Citations

Abstract Rationale: Since the initial descriptions of pulmonary arterial hypertension (PAH), there has been a significant increase in PAH diagnoses among the geriatric population. Studies suggest that older PAH patients exhibit unique hemodynamic profiles and treatment responses. We hypothesized that patients ≥80 years old would have a unique clinical profile and worse outcomes. Methods: The Pulmonary Hypertension Association Registry (PHAR) is a prospective cohort of PAH and chronic thromboembolic pulmonary hypertension (CTEPH) patients new to care at a Pulmonary Hypertension Care Center in the US. Individuals <18 years of age and those with CTEPH were excluded. Clinical data, quality of life measures, and functional capacity were recorded at time of enrollment and at follow up visits. Octogenarians were defined as those ≥80 years old and non-octogenarians as <80 years old. Associations between age subgroups with the change in six-minute walk distance (6MWD), and worsened WHO functional class (WHO FC) at the next visit, and time to all-cause mortality were assessed using linear, binomial, and Cox regression, respectively. Results: The study sample included 87 PAH octogenarian patients and 2,583 non-octogenarian patients at enrollment. The Table shows that octogenarian PAH patients were of similar sex and race distribution as others, but had lower body mass index. Octogenarians were more likely to have idiopathic or CTD-related PAH, and differed from younger patients in terms of several sociodemographic variables. PAH treatment, WHO FC, quality of life, and hemodynamic also differed between the groups. Octogenarians had a lower change in 6MWD (-26m, 95%CI -52 – -2, p = 0.066) and worse WHO FC (2.0, 95%CI 1.1 – 3.8, p = 0.038) over time compared to other adults after adjustment for sex, BMI, PAH etiology, annual income, marital status, right atrial pressure, mean pulmonary artery pressure, and PAH treatment. Octogenarians had an increased risk of death compared to younger adults (hazard ratio 1.7, 95%CI 1.1 – 2.6, p = 0.022) after adjustment for covariates. Conclusions: While the eldest PAH patients may have some comparable features to younger patients, they are different in a variety of socioeconomic variables, disease type, hemodynamics, and number of PAH therapies. The eldest PAH patients demonstrate worse exercise and functional capacity with time and a 70% increased risk of death compared to younger patients. Further studies are needed to better characterize PAH in the elderly, as this may lead to more effective treatments and enhanced quality of life.

Abstract A 77-year-old female with history of a right lower lobe adenocarcinoma (pT1a, pN0) underwent right lower lobectomy in August 2023, which subsequently was complicated by a bronchopleural fistula at the level of the right lower lobe bronchial stump. This led to a chronic hydropneumothorax, including a fungal empyema requiring placement of a 14-French thoracostomy tube and prolonged antimicrobial treatment over the next year. In June 2024 she underwent bronchoscopy, with application of argon plasma coagulation (APC) to cauterize the immediate area abutting the bronchopleural fistula and Gore VBX stent placement from the bronchus intermedius to the right middle lobe bronchus, bypassing the right lower lobe bronchial stump. There was no air leak immediately after that procedure and she continued with a 14-French thoracostomy tube in place for empyema drainage. Unfortunately, within the next 10 days the stent migrated requiring replacement. About a month later in July, 2024 the second stent was removed and revealed a persistent defect at the level of the bronchial stump with no apparent regression in size relative to the images captured prior to the initial bronchial stent placement. Under the expanded access pathway, a size 5 Spiration endobronchial valve was placed within the fistula in the right lower lobe bronchial stump (Figure 1). At the conclusion of the bronchoscopy procedure, a recruitment maneuver was performed while the suction on the thoracostomy tube was briefly increased to -40 cm H2O suction and no air leak was evident. The next CT chest 2 weeks later showed substantial improvement of the right hydropneumothorax. The air leak never returned and the thoracostomy tube was removed once the fluid drainage became negligible. The patient's dyspnea gradually improved and she was able to wean off supplemental oxygen. A follow-up CT chest 3 months later demonstrated a very small residual right pleural effusion with no gas component and stable positioning of the endobronchial valve. The multidisciplinary team involved in the patient's care intend to maintain the endobronchial valve in position indefinitely.

