Algorithms Identifying Patients With Acute Exacerbation of Interstitial Pneumonia and Acute Interstitial Lung Diseases Developed Using Japanese Administrative Data.

BACKGROUND: We aimed to develop algorithms to identify patients with acute exacerbation of interstitial pneumonia and acute interstitial lung diseases using Japanese administrative data. METHODS: This single-center validation study examined diagnostic algorithm accuracies. We included patients >18 years old with at least one claim that was a candidate for acute exacerbation of interstitial pneumonia, acute interstitial lung diseases, and pulmonary alveolar hemorrhage who were admitted to our hospital between January 2016 and December 2021. Diagnoses of these conditions were confirmed by at least two respiratory physicians through a chart review. The positive predictive value was calculated for the created algorithms. RESULTS: Of the 1,109 hospitalizations analyzed, 285 and 243 were for acute exacerbation of interstitial pneumonia and acute interstitial lung diseases, respectively. As there were only five cases of pulmonary alveolar hemorrhage, we decided not to develop an algorithm for it. For acute exacerbation of interstitial pneumonia, acute interstitial lung diseases, and acute exacerbation of interstitial pneumonia or acute interstitial lung diseases, algorithms with high positive predictive value (0.82, 95% confidence interval: 0.76-0.86; 0.82, 0.74-0.88; and 0.89, 0.85-0.92, respectively) and algorithms with slightly inferior positive predictive value but more true positives (0.81, 0.75-0.85; 0.77, 0.71-0.83; and 0.85, 0.82-0.88, respectively) were developed. CONCLUSION: We developed algorithms with high positive predictive value for identifying patients with acute exacerbation of interstitial pneumonia and acute interstitial lung diseases, useful for future database studies on such patients using Japanese administrative data.

Prognostic Factors for Discharge Directly Home in Patients With Thoracoscopic Surgery for Empyema: A Multicenter Retrospective Cohort Study.

Background: Video-assisted thoracoscopic surgery is a widely recommended treatment for empyema in advanced stages. However, only a few studies have evaluated prognostic factors among patients with empyema who underwent video-assisted thoracoscopic surgery. Furthermore, no studies have evaluated predictors of direct discharge home. Patients and Methods: This multicenter retrospective cohort study included 161 patients with empyema who underwent video-assisted thoracoscopic surgery in five acute-care hospitals. The primary outcome was the probability of direct discharge home. The secondary outcome was the length of hospital stay after surgery. We broadly assessed pre-operative factors and performed univariable logistic regression for the direct discharge home and univariable gamma regression for the length of hospital stay after surgery. Results: Of the 161 included patients, 74.5% were directly discharged home. Age (>70 years; -24.3%); altered mental status (-33.4%); blood urea nitrogen (>22.4 mg/dL; -19.4%); and pleural pH (<7.2; -17.6%) were associated with high probabilities of not being directly discharged home. Fever (15.2%) and albumin (> 2.7 g/dL; 20.2%) were associated with high probabilities of being directly discharged home. The median length of stay after surgery was 19 days. Age (>70 years; 6.2 days); altered mental status (5.6 days); purulence (2.7 days); pleural thickness (>2 cm; 5.1 days); bronchial fistula (14.6 days); albumin (>2.7 g/dL; 3.1 days); and C-reactive protein (>20 mg/dL; 3.6 days) were associated with a longer post-operation hospital stay. Conclusions: Physicians should consider using these prognostic factors to predict non-direct discharge to the home for patients with empyema.

Effectiveness of Immediate Video-Assisted Thoracoscopic Surgery for Empyema: A Multicentre, Retrospective Cohort Study.

BACKGROUND: Because of limitations in previous randomised controlled trials and observational studies, the effectiveness of immediate video-assisted thoracoscopic surgery (VATS) for patients with empyema in real-world settings remains unclear. OBJECTIVE: This study aimed to evaluate whether immediate VATS improves clinical outcomes in patients with empyema. METHODS: This multicentre retrospective cohort study included 744 patients with physician-diagnosed empyema from six hospitals between 2006 and 2021. The exposure was VATS performed within 3 days of empyema diagnosis, the primary outcome was 30-day mortality, and secondary outcomes were 90-day mortality, length of hospital stay, and time from diagnosis to discharge. We used propensity score weighting to account for potential confounders. For outcome analyses, we used logistic regression for mortality outcomes and gamma regression for the number of days. RESULTS: Among the 744 patients, 53 (7.1%) underwent VATS within 3 days, and 691 (92.9%) initially received conservative treatment. After propensity score weighting, the differences in 30- and 90-day mortalities between the immediate VATS and initial conservative treatment groups were 1.18% (95% confidence interval [CI], -10.7 to 13.0%) and -0.08% (95% CI, -10.3 to 10.2%), respectively. The differences in length of hospital stay and time from diagnosis to discharge were -3.22 (95% CI, -6.19 to -0.25 days) and -5.04 days (95% CI, -8.19 to -1.90 days), respectively. CONCLUSIONS: Our real-world study showed that immediate VATS reduced the length of hospital stay and the time from diagnosis to discharge. Considering the small sample and differences in protocols between countries, further large-scale studies are warranted.

