Publications by authors named "Akimasa Sekine"

96 Publications

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

Palliat Med Rep 2021 16;2(1):188-193. Epub 2021 Jun 16.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama City, Japan.

Dyspnea is a severe symptom of terminal-stage interstitial pneumonia (IP). We commonly use continuous morphine or midazolam for terminal refractory dyspnea. 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. This is a single-center retrospective study. 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. 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. 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.
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http://dx.doi.org/10.1089/pmr.2021.0010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244508PMC
June 2021

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

Respir Investig 2021 Jun 22. Epub 2021 Jun 22.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan.

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.
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http://dx.doi.org/10.1016/j.resinv.2021.05.010DOI Listing
June 2021

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

Respir Investig 2021 Jun 16. Epub 2021 Jun 16.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Japan.

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.
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http://dx.doi.org/10.1016/j.resinv.2021.05.003DOI Listing
June 2021

Fungus ball removal with video-cavernoscopy for complex aspergilloma.

Gen Thorac Cardiovasc Surg 2021 May 9. Epub 2021 May 9.

Departoment of Surgery, Yokohoma City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.

Objective: Complete resection with a clear margin is the only curative treatment for pulmonary aspergilloma. This requires a high-level technique, especially for complex aspergilloma (CA), because of patient conditions and wide dense adhesions. Fungus ball removal is used palliatively to control hemoptysis, rather than as a radical procedure, and may be performed using video-cavernoscopy as a simple and repeatable method. In this study, we examined this approach as an alternative treatment for CA.

Methods: Eight cases of fungus ball removal with video-cavernoscopy (video-cavernoscopic removal) treated at our center were retrospectively reviewed. The patient characteristics and surgical outcomes were compared with those of patients treated with one-stage radical surgery.

Results: There were 8 subjects (7 males, 1 female; median age 65 years) in the video-cavernoscopic removal group and 25 subjects (19 males, 6 females; median age 56 years) in the one-stage radical surgery group. The video-cavernoscopic removal group had a higher rate of emphysematous lung (p = 0.001), a lower body mass index (p = 0.039), and a lower percent vital capacity (p = 0.027). All cases in this group had preoperative hemoptysis that ceased after the procedure. Video-cavernoscopic removal was less invasive based on a shorter operative time (p = 0.000), less blood loss (p = 0.002), and a lower Common Terminology Criteria for Adverse Events grade (p = 0.023). However, four cases in this group (50%) relapsed with a median disease-free survival period of 471.5 days.

Conclusions: Fungus ball removal with video-cavernoscopy is a simple technique for the prevention and control of massive hemoptysis that may be an alternative treatment for CA.
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http://dx.doi.org/10.1007/s11748-021-01645-xDOI Listing
May 2021

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

Respir Investig 2021 Apr 27. Epub 2021 Apr 27.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Kanagawa, Japan. Electronic address:

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.
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http://dx.doi.org/10.1016/j.resinv.2021.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075813PMC
April 2021

Identification and Characteristics of Co-isolation of Multiple Nontuberculous Mycobacteria.

Intern Med 2021 Apr 26. Epub 2021 Apr 26.

Division of Pulmonary Medicine, Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Japan.

Objective Although multiple non-tuberculous mycobacteria (NTM) species can be isolated from the same patient, little has been reported on co-isolation. We clarified the trends and characteristics of the co-isolation of multiple NTM species. Methods To collect data on multiple NTM isolation, we first extracted all patients who visited our hospital from 2006 through 2015 with a diagnosis of NTM lung diseases other than Mycobacterium avium complex (MAC) and then reviewed their medical records to evaluate the co-isolation of multiple NTM species. Results Of 213 patients with non-MAC lung disease, the most common NTM species was M. gordonae (32%), followed by M. kansasii (20%) and M. abscessus (14%). Non-MAC NTM lung disease tended to be associated with middle age with a low body mass index and male predominance. Multiple NTM species were isolated from 55 (26%) of the 213 patients. The clinical characteristics associated with multiple NTM species isolation included female predominance, never smokers and the absence of cavity lesions in the lungs. The highest co-isolation rate was observed in patients with M. gordonae isolation (30%), followed by M. furtuitum isolation (26%) and M. abscessus isolation (20%). Only MAC was isolated when co-isolated with M. abscessus. Among M. szulgai, M. peregrinum and M. terrae isolation, no other NTM species were detected. Conclusion Co-isolation of multiple NTM species was not uncommon, with 26% of patients with non-MAC NTM lung diseases showing co-isolation with multiple NTM species. Each NTM species had distinct characteristics in terms of co-isolation.
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http://dx.doi.org/10.2169/internalmedicine.5300-20DOI Listing
April 2021

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

J Clin Med 2021 Feb 18;10(4). Epub 2021 Feb 18.

