Monogenic gene variants in lung transplant recipients with usual interstitial pneumonia

Question addressed by the studyThe prevalence of monogenic disease-causing gene variants in lung-transplant recipients with idiopathic pulmonary fibrosis is not fully known. Their impact on clinical outcomes before and after transplantation requires more evidence.Patients and MethodsWe retrospectively performed sequence analysis of genes associated with pulmonary fibrosis in a cohort of 23 patients with histologically confirmed usual interstitial pneumonia that had previously undergone double lung transplantation. We evaluated the impact of confirmed molecular diagnoses on disease progression, clinical outcomes and incidence of acute rejection or chronic lung allograft dysfunction after transplantation.ResultsFifteen patients out of 23 (65%) had a variant in a gene associated with interstitial lung disease. Eleven patients (48%) received a molecular diagnosis, of which nine involved genes for telomerase function. Five diagnostic variants were found in the gene for Telomerase reverse transcriptase. Two of these variants, p.(Asp684Gly) and p.(Arg774*), seemed to be enriched in Finnish lung-transplant recipients. Disease progression and the incidence of acute rejection and chronic lung allograft dysfunction was similar between patients with telomere-related disease and the rest of the study population. The incidence of renal or bone marrow insufficiency or skin malignancies did not differ between the groups.Answer to the questionGenetic variants are common in lung transplant recipients with pulmonary fibrosis and are most often related to telomerase function. A molecular diagnosis for telomeropathy does not seem to impact disease progression or the risk of complications or allograft dysfunction after transplantation.

Associations between resources and practices of ILD centers and outcomes in patients with idiopathic pulmonary fibrosis: data from the IPF-PRO Registry

Background Performance benchmarks for the management of idiopathic pulmonary fibrosis (IPF) have not been established. We used data from the IPF-PRO Registry, an observational registry of patients with IPF managed at sites across the US, to examine associations between the characteristics of the enrolling sites and patient outcomes. Methods An online survey was used to collect information on the resources, operations, and self-assessment practices of IPF-PRO Registry sites that enrolled ≥ 10 patients. Site variability in 1-year event rates of clinically relevant outcomes, including death, death or lung transplant, and hospitalization, was assessed. Models were adjusted for differences in patient case mix by adjusting for known predictors of each outcome. We assessed whether site-level heterogeneity existed for each patient-level outcome, and if so, we investigated potential drivers of the heterogeneity. Results All 27 sites that enrolled ≥ 10 patients returned the questionnaire. Most sites were actively following > 100 patients with IPF (70.4%), had a lung transplant program (66.7%), and had a dedicated ILD nurse leader (77.8%). Substantial heterogeneity was observed in the event rates of clinically relevant outcomes across the sites. After controlling for patient case mix, there were no outcomes for which the site variance component was significantly different from 0, but the p-value for hospitalization was 0.052. Starting/completing an ILD-related quality improvement project in the previous 2 years was associated with a lower risk of hospitalization (HR 0.60 [95% CI 0.44, 0.82]; p = 0.001). Conclusions Analyses of data from patients with IPF managed at sites across the US found no site-specific characteristics or practices that were significantly associated with clinically relevant outcomes after adjusting for patient case mix. Trial registration ClinicalTrials.gov, NCT01915511. Registered 5 August 2013, https://clinicaltrials.gov/ct2/show/NCT01915511

Smoking Mechanics and Impact on Smoking Cessation: Two Cases of Smoking Lapse Status Post Lung Transplantation

Background Smoking behavior includes mechanisms taken on by persons to adjust for certain characteristic changes of cigarettes. However, as lung function declines due to lung-specific diseases, it is unclear how mechanical smoking behavior changes affect persons who smoke. We review two cases of patients who stopped smoking prior to and then subsequently resumed smoking after lung transplantation. Methods A retrospective review of two patients who were recipients of lung transplantation and sustained from cigarette usage prior to transplantation. Results Patient A was a 54-year-old woman who received a double lung transplant secondary to chronic obstructive pulmonary disease (COPD) in October 2017. She had stopped smoking cigarettes in July 2015 (FEV1 .56 L). Patient B was a 40-year-old man who received a double lung transplantation due to sarcoidosis in January 2015. He stopped smoking cigarettes in February 2012 (FEV1 1.15 L). Post-transplant, Patient A resumed smoking on March 2018 where her FEV1 was at 2.12 L (5 months post-transplantation), and Patient B resumed smoking in April 2017 where his FEV1 was 2.37 L (26 months post-transplantation). Conclusion We report on two patients who resumed smoking after lung transplantation. While variations of smoking mechanics have been identified as a function of nicotine yield and type of cigarette, it lung mechanics may play a role in active smoking as well. Therefore, proper screening for tobacco usage post-lung transplantation should be considered a priority in order to preserve transplanted lungs.