Predictors of Mortality in Pulmonary Sarcoidosis

doi:10.1016/j.chest.2017.07.008

Chest

Volume 153, Issue 1, January 2018, Pages 105-113

https://doi.org/10.1016/j.chest.2017.07.008 Get rights and content

Objective

The goal of this study was to assess the prognostic strength of factors in predicting respiratory death in a large cohort of patients with sarcoidosis with at least 8 years’ follow-up.

Methods

Data were collected on age, sex, self-declared race, time of death, spirometry findings, diffusing capacity for carbon monoxide, chest radiograph stage, extent of fibrosis on high-resolution CT (HRCT) scanning, and presence of precapillary pulmonary hypertension (PH). The Gender-Age-Physiology (GAP) index and Walsh model criteria for high vs low risk were calculated.

Results

A total of 452 patients were identified who had complete pulmonary function testing and chest imaging. The median age at time of entry into the study was 50 years (range, 25-78 years). PH was confirmed by right heart catheterization in 29 (6.4%). Of 452 patients, 42 died during the time of the study, including 38 (8.4%) who died of sarcoidosis-associated respiratory failure and 4 who died of non-sarcoidosis causes. The overall mortality from sarcoidosis was 3.9% and 9.0% at 5 and 10 years, respectively. Alive patients were significantly younger than patients who died from sarcoidosis. Increased mortality was seen for black patients, stage 4 chest radiographs, > 20% fibrosis on HRCT scanning, or PH. The two composite scores (GAP and the Walsh model) were predictive of increased mortality according to univariate analysis. Using the Cox proportional hazards regression model, only age, extent of fibrosis on HRCT scanning, and PH were independent predictors of mortality.

Conclusions

Although most patients with sarcoidosis do well, increased mortality was seen in those patients who were older, had extensive fibrosis on HRCT scanning, or who had PH.

Section snippets

Patients and Methods

All patients seen at the University of Cincinnati Sarcoidosis Clinic seen between 2002 and 2008 with recorded spirometry and Dlco measurements were evaluated. Serial data collected at each clinic visit included vital signs, current medications, and most recent pulmonary function study results and chest roentgenogram reports. The diagnosis of sarcoidosis was confirmed according to the American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and Other Granulomatous

Results

A total of 452 of the 1,606 patients seen in the University of Cincinnati Sarcoidosis Clinic between 2002 and 2008 met the criteria for evaluation. The median age at time of study entry was 50 years (range, 25-78 years). Table 1 describes the sex, self-declared race, and organ involvement assessed by using the WASOG criteria.²² Although the lung was the most common organ involved, many patients exhibited extrapulmonary manifestations. In addition, 29 (6.4%) had precapillary pulmonary

Discussion

Over the past 40 years, the number of deaths attributed to sarcoidosis has increased.5, 6 In one study of death certificates, pulmonary fibrosis was a contributing factor in many of the sarcoidosis-associated deaths.⁵ Cardiac issues such as coronary artery disease were also contributing factors: however, the presence of sarcoidosis was protective from having a cardiac etiology contributing to death except in patients aged 35 to 44 years. In addition, that study found that < 2% of patients who

Conclusions

This study examined potential factors predictive for increased mortality from sarcoidosis. We found that advanced age along with either extensive pulmonary fibrosis or pulmonary hypertension were independent predictors of mortality. It seems unlikely that one feature will identify all patients who will die of pulmonary sarcoidosis. Therefore, scoring systems that combine features to predict respiratory death are appealing. We confirmed that the prognostic model developed by Walsh et al²⁰

Acknowledgments

Author contributions: R. P. B. takes responsibility for (is the guarantor of) the content of the manuscript, including the data and analysis. G. K. and R. P. B. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis, including and especially any adverse effects. All three authors contributed substantially to the study design, data analysis and interpretation, and the writing of the manuscript.

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Cited by (151)

