Proposed Clinical Algorithm for Pleuroparenchymal Fibroelastosis (PPFE).

Pleuroparenchymal fibroelastosis (PPFE) is characterized by fibrosis involving the pleura and subpleural lung parenchyma, predominantly in the upper lobes. As PPFE appears to occur in patients with heterogeneous etiologies, the disease course is thus also heterogenous, with some patients showing rapid progression while others have slow progression. Therefore, it is very difficult to predict prognosis with PPFE. Needless to say, this problematic matter has influenced the treatment strategy of PPFE patients. In fact, until now no evidence has been shown for use in creating an appropriate management algorithm for PPFE. We speculate that "uncoordinated breathing" is the most important reason for dyspnea in PPFE patients. Because monitoring of physique and not just pulmonary function and radiological evaluation is also very important, particularly in PPFE patients, this review focused on the characteristics of PPFE through an overview of previous studies in this field, and we proposed an algorithm as precision medicine based on the current evidence. Multiple views by the pulmonologist are needed to standardize a clinical algorithm that is necessary to correctly assess PPFE patients under the premise of maintenance of physique by providing appropriate nutritional care and pulmonary rehabilitation.

Correlation of CT-based radiomics analysis with pathological cellular infiltration in fibrosing interstitial lung diseases.

PURPOSE: We aimed to identify computed tomography (CT) radiomics features that are associated with cellular infiltration and construct CT radiomics models predictive of cellular infiltration in patients with fibrotic ILD. MATERIALS AND METHODS: CT images of patients with ILD who underwent surgical lung biopsy (SLB) were analyzed. Radiomics features were extracted using artificial intelligence-based software and PyRadiomics. We constructed a model predicting cell counts in histological specimens, and another model predicting two classifications of higher or lower cellularity. We tested these models using external validation. RESULTS: Overall, 100 patients (mean age: 62 ± 8.9 [standard deviation] years; 61 men) were included. The CT radiomics model used to predict cell count in 140 histological specimens predicted the actual cell count in 59 external validation specimens (root-mean-square error: 0.797). The two-classification model's accuracy was 70% and the F1 score was 0.73 in the external validation dataset including 30 patients. CONCLUSION: The CT radiomics-based model developed in this study provided useful information regarding the cellular infiltration in the ILD with good correlation with SLB specimens.

Bilateral Pneumothorax after a Transbronchial Lung Cryobiopsy for Interstitial Lung Disease.

We herein report a case of bilateral pneumothorax after a unilateral transbronchial lung cryobiopsy (TBLC). A 73-year-old man with no history of cardiothoracic surgery underwent a TBLC for the reevaluation of interstitial lung disease. Five hours later, he developed bilateral pneumothorax, pneumomediastinum, and subcutaneous emphysema. He underwent bilateral chest drainage and was discharged 18 days later. The lung biopsy specimens obtained from the TBLC contained visceral pleura and bronchial cartilage, suggesting bronchial injury as the cause of the bilateral pneumothorax.

High prevalence of upper lung field pulmonary fibrosis radiologically consistent with pleuroparenchymal fibroelastosis in patients with round atelectasis.

BACKGROUND: Upper-lung field pulmonary fibrosis (upper-PF), radiologically consistent with pleuroparenchymal fibroelastosis (PPFE), was reported to develop in patients with a history of asbestos exposure and tuberculous pleurisy, indicating that chronic pleuritis is correlated with upper-PF development. Round atelectasis reportedly emerges after chronic pleuritis. This study aimed to clarify the association between round atelectasis and upper-PF. METHODS: We examined the radiological reports of all consecutive patients with round atelectasis between 2006 and 2018 and investigated the incidence of upper-PF development. RESULTS: Among 85 patients with round atelectasis, 21 patients (24.7%) were confirmed to finally develop upper-PF lesions. Upper-PF was diagnosed after round atelectasis recognition in more than half of the patients (13/21, 61.9%), whereas upper-PF and round atelectasis were simultaneously detected in the remaining 8 patients. At the time of round atelectasis detection, almost all patients (19/21, 90.5%) had diffuse pleural thickening and round atelectasis was commonly observed in non-upper lobes of 19 patients (90.5%). Fourteen patients had round atelectasis in unilateral lung, and the remaining 7 patients had round atelectasis in bilateral lungs. Among all 14 patients with unilateral round atelectasis, upper-PF developed on the same (n = 11) or both sides (n = 3). Thus, upper-PF emerged on the same side where round atelectasis was present (14/14, 100%). The autopsy of one patient revealed a thickened parietal-visceral pleura suggestive of chronic pleuritis. Subpleural fibroelastosis was also observed. CONCLUSIONS: Upper-PF occasionally develops on the same side of round atelectasis. Upper-PF may develop as a sequela of chronic pleuritis.

