Bronchitis

Cigarette smoking has detrimental effects on nearly every organ in the body, leading to a higher incidence of diseases and contributing to a gradual deterioration of the smoker's health, including a progressive impairment of lung function. Cigarette smoking is linked to mild airway obstruction and a deceleration in the growth of lung function. Smokers may experience inflammation and narrowing of their airways, resulting in increased resistance to the outward flow of air during exhalation. This restriction in airflow can negatively impact respiratory parameters, exercise tolerance, and overall quality of life. Performing balloon-blowing exercises with abdominal and lumbar core muscles activation position leads to an improvement on pulmonary function and quality of life in smokers.

the inhaled nitroglycerin is expected to make vasodilatation of the pulmonary arteries and arterioles which are constricted in late stages of COBD leading to ventilation/perfusion mismatching and further aggravating COPD. it will also help in delivering better antibiotic concentrations to the alveoli which help in better control of infection.

Background: Almost 3 billion people worldwide, including 89% people in Bangladesh, are exposed to harmful household air pollutants (HAP) emitted from combustion of biomass fuel (wood, agricultural residue, cow dung, etc.) used for cooking. While health risks associated with air-pollution have been reasonably well-studied in developed countries, there is little evidence on health benefits achievable by HAP reduction through clean fuel use such as Liquid Petroleum Gas, especially in low- and middle-income countries (LMICs). Rationale: In the earlier GEOHealth (Round-I) study, the investigators have shown that LPG for 24 months, reduced personal PM2.5 exposure by 58.2 percent which induced novel changes in innate immune and inflammatory responses in women but the changes in chronic cardio-pulmonary markers were not prominent, most likely due to short duration of follow up and probably impact of ambient pollution. Moreover, sustained use of LPG could be challenging as earlier GEOHealth (Round-I) study provided the cook stove and supply of LPG free of cost. A post-completion screening showed \>70% households continued using LPG albeit not exclusively. It is plausible that an intervention using mobile phone-based application can improve the exclusive use of LPG in the communities. Hypothesis: 1. The mobile phone based (mHealth) Behavioural Change Communication (BCC) intervention can be easily incorporated in Government policy that can promote adoption, and increase exclusive use of LPG in the communities. The long-term effect of HAP reduction can be associated with- 2. subclinical measures of cardio-vascular and pulmonary dysfunction. 3. balanced changes in innate/ inflammatory and adaptive immune function (vaccine response). Objectives: To evaluate 1. The effects of a scalable educational intervention (using mHealth application) on adoption and exclusive use of LPG. 2. The long-term effects of HAP reduction on subclinical measures of cardio-vascular and pulmonary dysfunction. 3. The long-term effects of HAP reduction on innate/ inflammatory immune function among women and children and to investigate the influence of HAP exposure on antibody response to vaccines (adaptive immunity). Methods: The investigators will conduct a large household level randomized controlled trial by educational intervention using mobile phone (mHealth) based technology. In addition, the investigators will continue following the cohort and will conduct rigorous and repeated personalized (24 hours) and area-wise (over 5 days) assessments of PM2.5 and black carbon (BC) exposure to examine the long-term effects of HAP reduction on subclinical measures of cardio-pulmonary and immune dysfunction including effect of HAP exposure on antibody response to vaccine. Outcome measures/variables: Personal and surrounding area PM2.5 and BC level will be measured at pre- and post-intervention. Lung function and lung pathology will be assessed through spirometry, Chest X-ray, and High-resolution Computed tomography of the chest (HRCT). Preclinical makers of cardiovascular diseases (CVD) will include blood pressure and EKG. Markers of metabolic dysfunction will be assesses by measuring HbA1c and fasting lipid profile. Immune function will be assessed by phenotyping of Immune cells, functional cytotoxic killer cells, oxidative stress of lymphocytes.