Abstract Purpose: Frail and malnourished patients with bronchiectasis have worse outcomes. This study examines frailty and malnutrition as predictors of 30-day readmission after bronchiectasis exacerbation (BE). Methods: We utilized the 2018 Nationwide Readmissions Database to analyze hospitalizations for BE. Patients with BE were identified through principal and secondary ICD-10 diagnosis codes J47.0 and J47.1. Among those who survived the index hospitalization, only individuals discharged to home were included in the analysis. The primary objective was to identify predictors of 30-day readmission, with a specific focus on frailty and malnutrition. Frailty was measured using the validated Hospital Frailty Risk Score, as described by Gilbert et al. (Lancet, 2018), while malnutrition was identified using ICD-10 codes E43, E44.0, E44.1, and E46. Comorbidity burden was categorized using the Charlson Comorbidity Index: mild (score 0-2), moderate (3-5), and severe (≥6). A multivariate logistic regression model was employed to calculate adjusted odds ratios (ORs) for readmission, with statistical significance defined as p < 0.05. Results: Among 20,742 patients discharged home following bronchiectasis exacerbation, 4% (830) were readmitted within 30 days. Patients with readmission were younger (median age 63 vs. 69 years, p<0.01) and more likely to be treated at urban hospitals (84.9% vs. 80.0%, p=0.01). They also had higher rates of frailty (52.6% vs. 46.5%, p=0.01), malnutrition (21.0% vs. 14.7%, p<0.01), and Pseudomonas pneumonia (5.9% vs. 3.9%, p=0.03). The comorbidity burden was not different (p=0.29). After adjusting for age, malnutrition demonstrated a trend toward higher odds of readmission (OR 1.31, 95% CI 0.99-1.73, p=0.059), though this did not reach statistical significance. In contrast, frailty was significantly associated with increased readmission (OR 1.36, 95% CI 1.12-1.66). The presented Table describes the demographic characteristics and outcomes of ALL hospitalized patients with BE (n = 40, 789) stratified by frailty and malnutrition. Conclusions: Frailty is a significant predictor of 30-day readmission following BE. Targeted interventions addressing frailty in hospitalized patients with BE may help reduce readmission rates.

Abstract Rationale: Cardiopulmonary exercise testing is a unique tool for simultaneously assessing cardiopulmonary and metabolic responses at peak exercise, making it invaluable for diagnosing unexplained dyspnea and fatigue, common issues in cardiovascular and pulmonary clinics. However, its use is often limited by complex guidelines, restricted lab access, technical demands, and high costs. The Veterans Specific Activity Questionnaire (VSAQ), developed by Meyers et al., offers a practical way to estimate metabolic equivalents and maximum oxygen consumption to assess exercise capacity. While primarily validated in a male population, the VSAQ lacks sufficient research in diverse ethnic and gender groups. Broader validation could enhance personalized cardiopulmonary testing, support equitable healthcare resource allocation, and help lower costs. Methods: In this prospective observational study, participants were included if they were 18 years or older and capable of completing a cardiopulmonary exercise test. Participants were excluded if they had known abnormal breathing patterns at baseline and if they had any contraindication for cardiopulmonary exercise and pulmonary function testing. A total of 17 patients without known cardiopulmonary disease provided informed consent and completed the brief self-administered VSAQ following the cardiopulmonary exercise test. The VSAQ was used to estimate maximal exercise capacity in metabolic equivalents, which was then compared to the actual maximal exercise capacity achieved on a bike ergometer, as recorded in the electronic medical records. Results: A linear regression analysis indicated a marginal association between VSAQ results (METS) and CPET METS, accounting for 22.2% of the variance in CPET METS (p=0.056). This finding suggests a potential, though not statistically significant, positive relationship between VSAQ METS scores and CPET MET. A linear regression analysis indicated a marginal association between VSAQ calculated Peak VO₂ and observed CPET Peak VO₂ (o₂/kg/min), explaining 21.6% of the variance in CPET Peak VO₂ (p=0.060). This suggests a potential positive relationship between VSAQ calculated Peak VO₂ and CPET Peak VO₂, though the association did not reach statistical significance. Conclusion: In this preliminary sample of patients without known cardiopulmonary disease, the VSAQ demonstrated accuracy in predicting maximum oxygen consumption at peak exercise. With further validation and larger sample size, the VSAQ could become a valuable adjunctive tool for assessing patients with unexplained dyspnea and fatigue, supporting more efficient diagnostic evaluations. Additionally, the VSAQ may serve as a practical follow-up measure to track clinical improvement after therapeutic interventions in this specific population.