Kanagawa Cardiovascular and Respiratory Center, Department of Respiratory Medicine, Yokohama 236-8651, Japan.

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%, = 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, = 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.
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http://dx.doi.org/10.3390/jcm10040846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922642PMC
February 2021

Predictive factors for the long-term use of pirfenidone in patients with fibrosing interstitial lung disease.

Respir Investig 2021 Jul 19;59(4):414-420. Epub 2021 Feb 19.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan. Electronic address:

Background: Pirfenidone is an anti-fibrotic agent approved for idiopathic pulmonary fibrosis (IPF), and long-term treatment data and the effect of continuation after disease progression have been reported. The efficacy and safety of pirfenidone in fibrosing interstitial lung disease (ILD) patients without IPF have been recently reported in clinical trials; therefore, the benefits of long-term treatment are also expected. This study aims to analyze the long-term treatment data of pirfenidone and clarify the predictive factors for long-term use of pirfenidone in non-IPF patients.

Methods: We retrospectively reviewed the records of consecutive fibrosing ILD patients who started using pirfenidone between 2008 and 2014.

Results: Of the 266 fibrosing ILD patients, 167 patients had IPF, and 99 had non-IPF. Despite the non-significant differences in body size and pulmonary function between IPF and non-IPF patients, the non-IPF patients had better overall survival than the IPF patients (median 4.06 years vs. 2.09 years, p < 0.0001). In addition, the non-IPF patients had a significantly longer time to treatment discontinuation than the IPF patients (median 2.20 years vs. 1.20 years, p = 0.002). Multivariate logistic regression analysis for ≥2 years of use of pirfenidone showed that the percent predicted forced vital capacity (%FVC) and age were predictive factors common to both IPF and non-IPF patients.

Conclusions: Our results indicate that non-IPF patients can continue using pirfenidone for longer durations than IPF patients. Initiation of pirfenidone for fibrosing ILD patients with higher %FVC and younger age would lead to long-term use of pirfenidone.
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http://dx.doi.org/10.1016/j.resinv.2021.01.002DOI Listing
July 2021

Beneficial impact of weight loss on respiratory function in interstitial lung disease patients with obesity.

Respir Investig 2021 Mar 12;59(2):247-251. Epub 2020 Nov 12.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Japan.

Background: Interstitial lung disease (ILD) patients commonly become obese or overweight due to deteriorated daily living activities and the adverse effects of prednisolone. This study aimed to clarify the effect of weight loss on pulmonary function test (PFT) in ILD patients with obesity.

Methods: Among all consecutive ILD patients with a body mass index (BMI) ≥ 27 kg/m who received nutrition education for improving obesity between June 2014 and December 2018, we retrospectively included patients who successfully decreased their body weight by over 2 kg and underwent follow-up PFT within 6 months. The results of PFT at baseline and follow-up and the level of Krebs von den Lungen-6 (KL-6) were compared.

Results: Eleven patients (5 men and 6 women; median BMI of 34.1 kg/m), were enrolled. For PFT at baseline, the percentages of forced vital capacity (%FVC), functional residual capacity (%FRC), and diffusing capacity of the lung for carbon monoxide (%DLCO) were 69.3%, 59.9%, and 54%, respectively. The median KL-6 was 1035 U/mL. The median interval from baseline to the follow-up PFTs was 41 days. Compared to the baseline results of PFT, %FVC, %FRC, and %DLCO significantly increased (p = 0.018, 0.0006, and 0.024, respectively), and the changes in body weight and FVC were strongly correlated (p = 0.0004). In addition, the median serum level of KL-6 at follow-up tended to decrease by 206.5 U/mL (p = 0.083).

Conclusion: In ILD patients with obesity, weight loss is important and potentially improves their disease course.
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http://dx.doi.org/10.1016/j.resinv.2020.10.002DOI Listing
March 2021

Tumor mutation burden as a biomarker for lung cancer patients treated with pemetrexed and cisplatin (the JIPANG-TR).

