Objectives Immunosuppressive pharmacologic agents prescribed to patients with diffuse interstitial and inflammatory lung disease and lung transplant recipients are associated with potential risks for ...adverse reactions. Strategies for minimizing such risks include administering these drugs according to established, safe protocols; monitoring to detect manifestations of toxicity; and patient education. Hence, an evidence-based guideline for physicians can improve safety and optimize the likelihood of a successful outcome. To maximize the likelihood that these agents will be used safely, the American College of Chest Physicians established a committee to examine the clinical evidence for the administration and monitoring of immunosuppressive drugs (with the exception of corticosteroids) to identify associated toxicities associated with each drug and appropriate protocols for monitoring these agents. Methods Committee members developed and refined a series of questions about toxicities of immunosuppressives and current approaches to administration and monitoring. A systematic review was carried out by the American College of Chest Physicians. Committee members were supplied with this information and created this evidence-based guideline. Conclusions It is hoped that these guidelines will improve patient safety when immunosuppressive drugs are given to lung transplant recipients and to patients with diffuse interstitial lung disease.
BACKGROUND The clinical presentation and outcome of sarcoidosis varies by race. However, the race difference in mortality outcome remains largely unknown. METHODS We studied mortality related to ...sarcoidosis from 1999 through 2010 by examining data on multiple causes of death from the National Center for Health Statistics. We compared the comorbid conditions between sarcoidosis-related deaths with deaths caused by car accidents (previously healthy control subjects) and rheumatoid arthritis (chronic disease control subjects) in both African Americans and Caucasians. RESULTS From 1999 through 2010, sarcoidosis was reported as an immediate cause of death in 10, 348 people in the United States with a combined overall mean age-adjusted mortality rate of 2.8 per 1 million person-years. Of these, 6, 285 were African American and 3, 984 Caucasian. The age-adjusted mortality rate for African Americans was 12 times higher than for Caucasians. African Americans died at an earlier age than Caucasians. African Americans living in the District of Columbia and North Carolina and Caucasians living in Vermont had higher mortality rates. Although the total sarcoidosis age-adjusted mortality rate had not changed over the 12 year period studied, this rate increased for Caucasians ( R = 0.747, P = .005) but not for African Americans. Compared with the control groups, pulmonary hypertension was significantly more common in individuals with sarcoidosis. CONCLUSIONS This nationwide population-based study exposes a significant difference in ethnicity and sex among people dying of sarcoidosis in the United States. Pulmonary hypertension investigation should be considered in all patients with sarcoidosis, especially African Americans.
Background New evidence links nicotine to the regulation of T cell-mediated inflammation via α7 nicotinic cholinergic receptor activation, and chronic nicotine exposure (smoking) reduces the ...incidence of granulomatous diseases. We sought to determine whether nicotine treatment was well tolerated while effectively normalizing immune responses in patients with active pulmonary sarcoidosis. Methods Consenting adults with symptomatic sarcoidosis (n = 13) were randomly assigned to receive 12 weeks of nicotine treatment plus conventional therapy or conventional therapy alone. Obtained blood cells were evaluated for their responsiveness to selected Toll-like receptor (TLR) and nucleotide oligomerization domain-like receptor ligands and T cell surface marker expression before and after nicotine treatment. Asymptomatic patients (n = 6) and disease-free subjects (n = 6) served as comparative control subjects. Adverse events were monitored for the duration of the study. Results Compared with the asymptomatic group, symptomatic patients had impaired peripheral responses to TLR2, TLR4, and TLR9 ligands (anergy) and reduced peripheral populations of CD4+ FoxP3+ regulatory T cells (Tregs). Nicotine treatment was associated with restoration of TLR2 and TLR9 responsiveness, and expansion of Tregs, including the CD4+ CD25− FoxP3+ phenotype. There were no serious adverse events or signs of nicotine dependency. Conclusions Nicotine treatment in active pulmonary sarcoidosis was well tolerated and restored peripheral immune responsiveness to TLR2 and TLR9 agonists and expansion of FoxP3+ Tregs, including a specific “preactivated” (CD25− ) phenotype. The immune phenotype of patients with symptomatic sarcoidosis treated with nicotine closely resembled that of asymptomatic patients, supporting the notion that nicotine treatment may be beneficial in this patient population. Trial registry ClinicalTrials.gov ; No.: NCT00701207; URL: www.clinicaltrials.gov
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
PDF
