Pulmonology Commons^™

Bronchoalveolar Lavage Neutrophils And Matrix Metalloproteinase-9 In Sarcoidosis Clinical Phenotypes: Implications For Tissue Remodeling Leading To Pulmonary Fibrosis, Rafael L. Perez, Md, Jeff Ritzenthaler, E. Torres-Gonzalez, Prarthna Chandar, Md, Daniel Kramer, Md, Jesse Roman, Md

Division of Pulmonary, Allergy, and Critical Care Medicine Posters

Introduction

Pulmonary sarcoidosis may resolve or progress to advanced stages. Increased lung neutrophils obtained by bronchoalveolar lavage are found in advanced pulmonary sarcoidosis. Persistence of a neutrophilic alveolitis has been postulated to result in tissue injury and remodeling that leads to fibrosis and clinical features of advanced disease. Since neutrophils are a source of matrix-degrading proteins like matrix metalloproteinases (MMPs), we hypothesized that PMNs promote disease progression through the release of MMPs. This work explores the relationship between lung neutrophils and MMP9 levels and activity and how they are associated with sarcoidosis clinical phenotypes.

Issue 9: Pulmonary & Critical Care Insider, Bharat Bajantri Md, Sarah Ellsworth-Hoffman Mls, Ya Gao Md, Sivaprakash Sivaji Do, Caleb Hoppe Pharmd

Critical Care & Pulmonary

Pulmonary & Critical Care Insider Issue 9

Compiled by Bharat Bajantri, MD, and librarian Sarah Ellsworth, MLS for the clinicians of the Pulmonary and Critical Care team of Parkview.

The Pulmonary & Critical Care Insider newsletter was created by Dr. Bharat Bajantri, MD and Sarah Ellsworth, MLS in 2023 as a form of current awareness for current practice at our hospital, Parkview Health.

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Topics:

VIEWPOINTS:

Non-Shockable Cardiac Arrest Management

Try and try again till CPAP succeeds!

ORIGINAL STUDY SUMMARY & PERSPECTIVE:

Fungal Pneumonias in the ICU: Clinical Insights and Diagnostic Strategies.

ARDS Update and Guidance

SNAPSHOTS:

Making sure massive …

Breathless Laughter: Tackling Tussive Syncope In The Shadows Of Obstructive Sleep Apnea, Milan Terzic, Yash B. Patel

Graduate Medical Education Research Journal

Cough is a common complaint in the inpatient and outpatient setting. Most cases are caused by upper airway syndrome, gastroesophageal reflux disease, asthma, bronchitis, or infections. Complications that can be life-threatening include syncope and arrhythmias. Our case is of a 67-year-old obese male who had a chronic cough that led to syncope. The chronic cough was present for months, non-responsive to symptomatic treatment, and negative on outpatient work up with no clear common causes leading to hospitalization. After extensive imaging and cardiopulmonary work up yielding normal results, his underlying obstructive sleep apnea and therapy noncompliance was a likely cause. After …

Association Of Mildly Elevated Pulmonary Vascular Resistance With Major Cardiovascular Events In Pulmonary Hypertension And Chronic Kidney Disease: A Retrospective Cohort Analysis, Jose M. Martinez Manzano, Alexander Prendergast, Tara John, Raul Leguizamon, Ian Mclaren, Rasha Khan, Andrew Geller, Phuuwadith Wattanachayakul, John Malin, Simone A. Jarrett, Kevin Bryan Lo, Sadia Benzaquen, Christian Witzke

Einstein Health Papers

Pulmonary hypertension (PH) is associated with adverse outcomes in chronic kidney disease (CKD) patients. Our study suggests mildly elevated pulmonary vascular resistance ( > 2 to ≤ 3) is independently associated with major adverse cardiovascular events at 1-year follow-up. Early diagnosis of precapillary PH in CKD patients can potentially improve clinical outcomes.