Prognostic Value of Computed Tomography in Empyema: A Multicenter Retrospective Cohort Study.

Rationale: Chest computed tomography is performed in patients with empyema for various reasons. However, its predictive ability for patient outcomes in empyema has not been evaluated. Objectives: To evaluate the predictive ability of computed tomography findings (pleural thickness, loculation, interlobar pleural effusion, lung abscess, and bronchopleural fistula) for 90-day mortality in empyema. Methods: This multicenter retrospective cohort study was conducted across six acute care hospitals in Japan. We included patients with confirmed empyema diagnoses who underwent chest computed tomography within 7 days of diagnosis. Imaging findings were defined as pleural thickness, loculation, interlobar pleural effusion, lung abscess, or bronchopleural fistula. One radiologist interpreted the computed tomography scans without patient information. The primary outcome was 90-day mortality. We calculated the differences in 90-day mortality between the presence and absence of each computed tomography finding using logistic regression with or without adjustment for early thoracic surgery. Results: A total of 711 patients were included in our study. Thoracic surgery was performed in 27% of patients, and the 90-day mortality rate was 10%. The differences (95% confidence intervals) in 90-day mortality without and with adjustment for early thoracic surgery were as follows: pleural thickness, 3.09% (-1.35% to 7.54%) and 2.70% (-1.80% to 7.20%); loculation, -4.01% (-8.61% to 0.60%) and -3.80% (-8.41% to 0.81%); interlobar pleural effusion, -9.15% (-14.58% to -3.72%) and -8.96% (-14.39% to -3.53%); lung abscess, 7.04% (-1.16% to 15.2%) and 6.86% (-1.34% to 15.05%); and bronchopleural fistula, 13.80% (7.66% to 19.94%) and 13.63% (7.50% to 19.77%), respectively. Conclusions: Although interlobar pleural effusion predicted lower 90-day mortality regardless of early thoracic surgery, the presence of bronchopleural fistula predicted higher 90-day mortality with empyema. Our results warrant further validation.

Clinical phenotypes from fatal cases of acute respiratory distress syndrome caused by pneumonia.

There have been no report of objective clinical characteristics or prognostic factors that predict fatal outcome of acute respiratory distress syndrome (ARDS) since the Berlin definition was published. The aim of this study is to identify clinically available predictors that distinguish between two phenotypes of fatal ARDS due to pneumonia. In total, 104 cases of Japanese patients with pneumonia-induced ARDS were extracted from our prospectively collected database. Fatal cases were divided into early (< 7 days after diagnosis) and late (≥ 7 days) death groups, and clinical variables and prognostic factors were statistically evaluated. Of the 50 patients who died within 180 days, 18 (36%) and 32 (64%) were in the early (median 2 days, IQR [1, 5]) and late (median 16 days, IQR [13, 29]) death groups, respectively. According to multivariate regression analyses, the APACHE II score (HR 1.25, 95%CI 1.12-1.39, p < 0.001) and the disseminated intravascular coagulation score (HR 1.54, 95%CI 1.15-2.04, p = 0.003) were independent prognostic factors for early death. In contrast, late death was associated with high-resolution computed tomography (HRCT) score indicating early fibroproliferation (HR 1.28, 95%CI 1.13-1.42, p < 0.001) as well as the disseminated intravascular coagulation score (HR 1.24, 95%CI 1.01-1.52, p = 0.039). The extent of fibroproliferation on HRCT, and the APACHE II scores along with coagulation abnormalities, should be considered for use in predictive enrichment and personalized medicine for patients with ARDS due to pneumonia.

The effects of switching EGFR-TKI treatments for non-small cell lung cancer because of adverse events.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are used to treat patients with non-small cell lung cancer (NSCLC) and EGFR driver mutations. Although some patients discontinued these treatments because of adverse events, it is unclear whether switching EGFR-TKI because of adverse events provides a benefit. METHODS: This retrospective study evaluated data from 22 patients with EGFR mutation-positive NSCLC who received at least two EGFR-TKIs that were switched because of adverse events (March 2011 to September 2017). Progression-free survival 2 (PFS2) was defined as the time from starting of the first EGFR-TKI treatment to disease progression during the second EGFR-TKI treatment. RESULTS: Seventeen patients received gefitinib as the first EGFR-TKI treatment, while four patients received afatinib and one patient received erlotinib. The median time to failure of the first EGFR-TKI treatment was 1.6 months. The EGFR-TKIs were switched because of hepatotoxicity (n = 16), interstitial lung disease (n = 3), and other reasons (n = 3). The median washout period was 1.1 months. Seventeen patients received erlotinib as the second EGFR-TKI treatment, while three patients received gefitinib and two patients received afatinib. The median PFS for the second EGFR-TKI treatment was 15.2 months. The median PFS2 was 17.7 months and the median overall survival was 32.8 months. CONCLUSIONS: Switching EGFR-TKIs because of adverse events provided a clinical benefit for patients with EGFR mutation-positive NSCLC. Appropriate judgment regarding switching from one EGFR-TKI to another may improve the performance status and prognosis of patients with EGFR mutation-positive NSCLC.