Very-late-onset interstitial pneumonia suspected to be related to liver transplantation more than 10 years ago.

Pulmonary complications after liver transplantation are common in the postoperative period, becoming less frequent in the subsequent months, and rare after 1 year. However, we encountered two cases of very-late-onset interstitial pneumonia suspected to be related to liver transplantation after 14 and 15 years. Both patients presented with non-specific interstitial pneumonia patterns, which significantly improved with corticosteroid therapy. Physicians should be aware of such complications and monitor them after liver transplantation.

Safety and Efficacy of Combination Therapy of Remdesivir, Baricitinib, and High-dose Steroids in Patients Hospitalized with Moderate to Severe COVID-19.

Objective Dexamethasone, remdesivir (REM), and baricitinib (BAR) are commonly used to treat coronavirus disease 2019 (COVID-19). High-dose steroids have also been reported to be well tolerated, even when used in combination with multiple drugs. In this retrospective study, we assessed the safety and therapeutic efficacy of a three-drug combination of high-dose steroids, REM, and BAR in hospitalized COVID-19 patients. Methods We retrospectively evaluated the safety and efficacy of three-drug combination therapy. Patients We evaluated 107 patients hospitalized with moderate or severe COVID-19 who underwent 3-drug combination therapy with high-dose steroids (80 mg of methylprednisolone or more, REM, and BAR) in our institution from December 2020 to June 2021. The mean age was 62.1±13.7 years old, and 71.2% were men. The severity of the study patients was as follows: 18 (16.8%) with an 8-category ordinal score of 4, 84 (78.5%) with a score of 5, and 5 (4.7%) with a score of 6. Results The frequency of high-grade adverse events was low, except for hyperglycemia (n=59, 45.8%). The median duration from symptom onset to the start of three-drug combination therapy was eight days. All but one of the patients treated with the combination therapy improved. The median time to improvement by 1 category of the eight-category ordinal score was 6 days, and the 28-day mortality was 0.9%. Conclusion This study showed the safety profile of three-drug combination therapy of high-dose steroids, REM, and BAR in moderate to severe COVID-19 patients. The three-drug combination therapy is well tolerated and has the potential to prevent exacerbation of severity.

Timeline of Oxygen Demand in Patients with COVID-19 Pneumonia.

Objective In patients with coronavirus disease 2019 (COVID-19), understanding the timeline of oxygen demand and severe respiratory failure, such as intensive care unit (ICU) admission, may clarify the therapeutic window when home-care treatment is possible and help determine the timing of treatment in hospitalized patients to improve the respiratory status. We examined the timeline of respiratory status in hospitalized patients with moderate-to-severe COVID-19 in terms of oxygen demand and ICU admission. Methods We retrospectively assessed all patients with COVID-19 who were admitted to our hospital between February 2020 and February 2021 and required supplemental oxygen. This study included 66 patients who were transferred to the ICU (ICU patients) and 144 patients who were not transferred to the ICU (non-ICU patients). Results In the total cohort, the median duration from symptom onset to the need for supplemental oxygen was 8 [interquartile range (IQR) 6-10] days. This duration was significantly shorter in ICU patients than in non-ICU patients [8 (IQR 6-9) vs. 9 (IQR 6-10) days, p=0.02]. The median duration from symptom onset to ICU admission was 9 (IQR 8-11) days in severely ill patients. The median duration from the initiation of supplemental oxygen to ICU admission was 1.0 (IQR 1-2.75) days. Only 2 of 66 patients (3.0%) were admitted to the ICU six days or later after the initiation of supplemental oxygen. Conclusion Physicians should carefully monitor each patient's condition after eight days from symptom onset. New therapies and their early administration are needed to reduce the frequency of respiratory failure in COVID-19 patients.

