal hyphae within the mucus plugs, but crucially, in ABPA, the fungi do not invade the airway wall or lung tissue, distinguishing it from invasive aspergillosis.
Figure 2. Finger-in-Glove Sign in ABPA
Figure 2: Chest radiograph showing the “finger-in-glove” sign (arrows) caused by left upper lobe mucus impaction in a patient with allergic bronchopulmonary aspergillosis. This classic radiographic sign is indicative of bronchial obstruction by mucus plugs.
Figure 3. Lung Collapse in ABPA
Figure 3: Chest radiograph showing (A) collapsed right upper lobe from mucus impaction in a patient with allergic bronchopulmonary aspergillosis before treatment, and (B) resolution of the collapse after bronchoscopic treatment. Prompt removal of mucus plugs can reverse significant complications like lobar collapse.
Figure 4. Lamellated Appearance of Allergic Mucin
Figure 4: Microscopic appearance of mucus plugs in mucoid impaction of bronchi and allergic bronchopulmonary aspergillosis (allergic mucin), showing the characteristic lamellated appearance under low magnification (40×). This layered structure is a hallmark of allergic mucin.
Figure 5. Eosinophils and Fibrin in Allergic Mucin
Figure 5: Microscopic appearance of allergic mucin under high magnification, showing alternating layers of mucin (pale) and fibrin (dark). Numerous eosinophils and Charcot-Leyden crystals are present throughout (magnification, 200×). The presence of eosinophils and fibrin within the mucus plug highlights the inflammatory nature of ABPA.
Figure 6. Charcot-Leyden Crystals
Figure 6: Charcot-Leyden crystals within allergic mucin in allergic bronchopulmonary aspergillosis (A, B). These bipyramidal crystals (arrow in A) are a marker of eosinophil-rich inflammation. Degenerating eosinophils are also visible in the background (arrows in B). (magnification, 400×).
Treatment for ABPA involves not only removing the obstructing mucus plugs but also long-term corticosteroid therapy, considered the cornerstone of management. Antifungal treatment is often used as an adjunct. Recurrence of obstructive symptoms is possible, necessitating close follow-up, potential repeat bronchoscopy, and systemic therapy.
Plastic Bronchitis (PB)
Plastic Bronchitis (PB) is a rare condition characterized by the formation of large, branching bronchial casts that obstruct the airways. It has been known by many names, including pseudomembranous bronchitis, mucoid impaction, and cast bronchitis. PB is more common in children, typically around 6 years old, but can also occur in adults. Its exact incidence is unclear due to its rarity and potential for underdiagnosis.
PB is characterized by these tree-like bronchial casts that cause respiratory distress. These casts are broadly classified into two types based on their presumed cause. Type I casts (inflammatory) are rich in eosinophils and are mainly seen in children with asthma or cystic fibrosis. Type II casts (acellular) are less cellular and are found in patients with surgically corrected cyanotic congenital heart disease. Acellular casts have also been linked to chyle leakage from the lymphatic system into the airways. In essence, Type I PB shares pathological and pathogenic overlaps with asthma and ABPA, while Type II PB seems to be a distinct entity.
Clinically, PB presents with wheezing, low-grade fever, upper respiratory infection symptoms, dyspnea, expectoration of tree-like casts, and often hemoptysis. It can mimic foreign body aspiration or severe asthma, requiring urgent bronchoscopy for diagnosis and treatment. Imaging typically reveals atelectasis, lung infiltrates, hyperinflation of the opposite lung, or bronchial cutoff. Advanced cases might resemble bronchiectasis on imaging. For patients with suspected PB and respiratory distress, immediate bronchoscopy is recommended.
The mucus plugs in PB are described as bronchial casts because they perfectly mold to the shape of the bronchi they fill. While their gross appearance can be striking, the microscopic appearance of Type II casts is often less remarkable, consisting mainly of mucin, fibrin, and a few lymphocytes and macrophages.
Figure 7. Mucus Plug in Plastic Bronchitis (Microscopic)
Figure 7: Low magnification microscopic view of a mucus plug in plastic bronchitis. It contains mucin (short black arrow), fibrin (long black arrow), macrophages (short white arrow), and a few lymphocytes (long white arrow) (magnification, 200×). The cellularity and composition can vary depending on the type of plastic bronchitis.
