A5065906558- Asthma and respiratory diseases
- Nitric Oxide and Endothelin Effects
- Neuroscience of respiration and sleep
- Neonatal Respiratory Health Research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Cystic Fibrosis Research Advances
- Respiratory and Cough-Related Research
- Inhalation and Respiratory Drug Delivery
- Sulfur Compounds in Biology
- Respiratory Support and Mechanisms
- IL-33, ST2, and ILC Pathways
- Respiratory viral infections research
- Hemoglobin structure and function
- High Altitude and Hypoxia
- Pediatric health and respiratory diseases
- Tracheal and airway disorders
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cancer, Hypoxia, and Metabolism
- Analytical Chemistry and Sensors
- Immune Cell Function and Interaction
- Allergic Rhinitis and Sensitization
- Redox biology and oxidative stress
- Neuroscience and Neuropharmacology Research
- Gastroesophageal reflux and treatments
- Pulmonary Hypertension Research and Treatments
Riley Hospital for Children
2019-2025
Indiana University
2020-2025
Indiana University Health
2025
Indiana University School of Medicine
2019-2024
Indiana University – Purdue University Indianapolis
2019-2024
Case Western Reserve University
2014-2024
University School
2014-2024
University of Virginia
2008-2023
Indiana University Indianapolis
2020-2023
Herman Miller (United States)
2023
Rationale: The Severe Asthma Research Program cohort includes subjects with persistent asthma who have undergone detailed phenotypic characterization. Previous univariate methods compared features of mild, moderate, and severe asthma.Objectives: To identify novel phenotypes using an unsupervised hierarchical cluster analysis.Methods: Reduction the initial 628 variables to 34 core was achieved by elimination redundant data transformation categorical into ranked ordinal composite variables....
Nitric oxide synthase (NOS) produces nitric oxide, a mediator of potential importance in numerous physiologic and inflammatory processes the lung. We localized constitutive NOS (c-NOS) inducible (i-NOS) within lung tissue by immunoperoxidase labeling with specific antibodies or histochemical demonstration characteristic NADPH diaphorase activity NOS. analyzed human airway (n = 4) parenchyma 10) specimens obtained from uninvolved areas surgical tumor resections. also studied fetal samples 6)...
Airway concentrations of many reactive nitrogen and oxygen species are high in asthma. The stability bioactivities these pH-dependent; however, the pH airway during acute asthma has not previously been studied. As with gastric urinary acidification, asthmatic acidification could be expected dramatically to alter bioactivities/cytotoxicities endogenous oxides. Here, we demonstrate that deaerated exhaled vapor condensate is over two log orders lower patients (5.23 ± 0.21, n = 22) than control...
Recent discoveries suggesting essential bioactivities of nitric oxide (NO.) in the lung are difficult to reconcile with established pulmonary cytotoxicity this common air pollutant. These conflicting observations suggest that metabolic intermediaries may exist modulate bioactivity and toxicity NO.. We report S-nitrosothiols (RS-NO), predominantly adduct glutathione, present at nano- micromolar concentrations airways normal subjects their levels vary different human pathophysiologic states....
Histochemical activity and immunoreactivity of nitric oxide synthase (NOS, EC 1.14.13.39) have been recently demonstrated in human lung epithelium. However, the molecular nature NOS regulation function enzyme(s) airway is not known. A549 cells (human alveolar type II epithelium-like), BEAS 2B (transformed bronchial epithelial cells), primary cultures all exhibited constitutive that was calcium dependent inhibitable by inhibitor NG-monomethyl-L-arginine. Nitric production enhanced culture...
Many hereditary and sporadic neurodegenerative disorders are characterized by the accumulation of aberrant proteins. In Parkinson's disease, representing most prevalent movement disorder, oxidative nitrosative stress believed to contribute disease pathogenesis, but exact molecular basis for protein aggregation remains unclear. case autosomal recessive-juvenile Parkinsonism, mutation in E3 ubiquitin ligase parkin is linked death dopaminergic neurons. Here we show both vitro vivo that leads S...
Reducing asthma exacerbation frequency is an important criterion for approval of therapies, but the clinical features exacerbation-prone (EPA) remain incompletely defined.To describe clinical, physiologic, inflammatory, and comorbidity factors associated with EPA.Baseline data from NHLBI Severe Asthma Research Program (SARP)-3 were analyzed. An was defined as a burst systemic corticosteroids lasting 3 days or more. Patients classified by their number exacerbations in past year: none, few...
Five to ten percent of asthma cases are poorly controlled chronically and refractory treatment, these severe account for disproportionate asthma-associated morbidity, mortality, health care utilization. While persons with tend have more airway obstruction, it is not known whether they represent the tail a unimodal population, or phenotype. We hypothesized that has characteristic physiology we evaluated spirometry, lung volumes, reversibility during stable interval in 287 382 nonsevere...
Severe asthma (SA) remains poorly understood. Mast cells (MC) are implicated in pathogenesis, but it unknown how their phenotype, location, and activation relate to severity.
Rationale: Exhaled nitric oxide (FeNO) is a biomarker of airway inflammation in mild to moderate asthma. However, whether FeNO levels are informative regarding patients with severe asthma, who refractory conventional treatment, unknown. Here, we hypothesized that classification asthma based on as defined by would identify more reactive, at-risk phenotype.Methods: and major features including inflammation, airflow limitation, hyperinflation, hyperresponsiveness, atopy, were determined 446...
The National Heart, Lung, and Blood Institute Severe Asthma Research Program (SARP) has characterized over the past 10 years 1,644 patients with asthma, including 583 individuals severe asthma. SARP collaboration led to a rapid recruitment of subjects efficient sharing samples among participating sites conduct independent mechanistic investigations Enrolled underwent detailed clinical, physiologic, genomic, radiological evaluations. In addition, investigators developed safe procedures for...
Neutrophil cytoplasts promote T H 17 inflammation.
Caspase-3 is a cysteine protease located in both the cytoplasm and mitochondrial intermembrane space that central effector of many apoptotic pathways. In resting cells, subset caspase-3 zymogens S-nitrosylated at active site cysteine, inhibiting enzyme activity. During Fas-induced apoptosis, caspases are denitrosylated, allowing catalytic to function. current studies, we sought identify subpopulation regulated by S-nitrosylation. We report majority mitochondrial, but not cytoplasmic, contain...
Exhaled breath condensate (EBC) pH is low in several lung diseases and it normalises with therapy. The current study examined factors relevant to EBC monitoring. Intraday intraweek variability were studied 76 subjects. of collected orally from isolated lower airways was compared an additional 32 Effects ventilatory pattern (hyperventilation/hypoventilation), airway obstruction after methacholine, temperature (-44 +13 degrees C) duration collection (2-7 min), sample storage (up 2 yrs)...