Citations

Background/Objective: To investigate the effect of mycophenolate mofetil (MMF) and rituximab (RTX) on pulmonary function test (PFT) results in a mixed cohort of patients with connective tissue disease-associated interstitial lung disease (CTD-ILD), longitudinally followed up for 1 year in a single academic center. Methods: Patients with CTD-ILD were identified in electronic medical records from 1 January 2009 to 30 April 2019. Prescribed MMF and RTX doses, dosage changes, and therapy plans were analyzed individually with improvement in PFT outcomes determined using multivariable linear regression models during 12-month follow-up. Results: Forty-seven patients with CTD-ILD, treated with MMF, RTX, or both, were included. Patients on combined MMF and RTX had worse PFT outcomes at baseline compared with patients on monotherapy. Substantial improvement was observed among all PFT outcomes from baseline to 12 months, regardless of medication dosage or therapy plans. The diffusing capacity of the lungs for carbon monoxide (DLCO) worsened by an average of 7.21 mL/(min*mmHg) (95% CI, 4.08–10.33; p < 0.001) among patients on RTX compared to combined therapy. Patients on higher doses of MMF at baseline experienced an average increase of 0.93 (95% CI, 0.04–1.82) units in DLCO from baseline to 6 months (p = 0.04) and a 2.79% (95% CI, 0.61–4.97%) increase in DLCO from 6 to 12 months (p = 0.02) within patients on concurrent RTX at 6-month follow-up. Conclusions: The treatment of CTD-ILD with MMF and/or RTX was associated with overall improvement in PFT outcomes. Combined therapy resulted in significant improvements in DLCO compared with monotherapy. Higher doses of MMF also provided greater improvements in DLCO.

Introduction: Laryngotracheoesophageal clefts (LTEC) are well-known aspiration-associated lesions. Results of swallow studies, and respiratory, feeding, and swallowing symptoms are commonly used indications for repair, despite being unclear predictors of disease. Although lung inflammation and injury are primary concerns, such findings are uncommonly and inconsistently evaluated and reported and therefore it remains unclear how well swallow studies predict lung disease. Methods: Children seen in our Aerodigestive program 10/1/2012 and 9/30/2023, with a LTEC and a videofluoroscopic swallow study (VFSS) or flexible endoscopic evaluation of swallowing (FEES) were included. Data regarding clinical history and risk factors, BAL, chest CT, and impedance probe results were abstracted, along with VFSS/FEES results and functional oral intake scale (FOIS-P/I) at baseline and follow-up. Results: 82 subjects identified. Lung inflammation and bronchiectasis were common and correlated. Clinical factors, impedance probe, and the presence/severity of swallowing abnormalities on VFSS/FEES were not predictive of lung disease. 57 patients underwent LTEC repair for a range of indications, only 49% based on CT and/or BAL findings. LTEC repair was associated with a trend towards improvement feeding and swallowing, yet none of these met statistical significance. Discussion: Children with LTEC have a high prevalence of inflammatory lung disease and injury and undergo repair for a variety of reasons. The insufficient ability of swallow study to identify patients with lung disease suggests that such studies identify functional abnormalities but not a disease state, per se. Nevertheless, LTEC repair is associated with improvements in feeding and swallowing in a subset of patients.