Comparisons between tumor burden and other prognostic factors that influence survival of patients with non-small cell lung cancer treated with immune checkpoint inhibitors.

BACKGROUND: The use of baseline tumor burden (TB) as a prognostic factor for non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs) and associations between TB and other prognostic biomarkers remain unclear. In this study, we investigated the association between TB and survival in NSCLC patients treated with ICIs in comparison with other biomarkers. METHODS: We retrospectively evaluated 83 NSCLC patients with ICIs administered between February 2016 and December 2018. TB was measured as the sum of the unidimensional diameters of up to five target lesions. RESULTS: The median observation period was 14.2 months. A total of 42 patients died during the follow-up. Univariate Cox regression analysis showed that baseline TB was associated with OS. Cox regression analysis adjusted for Eastern Cooperative Oncology Group performance status (ECOG PS) alone or with addition of programmed cell death ligand 1 expression and treatment line showed that TB was a prognostic factor for OS. Using time-dependent receiver operating characteristic curve analysis, the optimal TB cutoff for predicting OS was 12 cm, and patients were divided into a high TB group (n = 21) and a low TB group (n = 62). The low TB group achieved significantly longer OS than the high TB group (median OS: 18.5 months, [95% CI = 11.7-not reached] vs. 2.3 months [95% CI = 1.3-2.9], P < 0.001). CONCLUSION: TB is a useful, clinically measurable prognostic factor of survival in NSCLC patients treated with ICIs.

The association between tumor burden and severe immune-related adverse events in non-small cell lung cancer patients responding to immune-checkpoint inhibitor treatment.

OBJECTIVES: The use of immune checkpoint inhibitors (ICIs) for advanced non-small cell lung cancer (NSCLC) has demonstrated survival benefits, although some treatment responders (defined as patients with non-progressive disease) are forced to discontinue treatment because of severe immune-related adverse events (irAEs). An association between treatment efficacy and irAEs has been reported. However, it is unclear which treatment responders are likely to develop severe irAEs. We aimed to examine risk factors for ICI-related severe irAEs in patients with NSCLC. MATERIALS AND METHODS: Between February 2016 and October 2018, we retrospectively evaluated 42 patients with NSCLC at our institution who responded to ICI treatment. Tumor burden was measured as the sum of the unidimensional diameters of up to five target lesions, according to the Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: ICIs were discontinued in 15 of 42 treatment responders because of severe irAEs. Tumor burden was a significant independent predictor of severe irAEs (p = 0.03). The odds ratio of severe irAEs and tumor burden over 90 mm was 8.62 (95% confidence interval = 1.96-37.9, p = 0.004). CONCLUSION: A high tumor burden was a risk factor for severe irAEs in patients with NSCLC who responded to ICI treatment.

Case report: continued treatment with alectinib is possible for patients with lung adenocarcinoma with drug-induced interstitial lung disease.

BACKGROUND: Alectinib, a second-generation anaplastic lymphoma kinase (ALK) inhibitor, is a key drug for ALK rearranged lung adenocarcinoma. Interstitial lung disease (ILD) is an important adverse effect of alectinib, which generally requires termination of treatment. However, we treated two patients with drug-induced ILD who continued to receive alectinib. CASE PRESENTATION: Patient 1 was a 57-year-old male with an ALK-rearranged Stage IV lung adenocarcinoma who was administered alectinib as first-line therapy. Computed tomography (CT) detected asymptomatic ground-glass opacity (GGO) on day 33 of treatment. Alectinib therapy was therefore discontinued for 7 days and then restarted. GGO disappeared, and the progression of ILD ceased. Patient 2 was a 64-year-old woman with an ALK-positive lung adenocarcinoma who was administered alectinib as third-line therapy. One year later, CT detected GGO; and she had a slight, nonproductive cough. Alectinib therapy was continued in the absence of other symptoms, and GGO slightly diminished after 7 days. Two months later, CT detected increased GGO, and alectinib therapy was continued. GGO diminished again after 7 days. The patient has taken alectinib for more than 2 years without progression of ILD. CONCLUSIONS: Certain patients with alectinib-induced ILD Grade 2 or less may continue alectinib therapy if they are closely managed.