C75-11 Evaluation of Diaphragmatic Weakness - Lessons From a Dedicated Clinic at a Tertiary Care Center

Abstract Rationale Diaphragmatic weakness is an understudied condition with various causes. Symptomatic patients with dyspnea or respiratory failure related to unilateral or bilateral diaphragmatic dysfunction often do not have clear therapies due to a lack of guidance regarding evaluation and treatment options. Given the rarity of these conditions, there are often limitations in obtaining testing and therapies due to under-recognition by insurance guidelines. Cohort studies have suggested modest rates of spontaneous recovery in this group on the scale of months to years. What specifically places these patients at risk of developing diaphragm weakness and what factors impact likelihood and speed of recovery is unknown. Methods Our research group developed a multi-disciplinary diaphragmatic weakness evaluation clinic composed of pulmonary, sleep and physical medicine and rehabilitation physicians to see patients referred for suspected diaphragmatic or phrenic nerve injury. All 151 patients determined to have a qualifying injury as defined by abnormal pulmonary function tests (30% drop in FEV1/FVC when supine), elevated diaphragm on imaging, or abnormal diaphragmatic ultrasound were entered into our database and tracked over time. Results Of 151 patients, 91 (60.26%) had hypertension, 79 (52.32%) diabetes mellitus, 72 (47.68%) hyperlipidemia, 61 metabolic syndrome (40.4%), and 121 (80.3%) had at least one component of metabolic syndrome. Our cohort also demonstrated 64 (42.38%) were former smokers, 3 (1.99%) were current smokers, and the rest were never smokers. Conclusions This descriptive study attempts to categorize risk factors for this under-recognized disease cohort at our center. Our patients with diaphragmatic weakness or phrenic neuropathy are highly over-represented in the presence of metabolic risk factors. Both experimental and clinical models have demonstrated a potential causative relationship between metabolic syndrome and neuroinflammation. Clinical data suggests obesity, diabetes and hyperlipidemia confer complementary but independent risk of peripheral neuropathy. The phrenic nerve is likely at similar risk, with nerve-conduction studies in asymptomatic diabetic and pre-diabetic patients showing phrenic nerve derangements compared to matched peers. In a disease-state with limited non-surgical treatment options, we may already have potential treatments at hand. Murine and human studies have shown promise for DPP4 inhibitors, GLP-1 receptor agonists, SGLT-2 inhibitors, metformin, and statins in reducing nerve inflammation. Exercise has shown faster rates of reinnervation of peripheral nerves in humans. While large-scale studies of these interventions were not powered to study peripheral nerve, and certainly not phrenic nerve, effects, targeted studies at specialty centers are needed to guide treatment for this vulnerable patient population. This abstract is funded by: None