Organ involvement in newly diagnosed sarcoidosis patients in the Netherlands: The first large European multicentre prospective study
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Clinical presentation and prevalence of organ involvement is highly variable in sarcoidosis and depends on ethnic, genetic and geographical factors. These data are not extensively studied in a Dutch population.
To determine the prevalence of organ involvement and the indication for systemic immunosuppressive therapy in newly diagnosed sarcoidosis patients in the Netherlands.
Two large Dutch teaching hospitals participated in this prospective cohort study. All adult patients with newly diagnosed sarcoidosis were prospectively included and a standardized work-up was performed. Organ involvement was defined using the WASOG instrument.
Between 2015 and 2020, a total of 330 patients were included, 55% were male, mean age was 46 (SD 14) years. Most of them were white (76%). Pulmonary involvement including thoracic lymph node enlargement was present in 316 patients (96%). Pulmonary parenchymal disease was present in 156 patients (47%). Ten patients (3%) had radiological signs of pulmonary fibrosis. Cutaneous sarcoidosis was present in 74 patients (23%). Routine ophthalmological screening revealed uveitis in 29 patients (12%, n = 256)). Cardiac and neurosarcoidosis were diagnosed in respectively five (2%) and six patients (2%). Renal involvement was observed in 11 (3%) patients. Hypercalcaemia and hypercalciuria were observed in 29 (10%) and 48 (26%, n = 182) patients, respectively. Hepatic involvement was found in 6 patients (2%). In 30% of the patients, systemic immunosuppressive treatment was started at diagnosis.
High–risk organ involvement in sarcoidosis is uncommon at diagnosis. Indication for systemic immunosuppressive therapy was present in a minority of patients.
High-Resolution CT Scan Fibrotic Patterns in Stage IV Pulmonary Sarcoidosis: Impact on Pulmonary Function and Survival
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Different patterns of fibrosis on high-resolution CT scans (HRCT) have been associated with reduced survival in some interstitial lung diseases. Nothing is known about HRCT scan patterns and survival in sarcoidosis.
Will a detailed description of the extent and pattern of HRCT scan fibrosis in patients with stage IV pulmonary sarcoidosis impact pulmonary function and survival?
Two hundred forty patients with stage IV sarcoidosis at two large tertiary institutions were studied. The earliest HRCT scan with fibrosis was reviewed for extent of fibrosis (< 10%, 10%-20%, and > 20%) and presence of bronchiectasis, upper lobe fibrocystic changes, basal subpleural honeycombing, ground-glass opacities (GGOs), large bullae, and mycetomas. Presence of sarcoidosis-associated pulmonary hypertension (SAPH) and pulmonary function testing performed within 1 year of HRCT were recorded. Patients were followed up until last clinic visit, death, or lung transplantation.
The mean age was 58.4 years. Seventy-four percent were Black, 63% were female, and mean follow-up was 7.4 years. Death or LT occurred in 53 patients (22%). Thirty-one percent had > 20% fibrosis, 25% had 10%-20% fibrosis, and 44% had < 10% fibrosis. The most common HRCT abnormalities were bronchiectasis (76%), upper lobe fibrocystic changes (36%), and GGOs (28%). Twelve percent had basal subpleural honeycombing, and 32% had SAPH. Patients with > 20% fibrosis had more severe pulmonary impairment, were more likely to have SAPH (53%), and had worse survival (44% mortality; P < .001). Upper lobe fibrocystic changes, basal subpleural honeycombing, and large bullae were associated with worse pulmonary function and worse survival. Patients with basal subpleural honeycombing had the worst pulmonary function and survival (55% mortality; P < .001). GGOs were associated with worse pulmonary function but not worse survival, and mycetomas were associated with worse survival but not worse pulmonary function. A Cox proportional hazards model indicated that basal subpleural honeycombing (hazard ratio, 7.95), diffusion capacity for carbon monoxide < 40% (HR, 5.67) and White race (hazard ratio, 2.61) were independent predictors of reduced survival.
HRCT scan features of fibrotic pulmonary sarcoidosis had an impact on pulmonary function and survival. Presence of >20% fibrosis and basal subpleural honeycombing are predictive of worse pulmonary function and worse survival in patients with stage IV pulmonary sarcoidosis.
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Sarcoidosis-Associated Pulmonary Hypertension
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Fibrotic Pulmonary Sarcoidosis
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View all citing articles on Scopus

: FUNDING/SUPPORT: The authors have reported to CHEST that no funding was received for this study.

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Chest

Original Research: Diffuse Lung DiseasePredictors of Mortality in Pulmonary Sarcoidosis

Objective

Methods

Results

Conclusions

Section snippets

Patients and Methods

Results

Discussion

Conclusions

Acknowledgments

Lancet

Chest

Chest

Chest

Lancet Respir Med

Int J Cardiol

Chest

Lancet Respir Med

Clin Chest Med

Chest

Chest

Chest

Sarcoidosis: epidemiology and prognosis. A 15-year European study

Am Rev Respir Dis

Prognostic factors predicting the outcome of sarcoidosis: an analysis of 818 patients

Q J Med

Predicting respiratory failure in sarcoidosis patients

Sarcoidosis

Sarcoidosis-related mortality in the United States from 1988 to 2007

Am J Respir Crit Care Med

Racial difference in sarcoidosis mortality in the United States

Chest

In-Hospital disease burden of sarcoidosis in Switzerland from 2002 to 2012

PLoS One

Hospitalization for patients with sarcoidosis: 1979-2000

Sarcoidosis Vasc Diffuse Lung Dis

Original Research: Diffuse Lung Disease
Predictors of Mortality in Pulmonary Sarcoidosis