Cancer Sci 2021 Jan 30;112(1):388-396. Epub 2020 Nov 30.

Department of Genome Biology, Kindai University Faculty of Medicine, Osaka-sayama, Japan.

The JIPANG study is a randomized phase III study of pemetrexed/cisplatin (Pem/Cis) versus vinorelbine/cisplatin (Vnr/Cis) for completely resected stage II-IIIA non-squamous non-small cell lung cancer (Ns-NSCLC). This study did not meet the primary endpoint (recurrence-free survival, RFS) but Pem/Cis had a similar efficacy to Vnr/Cis with a better tolerability. Tumor mutation burden (TMB) is thought to have a predictive value of immune checkpoint inhibitors. However, the relevance of TMB to cytotoxic chemotherapy remains unknown. This exploratory study investigates the relationship between tumor mutation profiles and clinical outcome of Pem/Cis. Formalin-fixed, paraffin-embedded tumor tissues (n = 389) were obtained from the patients. Mutation status of tissue DNA was analyzed by targeted deep sequencing. Epidermal growth factor receptor (EGFR) mutations were detected frequently in Ns-NSCLC (139/374). Patients without any EGFR mutations experienced longer RFS in the Pem/Cis arm versus Vnr/Cis arms. Pem/Cis in patients with high TMB (≥12-16 mut/Mb) tended to have improved survival. In patients with wild-type EGFR, TMB ≥ 12 mut/Mb was significantly associated with improved RFS with Pem/Cis versus Vnr/Cis (not reached vs 52.5 months; hazard ratio (HR) 0.477). It could be proposed that TMB was predictive of RFS benefit with Pem/Cis versus Vnr/Cis in Ns-NSCLC. Further investigation is required to determine whether TMB combined with EGFR mutation status could be used as a predictive biomarker.
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http://dx.doi.org/10.1111/cas.14730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780021PMC
January 2021

Randomized phase II trial of carboplatin + nab-paclitaxel versus cisplatin + gemcitabine for chemotherapy-naïve squamous cell carcinoma: North Japan lung cancer study group 1302.

Int J Clin Oncol 2021 Mar 13;26(3):515-522. Epub 2020 Nov 13.

Department of Pulmonary Medicine, Sendai Kousei Hospital, 4-15 Hirosemachi, Aoba-ku, Sendai, 980-0873, Japan.

Background: A subset analysis of the CA031 trial showed significant improvement in the overall response rate after administration of carboplatin plus weekly albumin-bound paclitaxel compared to carboplatin plus paclitaxel for squamous cell carcinoma of the lung (SQ). We conducted this phase II study to compare carboplatin plus weekly albumin-bound paclitaxel (CnP) to cisplatin plus gemcitabine (CG), a standard regimen for SQ.

Methods: Chemotherapy-naïve patients with SQ were randomly assigned to receive cisplatin (80 mg/m) on day 1 plus gemcitabine (1000 mg/m) on days 1 and 8 every 3 weeks or carboplatin (area under the curve: 6 mg/mL/min) on day 1 plus nab-paclitaxel (75 mg/m) on days 1, 8, and 15 every 3 weeks. The primary endpoint was overall response rate. The secondary endpoints were progression-free survival, overall survival, disease control rate, and toxicity.

Results: Between June 2013 and October 2018, 71 patients were enrolled and assigned to either the CG arm (n = 35) or the CnP arm (n = 36) of the study. The overall response rate was 43% [95% confidence interval (CI) 27.3-58.5] in the CG arm and 47% (95% CI 31.7-62.7) in the CnP arm. Although drug combination efficacies did not differ, there were differences in toxicity: hematologic toxicities (leukopenia, neutropenia, and thrombocytopenia) were found mostly in the CG arm, whereas anemia and sensory neuropathy were more common in the CnP arm.

Conclusions: CnP had similar response as CG despite being a carboplatin-based regimen and toxicities differed between arms. Regarding ORR, CnP was comparable to CG for SQ.
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http://dx.doi.org/10.1007/s10147-020-01828-1DOI Listing
March 2021

Evaluation of lymphocytic infiltration in the bronchial glands of Sjögren's syndrome in transbronchial lung cryobiopsy.

BMC Pulm Med 2020 Oct 23;20(1):277. Epub 2020 Oct 23.

Department of Respiratory medicine, Kanagawa Cardiovascular and Respiratory Center, 6-16-1 Tomioka-Higashi, Kanazawa-ku, Yokohama city, Kanagawa, 236-0051, Japan.

