Diaphragm muscle weakness linked to persistent shortness of breath following COVID-19
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Key takeaways:
- A little over 1 year after COVID-19 hospitalization, exertional dyspnea was reported in many patients.
- Patients with a past COVID-19 infection displayed reduced diaphragm muscle strength vs. healthy patients.
Fifteen months following COVID-19 hospitalization, both ventilated and nonventilated patients displayed diaphragm muscle weakness, according to results published in American Journal of Respiratory and Critical Care Medicine.
Further, this impairment was linked to shortness of breath when conducting physical efforts, according to researchers.
“Diaphragm weakness might explain exertional dyspnea reported by patients with long COVID in the absence of other pulmonary or cardiac function abnormalities,” Binaya Regmi, MD, of the department of pneumology and intensive care medicine at University Hospital RWTH Aachen, Germany, and colleagues wrote.
In a prospective noninterventional study, Regmi and colleagues analyzed 50 patients (mean age, 58 years; 36 men) 15 months after COVID-19 hospitalization to understand if diaphragm muscle strength is linked to unexplained dyspnea during physical efforts.
To capture pulmonary, cardiac and diaphragm function, researchers had patients complete several assessments: pulmonary function testing, 6-minute walk test, echocardiography, twitch transdiaphragmatic pressure after cervical magnetic stimulation of the phrenic nerve roots and diaphragm ultrasound.
Researchers then evaluated patients’ diaphragm function against the diaphragm function of nine healthy controls (mean age, 57.11 years; five men).
Half of the total cohort received mechanical ventilation, whereas the other half only required supplemental oxygen therapy while in the hospital and had a shorter mean length of stay (13 days vs. 50 days), according to researchers.
Of the total cohort, 24 patients (48%) reported moderate dyspnea when conducting physical efforts (10 ventilated patients vs. 14 nonventilated patients), and 12 patients (24%) reported severe dyspnea (eight ventilated patients vs. four nonventilated patients).
Notably, researchers did not find any significant abnormalities through pulmonary function testing, capillary blood gas analysis or echocardiography, suggesting that patients had normal lung and cardiac function. Patients’ 6-minute walk test results were impaired, and this did not significantly differ based on ventilation usage.
When compared with twitch transdiaphragmatic pressure values in healthy individuals (21 ± 3 cm H2O), researchers found reduced values among both mechanically ventilated (14 ± 8 cm H2O) and nonventilated (15 ± 8 cm H2O) patients, demonstrating diaphragm muscle weakness.
Further, twitch transdiaphragmatic pressure was significantly related to dyspnea severity during physical efforts (P = .03), according to researchers.
“Additional research is needed to determine whether specific interventions targeting diaphragm muscle weakness, such as inspiratory muscle training, could be an effective intervention to address exertional dyspnea in patients with long COVID,” Regmi and colleagues wrote.
This work conducted by Regmi and colleagues contributes to growing literature on the incidence of dyspnea following a COVID-19 infection and brings attention to the role diaphragm impairment may play in this condition, according to an accompanying editorial by Michael I. Polkey, PhD, FRCP, consultant chest physician at Royal Brompton Hospital and an honorary professor at the National Heart and Lung Institute, Imperial College London.
“This study adds to an emerging body of evidence that phrenic nerve and/or diaphragm dysfunction is a contributor in some patients,” Polkey wrote. “This is helpful because although there is no proven way of restoring diaphragm or phrenic nerve function, the experience from neuralgic amyotrophy is that function usually returns over a 2- to 5-year time frame, which patients and their physicians may find reassuring.”
Reference:
Perspective
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This study provides a novel approach to the long-standing problem of persistent dyspnea following COVID-19 infections. A large cohort of long-COVID patients experience persistent dyspnea on exertion, well out of proportion to what would be expected based on standard cardiopulmonary testing such as pulmonary function testing and echocardiography. The large percentage of patients in this cohort with confirmed, persistent diaphragm dysfunction is surprising.
Respiratory muscle dysfunction, especially diaphragm dysfunction, is a well-documented, albeit underdiagnosed, source of dyspnea. Dysfunction of the diaphragm ranges from weakness to complete paralysis, either unilaterally or bilaterally. Etiologies of diaphragm dysfunction are myriad, ranging from metabolic derangements, central and peripheral neurologic conditions, anatomic changes, traumatic and viral infections, and can occur secondary to mechanical ventilation. For many causes of diaphragm injury, such as critical illness and ventilator-associated injury, significant recovery is expected by the year mark.
The body of evidence that COVID contributes to long-standing diaphragm dysfunction is growing, and this study, utilizing the gold standard for diaphragm assessment of twitch diaphragm assessment, is a very well-conducted, strong piece of supporting evidence for long-term diaphragmatic injury post-viral infection. In my own practice, there has been an anecdotal increase in persistent diaphragm dysfunction that correlates with COVID infections, part of which may be explainable by the findings of this study.
This novel study also suggests the need for further research, both in terms of noninvasive forms of diagnosis and treatment modalities. Further noninvasive diagnostic tools could include positional spirometry, assessment of maximum inspiratory and expiratory pressure ratios, evaluation of sleep-disordered breathing and further utilization of diaphragm ultrasound to assess for weakness or paradoxical motion. Potential interventions such as early initiation of pulmonary rehab and inspiratory muscle training threshold training post-COVID would be treatment avenues to pursue, as well as more invasive forms of diaphragm reconditioning such as diaphragm pacing, which is currently being evaluated for other clinical scenarios.
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