Clara cell 10-kDa protein (CC10), the predominant product from nonciliated cells in the epithelial lining of bronchioles (Clara cells), has been shown to have immunomodulatory and antiinflammatory activity and may play a role in controlling airway inflammation. This study was designed to measure serum CC10 concentrations in healthy and asthmatic nonsmokers. Serum CC10 concentrations in asthmatic nonsmokers were significantly lower than in healthy nonsmokers. Asthmatic patients with a long duration of the disease (>/=10 years) had significantly lower serum CC10 levels than those with a short duration of the disease (<10 years). There was no significant difference in serum CC10 levels in asthmatic patients between the time of the asthmatic attack and the stable condition. Serum CC10 levels may reflect decreased production of CC10 caused by remodeling of the small airways in asthma.

Objectives: Patients with concomitant advanced non-small cell lung cancer (NSCLC) and interstitial lung disease (ILD) are excluded from most clinical chemotherapy trials because of the high risk of exacerbating the latter condition. This study prospectively investigated the efficacy and safety of albumin-bound paclitaxel (nab-paclitaxel) in combination with carboplatin in patients with both advanced NSCLC and ILD. Patients and methods: The enrolled patients had treatment-naïve, advanced NSCLC with ILD. Patients received 100 mg/m 2 nab-paclitaxel weekly and carboplatin at an area under the concentration-time curve of 6 once every 3 weeks for 4-6 cycles. The primary endpoint was the overall response rate (ORR); secondary endpoints included toxicity, progression-free survival (PFS), and overall survival (OS). Results: Thirty-six patients were enrolled between April 2014 and September 2017. Sixteen patients (44.4%) had adenocarcinoma, 15 (41.7%) had squamous cell carcinoma (Sq), and 5 (13.9%) had nonsmall cell carcinoma. The median number of cycles administered were 4 (range: 1-6). The ORR was 55.6% (95% confidence interval [CI]: 39.6-70.5). The median PFS and OS were 5.3 months (95% CI: 3.9-8.2) and 15.4 months (95% CI: 9.4-18.7), respectively. A greater proportion of patients with Sq experienced improvements than did those with non-Sq: ORRs, 66.7% (95%

Background Immune checkpoint inhibitors (ICIs) have provided more options in the treatment of lung cancer. However, ICIs can cause several unfavorable reactions generally referred to as immune-related adverse effects. Case presentation In this report, we present the case of a 52-year-old woman with successful regression of pleomorphic carcinoma of the lung following nivolumab therapy. She developed purpura fulminans (PF) ultimately resulting in amputation of both lower extremities. Blood tests revealed thrombocytopenia with increased serum soluble IL-2 receptor, ferritin, and triglyceride levels suggesting hemophagocytic lymphohistiocytosis (HLH). In addition, serum A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 activity was decreased, suggesting thrombotic thrombocytopenic purpura (TTP). Further detailed analysis revealed severe hypercytokinemia including increased levels of IL-1β, IL-6, IL-10, TNFα, IFNγ, and G-CSF. Conclusion The severe systemic inflammatory reaction and impaired peripheral circulation in this patient was attributed to excessive immunological effect induced by nivolumab resulting in cytokine release syndrome (CRS). This is the first report of a patient with multiple pathological conditions including HLH, TTP-like condition, and PF presumably arising from ICI-induced CRS. Further accumulating thoroughly investigated cases would lead to better understanding of the disease and development of reliable cancer immunotherapy.

CT densitometry showed a distinct lobar distribution of emphysema. Pulmonary function is significantly different between predominantly upper- and lower-lobe emphysema groups.

