What are the differential diagnoses and recommended evaluation for a brassy (harsh, metallic‑sounding) cough?

Brassy Cough: Differential Diagnoses and Evaluation

Primary Diagnosis to Consider

A brassy (harsh, metallic-sounding) cough is most characteristically associated with tracheomalacia, with a sensitivity of 0.57 and specificity of 0.81 for this diagnosis. 1

Key Differential Diagnoses

Airway Structural Abnormalities

• Tracheomalacia is the most validated diagnosis for brassy cough, with good interobserver and intraobserver clinician agreement (0.79; 95% CI, 0.73 to 0.86) 1
• Broncholithiasis presents with harsh, sometimes abrupt-onset cough, often associated with hemoptysis and calcified perihilar structures on imaging 1
• Airway foreign bodies cause persistent harsh cough, particularly when aspiration is unwitnessed or unsuspected 1
• Tracheobronchial amyloidosis can present with cough and wheezing, often initially misdiagnosed as asthma, with diffuse submucosal infiltration visible on bronchoscopy 1

Mediastinal and Extrinsic Compression

• Mediastinal masses (esophageal cysts/tumors, Hodgkin lymphoma, mediastinal lipomatosis) can impinge on airways and cause chronic cough as the primary manifestation 1
• Neuromas and neurilemmomas of the vagus nerve or internal laryngeal nerve have been described as primary causes of severe cough 1

Post-Surgical Complications

• Endobronchial sutures (metallic or nonmetallic) following lung surgery can irritate airway mucosa and cause cough, with associated granulation tissue contributing to symptoms 1

Recommended Evaluation Algorithm

Initial Clinical Assessment

• Carefully evaluate for symptoms and signs of underlying respiratory or systemic disease (termed "specific pointers") 1
• Recognize that the quality of cough can be diagnostically useful in children (unlike adults where cough characteristics are not diagnostically helpful) 1
• Assess for exacerbating factors regardless of underlying etiology 1

Diagnostic Testing Sequence

Step 1: Chest Radiography

• Obtain chest radiograph to identify calcified structures (suggesting broncholithiasis), mediastinal masses, or radiopaque foreign bodies 1, 2

Step 2: High-Resolution CT (HRCT)

• HRCT is the gold standard for evaluating small airway structural integrity and is more sensitive than spirometry 1
• Critical caveat in children: Balance diagnostic utility against increased lifetime cancer mortality risk (1 in 1,000 to 2,500 for a 2.5-year-old child at 200 mA), as children have 10 times the increased risk compared to middle-aged adults 1
• HRCT should be performed uncommonly in children unless other symptoms are present 1

Step 3: Flexible Bronchoscopy

• Indicated when there is suspicion of airway abnormality, localized radiologic changes, or suspected foreign body 1
• Bronchoscopy is the most definitive diagnostic test for broncholithiasis and can be therapeutic (48% of partially eroding broncholiths and all free broncholiths successfully removed) 1
• Allows visualization of tracheomalacia, tracheobronchial amyloidosis (appears as diffuse submucosal infiltrative process, nodular, tumor-like, or polypoid), and endobronchial sutures 1
• Biopsy of airway lesions is diagnostic for amyloidosis 1

Additional Investigations for Specific Scenarios

• Video fluoroscopic evaluation of swallowing if aspiration is suspected 1
• Echocardiography to evaluate cardiac causes 1
• Complex sleep polysomnography if sleep-related airway collapse is suspected 1

Common Pitfalls to Avoid

• Do not dismiss brassy cough as nonspecific: Unlike most cough characteristics in adults, brassy cough has been formally validated with reasonable sensitivity and specificity for tracheomalacia 1
• Do not overlook mediastinal pathology: Cough as the sole manifestation of mediastinal lesions is often overlooked 1
• Do not assume all harsh coughs are infectious: Consider structural and compressive etiologies, particularly when cough is persistent despite treatment for common causes 1
• Avoid premature extensive testing in children: Given the significantly increased radiation risk, reserve CT scanning for cases with additional concerning features 1

Treatment Considerations

• Broncholithiasis: Bronchoscopic extraction is first-line when feasible, though complications include hemorrhage (may require thoracotomy) and transient dyspnea 1
• Tracheobronchial amyloidosis: Local therapy (bronchoscopic debulking, laser ablation) or systemic chemotherapy, though recurrence is common and repeat treatments often required 1
• Endobronchial sutures: Bronchoscopic removal of exposed loose sutures almost always alleviates cough 1
• Tracheomalacia: Management depends on severity and may require surgical intervention in severe cases 1