Disease activity of lung cancer at the time of acute exacerbation of interstitial lung disease during cytotoxic chemotherapy.

BACKGROUND: The prognosis of lung cancer patients with interstitial lung disease (ILD) is poor, and acute exacerbation (AE) of ILD can occur during chemotherapy as a fatal adverse event. Although AE-ILD development is correlated with various factors, no reports are investigating the disease activity of lung cancer at the time of AE-ILD development. METHODS: All consecutive lung cancer patients with ILD who developed chemotherapy-related AE-ILD within 28 days after the last administration of cytotoxic chemotherapy between 2011 and 2020 were retrospectively reviewed. RESULTS: Among 206 lung cancer patients with ILD who were treated with cytotoxic chemotherapy, 30 patients were included. The median age was 72 years and all patients were men with smoking history. Usual interstitial pneumonia (UIP) and non-UIP patterns of ILD was observed in 17 and 13 patients. Most of AE-ILD occurred during second- or later-line (22/30, 73.3%) and developed within first or second courses during chemotherapy (19/30, 63.3%). Regarding tumor response to chemotherapy at AE-ILD development, majority of patients (18 patients, 60.0%) experienced progressive disease and only one patient (3.3%) experienced a partial response. Notably, 27 patients (90.0%) did not exhibit any tumor shrinkage of the thoracic lesions. CONCLUSION: Lung cancer was uncontrolled with cytotoxic chemotherapy at the time of AE-ILD development. Although AE-ILD during chemotherapy has been generally discussed in terms of drug-specific adverse effects, uncontrolled lung cancer may be also correlated with AE-ILD development.

Randomized phase II study of nintedanib with or without pirfenidone in patients with idiopathic pulmonary fibrosis who experienced disease progression during prior pirfenidone administration.

INTRODUCTION: A subgroup analysis of the CAPACITY and ASCEND trials showed that pirfenidone use beyond disease progression reduced the risk of subsequent forced vital capacity (FVC) decline and death. Our study aimed to compare the efficacy and safety of nintedanib with or without pirfenidone for patients with idiopathic pulmonary fibrosis (IPF) who experienced disease progression during previous pirfenidone therapy. METHODS: In this randomized, open-label, selection design phase II trial, patients with IPF and a ≥5% relative decline in FVC within 6 months of the pirfenidone administration period were randomly assigned to nintedanib (switch group) or nintedanib plus pirfenidone (combination group). The primary endpoint was the incidence of a ≥5% relative decline in FVC or death during the first 6 months. RESULTS: Only 7 patients were enrolled (4 in the switch group and 3 in the combination group). Although the switch group continued with nintedanib for 1 year or more, 2 patients (66.7%) in the combination group discontinued nintedanib within 6 months due to severe adverse events. Given the slow case registration and safety concerns in the combination group, the trial was terminated without extending the registration. The incidence of a ≥5% relative decline in FVC during the first 6 months was 50.0% in the switch group and 66.7% in the combination group. There were no deaths during the observation period. CONCLUSIONS: Clinical trials verifying the use of pirfenidone after disease progression in IPF may be difficult to enroll patients. Definitive conclusions on both safety and efficacy cannot be drawn from the results of this study alone. TRIAL REGISTRATION: UMIN Clinical Trial Registry; registration number, UMIN000019436; date of first registration, 21/10/2015; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000022471.

Clinical characteristics of pulmonary hypertension in patients with pleuroparenchymal fibroelastosis.

