The administration of inhaled corticosteroids and worldwide usage of several asthma guidelines have improved asthma mortality. Elderly patients with asthma show high mortality rates, and may have ...several comorbidities, including overlap with chronic obstructive pulmonary disease (COPD). Among patients showing asthma overlapped with COPD (asthma-COPD overlap syndrome; ACOS), mortality is worse than for asthma alone. Therefore, we investigated comorbidities, malignancies, and causes of death in patients with asthma and ACOS.
This was a retrospective study. From January 2000 to March 2012, 650 patients were followed up at Tottori University Hospital. Medical records were reviewed to collect data regarding patient characteristics and comorbidities, and causes of death were recorded for patients who died during the study period.
Eighty-seven patients died during the study period. The most frequent cause of death was malignancy. The proportion of malignant disease was 21.7% in all patients, 19.4% in patients with asthma alone, and 32.4% in patients with ACOS. One patient died from an asthma attack during this period.
The most frequent cause of death in patients with asthma and ACOS was malignant disease. It is necessary to control not only asthma but also comorbidities in patients with asthma, especially in those with ACOS.
Immune checkpoint inhibitors (ICIs), including nivolumab, have exhibited substantial benefits in the treatment of several types of cancers. However, treatment with ICIs is often accompanied by ...immune-related adverse events (irAEs), and a clear understanding of the precise indications and management of irAEs is important for harnessing the full potential of these agents. While skin- or gastrointestinal-associated irAEs have been relatively well studied, there are few reports regarding nivolumab-induced cholangitis. We retrospectively reviewed data from patients with advanced or recurrent non-small cell lung cancer who were treated with nivolumab between December 2015 and December 2018 at Tottori University in Japan. Among the 59 patients, we identified four patients who experienced nivolumab-induced cholangitis. Of these four patients, stable disease (SD) was observed in two patients (50%), while partial response (PR) was achieved in two patients (50%) under nivolumab treatment. Patients were treated with corticosteroid alone (n=2) or in combination with mycophenolate mofetil (MMF) (n=2); these treatments resulted in improvements in nivolumab-induced cholangitis in three patients. In conclusion, the present retrospective study identified four cases of nivolumab-induced cholangitis. The combination of corticosteroid and MMF was effective in two cases with grade 4 nivolumab-induced cholangitis. Further reports are needed to establish the optimal management of patients with this irAE.
Aseptic meningitis is a rare immune-related adverse event (irAE), which occurs during treatment with immune checkpoint inhibitors (ICIs). This condition has non-specific symptoms and exhibits no ...clear signs on magnetic resonance imaging (MRI). There are only a few reports of aseptic meningitis caused by pembrolizumab treatment for non-small cell lung cancer (NSCLC). The present study includes a report of such a case and a review of the related literature. A 67-year-old Japanese man received first-line pembrolizumab treatment for NSCLC and subsequently developed severe nausea and vomiting. No significant findings were observed following a computed tomography (CT) scan, MRI of the brain and upper gastrointestinal tract, or upper gastrointestinal endoscopy. Cerebrospinal fluid analysis revealed lymphocyte infiltration and elevation of the IgG index, without indications of metastasis or infection, which suggested the presence of aseptic meningitis. The symptoms immediately improved following prednisolone treatment, and aseptic meningitis was diagnosed as an irAE related to pembrolizumab treatment. Given that aseptic meningitis can cause non-specific symptoms, including headache and nausea, the possibility of an irAE should be considered in patients with non-specific symptoms who are receiving ICIs, and a cerebrospinal fluid examination should be performed.
A 70-year-old man was admitted to our hospital because of dyspnea after taking an antihistaminic agent (homochlorcyclizine hydrochloride) for itching. Chest roentgenogram showed infiltration in the ...left lung field, and laboratory data revealed eosinophilia. Examination of the bronchoalveolar lavage fluid revealed an increased eosinophil count. A drug lymphocyte stimulation test was positive only for calcium stearate, an additive contained in the homochlorcyclizine hydrochloride tablet. The pulmonary infiltration and clinical symptoms subsided after withdrawal of all drugs and initiation of glucocorticoid therapy. Therefore, we concluded that this patient's pulmonary disease was caused by calcium stearate, an additive for an antihistaminic drug. An allergic reaction to a drug's additive material should be considered as a rare cause of drug-induced acute eosinophilic pneumonia.
ABSTRACT Background Weight loss in patients with cancer is caused by cancer cachexia and chemotherapy-induced nausea and vomiting (CINV). Recent developments in antiemetic drugs have substantially ...improved CINV, but nutritional intervention did not improve body weight. This study aimed to investigate the effects of nutrition intervention with appropriate antiemetic treatment in patients with non-small-cell lung cancer during chemotherapy. Methods Patients received individualized nutrition counseling by a registered dietitian and were provided with oral supplements for 90 days. Body weight and other parameters were measured at baseline and after 90-day intervention. To evaluate this nutrition intervention, patients were also retrospectively set as control, and then body weight change was compared with inverse probability of treatment weights (IPTW) analysis. Results Ten patients received individualized nutrition counseling and were provided with oral supplements for 90 days. Of them, 7 patients consumed nutritional supplements, and the mean intake was 130kcal/day. After 90-day intervention, the patients did not show significant weight and BMI loss during the course of cytotoxic chemotherapy. A total of 38 patients were retrospectively enrolled as controls. The number of the patients who gain the body weight after 90 days in the study cohort was significantly larger than that in the retrospective controls with the IPTW analysis (Odds Ratio (OR)=8.4; 95% Confidence Interval (CI): 1.6-42; P=0.01). Conclusion Early intensive nutrition intervention with appropriate antiemetic treatment prevents weight loss. Nutrition interventions might be also beneficial for quality of life, treatment response and survival.
