Respiratory System Commons^™

Cellular And Molecular Mechanisms Of Lung Regeneration, Repair, And Fibrosis, Volume Ii, Yong Qiu, Xiao Xiao Tang, Shigeyuki Shichino, Prem Prakash Kushwaha, Yan Y. Sanders, Remo Castro Russo, Chunheng Mo

Department of Biomedical and Translational Sciences Faculty Publications

[Introduction] Organ fibrosis represents a substantial a major contributor to global disease burden, implicated in over 30% of cases leading to disability-associated and fatal conditions. Among these conditions, idiopathic pulmonary fibrosis (IPF) stands as a progressive and frequently fatal interstitial lung disease characterized by aberrant extracellular matrix deposition and parenchymal scarring. The prognosis for IPF patients is poor, with a median survival time of just 3–5 years (Bhattacharya and Ramachandran, 2023; Lederer and Martinez, 2018, Ma et al., 2024, Wei et al., 2024). Current FDA-approved therapeutics, Pirfenidone and Nintedanib, demonstrate capacity to attenuate functional decline in pulmonary fibrosis but remain …

Exploring The Impact Of Swimming On Asthma Management In Asian Americans, Trishtine Tran

Nursing | Senior Theses

Asthma is a respiratory disease that leads to narrowing of the airways in the lungs due to inflammation and mucus. Common symptoms include cough, wheezing, asthma attacks, excess mucus production, and decreased exercise tolerance. Pharmacological treatment methods for asthma include bronchodilators, corticosteroids, and allergy medications. Nonpharmaceutical treatments include monitoring of exposure to allergens and breathing exercises, however swimming is not as commonly suggested. The purpose of this study is to investigate whether implementation of a swimming education class will influence the effectiveness of swimming on asthma management in Asian Americans. This study aims to examine quality of life, changes in …

Prorelaxant E-Type Prostanoid Receptors Functionally Partition To Different Procontractile Receptors In Airway Smooth Muscle, Ajay P. Nayak, Elham Javed, Dominic R. Villaba, Yinna Wang, Henry P. Morelli, Sushrut D. Shah, Nicholas Kim, Rennolds S. Ostrom, Reynold A. Pannettieri Jr., Steven S. An, Dale D. Tang, Raymond B. Penn

Pharmacy Faculty Articles and Research

Prostaglandin E2 imparts diverse physiological effects on multiple airway cells through its actions on four distinct E-type prostanoid (EP) receptor subtypes (EP1–EP4). Gs-coupled EP2 and EP4 receptors are expressed on airway smooth muscle (ASM), yet their capacity to regulate the ASM contractile state remains subject to debate. We used EP2 and EP4 subtype-specific agonists (ONO-259 and ONO-329, respectively) in cell- and tissue-based models of human ASM contraction—magnetic twisting cytometry (MTC), and precision-cut lung slices (PCLSs), respectively—to study the EP2 and EP4 regulation of ASM contraction and signaling under conditions of histamine or methacholine (MCh) stimulation. ONO-329 was superior (<0.05) to ONO-259 in relaxing MCh-contracted PCLSs (log half maximal effective concentration [logEC50]: 4.9 × 10−7 vs. 2.2 × 10−6; maximal bronchodilation ± SE, 35 ± 2% vs. 15 ± 2%). However, ONO-259 and ONO-329 were similarly efficacious in relaxing histamine-contracted PCLSs. Similar differential effects were observed in MTC studies. Signaling analyses revealed only modest differences in ONO-329– and ONO-259–induced phosphorylation of the protein kinase A substrates VASP and HSP20, with concomitant stimulation with MCh or histamine. Conversely, ONO-259 failed to inhibit MCh-induced phosphorylation of the regulatory myosin light chain (pMLC20) and the F-actin/G-actin ratio (F/G-actin ratio) while effectively inhibiting their induction by histamine. ONO-329 was effective in reversing induced pMLC20 and the F/G-actin ratio with both MCh and histamine. Thus, the contractile-agonist–dependent differential effects are not explained by changes in the global levels of phosphorylated protein kinase A substrates but are reflected in the regulation of pMLC20 (cross-bridge cycling) and F/G-actin ratio (actin cytoskeleton integrity, force transmission), implicating a role for compartmentalized signaling involving muscarinic, histamine, and EP receptor subtypes.

Community-Based Asthma Assessment In Young Children: Adaptations For A Multicentre Longitudinal Study In South Asia, Mohammad Shahidul Islam, Samin Huq, Steven Cunningham, Jurgen Schwarze, Asmd Ashraful Islam, Mashal Amin, Farrukh Raza, Benazir Baloch, Muhammad Imran Nisar, Sajid Bashir Soofi

Department of Paediatrics and Child Health

Background: Systematic assessment of childhood asthma is challenging in low- and middle-income country (LMIC) settings due to the lack of standardised and validated methodologies. We describe the contextual challenges and adaptation strategies in the implementation of a community-based asthma assessment in four resource-constrained settings in Bangladesh, India, and Pakistan.
Method: We followed a group of children of age 6-8 years for 12 months to record their respiratory health outcomes. The study participants were enrolled at four study sites of the 'Aetiology of Neonatal Infection in South Asia (ANISA)' study. We standardised the research methods for the sites, trained field staff …

Interaction Between Genetic Risk Scores For Reduced Pulmonary Function And Smoking, Asthma And Endotoxin, Sinjini Sikdar, Annah B. Wyss, Mi Kyeong Lee, Thanh T. Hoang, Marie Richards, Laura E. Beane Freeman, Christine Parks, Peter S. Thorne, John L. Hankinson, David M. Umbach, Alison Motsinger-Reif, Stephanie J. London

Mathematics & Statistics Faculty Publications

Rationale Genome-wide association studies (GWASs) have identified numerous loci associated with lower pulmonary function. Pulmonary function is strongly related to smoking and has also been associated with asthma and dust endotoxin. At the individual SNP level, genome-wide analyses of pulmonary function have not identified appreciable evidence for gene by environment interactions. Genetic Risk Scores (GRSs) may enhance power to identify gene–environment interactions, but studies are few.

