Asthma, Dyspnea, and Respiratory Manifestations of EDS

Respiratory Manifestations of Ehlers-Danlos Sydrome

Although hypermobile Ehlers-Danlos Syndrome (hEDS) is not classically associated with primary lung disease, many patients experience debilitating respiratory symptoms that are often misdiagnosed or misunderstood. Shortness of breath, chest tightness, and breathlessness with exertion are common complaints, yet pulmonary function tests are frequently normal. Emerging evidence suggests that these symptoms arise not from intrinsic lung pathology, but from a complex interplay of autonomic dysfunction, altered perception of breathing, impaired motor control, biomechanical limitations, and comorbidities such as gastroesophageal reflux or mast cell activation.

Dyspnea in hEDS: Real but Hard to Measure

A 2024 study by Cohen et al. found that nearly 70% of individuals with hEDS report dyspnea (difficulty breathing)—even in the absence of detectable pulmonary disease. This group experienced higher levels of physical and social disability than those without dyspnea, despite no significant differences in spirometry, oxygen saturation, or imaging results.

The authors proposed that functional respiratory complaints, such as air hunger and chronic breathlessness, may reflect altered central control and perception of breathing. Additionally, hyperventilation and unexplained hypoxia were sometimes observed in hEDS patients, though inconsistently.

Impaired Perception and Breathing Control

A 2024 study by Hakimi et al. used objective testing to assess lung volume perception and breathing control in hEDS. Participants with hEDS showed:

• Significantly overestimated lung volumes, particularly during inspiration.
• Reduced maximal inspiratory pressures, reflecting weaker inspiratory muscle strength.
• Poor coordination between respiratory movements and voluntary motor activity (e.g., walking or speaking).

These findings support the idea that dyspnea in hEDS may reflect a mismatch between actual respiratory mechanics and the brain’s interpretation of breathing effort—what the authors describe as an "inaccurate sensorimotor model of breathing."

The Role of Autonomic Dysfunction

Jones et al. (2024) investigated cardiovascular autonomic reactivity and its relationship to respiratory symptoms in hEDS. They found a high prevalence of:

• Postural Orthostatic Tachycardia Syndrome (POTS)
• Orthostatic hypotension
• Reduced baroreflex sensitivity

Patients with these forms of dysautonomia were more likely to report breathlessness when upright, which may reflect compensatory changes in ventilation tied to blood pressure instability or poor cerebral perfusion. This offers a mechanistic explanation for why many hEDS patients experience dyspnea despite normal lung function.

Additional Factors: Chest Wall Instability and Fatigue

The narrative review by Raghavan et al. (2023) highlights chest wall instability, scoliosis, and fatigue-related deconditioning as additional contributors to respiratory symptoms. Chest wall laxity may result in paradoxical or inefficient breathing, particularly during exertion. Fatigue, common in hEDS, may exacerbate perceived breathing difficulty by impairing neuromuscular endurance during respiration.

When Asthma Isn’t Asthma: hEDS and Asthma-Like Symptoms

One of the most important clinical insights from these studies is the high rate of misdiagnosed asthma in hEDS.

Key points:

• Wheezing, coughing, and chest tightness can mimic asthma but may instead result from air hunger, dysautonomia, or gastroesophageal reflux—all common in hEDS.
• Mast cell activation syndrome (MCAS), frequently co-occurring in hEDS, can cause bronchospasm and asthma-like symptoms, but responds better to antihistamines and mast cell stabilizers than to bronchodilators.
• Objective testing, such as spirometry with bronchodilator response, is essential to confirm true asthma.

In one cited case series, over 50% of hEDS patients prescribed asthma medications had normal spirometry and no evidence of reactive airway disease. This highlights the need to reconsider asthma diagnoses in patients whose symptoms persist despite standard treatment.

References

• Cohen, C. A., Regnault, H., Gautier, J., Maron, M., Martino, E., Hakimi, A., ... & Mucci, P. (2024). Dyspnea in hypermobile Ehlers-Danlos syndrome: A cross-sectional study. Respiratory Physiology & Neurobiology, 323, 104799. https://doi.org/10.1016/j.resp.2024.104799
• Hakimi, A., Bergoin, C., De Jesus, A., Hermand, E., Fabre, C., & Mucci, P. (2024). Impairment of lung volume perception and breathing control in hypermobile Ehlers-Danlos syndrome. Scientific Reports, 14(1), 8119. https://doi.org/10.1038/s41598-024-58890-2
• Jones, J., Teasdall, R., Regnault, H., Frigon, C., Franchitto, N., Gautier, J., ... & Hakimi, A. (2024). A Cross-Sectional Study of Cardiovascular Autonomic Reactivity in Ehlers-Danlos Syndrome. Clinical Autonomic Research, Advance online publication. https://doi.org/10.1007/s10286-024-00960-6
• Raghavan, V., Nasser, J., Swanson, A. D., Nair, V., & Chopra, P. (2023). Respiratory manifestations and their management in hypermobile Ehlers-Danlos syndrome: A narrative review. Journal of Multidisciplinary Healthcare, 16, 2035–2046. https://doi.org/10.2147/JMDH.S430872

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