Physiological predictors of survival in patients with sarcoidosis-associated pulmonary hypertension: results from an international registry.

INTRODUCTION: Sarcoidosis-associated pulmonary hypertension (SAPH) is associated with reduced survival in single-centre studies. The international Registry for SAPH (ReSAPH) with long-term follow-up was established to enrich our knowledge of this complication of sarcoidosis. This analysis aims to elucidate factors associated with reduced transplant-free survival in SAPH patients. METHODS: ReSAPH contains prospectively collected outcomes of SAPH patients since the time of registry enrolment. Information analysed includes right heart catheterisation data, pulmonary function testing, chest radiography, Scadding stage and 6-min walk distance (6MWD), among others. Cox regression models were used to identify independent predictors of transplant-free survival. RESULTS: Data from 215 patients followed for a mean±sd 2.5±1.9 years were available for analysis. In the 159 precapillary patients, the Kaplan-Meier-adjusted 1-, 3- and 5-year transplant-free survival was 89.2%, 71.7% and 62.0%, respectively. Kaplan-Meier-adjusted 1-, 3- and 5-year transplant-free survival in the incident group was 83.5%, 70.3% and 58.3%, respectively, and in the prevalent group was 94.7%, 72.2% and 66.3%, respectively. Patients with reduced diffusing capacity of the lung for carbon monoxide (D LCO) (<35% predicted) and 6MWD <300 m in the precapillary cohort had significantly worse transplant-free survival. Reduced 6MWD and preserved forced expiratory volume (FEV1)/forced vital capacity (FVC) ratio were identified as independent risk factors for reduced transplant-free survival in the precapillary cohort. CONCLUSION: Reduced D LCO (<35% pred) and 6MWD (<300 m) at the time of registry enrolment were associated with reduced transplant-free survival in the overall precapillary cohort. Preserved FEV1/FVC ratio was identified as an independent risk factor for worsened outcomes.

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.

A Telemedicine-Based Intervention Reduces the Frequency and Severity of COPD Exacerbation Symptoms: A Randomized, Controlled Trial.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) may not recognize worsening symptoms that require intensification of therapy. They may also be reluctant to contact a healthcare provider for minor worsening of symptoms. A telemedicine application for daily symptom reporting may reduce these barriers and improve patient outcomes. MATERIALS AND METHODS: Patients hospitalized for a COPD exacerbation within the past year or using supplemental O2 were approached for participation. Patients received optimal COPD care and were given a telecommunication device for symptom reporting. Initial symptom scores were obtained while patients were in their usual state of health. Patients were randomly assigned to an intervention group or a control group (usual medical care). The control group patients were instructed to seek medical care if their condition worsened. The intervention group symptom scores were assessed by a computer algorithm and compared with initial values. Scores 1 or more points above the initial score generated an "alert," and patients were reviewed by a nurse and referred to a physician who prescribed treatment. RESULTS: Eighty-six patients were screened; 79 met entry criteria and were randomized (intervention group, n=39; control group, n=40). Twelve patients submitted five or fewer symptom reports (5 intervention; 7 control) and were excluded from the analysis. Daily peak flow and dyspnea scores improved only in the intervention group. There were no differences in hospitalization and mortality rates between groups. No serious adverse events were reported. CONCLUSIONS: A telemedicine-based symptom reporting program facilitated early treatment of symptoms and improved lung function and functional status.

Sarcoidosis-associated pulmonary hypertension.

PURPOSE OF REVIEW: Pulmonary hypertension is a serious complication of sarcoidosis. This review discusses clinical characteristics of patients with sarcoid-associated pulmonary hypertension (SAPH) and pitfalls in the diagnosis, and highlights potential therapies. RECENT FINDINGS: SAPH is common in patients with advanced disease, but it can occur in patients with minimal disease burden. Risk factors for SAPH include restrictive lung physiology, hypoxemia, advanced Scadding chest X-ray stage, and low carbon monoxide diffusion capacity. Echocardiogram is a good initial screening tool in the diagnosis of pulmonary hypertension, but right heart catheterization is necessary to confirm the diagnosis. Treatment with pulmonary vasodilators, including endothelin antagonists, can lead to improvements in pulmonary hemodynamics in some patients but may not improve their exercise capacity. Forced vital capacity is an important predictor of exercise performance in patients with SAPH. Clinical observations and response to specific therapies for pulmonary hypertension suggest the presence of different SAPH phenotypes. SUMMARY: Patients who complain of persistent dyspnea should be screened for the presence of pulmonary hypertension. The prognosis of SAPH is poor and it is prudent to consider referral of these patients for lung transplantation. In some patients with SAPH, treatment with anti-inflammatory agents and pulmonary vasodilators can lower pulmonary arterial pressures, improve dyspnea and functionality, and enhance overall quality of life.