Figure 8. Bronchoscopic View of Bronchial Cast in PB
Figure 8: Bronchoscopic view showing complete obstruction of the right main bronchus by a large bronchial cast in a patient with plastic bronchitis. Bronchoscopy is crucial for both diagnosis and removal of these obstructive casts.
Removing these large, rubbery mucus plugs is therapeutically challenging as they are often too soft for forceps and too thick for suction. After removal, immersing the plug in saline or formalin helps to demonstrate its characteristic branching pattern, revealing its perfect cast-like structure. The presence of blood within the specimen doesn’t change the diagnosis. Other therapies used for mucus clearance include mucolytics, chest physiotherapy, intratracheal recombinant human deoxyribonuclease, hydration, and aerosolized acetylcysteine. Anti-inflammatory therapies like corticosteroids and macrolides have also been reported with varying success. In PB cases linked to lymphatic issues, a low-fat, medium-chain triglyceride diet or thoracic duct ligation might be beneficial. Close monitoring for early bronchoscopic intervention is crucial to prevent further complications in PB patients.
Figure 9. Bronchial Casts Removed in PB
Figure 9: (A) Left-sided airway cast removed via rigid bronchoscopy from a patient with plastic bronchitis. (B) Airway cast resembling the entire bronchial tree, also removed via rigid bronchoscopy. These images illustrate the size and branching nature of bronchial casts in plastic bronchitis.
Asthma
Mucus plugging is a common finding in autopsies of patients who died from fatal asthma attacks (status asthmaticus). Airway lumen obstruction by mucus and cellular debris is a major factor in fatal asthma. Autopsy studies have shown significantly more luminal occlusion by mucus and cells in asthma-related deaths compared to sudden deaths from non-pulmonary causes. Mucus plugs can occur in both children with severe asthma and those in remission, affecting both small and large airways. Adults with asthma are also susceptible. While multilobe involvement is common, obstructions are more frequent in the right lung. Mucus plugs have also been reported post-bronchial thermoplasty in asthma patients.
The causes of mucus plugging in asthma are likely multifactorial. Key contributors include marked hypertrophy and hyperplasia of goblet cells in the airways, increased expression of the MUC5AC gene, and stimulated secretions, all leading to excessive mucus production.
Figure 10. Mucus Plugging in Fatal Asthma
Figure 10: Autopsy specimen from a patient with fatal asthma. (A) Bronchial wall showing thick mucoid secretions, eosinophilic infiltration, smooth muscle hypertrophy, and basement membrane thickening. (B) Gross specimen highlighting mucus plugging in the airway (arrow). Mucus plugging is a critical pathological feature in fatal asthma.
Figure 11. Mucus Plug Post-Bronchial Thermoplasty in Asthma
Figure 11: (A-C) Mucus plug obstructing the right lower and middle lobe bronchi after bronchial thermoplasty in an asthma patient. (B) Histology showing fibrin mixed with mucus and inflammatory cells. (C) Gross specimen showing a bronchus-shaped mucus plug. This illustrates that mucus plugs can be a complication even of asthma treatments.
Mucus plugs in asthma are composed of mucin, fibrin, and varying numbers of inflammatory cells like macrophages, neutrophils, eosinophils, and T-lymphocytes. Microscopically, they lack the distinctive lamellated appearance and high eosinophil counts seen in ABPA and mucoid impaction of bronchi. Curschmann spirals, spiral-shaped mucus structures from distal small airways, can be found in sputum samples of asthmatics. While classically associated with asthma, they can also occur in asymptomatic smokers, lung cancer patients, chronic bronchitis, and those exposed to urban pollution. Asthmatic mucus may also contain Charcot-Leyden crystals and Creola bodies, clusters of benign ciliated bronchial cells. Radiography detects mucus plugs in only about 2.2% of asthma patients. However, coaxial chest CT scans can reveal mucus impaction and other abnormalities that correlate with asthma severity and decreased lung function (FEV1). High-density mucus in asthma should always prompt consideration of ABPA.
