Effect of antifibrotic therapy in patients with idiopathic pulmonary fibrosis undergoing lung transplant in the peri and post-operative period.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a rapidly progressive interstitial lung disease with high mortality. Lung transplant remains a cornerstone of treatment despite the advent of antifibrotic therapy. In light of the increasing number of patients on antifibrotic therapy prior to lung transplantation it is paramount to demonstrate these medications do not augment postoperative complications following transplant. RESEARCH QUESTION: Does antifibrotic therapy increase perioperative complications and mortality in lung transplant recipients? STUDY DESIGN AND METHODS: We conducted a retrospective chart review of all patients actively listed for lung transplant at Temple University Hospital from June 2014 to April 2017 with a listing diagnosis of IPF. Subjects who received treatment with antifibrotic therapy (either pirfenidone or nintedanib) up until the time of lung transplantation were compared to subjects not on therapy. Data was collected regarding baseline demographics, pulmonary function tests, IPF exacerbations, perioperative bleeding and cardiac events, and outcomes in the postoperative period. RESULTS: A total of 94 subjects were included in the study: 42 subjects on antifibrotic therapy (28 pirfenidone, 14 nintedanib) and 52 subjects not on therapy in the pre-transplant period. Baseline characteristics were similar between study groups. Subjects treated with antifibrotic therapy pre-transplant were noted to have less FVC decline, fewer hospitalizations, and greater weight loss while on the transplant waiting list. No difference in post-transplant airway anastomosis complications, bleeding or mortality was observed between study groups. INTERPRETATION: Subjects with IPF on antifibrotic therapy prior to lung transplantation had better preservation of lung function in the pre-transplant period, and similar outcomes in the postoperative period compared to those not on antifibrotic therapy before lung transplant.

Guiding therapeutic plasma exchange for antibody-mediated rejection treatment in lung transplant recipients - a retrospective study.

Antibody-Mediated Rejection (AMR) due to donor-specific antibodies (DSA) is associated with poor outcomes after lung transplantation. Currently, there are no guidelines regarding the selection of treatment protocols. We studied how DSA characteristics including titers, C1q, and mean fluorescence intensity (MFI) values in undiluted and diluted sera may predict a response to therapeutic plasma exchange (TPE) and inform patient prognosis after treatment. Among 357 patients consecutively transplanted without detectable pre-existing DSAs between 01/01/16 and 12/31/18, 10 patients were treated with a standardized protocol of five TPE sessions with IVIG. Based on DSA characteristics after treatment, all patients were divided into three groups as responders, partial responders, and nonresponders. Kaplan-Meier Survival analyses showed a statistically significant difference in patient survival between those groups (P = 0.0104). Statistical analyses showed that MFI in pre-TPE 1:16 diluted sera was predictive of a response to standardized protocol (R2  = 0.9182) and patient survival (P = 0.0098). Patients predicted to be nonresponders who underwent treatment with a more aggressive protocol of eight TPE sessions with IVIG and bortezomib showed improvements in treatment response (P = 0.0074) and patient survival (P = 0.0253). Dilutions may guide clinicians as to which patients would be expected to respond to a standards protocol or require more aggressive treatment.

COVID-19 in lung transplant recipients.

Solid organ transplant recipients are considered at high risk for COVID-19 infection due to chronic immune suppression; little data currently exists on the manifestations and outcomes of COVID-19 infection in lung transplant recipients. Here we report 8 cases of COVID-19 identified in patients with a history of lung transplant. We describe the clinical course of disease as well as preexisting characteristics of these patients.

Pneumothorax After Transbronchial Biopsy in Pulmonary Fibrosis: Lessons from the Multicenter COMET Trial.

PURPOSE: Some patients with diffuse interstitial lung disease (ILD) undergo bronchoscopy with transbronchial biopsy (TBB) as part of their diagnostic evaluation. It is unclear what the incidence and risk factors for pneumothorax (PTX) following TBB are in this patient population. METHODS: Ninety-seven subjects with pulmonary fibrosis who underwent a research bronchoscopy with TBB as part of the multicenter correlating outcomes with biochemical markers to estimate time-progression in idiopathic pulmonary fibrosis (COMET) trial were retrospectively reviewed. We compared subjects who developed a PTX during research bronchoscopy with TBB versus those who did not. RESULTS: Seven patients (7.2%) experienced a PTX during research bronchoscopy with TBB. Subjects who experienced PTX during TBB had significantly lower DLCO percent predicted (29 ± 8 vs. 45 ± 15, P = 0.006) and had lower resting room air saturation of peripheral oxygen (SPO2) on 6-min walk testing (91 ± 10 vs. 95 ± 3, P = 0.02). No differences between groups were found with respect to age, gender, race, BMI, HRCT characteristics, or the number of transbronchial biopsies performed. CONCLUSION: The incidence of PTX following research bronchoscopy with TBB in patients with pulmonary fibrosis was found to be 7.2% in this study. Patients who developed a pneumothorax had greater impairments in gas exchange at baseline evidenced by a lower DLCO  % predicted and a lower resting room air SPO2 compared with subjects without PTX as a complication.