Pulmonary hemodynamics and transplant-free survival in sarcoidosis-associated pulmonary hypertension: Results from an international registry.

Pulmonary hypertension (PH) is a risk factor for mortality in patients with sarcoidosis. Severe PH in chronic lung disease has previously been defined as mean pulmonary arterial pressure (mPAP) ≥ 35 mmHg or mPAP 25 ≥ mmHg with cardiac index (CI) ≤ 2 L/min/m2. However, there is no clear definition denoting severity of sarcoidosis-associated PH (SAPH). We aimed to determine pulmonary hemodynamic cut-off values where transplant-free survival was worse among patients with SAPH. This was a retrospective cohort analysis of the Registry of SAPH database focusing on pulmonary hemodynamic predictors of transplant-free survival among patients with precapillary SAPH. Cox regression was performed to determine which pulmonary hemodynamic values predicted death or lung transplantation. Kaplan-Meier survival analysis was performed on statistically significant predictors to determine pulmonary hemodynamic cut-off values where transplant-free survival was decreased. Decreased transplant-free survival occurred among SAPH patients with mPAP ≥ 40 mmHg and SAPH patients with pulmonary vascular resistance (PVR) ≥ 5 Woods units (WU). Transplant-free survival was not decreased in patients who fulfilled prior criteria of severe PH in chronic lung disease. We identified new cut-offs with decreased transplant-free survival in the SAPH population. Neither cut-off of mPAP ≥ 40 mmHg nor PVR ≥ 5 WU has previously been shown to be associated with decreased transplant-free survival in SAPH. These values could suggest a new definition of severe SAPH. Our PVR findings are in line with the most recent European Society of Cardiology/European Respiratory Society guideline definition of severe PH in chronic lung disease.

Predictors of lung transplant waitlist mortality for sarcoidosis.

RATIONALE: Unlike in other chronic lung diseases, criteria for lung transplant referral in sarcoidosis is not well-established. Waitlist mortality may offer clues in identifying clinical factors that warrant early referral. We aim to identify predictors for transplant waitlist mortality to improve referral criteria for patients with sarcoidosis. METHODS: We conducted a retrospective analysis of 1034 sarcoidosis patients listed for lung transplantation from May 2005 to May 2019 in the Scientific Registry of Transplant Recipients (SRTR) database. All patients were listed after the establishment of the Lung Allocation Score (LAS). We compared patients who died on the transplant waitlist to those who survived to transplantation. Potential predictors of waitlist mortality were assessed utilizing univariate and multivariate analysis performed via logistic regression modeling. RESULTS: Of 1034 candidates listed after LAS implementation, 704 were transplanted and 110 died on the waitlist. Significant predictors of waitlist mortality on multivariate analysis include female gender (OR 2.445; 95% CI 1.513-3.951; p = 0.0003) and severe pulmonary hypertension (OR 1.619; 95% CI 1.067-2.457; p = 0.0236). Taller minimum donor height (OR 0.606; 95% CI 0.379-0.969; p = 0.0365) and blood type B (OR 0.524; 95% CI 0.281-0.975 p = 0.0415) were associated with decreased likelihood of death on the waitlist. CONCLUSION: Among patients with sarcoidosis on the lung transplant waitlist, taller minimum donor height and blood type B were found to be protective factors against death on the waitlist. Female gender and severe pulmonary hypertension have a higher likelihood of death and earlier referral for transplantation in patients with these characteristics should be considered.

The six-minute walk test in sarcoidosis associated pulmonary hypertension: Results from an international registry.

INTRODUCTION: Sarcoidosis associated pulmonary hypertension (SAPH) is a leading contributor to sarcoidosis-related mortality. The 6-min walk test (6MWT) is widely used in assessment of cardiorespiratory conditions. A reduced 6-min walk distance (6MWD) has been associated with increased mortality in SAPH. We examined patients from the Registry of Sarcoidosis Associated Pulmonary Hypertension (ReSAPH) who had performed 6MWT at enrollment to identify variables that affect 6MWD, and the prognostic value of 6MWT variables regarding death or lung transplantation. MATERIAL AND METHODS: ReSAPH patients with available 6MWT were included. Variables analyzed using pre-defined cutoffs included 6MWD, initial and end of test Borg dyspnea score, oxygen saturation, and heart rate at beginning, end, and after 1-min recovery, absolute change in oxygen saturation, modified distance-saturation product (mDSP), and the heart rate recovery at 1-min (HRR). FINDINGS: 174 patients met inclusion criteria; 48 patients died and 8 underwent lung transplantation. Patients with 6MWD<300 m had a higher chance of dying or undergoing transplantation compared to those with 6MWD>300 m (p = 0.012). No associations with outcome were observed with mDSP cutoff 200 m%, desaturation≥5% and oxygen saturation<88% at end of 6MWT, or multiple HRR cutoffs (13,14,16). 6MWD correlated with initial Borg score, (p = 0.001), DLCO% (p = 0.0001) and sPAP (p = 0.031) on multivariate analysis. These variables were significant for both pre- and post-capillary PH subgroups. 6MWD also correlated with fatigue assessment scale (FAS) (p = 0.015). CONCLUSION: Of the parameters evaluated, 6MWD had the greatest prognostic value in SAPH which correlated with other physiologic and hemodynamic variables. 6MWT captures the multidimensional effects of sarcoidosis.

