Single-Cell Reconstruction of Human Basal Cell Diversity in Normal and Idiopathic Pulmonary Fibrosis Lungs.

Rationale: Declining lung function in patients with interstitial lung disease is accompanied by epithelial remodeling and progressive scarring of the gas-exchange region. There is a need to better understand the contribution of basal cell hyperplasia and associated mucosecretory dysfunction to the development of idiopathic pulmonary fibrosis (IPF).Objectives: We sought to decipher the transcriptome of freshly isolated epithelial cells from normal and IPF lungs to discern disease-dependent changes within basal stem cells.Methods: Single-cell RNA sequencing was used to map epithelial cell types of the normal and IPF human airways. Organoid and air-liquid interface cultures were used to investigate functional properties of basal cell subtypes.Measurements and Main Results: We found that basal cells included multipotent and secretory primed subsets in control adult lung tissue. Secretory primed basal cells include an overlapping molecular signature with basal cells obtained from the distal lung tissue of IPF lungs. We confirmed that NOTCH2 maintains undifferentiated basal cells and restricts basal-to-ciliated differentiation, and we present evidence that NOTCH3 functions to restrain secretory differentiation.Conclusions: Basal cells are dynamically regulated in disease and are specifically biased toward the expansion of the secretory primed basal cell subset in IPF. Modulation of basal cell plasticity may represent a relevant target for therapeutic intervention in IPF.

Cost-Minimization Analysis of Direct Cost of Sevelamer Carbonate and Lanthanum Carbonate in the Treatment of Patients with Chronic Kidney Disease Not on Dialysis in Bulgaria.

BACKGROUND: Hyperphosphatemia is associated with significant pathophysiology in chronic kidney disease (CKD). Control of hyperphosphatemia in patients with stage 3 to 5D CKD is now regarded as a high priority. OBJECTIVE: The primary purpose of this study was to perform an economic analysis of the newly available treatments sevelamer carbonate (SC) and lanthanum carbonate (LC) for the treatment of hyperphosphatemia in patients not on dialysis in Bulgaria. METHODS: Both treatment options demonstrate equal efficacy in controlling hyperphosphatemia, as well as having a similar safety profile in regard to adverse effects. To differentiate between them, a cost-minimization analysis was performed. A time period of 4 years was chosen to perform a budget impact analysis. The robustness of the results was tested through sensitivity analysis using Tornado diagrams. RESULTS: The estimated cost per patient per year with SC and LC would be €1441.75 and €1569.50, respectively, at the weighted average daily dose regimen of 4000 mg SC and 2000 mg LC, whereas the cost would be €2306.80 and €2354.25 for 6400 mg SC and 3000 mg LC, respectively. Expected cost savings (discounted) for the 4-year period of the analysis can reach between €1,363,601 and €2,727,201 at 4000 mg SC and 2000 mg LC dose regimen, whereas these can reach between €506,480 and €1,012,961 at 6400 mg SC and 3000 mg LC, respectively. CONCLUSIONS: The equal efficacy, similar adverse effect profile, and lower cost of SC when used for the treatment of hyperphosphatemia in patients with CKD not on dialysis should make it a preferred alternative.