Navigating Diagnostic And Treatment Challenges Of Pulmonary Hypertension In Infants With Bronchopulmonary Dysplasia., Nidhy P. Varghese, Gabriel Altit, Megan M. Gubichuk, Roopa Siddaiah

Manuscripts, Articles, Book Chapters and Other Papers

Advances in perinatal intensive care have significantly enhanced the survival rates of extremely low gestation-al-age neonates but with continued high rates of bronchopulmonary dysplasia (BPD). Nevertheless, as the survival of these infants improves, there is a growing awareness of associated abnormalities in pulmonary vascular development and hemodynamics within the pulmonary circulation. Premature infants, now born as early as 22 weeks, face heightened risks of adverse development in both pulmonary arterial and venous systems. This risk is compounded by parenchymal and airway abnormalities, as well as factors such as inflammation, fibrosis, and adverse growth trajectory. The presence of pulmonary hypertension in …

The Emerging Biomarkers In Chronic Obstructive Pulmonary Disease: A Narrative Review, Kaitlin M Phillips, Philip F Lavere, Nicola A Hanania, Muhammad Adrish

Faculty, Staff and Students Publications

The burden of chronic obstructive pulmonary disease (COPD) is increasing, especially for women in low-to-middle income countries. Biomarkers provide ever-increasing diagnostic precision for COPD and show promise for primary, secondary, and tertiary disease prevention. This review describes emerging applications for biomarkers in COPD, especially as they align with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) emphasis on prevention, early diagnosis, and response to therapy. These biomarkers include blood eosinophils; IgE; C-reactive protein; fibrinogen; procalcitonin; interleukins 6, 8, and 33; tumor necrosis factor alpha; and soluble receptor for advanced glycated products (sRAGE). They have been used in various ways …

Community-Acquired Pneumonia: The Importance Of The Early Detection Of Drug-Resistant Organisms, Sai Doppalapudi, Muhammad Adrish

Faculty, Staff and Students Publications

Pneumonia is a disease associated with significant healthcare burden with over 1.5 million hospitalizations annually and is the eighth leading cause of death in the United States. While community-acquired pneumonia (CAP) is generally considered an acute time-limited illness, it is associated with high long-term mortality, with nearly one-third of patients requiring hospitalization dying within one year. An increasing trend of detecting multidrug-resistant (MDR) organisms causing CAP has been observed, especially in the Western world. In this editorial, we discuss about a publication by Jatteppanavar

Driving Pressure Decoded: Precision Strategies In Adult Respiratory Distress Syndrome Management, Muhammad Adrish, Sai Doppalapudi, Dmitry Lvovsky

Faculty, Staff and Students Publications

Mechanical ventilation (MV) is an important strategy for improving the survival of patients with respiratory failure. However, MV is associated with aggravation of lung injury, with ventilator-induced lung injury (VILI) becoming a major concern. Thus, ventilation protection strategies have been developed to minimize complications from MV, with the goal of relieving excessive breathing workload, improving gas exchange, and minimizing VILI. By opting for lower tidal volumes, clinicians seek to strike a balance between providing adequate ventilation to support gas exchange and preventing overdistension of the alveoli, which can contribute to lung injury. Additionally, other factors play a role in optimizing …

Identification Of Sleep Phenotypes In Copd Using Machine Learning-Based Cluster Analysis, Javad Razjouyan, Nicola A Hanania, Sara Nowakowski, Ritwick Agrawal, Amir Sharafkhaneh

Faculty, Staff and Students Publications

BACKGROUND: Disturbed sleep in patients with COPD impact quality of life and predict adverse outcomes.

RESEARCH QUESTION: To identify distinct phenotypic clusters of patients with COPD using objective sleep parameters and evaluate the associations between clusters and all-cause mortality to inform risk stratification.

STUDY DESIGN AND METHODS: A longitudinal observational cohort study using nationwide Veterans Health Administration data of patients with COPD investigated for sleep disorders. Sleep parameters were extracted from polysomnography physician interpretation using a validated natural language processing algorithm. We performed cluster analysis using an unsupervised machine learning algorithm (K-means) and examined the association between clusters and mortality …

Risk Factors For Early Mortality From Lung Cancer: Evolution Over The Last 20 Years In The French Nationwide Kbp Cohorts, T C T Hoang, D Debieuvre, A-S Bravard, S Martinez, G Le Garff, S Jeandeau, L Petit, D Marquette, K Amrane, P Demontrond, M Tiercin, B Jarjour, A Turlotte, P Masson, M Jaafar, P-A Hauss, H Morel

Faculty, Staff and Students Publications

BACKGROUND: The impact of the most recent advances, including targeted therapies and immune checkpoint inhibitors, on early (3-month) mortality in lung cancer is unknown. The aims of this study were to evaluate the real-world rate of and risk factors for early mortality, as well as trends in early mortality over the last 20 years.