Briefly, during a one to two hour visit, subjects will provide written informed consent and then undergo: 1. brief medical history and vital signs, 2. full pulmonary function tests, 3. proton MRI, 4. spin-density, diffusion weighted, and/or dissolved phase 129-Xe MRI, 5. Low-dose thoracic CT Full pulmonary function tests including spirometry, plethysmography and diffusing capacity of carbon monoxide (DLCO), Multiple Breath Nitrogen Washout (MBNW) to measure Lung Clearance Index (LCI), and Forced Oscillation Technique (FOT) will be performed according to American Thoracic Society (ATS) guidelines. MedGraphics Elite Series, MedGraphics Corporation. St. Paul, Minnesota USA and/or nDD EasyOne Spirometer, nDD Medical Technologies Inc. Andover, Massachusetts USA will be used. All measurements will be performed in the Pulmonary Function Laboratory at Robarts Research Institute. Subjects will be placed in the 3T Magnetic Resonance (MR) scanner with one of three 129-Xe chest coils fitted over their torso and chest. Hearing protection will be provided to each subject to muffle the noise produced by the gradient radiofrequency (RF) coils. A pulse oximeter lead will be attached to all of the subjects to monitor their heart rate and oxygen saturation. MRI will be performed for up to a period of 30 minutes. All subjects will have supplemental oxygen available via nasal cannula at a flow-rate of 2 liters per minute as a precaution in the event of oxygen desaturation. Thoracic low dose CT will be performed with the same inhalation breath-hold volume and maneuver (nitrogen gas only) used for MRI to obtain participant-specific high resolution images of lung anatomy (tissue structure and airway morphology).

This study focuses on the markers that are derived from the interaction of 129Xe with pulmonary capillary red blood cells (RBCs). Specifically, the investigators focus on RBC transfer MRI, cardiogenic oscillations in 129Xe-RBC signal amplitude, and the 129Xe-RBC chemical shift. In addition to healthy volunteers, the population to be studied will consist of patients scheduled to undergo either transfusion or phlebotomy, those with dyspnea, those with a physician diagnosis of interstitial lung disease (ILD), idiopathic pulmonary fibrosis (IPF), non-specific interstitial pneumonias (NSIP), chronic hypersensitivity pneumonitis (cHP), and sarcoid, as well as those with either chronic thromboembolic pulmonary hypertension (CTEPH) and acute pulmonary embolism.

