KIF15 missense variant is associated with the early onset of idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) has an unknown aetiology and limited treatment options. A recent meta-analysis identified three novel causal variants in the TERT, SPDL1, and KIF15 genes. This observational study aimed to investigate whether the aforementioned variants cause clinical phenotypes in a well-characterised IPF cohort. METHODS: The study consisted of 138 patients with IPF who were diagnosed and treated at the Helsinki University Hospital and genotyped in the FinnGen FinnIPF study. Data on > 25 clinical parameters were collected by two pulmonologists who were blinded to the genetic data for patients with TERT loss of function and missense variants, SPDL1 and KIF15 missense variants, and a MUC5B variant commonly present in patients with IPF, or no variants were separately analysed. RESULTS: The KIF15 missense variant is associated with the early onset of the disease, leading to progression to early-age transplantation or death. In patients with the KIF15 variant, the median age at diagnosis was 54.0 years (36.5-69.5 years) compared with 72.0 years (65.8-75.3 years) in the other patients (P = 0.023). The proportion of KIF15 variant carriers was 9- or 3.6-fold higher in patients aged < 55 or 65 years, respectively. The variants for TERT and MUC5B had similar effects on the patient's clinical course, as previously described. No distinct phenotypes were observed in patients with the SPDL1 variant. CONCLUSIONS: Our study indicated the potential of KIF15 to be used in the genetic diagnostics of IPF. Further studies are needed to elucidate the biological mechanisms of KIF15 in IPF.

Evaluation of CPAP mask performance during 3 years of mask usage: time for reconsideration of renewal policies?

BACKGROUND: Continuous positive airway pressure (CPAP) mask renewal policies vary inside and between countries. There are no independent studies on the optimal mask renewal frequency. We aimed to evaluate CPAP mask function over time in a real-life clinical setting, and to compare the results against current renewal policies. METHODS: Daily performance data of 1846 CPAP masks (65% nasal, 22% nasal pillows, 12% oronasal) were recorded from 450 participants (68% male, mean age 59 years) with obstructive sleep apnoea. The unintentional leak, Apnoea-Hypopnoea Index (CPAP-AHI) and usage data were exported from the CPAP device. RESULTS: Of 656 324 nights of CPAP usage, the mean renewal time was 497 days (SD 327), mean leak 5.7 L/min (SD 8.1) and CPAP-AHI 3.8 events/h (SD 3.6). The difference in mean leak between one (5.2 L/min, SD 7.5), 12 (6.0 L/min, SD 10.2) and 24 months (5.8 L/min, SD 7.5) was minimal (p=0.59). Mean CPAP-AHI remained normal and unchanged in nasal masks and pillows up to 30 months, and was highest in oronasal masks. Different mask manufacturers performed similarly. Masks' daily or total usage did not affect the results. Shifting the mask renewal policy to 24 months could reduce the mask-related cost up to 50%-88%. CONCLUSIONS: Nasal masks and pillows could be used at least 2 years without significant changes in unintentional leak and CPAP-AHI. We suggest updating the mask renewal policies of nasal masks and pillows; results on oronasal masks and other manufacturers CPAP devices need further verification.