IL-6 Inhibitor Induction in Coculture Of Bronchial Epithelial Cells and Eosinophils

IL-6 Inhibitor
Eosinophil infiltration of the mucosa is a feature of asthmatic airways. Their adhesion to bronchial epithelial cells has been proposed to lead to the generation of inflammation mediators which may contribute to asthma pathology. Bronchial epithelial cells (BEAS-2B cell line) and peripheral blood eosinophils were cultured alone or in combination and the production of an inflammatory cytokine, IL-6, was measured. IL-6 was produced principally by epithelial cells and the production was enhanced more than 10-fold in the presence of eosinophils. Significant augmentation of epithelial IL-6 production persisted even when eosinophils were fixed with paraformaldehyde. The eosinophil-induced IL-6 production was extensively inhibited by inhibitors of p38 mitogen-activated protein (MAP) kinase or nuclear factor ??B (NF??B). (more…)

Long-Acting Beta Agonists: Salmeterol and Formeterol

Salmeterol and Formeterol
Two long-acting ß 2 -adrenergic agonists (LABAs), salmeterol and formoterol, have been demonstrated to be safe and effective agents in children, both in terms of bronchodilation and prevention of exercise-induced bronchospasm. Their onsets of action differ, with formoterol having an onset similar to albuterol (3 minutes), while salmeterol has a slower onset of action (10–20 minutes). Following a single-dose administration, both agents demonstrate durations of action up to 12 hours. Following regular twice-daily administration, bronchodilation remains effective; however, a level of tolerance (or tachyphylaxis) (more…)

Cromolyn, Nedocromil, Theophylline: Asthma Medications

asthma medications
Cromolyn sodium and nedocromil sodium are inhaled agents that are alternatives to inhaled corticosteroids (ICS) in the management of mild persistent asthma in children. Both drugs have been shown to possess anti inflammatory properties through nonsteroidal mechanisms, although the exact mechanisms for their actions remain unclear. (more…)

Vocal Cord Dysfunction: A Functional Respiratory Tract Disorder

Vocal Cord Dysfunction
Vocal cord dysfunction (VCD) is a functional respiratory tract disorder resulting from paradoxical adduction of the vocal cords, complicates the diagnosis and management of common respiratory tract problems, including asthma. The recognition of VCD in a patient with atypical or difficult-to-control asthma is critical in minimizing symptoms and potential side-effects associated with treatment of severe asthma. The symptoms of VCD are not unique to the disorder and include cough, wheeze, stridor, dyspnea, hoarseness, and choking. (more…)

Exposure to Inhalant Allergens Increase the Severity of Asthma

allergens asthma
Exposure and allergic sensitization to cockroach was associated with a significantly greater risk of asthma hospitalization and greater healthcare utilization among 476 children aged 4 to 9 years who participated in the National Cooperative Inner-City Asthma Study. Allergic sensitization to the mold Alternaria has been identified as a significant allergen in terms of increasing airway hyperresponsiveness and was associated with a nearly 200-fold increased risk of respiratory arrest due to asthma, emphasizing the importance of determining underlying allergic sensitivities in patients with asthma and providing patients with accurate and practical advice on allergen avoidance techniques. (more…)

Aspirin-Induced Asthma Treatment with Antileukotrienes

Aspirin Asthma
The prevalence of aspirin-sensitive asthma is uncertain although it may exist in up to 20% of all asthmatics patients. The characteristic features include profound bronchoconstriction asthma following aspirin ingestion, rhinosinusitis, nasal polyps, and abdominal cramps. Aspirin and nonsteroidal antiinflammatory drugs selectively inhibit COX-1, which in turn shunts arachidonic acid down the 5-lipoxygenase activating protein pathway, causing overproduction of cysteinyl leukotrienes. As a consequence, elevated levels of cysteinyl leukotrienes can be found in bronchial asthma and nasal aspirates, and in urine following aspirin challenge. (more…)

Asthma Progression of Disease with Abnormality in Pulmonary Function

asthma progression
More severe asthma can persist from childhood into adulthood without remission. Another important tendency in the natural history is for symptoms to remit in adolescence only to return again in adulthood. In general, the amount of wheezing in early adolescence seems to be a guide for severity in early adult years, with 73% of those with few symptoms at age 14 years continuing to have little or no asthma progression at age 28 years. Similarly 68% of those with frequent wheezing at 14 years still suffered from recurrent asthma at age 28 years. Most subjects with frequent wheezing at 21 years continued to have comparable asthma at 28 years. In addition to the importance of symptoms in childhood, childhood degree of bronchial responsiveness in combination with a low FEV-1 were also related to the outcome of asthma in adulthood. (more…)

Airway Fibroblasts Exhibit A Synthetic Phenotype in Severe Asthma

Airway Fibroblasts
Airway remodelling is considered to be of major importance in the pathology of asthma, with subepithelial basement membrane thickening in particular being indicative of early development of the disease and characteristic of its progression. Airway fibroblasts are central cells in the processes of remodelling: increased deposition of fibroblast-derived connective tissue proteins and differentiation of fibroblasts into contractile myofibroblasts are consistent observations in morphological studies of moderate to severe asthmatic airways. The secretory function of fibroblasts is under the control of locally produced growth factors such as vascular endothelial cell growth factor (VEGF, see below) and platelet-derived growth factor (PDGF). (more…)

Requirement for Leukotriene B4 Receptor 1 in Allergen-Induced Airway Hyper-Responsiveness

Airway Hyper-Responsiveness
A role for Leukotriene B4 in the induction of airway hyper-responsiveness was explored through the use of transgenic mice deficient in the BLT1 receptor for LTB4 . Ovalbumin challenge of sensitized wild-type mice resulted in the usual features of experimental asthma, including goblet cell hyperplasia, hyper-responsiveness to inhaled methacholine and elevated BAL fluid concentrations of the Th2 cytokine IL-13. In contrast, BLT1 –/– mice (i.e. genetically modified mice lacking the gene coding for the BLT1 receptor) exhibited significantly lower responses. BLT1 –/– mice also exhibited lower numbers of IL-13-positive T lymphocytes of both the helper (CD4 T Cells) and cytotoxic/suppressor (CD8 + ) types. (more…)

Antileukotrienes in Acute Asthma: Zafirlukast, Montelukast, Leukotriene Receptor Antagonists

Leukotriene Receptor Antagonists
Leukotrienes can be found in the airway and urine following both spontaneous exacerbations of asthma and acute exposure to bronchoconstrictor stimuli in the laboratory. This in turn indicates that they may have a role in the pathogenesis of acute episodes of bronchoconstriction. Although antileukotrienes are not currently advocated in the management of acute asthma, there are data to suggest that they might be of some potential benefit. Prior treatment with montelukast asthma has been shown in several studies to significantly shorten the time taken to recover (in terms of FEV 1 ) following exposure to a bronchoconstrictor stimulus. (more…)

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