Epidermal growth factor receptor (EGFR) gene mutation testing is essential for choosing appropriate treatment options in patients with advanced non-small cell lung cancer (NSCLC). However, a time ...delay occurs between histological diagnosis and molecular diagnosis in clinical situations. To minimize this delay, we developed a novel point-of-care test for EGFR mutations, based on a high-speed real-time polymerase chain reaction (PCR) system designated here as ultrarapid PCR combined with highly accurate bronchoscopic sampling. We investigated whether our system for detecting EGFR mutations was valid by comparing test results with those obtained using a commercialized EGFR mutation test. We obtained small amounts of bronchial lavage fluids after transbronchial biopsies (TBBs) were performed on enrolled patients (n=168) who underwent endobronchial ultrasonography using a guide sheath (EBUS-GS). EGFR mutation analysis was performed by ultrarapid PCR immediately after EBUS-GS-TBBs were obtained (on the same day). After pathological diagnoses of NSCLC, EGFR mutation status in formalin-fixed, paraffin- embedded samples was confirmed by the PCR-invader method, and the concordance rates between the PCR methods were compared. The total diagnostic yield of EBUS-GS-TBB was 91.0%. The positive concordance rates for detecting 19del and L858R with the ultrarapid PCR and PCR-invader methods were both 100%. Negative concordance rates were 97.2 and 98.1%, respectively. We also demonstrated a dramatic effect of early erlotinib administration, based on ultrarapid PCR results, for a 52-year-old woman suffering from respiratory failure due to severe intrapulmonary metastases with poor performance status. In conclusion, ultrarapid PCR combined with EBUS-GS-TBB enabled rapid and reliable point-of-care testing for EGFR mutations.
Previously we showed that Akt-suppressing agents, combined with amrubicin, synergistically inhibited the growth of small cell lung cancer cells. The combined effects of chemotherapeutic agents and ...Akt-suppressing agents, including epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, were evaluated in A549 lung adenocarcinoma cells harboring K-ras mutation and wild-type EGFR. Only amrubicin and not other chemotherapeutics (cisplatin, pemetrexed and paclitaxel) synergistically inhibited cell growth when combined with an Akt inhibitor, LY294002. The combination of amrubicin and LY294002 enhanced Annexin V binding to cells. A non-specific tyrosine kinase inhibitor, genistein, suppressed Akt and showed synergistic interaction in combination with amrubicin. Two EGFR tyrosine kinase inhibitors (EGFR-TKIs), gefitinib and erlotinib, suppressed Akt activity at clinically achievable concentrations and demonstrated synergism when combined with amrubicin. The suppression of K-ras expression by siRNA interfered with this synergism and inhibited both EGFR and Akt activity in A549 cells. In Ma10 cells, which harbor wild-type EGFR and K-ras, EGFR-TKIs neither suppressed Akt activity nor exhibited such synergism when combined with amrubicin. We concluded that the synergism by the combination of EGFR-TKI and amrubicin is attributable, at least partially, to K-ras mutation in A549 cells. The combination of EGFR-TKI and amrubicin may be a promising treatment for lung cancer with wild-type EGFR and K-ras mutation.
Nitrogen-containing bisphosphonates (N-BPs), which are usually used for the treatment of advanced cancer with bone metastasis, occasionally cause fever following the first administration. However, it ...is unclear as to how the development of fever following the first administration of N-BP is associated with clinical outcome. The aim of the present study was to determine the prognostic value of the development of fever following the first administration of N-BP in advanced non-small cell lung cancer patients with bone metastases. The present study reviewed the data of 46 patients with advanced non-small cell lung cancer who were administered zoledronate (ZOL), an N-BP, for bone metastasis, between March 2009 and March 2011 in the Department of Medical Respirology at Tottori University Hospital. Clinicopathological factors were evaluated using univariate and multivariate analyses, and these factors were compared between the fever and non-fever groups. Of the 46 patients, 15 (32.6%) developed fever following the first administration of ZOL. No significant differences were observed in the clinicopathological characteristics between the two groups. The overall survival in the fever group was significantly longer compared with the non-fever group (median survival time: 33.4 vs. 15.7 months, P=0.04), and the development of fever following the first ZOL administration was independently associated with longer overall survival. The development of fever following the first ZOL administration was an independent prognostic factor in advanced non-small cell lung cancer patients with bone metastases. Thus, ZOL-associated fever may be a predictive factor for an undefined, survival-promoting effect of ZOL.
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