Oksana A. Shlobin

Original ResearchPulmonary HypertensionTreatment of Sarcoidosis-Associated Pulmonary Hypertension: A Two-Center Experience

BACKGROUNDnPulmonary hypertension (PH) is a common complication of sarcoidosis that is associated with increased mortality. The pathogenesis of PH in sarcoidosis is uncertain, and the role of pulmonary arterial hypertension (PAH)-specific therapies remains to be determined.nnnMETHODSnWe conducted a retrospective study of patients with sarcoidosis and PH at two referral centers. New York Heart Association (NYHA) functional class, exercise capacity, hemodynamic data, pulmonary function tests, and survival were collected and analyzed.nnnRESULTSnTwenty-two sarcoidosis patients treated with PAH-specific therapies were identified. After a median of 11 months of follow-up, NYHA class was improved in nine subjects. Mean 6-min walk distance (n = 18) increased by 59 m (p = 0.032). Patients with a higher FVC experienced a greater increment in exercise capacity. Among 12 patients with follow-up hemodynamic data, mean pulmonary artery pressure was reduced from 48.5 +/- 4.3 to 39.4 +/- 2.8 mm Hg (p = 0.008). The 1- and 3-year transplant-free survival rates were 90% and 74%, respectively.nnnCONCLUSIONSnPAH-specific therapy may improve functional class, exercise capacity, and hemodynamics in PH associated with sarcoidosis. Prospective, controlled trials of PAH therapies for sarcoidosis are warranted to verify this apparent benefit. Mortality among the study population was high, highlighting the need for urgent evaluation at a lung transplant center.

Persistent Cytomegalovirus-Specific Memory Responses in the Lung Allograft and Blood following Primary Infection in Lung Transplant Recipients

Primary CMV infection in lung transplant recipients (LTRs) is associated with increased mortality. We studied 22 donor CMV-positive, recipient-negative (D+R−) LTRs for the development of posttransplant CMV-specific immunity. We found that 13 of 22 D+R− LTRs (59.1%) seroconverted (CMV IgG Ab+). Using pooled peptides of the immunodominant CMV Ags pp65 and IE1, we detected CMV-specific CD8+IFN-γ+ T cells in the PBMC of 90% of seroconverted individuals following primary infection by intracellular cytokine staining. In contrast, few seroconverters had detectable CMV-specific CD4+IFN-γ+ T cells during viral latency. However, the majority of IgG+ LTRs demonstrated CMV-specific CD4+ and CD8+ T cell proliferative responses from PBMC, with CD4+IFN-γ+ T cells detectable upon re-expansion. Examination of lung allograft mononuclear cells obtained by bronchoalveolar lavage revealed both CMV-specific CD4+ and CD8+IFN-γ+ T cells, including patients from whom CD4+IFN-γ+ T cells were simultaneously undetectable in the PBMC, suggesting differential effector memory populations between these compartments. Moreover, both responses in the PBMC and lung allograft were found to persist, despite substantial immunosuppression, long after primary infection. Clinical correlation in this cohort demonstrated that the acquisition of CMV immunity was associated with freedom from CMV disease (p ≤ 0.009) and preservation of allograft function (p ≤ 0.02) compared with those who failed to develop CMV immunity. Together, our data reveal immunologic heterogeneity in D+R− LTRs, with the development and persistence of primary CMV responses that may provide clinical benefit.

Management of end-stage sarcoidosis: pulmonary hypertension and lung transplantation

Sarcoidosis is not only a multisystem, but also a multinational disease that is prevalent throughout the world, including Europe, the USA and Japan. Lung involvement in sarcoidosis is seemingly invariable, with up to 95% of patients manifesting some form of pulmonary disease during the course of their lifetime. The natural history of sarcoidosis in the lung is quite variable and spans the spectrum from spontaneous resolution to advanced fibrocystic disease in ∼5% of cases. Advanced sarcoidosis will be the subject of this review with a special focus on pulmonary hypertension and lung transplantation as a last-resort treatment option for some patients with end-stage disease.

Pulmonary hypertension secondary to interstitial lung disease

Interstitial lung diseases (ILDs) may be complicated by the development of pulmonary hypertension (PH), which is associated with worse functional impairment and a poorer prognosis. This article reviews the current state of knowledge on the prevalence, pathogenesis, diagnosis and prognosis of ILD-related PH. Whether the treatment of ILD-related PH changes clinical outcomes is currently unknown, but the current studies are summarized and the authors’ perspective is offered.

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

BACKGROUNDnPulmonary hypertension (PH) is a significant cause of morbidity and mortality in sarcoidosis. We established a multi-national registry of sarcoidosis associated PH (SAPH) patients.nnnMETHODSnSarcoidosis patients with PH confirmed by right heart catheterization (RHC) were studied. Patients with pulmonary artery wedge pressure (PAWP) of 15u202fmmHg or less and a mean pulmonary artery pressure (mPAP)u202f≥u202f25 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).nnnRESULTSnA 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 (Rhou202f=u202f-0.228, pu202f=u202f0.0068) and pulmonary vascular resistance (PVR) (Rhou202f=u202f-0.362, pu202f<u202f0.0001). PVR was significantly higher in stage 4 disease than in stage 0 or 1 disease (pu202f<u202f0.05 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, pu202f=u202f0.0008) sites.nnnCONCLUSIONSnThe 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.