Does caring for patients with advanced non-small cell lung cancer affect health-related quality of life of caregivers? A multicenter, cross-sectional study.

PURPOSE: Patients with advanced non-small cell lung cancer (NSCLC) mostly receive essential routine care and support from informal caregivers, who usually experience poorer health-related quality of life (HRQoL). The study aimed to evaluate the HRQoL and its predictors among informal caregivers of patients with advanced NSCLC in China. METHODS: We interviewed the adult caregiver population of patients with advanced NSCLC (stage IIIB~IV) in nine tertiary hospitals from multiple provinces in China between November 2020 and June 2021. The EQ-5D-5L instrument measured the HRQoL of caregivers, as analyzed by employing descriptive analysis, univariate analysis, Tobit regression, and multivariate logistic regression, and investigated the important influencing factors further. RESULTS: A valid sample of 553 caregivers was analyzed. The mean EQ-5D-5L utility score of caregivers was 0.92 (SD = 0.14). Caregivers reported the greatest problems in mental health, with 45.39% reporting slight, moderate, severe, or extreme anxiety/depression. The potential influencing factors of HRQoL in caregivers included patients' age and cancer histology, relationship with the patients, and daily caregiving hours. Compared to other caregivers, patients' spouses had the lowest HRQoL. In addition, over six hours of caregiving per day was associated with lower HRQoL in caregivers of patients with advanced NSCLC. CONCLUSIONS: The HRQoL of caregivers for patients with advanced NSCLC was investigated for the first time in China. The informal caregivers experience decreased HRQoL, with anxiety /depression problems being reported the most. The findings of this study would provide extensive information on the HRQoL of advanced NSCLC patients' caregivers for future health-promoting self-care.

Measuring direct non-medical burden among patients with advanced non-small cell lung cancer in China: is there a difference in health status?

Objective: This study was conducted to estimate the direct non-medical cost of advanced non-small cell lung cancer (NSCLC) patients and explore whether its associated factors vary by health status. Methods: Data were obtained from 13 centers in five provinces for patients with advanced NSCLC in China. The direct non-medical cost of patients since the patients were diagnosed with NSCLC included the cost of transportation, accommodation, meal, hired caregiving, and nutrition. We measured patients' health status by EQ-5D-5L instrument and divided them into good (≥0.75) and poor (<0.75) groups based on the utility score. A generalized linear model (GLM) was used to assess independent associations between statistically significant factors and non-medical financial burden in health status subgroups. Results: Data from 607 patients were analyzed. The direct non-medical cost associated with advanced NSCLC since diagnosis was $2,951 per case ($4,060 in the poor health group and $2,505 in the other), with nutrition costing the most. GLM results showed that residence(Urban area vs. Rural area: -1.038, [-2.056, -0.02]), caregivers' occupation type (Farmer vs. Employee: -1.303, [-2.514, -0.093]), hospitalization frequency (0.077, [0.033, 0.12]), average length of hospital stay (0.101, [0.032, 0.17]), and pathological type (Squamous carcinoma vs. Non-squamous carcinoma: -0.852, [-1.607, -0.097]) were independent factors influencing direct non-medical cost in the poor health group. Among participants with good health status, residence (Urban area vs. Rural area: -0.621, [-1.005, -0.236]), marital status (Others vs. Married: 0.762, [0.035, 1.488]), patients' employment status, current caregiving time per day (more than 9 hours per day vs. less than 3 hours per day: 0.471, [0.134, 0.807]), duration of disease (0.015, [0.007, 0.024]), and hospitalization frequency (0.091, [0.068, 0.113]) were statistically associated factors. Conclusion: The direct non-medical economic burden of advanced NSCLC patients in China is considerable and differs by health status. Strengthening accessibility for more effective therapies and early nutritional intervention to improve prognosis, and further promoting accessible care forms within relevant healthcare insurance coverage may be potentially feasible approaches to alleviate the direct non-medical economic burden for patients and their families.

Measuring the indirect cost associated with advanced non-small cell lung cancer: a nationwide cross-sectional study in China.

