Conflict of interest: RCB is the Chairman of the Board of Parion Sciences. Parion Sciences is a privately held UNC spin-out company focused on developing therapies for CF. RCB reports having equity in Parion Sciences and receiving monetary compensation as board chair. BJS holds patents assigned to Duke related to the 19 F imaging technology. HCC holds patents assigned to Duke related to the 19 F imaging technology.

With the growing class of CFTR modulator therapy available to more patients and with increasing pregnancies in individuals with CF, there is a growing need to understand the effects of these agents during pregnancy. There are few reports of their continued use in the literature, although it is likely that this is not an uncommon occurrence. We report the uncomplicated and successful pregnancy of a woman treated with lumacaftor/ivacaftor, as well as the clinical course of the infant during the first 9 months of life. We also report drug levels in plasma from the mother, cord blood, breast milk, and infant to estimate fetal and infant drug exposure.

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Rationale: The rate of progression of most interstitial lung diseases (ILD) is unpredictable. Fibrocytes are circulating bone marrow-derived cells that have been implicated in the pathogenesis of lung fibrosis. Hermansky-Pudlak syndrome (HPS), a genetic cause of ILD in early adulthood, allows for study of biomarkers of ILD in a homogeneous population at near-certain risk of developing fibrotic lung disease.Objectives: To test the hypothesis that, in subjects with HPS, the number or phenotype of circulating fibrocytes predicts progression and outcome of ILD.Methods: We measured circulating fibrocyte counts and chemokine levels in a cohort of subjects with HPS and healthy control subjects and correlated the results to disease outcome. Measurements and Main Results:In a cross-sectional analysis, peripheral blood fibrocyte concentrations were markedly elevated in a subset of subjects with HPS who had ILD but not subjects without lung disease or normal control subjects. The blood concentration of fibrocytes expressing the chemokine receptor CXCR4 correlated significantly with the plasma concentration of the CXCR4 ligand, CXCL12. In a longitudinal study, we found marked episodic elevations in circulating fibrocyte counts over a median follow-up period of 614 days. Elevations in both maximal values and final values of peripheral blood CXCR4 1 fibrocyte concentration were strongly associated with death from ILD. Conclusions: CXCR41 fibrocyte concentration may be useful as a biomarker for outcome of ILD in subjects with HPS.

Ivacaftor use can lead to dramatic health improvements in cystic fibrosis (CF) patients with gating mutations. Here, we report five instances of dramatic clinical decline following withdrawal of ivacaftor in three individuals with the G551D-CFTR mutation. In each case, the patient's lung function and symptoms rapidly deteriorated after cessation of treatment. Awareness of this phenomenon should inform both clinical practices as well as the design of future clinical trials of highly active CFTR modulators.