BACKGROUND: This study aimed to investigate the clinical characteristics and prognosis of patients with pleuroparenchymal fibroelastosis (PPFE) and pulmonary hypertension (PH). METHODS: We retrospectively analyzed the data of patients who were diagnosed with PPFE and underwent transthoracic echocardiography (TTE) for the evaluation of their right heart systems within 3 months of their first visit between 2011 and 2018. Patients were divided into the PH and non-PH groups based on their peak tricuspid regurgitation velocity (TRV) on TTE (cutoff, 2.8 m/s). The clinical characteristics of PH and association between PH and survival among patients with PPFE were investigated. RESULTS: In total, 83 patients were enrolled. Sixteen (19.3%) patients were included in the PH group. The PH group had a lower body mass index, percent predicted forced vital capacity (FVC), 6-min walk distance, and partial pressure of arterial oxygen than the non-PH group. There was no significant difference in the presence of usual interstitial pneumonia patterns in the lower lobes between the two groups. The survival period was significantly shorter in the PH group than in the non-PH group (median survival 16.3 versus 50.2 months, log-rank p < 0.001). The multivariate Cox proportional hazard model showed that male sex (hazard ratio [HR] = 4.83, p < 0.001), Krebs von den Lungen-6 (KL-6) > 550 U/mL (HR = 3.48, p = 0.005), %FVC < 50% (HR = 3.04, p = 0.028), and peak TRV > 2.8 m/s (HR = 3.26, p = 0.038) were independently associated with poor survival. CONCLUSIONS: PH was not rare in patients with PPFE. Male sex, increased KL-6, lower FVC, and PH were independently associated with poor survival in patients with PPFE.

The new useful high-resolution computed tomography finding for diagnosing fibrotic hypersensitivity pneumonitis: "hexagonal pattern": a single-center retrospective study.

BACKGROUND: Centrilobular nodules, ground-glass opacity (GGO), mosaic attenuation, air trapping, and three-density pattern were reported as high-resolution computed tomography (HRCT) findings characteristic of fibrotic hypersensitivity pneumonitis (HP). However, it is often difficult to differentiate fibrotic HP from idiopathic pulmonary fibrosis (IPF). In fibrotic HP, the HRCT sometimes shows tortoiseshell-like interlobular septal thickening that extends from the subpleural lesion to the inner layers. This finding is called "hexagonal pattern," and this study is focused on the possibility that such finding is useful for differentiating fibrotic HP from IPF. METHODS: This study included patients with multidisciplinary discussion (MDD) diagnosis of fibrotic HP or IPF undergoing surgical lung biopsy between January 2015 and December 2017 in Kanagawa Cardiovascular and Respiratory Center. Two radiologists have evaluated the HRCT findings without clinical and pathological information. RESULTS: A total of 23 patients were diagnosed with fibrotic HP by MDD and 48 with IPF. Extensive GGO, centrilobular nodules, and hexagonal pattern were more frequent findings in fibrotic HP than in IPF. No significant difference was observed between the two groups in the presence or absence of mosaic attenuation, air trapping, or three-density pattern. In the multivariate logistic regression, the presence of extensive GGO and hexagonal pattern was associated with increased odds ratio of fibrotic HP. The sensitivity and specificity of the diagnosis of fibrotic HP in the presence of the hexagonal pattern were 69.6% and 87.5%, respectively. CONCLUSION: Hexagonal pattern is a useful finding for differentiating fibrotic HP from IPF.

Successful Treatment of Chylothorax and Chylopericardium by Radiotherapy in Lung Cancer.

A 58-year-old man was diagnosed with stage IVB lung adenocarcinoma in the right upper lobe and underwent systemic chemotherapy. Seven months after the diagnosis, large left pleural and pericardial effusion was detected. The patient developed both chylothorax and chylopericardium following superior vena cava (SVC) obstruction with mediastinal lymphadenopathy caused by lung carcinoma. Since conservative treatment of the chyle leakage was ineffective, we administered radiotherapy to treat the SVC obstruction and mediastinal lymphadenopathy. After radiotherapy, the chylothorax and chylopericardium gradually resolved, and no further chyle leaks were identified on follow-up computed tomography. This case indicates that radiotherapy can be used to ameliorate lung cancer-related chylothorax and chylopericardium.

