Chhabria, Mamta

Abstract Introduction We report a case of an 87-year-old male presenting with debilitating fatigue and multifocal airspace opacities that improved with corticosteroid therapy, later diagnosed as VEXAS syndrome. Case Presentation An 87-year-old man with a history of atrial fibrillation (on Xarelto), diastolic heart failure, coronary artery disease, sick sinus syndrome status post pacemaker placement, hypertension, and chronic kidney disease presented with profound fatigue and failure to thrive over the last few months. A CT chest showed multifocal consolidative airspace opacities (Figure 1a) interpreted as “non-resolving pneumonia.” Despite multiple antibiotic courses, symptoms persisted. Notably, the patient had no respiratory complaints and maintained oxygen saturation of 98-99% on room air. Bronchoscopy revealed bronchoalveolar lavage (BAL) fluid with lymphocytic predominance, but cultures were negative and transbronchial biopsy was non-diagnostic and lymph node biopsies revealed normal lymphocytic tissue. Hematologic evaluation for plasma cell dyscrasia and amyloidosis was negative, though he was noted to have monoclonal gammopathy of undetermined significance. Additional workup revealed EBV positivity in BAL and serum (IgG+, IgM-), and weakly positive ANA and p-ANCA levels. Rheumatology consultation concluded that clinical features were not consistent with ANCA-associated vasculitis, additionally there was no evidence of diffuse alveolar hemorrhage on bronchoscopy. Empirical prednisone therapy led to a marked improvement in fatigue and interval resolution of the pulmonary opacities (Figure 1b). However, repeated steroid tapering attempts resulted in recurrent weakness, failure to thrive, and anemia, which normalized only during corticosteroid use. Given the relapsing course, bone marrow next-generation sequencing was pursued, identifying a pathogenic UBA1 mutation, confirming VEXAS syndrome. The patient has since been initiated on a JAK2 inhibitor and is tapering off steroids. Conclusion VEXAS syndrome is a late-onset, X-linked autoinflammatory disorder caused by somatic mutations in the UBA1 gene. It typically manifests with systemic inflammation, cytopenias, and multi-organ involvement, including pulmonary infiltrates, fevers, vasculitis, neutrophilic dermatoses, and bone marrow vacuolization of myeloid and erythroid precursors. The disease is often refractory to standard immunosuppressive therapy, with management focusing on corticosteroids and JAK inhibitors. This case underscores the importance of considering VEXAS syndrome in elderly men with unexplained systemic inflammation, autoimmune-like features and hematological abnormalities. This abstract is funded by: None

Abstract Introduction Central sleep apnea (CSA) may occur as an adverse effect of sodium oxybates, a medication commonly used to treat narcolepsy with cataplexy. Management is challenging, as sodium oxybates remain essential for symptom control in many patients, yet untreated CSA poses substantial respiratory risk. We present a rare case of sodium-oxybate–associated CSA successfully treated with adaptive servo ventilation (ASV), representing, to our knowledge, the first documented use of ASV for this indication. Methods A 49-year-old woman with longstanding narcolepsy with cataplexy presented with worsening daytime sleepiness despite stable use of sodium oxybate. She had been receiving a very high dose prescribed by an outside provider (6.75 g twice nightly), exceeding the recommended maximum of 4.5 g twice nightly, and her dose was subsequently adjusted to 4.5 g twice nightly. An in-lab polysomnogram revealed moderate central sleep apnea (AHI 21; RDI 23) with predominantly central events. Because the patient did not wish to wean or discontinue sodium oxybate—reporting that it remained the only therapy that consistently improved her sleep and cataplexy—adaptive servo ventilation (ASV) titration was pursued as the next step in management. She had previously failed multiple stimulants, wake-promoting agents, and SSRIs due to either limited efficacy or intolerable side effects. Her BMI was 18 kg/m2, she was not taking any CNS depressant medications, and her echocardiogram demonstrated a normal ejection fraction. Results The patient tolerated ASV well. Final settings included an EPAP of 5 cm H₂O with a pressure support range of 3–15 cm H₂O and minimal leak. Her adherence was excellent, with more than 93% of nights exceeding four hours of use. Residual AHI improved to 4.6 events per hour, accompanied by noticeable improvement in daytime alertness. She continued sodium oxybate without any respiratory complications. Conclusion ASV may be an effective and well-tolerated therapy for sodium-oxybate–induced CSA in patients who must continue the medication. Sodium oxybate can induce CSA by acting on GABA-B receptors in the Kölliker–Fuse and pre-Bötzinger complex, suppressing respiratory drive and depressing hypoglossal motor output. This case highlights the successful use of ASV in treating CSA secondary to oxybates when the medication cannot be weaned or discontinued. Support (if any)

