Daily Ards Research Analysis

BACKGROUND: Well-established side effects of trimethoprim/sulfamethoxazole include cutaneous and liver toxicity, hypersensitivity syndrome and blood dyscrasias. Trimethoprim/sulfamethoxazole has also been associated with severe lung toxicity (LT) but reports are scarce. METHODS: We investigated pharmacovigilance data and reviewed spontaneous reports of trimethoprim/sulfamethoxazole-related LT recorded in the French national pharmacovigilance database (FPVD) and the WHO global database of adverse events (VigiBase®) up to 31 December 2023. We performed disproportionality analysis to detect a possible pharmacovigilance signal. RESULTS: A total of 755 patients with trimethoprim/sulfamethoxazole-related LT were reported in VigiBase®, 17 of which were from the FPVD. In VigiBase®, interstitial lung disease was the most frequent LT pattern (30.5%). A fatal outcome was reported in 197 patients (26.1%). Significant reporting ORs were observed for the following trimethoprim/sulfamethoxazole-related LT patterns: interstitial lung disease 1.5 (95% CI: 1.3-1.7); acute respiratory distress syndrome 2.9 (95% CI: 2.5-3.5); eosinophilic pneumonia 4.1 (95% CI: 3.2-5.2); diffuse alveolar damage 3.7 (95% CI: 2.6-5.3); organizing pneumonia 2.1 (95% CI: 1.4-3.1); pulmonary toxicity 1.9 (95% CI: 1.3-2.9); acute lung injury 7.5 (95% CI: 4.9-11.6) and hypersensitivity pneumonitis 2.7 (95% CI: 1.7-4.2). CONCLUSIONS: We highlight statistically significant disproportionality for several trimethoprim/sulfamethoxazole-related LT patterns, which constitutes a pharmacovigilance signal. Trimethoprim/sulfamethoxazole-related LT is rare, but may be critical and even life-threatening. Physicians should be aware of potential trimethoprim/sulfamethoxazole-related LT and should inform their patients, since early intervention could prevent severe outcome.

OBJECTIVES: Pulmonary involvement is common in systemic lupus erythematosus (SLE), but the relative risk of pulmonary manifestations in SLE versus non-SLE subjects remains unclear. This study aimed to evaluate the risk of pulmonary manifestations in SLE subjects compared with matched controls. METHODS: Using data from the Korean National Health Insurance Service (2009-2017), we identified 6074 individuals aged ≥20 years with newly diagnosed SLE and 60 740 matched controls by age and sex (1:10 ratio) who did not have prior pulmonary manifestations. RESULTS: Over a mean follow-up of 9.3±2.7 years, the incidence of pulmonary manifestations was 15.2 per 1000 person-years in the SLE cohort and 4.5 per 1000 person-years in the matched cohort. The SLE cohort had a significantly higher risk of pulmonary manifestations (adjusted HR (aHR) 3.26; 95% CI 2.99 to 3.56). The highest risk was observed for pulmonary hypertension (aHR 14.66; 95% CI 9.43 to 22.80), followed by interstitial lung disease (aHR 9.58; 95% CI 7.99 to 11.49), pleural disorders (aHR 3.29; 95% CI 2.84 to 3.81), pulmonary embolism (aHR 2.66; 95% CI 2.06 to 3.43), tuberculosis (aHR 2.35; 95% CI 1.88 to 2.93), acute respiratory distress syndrome and haemorrhage (aHR 1.85; 95% CI 1.51 to 2.25) and lung cancer (aHR 1.41; 95% CI 1.02 to 1.95). CONCLUSIONS: Subjects with SLE have an approximately 3.3-fold higher risk of pulmonary manifestations compared with matched controls. Notably, the risks of pulmonary hypertension and interstitial lung disease are particularly elevated.

PURPOSE: Patients with coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS) who lack clinical improvement are frequently treated with high-dose corticosteroids (HDS). Since HDS is used to reduce hyperinflammation in these patients, levels of (pro-)inflammatory biomarkers after commencing HDS treatment could be useful in predicting mortality. This study aims to evaluate biomarker levels after commencing HDS over time, along with their capacity to predict mortality. PATIENTS AND METHODS: This retrospective cohort study included patients with COVID-19 ARDS treated with HDS in the intensive care unit (ICU) at an academic hospital in the Netherlands between March 2020-March 2022. Inflammatory biomarkers (ie, C-reactive protein (CRP), D-dimer, ferritin, leukocyte count, interleukin-6 (IL-6), lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR), and procalcitonin (PCT)) were assessed daily from start of HDS (ie baseline) until day 7. Associations between biomarker levels and all-cause-hospital-mortality were evaluated each day using logistic regression, with cut-offs identified by optimizing sensitivity (Se) and specificity (Sp). RESULTS: Of the 122 patients included, 53 (43.4%) died during hospitalization. HDS was initiated for a median 7 days (IQR=1-11) after ICU admission. At baseline, a moderately high predictive capacity for mortality was observed at a ferritin level >1281 µg/L (Se=62%/Sp=64%), leukocyte count >13.7 × 109/L (Se=42%/Sp=79%), and NLR >12.1 (Se=61%/Sp=77%). During follow-up, CRP >50 mg/L on day 6 (Se=50%/Sp=75%) and >42 mg/L on day 7 (Se=50%/Sp=75%), ferritin >1082 µg/L on day 6 (Se 63%/Sp=71%) and >1852 µg/L on day 7 (Se=31%/Sp=79%), IL-6 >67 mg/L on day 7 (Se=56%/Sp=79%) and LDH >396U/L on day 6 (Se=38%/Sp=83%) and >373 U/L on day 7 (Se=47%/Sp=72%) showed moderate capacity to predict mortality. NLR was consistently associated with mortality for all days, except day 1 (Se=36-68%/Sp=72-92%). CONCLUSION: In COVID-19 ARDS patients receiving HDS, several clinically available inflammatory biomarkers moderately predicted all-cause-hospital-mortality after the start of HDS, particularly on days 6 and 7. NLR demonstrated the most consistent association with mortality over time. The use of these markers requires validation in larger cohorts.