Real-life application of the optical beta-adrenergic sweat test for people with cystic fibrosis

Cystic fibrosis (CF) has become increasingly treatable with Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-targeted therapies. However, the availability and efficacy of these treatments depend on each patient's CFTR genotype, necessitating careful follow-up to detect effective benefits. This study builds on our previous findings by applying the Optical Beta-Adrenergic Sweat Test (OBAST) as a complement to the classical sweat Cl^- testing (ST) to better evaluate the restoration of CFTR activity in vivo. We quantified the sweat droplet number (SDN) and the ratio between CFTR-dependent (beta-adrenergic Cocktail-induced, C-phase) and the CFTR-independent (Methacholine-induced, M-phase) sweat rates (C/M ratio) in 128 non-CF subjects and 143 people with CF (PwCF). Among the PwCF, 39 were treated with various combinations of the CFTR modulators, including Lumacaftor/Ivacaftor (LI), Tezacaftor/Ivacaftor (TI) and/or Elexacaftor/Tezacaftor/Ivacaftor (ETI). SDN detected an earlier response to CFTR modulators, yielding lower p-values than the C/M rate ratio, particularly during ETI therapy. Thus, SDN counting provides a simpler and faster method than C/M ratio for monitoring the effects of CFTR modulators on CFTR function, without compromising sensitivity or reliability. This enables more precise tracking of drug efficacy in individual subjects. In six PwCF, who underwent at least two different CFTR-targeted therapies, we also assessed lung function and nasal potential difference (NPD) in addition to ST, SDN, and the C/M ratio. We propose OBAST as a reliable complementary tool to standard tests, especially valuable when CFTR-targeted drugs are not approved for rare CFTR genotypes, when clinical response appears limited, and/or when sweat [Cl^-] results are inconclusive.