The aim of this study was to determine the relationship between the radiological pattern of Mycoplasma pneumoniae and the level of cell-mediated immunity of the host.Computed tomographic (CT) scans of the chest and the results of the purified protein derivative (PPD) test were studied during the acute stage of infection in 54 patients with M. pneumoniae pneumonia. The CT findings were used to divide the patients into two groups: one group had a predominance of nodular opacities with a centrilobular distribution (Group N; n=29); and the other showed a predominance of an airspace consolidation (Group C; n=25).Forty out of 54 subjects had negative tuberculin skin tests (<10 mm induration). The positive rate of PPD reaction was higher in Group N (13 out of 29) compared to Group C (1 out of 25) (p=0.0005); whilst pleural effusion appeared more frequently in Group C (10 out of 25) than in Group N (3 out of 29) (p=0.023). There was no significant difference between Groups N and C in white blood cell and lymphocyte counts, level of antibodies to M. pneumoniae in sera, and severity of the disease.These findings suggest that the characteristics of the host cell-mediated immunity might influence the pattern of pulmonary lesions in M. pneumoniae infection. Eur Respir J., 1996, 9, 669-672. The cell-mediated immunity (CMI) of the host plays an important role in the development of Mycoplasma pneumoniae pneumonia (MP) [1,2]. MIZUTANI et al. [3] reported that the delayed hypersensitivity skin reactions to M. pneumoniae antigen appeared to correlate with severity of pneumonia in human MP. FOY et al. [4] reported that MP infection in patients with immunodeficiency syndrome had a lack of radiological chest findings. PUTMAN et al. [5] reported a bilateral reticulonodular pattern when MP was associated with sarcoidosis. These manifestations suggest that pulmonary infiltrates of MP might be a result of the immunological reaction of the host.The purified protein derivative (PPD) reaction is used to confirm past infection by Mycobacterium tuberculosis, and to determine the CMI of the host. In Japan, most individuals have CMI to PPD due to the nearly universal bacille Calmette-Guérin (BCG) vaccination in childhood. Transient tuberculin anergy has been observed (57-61%) [6,7] during the early stage of MP. TSUNEKAWA et al. [7] reported that blastogenic lymphocyte response to PPD and PPD-induced gamma-interferon (IFN-γ) production were significantly reduced in tuberculin-negative patients with MP. However, the relationship between the pattern of pulmonary lesions and host CMI level in MP has not been evaluated.The findings of chest radiography of MP are varied; CLYDE [8] noted four frequent patterns suggesting MP: bronchopneumonia; nodular infiltration; plate-like atelectasis; and hilar adenopathy. Bronchopneumonia of MP is accompanied by thickening of bronchi, streaks of interstitial infiltration, and small areas of subsegmental atelectasis. The changes are produced by the presence of peribronchial inflammatory cell infiltrati...

Notch signaling in tumorigenesis functions as an oncogene or tumor suppressor according to the type of malignancy. Numb represses intracellular Notch signaling. Previous studies have demonstrated that Notch signaling suppresses the proliferation of small cell lung cancer (SCLC) cell lines. However, in SCLC, the association between Notch1 and Numb expression and clinicopathological factors or prognosis has remained unclear. In this study, we evaluated the expression of Notch1 and Numb in SCLC. We immunohistochemically assessed 125 SCLCs that were surgically resected at 16 institutions participating in either the Hokkaido Lung Cancer Clinical Study Group Trial (HOT) or the Fukushima Investigative Group for Healing Thoracic Malignancy (FIGHT) between 2003 and 2013. Correlations between Notch1 or Numb expression and various clinicopathological features were evaluated. Notch1 expression was associated with ECOG performance status. Numb expression was associated with age, sex, and pathological histology (SCLC or Combined SCLC). Analysis of cellular biological expression did not demonstrate a significant correlation between the expression of Notch1 and of Numb. Multivariate Cox regression analysis showed that high Notch1 expression was an independent favorable prognostic factor for SCLC(hazard ratio = 0.503, P = 0.023). High Notch1 expression, but not Numb expression, is associated with favorable prognosis in SCLC.

No abstract

The limited number of available treatments for patients with small-cell lung cancer (SCLC) has prompted us to further investigate the biology of SCLC by molecular profiling. We collected formalin-fixed paraffin-embedded tumor samples from 127 patients with SCLC, who had undergone surgery at 16 institutions between January 2003 and January 2013, and analyzed the association between disease-specific survival and protein expression of c-kit, c-Met, epidermal growth factor receptor, human EGFR-related 2, vascular endothelial growth factor receptor II, anaplastic lymphoma kinase, mediator complex subunit 12 (MED12), and transforming growth factor beta receptor II (TGF-βRII) by immunohistochemistry (IHC). Of the 125 evaluable samples, all tumors expressed MED12, and 123 samples (98.4%) expressed TGF-βRII. MED12 was highly expressed in the nucleus in 92% of the positive samples while TGF-βRII was highly expressed in the cytoplasm in 55% of the positive samples. High c-kit expression was an independent favorable prognostic marker confirmed by multivariate analysis (hazard ratio: 0.543, 95% confidence interval: 0.310–0.953, p = 0.033). Both the relapse free-survival and overall survival of patients who underwent adjuvant chemotherapy were statistically longer in those with high c-kit expression (n = 38) than those with intermediate, low, or no c-kit expression (n = 19) (not reached vs 11.6 months, p = 0.021; not reached vs 25.9 months, p = 0.028). IHC for c-kit may offer a prognostic marker for early-stage SCLC, and the results for MED12 and TGF-βRII may suggest the biological characteristics of SCLC. Further investigation of the roles of their related molecules in early stage SCLC is required.