Asthma is one of the most common of medical illnesses and is treated in part by drugs that activate the beta-2-adrenoceptor (β2-AR) to dilate obstructed airways. Such drugs include long acting beta agonists (LABAs) that are paradoxically linked to excess asthma-related mortality. Here we show that LABAs such as salmeterol and structurally related β2-AR drugs such as formoterol and carvedilol, but not short-acting agonists (SABAs) such as albuterol, promote exaggerated asthma-like allergic airway disease and enhanced airway constriction in mice. We demonstrate that salmeterol aberrantly promotes activation of the allergic disease-related transcription factor signal transducer and activator of transcription 6 (STAT6) in multiple mouse and human cells. A novel inhibitor of STAT6, PM-242H, inhibited initiation of allergic disease induced by airway fungal challenge, reversed established allergic airway disease in mice, and blocked salmeterol-dependent enhanced allergic airway disease. Thus, structurally related β2-AR ligands aberrantly activate STAT6 and promote allergic airway disease. This untoward pharmacological property likely explains adverse outcomes observed with LABAs, which may be overcome by agents that antagonize STAT6.

The beta-2 adrenergic receptor (ADRB2) Arg16Gly polymorphism may alter the bronchodilation response to long-acting beta2-agonists, thereby influencing the clinical effectiveness of LABAs plus corticosteroids (ICS) treatment. But the results of individual studies are inconclusive.

Beta2-adrenergic receptors (beta2AR) play important regulatory roles in a variety of cells and organ systems and are important therapeutic targets in the treatment of airway and cardiovascular disease. Prolonged use of beta-agonists results in tolerance secondary to receptor down-regulation resulting in reduced therapeutic efficiency. The purpose of this work is to evaluate the signaling capabilities of the beta2AR expressed by a recombinant adeno-associated viral (AAV) vector that also included an enhanced green fluorescent protein (EGFP) gene (AAV-beta2AR/EGFP).

The cardiovascular safety of inhaled long-acting β2-agonists (LABAs) in patients with chronic obstructive pulmonary disease (COPD) is a controversial problem. Certain studies have suggested that inhaled LABAs lead to an increased risk of cardiovascular events in patients with COPD. This meta-analysis aimed to assess the cardiovascular safety of inhaled LABAs in COPD.

Glucocorticosteroids (GCS) are used to treat asthma that does not respond to accepted first-line therapy. Because they have potent anti-inflammatory properties, facilitate beta-adrenergic responsiveness, suppress the late-phase reaction and reduce secretion of mucus, GCS are indicated in the treatment of severe acute asthma and chronic asthma not responsive to beta-agonists and methylxanthines. They are also useful as a diagnostic tool to determine reversibility of airway obstruction in some patients with chronic obstructive pulmonary disease. Maximal antiasthmatic effect is achieved by prescribing daily divided doses of intermediate-acting systemic GCS and reducing the dosage to alternate days after the asthma has been controlled. Inhaled GCS have minimal systemic effects when used properly, and in selected cases may be as effective as the oral preparations. Improper use of these drugs may provoke side effects which are undesirable and dangerous. Proper patient education in the use of these drugs is necessary to avoid such severe adverse effects.