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Background: High-mobility group box 1 (HMGB1) is a pro-inflammatory protein associated with the pathophysiology of lung injury and lung tumorigenesis. Here, we investigated the predictive potential of serum HMGB1 levels for radiation pneumonitis in patients with lung cancer. Methods: This was a retrospective biomarker study of 73 patients with non-small cell lung cancer treated with definitive thoracic radiotherapy between August 2007 and January 2021. We measured HMGB1 levels in serum stored before treatment, and analyzed its association with the development of grade ≥ 2 or grade ≥ 3 radiation pneumonitis. Additionally, baseline characteristics affecting HMGB1 levels were identified. Results: Of the 73 patients, 21 (28.8%) and 6 (8.2%) patients experienced grade 2 and ≥ 3 radiation pneumonitis, respectively. Univariate and multivariate logistic regression analyses revealed that higher baseline levels of serum HMGB1 were significantly associated with a higher risk of grade ≥ 3, but not grade ≥ 2, radiation pneumonitis. The incidence of grade ≥ 3 radiation pneumonitis was higher in patients with HMGB1 levels ≥ 6.2 ng/mL than in those with levels < 6.2 ng/mL (25.0% vs. 3.5%, p = 0.019). Baseline serum levels of HMGB1 were independently and positively associated with gross tumor volume. Conclusions: Higher serum HMGB1 levels were significantly associated with the risk of grade ≥ 3 radiation pneumonitis in patients with lung cancer, and therefore, HMGB1 could be a potential blood biomarker for predicting severe radiation pneumonitis. [ABSTRACT FROM AUTHOR]

Purpose: Cytotoxic chemotherapy-induced lung injury is a fatal complication in patients with lung cancer and interstitial lung disease (ILD). We aimed to evaluate the association between hyperglycemia and this form of lung injury in patients with lung cancer concomitant with ILD. Methods: From 1147 patients with advanced lung cancer, we retrospectively enrolled 98 patients with ILD whose hemoglobin A1c (HbA1c) levels were measured, and investigated the association between HbA1c levels and cytotoxic chemotherapy-induced lung injury. In 73 patients whose serum samples were retained, we measured serum levels of advanced glycation end products (AGE) and assessed the association of AGE levels with HbA1c levels and cytotoxic chemotherapy-induced lung injury. Results: The incidence of cytotoxic chemotherapy-induced lung injury was significantly higher in patients with HbA1c levels ≥ 5.8% than in those with HbA1c levels < 5.8%, but not in those with HbA1c levels ≥ 6.5% than in those with HbA1c levels < 6.5%. The multivariate logistic regression model revealed that HbA1c level ≥ 5.8% was a significant risk factor for this complication [odds ratio 3.178 (95% confidence interval 1.057–9.556), P = 0.040]. In addition, serum AGE levels were significantly higher in patients with HbA1c levels ≥ 5.8% than in those with HbA1c levels < 5.8% [median (interquartile range); 0.129 (0.023–0.290) and 0.474 (0.213–1.109) μg/mL, P = 0.001]. Conclusion: Glucose intolerance (e.g., HbA1c level ≥ 5.8%) may be a risk factor of cytotoxic chemotherapy-induced lung injury, which might be associated with elevated AGE production due to hyperglycemia. [ABSTRACT FROM AUTHOR]

Postoperative acute exacerbation of interstitial lung disease (AE-ILD) can be fatal in patients with lung cancer concomitant with ILD. We aimed to elucidate the predictive potential of high-mobility group box 1 (HMGB1), which is associated with the development and severity of lung injury, for evaluating the risk of this complication. We included 152 patients with lung cancer and ILD who underwent radical surgery between January 2011 and August 2019. We evaluated the preoperative levels of serum HMGB1 and its predictive potential for postoperative AE-ILD. Postoperative AE-ILD developed in 17 patients. Serum levels of HMGB1 were significantly higher in patients with postoperative AE-ILD than in those without (median [interquartile range]: 5.39 [3.29–11.70] ng/mL vs. 3.55 [2.07–5.62] ng/mL). Univariate and multivariate logistic regression analyses revealed that higher HMGB1 levels were significantly associated with the development of postoperative AE-ILD in entire studied patients (n = 152). In the subgroup analysis, higher HMGB1 levels were associated with a significantly increased risk of this complication in patients who underwent lobectomy (n = 77) than in those who underwent sublobar resection (n = 75). Serum HMGB1 could be a promising marker for evaluating the risk of postoperative AE-ILD, specifically in patients who underwent lobectomy. [ABSTRACT FROM AUTHOR]