While mucus plugs contribute to airway obstruction in status asthmaticus, mucolytic therapies haven’t proven effective in improving outcomes. Current asthma guidelines do not recommend chest physiotherapy or mucolytics like N-acetyl cysteine for status asthmaticus. However, glucocorticoids and anticholinergic agents can help regulate mucus hypersecretion.
Diseases That May Feature Mucus Plugs or Airway Plugs of Other Types
While the conditions above are primarily defined by mucin-rich mucus plugs, other diseases can also present with airway plugs, though the composition might differ.
Aspergillus Tracheobronchitis (AT)
Aspergillus tracheobronchitis (AT) is a less common but severe form of aspergillosis affecting the tracheobronchial tree. It’s more prevalent in immunocompromised individuals, those with neutropenia, and lung transplant or chemotherapy recipients. AT is classified into obstructive, ulcerative, and pseudomembranous forms. The obstructive and pseudomembranous types are associated with mucus plugging.
Figure 12. Inflammatory Exudates in Aspergillus Tracheobronchitis
Figure 12: Gross autopsy specimen of the trachea showing inflammatory exudates in a patient with Aspergillus tracheobronchitis. This highlights the inflammatory component often associated with AT.
Obstructive AT was first recognized in AIDS patients who expectorated thick mucus plugs containing Aspergillus with minimal inflammation or invasive/allergic disease signs. It has also caused middle lobe atelectasis in heart transplant recipients. Symptoms can be subtle, and bronchoscopy is often needed for diagnosis and plug removal. Mucoid obstruction can progress to invasive tracheobronchitis in immunocompromised hosts, and lung transplant recipients are particularly vulnerable to airway complications from Aspergillus infection. Large, fibrinous, Aspergillus-laden mucus plugs have been observed obstructing central airways, leading to rapid lung function decline (FEV1). Steroids and itraconazole have been used successfully to resolve these complications. Lobar collapse due to major lobar bronchi involvement has also been reported in liver transplant recipients.
Figure 13. Lung Collapse in Aspergillus Tracheobronchitis
Figure 13: CT scan of the chest in a liver transplant recipient with Aspergillus tracheobronchitis showing complete collapse of the left lower lobe in (A, B) mediastinal and (C, D) lung windows. This illustrates the severe consequences of airway obstruction in AT.
Figure 14. Bronchoscopic Removal of Mucus Plug in AT
Figure 14: (A) Bronchoscopic view of a completely obstructed left main bronchus by a large mucus plug in Aspergillus tracheobronchitis. (B, C) The plug after removal. (D) Distal mucus plugs still visible in lobar bronchi after initial removal, subsequently aspirated. Bronchoscopy is essential for removing these obstructive plugs and improving airway patency.
The pathological features of mucus plugs in obstructive AT are not well-defined. They are thought to be rich in Aspergillus hyphae and eosinophils, with superficial invasion, differentiating it from invasive aspergillosis. While airway and anastomotic site colonization occurs in 50-70% of lung transplant recipients, eosinophils, large mucus plugs, and main bronchi invasion with lobar collapse are less common.
Pseudomembranous AT, another form of invasive aspergillosis, involves extensive pseudomembrane formation and necrotic epithelium sloughing in the airways. It is more frequent in hematologic malignancy patients than lung transplant recipients. Patients often present with fever, inspiratory wheezing, dyspnea, and nonproductive cough. Severe cases can lead to atelectasis, airway obstruction, and acute respiratory failure. Bronchoscopy is vital for obtaining microbiologic and pathologic specimens for diagnosis. Bronchoscopic aspirates often contain abundant fungal hyphae and mucosal slough, with tissue invasion evident on biopsy. Removing and biopsying pseudomembranes carries a risk of bleeding due to Aspergillus‘s propensity for vascular invasion, especially in thrombocytopenic patients.
For unclear endobronchial specimens, endobronchial ultrasound-guided transbronchial needle aspiration of lung lesions near airways can be helpful. The Infectious Diseases Society of America recommends voriconazole as primary treatment for invasive AT, with alternatives like liposomal amphotericin B, caspofungin, micafungin, posaconazole, or itraconazole. Bronchoscopic removal of pseudomembranes and endobronchial masses can be a useful adjunct to systemic therapy as antifungals may struggle to penetrate fungal masses. However, bronchoscopic removal carries a high bleeding risk and should be approached with extreme caution.
