Background/Purpose: Our goal was to examine lung disease and types of pulmonary manifestations observed in patients with SLE. We studied population-based register data from Sweden to determine the incidence of pulmonary diagnoses among incident and prevalent SLE patients compared to the general population.

Methods: Using data from a linkage of Swedish registers we identified patients with SLE (at least 2 SLE coded discharge diagnoses and at least 1 SLE-specific discharge diagnosis by a specialist who manages SLE) and matched them to individuals from the general population on age, sex, and county of residence when the SLE index case first presented with SLE. Pulmonary diagnoses were identified using ICD codes from the National Patient Register’s (NPR) discharge diagnoses for inpatient and outpatient visit data. Those with a history of pulmonary disease were excluded. Individuals were followed until they had their first pulmonary diagnosis, died, emigrated, or reached the study end. We calculated incidence rates and corresponding 95% confidence intervals (95% CI) overall and by type of pulmonary disease, for incident (2003-2013) and prevalent SLE (2001-2013). To be classified as incident SLE, an individual’s first SLE diagnosis code had to occur in 2003 or later. Cox proportional hazards models estimated hazard ratios (HR) and 95% CIs for the association between SLE and pulmonary disease in age and sex adjusted models. Sensitivity analyses assessed the robustness of results using semi-automated approach to quantitative probabilistic bias analysis to account for potential bias due to unmeasured confounding by smoking.

Results: 3,209 incident SLE cases were identified using NPR data in Sweden contributing a median 4.8 person-years of follow-up time (vs. 5.1 among non-SLE comparators). We also identified a contemporary cohort of 6,908 individuals with prevalent SLE. The incidence rate for new onset pulmonary disease (about 14 cases per 1000 person-years) was similar in prevalent and incident SLE. Those with incident SLE had a nearly six-times higher rate of new onset pulmonary disease compared to the non-SLE comparator (HR=5.80 (4.84,6.95)) and were comparable in male and female patients. Incident and prevalent SLE was associated with an increased rate of interstitial lung disease (ILD), (HR=19.0 (10.7, 34.0) and 14.3 (10.8-18.8), respectively). Bias due to unmeasured confounding by smoking was unlikely to explain our findings in sensitivity analyses.

Conclusion: Lung disease is common among SLE patients, and particularly increased when compared to the general population. Clinicians caring for SLE patients should have a heightened suspicion for lung disease, including ILD, even early within the disease course.

Table. Relative risk of pulmonary disease among SLE compared to non-SLE general population comparators overall and by type of pulmonary disease, presented as age- and sex-adjusted hazard ratios and 95% confidence intervals.