The urinary antigen test (UAT) is a rapid diagnostic method for pneumococcal pneumonia, but the high false-negative rate of 30% may affect its reliability. To maximize the utility of UAT, it is necessary to investigate the patient factors affecting UAT results. However, there is no report elucidating the association between its utility and pre-existing lung abnormalities. We retrospectively reviewed 388 patients with pneumococcal pneumonia confirmed by blood and/or sputum culture tests. Finally, 94 of 388 patients who had the results of UAT and computed tomography scans were enrolled to evaluate the association between the utility of UAT and patient factors including pulmonary emphysema and fibrosis. The overall positive rate of UAT was 69.1%. The positive rates of UAT in the patients with emphysema were significantly lower than those in individuals without emphysema (33.3% and 77.6%, p < 0.001). Univariate logistic regression analysis showed that the presence of emphysema was associated with a low positive rate (odds ratio 6.944, 95% confidence interval 2.268–21.231). Multivariate logistic analysis showed that the presence of emphysema and lower levels of serum blood urea nitrogen (BUN) were significantly and independently associated with a low positive rate. The combination of emphysema and BUN can potentially stratify the positive rate of UAT in patients with pneumococcal pneumonia. Patients with pneumococcal pneumonia and emphysema have a lower positive rate of UAT. Additionally, the combination of emphysema and serum BUN value may be useful to evaluate the reliability of the negative results of pneumococcal UAT. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated the safety and efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) re-administration after recovery from EGFR-TKI-induced interstitial lung disease (ILD). Methods: This multicenter retrospective study collected data from consecutive advanced NSCLC patients who underwent EGFR-TKI re-administration after recovery from EGFR-TKI-induced ILD. Results: Fifty-eight patients were registered. The grades of initial TKI-induced ILD were grade 1 to 4. TKIs used for re-administration were erlotinib for 15 patients, osimertinib for 15, gefitinib for 14, afatinib for 13 patients, and dacomitinib for 1 patient. ILD recurred in 13 patients (22.4%), comprising 3 patients with grade 1, 6 patients with grade 2, and 4 patients with grade 3. No significant associations were found between ILD recurrence and age, smoking history, performance status, time from initial ILD to TKI re-administration, or concomitant corticosteroid use. However, the incidence of ILD recurrence was high in cases of repeated use of gefitinib or erlotinib or first time use of osimertinib at TKI re-administration. The ILD recurrence rate was lowest in patients treated with first time use of gefitinib (8%) or erlotinib (8%), followed by patients treated with repeated use of osimertinib (9%). The response rate, median progression-free survival by TKI re-administration, and median overall survival were 55%, 9.6 and 84.8 months, respectively. Conclusion: This study showed that EGFR-TKI re-administration is a feasible and effective treatment for patients who recovered from EGFR-TKI-induced ILD. Our results indicate that re-administration of EGFR-TKI is an important option for long-term prognosis after recovery from EGFR-TKI-induced ILD. [ABSTRACT FROM AUTHOR]

Background: Anti-programmed cell death receptor (PD)-1 antibody treatment results in better prognosis than standard chemotherapy in patients with non-small cell lung cancer (NSCLC), especially those with high PD-ligand 1 (PD-L1) expression. However, several studies have reported a lack of antitumor effect of PD-1 antibody, even in patients with high PD-L1 expression. Therefore, reliable predictors of treatment response are urgently needed. The albumin–globulin ratio (AGR) is associated with prognosis in several cancers. We aimed to determine whether AGR is a predictive biomarker of anti-PD-1 antibody response in patients with NSCLC. Patients and methods: Seventy-four NSCLC patients treated with anti-PD-1 antibody were retrospectively enrolled. Patients with driver mutations were excluded. Results: The mean AGR was significantly higher in the disease control (DC) group than in the progressive disease (PD) group (p < 0.001). Receiver operating characteristic curve analysis revealed an AGR cutoff value for dividing patients into the DC or PD groups of 1.17. Multivariate logistic regression analysis showed that a high AGR (≥1.17, cutoff value) was an independent predictor of DC (p = 0.001). Progression-free survival (PFS) and overall survival (OS) were significantly longer in the high-AGR group than in the low-AGR group (p = 0.008, p = 0.002, respectively). Multivariate Cox regression analysis of PFS and OS showed that high AGR was an independent prognostic factor (p = 0.020, p < 0.001, respectively). Conclusion: Pretreatment serum AGR may be a useful predictor for DC and prognostic factor of anti-PD-1 antibody in patients with NSCLC. The clinical utility of AGR still needs to be confirmed in a prospective analysis. [ABSTRACT FROM AUTHOR]

Preserved ratio impaired spirometry (PRISm) is defined by reduced FEV1 with a preserved FEV1/FVC ratio; some individuals with PRISm can also have restrictive ventilatory abnormality. The aim of this study was to clarify clinical features of restrictive and non-restrictive PRISm. In total, 11,246 participants (mean, 49.1 years; range, 35–65 years) from five healthcare centres were included in this study. We evaluated baseline characteristics of participants with restrictive PRISm (FEV1/FVC ≥ 0.7, FEV1 < 80% and FVC < 80%) and non-restrictive PRISm (FEV1/FVC ≥ 0.7, FEV1 < 80% and FVC ≥ 80%), and airflow obstruction (FEV1/FVC < 0.7). We examined the longitudinal risk of developing airflow obstruction by comparing spirometry results at baseline and 5 years post-baseline among 2141 participants. Multivariate analysis demonstrated that a history of asthma or smoking could constitute an independent risk factor for non-restrictive PRISm, and that non-restrictive PRISm was independently associated with the risk of developing airflow obstruction. In contrast, female sex, advanced age, and high BMI, but not history of asthma or smoking, were risk factors for restrictive PRISm. Restrictive PRISm was not associated with the development of airflow obstruction. In conclusion, our results indicate that PRISm can be categorized according to the presence or absence of restrictive abnormality. Non-restrictive PRISm, which does not meet the conventional criteria of obstructive and restrictive ventilatory abnormalities, may be a precursor of chronic obstructive pulmonary disease and merits increased monitoring. [ABSTRACT FROM AUTHOR]