MATERIALS AND METHODS: The KBP prospective observational multicenter studies have been conducted every 10 years since 2000. These studies collect data on all newly diagnosed patients with lung cancer (all stages and histologies) over 1 year in non-academic public hospital pulmonology or oncology units in France. …

Pulmonary Hypertension And Hyperglycemia-Not A Sweet Combination, Or Bruck, L M Pandit

Faculty, Staff and Students Publications

Hyperglycemia and pulmonary hypertension (PH) share common pathological pathways that lead to vascular dysfunction and resultant cardiovascular complications. These shared pathologic pathways involve endothelial dysfunction, inflammation, oxidative stress, and hormonal imbalances. Individuals with hyperglycemia or pulmonary hypertension also possess shared clinical factors that contribute to increased morbidity from both diseases. This review aims to explore the relationship between PH and hyperglycemia, highlighting the mechanisms underlying their association and discussing the clinical implications. Understanding these common pathologic and clinical factors will enable early detection for those at-risk for complications from both diseases, paving the way for improved research and targeted therapeutics.

Not Your Typical Recurrent Pericarditis Patient!, Tarek Alsibai, Naomi Cret, Shaiva G. Meka

Conference Presentation Abstracts

No abstract provided.

From Immune Checkpoint Inhibition To Intubation, Sabena Toor, Samridhi Gulati, Shaiva G. Meka

Conference Presentation Abstracts

No abstract provided.

The Calcineurin-Nfatc Pathway Modulates The Lipid Mediators In Bal Fluid Extracellular Vesicles, Thereby Regulating Microvascular Endothelial Cell Barrier Function, Manjula Karpurapu, Yunjuan Nie, Sangwoon Chung, Jiasheng Yan, Patrick Dougherty, Sonal Pannu, Jon Wisler, Ryan Harkless, Narasimham Parinandi, Evgeny Berdyshev, Dehua Pei, John W Christman

Faculty, Staff and Student Publications

Extracellular vesicles mediate intercellular communication by transporting biologically active macromolecules. Our prior studies have demonstrated that the nuclear factor of activated T cell cytoplasmic member 3 (NFATc3) is activated in mouse pulmonary macrophages in response to lipopolysaccharide (LPS). Inhibition of NFATc3 activation by a novel cell-permeable calcineurin peptide inhibitor CNI103 mitigated the development of acute lung injury (ALI) in LPS-treated mice. Although pro-inflammatory lipid mediators are known contributors to lung inflammation and injury, it remains unclear whether the calcineurin-NFATc pathway regulates extracellular vesicle (EV) lipid content and if this content contributes to ALI pathogenesis. In this study, EVs from mouse …

High All-Cause Mortality And Increasing Proportion Of Older Adults With Tuberculosis In Texas, 2008–2020, Belinda A Medrano, Miryoung Lee, Gretchen Gemeinhardt, Lana Yamba, Blanca I Restrepo

Faculty, Staff and Student Publications

Pulmonary tuberculosis (PTB) elimination efforts must consider the global growth of the ageing population. Here we used TB surveillance data from Texas, United States (2008-2020; total n = 10656) to identify unique characteristics and outcomes in older adults (OA, ≥65 years) with PTB, compared to young adults (YA, 18-39 years) or middle-aged adults (40-64 years). We found that the proportion of OA with PTB increased from 15% in 2008 to 24% in 2020 (trend p < 0.05). Diabetes was highly prevalent in OA (32%) but not associated with adverse outcomes. Death was 13-fold higher in OA compared to YA and was 7% at the time of diagnosis which suggests diagnostic delays. However, once TB was suspected, we found no differences in culture, smear, or nucleic acid detection of mycobacteria (although less lung cavitations) in OA. During treatment, OA had less drug-resistant TB, few adverse reactions and adhered with TB treatment. We recommend training healthcare workers to 'think TB' in OA, for prompt treatment initiation to diminish deaths. Furthermore, OA should be added as a priority group to the latent TB treatment guidelines by the World Health Organization, to prevent TB disease in this highly vulnerable group.