Abstract Background: Expiratory central airway collapse (ECAC) is defined by excessive inward bulging of either posterior tracheobronchial membrane or anterolateral cartilage. ECAC commonly coexists with COPD, asthma, GERD, and obstructive sleep apnea. ECAC association with bronchiectasis is yet to be documented. Common conditions leading to bronchiectasis are obstructive lung diseases predisposing to recurrent infections, cystic fibrosis, COPD, or idiopathic. This study aims to evaluate the occurrence of bronchiectasis in patients with ECAC as the primary outcome and the correlation between the severity of bronchiectasis and the severity of ECAC as a secondary outcome. Methods: A retrospective single-center study evaluated patients diagnosed with ECAC using dynamic bronchoscopy in Mayo Clinic, Florida, from June 2019 to December 2020. Radiologists analyzed dynamic, or non-contrast chest computed tomography (CT) scans to evaluate the presence of bronchiectatic changes and the prevalence of bronchiectasis in this population. Bronchiectatic changes were documented using the Brody scoring system which recorded the bronchiectasis size, extent and tree in bud appearance in individual lobes. The final score had a range from 0 to 72. The bronchiectasis scores for individual lung lobes were analyzed to interpret distribution of bronchiectasis in ECAC population. The combined bronchiectasis scores of severe ECAC and non-severe ECAC cohorts were compared to assess if severe ECAC had higher bronchiectatic involvement. Results: Out of the 166 patients diagnosed with ECAC through dynamic bronchoscopy, 133 patients (80.1%) presented bronchiectatic changes in their CT scans. Of the 59 patients with severe ECAC, 51 patients (86.4%) were diagnosed with bronchiectasis. Of the 107 patients with non-severe ECAC, 82 (76.6 %) had bronchiectasis. The mean bronchiectasis scores are greater in right and left lower lobes, followed by middle lobes. The median values between severe and non-severe ECAC were 3 and 3 respectively with a p value of 0.34. The inter quartile range was 9 in severe ECAC group and 6 in non-severe ECAC (graph 1). Discussion: The outcomes of this study showed a significant presence of bronchiectatic changes in the ECAC population, implying the importance of evaluating for other pathologies. It can signify a pathological process similar to other pathologies which predispose to recurrent infections except for cystic fibrosis, which has an upper lobe involvement. The correlation of severity between ECAC and bronchiectasis requires more studies with a larger cohort for significant outcomes.

