Prognostic impact of pre-existing interstitial lung disease in non-HIV patients with Pneumocystis pneumonia.

BACKGROUND: The increasing incidence of life-threatening Pneumocystis pneumonia (PCP) in non-HIV immunocompromised patients is a global concern. Yet, no reports have examined the prognostic significance of pre-existing interstitial lung disease (ILD) in non-HIV PCP. METHODS: We retrospectively reviewed the medical records of non-HIV PCP patients with (ILD group) or without (non-ILD group) pre-existing ILD. The clinical features and outcomes of the ILD group were compared with those of the non-ILD group. Cox regression models were constructed to identify prognostic factors. RESULTS: 74 patients were enrolled in this study. The 90-day mortality was significantly higher in the ILD group than in the non-ILD group (62.5% versus 19.0%, p<0.001). In the ILD group, patients with a higher percentage of bronchoalveolar lavage fluid neutrophils had worse outcomes compared to those having a lower percentage (p=0.026). Multivariate analyses revealed that pre-existing ILD (p=0.002) and low levels of serum albumin (p=0.009) were independent risk factors for 90-day mortality. Serum levels of ß-d-glucan were significantly reduced after treatment of PCP in both groups, whereas levels of Krebs von den Lungen-6 (KL-6) significantly increased in the ILD group. In the ILD group, the 90-day mortality of patients with increasing KL-6 levels after treatment was significantly higher than those with decreasing levels (78.9% versus 0%, p=0.019). CONCLUSION: In non-HIV PCP patients, pre-existing ILD is associated with a poorer prognosis. Prophylaxis for PCP is needed in patients with pre-existing ILD under immunosuppression.

Asymmetric total synthesis of (+)-phoslactomycin B.

(+)-Phoslactomycin B was synthesized by a highly enantio- and stereoselective approach involving asymmetric pentenylation, Suzuki-Miyaura coupling, ring-closing metathesis, asymmetric dihydroxylation, and Stille coupling. The synthetic method developed enables us to synthesize three other isomers concerning the C11-OH and Delta12-double bond.

Role of lipid-derived free radical in bleomycin-induced lung injury in mice: availability for ESR spin trap method with organic phase extraction.

Bleomycin is well known as causative molecule for acute lung injury and interstitial pneumonia. The free radical production from bleomycin is thought to play an important role in the pathogenesis of acute lung injury and interstitial pneumonia. However, there was no direct evidence of free radical production in this model. Therefore, we examined in vivo radical production by mice treated with a bleomycin using electron spin resonance with the spin trap, alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone. Six hours after instillation of bleomycin, the lung exposed to bleomycin gave a lipid-derived free radical adduct, which would support evidence for in vitro lipid peroxidation resulting from bleomycin administration. In the treatment of deferoxamine, chelating agent for iron and other metals, to reduce the bleomycin induced free radical production, parallel to decrease the lipid-derived free radical production by deferoxamine, pathophysiological findings of lung injuries were improved by deferoxamine. In conclusion, this is a first paper of in vivo direct evidence of production of free radical from bleomycin-induced lung injury. It is suggested that this method may be used in many kinds of lung disease models, which have potentials of free radical production to cause lung damage.