Incidence, etiology, and outcome of hospital-acquired pneumonia in patients with acute exacerbation of fibrotic idiopathic interstitial pneumonia.

BACKGROUND: Acute exacerbations (AEs) of fibrotic idiopathic interstitial pneumonia (fIIP) that require hospitalization occur in some patients. During hospitalization, these patients can develop hospital-acquired pneumonia (HAP), a common hospital-acquired infection with a high mortality rate. However, the characteristics of HAP in AE-fIIP remain unknown. The purpose of this study was to determine the incidence, causative pathogens, and outcomes of HAP in patients with AE-fIIP. METHODS: The medical records of consecutive patients who were hospitalized with AE-fIIP from January 2008 to December 2019 were analyzed for the incidence, causative pathogen, and survival of HAP. The records of patients with an obvious infection-triggered AE were excluded from analysis. RESULTS: There were 128 patients with AE-fIIP (89 with idiopathic pulmonary fibrosis [IPF] and 39 with non-IPF fIIP) who were hospitalized a total of 155 times (111 with IPF and 44 with non-IPF fIIP). HAP occurred in 49 patients (40 with IPF and 9 with non-IPF fIIP). The incidence and the in-hospital mortality rates of HAP in patients with AE-fIIP were high, at 32.2% and 48.9%, respectively. Corynebacterium spp. was the most common causative pathogen, which was followed by human cytomegalovirus (HCMV). CONCLUSIONS: The incidence and the in-hospital mortality rates of HAP in patients with AE-fIIP are high. To improve their survival, patients with fIIP who had AEs and HAP should receive prompt empirical treatment for possible infections with Corynebacterium spp. and testing for HCMV.

Clinical implications of bronchoscopy for immune checkpoint inhibitor-related pneumonitis in patients with non-small cell lung cancer.

BACKGROUND: The utility of bronchoscopy for patients with suspected immune checkpoint inhibitor (ICI)-related pneumonitis is currently debatable. The purpose of this study was to examine the findings of bronchoalveolar lavage (BAL) analysis and transbronchial lung biopsy (TBLB) in non-small cell lung cancer (NSCLC) patients with ICI-related pneumonitis, and to elucidate the clinical significance of bronchoscopy for this health condition. PATIENTS AND METHODS: Consecutive NSCLC patients treated with ICIs, diagnosed with ICI-related pneumonitis after undergoing bronchoscopy between October 2015 and March 2019 were retrospectively screened. Findings of BAL fluid analysis and/or TBLB specimen histology were reviewed. RESULTS: Twelve patients underwent bronchoscopy for the diagnosis of ICI-related pneumonitis, ten of whom underwent BAL. An increase in the proportion of lymphocytes higher than 20% was observed in all ten patients. An increase in the proportion of neutrophils (> 10%) and eosinophils (> 10%) was observed in two and one patient, respectively. TBLB specimens were analyzed for eight patients. Major histologic findings included alveolitis in seven (87.5%) and organizing pneumonia (OP) in five (62.5%) patients. Other findings included acute lung injury and fibrosis. All twelve patients demonstrated favorable outcomes. CONCLUSION: A major characteristic of BAL analysis in ICI-related pneumonitis with NSCLC was an increased proportion of lymphocytes. The histologic features of lung tissue included alveolitis and/or OP. Acute lung injury and fibrosis were observed. Although the necessity of bronchoscopy should be determined on a case-by-case basis, it is necessary to assess these parameters when proper differential diagnosis is needed.

Dinitropyrenes induce gene mutations in multiple organs of the lambda/lacZ transgenic mouse (Muta Mouse).

Dinitropyrenes (DNPs), 1,3-, 1,6- and 1,8-dinitropyrene, are carcinogenic compounds found in diesel engine exhaust. DNPs are strongly mutagenic in the bacterial mutation assay (Ames test), mainly inducing frameshift type mutations. To assess mutagenicity of DNPs in vivo is important in evaluating their possible involvement in diesel exhaust-induced carcinogenesis in human. For this purpose, we used the lambda/lacZ transgenic mouse (Muta Mouse) to examine induction of mutations in multiple organs. A commercially available mixture of DNPs (1,3-, 1,6-, 1,8-, and unidentified isomer (s) with a content of 20.2, 30.4, 35.2, and 14.2%, respectively) was injected intragastrically at 200 and 400mg/kg once each week for 4 weeks. Seven days after the final treatment, liver, lung, colon, stomach, and bone marrow were collected for mutation analysis. The target transgene was recovered by the lambda packaging method and mutation of lacZ gene was analyzed by a positive selection with galE(-) E. coli. In order to determine the sequence alterations by DNPs, the mutagenicity of the lambda cII gene was also examined by the positive selection with hfl(-) E. coli. Since cII gene (294bp) is much smaller than the lacZ (3024bp), it facilitated the sequence analysis. Strongest increases in mutant frequencies (MFs) were observed in colon for both lacZ (7.5x10(-5) to 43.3x10(-5)) and cII (2.7x10(-5) to 22.5x10(-5)) gene. Three-four-fold increases were observed in stomach for both genes. A statistically significant increase in MFs was also evident in liver and lung for the lacZ gene, and in lung and bone marrow for the cII gene. The sequence alterations of the cII gene recovered from 37 mutants in the colon were compared with 50 mutants from untreated mice. Base substitution mutations predominated for both untreated (91%) and DNP-treated (84%) groups. The DNPs treatment increased the incidence of G:C to T:A transversion (2-43%) and decreased G:C to A:T transitions (70-22%). The G:C to T:A transversions, characteristic to DNPs treatment, is probably caused by the guanine-C8 adduct, which is known as a major DNA-adduct induced by DNPs, through an incorporation of adenine opposite the adduct ("A"-rule). The present study showed a relevant use of the cII gene as an additional target for mutagenesis in the Muta Mouse and revealed a mutagenic specificity of DNPs in vivo.