Abstract Introduction: Trastuzumab emtansine (T-DM1) is a standard therapeutic agent for advanced stages of HER2-positive breast cancer, known to improve survival rates. However, it is associated with side effects including fatigue, anemia, and mild-to-moderate bleeding. We present a rare case of pulmonary arteriovenous malformations (PAVMs) potentially linked to T-DM1 therapy, with clinical manifestations resembling hereditary hemorrhagic telangiectasia (HHT). Case Presentation: A 57-year-old female presented with chronic hypoxia on 3 L/min nasal oxygen. Her history included two years of worsening exertional dyspnea and hypoxemia during T-DM1 therapy for HER2-positive breast cancer, diagnosed 10 years earlier. She underwent bilateral mastectomy and was treated with T-DM1 and anastrozole. Echocardiography suggested a right-to-left shunt, while right heart catheterization excluded pulmonary hypertension. Subsequent CT angiography revealed small peripheral PAVMs, confirmed by Tc-99m MAA scintigraphy with a 30% right-to-left shunt. Lab results showed PaO2 at 52 mmHg, HCO3 at 20.3 mmol/L, O2 saturation at 86.4%, and PCO2 at 31 mmHg. Pulmonary function tests indicated restrictive lung volumes and severe diffusion impairment (FVC: 2.66 L, FEV1: 2.06 L, FEV1/FVC: 77.5%, TLC: 3.99 L, DLCO-SB: 20.7% predicted). Following discontinuation of T-DM1, patient experienced slight improvement in telangiectasias and dyspnea over three months but continued to require 10-15 L/min of oxygen during exertion. Arterial blood gas analysis showed a PaO2 of 56.4 mmHg, HCO3 of 20.7 mmol/L, resting O2 saturation of 88.4%, PCO2 of 26.8 mmHg, and PaO2 of 180.9 mmHg on 100% oxygen via a non-rebreather mask, indicating a persistent right-to-left shunt. Discussion: Arteriovenous malformations (AVMs) are abnormal artery-vein connections linked to HHT, with PAVMs present in 80-90% of HHT cases, leading to right-to-left shunts. This patient's prolonged T-DM1 therapy appears associated with PAVMs and HHT-like symptoms. While T-DM1 has been linked to pulmonary and portal hypertension, as well as cerebral AVMs, this is the first report associating it with PAVMs, possibly through disruption of endothelial function and HHT pathways like ALK1 and ENG. Diagnosing PAVMs can be challenging due to their often-asymptomatic nature; however, in this case, they were identified through repeated CT imaging and Tc-99m MAA scintigraphy. Embolization, a typical intervention for PAVMs, was not feasible due to the small size of the malformations. The patient's condition improved after discontinuing T-DM1, suggesting a potential link between the drug and PAVMs. Understanding the mechanisms by which T-DM1 induces vascular abnormalities is crucial for developing targeted interventions and improving patient outcomes.

Abstract Introduction Abemaciclib is a selective CDK4/6 inhibitor approved for metastatic breast cancer. We report the clinical course of Abemaciclib-induced pneumonitis, emphasizing the need for vigilant monitioring for interstitial lung disease (ILD) in patients receiving this therapy. Case description An 85-year-old woman with a history of HR-positive, HER2-negative breast cancer, Atrial fibrillation, and stage 3 chronic kidney disease presented with cough and weakness and a temperature of 100.1° F. She was hypoxic, requiring 4 liters of oxygen, she was in atrial fibrillation with a heart rate of 114, and blood pressure was 98/46. Laboratory testing showed an NT-Pro BNP: 5768, leukocytes: 2900 with 420 lymphocytes and an acutely elevated creatinine of 1.83 mg/dL (basline 1.3-1.4 mg/dL). Her CRP was 245 mg/L. Chest X-Ray revealed diffuse interstitial opacities. She was treated for pneumonia with cefepime and azithromycin, volume resuscitation and subsequent diuresis. However, her hypoxia continued to worsen. A chest CTA excluded pulmonary embolism but revealed progression of diffuse ground-glass and reticular opacities with a basilar apical gradient and enlarged mediastinal and hilar lymph nodes. An echocardiogram showed a mildly enlarged right ventricle and elevated right ventricular systolic pressure of 60. Subsequent infectious and autoimmune workups were inconclusive, bronchoscopy evaluation was deferred due worsening respiratory status. Given the concern for drug induced pneumonitis she was started on a steroid taper with 2 mgs/kg of IV Methylprednisolone. Over two weeks, her condition improved, and she was discharged without supplemental oxygen. Discussion Pneumonitis is a rare adverse effect of abemaciclib likely driven from CDK4/6 inhibitors. In a safety analysis of the MONARCH 2&3 trials, the incidence of pneumonitis was 2-5%, compared to 0.4-0.6% in the placebo arms. In these trials, two and one patients died of pneumonitis respectively. Our patient received abemaciclib for 2 years and 10 months, during which her follow up PET CT scan few months after treatment initiation demonstrated a new ground-glass and reticular opacities that continued to worsen on subsequent surveillance PET CT scans with significant progression noted on admission CT. In the absence of other contributing factors, our patient was diagnosed with Grade 3 lung toxicity, and abemaciclib was discontinued. The progression of her imaging before admission highlights the need for close monitoring for interstitial lung disease in patients receiving abemaciclib, to determine if dose reduction or treatment adjustment is warranted.