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.

Clinical predictors and explant lung pathology of acute exacerbation of idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterised by constant threat of acute exacerbation of IPF (AE-IPF). It would be significant to identify risk factors of AE-IPF. We sought to determine the prognostic value of lung transplantation candidacy testing for AE-IPF and describe explant pathology of recipients with and without AE-IPF before lung transplantation. METHODS: Retrospective cohort study of 89 IPF patients listed for lung transplantation. Data included pulmonary function testing, echocardiography, right heart catheterisation, imaging, oesophageal pH/manometry and blood tests. Explanted tissue was evaluated by pulmonary pathologists and correlated to computed tomography (CT) findings. RESULTS: Out of 89 patients with IPF, 52 were transplanted during stable IPF and 37 had AE-IPF before transplantation (n=28) or death (n=9). There were no substantial differences in candidacy testing with and without AE-IPF. AE-IPF had higher rate of decline of forced vital capacity (FVC) (21±22% versus 4.8±14%, p=0.00019). FVC decline of >15% had a hazard ratio of 7.2 for developing AE-IPF compared to FVC decline of <5% (p=0.004). AE-IPF had more secondary diverse histopathology (82% versus 29%, p<0.0001) beyond diffuse alveolar damage. There was no correlation between ground-glass opacities (GGO) on chest CT at any point to development of AE-IPF (p=0.077), but GGO during AE-IPF predicted secondary pathological process beyond diffuse alveolar damage. CONCLUSIONS: Lung transplantation candidacy testing including reflux studies did not predict AE-IPF besides FVC absolute decline. CT did not predict clinical or pathological AE-IPF. Secondary diverse lung pathology beyond diffuse alveolar damage was present in most AE-IPF, but not in stable IPF.

Pulmonary vasculopathy in explanted lungs from patients with interstitial lung disease undergoing lung transplantation.

BACKGROUND: Pulmonary hypertension (PH) causes increased morbidity and mortality in patients with interstitial lung diseases (ILD). Classification schemes, while well-characterised for the vasculopathy of idiopathic PH, have been applied, unchallenged, to ILD-related PH. We evaluated pulmonary arterial histopathology in explanted human lung tissue from patients who were transplanted for advanced fibrotic ILD. METHODS: Lung explants from 38 adult patients who underwent lung transplantation were included. Patients were divided into three groups: none, mild/moderate and severe PH by mean pulmonary artery pressure (mPAP) measured at pre lung transplantation right heart catheterisation (RHC). Grading of pulmonary vasculopathy according to Heath and Edwards scheme, and prelung transplantation evaluation data were compared between the groups. RESULTS: 38 patients with fibrotic ILDs were included, the majority (21) with idiopathic pulmonary fibrosis. Of the 38 patients, 18 had severe PH, 13 had mild/moderate PH and 7 had no PH by RHC. 16 of 38 patients had severe pulmonary arterial vasculopathy including vascular occlusion with intimal fibrosis and/or plexiform lesions. There were no correlations between mPAP and lung diffusion with the severity of pulmonary arterial pathological grade (Spearman's rho=0.14, p=0.34, rho=0.11, p=0.49, respectively). CONCLUSIONS: Patients with end stage ILD had severe pulmonary arterial vasculopathy in their explanted lungs irrespective of the presence and/or severity of PH as measured by RHC. These findings suggest that advanced pulmonary arterial vasculopathy is common in patients with advanced fibrotic ILD and may develop prior to the clinical detection of PH by RHC.

Effect of Acute Exacerbation of Idiopathic Pulmonary Fibrosis on Lung Transplantation Outcome.

BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) has an expected median survival of 3 months. Lung transplantation is a potentially lifesaving therapy for AE-IPF. However, the current knowledge of transplantation outcomes during AE-IPF is limited to a few small retrospective studies, reporting only 1-year post-transplantation survival. METHODS: Study population included patients with IPF consecutively listed for lung transplantation at a single institution between the years 2012 and 2016. We collected lung allocation score (LAS), hospitalization, and survival data. The primary outcome was survival among patients transplanted during stable IPF vs during AE-IPF. RESULTS: Of 89 patients with IPF listed for lung transplantation, 52 were transplanted during stable IPF and 37 were hospitalized due to AE-IPF. Of these 37 patients, nine died before transplantation, and 28 were transplanted during AE-IPF. Fifty percent of patients transplanted during AE-IPF died in a mean follow-up of 1.6 ± 1.2 years compared with 12% of patients transplanted during stable IPF who died in a mean follow-up of 2.6 ± 1.2 years. The Kaplan-Meier survival curves post-transplantation after 1 and 3 years for patients who were transplanted during stable IPF were 94% and 90% vs 71% and 60% in patients who were transplanted during AE-IPF (P = .0001). LAS above 80 conferred a 3-year hazard ratio for mortality of 5.7 vs LAS lower than 80 (95% CI, 2.33-14.0; P < .0005). CONCLUSIONS: Patients with IPF transplanted during AE-IPF had significantly worse short-term and long-term survival compared with patients transplanted during stable IPF. Patients with AE-IPF and very high LAS may not experience the survival advantage expected from lung transplantation.

Clinical features of sarcoidosis associated pulmonary hypertension: Results of a multi-national registry.

BACKGROUND: Pulmonary hypertension (PH) is a significant cause of morbidity and mortality in sarcoidosis. We established a multi-national registry of sarcoidosis associated PH (SAPH) patients. METHODS: Sarcoidosis patients with PH confirmed by right heart catheterization (RHC) were studied. Patients with pulmonary artery wedge pressure (PAWP) of 15 mmHg or less and a mean pulmonary artery pressure (mPAP) ≥ 25 Hg were subsequently analyzed. Data collected included hemodynamics, forced vital capacity (FVC), diffusion capacity of carbon monoxide (DLCO), chest x-ray, and 6-min walk distance (6MWD). RESULTS: A total of 176 patients were analyzed. This included 84 (48%) cases identified within a year of entry into the registry and 94 (53%) with moderate to severe PH. There was a significant correlation between DLCO percent predicted (% pred) andmPAP (Rho = -0.228, p = 0.0068) and pulmonary vascular resistance (PVR) (Rho = -0.362, p < 0.0001). PVR was significantly higher in stage 4 disease than in stage 0 or 1 disease (p < 0.05 for both comparisons). About two-thirds of the SAPH patients came from the United States (US). There was a significant difference in the rate of treatment between US (67.5%) versus non-US (86%) (Chi Square 11.26, p = 0.0008) sites. CONCLUSIONS: The clinical features of SAPH were similar across multiple centers in the US, Europe, and the Middle East. The severity of SAPH was related to reduced DLCO. There were treatment differences between the US and non-US centers.

Full face mask for noninvasive positive-pressure ventilation in patients with acute respiratory failure.

BACKGROUND: Noninvasive positive-pressure ventilation (NPPV) is commonly used to improve ventilation and oxygenation in patients with acute respiratory failure (ARF). Mask leak and intolerance due to facial discomfort or claustrophobia often occur with NPPV and are frequently cited reasons for treatment failure. METHODS: Retrospective review of patient records from a tertiary-care referral hospital. RESULTS: We report the effectiveness of a full face mask in the application of NPPV for 10 nonambulatory patients (mean [SD], 61 [9] years) who had a combined total of 13 episodes of ARF. After these patients were unable to receive NPPV therapy via the more commonly available nasal or oronasal masks, care was provided using full face masks. Eight of 10 patients had hypercapnic respiratory failure; 2 patients, hypoxemic respiratory failure. All patients were placed on ventilation initially using a bi-level positive airway pressure device. Subsequently, patient ventilation was achieved using a Puritan Bennett 7200a ventilator for on-line respiratory monitoring. The mean (SD) duration of treatment with NPPV was 9.7 (2.7) hours per day for 3.0 (1.6) days. Following NPPV via full face mask, the patients' Paco(2) decreased (65 [20] vs 82 [27] mm Hg, P=.09) and pH increased significantly (7.36 [0.07] vs 7.26 [0.07], P<.05) in less than 2 hours. Moreover, the patients demonstrated decreased respiratory rate (18 [7] vs 32 [8] breaths/min, P<.01), heart rate (106 [13] vs 124 [16] beats/min, P=.008), and Acute Physiology and Chronic Health Evaluation II scores (12 [3] vs 17 [4], P<.005) after NPPV via full face mask. These cardiorespiratory alterations occurred as early as 1 hour after NPPV initiation and were maintained throughout treatment. Two patients required endotracheal intubation because of copious purulent secretions. CONCLUSION: For individuals with hypercapnic respiratory failure who cannot tolerate NPPV using nasal or oronasal masks, use of full face masks may improve outcomes, allowing physicians to avoid ordering endotracheal intubation and mechanical ventilation.