PURPOSE: This study was conducted to estimate the indirect cost of locally advanced and metastatic non-small cell lung cancer (NSCLC) without sensitizing EGFR and ALK alterations in China and explore the predictors from both patient and caregiver perspectives. METHODS: Data were obtained from a nationwide cross-sectional study for the patients with advanced NSCLC (stage IIIB-IV) and their caregivers. Indirect medical cost was estimated as health productivity loss based on self-reported income and loss of work time. The generalized linear model was used to assess the independent associations between statistically significant variables and indirect economic burden. RESULTS: 611 pairs of patients and patient caregivers from 13 medical centers in five provinces in China participated in this investigation. The indirect medical cost associated with advanced NSCLC since the patient diagnosed was $1413 per capita in China. General linear regression results showed that the indirect medical cost was significantly influenced by duration of disease since diagnosis, treatment options, caregivers' occupation and age (P < 0.05). CONCLUSION: The indirect economic burden linked to advanced NSCLC in China is considerable on patients, and their caregivers. To minimize the severe challenges of indirect economic burden related to advanced NSCLC, expanding the coverage of the medical insurance and assistance system to reimburse part of the indirect costs related to cancer, as well as strengthening the accessibility for more effective therapies to improve the prognosis of advanced NSCLC, and further promote the patients and their caregivers to return to work or normal life may be the potentially feasible approaches.

Successful Treatment of an Elderly Patient With Combined Small Cell Lung Cancer Receiving Anlotinib: A Case Report.

Combined small-cell lung cancer (C-SCLC) is a relatively rare subtype of SCLC and is defined by the combination of SCLC and any elements of non-small-cell lung carcinoma. Anlotinib is a novel oral multitarget tyrosine kinase inhibitor that led to significant improvements in progression-free survival and overall survival in third-line therapy of advanced SCLC in the ALTER1202 study. Antiangiogenic therapy with anlotinib in C-SCLC has not previously been reported. An 80-year-old man was admitted with a 20-day history of blood-stained sputum. Chest computed tomography revealed a soft mass (45 × 43 mm) in the right upper lobe and a mediastinal lymph node and additional lung lesions in the homo lung. Pathology confirmed C-SCLC after an ultrasound-guided percutaneous puncture biopsy of the right lung tumor. The elderly patient was given anlotinib monotherapy at a dose of 10 mg/day on days 1-14 of a 21-day cycle after providing informed consent, and the outcome was assessed as continued partial response. As of the last follow-up evaluation, the patient's progression-free survival was more than 7 months, and the treatment showed satisfactory safety. Our findings provide direct evidence of the efficacy of anlotinib in an elderly patient with C-SCLC. More studies are needed to confirm our observations.

Elevated levels of interleukin-35 and interleukin-37 in adult patients with obstructive sleep apnea.

BACKGROUND: Systemic inflammation has a critical role in the pathogenesis of obstructive sleep apnea (OSA). Interleukin (IL)-35 and IL-37 have been identified as novel immune-modulating cytokines with anti-inflammatory activities in numerous types of inflammatory disease. The present study aimed to examine the serum levels of IL-35 and IL-37 in patients with OSA, and to investigate their associations with the severity of OSA. METHODS: A total of 97 patients, including 67 cases of OSA and 30 age- and gender-matched healthy control subjects, were enrolled in the present study. All subjects were evaluated by overnight polysomnography. Serum IL-35, IL-37, and pro-inflammatory cytokine IL-1ß levels were examined by ELISA. RESULTS: Compared with those in the control subjects, serum IL-35, IL-37, and IL-1ß levels were significantly elevated in patients with mild, moderate, or severe OSA. Furthermore, a severity-dependent increase in serum IL-35 and IL-37 levels was observed in patients with OSA. IL-35 and IL-37 levels were positively correlated with the apnea-hypopnea index (r = 0.742 and 0.578, respectively; both p < 0.001), while they were negatively correlated with the mean oxygen saturation (r = -0.461 and -0.339, respectively; both p < 0.001) and lowest oxyhaemoglobin saturation (r = -0.616 and -0.463, respectively; both p < 0.001) in patients with OSA. In addition, a positive correlation was observed between IL-35 or IL-37 and IL-1ß levels (all p < 0.001). CONCLUSION: The serum levels of IL-35 and IL-37 were significantly increased in patients with OSA and associated with the severity of OSA, implying that IL-35 and IL-37 may have a protective role in OSA by counteracting inflammatory responses.

