Examining the Link Between Obesity, Inflammation, and Response to Asthma Medications
AsthmaObesityAsthma is a common, long-term disease that is caused by inflammation of the airways. Inflammation also plays a role in obesity and may affect the way a person responds to asthma medication. This study will examine the relationship between obesity and inflammation and the effect they have on response to corticosteroid asthma medications.
Predicting the Diagnosis of Asthma
AsthmaDespite the development of effective medications for treatment, asthma remains a significant contributor of morbidity, mortality, and financial hardship to patients with the disease. An estimated 300 million people worldwide have asthma, making it one of the most common chronic diseases in the world. Asthma accounts for 250,000 deaths per year worldwide, and 1.7 million emergency room visits per year in the United States. Cost of asthma in the United States was an estimated $12.7 billion dollars per year in 1998, and the prevalence is increasing. In 2002, there were 13.9 million outpatient asthma visits to private physician offices and hospital outpatient departments, and 484,000 asthma hospitalizations. Children 5-17 years of age missed 14.7 million school days, and adults missed 11.8 million work days due to asthma in 2002. There is no single diagnostic test or symptom that defines asthma. Asthma is a syndrome consisting of a constellation of symptoms that include wheeze, cough, shortness of breath, and chest tightness. The diagnosis of asthma takes into account history, physical examination findings, and objective measures of pulmonary function and markers of inflammation. In many cases the diagnosis is not in question, allowing for early recognition and appropriate treatment. In other cases, confounding factors makes the diagnosis both challenging and time consuming for the physician and the patient. According to the National Asthma Education and Prevention Program Expert Panel Report 2, asthma is defined as: "a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role, in particular, mast cells, eosinophils, T lymphocytes, macrophages, neutrophils, and epithelial cells. In susceptible individuals, this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. These episodes are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment. The inflammation also causes an associated increase in the existing bronchial hyperresponsiveness to a variety of stimuli." Airway obstruction and reversibility is measured by pulmonary function testing before and after inhalation of a short acting beta agonist. Airway hyperresponsiveness is measured by methacholine challenge. Estimates of asthma prevalence are generated by the use of written questionnaires in epidemiologic studies. , One of the difficulties with reliance on questionnaires is that patients often misinterpret the questions or fail to answer the question altogether. In this study, a physician will review the questionnaire with the patient in order to clarify each question. The goal in this study is to evaluate a simplified set of questions that can be easily implemented into clinical practice that will predict the presence or absence of asthma. Hypothesis A simplified questionnaire will predict asthma in adults. Study Objectives § Primary Objective o To evaluate the predictive value of a questionnaire designed to diagnose asthma in adults
Markers of Airway Inflammation in BAL Fluid From Children With Asthma
AsthmaThe study compares the biochemical markers in bronchoalveolar lavage samples from asthmatic children to those markers found in non-asthmatic children with other respiratory diseases. The investigators hypothesize that certain markers will be associated specifically with asthma.
A Study of Inhalation of 20,000 EU CCRE in Normal Volunteers Compared to Allergic Asthmatic Individuals...
AsthmaHypersensitivityThis will be a single center, open label study comparing baseline characteristics of recovered sputum cells (collected on screening day) to those of cells recovered 6 hours after inhalational challenge with 20,000 EU Clinical Center Reference Endotoxin (CCRE, a component of air pollution)) within each group as well as cross group comparisons between individuals with allergic asthma (AA's)and normal volunteers (NV's). The primary objective of this study is to test the hypothesis that persons with allergic asthma will have an increased neutrophil response to challenge with 20,000 EU CCRE compared to normal volunteers. Secondary objectives include post CCRE comparison between AA's and NV's with regard to changes in airway cells and blood as well as changes in mucociliary clearance (MCC) in response to inhalation of 20,000 EU CCRE.
p38 Mitogen-Activated Protein Kinase (MAPK) and Steroid Insensitivity in Asthma
AsthmaThis research aims to find out how the inflammation in patients suffering from severe asthma is different from that in non-severe asthma, and how it may prevent corticosteroids from working efficiently in severe asthma. It will look,in particular, at a protein enzyme called p38 mitogen-activated protein kinase (p38 MAPK for short)which controls the activation of several important pathways in the cell. We wish to find out whether this enzyme is more active in cells obtained from patients with severe asthma compared to those with non-severe asthma. We would like to understand how this enzyme can cause the cell to respond less well to the anti-inflammatory effects of corticosteroids. We also wish to find out whether any specific inhibitors of p38 MAPK can improve severe asthma by improving the effects of corticosteroids on these cells. We hypothesise that activation of the intracellular MAPK signalling pathway underlies the inflammatory processes of severe asthma, and leads to the diminution of the anti-inflammatory actions of CS through histone modification.