A Case Study On The Effects Of Pregnancy On Expiratory Flow Limitation (Efl) And Operating Lung Volumes During Exercise, Hannah Young

Masters Theses, 2020-current

The purpose of this study was to examine the effects of pregnancy on expiratory flow limitation (EFL) and operating lung volumes (end expiratory lung volume and end inspiratory lung volume; EELV and EILV) during exercise, with an exploratory aim to assess differences in the above measures between exercise modalities. EFL has been shown to occur in several other subgroups but has never been studied in pregnant individuals. We followed one 35-year-old pregnant subject throughout her pregnancy, completing exercise and pulmonary testing every other week from 8 weeks gestation to 38 weeks gestation, and once again ~8 weeks postpartum. Testing was …

Ras G-Domains Allosterically Contribute To The Recognition Of Lipid Headgroups And Acyl Chains, Neha Arora, Huanwen Mu, Hong Liang, Wenting Zhao, Yong Zhou

Faculty, Staff and Student Publications

Mutant RAS are major contributors to cancer and signal primarily from nanoclusters on the plasma membrane (PM). Their C-terminal membrane anchors are main features of membrane association. However, the same RAS isoform bound to different guanine nucleotides spatially segregate. Different RAS nanoclusters all enrich a phospholipid, phosphatidylserine (PS). These findings suggest more complex membrane interactions. Our electron microscopy-spatial analysis shows that wild-types, G12V mutants, and membrane anchors of isoforms HRAS, KRAS4A, and KRAS4B prefer distinct PS species. Mechanistically, reorientation of KRAS4B G-domain exposes distinct residues, such as Arg 135 in orientation state 1 (OS1) and Arg 73/Arg 102 in OS2, …

Bronchopulmonary Dysplasia: Pathophysiology And The Effects Of The Microbiome, Anjali Jacob

Senior Honors Theses

Bronchopulmonary dysplasia (BPD) is a chronic neonatal lung disease that occurs in over 50% of premature infants. BPD is characterized by damage to the alveoli and bronchioles and improper vasculature formation. It is primarily caused by overexposure to oxygen through mechanical ventilation, but there are other risk factors that make infants more susceptible to BPD. Microbial composition impacts risk for developing BPD, and research is ongoing about the effects of the microbiome on BPD pathogenesis; this information is also valuable for preventative treatment. This paper reviews the normal function of the lungs, pathogenesis of BPD and how it affects normal …

The Utility Of The Pap Nap For Increasing Patient Utilization Of Positive Airway Pressure Therapy, Erin Creighton, Md, Nicole Molin, Md, Dimitri Markov, Md, Ritu Grewal, Md

Health Equity and Quality Improvement (HEQI) Summit

Background

Problem Statement:

• An estimated 9-38% of adults have obstructive sleep apnea (OSA), and about 80% is undiagnosed.
• OSA has been linked to excessive sleepiness, neurocognitive impairments, reduced quality of life, diabetes, heart disease, stroke, hypertension, and motor vehicle and workplace accidents
• Approximately85% of people with diagnosed OSA receive PAP and only 35-60% remain compliant long term
• Many factors impact CPAP use: disease and patient characteristics, titration procedures, device factors, side effects, psychological and social factors

Project AIM: Evaluate whether a daytime, abbreviated cardio-respiratory sleep study (AKA the PAP NAP -developed to help improve adherence in patients with OSA and …

Pleural Epithelioid Hemangioendothelioma: An Ultra Rare Etiology For Recurrent Pleural Effusion, Ali Khreisat, Paul Bozyk

Conference Presentation Abstracts

Introduction Epithelioid hemangioendothelioma (EHE) is an extremely rare sarcoma of vascular origin. EHE has an incidence of less than 0.1 per 100,000 patients per year. It can involve multiple organs; pleural involvement is relatively rare and under-reported in the medical literature. We present a unique case of pleural EHE presenting with recurrent pleural effusion, severe pleuritis, scarring, and trapped lung syndrome. Case presentation A 54-year-old Caucasian female was referred to the pulmonary clinic for two months of progressive dyspnea, fatigue, and right pleuritic chest pain. Initial chest x-ray showed a large right pleural effusion. Thoracentesis identified exudative lymphocyte predominant pleural …