Serum periostin and TNF-α levels in patients with obstructive sleep apnea-hypopnea syndrome.

PURPOSE: Obstructive sleep apnea-hypopnea syndrome (OSAHS) may cause pulmonary diseases, and periostin plays an important role on the development of pulmonary diseases. In addition, periostin and pro-inflammatory cytokine TNF-α can regulate each other in vivo. This study aimed to observe the changes of serum periostin and TNF-α levels in patients with OSAHS compared with healthy volunteers and to investigate their correlation. METHODS: A convenience sample of 67 patients with OSAHS in our hospital from December 2018 to December 2019 was selected and categorized into mild, moderate, and severe groups according to apnea-hypopnea index by polysomnography. In addition, 21 healthy volunteers were selected as the control group. Serum levels of periostin and TNF-α were determined by enzyme-linked immunosorbent assay (ELISA). Results were analyzed using the SPSS software. RESULTS: Both serum periostin and TNF-α levels in all the three OSAHS groups were higher than those of the control group and increased with severity of OSAHS. The severe group had significantly higher serum periostin and TNF-α levels than the mild and moderate groups (p < 0.05). For patients with OSAHS, serum periostin and TNF-α levels positively correlated with the apnea-hypopnea index (AHI) (p < 0.01) and negatively correlated with the lowest saturation oxygen (LSaO2) and mean saturation oxygen (MSaO2) (both p < 0.01). In addition, there was a positive correlation between serum periostin and TNF-α levels in patients with OSAHS (p < 0.001). CONCLUSIONS: Serum periostin and TNF-α levels were significantly increased in patients with OSAHS and may serve as a potential biomarker for severity of OSAHS. These findings suggest that it may be fruitful to study the role of periostin and TNF-α in OSAHS-induced pulmonary diseases.

IL-22 Up-Regulates ß-Defensin-2 Expression in Human Alveolar Epithelium via STAT3 but Not NF-κB Signaling Pathway.

Human ß-defensin-2(HBD-2) is one of the two major vertebrate antimicrobial peptide families (α and ß), which is highly expressed by proinflammatory induction in the lung and exhibit broad-spectrum antimicrobial activity. We observed that IL-22 receptors high expressed on the membrane of A549 cells; HBD-2 mRNA was expressed in a time- and concentration-dependent manners in A549 cells when treated with IL-22; further studies demonstrated that HBD-2 expression was attenuated by AG490, but to JSH-23, inhibitors of p-STAT3 DNA binding and NF-κB/p65 subunit nuclear translocation, respectively. These results support that IL-22-mediated signalling pathway of HBD-2 gene expression involved STAT3 but not NF-κB in human alveolar epithelium. These findings provide a new insight into how IL-22 may play an important link between innate and adaptive immunity, thereby anti-infection locally in the alveolar epithelium.

Paeoniflorin upregulates ß-defensin-2 expression in human bronchial epithelial cell through the p38 MAPK, ERK, and NF-κB signaling pathways.

Paeoniflorin (PF) is one of the principal components of peony, a plant widely used in traditional Chinese medicine for its anti-inflammatory and immunomodulatory effects. Human ß-defensin-2 (hBD-2) is an antimicrobial peptide that acts as the first line of defense against bacterial, viral, and fungal infections. This study aims to determine whether or not PF can regulate the expression of hBD-2 and its possible molecular mechanism in human bronchial epithelial cells (HBECs). Real-time quantitative reverse transcription PCR showed that PF can enhance the mRNA expression level of hBD-2 in a concentration- and time-dependent manner in HBECs. Further studies demonstrated that the mRNA and protein expression levels of hBD-2 were attenuated by the p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580, the extracellular signal-regulated kinase (ERK) inhibitor PD98059, and the nuclear factor kappa B (NF-κB) inhibitor (pyrrolidine dithiocarbamate (PDTC)). The phosphorylation of p38 MAPK, ERK, and c-Jun N-terminal kinase was detected by Western blot analysis, and the NF-κB translocation of 16HBECs after PF treatment was analyzed by immunofluorescence. These results support that PF upregulates hBD-2 expression in HBECs through the p38 MAPK, ERK, and NF-κB signaling pathways. These findings provide a new pharmacological mechanism of PF for the treatment of microbial infections by strengthening epithelial antimicrobial barriers.