Lung transplantation for idiopathic pulmonary fibrosis enriches for individuals with telomere-mediated disease.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is the most common indication for lung transplantation in North America and variants in telomere-maintenance genes are the most common identifiable cause of IPF. We reasoned that younger IPF patients are more likely to undergo lung transplantation and we hypothesized that lung transplant recipients would be enriched for individuals with telomere-mediated disease due to the earlier onset and more severe disease in these patients. METHODS: Individuals with IPF who underwent lung transplantation or were evaluated in an interstitial lung disease specialty clinic who did not undergo lung transplantation were examined. Genetic evaluation was completed via whole genome sequencing (WGS) of 426 individuals and targeted sequencing for 5 individuals. Rare variants in genes previously associated with IPF were classified using the American College of Medical Genetics guidelines. Telomere length from WGS data was measured using TelSeq software. Patient characteristics were collected via medical record review. RESULTS: Of 431 individuals, 149 underwent lung transplantation for IPF. The median age of diagnosis of transplanted vs non-transplanted individuals was significantly younger (60 years vs 70 years, respectively, p<0.0001). IPF lung transplant recipients (IPF-LTRs) were twice as likely to have telomere-related rare variants compared to non-transplanted individuals (24% vs 12%, respectively, p=0.0013). IPF-LTRs had shorter telomeres than non-transplanted IPF patients (p=0.0028) and >85% had telomeres below the age-adjusted mean. Post-transplant survival and CLAD were similar amongst IPF-LTRs with rare variants in telomere-maintenance genes compared to those without, as well as in those with short telomeres versus longer telomeres. CONCLUSIONS: There is an enrichment for telomere-maintenance gene variants and short telomeres among IPF-LTRs. However, transplant outcomes of survival and CLAD do not differ by gene variants or telomere length within IPF-LTRs. Our findings support individual with telomere-mediated disease should not be excluded from lung transplantation and focusing research efforts on therapies directed toward individuals with short-telomere mediated disease.

Nurse-Led Palliative Care Clinical Trial Improves Knowledge and Preparedness in Caregivers of Patients with Idiopathic Pulmonary Fibrosis.

Rationale: Patients with idiopathic pulmonary fibrosis (IPF) and their caregivers experience stress, symptom burden, poor quality of life, and inadequate preparedness for end-of-life (EOL) care planning as the disease progresses. The hypothesis for this study was that the early introduction of palliative care in the course of IPF would improve knowledge and preparation for EOL, patient-reported outcomes, and advance care planning in patients with IPF and their caregivers. Objectives: We sought to determine the feasibility, acceptability, and efficacy of a nurse-led early palliative care intervention entitled "A Program of SUPPORT" (Symptom management, Understanding the disease, Pulmonary rehabilitation, Palliative care, Oxygen therapy, Research participation, and Transplantation) in patients with IPF and their caregivers. Methods: Patients with IPF (diagnosed in the year previous to their initial center visit) from the University of Pittsburgh Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease at University of Pittsburgh Medical Center-together with their caregivers-were randomized to receive the intervention "A Program of SUPPORT" or usual care. This included a total of three research visits aligned with their clinic visit over a period of 6 to 8 months. We measured feasibility, acceptability, and efficacy of this intervention. Results: A total of 136 patient/caregiver dyads were eligible, and a total of 76 dyads were enrolled and participated. Participants were predominately White males >65 years old. Thirteen percent did not have an identified caregiver. Feasibility was limited; 56% of eligible dyads were enrolled. Eligible dyads (24%) were interested in participating but too fatigued to stay after their clinic visit. There was high attrition (20% of participants died before the study was completed). "A Program of SUPPORT" was acceptable to participants. Efficacy demonstrated a significant improvement in caregiver's knowledge, disease preparedness, and confidence in caring for the patient as well as an improvement in knowledge and advance care planning completion in patient participants. Conclusions: Patients with IPF and their caregivers have unmet needs regarding knowledge of their disease, self-management strategies, and preparedness for EOL planning. This nurse-led intervention demonstrated acceptability and efficacy in knowledge and advance care planning completion in patients and in knowledge, disease preparedness, and confidence in caregivers. Future research should identify additional strategies, including telemedicine resources to reach additional patients and their caregivers earlier in their disease course. Clinical trial registered with clinicaltrials.gov (NCT02929017).