Low Body Mass Index and Smoking Are Associated With a Lower Risk of Sarcoidosis: A Population-Based Nested Case-Control Study

Background/Purpose: Sarcoidosis is a systemic disorder characterized by the presence of non-caseating granuloma. The etiology of sarcoidosis is unknown. It has been hypothesized that the interaction between genetic predisposition and environmental factors plays an essential role in the pathogenesis. Recent studies have found an association between body mass index, smoking and risk of sarcoidosis although the results were conflicting. Moreover, most of studies were referral-based studies that could be at risk of selection bias.

Methods: 345 patients (50% female; 90% Caucasian, 5% African-American; mean age 45.6 years) with incident sarcoidosis in 1976-2013 in a geographically well-defined population were identified based on comprehensive individual medical record review. Inclusion required physician diagnosis supported by histopathology and radiologic features of intrathoracic sarcoidosis, compatible clinical presentation, and exclusion of other granulomatous diseases. 345 sex and age-matched controls (50% female; 95% Caucasian, 1% African-American; mean age 45.4 years) were also identified from the same underlying population. Index date for controls was the same as diagnosis date of corresponding cases. Data on body weight, height and smoking status (never, prior and current smoker) were abstracted from clinical notes and health information questionnaires completed by patients. Overweight was defined as body mass index (BMI) ≥ 25 kg/m² but < 30 kg/m². Obesity was defined as BMI ≥ 30 kg/m². BMI within 1 year before to 3 months after index date was used in this study. Odds ratios (ORs) with 95% confidence intervals (CIs) for the association between smoking status, overweight and obesity and sarcoidosis with adjustment for age, sex and African-American race were calculated.

Results: Information on smoking status was available in 94% of subjects.  Among cases, 60% were never smokers, 21% were former smokers and 19% were current smokers. Among controls, 42% were never smokers, 22% were former smokers and 36% were current smokers. Current smokers had a lower risk of sarcoidosis with adjusted OR of 0.34 (95% CI, 0.23 – 0.51) compared with participants who never smoked and adjusted OR of 0.39 (95% CI, 0.27 – 0.56) compared with participants who never smoked and former smokers.             BMI within the defined period was available in 74% of subjects. Among cases, 41% were obese, 33% were overweight and 26% had normal/low BMI. Among controls, 24% were obese, 41% were overweight and 35% had normal/low BMI.  Subjects with obesity had a higher risk of sarcoidosis compared with those with normal/low BMI with adjusted OR of 2.47 (95% CI, 1.54 – 3.96).  However, overweight was not significantly associated with a higher risk of sarcoidosis compared with subjects with normal/low BMI (adjusted OR 1.12; 95% CI 0.71 – 1.75).  

Conclusion: Obesity was associated with a higher risk of sarcoidosis while smoking was associated with a lower risk in this cohort. The potential causal relationship of these exposures to the risk of developing sarcoidosis requires further investigation.