Abstract Introduction: Abemaciclib is a cyclin-dependant kinase 4/6 inhibitor used to treat HR+/HER2- advanced or metastatic breast cancer with disease progression following endocrine or chemotherapy. In 2023, the FDA expanded its indication alongside endocrine therapy for early HR+/HER2- breast cancer with high risk of recurrence. We present a case of Abemaciclib induced pneumonitis to raise awareness of this rare complication in a relatively new treatment with growing use. Case Presentation: An 85 year old female with HFpEF, atrial fibrillation on Rivaroxaban and metastatic breast adenocarcinoma on Letrozole/Abemaciclib for three years, was admitted with non-productive cough, dyspnea and low-grade fever. On initial evaluation she was hypoxemic requiring 4L/min of oxygen, and in atrial fibrillation at 140bpm. Chest x-ray showed bilateral airspace and interstitial opacities with vascular congestion. Respiratory viral panel was negative, and labs showed lymphopenia, elevated BNP (5768pg/mL), elevated CRP (245mg/L) and ESR (135mm/h). Ceftriaxone and Azithromycin was started, and Letrozole/Abemaciclib held. After 72h, despite antibiotics, rate control and diuresis, her hypoxemia persisted. On reviewing prior PET-CT scans from her oncological monitoring, early mosaic attenuation in both lungs was noted. Chest CT was obtained and revealed diffuse ground-glass and reticular opacities with basilar apical gradient. Due to fragile respiratory status, bronchoscopy was deferred and induced-sputum obtained. Extensive testing was negative including autoimmune studies, serum beta-D-glucan and galactomannan, Histoplasma/Blastomyces, Pneumocystis jirovecii, AFB stain, sputum and blood cultures. With a negative workup and chest CT suggesting non-infectious pneumonitis, she was treated with Methylprednisolone for a Grade 4 Drug-Induced Interstitial Lung Disease (DIILD). Treatment resulted in rapid improvements, and she was eventually weaned off oxygen. She was discharged with prednisone taper and outpatient Pulmonology follow up with repeat CT in 6-8 weeks. Discussion: Abemaciclib is associated with severe, potentially fatal DIILD. In clinical trials MONARCH 1-3, 3.4% of patients had pneumonitis of any grade, 0.6% had Grade 3-4, and in 0.4% it was fatal. Many agencies including the FDA and MHRA (United Kingdom) released post-marketing surveillance warnings to raise awareness of this toxicity. Our case highlights an important differential when autoimmune or microbiological workup is negative, and the patient is not improving despite diuresis and antibiotics. PET-CT imaging is frequently done in these patients for oncological monitoring, and re-review of these prior scans during acute admissions can evaluate for early evidence of non-infectious pneumonitis. Prompt recognition, discontinuation of Abemaciclib and early steroid therapy can prevent progression to severe respiratory failure or death.

