What is the recommended management for a patient with Ehlers-Danlos Syndrome (EDS) experiencing respiratory symptoms, specifically cough?

Management of Respiratory Cough in Ehlers-Danlos Syndrome

Patients with EDS presenting with cough require systematic evaluation for structural airway abnormalities, gastroesophageal reflux disease, and asthma-like symptoms, as these are the most common respiratory manifestations in this population and require targeted management distinct from typical chronic cough protocols. 1, 2

Initial Diagnostic Approach

Rule Out Structural Complications First

• Assess for tracheobronchomalacia, which is a recognized structural manifestation in EDS causing cough, dyspnea, and noisy breathing that may be misdiagnosed as asthma 2, 3
• Evaluate chest wall abnormalities including pectus deformities, scoliosis, and recurrent rib subluxations that can contribute to respiratory symptoms 2, 3
• Obtain chest imaging to exclude pneumothorax, particularly if the patient has vascular EDS subtype where spontaneous pneumothorax is a major complication 2, 3
• Consider bronchoscopy if symptoms suggest airway collapse or tracheobronchomalacia, as direct visualization may be necessary 2

Evaluate for Functional Aerodigestive Disorders

• Screen for inducible laryngeal obstruction (previously called vocal cord dysfunction), which is commonly misdiagnosed as asthma in EDS patients and presents with cough, dyspnea, and noisy breathing 2
• Assess for gastroesophageal reflux disease, as gastro-esophageal dysmotility and reflux are common contributing factors to respiratory symptoms in EDS 2, 3
• Perform laryngoscopy if dysphonia or noisy breathing accompanies the cough, as vocal cord dysfunction is a recognized manifestation 1

Assess Respiratory Muscle Function

• Measure respiratory muscle strength with maximal inspiratory and expiratory pressures, as reduced respiratory muscle function is documented in hypermobile EDS 1, 2
• Consider pulmonary function testing to identify restrictive or obstructive patterns that may guide therapy 1, 3

Treatment Algorithm

Step 1: Address GERD if Present

• Initiate high-dose PPI therapy (omeprazole 40mg once daily before meals) combined with dietary modifications 4, 5
• Implement lifestyle changes: avoid eating 2-3 hours before bedtime, elevate head of bed, eliminate coffee, tea, chocolate, citrus, and alcohol 4
• Allow 4-8 weeks for therapeutic trial before escalating therapy, as GERD-related cough requires patience unlike other causes 4, 5
• Escalate to twice-daily PPI (omeprazole 20-40mg twice daily) and add prokinetic agent if inadequate response 4

Step 2: Treat Asthma-Like Symptoms

• Recognize that "asthma" in EDS may not be true asthma but rather tracheobronchomalacia, inducible laryngeal obstruction, or mast cell activation 2, 3
• Trial inhaled bronchodilators and corticosteroids if bronchial hyperresponsiveness is documented, but avoid if testing is negative 5
• Consider mast cell stabilizers for inflammatory manifestations including localized respiratory allergic and nonallergic mast cell activation 2

Step 3: Respiratory Muscle Training

• Implement inspiratory muscle training for patients with documented reduced respiratory muscle function, as this has shown benefit in hypermobile EDS 1
• Refer to physical therapy for exercise training and respiratory muscle strengthening 1

Step 4: Manage Structural Abnormalities

• Refer to otolaryngology for vocal cord strengthening exercises if dysphonia or inducible laryngeal obstruction is present 1
• Consider positive expiratory pressure therapy if tracheomalacia is contributing to symptoms and recurrent infections 6
• Surgical consultation may be necessary for severe tracheobronchomalacia or chest wall deformities causing significant impairment 2

Critical Pitfalls to Avoid

• Do not assume asthma without objective testing, as multiple EDS-specific conditions mimic asthma including tracheobronchomalacia and inducible laryngeal obstruction 2, 3
• Do not overlook GERD as a contributor, even in the absence of typical heartburn symptoms, as up to 75% of GERD-related cough lacks GI symptoms 4
• Do not miss vascular EDS complications - spontaneous pneumothorax or hemothorax in a young patient should prompt evaluation for vascular EDS, as these often precede diagnosis by years 3
• Do not attribute all symptoms to anxiety or deconditioning - respiratory symptoms in EDS have identifiable structural and functional causes requiring specific interventions 1, 2

Monitoring and Follow-Up

• Establish baseline pulmonary function testing to track progression and response to interventions 1
• Screen for obstructive sleep apnea, which has high prevalence in non-vascular EDS and can worsen respiratory symptoms 3
• Coordinate multidisciplinary care involving pulmonology, gastroenterology, and otolaryngology given the complex aerodigestive manifestations 2