Abstract Rationale Among tobacco-exposed persons with preserved spirometry (TEPSs), we previously demonstrated that different lung volume indices—specifically, elevated total lung capacity (TLC) versus elevated ratio of functional residual capacity to TLC (FRC/TLC)—identify different lung disease characteristics in the COPDGene cohort. Objective We sought to determine differential disease characteristics and trajectories associated with lung volume indices among TEPSs in the SPIROMICS cohort. Methods We categorized TEPSs (n = 814) by tertiles (low, intermediate, and high) of TLC or residual volume–to-TLC ratio (RV/TLC) derived from baseline computed tomography images and then examined clinical and spirometric disease trajectories in mutually exclusive categories of participants with high TLC without high RV/TLC ([TLC]high) versus high RV/TLC without high TLC ([RV/TLC]high). We examined differences in computed tomography–measured emphysema (Hounsfield units [HU] ⩽−950; parametric response mapping [PRM] of emphysema), air trapping (HU⩽−856; PRM of functional small airway disease; a disease probability measure for non-emphysematous gas trapping), airway geometry (the mean square root of wall area of a hypothetical airway with 10 mm internal perimeter), respiratory symptoms (on the modified Medical Research Council Dyspnea Scale; COPD Assessment Test [CAT]; St. George’s Respiratory Questionnaire [SGRQ]; and Short Form-12 [SF12]), and outcomes (annualized exacerbation rate) between the two categories at baseline and over follow-up time up to 8.5 years, using regression modeling adjusted for age, sex, height, weight, and smoking status (current vs. former smoker) and burden (pack-years). Results In TEPSs, the pattern of spirometric disease progression differed between participants with [TLC]high and those with [RV/TLC]high: There was increased forced vital capacity with stable forced expiratory volume in 1 second in participants with [TLC]high, versus unchanged forced vital capacity but nominally decreased forced expiratory volume in 1 second in those with [RV/TLC]high. Compared with participants with [TLC]high, TEPSs with [RV/TLC]high had less emphysema (by HU ⩽−950) but more airway disease (by HU ⩽−856; PRM of functional small airway disease; disease probability measure for gas trapping, and mean square root of wall area of a hypothetical airway with 10 mm internal perimeter), more respiratory symptoms (on the modified Medical Research Council Dyspnea Scale, CAT, SGRQ, and SF12), and more severe exacerbations at baseline. Over an average follow-up of 4.1 ± 2.4 years (range = 0.5–8.5 yr), TEPSs with [RV/TLC]high also had a higher likelihood of developing more severe spirometric disease (preserved ratio impaired spirometry or Global Initiative for Chronic Obstructive Lung Disease Classification 2) and worsening of their respiratory symptoms (on the CAT and SGRQ). Although the incidence rates of respiratory exacerbations, hospitalizations, and mortality were not significantly different between the two categories over the follow-up period, TEPSs with [RV/TLC]high were more likely to have been prescribed a respiratory inhaler at their last follow-up visit. Conclusions In these TEPSs from the SPIROMICS cohort, lung volume stratification by TLC versus RV/TLC identifies two pre-COPD phenotypes with distinct respiratory symptoms, radiographic features, and clinical trajectories. The characteristics of these pre-COPD phenotypes match those previously described in the COPDGene cohort using TLC versus FRC/TLC stratification.

Background: For patients undergoing abdominal surgery, postoperative pulmonary complications (PPCs) are a major source of morbidity and mortality. The use of point-of-care ultrasonography (POCUS), and specifically POCUS of the lungs, has seen many advancements in recent years. Objectives: We hypothesize that perioperative lung ultrasonography can be used as a predictor for PPCs. Methods: In a Single, 1000 beds, trauma level I medical center, patients presenting for elective intra-abdominal surgery with no severe pulmonary or cardiac diseases were evaluated preoperatively with a standardized 12-point lung ultrasound exam. A second identical exam was performed after surgery in the post-anesthesia care unit. PPCs were also documented. All lung ultrasound exams were presented to a blinded researcher and a lung ultrasound score (LUS) was calculated. Statistical analysis comparing pre- and postoperative LUS and PPC scores were performed. Results: A total of 61 patients were evaluated. The pre-surgery median LUS was 0 (in the range of 0–6) and the post-surgery median LUS was 3 (in the range of 0–14). The pre- to postsurgical LUS delta was 3.4 (standard deviation of 3.3). A postoperative LUS of 6 or more was defined as “high.” A High LUS did not correlate with prolonged post-anesthesia care unit or hospital stay, prolonged oxygen support, or number of desaturation events. Conclusion: For elective abdominal surgery in relatively healthy patients, preoperative LUS usually begins at a normal level and becomes worse after general anesthesia. However, this difference in LUS is not significantly associated with clinically relevant postoperative pulmonary complications such as prolonged oxygen therapy, pneumonia, and noninvasive or invasive mechanical ventilation. Trial registration: Clinicaltrials.gov identifier: NCT05502926. Summary: This paper explores the use of point-of-care ultrasonography as a predictor for postoperative pulmonary complications. The findings suggest that while the lung ultrasound score worsens with general anesthesia, the differences are not significantly associated with postoperative pulmonary complications.

A 40 year old woman who underwent combined heart-lung transplant for familial severe pulmonary hypertension experienced episodes of nonsustained ventricular tachycardia followed by sudden ventricular fibrillation arrest 8 days after transplant. Postarrest investigations revealed left lower lobe herniation into the right lower hemithorax, prompting emergent reoperation, and hernia reduction. Arrhythmias resolved following reduction of the herniated lung and facilitated rapid weaning from vasopressor and ventilatory support. To our knowledge, this is the first reported case of cardiac arrest due to lung herniation after combined heart-lung transplantation. Herein, we describe this rare presentation and offer insights and management strategies for the cardiac intensivist.