Hyper-IgE Syndromes (HIES)
Hyper-IgE syndromes (HIES) are primary immunodeficiency syndromes characterized by very high IgE levels (>2,000 IU/mL), recurrent skin infections, eczema, and lung infections. Two main clinical forms exist: autosomal-dominant and autosomal-recessive HIES. Several gene mutations are linked to HIES, with STAT3 and DOCK8 mutations being most common.
Clinical manifestations vary with the specific mutation, but recurrent lung and skin infections are hallmark features. Staphylococcus aureus and Streptococcus pneumoniae are the most frequently isolated bacteria in HIES. Recurrent pneumonia can lead to long-term complications like pneumatoceles and bronchiectasis. Pneumatoceles are not seen in autosomal-recessive HIES, but recurrent pneumonia is still common. Patients with these lung complications are also prone to secondary Aspergillus and gram-negative bacterial infections, and opportunistic infections like Pneumocystis pneumonia have been reported. Mucus plugging of airways is often seen during these secondary infections. Bronchoscopy is indicated for both microbiologic diagnosis and airway clearance.
Pulmonary complications are the leading cause of death in HIES. Postmortem studies show pneumonia in all HIES patients at death, with Aspergillus and Pseudomonas being the most common causes. Mucus plugs obstructing airways, leading to pneumonia, is a typical clinical presentation of HIES.
Figure 15. Mucus Plugging in Hyper-IgE Syndrome
Figure 15: CT scan of the chest showing mucus plugging causing obstruction of multiple airways and distal consolidation in a patient with hyper-IgE syndrome. Mucus plugging is a frequent and serious pulmonary complication in HIES.
HIES treatment is primarily supportive. Antibiotic prophylaxis against S. aureus with sulfamethoxazole and secondary antifungal prophylaxis are recommended to reduce recurrent infections. Immunomodulatory therapy with intravenous immunoglobulin has had variable success. Surgical intervention, like lobectomy, is sometimes needed, but carries high risks such as bronchopleural fistulae and impaired lung expansion.
Lipoid Pneumonia
Lipoid pneumonia involves lipid or lipid-like material accumulation in the lungs. Exogenous lipoid pneumonia is caused by aspirating external oily substances (mineral, vegetable, or animal oils). Common culprits include liquid paraffin and mineral oil used for constipation. Other implicated substances include petroleum-based lubricants, oily nose drops, laxatives, spray lubricants, and lip gloss. Risk factors for aspiration include gastroesophageal reflux disease and neurologic or psychiatric conditions. Occupational exposure, like in abalone divers inhaling aerosolized mineral oil, can also cause it.
“Exogenous” signifies that the lipid-like material originates from outside the body. In contrast, “endogenous lipoid pneumonia” is a common, nonspecific consequence of airway obstruction from various causes (tumors, infection, inflammation, etc.). The lipid in endogenous lipoid pneumonia comes from cell membranes of macrophages that accumulate due to blocked airways. These macrophages disintegrate, and their lipid is ingested by other macrophages, creating a “foamy” appearance. This accumulation gives the lung a golden hue, hence terms like “golden pneumonia” or “cholesterol pneumonia,” and similar golden material may fill the airways.
Many patients with exogenous lipoid pneumonia are asymptomatic. Symptomatic individuals usually present insidiously with persistent cough, dyspnea, fever, and weight loss. Chest CT scans mainly show airspace disease, but also ground-glass nodules, solid nodules, and crazy paving patterns. Lung involvement is typically bilateral and multilobar, with lower lobe predominance. Density measurements between -30 and -150 Hounsfield units suggest fat presence and point towards lipoid pneumonia.
