Cystic Fibrosis Diagnosis in Newborns, Children, and Adults

Carlo Castellani, MD; Barry Linnane, MB, BCh, BAO, DCH, MRCPI, MRCPCH, MD; Iwona Pranke, PhD; Federico Cresta, MD; Isabelle Sermet-Gaudelus, MD, PhD; Daniel Peckham, MD

Disclosures

Semin Respir Crit Care Med. 2019;40(6):701-714. 

In This Article

Intestinal Current Measurement

Intestinal current measurement (ICM) has been used to study CFTR function in human colonic epithelia and can be employed in cases of inconclusive NPD. Freshly obtained human rectal biopsies are placed in a micro-Ussing chamber for measurement of ex vivo transepithelial short-circuit current (Isc), which indicates net ion fluxes across the tissue and their changes once exposed to a series of Cl secretagogues (e.g., the cAMP agonist forskolin and the Ca2+ agonist carbachol). Biopsy specimens are immediately mounted between the two half-cells of the Ussing chamber. This is then filled with Meyler's buffer and secretagogues are added according to a standardized protocol.[159] In CF, the Isc response to forskolin is absent or reduced. The response to carbachol is reversed due to the apical potassium efflux in the absence of a Cl efflux or biphasic due to residual CFTR-mediated Cl efflux in milder forms of CF.

Advantages of ICM are that it is minimally invasive, and applicable to all ages. Suction biopsies are not painful, and are performed in 5 minutes. Clear-cut reference/threshold values between CF-PS and control subjects have been identified, supporting the role of ICM in the diagnosis of CF.[159–162] Future efforts should be put into the description of ICM values in larger groups of obligate heterozygotes and patients with CFTR-related disorders.

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