Thoracoscopic lung biopsy under regional anesthesia for interstitial lung disease.

BACKGROUND: Interstitial lung disease (ILD) management guidelines support lung biopsy-guided therapy. However, the high mortality associated with thoracoscopic lung biopsy using general anesthesia (GA) in patients with ILD has deterred physicians from offering this procedure and adopt a diagnostic approach based on high-resolution CT. Here we report that thoracoscopy under regional anesthesia could be a safer alternative for lung biopsy and effectively guide ILD treatment. METHODS: This was a single-center retrospective review of prospectively maintained database and consisted of patients who underwent thoracoscopic lung biopsy between March 2016 and March 2018. Patients were divided into two groups: (A) GA, and (B) regional anesthesia using monitored anesthesia care (MAC) and thoracic epidural anesthesia (TEA). RESULTS: During the study period, 44 patients underwent thoracoscopic lung biopsy. Of these, 15 underwent MAC/TEA. There were no significant differences between the two groups with regard to pulmonary function test and clinicodemographic profile. However, operative time and hospital stay were shorter in MAC/TEA group (32.5±18.5 min vs 50.8±18.4; p=0.004, 1.0±1.3 days vs 10.0±34.7 days; p<0.001, respectively). Eight patients in the GA group, but none in the MAC/TEA group, experienced worsening of ILD after lung biopsy (p=0.03). Additionally, one patient in the GA group died due to acute ILD worsening. No cases of MAC/TEA group had to be converted to GA. In all cases a pathological diagnosis could be made. CONCLUSIONS: Thoracoscopy using regional anesthesia might be a safer alternative to lung biopsy in patients with ILD.

The effect of rosuvastatin in a murine model of influenza A infection.

RATIONALE: HMG-CoA reductase inhibitors such as rosuvastatin may have immunomodulatory and anti-inflammatory effects that may reduce the severity of influenza A infection. We hypothesized that rosuvastatin would decrease viral replication, attenuate lung injury, and improve mortality following influenza A infection in mice. METHODS: C57Bl/6 mice were treated daily with rosuvastatin (10 mg/kg/day) supplemented in chow (or control chow) beginning three days prior to infection with either A//Udorn/72 [H3N2] or A/WSN/33 [H1N1] influenza A virus (1×10(5) pfu/mouse). Plaque assays were used to examine the effect of rosuvastatin on viral replication in vitro and in the lungs of infected mice. We measured cell count with differential, protein and cytokines in the bronchoalveolar lavage (BAL) fluid, histologic evidence of lung injury, and wet-to-dry ratio on Day 1, 2, 4, and 6. We also recorded daily weights and mortality. RESULTS: The administration of rosuvastatin had no effect on viral clearance of influenza A after infection. Weight loss, lung inflammation and lung injury severity were similar in the rosuvastatin and control treated mice. In the mice infected with influenza A (A/WSN/33), mortality was unaffected by treatment with rosuvastatin. CONCLUSIONS: Statins did not alter the replication of influenza A in vitro or enhance its clearance from the lung in vivo. Statins neither attenuated the severity of influenza A-induced lung injury nor had an effect on influenza A-related mortality. Our data suggest that the association between HMG CoA reductase inhibitors and improved outcomes in patients with sepsis and pneumonia are not attributable to their effects on influenza A infection.

Proteasomal inhibition after injury prevents fibrosis by modulating TGF-ß(1) signalling.

BACKGROUND: The development of organ fibrosis after injury requires activation of transforming growth factor ß(1) which regulates the transcription of profibrotic genes. The systemic administration of a proteasomal inhibitor has been reported to prevent the development of fibrosis in the liver, kidney and bone marrow. It is hypothesised that proteasomal inhibition would prevent lung and skin fibrosis after injury by inhibiting TGF-ß(1)-mediated transcription. METHODS: Bortezomib, a small molecule proteasome inhibitor in widespread clinical use, was administered to mice beginning 7 days after the intratracheal or intradermal administration of bleomycin and lung and skin fibrosis was measured after 21 or 40 days, respectively. To examine the mechanism of this protection, bortezomib was administered to primary normal lung fibroblasts and primary lung and skin fibroblasts obtained from patients with idiopathic pulmonary fibrosis and scleroderma, respectively. RESULTS: Bortezomib promoted normal repair and prevented lung and skin fibrosis when administered beginning 7 days after the initiation of bleomycin. In primary human lung fibroblasts from normal individuals and patients with idiopathic pulmonary fibrosis and in skin fibroblasts from a patient with scleroderma, bortezomib inhibited TGF-ß(1)-mediated target gene expression by inhibiting transcription induced by activated Smads. An increase in the abundance and activity of the nuclear hormone receptor PPARγ, a repressor of Smad-mediated transcription, contributed to this response. CONCLUSIONS: Proteasomal inhibition prevents lung and skin fibrosis after injury in part by increasing the abundance and activity of PPARγ. Proteasomal inhibition may offer a novel therapeutic alternative in patients with dysregulated tissue repair and fibrosis.