Endogenous epinephrine, a potent β-agonist, is an (R)-isomer compound that results in airway bronchodilation in the setting of increased sympathetic activity.
3 Modification of the β
2 molecules resulted in a class of β
2-agonists, a 50:50 combination of both (R)- and (S)-isomers known as albuterol. The most recent member of this class, levalbuterol, is a pure (R)-isomer.
8 Research has demonstrated that the racemic formulas (albuterol, fenoterol, formoterol fumarate, salmeterol, and terbutaline sulfate) exhibit both bronchoconstricting and bronchodilating properties, which have led to paradoxical bronchoconstriction in some patients with reactive airway disease.
3 The (R)-isomer binds to the β
2 receptor, resulting in decreased intracellular calcium and decreased airway reactivity. Comparatively, the (S)-isomer has been shown to function as an adrenergic antagonist with pro-inflammatory effects in both in vitro and in vivo experimental models and may be harmful, particularly in patients who have asthma.
9 Recent data suggest that the (S)-isomer is metabolized 10 times slower than the bronchodilating (R)-isomer,
5 and therefore may remain in the body at higher levels and for a longer time with possible detrimental airway effects. Because levalbuterol does not have this adrenergic antagonist, it is not expected to cause paradoxical bronchoconstriction.
In the present case, the prebronchodilator spirometry demonstrated a decreased FEV
1/FVC ratio (67; normal >70) as well as a decreased percent predicted FEV
1 (80%; normal >80%). These values indicate a mild obstructive abnormality before levalbuterol administration.
10 According to the American Thoracic Society guidelines, a positive response to bronchodilators—indicating reversible airway disease—is defined as a 12% and 200-mL increase in either the FEV
1 or the FVC.
10 In our patient, 90 μg of levalbuterol via an MDI produced a 460-mL (14%) decrease in FEV
1 and a 220-mL (4%) decrease in FVC, thereby qualifying as a paradoxical response to levalbuterol.
In the previously reported case of paradoxical bronchospasm,
7 the patient had several comorbidities and was treated in an acute setting. In addition, medications such as β-blockers, diuretics, digoxin, monoamine oxidase inhibitors, and tricyclic antidepressants are known to interact harmfully in some patients using levalbuterol and racemic albuterol.
8 However, the patient in the present report did not have comorbidities and was not taking interfering medications, yet his pulmonary function documentation revealed the untoward effects. The bronchoconstrictive response to nebulized levalbuterol upon repeated spirometry suggests that the first paradoxical response was not a reaction to an adulterant in the hydrofluoroalkane product. Therefore, we are confident that our findings of decreased pulmonary function within minutes of levalbuterol inhalation in our patient were a paradoxical response to the drug.