Impact of interstitial pneumonia complications on palliative medication for terminal lung cancer: A single-center retrospective study.

BACKGROUND: Interstitial pneumonia (IP) is associated with high comorbidity of lung cancer (LC). We aimed to investigate whether concomitant IP affects palliative pharmacotherapy for end-stage symptom relief in patients with LC. METHODS: We retrospectively examined the clinical records of LC patients who died in our hospital between 2015 and 2017. The patients were divided into the IP-LC (LC with comorbid IP) and LC (LC without IP) groups according to the presence of IP to compare the use of opioid and midazolam in their terminal period. RESULTS: In total, 236 patients were enrolled in this study and divided into the IP-LC (n = 70) and LC (n = 166) groups. Among them, 51.2% and 65.7% patients in the LC and IP-LC groups, respectively, required continuous opioid administration to relieve dyspnea and/or pain. There were no significant between-group differences in the median initial and maximum doses and continuous opioid administration duration. The frequency of concomitant use of continuous midazolam and opioids was higher in the IP-LC group than in the LC group (20.5% vs. 7.1%; p = 0.01), primarily because of refractory dyspnea in all patients in both groups. The median survival time after the initiation of continuous opioid administration did not change irrespective of continuous midazolam administration. CONCLUSIONS: Compared with patients with LC, those with IP-LC are more likely to require continuous midazolam administration because continuously administered opioids alone are not sufficiently effective in relieving end-stage dyspnea among the latter.

Patients with Terminal Interstitial Pneumonia Require Comparable or More Palliative Pharmacotherapy for Refractory Dyspnea than Patients with Terminal Lung Cancer.

Background: Dyspnea is a severe symptom of terminal-stage interstitial pneumonia (IP). We commonly use continuous morphine or midazolam for terminal refractory dyspnea. Objective: We aimed to determine whether there is a difference in the use of continuous morphine and midazolam for terminal dyspnea between IP patients and lung cancer (LC) patients. Design: This is a single-center retrospective study. Setting/Subjects/Measurements: We retrospectively examined the clinical records of IP and LC patients who had died in our hospital. These patients were divided into the IP and LC groups to compare the use of morphine and midazolam. Results: Continuous morphine was administered to 50.0% of those in the IP group and 38.0% of those in the LC group for terminal dyspnea. There was no difference in the effect at six hours after morphine initiation between the two groups, but the concomitant use of continuous midazolam and morphine was more common in the IP group than in the LC group. The dose of continuous midazolam was significantly higher in the IP group than in the LC group, and the survival time after morphine initiation was significantly shorter in the IP group. Conclusions: The efficacy of continuous morphine administration for terminal dyspnea in IP patients was similar to that in LC patients for a short time after initiation, but just before death, more patients in the IP group required concomitant use of midazolam and morphine. Thus, IP patients require comparable or more palliative treatment than LC patients.

Spontaneous regression following endobronchial ultrasound-guided transbronchial needle aspiration in lung cancer patients.

Spontaneous regression (SR) is defined as a complete or partial, temporary or permanent disappearance of a tumor without anticancer treatment, which potentially develops after surgery or biopsy for primary and metastatic tumors despite unknown incidence rate. Here, we report the incidence rate of SR after endobronchial ultrasound-guided transbronchial nodal needle aspiration (EBUS-TBNA) in lung cancer patients. Among 96 patients evaluable with chest CT before and after EBUS-TBNA, SR was found in three patients (3.1%). With regards to patient characteristics, two patients had small cell lung cancer (SCLC), and one patient had adenocarcinoma. All patients had stage 3 disease with a bulky N2 stage and a history of smoking. Two patients also had interstitial lung disease. Notably, SR was observed not only at the biopsied site, but also at the non-biopsied site. Our results indicate that SR can develop following EBUS-TBNA in a substantial proportion of lung cancer patients.

