TABLE 3.
RECOMMENDATIONS FOR FUTURE STUDIES REQUIRED TO OPTIMIZE THE USE OF NASAL POTENTIAL DIFFERENCE, SWEAT CHLORIDE, AND OTHER MEASURES OF CFTR AS OUTCOMES FOR EARLY-PHASE CYSTIC FIBROSIS STUDIES
| A. Nasal Potential Difference |
| Technical |
| Validation of standardized solution preparation, distribution, and stability testing* |
| Comparison of NPD devices in subjects with CF* |
| Testing of disposable, premanufactured NPD equipment |
| Comparison of CFTR agonist solutions (e.g., isoproterenol vs. terbutaline, albuterol, or adenosine) |
| Effect of simplified perfusion protocols on data validity |
| Validation of electronic data capture |
| Biological |
| Establishment of normal values (non-CF, partial CFTR function, severe CFTR dysfunction) applicable to all centers within research networks* |
| Correlation of NPD parameters with clinically meaningful outcome in the context of a therapeutic trial of a CFTR/ion transport modulator |
| Effect of concomitant medication use on NPD parameters (e.g., use of β2-agonists, hypertonic saline, ion transport–active agents such as denufosol sodium) |
| Variability in scoring among blinded overreaders |
| Consensus regarding best statistical methods |
| B. Sweat Chloride |
| Repeatability of sweat electrolyte determinations |
| By genotype |
| Over different time frames (daily, weekly, monthly, yearly) |
| With different personnel performing collection |
| Across sites |
| Technical aspects of sweat collection |
| Effect of collection time of day |
| Different voltages applied for iontophoresis |
| Effect of salt intake, aldosterone levels, and volume status |
| Relationship of sweat electrolyte levels to aldosterone levels |
| Relationship to sweat potassium |
| Local (skin) administration of agents with CFTR activity or ENaC activity |
| C. Other CFTR Measures |
| Validation of immunohistochemical localization of CFTR and CFTR mRNA expression in a cross-section of subjects with CF expressing various mutation classes* |
| Evaluation of colocalization techniques to improve discrimination of surface-localized CFTR from the total CFTR pool* |
| Correlation of CFTR mRNA expression levels to therapeutic responses of CFTR-active therapies |
| Simplification of the measurement of CFTR ion transport in nasal cells evaluated ex vivo, and validation of related techniques |
| Further exploration of biochemical and other nonfunctional measures of CFTR maturation |
Definition of abbreviations: CF = cystic fibrosis; ENaC = epithelial sodium channel; NPD = nasal potential difference.
*
Studies currently in progress.