Abstract Introduction: Calcineurin inhibitor (CNI) nephrotoxicity is a common complication following lung transplant. This is usually treated with dose reduction of CNI, addition of mammalian target of rapamycin inhibitor (mTORi), or rarely, CNI withdrawal which poses the risk of acute and chronic lung allograft rejection. Complete CNI withdrawal and transition to a mTORi based regimen for renal protection is scarcely described in literature with mixed results. Methods: We performed a single center, retrospective chart review of adult lung transplant recipients from January 2010-December 2022 to identify those who underwent complete CNI withdrawal and transition to a mTORi based immunosuppression regimen. Dual organ transplants and external transplant surgeries were excluded. Demographics, and clinical information on immunosuppressive regimens, renal function, rejection episodes, and outcomes were collected. This study was approved by the Mayo Clinic Institutional Review Board. Descriptive statistics were employed. Data is presented as N (%) or median (IQR). Results: A total of 52 patients who underwent CNI withdrawal were identified, and 38 patients (73.1%) were transitioned to a mTORi based regimen for renal failure. The median age at transplant was 59.1 years (IQR 54.2-63.3) and 57.9% were male. The most common transplant indication was pulmonary fibrosis (N = 21, 55.3%). No patients had pre-transplant chronic kidney disease stage 3 or higher. The median length of time from transplant to CNI withdrawal was 13.0 months (IQR 10.0-28.6). Most patients (N = 35 out of 38, 92%) discontinued mTORi and returned to a CNI based regimen after a median duration of use of 4.5 months (IQR 2.4-12.0) for an upcoming procedure/facilitate wound healing (N = 7, 20%), hypervolemia (N =7, 20%), death (N = 6, 17%), lung toxicity (N = 5, 14%), or worsening allograft function (N=5, 14%). Five patients (13.2%) developed ≥ A2 acute cellular rejection. Ten patients (26.3%) developed chronic lung allograft dysfunction. There was no change in creatinine at baseline (just prior to CNI withdrawal) compared to 12 (+/- 3) months after mTORi initiation (p = 0.36). Thirteen patients required dialysis (34.2%), four patients received renal transplants (10.5%), and 1 patient died on the renal transplant waitlist. Conclusions: Our case series demonstrates complete CNI withdrawal and transition to mTORi regimen is associated with short duration of therapy for most patients due to side effects and no change in creatinine one year after transition.

Abstract RATIONALE: Long-term survival after lung transplantation is challenging, with limited research on risk and protective factors. Clinical factors such as younger age, female sex, fewer acute rejection hospitalizations, and double lung transplants are associated with better outcomes. However, the role of psychosocial health and socioeconomic status (SES) remains underexplored. This study aimed to assess the influence of pre-transplant psychosocial health and SES on long-term survival in adult lung transplant recipients. METHODS: We conducted a single-center, retrospective case-control study using the Mayo Clinic Rochester lung transplant registry. Cases (survivors ≥ 6 years) and controls (survivors <6 years) were matched by transplant date (+/- 5 years) and indication for transplant, resulting in 190 subjects (63 cases, 127 controls). We assessed the impact of pre-transplant psychosocial health and SES on long-term survival using initial PACT scores (<2), the HOUSES index, and the national/state area deprivation index (ADI). Additional factors included proximity to the transplant center, insurance type, marital status, primary caregiver status, and employment status. Statistical analyses used the paired Wilcoxon rank-sum test for continuous variables and McNemar's test for categorical variables, with results reported as median (IQR) or percentages. RESULTS: Donor characteristics (age, sex, smoking history, risk criteria, cause of death) and recipient characteristics (age at transplant, sex, BMI, medical condition, functional status, type of transplant) were similar between cases and controls, with no statistically significant differences (all p>0.05). CMV mismatch, waitlist time, and transplant hospital length of stay were also comparable (all p>0.05). Psychosocial health indicators, including proximity to the transplant center, pre-transplant initial PACT score, insurance type, marital status, primary caregiver, and employment status, did not differ significantly between groups (all p>0.05). The HOUSES index was similar between cases and controls (p=0.179). However, long-term survivors had significantly higher national and state ADI scores than controls (national ADI: p=0.029; state ADI: p=0.019). CONCLUSIONS: Pre-transplant psychosocial health indicators, including proximity to the transplant center, initial PACT score, and caregiver support, did not differ significantly between long-term lung transplant survivors and those with shorter survival. Although SES measured by the HOUSES index was not associated with long-term survival, higher national and state ADI scores were linked to increased long-term survival, suggesting unique protective factors for patients from socioeconomically deprived areas. These findings highlight the complex role of socioeconomic factors in lung transplant outcomes and underscore the need for further research into how specific socioeconomic and environmental factors influence long-term survival.