Asbestos exposure and tuberculous pleurisy as developmental causes of progressive unilateral upper-lung field pulmonary fibrosis radiologically consistent with pleuroparenchymal fibroelastosis.

BACKGROUND: Unilateral upper-lung field pulmonary fibrosis (upper-PF), which is radiologically consistent with pleuroparenchymal fibroelastosis, develops after thoracic surgery. In most patients with unilateral upper-PF, aberrant intra-/extra thoracic air commonly emerges and an autopsy shows chronic pleuritis, which indicates that pleural involvement is associated with upper-PF development. If so, there may be patients with unilateral upper-PF who have a history of pleural involvement, including tuberculous pleurisy (TP) or asbestos exposure (AE). This study aimed to examine this supposition. METHODS: We examined the radiological reports of all consecutive patients from 2012 to 2018 to investigate whether there were patients having unilateral upper-PF and a history of TP or AE. RESULTS: Eight patients were included in the study. Five patients had a history of TP, and the remaining three had that of AE. All patients were men and had respiratory symptoms, and seven patients presented with restrictive ventilatory impairment. The interval between TP or last AE and upper-PF development was long, with a median of over 20 years. The upper-PF lesion was commonly located in the right lung, and aberrant intrathoracic air was observed in five patients during their clinical course. Additionally, the upper-PF lesion transformed into a cystic lesion in six patients, which resulted in Aspergillus infection in two patients. The prognosis was poor, with a median overall survival of 38 months. CONCLUSIONS: Unilateral upper-PF developed even in patients with a history of pleural involvement. Our results indicate that pleural involvement plays an important role in the development of unilateral upper-PF.

Serum Krebs von den Lungen-6 levels are associated with mortality and severity in patients with coronavirus disease 2019.

BACKGROUND: The serum Krebs von den Lungen-6 (KL-6) level is a predictive factor for acute respiratory distress syndrome (ARDS). The development of ARDS has been reported in patients with coronavirus disease 2019 (COVID-19). This study aimed to determine whether serum KL-6 levels are associated with mortality and severity in patients with COVID-19. METHODS: Among 361 Japanese patients with COVID-19 who were hospitalized at Kanagawa Cardiovascular and Respiratory Center between February 2020 and December 2020, 356 patients with data on serum KL-6 levels were enrolled and their medical records were retrospectively analyzed. RESULTS: A negative correlation was observed between KL-6 levels and the ratio of the arterial partial pressure of oxygen to the fraction of inspired oxygen on admission. The KL-6 levels on admission and the maximal KL-6 levels were higher in patients with severe disease (n = 60) than in those with nonsevere disease (n = 296). Furthermore, the maximal KL-6 levels were higher in nonsurvivors (n = 6) than in survivors (n = 350). In nonsurvivors, the KL-6 levels increased as the disease progressed. The optimal cutoff value of the maximal KL-6 level for discriminating between survivors and nonsurvivors was 684 U/mL, with a sensitivity of 83.3%, a specificity of 90.5%, and an area under the curve of 0.89. CONCLUSIONS: The serum KL-6 level was associated with disease severity. Patients with KL-6 levels ≥684 U/mL had a significantly poorer outcome than those with KL-6 levels <684 U/mL.

Comparison of Clinical Characteristics and Outcomes between Idiopathic and Secondary Pleuroparenchymal Fibroelastosis.