Angiotensin-II (ANG-II) is the end-product of the renin-angiotensin cascade, and acts as a potent endogenous vasoconstrictor through binding to the angiotensin receptor (AT1) on arteriolar vascular smooth muscle. With advancing age, there is a notable decline in plasma renin activity accompanied by decrements in circulating ANG-II and an increase in AT1 receptor density. However, the functional consequence of this age-related adaptation of the renin-angiotensin system (RAS) on the peripheral circulation is not well understood. Likewise, in recent years it has become apparent that cardiovascular disease is a major cause of morbidity in COPD, which may be related to vascular dysfunction and associated adoption of a sedentary lifestyle. In these patients, changes in RAS activity have been linked to peripheral vascular dysfunction, with compelling evidence for improvements in peripheral oxygen use following angiotensin-converting enzyme (ACE) inhibition. Like the aging population, systematic studies evaluating AT1 receptor sensitivity and the efficacy of AT1 receptor blockade on peripheral hemodynamics have not been undertaken. The ubiquitous substance nitric oxide (NO) is now recognized as a key pathway for endothelium-dependent vasodilation, with the bioavailability of NO serving as an indicator for overall vascular health. Cardiac risk factors have been shown to cause impairment in endothelial vasodilator function in both the peripheral and coronary arteries. Coronary vascular dysfunction is an important phase in atherogenesis and is associated with myocardial ischemia. Furthermore, peripheral vascular function has been linked to coronary vascular dysfunction which could have important clinical implications in terms of health screening. Impaired endothelium-dependent vasodilation has been associated with the elderly, patients with COPD, and most cardiovascular diseases including pulmonary hypertension, and heart failure (HF), though the functional consequence of this adaptation on peripheral blood flow regulation remains unclear. Thus, we propose the use of a compound which inhibits the enzyme responsible for NO production in endothelial cells, N-monomethyl-L-arginine (L-NMMA), to temporarily block production of NO and thus determine the importance of this pathway at rest and during physical activity. Additionally, we propose the use of acetylcholine (Ach) to determine endothelial-dependent vasodilation and sodium nitroprusside (SNP) and nitroglycerin (NTG) to determine the endothelial-independent vasodilation in the coronary arteries and the periphery. Oxidative stress associated with aging has been shown to reduce vascular function and antioxidant supplementation restores vascular function to levels that are indistinguishable from healthy young adults. The manner by which this improvement in vascular function occurs is not known by may be acting through a NO dependent mechanism. Histamine has been reported to mediate sustained post-exercise vasodilation through histamine-1 (H1) and histamine-2 (H2) receptor activity, which results in a \~50% elevation in femoral artery blood flow (above resting levels) that lasts for more than 100 minutes after a single bout of moderate-intensity dynamic exercise. Vasodilation can be markedly reduced by giving either fexofenadine (Allegra, a selective H1-receptor antagonist) or ranitidine (Zantac, a selective H2-receptor antagonist). The combination of H1/H2 blockade abolishes \~80% of the post-exercise vasodilation seen after whole-body exercise such as cycling and this observation has been observed in multiple studies in young sedentary, recreationally active, and endurance trained men and women. The impact of histamine on the post-exercise vasodilatory response is substantial; however, the role of H1/H2 receptors in regulating skeletal muscle blood flow during exercise is unknown. Thus, we intend to investigate the role of H1/H2 receptors in the regulation of skeletal muscle blood during exercise as this may be an important pathway in age and disease related reductions in blood flow during exercise. Exercise training and rehabilitation can be used as an alternative approach to combat the deleterious effects oxidative stress on aging and disease. An effective exercise training intervention can decrease sympathetic nervous system activity, improve arterial compliance and vascular endothelial function, and alter the pro- and antioxidant balance resulting in improved endogenous antioxidant defense mechanisms. Moreover, exercise training concomitantly improves musculoskeletal strength and function, glucose regulation and insulin sensitivity, cardiovascular function, body composition, blood chemistry (decreased triglyceride and cholesterol levels), and overall well-being. The physiologic effect of an exercise rehabilitation program in diseases such as COPD, and pulmonary arterial hypertension (PAH) is incompletely understood. However, recent studies suggest that exercise training in this patient population is well tolerated and associated with clinically significant physiologic improvements as well as improvements in various quality of life scores. A unique feature of the proposed studies identified herein is the inclusion of a novel methodological approach to comprehensively evaluate the functional outcome of the proposed pharmacologic interventions. The recent development of a unique combination of nuclear magnetic resonance (NMR) techniques by members of our group enables near-simultaneous measurements of both muscle perfusion and metabolism in vivo. The arterial spin labeling (ASL) technique allows the measurement of both spatially and temporally resolved quantification of perfusion, while the kinetics of phosphocreatine (PCr) depletion and recovery provide high resolution measurements of muscle energetics. The interweaving of these imaging and spectroscopic modules provides the opportunity for determination of skeletal muscle perfusion and metabolism kinetics during and following the stress of physical exercise. Thus, this NMR-based approach, combined with direct measures of muscle fatigue, offers the potential to further define the individual and collective contribution of these variables to the attenuated limb blood flow in the elderly and in patients with COPD and PAH. We propose that each of these pathways outlined above represent an avenue by which vascular function is compromised in the elderly and in patients with COPD, PAH and cardiovascular disease. However, because these pathways are not mutually exclusive, the proposed studies are designed to systematically evaluate hemodynamic responses to intra-arterial or intravenous administration of pharmacologic agents specific for the AT1 receptor (ANG-II and Diovan, AT1 agonist and antagonist, respectively), the Endothelin receptor Type-A (ETA receptor) (BQ-123, ETA antagonist), and the NO pathway (L-NMMA, Ach, and SNP) both before and after exercise training.

The primary efficacy objective is to assess the effect of BLU-5937 on 24-hour cough frequency in adults with refractory chronic cough (including unexplained chronic cough) at 24 weeks.

The purpose of this study is to evaluate the influence of exercise capacity and safety of iNO at doses of 10 ppm or 40 ppm for 2 hours per day after continuous treatment for one week, which is of great significance for finding safe and effective methods for treating COPD.

This clinical trial aims to assess the impact on exercise tolerance and the safety of inhaled nitric oxide in subjects with moderate-to-severe COPD. The findings are expected to contribute to the development of safe and effective therapeutic strategies for COPD management.

This is a randomized, double-blind, placebo-controlled, dose escalation, multicenter study design. The purpose is to evaluate the safety, tolerability, pharmacokinetics, and pharmacokinetic characteristics of TQC3721 inhalation powder in Chronic Obstructive Pulmonary Disease(COPD) patients with single/multiple dose escalation.