Comprehensive assessment of multiple tryptophan metabolites as potential biomarkers for immune checkpoint inhibitors in patients with non-small cell lung cancer.

PURPOSE: Tryptophan metabolites have immunomodulatory functions, suggesting possible roles in cancer immunity. METHODS: Plasma tryptophan metabolites were measured using liquid chromatography/mass spectrometry before immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC). RESULTS: The 19 patients with NSCLC had significantly lower levels of tryptophan (p = 0.002) and xanthurenic acid (p = 0.032), and a significantly higher level of 3-hydroxyanthranilic acid (3-HAA) (p = 0.028) compared with the 10 healthy volunteers. The patients achieving objective responses had significantly lower levels of 3-HAA than those who did not (p = 0.045). Receiver operating characteristic analyses determined that the cutoff value of 3-HAA for objective response was 35.4 pmol/mL (sensitivity: 87.5% and specificity: 83.3%). The patients with 3-HAA < 35.4 pmol/mL had significantly longer median progression-free survival (7.0 months) than those without (1.6 months, p = 0.022). CONCLUSIONS: Tryptophan metabolites may have a potential for predicting the efficacy of ICIs. REGISTRATION NUMBER: University Hospital Medical Information Network Clinical Trial Registry 000026140.

Respiratory impedance is correlated with airway narrowing in asthma using three-dimensional computed tomography.

BACKGROUND: Respiratory impedance comprises the resistance and reactance of the respiratory system and can provide detailed information on respiratory function. However, details of the relationship between impedance and morphological airway changes in asthma are unknown. OBJECTIVE: We aimed to evaluate the correlation between imaging-based airway changes and respiratory impedance in patients with asthma. METHODS: Respiratory impedance and spirometric data were evaluated in 72 patients with asthma and 29 reference subjects. We measured the intraluminal area (Ai) and wall thickness (WT) of third- to sixth-generation bronchi using three-dimensional computed tomographic analyses, and values were adjusted by body surface area (BSA, Ai/BSA, and WT/the square root (√) of BSA). RESULTS: Asthma patients had significantly increased respiratory impedance, decreased Ai/BSA, and increased WT/√BSA, as was the case in those without airflow limitation as assessed by spirometry. Ai/BSA was inversely correlated with respiratory resistance at 5 Hz (R5) and 20 Hz (R20). R20 had a stronger correlation with Ai/BSA than did R5. Ai/BSA was positively correlated with forced expiratory volume in 1 second/forced vital capacity ratio, percentage predicted forced expiratory volume in 1 second, and percentage predicted mid-expiratory flow. WT/√BSA had no significant correlation with spirometry or respiratory impedance. CONCLUSIONS & CLINICAL RELEVANCE: Respiratory resistance is associated with airway narrowing.

Chronological effects of rifampicin discontinuation on cytochrome P450 activity in healthy Japanese volunteers, using the cocktail method.

Cytochrome P450 (CYP) 1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A are major factors involved in the metabolism of clinically prescribed drugs. Because the time course after drug treatment discontinuation has received little attention, we aimed to clarify the chronological changes of rifampicin-induced CYP enzyme activities after rifampicin discontinuation. Thirteen volunteers took 450 mg of rifampicin once daily, and the cocktail method, which uses caffeine, losartan, omeprazole, dextromethorphan, and midazolam as CYP-specific probes, was repeatedly used for the evaluation of CYP levels. Concentrations of probes and metabolites were determined by liquid chromatography-tandem mass spectrometry. Seven-day rifampicin administration increased CYP2C19 and CYP3A enzyme activities. The induced CYP2C19 and CYP3A activities remained elevated at 4 days after rifampicin discontinuation and returned to baseline levels 8 days after rifampicin discontinuation. CYP1A2 and CYP2D6 enzyme activities showed no significant changes, and CYP2C9 enzyme activity was increased with rifampicin administration, with a tendency toward statistical significance. Drug interactions can occur even after rifampicin discontinuation.

Pulmonary dendritic cell accumulation in usual interstitial pneumonia and nonspecific interstitial pneumonia.

BACKGROUND: Pulmonary dendritic cells (DCs) are key regulators of immune responses. An increased accumulation of DCs was reported in the lungs of patients with idiopathic interstitial pneumonia (IIP). OBJECTIVE: This study aimed to investigate the number of pulmonary DCs in patients with collagen vascular disease associated interstitial lung diseases (CVD-ILDs). DESIGN: Lung tissue samples obtained from 27 patients with IIP and 39 patients with CVD-ILD were detected using monoclonal antibodies against CD1a, CD1c, CD83, Langerin and DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN). RESULTS: No significant differences in the number or distribution of DCs were observed between patients with IIP and CVD-ILDs. When DC marker expression was analyzed according to pathological subgroup, patients with idiopathic usual interstitial pneumonia (UIP) showed increased DC-SIGN staining when compared with CVD-UIP (p < 0.05). CONCLUSION: Both mature and immature DCs accumulate in CVD-ILDs. The number of DCs expressing DC-SIGN in CVD-UIP was decreased compared with that in idiopathic UIP. The variation in accumulated DC-SIGN-positive cells might help to explain the differences in the development and maintenance of lung inflammation between idiopathic UIP and CVD-UIP.

Absorption of nitrogen dioxide in organic solvents.

The absorption of NO(2) at low levels in nitrogen, by N,N-dimethylformamide (DMF) and dimethyl sulphoxide (DMSO), has been investigated. Parts-per-million levels of NO(2), were collected with an efficiency of 90% in DMF and 65-70% in DMSO. The absorption efficiency in DMF depends on the gas flow-rate and the bubbling time, but in DMSO it is independent of time.