Pirfenidone and nintedanib for pulmonary fibrosis in clinical practice: Tolerability and adverse drug reactions.

BACKGROUND AND OBJECTIVE: The real-world tolerability of pirfenidone and nintedanib in non-clinical trial patients is unknown. Many patients with pulmonary fibrosis have significant medical co-morbidities or baseline characteristics that exclude them from clinical trial participation. METHODS: We conducted a retrospective chart review study on subjects prescribed nintedanib or pirfenidone for pulmonary fibrosis treatment (any aetiology) from September 2014 to February 2016. A total of 186 subjects were included: 129 received pirfenidone and 57 were prescribed nintedanib and followed up for mean observation periods of 52 ± 17 weeks for pirfenidone and 41 ± 15 weeks for nintedanib. The primary outcome was drug discontinuation as a result of an adverse event. RESULTS: Subjects had significant respiratory impairment at baseline, 63% required home oxygen therapy and mean diffusion capacity of carbon monoxide (DLCO) was 36 ± 14% predicted. Drug discontinuation as a result of an adverse event occurred in 20.9% of subjects on pirfenidone and 26.3% on nintedanib. Drug discontinuation rates for both pirfenidone and nintedanib did not significantly differ from corresponding large clinical trials (ASCEND/CAPACITY and INPULSIS 1 and 2, respectively). Adverse events that occurred with highest frequency on pirfenidone were nausea (26.4%), rash/photosensitivity (14.7%) and dyspepsia/gastroesophageal reflux disease (GERD) (12.4%). Diarrhoea (52.6%) and nausea (29.8%) were reported most often with nintedanib therapy. CONCLUSION: Patients with pulmonary fibrosis treated with nintedanib or pirfenidone in routine clinical practice had drug tolerability and adverse event profiles comparable with subjects enrolled in clinical trials despite having a greater degree of respiratory impairment and a high prevalence of co-morbid medical conditions.

Home non-invasive ventilation use following acute hypercapnic respiratory failure in COPD.

RATIONALE: Patients with COPD and hypercapnic respiratory failure have a worse prognosis and experience a faster deterioration in their pulmonary function. The benefit of home NPPV following an acute exacerbation of COPD with hypercapnic respiratory failure is not well understood. OBJECTIVES: To evaluate the effect of home NPPV use in patients following a hospitalization for AECOPD with acute hypercapnic respiratory failure on event-free survival after an index admission. METHODS: We conducted a retrospective, single-center, chart review on patients hospitalized in 2011 with a diagnosis of AECOPD, hypercapnia, and used NPPV during hospitalization. 166 patients were included and were divided into two groups: patients who used NPPV post discharge and patients who did not. RESULTS: Patients in the NPPV post discharge group demonstrated superior event-free survival compared to the no-NPPV post discharge group (y2 = 23.8, p < 0.0001). The NPPV post discharge group had a statistically significant reduction in hospital readmissions (40% versus 75%, p < 0.0001) through 180 days from the index admission. CONCLUSIONS: Patients who used NPPV following an admission for AECOPD with hypercapnic respiratory failure had lower readmission rates and improved event-free survival after 180 days from an index admission compared to patients who did not use NPPV post discharge.

Cannabinoid hyperemesis syndrome.

Coinciding with the increasing rates of cannabis abuse has been the recognition of a new clinical condition known as Cannabinoid Hyperemesis Syndrome. Cannabinoid Hyperemesis Syndrome is characterized by chronic cannabis use, cyclic episodes of nausea and vomiting, and frequent hot bathing. Cannabinoid Hyperemesis Syndrome occurs by an unknown mechanism. Despite the well-established anti-emetic properties of marijuana, there is increasing evidence of its paradoxical effects on the gastrointestinal tract and CNS. Tetrahydrocannabinol, cannabidiol, and cannabigerol are three cannabinoids found in the cannabis plant with opposing effects on the emesis response. The clinical course of Cannabinoid Hyperemesis Syndrome may be divided into three phases: prodromal, hyperemetic, and recovery phase. The hyperemetic phase usually ceases within 48 hours, and treatment involves supportive therapy with fluid resuscitation and anti-emetic medications. Patients often demonstrate the learned behavior of frequent hot bathing, which produces temporary cessation of nausea, vomiting, and abdominal pain. The broad differential diagnosis of nausea and vomiting often leads to delay in the diagnosis of Cannabinoid Hyperemesis Syndrome. Cyclic Vomiting Syndrome shares several similarities with CHS and the two conditions are often confused. Knowledge of the epidemiology, pathophysiology, and natural course of Cannabinoid Hyperemesis Syndrome is limited and requires further investigation.