Landscape of Immune-Related Pneumonitis in Cancer Patients with Asthma Being Treated with Immune Checkpoint Blockade.
- 作者列表："Galant-Swafford J","Troesch A","Tran L","Weaver A","Doherty TA","Patel SP
INTRODUCTION:Predicting the factors that increase the risk of immune-related pneumonitis, a potentially life-threatening complication of treatment with immune checkpoint inhibitors for cancer, is a clinical challenge. Baseline clinical factors such as asthma may portend the development of pneumonitis due to pre-existing airway inflammation prior to immunotherapy. OBJECTIVE:The purpose of the study was to investigate whether a prior diagnosis of asthma is associated with an increased risk of immune-related pneumonitis in patients undergoing cancer immunotherapy. METHODS:Patients at the Moores Cancer Center at UC San Diego Health undergoing immunotherapy were identified on an IRB-approved protocol. Clinical charts were reviewed for asthma documented in the medical records and CT scans were reviewed during and after treatment. Pneumonitis was defined as the onset of new pulmonary symptoms with characteristic imaging findings during or after a patient's first course of immunotherapy that could not be readily explained as infection or a progression of malignancy. It was graded according to the Common Terminology Criteria for Adverse Events. RESULTS:A total of 187 patients were included. A diagnosis of asthma was found in the records of 26 cases (13.9%). Pneumonitis was found in 10 cases (5.35%); 50% were grade 2 and 50% were grade 3-4. Two of the grade 3-4 cases (40%) occurred in patients with non-small-cell lung cancer. Three patients with asthma developed pneumonitis (11.5% of patients with asthma), all grade 3-4. Only 28.6% of the non-asthma-pneumonitis cases were grade 3-4. All (100%) of the asthma-pneumonitis patients were former smokers, while 71.4% of the non-asthma-pneumonitis patients were former smokers. CONCLUSION:A history of asthma may be associated with a higher grade of pneumonitis if it develops, and a history of smoking may augment this relationship.
引言: 预测增加免疫相关性肺炎风险的因素是一个临床挑战，免疫检查点抑制剂治疗癌症可能危及生命的并发症。基线临床因素 (如哮喘) 可能预示着免疫治疗前由于预先存在的气道炎症而导致肺炎的发展。 目的: 本研究的目的是调查在接受癌症免疫治疗的患者中，哮喘的先前诊断是否与免疫相关性肺炎的风险增加有关。 方法: 在加州大学圣地亚哥分校Moores癌症中心接受免疫治疗的患者在IRB批准的方案中进行鉴定。回顾病历中记录的哮喘临床图表，并在治疗期间和治疗后回顾ct扫描。肺炎被定义为在患者第一次免疫治疗过程中或之后出现具有特征性影像学表现的新的肺部症状，其不能轻易解释为感染或恶性肿瘤的进展。根据不良事件的通用术语标准对其进行分级。 结果: 共纳入 187 例患者。在 26 例 (13.9%) 的记录中发现哮喘的诊断。肺炎 10 例 (5.35%); 50% 为 2 级，50% 为 3-4 级。3-4 级病例中有 2 例 (40%) 发生于非小细胞肺癌患者。3 例哮喘患者发生肺炎 (11.5% 的哮喘患者)，均为 3-4 级。仅 28.6% 的非哮喘-肺炎病例为 3-4 级。所有 (100%) 的哮喘-肺炎患者为既往吸烟者，而 71.4% 的非哮喘-肺炎患者为既往吸烟者。 结论: 哮喘病史可能与肺炎的严重程度有关，吸烟史可能会增加这种关系。
METHODS::The antimicrobial functions of neutrophils are facilitated by a defensive armamentarium of proteins stored in granules, and by the formation of neutrophil extracellular traps (NETs). However, the toxic nature of these structures poses a threat to highly vascularized tissues, such as the lungs. Here, we identified a cell-intrinsic program that modified the neutrophil proteome in the circulation and caused the progressive loss of granule content and reduction of the NET-forming capacity. This program was driven by the receptor CXCR2 and by regulators of circadian cycles. As a consequence, lungs were protected from inflammatory injury at times of day or in mouse mutants in which granule content was low. Changes in the proteome, granule content and NET formation also occurred in human neutrophils, and correlated with the incidence and severity of respiratory distress in pneumonia patients. Our findings unveil a 'disarming' strategy of neutrophils that depletes protein stores to reduce the magnitude of inflammation.
METHODS::Pneumonia is a common respiratory infectious disease that involves the inflammation of the pulmonary parenchyma. Periodontal disease is widespread and correlated with pneumonia. However, the relationship between periodontal treatment and clinical infectious outcomes in patients with pneumonia has remained undetermined. The aim of this study was to investigate the association between periodontal treatment and the risk of pneumonia events in the Taiwanese population. A nationwide population-based cohort study was conducted using data from the Taiwanese National Health Insurance Research Database (NHIRD). A total of 49,400 chronic periodontitis patients who received periodontal treatment from 2001 to 2012 were selected. In addition, 49,400 healthy individuals without periodontal diseases were picked randomly from the general population after propensity score matching according to age, gender, monthly income, urbanization, and comorbidities. The Cox proportional hazard regression analysis was adopted to assess the hazard ratio (HR) of pneumonia between the periodontal treatment cohort and the comparison cohort. The average ages of the periodontal treatment and comparison groups were 44.25 ± 14.82 years and 44.15 ± 14.5 years, respectively. The follow up durations were 7.66 and 7.41 years for the periodontal treatment and comparison groups, respectively. We found 2504 and 1922 patients with newly diagnosed pneumonia in the comparison cohort and the periodontal treatment cohort, respectively. The Kaplan-Meier plot revealed that the cumulative incidence of pneumonia was significantly lower over the 12 year follow-up period in the periodontal treatment group (using the log-rank test, p < 0.001). In conclusion, this nationwide population-based study indicated that the patients with periodontal treatment exhibited a significantly lower risk of pneumonia than the general population.
METHODS:OBJECTIVE:To describe the treatment of community-acquired pneumonia (CAP) in children under five years in Tanzania. METHODS:Between January and December 2017, children aged 2-59 months with chest radiography-confirmed CAP were enrolled. The parents were interviewed to collect information on the patients and home-based medication. Clinical information was derived from the patient files. Nasopharyngeal swab and blood samples were collected for isolation of the causative pathogens. Swab samples were analysed by quantitative PCR whereas blood samples were tested using BacT/Alert 3D. RESULTS:Overall, 109 children with CAP were included in this analysis. Provision of care to most children was delayed (median = 4.6 days). A quarter (26.6%) were given unprescribed/leftover antibiotics at home. Only one child had positive bacterial culture. Referrals were associated with nasopharyngeal carriage of Streptococcus pneumoniae (p = 0.003) and Haemophilus influenzae (p = 0.004). Of all admitted children, more than a quarter (n = 29) did not need to be hospitalised and inappropriately received injectable instead of oral antibiotics. CONCLUSION:We found high rates of home treatment, particularly with antibiotics. Appropriate health care was delayed for most children because of home treatment. Efforts are needed at the community level to improve awareness of antimicrobial resistance.