tiotropium-bromide and Gastroesophageal-Reflux

Asthma guidelines provide clinicians with evidence-based management strategies for this chronic condition. The preferred therapy for patient with persistent asthma is inhaled corticosteroids. However, ∼40% of the patients with persistent asthma continue to present with symptoms while treated according to the guidelines. Multiple factors are being explored to explain the variability in response to inhaled corticosteroids including asthma phenotype and genetic predisposition among others. The nonatopic asthma phenotype has been described in the literature. These patients tend to have milder symptoms of asthma and typically outgrow their asthma by adolescence. They present with chronic asthma symptoms in the absence of a positive allergy test, either skin prick test or specific immunoglobulin E blood test. Although patients with nonatopic asthma share many characteristics with patients with atopic asthma, there are several studies that suggest a different inflammatory pathway may be involved in their pathophysiology. Therefore, it is possible that children with nonatopic asthma could respond differently to inhaled corticosteroids compared with those with atopic asthma. Currently there is a variable definition of this phenotype. Furthermore, there is a paucity of therapeutic trial directed toward the patients with nonatopic asthma specifically. Future research should be guided toward identifying the inflammatory pathways in nonatopic asthma and potential phenotype-guided therapies.

Topics: Allergy and Immunology; Anti-Asthmatic Agents; Asthma; Bronchi; Child; Chronic Disease; Diagnosis, Differential; Gastroesophageal Reflux; Humans; Mometasone Furoate; Practice Guidelines as Topic; Proton Pump Inhibitors; Respiratory Mucosa; Respiratory Sounds; Tiotropium Bromide; Treatment Outcome

Despite inhaled medications that decrease exacerbation risk, some COPD patients experience frequent exacerbations. We determined prospective risk factors for exacerbations among subjects in the COPDGene Study taking inhaled medications.. 2113 COPD subjects were categorized into four medication use patterns: triple therapy with tiotropium (TIO) plus long-acting beta-agonist/inhaled-corticosteroid (ICS ± LABA), tiotropium alone, ICS ± LABA, and short-acting bronchodilators. Self-reported exacerbations were recorded in telephone and web-based longitudinal follow-up surveys. Associations with exacerbations were determined within each medication group using four separate logistic regression models. A head-to-head analysis compared exacerbation risk among subjects using tiotropium vs. ICS ± LABA.. In separate logistic regression models, the presence of gastroesophageal reflux, female gender, and higher scores on the St. George's Respiratory Questionnaire were significant predictors of exacerbator status within multiple medication groups (reflux: OR 1.62-2.75; female gender: OR 1.53 - OR 1.90; SGRQ: OR 1.02-1.03). Subjects taking either ICS ± LABA or tiotropium had similar baseline characteristics, allowing comparison between these two groups. In the head-to-head comparison, tiotropium users showed a trend towards lower rates of exacerbations (OR = 0.69 [95 % CI 0.45, 1.06], p = 0.09) compared with ICS ± LABA users, especially in subjects without comorbid asthma (OR = 0.56 [95% CI 0.31, 1.00], p = 0.05).. Each common COPD medication usage group showed unique risk factor patterns associated with increased risk of exacerbations, which may help clinicians identify subjects at risk. Compared to similar subjects using ICS ± LABA, those taking tiotropium showed a trend towards reduced exacerbation risk, especially in subjects without asthma.. ClinicalTrials.gov NCT00608764, first received 1/28/2008.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Aged; Asthma; Bronchodilator Agents; Cohort Studies; Comorbidity; Disease Progression; Drug Therapy, Combination; Female; Follow-Up Studies; Gastroesophageal Reflux; Humans; Logistic Models; Longitudinal Studies; Male; Middle Aged; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Risk Factors; Sex Factors; Tiotropium Bromide

Gastro-oesophageal reflux is frequent in chronic airway diseases and is considered a trigger for symptoms. In animal models, bilateral vagotomy or muscarinic antagonists prevent the increase in airway resistance and the microvascular leakage induced by acute oesophageal acid instillation. The present study investigates lung inflammation and remodelling in an animal model of chronic gastro-oesophageal reflux disease (GORD), and the effectiveness of pretreatments with tiotropium, atropine and dexamethasone. Mice were exposed to twice-daily intra-oesophageal HCl instillations for 21 days. Exposure to HCl causes: marked infiltration by inflammatory cells of the airways and of peribronchial areas; an increase in epithelial thickness; histological features of interstitial pneumonitis; an increase in cell numbers and in the levels of interleukin-8; and soluble intercellular adhesion molecule in bronchoalveolar lavage fluids, as well as of in vitro tracheal contractility. The administration of nebulised tiotropium or intraperitoneal atropine prior to each instillation of HCl, considerably inhibited all these changes. These results indicate a major role of acetylcholine in airway inflammation and remodelling in a GORD model, and demonstrate that tiotropium and atropine can prevent lung inflammation with an effectiveness similar to intraperitoneal dexamethasone, providing additional evidence that anticholinergics might contribute to the control of inflammatory processes in airway diseases.

Topics: Acetylcholine; Animals; Anti-Inflammatory Agents; Atropine; Biopsy; Bronchoalveolar Lavage Fluid; Bronchodilator Agents; Chronic Disease; Dexamethasone; Disease Models, Animal; Esophagitis; Gastroesophageal Reflux; Hydrochloric Acid; Lung; Male; Mice; Mice, Inbred BALB C; Muscle, Smooth; Pneumonia; Scopolamine Derivatives; Tiotropium Bromide; Trachea