A rare case of acute respiratory distress syndrome secondary to acute lithium intoxication.

Lithium carbonate is a widely administered antimanic drug used for the treatment of bipolar disorder, schizoaffective disorder, and depression. Despite the established clinical efficacy of lithium, its usage must be approached with caution due to its narrow therapeutic index. Lithium poisoning results in multisystem toxicity, and characteristic clinical manifestations are directly correlated to serum lithium concentration. We describe a rather rare but fatal side effect of lithium: acute respiratory distress syndrome (ARDS) in a 46-year-old female on lithium for the treatment of bipolar disease. She was referred for generalized weakness, found in hemodynamic compromise, and had laboratory data significant for a lithium level of 3.3 mmole/L, needing emergent hemodialysis. Subsequently, she developed hypoxic respiratory failure requiring intubation. Her chest x-rays showed new bilateral pulmonary edema, the computed tomography scan showed extensive alveolar consolidation and V/Q scan of low probability for pulmonary embolism. She underwent 3 dialysis sessions and supportive care and was able to be extubated in 5 days. To our knowledge, 4 cases of ARDS after the onset of lithium toxicity have been documented. All patients presented with altered mental status at serum lithium levels ranging from 3.8 to 4.9 mmole/L and cardiogenic etiologies in addition to other likely causes of ARDS were ruled out in each case. The patients were treated with saline hydration (50%) or hemodialysis (50%), indicating that hemodialysis may be a permissive factor in lithium-associated ARDS development rather than a required component. Taken together, we believe that lithium is a likely culprit in the initiation of ARDS and propose the addition of ARDS to the family of clinical manifestations of severe lithium toxicity.

Pathways activated during human asthma exacerbation as revealed by gene expression patterns in blood.

BACKGROUND: Asthma exacerbations remain a major unmet clinical need. The difficulty in obtaining airway tissue and bronchoalveolar lavage samples during exacerbations has greatly hampered study of naturally occurring exacerbations. This study was conducted to determine if mRNA profiling of peripheral blood mononuclear cells (PBMCs) could provide information on the systemic molecular pathways involved during asthma exacerbations. METHODOLOGY/PRINCIPAL FINDINGS: Over the course of one year, gene expression levels during stable asthma, exacerbation, and two weeks after an exacerbation were compared using oligonucleotide arrays. For each of 118 subjects who experienced at least one asthma exacerbation, the gene expression patterns in a sample of peripheral blood mononuclear cells collected during an exacerbation episode were compared to patterns observed in multiple samples from the same subject collected during quiescent asthma. Analysis of covariance identified genes whose levels of expression changed during exacerbations and returned to quiescent levels by two weeks. Heterogeneity among visits in expression profiles was examined using K-means clustering. Three distinct exacerbation-associated gene expression signatures were identified. One signature indicated that, even among patients without symptoms of respiratory infection, genes of innate immunity were activated. Antigen-independent T cell activation mediated by IL15 was also indicated by this signature. A second signature revealed strong evidence of lymphocyte activation through antigen receptors and subsequent downstream events of adaptive immunity. The number of genes identified in the third signature was too few to draw conclusions on the mechanisms driving those exacerbations. CONCLUSIONS/SIGNIFICANCE: This study has shown that analysis of PBMCs reveals systemic changes accompanying asthma exacerbation and has laid the foundation for future comparative studies using PBMCs.