Background: Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by deteriorated exocrine gland function with associated lymphocytic infiltration. However, there are few pathological studies on bronchial glands in SS. In this study, we aimed to clarify pathological features of bronchial glands in SS.

Methods: We retrospectively evaluated infiltration of lymphocytes in the bronchial glands incidentally collected by transbronchial lung cryobiopsy (TBLC), which were performed for the diagnosis of diffuse lung diseases. The degrees of lymphocyte infiltration in the bronchial glands were classified into four grades (grade 0-3). We compared the degrees of infiltration of SS with those of other diffuse lung diseases.

Results: TBLC for diagnosis of diffuse lung diseases were performed on 432 cases during the study period. The samples of 50 cases included bronchial glands. Of those, 20 cases were excluded due to insufficient size or influence of therapy. The remaining 30 cases included 17 of idiopathic interstitial pneumonias, 5 of chronic hypersensitivity pneumonia, 6 of connective tissue disease (SS; n = 4, systemic sclerosis; n = 1, dermatomyositis; n = 1) and 2 of other diseases. In SS, infiltration of lymphocytes was observed in all cases; grade 1 in one, grade 2 in one, and grade 3 in two cases. In contrast, 11 of 26 in other diseases showed no lymphocytes infiltration, with the remaining 15 of grade 1 infiltration. Grade 2 or more infiltration were found only in SS but not in other diseases.

Conclusion: Our results suggested that high-grade lymphocytic infiltration of bronchial glands is a distinct characteristics in SS.
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http://dx.doi.org/10.1186/s12890-020-01318-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585306PMC
October 2020

Intermediate bronchial kinking after right upper lobectomy for lung cancer.

Asian Cardiovasc Thorac Ann 2021 Jan 21;29(1):19-25. Epub 2020 Sep 21.

Department of Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Background: Bronchial kinking after lung lobectomy is likely, whereas that of the intermediate bronchus after right upper lobectomy is often not recognized. The aim of this study was to examine the clinical implications of this condition.

Methods: One-hundred cases of right upper lobectomy for primary lung cancer were reviewed. The cases were divided into groups with intermediate (group A) and non-intermediate (group B) bronchial kinking, and the patient characteristics and postoperative outcomes were compared. The remaining lower lobe deformation was also evaluated using the angle formed by the intrathoracic tracheal line and posterior fissure on reconstructed sagittal computed tomography.

Results: There were 23 cases in group A which had a higher rate of bronchial calcification, older age, and female sex, whereas and smoking and pulmonary emphysema were less frequent. Three cases in group A had respiratory symptoms such as wheezing and respiratory noise, while only one case of middle lobe atelectasis was found in group B. In multivariate analysis, upper mediastinal lymph node dissection was an independent factor for non-intermediate bronchial kinking. The lower lobe was significantly more expanded in group A than in group B.

Conclusions: Intermediate bronchial kinking correlates with postoperative respiratory symptoms and was less likely after upper mediastinal lymph node dissection.
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http://dx.doi.org/10.1177/0218492320960325DOI Listing
January 2021

First-line pembrolizumab vs chemotherapy in metastatic non-small-cell lung cancer: KEYNOTE-024 Japan subset.

Cancer Sci 2020 Dec 16;111(12):4480-4489. Epub 2020 Oct 16.

Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan.

