Pulmonary Sarcoidosis: Independent Predictors of Mortality

Age, the amount of fibrosis detected on high resolution computed tomography (HRCT), and pulmonary hypertension (PH) were found to be independent predictors of mortality in patients with pulmonary sarcoidosis, according to study results published in Chest.¹

Robert Baughman, MD, from the Department of Medicine, University of Cincinnati Medical Center, Ohio, and colleagues investigated predictors of mortality in pulmonary sarcoidosis.

United States population-based studies have reported that mortality rates for sarcoidosis between 1988 and 2007² and hospitalizations between 1998 and 2008³ have risen significantly. Increasing incidence, age, detection rates, or disease severity may be responsible for rising mortality trends⁴; however, the leading cause of mortality in sarcoidosis is respiratory failure.¹

The majority of patients with sarcoidosis have pulmonary involvement, with severity ranging from asymptomatic disease to chronic respiratory failure refractory to medical treatment.⁵ Lung transplantation is the final option for end-stage pulmonary sarcoidosis.⁵

Knowing the factors that may increase the risk for death in pulmonary sarcoidosis could benefit both patients and their healthcare team. New treatment options including second-line disease modifying antisarcoid drugs and third-line biological agents could be considered in patients refractory to glucocorticoids.⁶ In addition, lung transplantation may be underutilized.⁷

The researchers evaluated a cohort of patients with pulmonary sarcoidosis who had a minimum follow-up of 8 years from the University of Cincinnati Sarcoidosis Clinic to evaluate risk factors predicting respiratory death in pulmonary sarcoidosis.

All patients seen at the clinic between 2002 and 2008 with spirometry and diffusion lung carbon monoxide measurements were evaluated for study inclusion. Sarcoidosis was diagnosed based on the American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) statement.⁸

Of 1606 patients, 452 (median age, 50 years) met inclusion criteria. The most commonly involved organ was the lung with 6.4% of patients diagnosed with right heart confirmed precapillary pulmonary hypertension.

Sarcoidosis related respiratory failure resulted in 38 deaths, and 4 patients died from unrelated causes (2 from coronary artery disease and 2 from cancer). Overall mortality from sarcoidosis was 3.9% at 5 years and 9% at 10 years.

Pulmonary hypertension (hazard ratio [HR], 8.96; P <.0001), categorization with a Walsh, et al bad prognosis⁹ (HR, 3.21; P =.0009); fibrosis >20% on HRCT (HR, 2.8; P <.0178); black race (HR, 2.5; P =.0076); and gender, age, physiology (GAP) stage 2,3 (HR, 2.84; P =.0491) were associated with an increased risk of mortality.

Factoring survival time into the statistical analysis, Cox proportional-hazards regression revealed 3 variables remained independent predictors of mortality including age (P =.0093), >20% fibrosis on HRCT (P =.0255), and pulmonary hypertension (P =.0484).

The researchers concluded, “It seems unlikely that one feature will identify all patients who will die from pulmonary sarcoidosis. Therefore, scoring systems which combine features to predict respiratory death are appealing. We confirmed that the prognostic model developed by Walsh, et al identified those sarcoidosis patients with poor prognosis.”

Study Limitations

• Results may not apply to all patients with sarcoidosis since the study was performed at a tertiary sarcoidosis center
• Due to the small number of deaths, there may be other factors significantly associated with increased mortality that were not identified
• A retrospective study with possible selection bias due to only analyzing patients with HRCT and complete pulmonary function testing

Disclosures: Dr Lower has received grant support for studies in sarcoidosis by Mallinckrodt, Gilead, Novartis, Celgene, Bayer, and Genentech. Dr Baughman has received grant support for studies in sarcoidosis by Mallinckrodt, Gilead, Novartis, Celgene, Bayer, Genentech, and the National Institutes of Health. He has also been a consultant for Gilead, Genentech, Novartis, and Mallinckrodt, and is on the speaker’s bureau for Mallinckrodt and Genentech.

References

1. Kirkil G, Lower EE, Baughman RP. Predictors of mortality in pulmonary sarcoidosis [published online July 17, 2017]. Chest. doi:10.1016/j.chest.2017.07.008
2. Swigris JJ, Olson AL, Huie TJ, et al. Sarcoidosis-related mortality in the United States from 1988 to 2007. Am J Respir Crit Care Med. 2011;183(11):1524-1530.
3. Gerke AK, Yang M, Tang F, et al. Increased hospitalizations among sarcoidosis patients from 1998 to 2008: a population-based cohort study. BMC Pulm Med. 2012;12:19. doi:10.1186/1471-2466-12-19.:19-12
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7. Shlobin OA, Nathan SD. Management of end-stage sarcoidosis: pulmonary hypertension and lung transplantation. Eur Respir J. 2012;39(6):1520-1533.
8. Hunninghake GW, Costabel U, Ando M, et al. ATS/ERS/WASOG statement on sarcoidosis. American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and other Granulomatous Disorders. Sarcoidosis Vasc Diffuse Lung Dis. 1999;16(2):149-173.
9. Walsh SL, Wells AU, Sverzellati N, et al. An integrated clinicoradiological staging system for pulmonary sarcoidosis: a case-cohort study. Lancet Respir Med. 2014;2(2):123-130.