Even in the German cohort, the serum KL6 levels were significantly higher in patients with ILDs than HS. Because of differences in the genotype distribution of rs4072037, the KL-6 cutoff value for the German cohort that discriminated patients with ILDs from HS was significantly higher than the value in the Japanese cohort.

BackgroundA high incidence of interstitial lung disease (ILD) has been reported in patients with advanced non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), particularly in Japanese populations. A previous report from our laboratory demonstrated that KL-6 was a useful serum biomarker to assess the severity of drug-induced pneumonitis. Based on these observations, this study was conducted to evaluate the risk factors of EGFR-TKIs induced ILD and the usefulness of monitoring serum KL-6 levels in patients who developed EGFR-TKIs induced ILD in a large multi-institutional setting.MethodsWe retrospectively reviewed clinical records and radiographies of 341 patients with advanced NSCLCs who were treated with EGFR-TKIs, and analyzed risk factors for the development of EGFR-TKIs induced ILD. Changes of circulating levels of KL-6 were also evaluated in the patients who developed EGFR-TKIs induced ILD.ResultsAmong the 341 patients included in this study, 20 (5.9%) developed EGFR-TKIs induced ILD, and 9 (2.6%) died from ILD. Univariate analyses revealed that only preexisting pulmonary fibrosis was a significant risk factor for the development of EGFR-TKIs induced ILD (p = 0.003). Absolute levels of circulating KL-6 at neither baseline nor the onset of ILD could discriminate between life-threatening and non-life threatening EGFR-TKIs induced ILDs. However, we found that the ratios of serum KL-6 levels just after the onset of EGFR-TKIs induced ILD to those at baseline could quite precisely distinguish survivors from non-survivors (p = 0.006) as well as acute interstitial pneumonia (AIP) pattern from non-AIP pattern (p = 0.005).ConclusionsThe results of this study strongly support the potential of KL-6 as a diagnostic biomarker for life-threatening EGFR-TKIs induced ILD. Monitoring of KL-6 is also useful to evaluate the progression and severity of EGFR-TKIs induced ILD.

BackgroundSerum KL-6 is a useful biomarker for the diagnosis of interstitial lung diseases (ILD). However, KL-6 has not been used to discriminate different types of ILD. Serum KL-6 concentrations can vary depending on antigen exposure levels in patients with hypersensitivity pneumonitis (HP); however, seasonal changes in serum KL-6 concentrations in ILD have not been determined. We hypothesized that seasonal variation of serum KL-6 is greater in HP than for the other ILD. The aim of this study was to determine seasonal variation of serum KL-6 concentrations in various ILD.MethodsSerum KL-6 concentrations in the summer season from June 1 to September 30 and the winter season from November 1 to February 28 were retrospectively analyzed in patients with idiopathic pulmonary fibrosis (IPF, n = 16), non-specific interstitial pneumonia (NSIP, n = 16), collagen vascular disease-associated interstitial pneumonia (CVD-IP, n = 33), house-related HP (House-HP, n = 9), bird-related HP (Bird-HP, n = 9), and combined pulmonary fibrosis and emphysema (CPFE, n = 13).ResultsBird-HP and House-HP showed greater seasonal serum KL-6 variation than the other ILD. Serum KL-6 concentrations in Bird-HP were significantly increased in the winter and KL-6 concentrations in House-HP were significantly increased in the summer. Serum KL-6 variation was significantly greater in acute HP than chronic HP. Receiver operating characteristic curve analysis revealed that greater seasonal variation in serum KL-6 concentrations is diagnostic for Bird-HP.ConclusionHP should be considered in ILD with greater seasonal changes in serum KL-6 concentrations.

Summary It has been reported that coenzyme Q 10 (CoQ 10 ) functions as an electron transfer carrier in mitochondria, and can produce an improvement in heart diseases such as congestive heart failure. Its (2 Z )-isomer contains a cis -double bond at the 2-position of the decaprenyl side chain. As the original organic industrial synthesis of CoQ 10 resulted in a product that contained a small amount of this isomer, the efficacy and safety of CoQ 10 was determined using CoQ 10 containing this isomer; however, no toxicity data have been reported for the (2 Z )-isomer itself. Thus, we conducted single (2,000 mg/kg) and 4-wk repeated (1,000 mg/kg) oral dose toxicity studies in rats to compare the toxicological profiles of CoQ 10 and its (2 Z )-isomer. The two compounds displayed similar toxicological profiles, and it was concluded that neither CoQ 10 nor its (2 Z )-isomer produce toxic effects in rats in single or repeated doses.

Abstract:We herein report a case of pulmonary hyalinizing granuloma (PHG), which is a rare pulmonary mass. A 69-year-old man with no symptoms presented to our hospital because of the appearance of an abnormal shadow on chest X-ray. Computed tomography revealed a right middle-lobe mass with spicula and infiltration into the upper lobe. Since a bronchofiberscopic examination showed no malignant cells in the specimen, the patient underwent thoracoscopic surgery, which revealed PHG. Spiculation and interlobar infiltration, which comprise the characteristic features of primary lung cancer, are uncommon presentations of this rare entity.