Bronchoalveolar lavage (BAL) and transbronchial biopsy are helpful in diagnosing exogenous lipoid pneumonia. BAL fluid is often milky or oily and contains foamy macrophages with large, coarse vacuoles. Transbronchial or surgical lung biopsies confirm the diagnosis, showing foamy macrophages in airspaces and/or interstitium with coarse vacuoles. In contrast, endogenous lipoid pneumonia macrophages have fine, uniform vacuoles exclusively in airspaces. While the vacuoles in exogenous lipoid pneumonia are lipid remnants, the lipid is removed during formalin-fixation processing. Interstitial fibrosis and giant cell reactions to lipid are common in exogenous lipoid pneumonia. Cytologic profiles are nonspecific. Fat stains like oil red O on BAL fluid can be diagnostic if lipoid pneumonia is suspected. Bronchoscopy may reveal airway plugs, sometimes with aspirated food particles.
Figure 16. Oily BAL Fluid in Exogenous Lipoid Pneumonia
Figure 16: Gross appearance of BAL fluid in exogenous lipoid pneumonia in a patient taking Lorenzo’s oil. The milky or oily appearance of BAL fluid is a strong indicator of exogenous lipoid pneumonia.
Figure 17. Coarse Vacuoles in Exogenous Lipoid Pneumonia
Figure 17: Microscopic appearance of exogenous lipoid pneumonia. Macrophages containing coarse vacuoles of varying sizes fill the airspaces (short arrows). Similar macrophages are focally present in the interstitium (long arrow). This appearance is pathognomonic (magnification, 200×). The large, variable-sized vacuoles are characteristic of exogenous lipoid pneumonia.
Figure 18. Fine Vacuoles in Endogenous Lipoid Pneumonia
Figure 18: Microscopic appearance of endogenous lipoid pneumonia. Macrophages containing fine uniform vacuoles fill the airspaces (arrows). This is a common and nonspecific pathologic finding in lung specimens (magnification, 200×). The small, uniform vacuoles differentiate endogenous from exogenous lipoid pneumonia.
Figure 19. Airway Plugs in Exogenous Lipoid Pneumonia
Figure 19: (A) Bronchoscopic view of exogenous lipoid pneumonia with airway plugs. (B) Photograph of airway plugs removed from a patient with exogenous lipoid pneumonia. Airway plugs can be a component of exogenous lipoid pneumonia, contributing to airway obstruction.
Treatment for exogenous lipoid pneumonia centers on identifying and stopping the causative agent. Corticosteroids and whole lung lavage have been reported as successful treatments in some cases.
Pulmonary Alveolar Proteinosis (PAP)
Pulmonary alveolar proteinosis (PAP) results from abnormal surfactant phospholipoprotein accumulation in alveoli, thought to be due to alveolar macrophage dysfunction in surfactant clearance. PAP exists in congenital, secondary, and acquired forms. Congenital PAP presents acutely with rapid respiratory distress at birth. Secondary PAP is caused by conditions reducing alveolar macrophage number or function, like hematologic malignancies and infections. Acquired PAP (autoimmune PAP) is the most common adult form, typically affecting middle-aged individuals, with 90% being autoimmune, linked to anti-GM-CSF antibodies. PAP is more common in men and strongly associated with smoking.
Acquired PAP usually has an insidious onset with slowly progressive dyspnea and cough, though acute respiratory failure can occur. Diagnosis is often delayed, and about 30% are asymptomatic at presentation.
High-resolution CT scans are valuable in evaluating suspected PAP. Radiographic abnormalities are often disproportionately dramatic compared to symptoms. The classic finding is a crazy-paving pattern on HRCT, showing bilateral ground-glass opacities with smooth interlobular and intralobular septal thickening. However, this pattern is not specific to PAP and can be seen in other lung diseases. While PAP is defined by alveolar filling, the tracheobronchial tree can also be affected. Dense lipoproteinaceous material plugging distal small airways can cause segmental atelectasis.
Figure 20. Mucoid Plugs in PAP Airways
Figure 20: Bronchoscopic images showing mucoid plugs within the airways of a patient with pulmonary alveolar proteinosis. Note the thick, white-yellow appearance of the plugs. Airway involvement with mucoid plugs can occur in PAP.
Diagnosis of PAP is greatly aided by BAL and transbronchial lung biopsy. BAL fluid in PAP is milky and opaque, separating into a thick sediment and clear supernatant after settling. Microscopically, alveoli are filled with pathognomonic eosinophilic amorphous material, often with acicular spaces and dense eosinophilic globules. This material is typically PAS-positive and diastase-resistant. Alveolar septa are usually normal. Anti-GM-CSF antibody titers in BAL fluid correlate with disease severity.