Case Report: Post-Obstructive Pneumonia Secondary To Foreign Body Aspiration, Aashna Chaudhry, Andrew Vasta

Rowan-Virtua Research Day

Post-obstructive pneumonia is described as a pulmonary infiltrate that occurs proximal to the site of an obstructed bronchus. Studies show that post-obstructive pneumonia most commonly secondary to obstruction caused by neoplasms. According to a study done on post obstructive pneumonia in lung cancer, most cases of post obstructive pneumonias are associated with advanced neoplasms with up to 50% of those with advanced cancer getting endobronchial compromise. While neoplasms are the most common cause of post obstructive pneumonia, research is scarce on other potential causes of post obstructive pneumonia. This case reports presents a unique clinical case in which an adult …

Issue 8: Pulmonary & Critical Care Insider, Bharat Bajantri Md, Sarah Ellsworth-Hoffman Mls, Caterina Elliott Np, Pa, Donna Cota Md

Critical Care & Pulmonary

Pulmonary & Critical Care Insider Issue 8

Compiled by Bharat Bajantri, MD, and librarian Sarah Ellsworth, MLS for the clinicians of the Pulmonary and Critical Care team of Parkview.

The Pulmonary & Critical Care Insider newsletter was created by Dr. Bharat Bajantri, MD and Sarah Ellsworth, MLS in 2023 as a form of current awareness for current practice at our hospital, Parkview Health. The content resides within critical care and pulmonary related topics and this information is compiled into four main formats.

1. Original Study Summaries: New research publications are read, reviewed, then concisely summarized for clinical interpretation with professional …

Age At Lung Cancer Diagnosis In Females Versus Males Who Never Smoke By Race And Ethnicity, Batel Blechter, Jason Y Y Wong, Li-Hsin Chien, Kouya Shiraishi, Xiao-Ou Shu, Qiuyin Cai, Wei Zheng, Bu-Tian Ji, Wei Hu, Mohammad L Rahman, Hsin-Fang Jiang, Fang-Yu Tsai, Wen-Yi Huang, Yu-Tang Gao, Xijing Han, Mark D Steinwandel, Gong Yang, Yihe G Daida, Su-Ying Liang, Scarlett L Gomez, Mindy C Derouen, W Ryan Diver, Ananya G Reddy, Alpa V Patel, Loïc Le Marchand, Christopher Haiman, Takashi Kohno, Iona Cheng, I-Shou Chang, Chao Agnes Hsiung, Nathaniel Rothman, Qing Lan

Faculty, Staff and Student Publications

BACKGROUND: We characterized age at diagnosis and estimated sex differences for lung cancer and its histological subtypes among individuals who never smoke.

METHODS: We analyzed the distribution of age at lung cancer diagnosis in 33,793 individuals across 8 cohort studies and two national registries from East Asia, the United States (US) and the United Kingdom (UK). Student's t-tests were used to assess the study population differences (Δ years) in age at diagnosis comparing females and males who never smoke across subgroups defined by race/ethnicity, geographic location, and histological subtypes.

RESULTS: We found that among Chinese individuals diagnosed with lung cancer …

Safety And Efficacy Of Ivacaftor In Infants Aged 1 To Less Than 4 Months With Cystic Fibrosis., Paul Mcnally, Alvin Singh, Susanna A. Mccolley, Jane C. Davies, Mark Higgins, Meng Liu, Jennifer Lu, Violeta Rodriguez-Romero, Judy L. Shih, Margaret Rosenfeld, Vx15-770-124 Study Group

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Ivacaftor (IVA) has been shown to be safe and efficacious in children aged ≥4 months with cystic fibrosis (CF) and CFTR gating variants. We evaluated safety, pharmacokinetics (PK), and efficacy of IVA in a small cohort of infants aged 1 toCF.

METHODS: In this phase 3, open-label study, infants 1 toinfants, doses were adjusted at day 15 to better match median adult exposures based on individual PK measurements taken on day 4. Primary endpoints were safety and PK measurements.