Methods We analysed 2844 individuals of European ancestry with 1000 Genomes imputed GWAS data from a case–control study of adult asthma nested within a US agricultural cohort. Pulmonary function traits were FEV₁, …

Budesonide Enhances Agonist-Induced Bronchodilation In Human Small Airways By Increasing Camp Production In Airway Smooth Muscle, Cynthia J. Koziol-White, Timothy B. Johnstone, Maia L. Corpuz, Gaoyuan Cao, Sarah Orfanos, Vishal Parikh, Brian Deeney, Omar Tliba, Rennolds S. Ostrom, Ian Dainty, Reynold A. Panettieri Jr.

Pharmacy Faculty Articles and Research

The non-genomic mechanisms by which glucocorticoids modulate β₂ agonist-induced-bronchodilation remain elusive. Our studies aimed to elucidate mechanisms mediating the beneficial effects of glucocorticoids on agonist-induced bronchodilation. Utilizing human precision cut lung slices (hPCLS), we measured bronchodilation to formoterol, prostaglandin E₂ (PGE₂), cholera toxin (CTX) or forskolin in the presence and absence of budesonide. Using cultured human airway smooth muscle (HASM), intracellular cAMP was measured in live cells following exposure to formoterol, PGE₂, or forskolin in the presence or absence of budesonide. We showed that simultaneous budesonide administration amplified formoterol-induced bronchodilation and attenuated agonist-induced phosphorylation …

Hypersensitivity Of Vagal Pulmonary Afferents Induced By Tumor Necrosis Factor Alpha In Mice, Ruei-Lung Lin, Qihai Gu, Lu-Yuan Lee

Physiology Faculty Publications

Tumor necrosis factor alpha (TNFα), a pro-inflammatory cytokine, plays a significant role in the pathogenesis of allergic asthma. Inhalation of TNFα also induces airway hyperresponsiveness in healthy human subjects, and the underlying mechanism is not fully understood. A recent study reported that TNFα caused airway inflammation and a sustained elevation of pulmonary chemoreflex responses in mice, suggesting a possible involvement of heightened sensitivity of vagal pulmonary C-fibers. To investigate this possibility, the present study aimed to investigate the effect of a pretreatment with TNFα on the sensitivity of vagal pulmonary afferents in anesthetized mice. After TNFα (10 μg/ml, 0.03 ml) …

Assessing Two Spirometric Criteria Of Pre-Bronchodilator And Post-Bronchodilator Fev1/Fvc Ratio In Detecting Air Flow Obstruction, Zeeshan Waheed, Muhammad Irfan, Ahmed Suleman Haque, Najmul Hasan Siddiqui, Safia Awan, Beenish Syed, Javaid Khan

Section of Pulmonary & Critical Care

OBJECTIVES: To assess the Pre-bronchodilator criteria and the Post-bronchodilator criteria of FEV1/FVC ratio in diagnosing Airflow obstruction.

METHODS: An observational study was conducted from 1988 to 2006 at the Aga Khan University Hospital Patients referred to the pulmonary function test laboratory for spirometry with bronchodilator reversibility at the hospital during the above said period were enrolled. Forced spirometry was performed according to ATS guidelines. All patients who had pre-bronchodilator criteria of airflow obstruction were analyzed and compared with the post bronchodilator criteria.

RESULTS: A total of 4222 individuals underwent spirometry out of which 4072 individuals were studied. Using the pre …

Assessment Of Asthma Control Using The Asthma Control Test At A Tertiary Care Centre In Karachi, Pakistan, Sana Shoukat, Saqib Ali Gowani, Ameer Ali Khowaja, Javaid Khan

Section of Pulmonary & Critical Care

The aim of our study was to assess asthma control among asthmatics at a tertiary care setting in Karachi using ACT questionnaire. The ACT questionnaire was filled by known asthmatics in January 2007. A total of 150 questionnaires were filled of which, 61 (40%) were males and 89 (60%) females. Mean ACT score was 17.71 +/- 4.41. Association between sex and asthma control was not statistically significant. Significant association was seen with asthma control and Ipratropium bromide inhaler. Asthma control among patients at a tertiary care centre is moderate. ACT can be used to follow patients in the hospital.

Efficient Vasoactive Intestinal Polypeptide Hydrolyzing Autoantibody Light Chains Selected By Phage Display, Sonia Tyutyulkova, Qing-Sheng Gao, Austin Thompson, Stephen I. Rennard, Sudhir Paul

Journal Articles: Pulmonary & Critical Care Med

An immunoglobulin light chain (L chain) library derived from the peripheral blood lymphocytes of a patient with asthma was cloned into a phagemid vector. Phage particles displaying L chains capable of binding vasoactive intestinal polypeptide (VIP) were isolated by affinity chromatography. Two VIP binding L chains were expressed in Escherichia coli in soluble form and purified to electrophoretic homogeneity by metal chelating and protein L affinity chromatography. Both L chains catalyzed the hydrolysis of [tyr10-125I]VIP substrate. The catalytic activity eluted at the molecular mass of the monomer form of the L chain (28 kDa) from a gel filtration column. The …