Abstract Introduction Positive airway pressure (PAP) therapy is the standard treatment for obstructive sleep apnea (OSA); however, its use may be contraindicated in patients with recurrent pneumothorax, particularly in the presence of emphysematous lung disease and bleb formation. Hypoglossal nerve stimulation (HGNS) offers a non–positive-pressure alternative for appropriately selected patients. We describe what is, to our knowledge, the first reported case of successful HGNS therapy in an older adult with severe OSA and multiple recurrent pneumothoraces. Methods An 87-year-old man with severe OSA (baseline AHI 38, predominantly obstructive events) experienced multiple right-sided pneumothoraces beginning in December 2022, several of which were temporally associated with BiPAP use at 17/9 cm H₂O. His episodes required repeated interventions, including chest tubes, thoracoscopy with apical bleb resection and pleurodesis, and several pigtail catheter placements. Chest CT imaging demonstrated emphysema with multiple blebs, raising concern for the safety of continued PAP therapy. A mandibular advancement device was deemed inappropriate due to disease severity. The patient’s BMI was 27 kg/m2. HGNS was considered a suitable alternative. Results HGNS implantation was completed without complications. At activation, both the sensation and functional thresholds measured 0.8 V, with excellent tongue protrusion and waveform quality. The device was programmed to 0.8–1.8 V with a 30-minute start delay, 12-hour nightly duration, and 15-minute pause. On follow-up, the patient demonstrated excellent adherence (average 70 hours/week), progressed to level 8 (1.6 V), and reported significant clinical improvement with resolution of snoring and apneas. Functional threshold and waveform analysis at 1.6 V remained optimal. Importantly, the patient tolerated HGNS well without any further episodes of pneumothorax following implantation. Conclusion HGNS may represent a safe and effective alternative to PAP therapy in patients at risk for pneumothorax. While positive pressure ventilation can theoretically worsen pneumothorax by increasing pleural pressure, HGNS operates through an entirely different mechanism: it maintains upper airway patency without altering intrathoracic pressure dynamics, making it a potentially safer option for select high-risk OSA patients. Support (if any)

Abstract Background Patients with pulmonary hypertension due to interstitial lung disease (PH-ILD) have worse exercise capacity and survival than ILD patients without PH. Vasoreactivity with inhaled nitric oxide (NO) provides prognostic and therapeutic implications in pulmonary arterial hypertension, but little is known about its value in PH-ILD. We evaluated the pulmonary hemodynamic changes following inhaled NO and their association with outcomes in PH-ILD. Methods We measured pulmonary hemodynamics in patients with PH-ILD who underwent inhaled NO administration during right heart catheterization. We recorded baseline clinical, echocardiographic, and pulmonary function testing measures, and investigated the use of inhaled treprostinil as well as the rate of hospitalization, death, and lung transplantation. Results In 120 patients (age 67 ± 11 years, 62% women), the administration of inhaled NO resulted in a median (IQR) decrease in mean pulmonary artery pressure (mPAP) of −3 (−5, −1) mmHg, P < 0.001, and pulmonary vascular resistance (PVR) of −0.8 (−1.8, −0.2) wood units (WU), P < 0.001. The % change in mPAP and PVR were −6.3 (−10.9, −1.8) % and −16.8 (−27.3, −3.3) %, respectively. Factors associated with the % drop in PVR included baseline PVR (r = 0.30, P < 0.001), cardiac output (r = −0.19, P = 0.04), and WHO functional class (r = 0.25, P = 0.01). The median (IQR) follow-up was 14.5 (7, 25) months. During this time, 40 (33%) patients died, 8 (7%) underwent lung transplantation, and 76 (63%) experienced either hospitalization due to respiratory failure, transplantation, or death. The % drop in mPAP and PVR during inhalation of NO had no significant impact on these outcomes and was not associated with clinical response to inhaled treprostinil measured by changes in six-minute walk distance (6MWD) and forced vital capacity (FVC). Conclusion Inhaled NO caused a modest reduction in mPAP and PVR in patients with PH-ILD, but the acute hemodynamic response to inhaled NO was not associated with outcomes or response to inhaled treprostinil therapy.