RESULTS: Seven infants (residual function CFTR variants [n=5]; minimal function CFTR variants [n=2]) received ≥1 dose of IVA. Six infants …

Pulmonary Embolism In Pregnancy And Early Postpartum – Identifying Significant Variables To Improve Risk Stratification, Nida Haider, Bhavinkumar Dalal

Posters

• Pulmonary embolism (PE) resulting from deep vein thrombosis (DVT) is one of the leading causes of maternal deaths in developed countries1
• The causative Virchow triad (venous stasis, endothelial injury, and hypercoagulable state) is enhanced in pregnancy making pregnancy an independent risk factor1
• Due to significant overlap between normal physiological changes in pregnancy and clinical symptoms of PE, the threshold for CTPA, confirmatory imaging for PE with potentially harmful effects due to ionizing radiation, is low with increasing incidence of false positives2

The American Thoracic Society Research Program: Twenty Years Of Driving Discovery In Respiratory Medicine, Kamran Atabai, M. Safwan Badr, Jack Costello, Karen Ridge, Sharon Rounds, Michelle Turenne, Eric White, Jesse Roman

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

No abstract provided.

Evaluating The Association Of Influenza Vaccination On Long-Term Covid-19 Symptoms In U.S. Adults, Ratnakar Pingili

Capstone Experience: Master of Public Health

Objective. To evaluate the association of influenza vaccination in the past 12 months with Long COVID effects and clinical and sociodemographic factors.

Methods. Cross-sectional study with data from the 2022 Behavioral Risk Factor Surveillance System (BRFSS), covering 415,132 non-institutionalized U.S. adults with a confirmed COVID-19 diagnosis and influenza vaccination reported within the last 12 months. Logistic regression was conducted between influenza vaccination (exposure) and Long COVID (outcome), controlling for demographic variables, pre-existing health conditions, and socioeconomic status.

Results. Of 120,603 participants, 21.89% reported Long COVID symptoms and 42.04% had received an influenza vaccine. Findings indicate a statistically significant 13% reduction …

Clinical Differences In Isolated Post-Capillary Pulmonary Hypertension And Combined Pre- And Postcapillary Pulmonary Hypertension, Emily Schneider, Bhavinkumar D. Dalal

Posters

PULMONARY HYPERTENSION (PH) = RESTING MEAN PULMONARY ARTERY PRESSURE (MPAP) > 20 MMHG.

The World Health Organization recognizes five groups of pulmonary hypertensions:

• • Estimated that > 50% of patients with left heart disease are also affected by pulmonary hypertension.1
• 1 in 4 Americans will develop heart failure in their lifetime.
• Gold standard for diagnosis of PH is a right heart catheterization (RHC).3
• Global burden of PH remains unknown as this illness is poorly surveilled and cases remain underestimated.4,5

Understanding Infectious Disease Consultation Role For Septic Patients In The Medical Intensive Care Unit, Marisa Stratelak, Cloe Nazeer, Bhavinkumar Dalal

Posters

• Sepsis is a medical emergency requiring immediate recognition and prompt treatment.
• 1 in every 3 hospitalized patients who die have sepsis1.
• The mortality rate for patients with severe sepsis in the intensive care unit (ICU) is 32.2%2.
• Early intervention with fluid resuscitation and intravenous antibiotics can reduce mortality rates by 7-9%3.
• Infectious disease (ID) consultation on antimicrobial therapy in the ICU is associated with reduced ICU mortality and ICU length of stay (LOS)4.
• Gaps in literature exist regarding frequency of ID consultation for septic patients in the ICU, including comparing outcomes of patients with and without ID consultation.
• It is …

Pulmonary Endobronchial Hamartoma Presenting With Post-Obstructive Pneumonia, Diane S Habib, Pushan Jani, Bihong Zhao, Elakiya Anjali Jayaraman, Ramesh Kesavan

Faculty, Staff and Student Publications

Pulmonary hamartomas (PH) are rare but are the most common benign tumors found in the lungs. They are slow-growing and are usually found incidentally on chest imaging during the sixth decade of life. Approximately 10% of pulmonary hamartomas are endobronchial. Rarely, pulmonary hamartomas can cause a spectrum of pulmonary symptoms depending on their size and location. We present a case of endobronchial hamartoma causing airway obstruction and recurrent post-obstructive pneumonia.