Figure 21. Eosinophilic Material in PAP Alveoli
Figure 21: Microscopic findings in pulmonary alveolar proteinosis. Granular eosinophilic material fills the alveoli (black arrows). Alveolar septa (white arrows) are normal (magnification, 40×). The alveolar filling with eosinophilic material is the defining microscopic feature of PAP.
Therapeutic lung lavage is an established PAP treatment, improving clinical, symptomatic, and radiographic outcomes and reducing mortality. Most patients require repeat lavages. Exogenous GM-CSF is a newer therapy for autoimmune PAP but may be less effective and slower-acting than lung lavage.
Chronic Eosinophilic Pneumonia (CEP)
Chronic eosinophilic pneumonia (CEP) is an idiopathic inflammatory disorder characterized by high eosinophil counts in alveoli. It typically affects patients in their 30s and 40s, often with atopy or asthma history. Common symptoms include productive cough, fever, dyspnea, weight loss, and night sweats. CEP can also present with bronchoconstriction and mucus plugs in the lower lungs and has been reported in both children and middle-aged adults. The classic radiographic pattern is sometimes described as the “photographic negative of pulmonary edema,” but this is only present in about 25% of cases.
Mucus plugs occur in some CEP patients, appearing as thick, yellow-white impactions in the airways. The mucus plugging is likely due to eosinophil-rich inflammatory infiltrates, similar to asthma and ABPA. Diagnosis of CEP is confirmed by lung biopsy and BAL, both showing high eosinophil numbers. CEP is highly responsive to corticosteroid therapy.
Other Conditions
Mucus dysfunction and plugging can also occur in panbronchiolitis and immunodeficiencies (hypogammaglobulinemia, HIV, malignancy, transplant recipients). This can lead to secretion retention, mucus plugging, atelectasis, and bronchiectasis. Genetic markers like MUC5AC and MUC5B abnormalities have been linked to these conditions. Newer procedures like transtracheal oxygen catheters and bronchoscopic thermoplasty have also been shown to induce mucus plugs. Airway plugs can also be present in infectious pneumonias, but these differ histopathologically from mucin-containing plugs, and in chronic aspiration.
Figure 22. Tracheal Cast Post-Transtracheal Oxygen Catheter
Figure 22: (A) Tracheal cast in situ from a patient who died from complications of mucus plug after transtracheal oxygen catheter insertion. (B) Microscopic image showing a marbled pattern of proteinaceous zones alternating with necrotic cellular nuclei and inflammatory cells. This highlights that medical interventions can sometimes contribute to mucus plug formation.
Figure 23. Necrotic Debris Plugs in MRSA Pneumonia
Figure 23: Bronchoscopic images showing necrotic debris and plugs in (A) left main, (B) left upper, and (C) left lower lobe bronchi in a patient with community-acquired methicillin-resistant Staphylococcus aureus pneumonia. Plugs in infectious pneumonia are often composed of necrotic debris rather than primarily mucin.
Bronchoscopic Management of Mucus Plugs
Initial management of mucus plugs includes hydration, humidification, bronchodilation, and mucolytic agents via nebulization. If these measures fail, flexible bronchoscopy may be necessary, which can also provide diagnostic information. While most plugs are removable with suction, tenacious plugs may require advanced bronchoscopic techniques. Cryoadhesion, using a cryoprobe to freeze and adhere to the plug, has been used effectively to remove thick, adherent mucus plugs, blood clots, and foreign bodies. It is crucial to send retrieved mucus specimens for culture and detailed pathologic analysis, especially when the diagnosis is uncertain.
Conclusion
Mucus plugs are associated with a spectrum of respiratory disorders. While not all mucus plugs are the same, understanding their clinical, imaging, and pathologic features is key to accurate diagnosis and effective management of the underlying conditions. This guide has provided an overview of how to recognize, understand, and address mucus plugs in various respiratory diseases, emphasizing the importance of proper diagnosis and tailored treatment strategies.