Lung cancer is a leading cause of cancer-related mortality worldwide, characterized by its aggressive nature and poor prognosis. Matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, play a pivotal role in the progression of lung cancer. They contribute to tumor invasion, metastasis, angiogenesis, and the modulation of the tumor microenvironment by degrading extracellular matrix components and regulating various cellular signaling pathways. Elevated levels of specific MMPs, such as MMP-2, MMP-9, and MMP-14, have been associated with advanced disease stages and reduced survival rates. As such, MMPs have emerged as valuable biomarkers for the diagnosis, prognosis, and prediction of treatment responses in lung cancer. This review aims to provide a comprehensive overview of the current understanding of MMPs in lung cancer, highlighting their diagnostic and prognostic significance, as well as their potential as therapeutic targets. Despite the initial setbacks in developing broad-spectrum MMP inhibitors, recent advancements have spurred interest in more selective inhibitors that minimize off-target effects and enhance therapeutic efficacy. Furthermore, combining MMP-targeted therapies with conventional treatments, such as chemotherapy and immunotherapy, holds promise for improving clinical outcomes. Future research directions include exploring novel MMP inhibitors, understanding the regulatory mechanisms of MMP activity, and integrating MMP biomarkers into personalized medicine approaches. As the field progresses, targeting MMPs may offer new therapeutic avenues and improve the prognosis for lung cancer patients, making this a promising area of investigation.

Abstract Despite progress in screening and treatment, lung cancer remains the leading cause of cancer- related deaths worldwide. An overarching issue is the complexity and heterogeneous nature of the tumor microenvironment and eventual tumor spread. While aging is a key determinant, the relationship between aging and cancer is multi-faceted and extends beyond the accumulation of mutations. Therefore, a much-needed framework integrating the mechanistic principles that change with aging to drive neoplastic transformation beyond genetics will help us uncover predictive biomarkers that inform treatment decision-making and how we may use them to prevent, postpone, suppress tumor growth, and limit spread. Here, we investigate the role of age-related senescent cell accumulation in lung tumorigenesis and propose a potential strategy to delay tumor progression and spread by selectively targeting tumor-promoting senescent cells that arise with increasing age to sustain protective antitumor immunity. Citation Format: Luis Prieto. Effects of senescence on the lung tumor microenvironment [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr A014.

INTRODUCTION: There is a significant shortage of specialized Adult Congenital Heart Disease (ACHD) cardiologists despite a rising prevalence of adults with this condition. AIM: Our study explores the specific motivations and deterrents that influence adult and pediatric cardiologists’ ACHD career decisions, which could serve as the basis for future solutions to overcome this shortage in each specific region. METHODS: An anonymous global survey was distributed to adult and pediatric cardiologists and trainees via email, social media, and medical society newsletters. The survey included demographics, ACHD exposure, career considerations, Likert scale ratings, and open-ended inquiries on ACHD career recommendations. Respondents included non-ACHD and ACHD cardiologists (defined as those caring for ACHD with or without formal training). The analysis covered regional variations across continents. Responses with less than 75% completion were excluded. RESULTS: A total of 811 valid responses were collected (53.5% female, 48.3% aged 31-40, and 43.3% White). ACHD cardiologists were 21%, mostly practicing in North America (44.1%) and Europe (32.9%). Almost all ACHD cardiologists (94.7%) recommended it as a career. Among the 641 non-ACHD cardiologists, 85.7% had been exposed to ACHD, however, only 35.1% considered pursuing it themselves. For ACHD cardiologists the top global motivators for pursuing an ACHD career were awareness of the field and its significance, mentor's influence, and sufficient clinical exposure during residency (Figure 1A). Factors that deterred non-ACHD cardiologists included a lack of compensation compared to other cardiology subspecialties, limited job opportunities, and the longer duration of training (Figure 1B). Absence of specialized training and educational programs emerged as a major deterrent in all continents except North America. The lack of mentorship or role models in ACHD was particularly pronounced in Africa and Central and South America. Limited exposure to ACHD during training was a significant issue in Europe and Africa. CONCLUSION: Most ACHD cardiologists recommend a career in ACHD. However, only a few non-ACHD cardiologists recommend it. Influential mentors, clinical exposure motivate; low compensation, lengthy training deter. Regional disparities require targeted interventions for better ACHD cardiologist recruitment.