Bosentan for sarcoidosis-associated pulmonary hypertension: a double-blind placebo controlled randomized trial.

BACKGROUND: Sarcoidosis-associated pulmonary hypertension (SAPH) is a common problem in patients with persistent dyspneic sarcoidosis. The objective of this study was to determine the effect of bosentan therapy on pulmonary arterial hemodynamics in patients with SAPH. METHODS: This 16-week study was a double-blind, placebo-controlled trial of either bosentan or placebo in patients with SAPH confirmed by right-sided heart catheterization. Patients were enrolled from multiple academic centers specializing in sarcoidosis care. They were stable on sarcoidosis therapy and were receiving no therapy for pulmonary hypertension. The cohort was randomized two to one to receive bosentan at a maximal dose of 125 mg or placebo bid for 16 weeks. Pulmonary function studies, 6-min walk test, and right-sided heart hemodynamics, including pulmonary artery mean pressure and pulmonary vascular resistance (PVR), were performed before and after 16 weeks of therapy. RESULTS: Thirty-five patients completed 16 weeks of therapy (23 treated with bosentan, 12 with placebo). For those treated with bosentan, repeat hemodynamic studies at 16 weeks demonstrated a significant mean±SD fall in PA mean pressure (-4±6.6 mm Hg, P=.0105) and PVR (-1.7±2.75 Wood units, P=.0104). For the patients treated with placebo, there was no significant change in either PA mean pressure (1±3.7 mm Hg, P>.05) or PVR (0.1±1.42 Wood units, P>.05). There was no significant change in 6-min walk distance for either group. Two patients treated with bosentan required an increase of supplemental oxygen by >2 L after 16 weeks of therapy. CONCLUSIONS: This study demonstrated that bosentan significantly improved pulmonary hemodynamics in patients with SAPH. TRIAL REGISTRY: ClinicalTrials.gov; No: NCT00581607; URL: www.clinicaltrials.gov.

Medical pneumoplasty, surgical resection, or lung transplant.

Over the last decade, advances in bronchoscopic and surgical techniques have expanded our treatment armamentarium for patients with severe emphysema who previously would have received a pessimistic outlook from their physician. Advances in our understanding of the different COPD phenotypes and its natural history has refined our selection process as to which group of emphysema patients will derive maximum benefit from LVR, bullectomy, or lung transplantation. Because emphysema is a progressive disease, initial treatment with bronchoscopic or surgical LVR or bullectomy does not preclude lung transplantation in the future.

Treatment of Guillain-Barré syndrome induced by cyclosporine in a lung transplant patient.

We report the case of a 58-year-old man with severe chronic obstructive pulmonary disease who developed acute quadriparesis during the post-operative period following bilateral lung transplantation after receiving cyclosporine for immunosuppression. Electromyography with nerve conduction study and cerebrospinal fluid analysis supported a diagnosis of Guillain-Barré Syndrome, which improved upon the discontinuation of cyclosporine, replacement with tacrolimus, and initiation of plasmapheresis. We propose the discontinuation of cyclosporine and initiation of plasmapheresis as a treatment for cyclosporine-associated Guillain-Barré syndrome.

Lung volume reduction surgery as a bridge to lung transplantation.

Lung volume reduction surgery (LVRS) improves lung function, exercise capacity, and quality of life in patients with advanced emphysema. In some patients with emphysema who are candidates for lung transplantation, LVRS is an alternative treatment option to lung transplantation, or may be used as a bridge to lung transplantation. Generally accepted criteria for LVRS include severe non-reversible airflow obstruction due to emphysema associated with significant evidence of lung hyperinflation and air trapping. Both high resolution computed tomography (CT) scan of the chest and quantitative ventilation/perfusion scan are used to identify lung regions with severe emphysema which would be used as targets for lung resection. Bilateral LVRS is the preferred surgical approach compared with the unilateral procedure because of better functional outcome. Lung transplantation is the preferred surgical treatment in patients with emphysema with alpha1 antitrypsin deficiency and in patients with very severe disease who have homogeneous emphysema pattern on CT scan of the chest or very low diffusion capacity.