Inflammatory Markers in Exhaled Breath Condensates From Asthmatic Patients
AsthmaThis study aims to compare the inflammatory mediators in exhaled breathe condensates from allergic and non-allergic asthmatic patients.
Environmental Exposures, Genetics, and Exhaled Nitric Oxide in Pediatric Asthma
AsthmaAsthma is one of the most common childhood diseases. It is chronic and often severely disabling. The amount of nitric oxide that is exhaled while breathing increases with airway inflammation, a symptom of asthma. This study will examine the results from a previous study, the Cincinnati Asthma Prevention (CAP) study, to evaluate the effects of environmental and genetic factors on exhaled nitric oxide (eNO) levels and to determine the relationship between eNO and asthma severity.
Children With Asthma in New Orleans After Hurricane Katrina
AsthmaAllergiesThis study will examine whether exposure to the increased levels of mold and other allergens in New Orleans post-Hurricane Katrina affect symptoms in children with asthma. It will also determine if having an asthma counselor (AC) can reduce a child s asthma symptoms in this setting. An AC helps the families in the study obtain appropriate health care, medicines and social services for their asthmatic child and instructs them about avoiding allergens and ridding allergens from the home. Children between 4 and 12 years of age living in Orleans Parish or surrounding areas impacted by flooding who have moderate to severe asthma may be eligible for this study. Parents provide a family medical history and information about the child s asthma symptoms, medications and medical history. The children undergo the following procedures: Medical examination and blood tests Spirometry (for children 6 and older) or peak flow (for children under 6) test: For spirometry, the child wears a nose clip and breathes into a mouthpiece attached to a machine that measures how fast air moves out of the child s lungs. For the peak flow meter test, the child blows into a plastic tube after taking a deep breath. Allergy skin testing: 24 common allergens are applied to the arm by little pricks or scratches and the skin is observed for reactions to the allergens. Study staff visit the participants homes three times during the 1-year study to test for moisture, mold and other allergens. After the first visit, families are randomly assigned to one of two groups. Group 1 participants attend two educational group sessions about asthma and then three individual sessions. An AC visits the home one time during the study to instruct the family on how to use supplies provided to reduce allergens in the home. Group 2 participants have an individual special teaching meeting with the AC at the end of the study. After the meeting, the AC visits the home to instruct the family on use of the supplies. Families are surveyed by phone every 3 months during the study to answer questions about the child s asthma attacks, medicines used, doctor visits, school days, missed, or work days missed to care for the child. At the end of the study, the child has a final medical examination, blood test, and breathing test.
Role of Eosinophils in the Proliferation of Airway Smooth Muscle (ASM) Cells
AsthmaBeing a key player in Asthma, eosinophils constitute a potential target to interfere with the series of biological events leading to Asthma pathogenesis. In this proposal, the investigators hypothesize that the interaction between eosinophils and airway smooth muscle cells (ASM) cells plays an important role in airway remodeling. Hence the investigators will investigate the role of eosinophils in enhancing ASM cells proliferation resulting in airways remodeling. The investigators will also investigate the mechanism behind this phenomenon. This will then pave the way for medical (drug) interference at one or several sites in order to prevent one of the main potential reasons behind airway remodeling, namely eosinophil-derived ASM proliferation.
The Effect of Asthma on Systemic Inflammation, Oxidative Stress and Cardiovascular Morbidity
AsthmaAsthma is a chronic airway inflammation which involves the interplay of different types of inflammatory cells and cytokines in the airway. The presence of systemic inflammation and oxidative stress in asthma suggests that it has a propensity to develop cardiovascular morbidity. Recent small scale studies have demonstrated that asthma severity may be associated with both airway and systemic inflammation. The investigators' study aims at linking asthma severity to airway and systemic inflammation, and subsequently to cardiovascular morbidity if a significant association of the aforementioned is present. The role of airway inflammation in contribution to systemic inflammation , and potential interaction between these two conditions will also be studied.