Which mechanism best explains the 25% lower maximal FEV1 increase observed in some subjects after taking a B-agonist?

The observation of a 25% lower maximal FEV1 increase in some subjects after taking a β-agonist can be explained by receptor polymorphism with reduced signal transduction. In this context, receptor polymorphisms refer to genetic variations that can influence the responsiveness of β-adrenergic receptors located in bronchial smooth muscle.

When individuals have polymorphisms in the β-adrenergic receptor genes, it may lead to differences in the receptor's ability to activate downstream signaling pathways after binding to the agonist. This diminished signaling can result in a less effective bronchodilatory response, thus causing a lower increase in forced expiratory volume in 1 second (FEV1) after β-agonist administration.

These genetic variations can affect how well the receptor couples with G-proteins and other molecules involved in the signal transduction pathway. As a result, even if the drug is administered correctly and binds to the receptor, the subsequent physiological response may be suboptimal in certain individuals due to these intrinsic differences in receptor function.

Thus, receptor polymorphism represents a significant and actionable explanation for why some subjects experience reduced efficacy of β-agonists, impacting their respiratory function.