BACKGROUND: Pleuroparenchymal fibroelastosis (PPFE) is a unique clinical, radiologic, and histopathologic entity for which several potential etiologies have been reported recently. However, there has been no comprehensive study of secondary PPFE. OBJECTIVE: Assessment of the clinical characteristics, outcomes, and prognostic factors of secondary and idiopathic PPFE. METHODS: We retrospectively reviewed the medical records of consecutive PPFE patients between January 1999 and December 2018. We identified 132 idiopathic PPFE patients and 32 secondary PPFE patients. RESULTS: The incidence of interstitial lung disease (ILD) pattern different from the usual interstitial pneumonia (UIP) pattern in the lower lobes was higher in secondary PPFE patients (38.5%) than in idiopathic PPFE patients (61.5%, p = 0.02). The idiopathic and secondary PPFE groups did not differ significantly in terms of laboratory data, respiratory complications, and survival (median: 5.0 years vs. 4.1 years, p = 0.95). The presence of UIP pattern was independently associated with increased mortality in multivariate analyses in idiopathic PPFE patients, but not in secondary PPFE patients. CONCLUSIONS: The frequency and prognostic impact of UIP-pattern ILD differed between idiopathic and secondary PPFE patients. Lung transplantation should be considered in secondary PPFE patients with low diffusing capacity of the lungs for carbon monoxide (DLCO) regardless of lower-lobe ILD pattern.

Clinical characteristics of Japanese patients with moderate to severe COVID-19.

INTRODUCTION: Although several reports on the risk factors for severe disease of COVID-19 already exist, reports on effective early indicators are still limited, especially from Japan. This study was conducted to clarify the patient's characteristics whose disease progressed to severe status. METHODS: The medical records of all consecutive 300 Japanese patients hospitalized at our institution between February and November 2020 were retrospectively reviewed. The clinical characteristics were evaluated to compare between mild (no oxygen needed), moderate (oxygen needs of 1-4 L/min), and severe diseases (oxygen needs of 5 L/min or more). RESULTS: The median age was 68 years old, with 123 (41.0%) males and 177 (59.0%) females. Of these, 199 patients (66.3%), 55 patients (18.3%), 46 patients (15.3%) patients were in the mild disease, moderate disease, severe disease groups, respectively. Patients with severe disease were more likely to be older, have more comorbidities, and tended to have higher body mass index. In laboratory data, lymphocyte count, levels of C-reactive protein (CRP), LDH, and AST on admission were significantly associated with the severity. In multivariate analysis, age and CRP were the independent risk factors for severe disease (OR = 1.050, 1.130, respectively). The optimal cut-off value for age was 74 years old and that for CRP was 3.15 mg/dL. CONCLUSIONS: Age and CRP were independently associated with disease severity of COVID-19 in multivariate analysis. Additionally, the numbers of underlying disease, lymphocyte count, and inflammatory markers such as LDH and D-dimer may also be related to disease severity.

Tolerability and safety of nintedanib in elderly patients with idiopathic pulmonary fibrosis.

BACKGROUND: In the phase III trial of nintedanib, only 10.8% of participants were aged ≥75 years. Here, we aimed to evaluate the tolerability and safety of nintedanib in elderly patients with idiopathic pulmonary fibrosis (IPF). METHODS: In total, 71 consecutive patients with (1) IPF, (2) age ≥75 years, and (3) newly prescribed nintedanib from September 2015 to April 2018 (elderly group) were retrospectively reviewed. Patient characteristics, treatment status, and adverse events (AEs) were compared between the elderly group and 126 patients with IPF, aged <75 years, with newly prescribed nintedanib during the same period (non-elderly group). RESULTS: In the elderly group, 32 patients (46.4%) discontinued nintedanib within 6 months. Body size was significantly smaller, the incidence rates of anorexia and nausea were significantly higher, and early termination within 6 months were more common in the elderly than in the non-elderly group. In elderly patients, a univariate logistic regression analysis showed that body mass index (BMI) and percentage forced vital capacity (FVC) were risk factors for early termination (p = 0.02 and 0.03, respectively). A low initial nintedanib dose did not reduce the incidence of AEs and early termination rate in the elderly group. CONCLUSIONS: In elderly patients with IPF, the incidence of early nintedanib termination was higher, and anorexia and nausea were common AEs compared with those in non-elderly IPF patients. Treatment was frequently discontinued in elderly patients with low BMI and FVC, and chest physicians should be aware that nintedanib therapy may result in early termination in these patients.