This prespecified subanalysis of the global, randomized controlled phase III KEYNOTE-024 study of pembrolizumab vs chemotherapy in previously untreated metastatic non-small-cell lung cancer without EGFR/ALK alterations and a programmed death ligand 1 (PD-L1) tumor proportion score of 50% or higher evaluated clinical outcomes among patients enrolled in Japan. Treatment consisted of pembrolizumab 200 mg every 3 weeks (35 cycles) or platinum-based chemotherapy (four to six cycles). The primary end-point was progression-free survival; secondary end-points included overall survival and safety. Of 305 patients randomized in KEYNOTE-024 overall, 40 patients were enrolled in Japan (all received treatment: pembrolizumab, n = 21; chemotherapy, n = 19). Median progression-free survival was 41.4 (95% confidence interval [CI], 4.2-42.5) months with pembrolizumab and 4.1 (95% CI, 2.8-8.3) months with chemotherapy (hazard ratio [HR], 0.27 [95% CI, 0.11-0.65]; one-sided, nominal P = .001). Median overall survival was not reached (NR) (95% CI, 22.9-NR) and 21.5 (95% CI, 5.2-35.0) months, respectively (HR, 0.39 [95% CI, 0.17-0.91]; one-sided, nominal P = .012). Treatment-related adverse events occurred in 21/21 (100%) pembrolizumab-treated and 18/19 (95%) chemotherapy-treated patients; eight patients (38%) and nine patients (47%), respectively, had grade 3-5 events. Immune-mediated adverse events and infusion reactions occurred in 11 pembrolizumab-treated patients (52%) and four chemotherapy-treated patients (21%), respectively; four patients (19%) and one patient (5%), respectively, had grade 3-5 events. Consistent with results from KEYNOTE-024 overall, first-line pembrolizumab improved progression-free survival and overall survival vs chemotherapy with manageable safety among Japanese patients with metastatic non-small-cell lung cancer without EGFR/ALK alterations and a PD-L1 tumor proportion score of 50% or higher. The trial is registered with Clinicaltrials.gov: NCT02142738.
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http://dx.doi.org/10.1111/cas.14647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734005PMC
December 2020

Outcome of early-stage combination treatment with favipiravir and methylprednisolone for severe COVID-19 pneumonia: A report of 11 cases.

Respir Investig 2020 Aug 28. Epub 2020 Aug 28.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan. Electronic address:

Although the use of corticosteroids is not recommended in the World Health Organization statement for the treatment of coronavirus disease 2019 (COVID-19), steroid therapy may be indicated for critical cases in specific situations. Here, we report the successful treatment of 11 cases of severe COVID-19 pneumonia with favipiravir and methylprednisolone. All cases were severe and patients required oxygen administration or had a blood oxygen saturation ≤93% on room air. All were treated with favipiravir and methylprednisolone, and 10 of 11 patients responded well and required no further oxygen supplementation or ventilator management. This study shows the importance of the early-stage use of a combination of favipiravir and methylprednisolone in severe cases to achieve a favorable clinical outcome.
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http://dx.doi.org/10.1016/j.resinv.2020.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455106PMC
August 2020

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

Respir Investig 2021 Jan 3;59(1):99-105. Epub 2020 Sep 3.

Kanagawa Cardiovascular and Respiratory Center, Department of Respiratory Medicine, Tomioka-Higashi 6-16-1, Kanazawa-ku, Yokohama, 236-0051, Japan. Electronic address:

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.
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http://dx.doi.org/10.1016/j.resinv.2020.08.003DOI Listing
January 2021

Small-cell lung carcinoma transformation of lung adenocarcinoma diagnosed by pericardial effusion: A case report.

Mol Clin Oncol 2020 Aug 3;13(2):129-132. Epub 2020 Jun 3.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Kanagawa 236-0051, Japan.

The present report describes a case of a 68-year-old male patient with epidermal growth factor receptor (EGFR)-mutant non-small cell lung carcinoma (NSCLC). After cytotoxic chemotherapy of three regimens following 22 months of treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs), including osimertinib, the patient underwent S-1 treatment. Despite a decrease in carcinoembryonic antigen 1 month after initiating S-1 treatment, the patient developed cardiac tamponade. The evaluation of pericardial effusion confirmed small-cell lung carcinoma (SCLC) transformation. Subsequently, a combination therapy of carboplatin and etoposide was administered, which led to a marked improvement in imaging. In patients with NSCLC who develop pericardial effusion after long-term EGFR-TKI therapy, including osimertinib treatment, it is important to investigate whether SCLC transformation occurs or not as a treatable entity.
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http://dx.doi.org/10.3892/mco.2020.2059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366234PMC
August 2020

Unilateral upper lung-field pulmonary fibrosis radiologically consistent with pleuroparenchymal fibroelastosis after thoracic surgery: Clinical and radiological courses with autopsy findings.

Respir Investig 2020 Jul 10. Epub 2020 Jul 10.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan.

Background: Pleuroparenchymal fibroelastosis (PPFE) is a rare idiopathic interstitial pneumonia characterized by pleural and parenchymal involvements predominantly in the upper lobes. Unilateral upper-lung field pulmonary fibrosis (upper-PF) radiologically consistent with PPFE was recently reported in patients with a history of open thoracotomy and presented with impaired thoracic movements in the operated side with unknown mechanisms. This retrospective study aimed to elucidate the clinical and radiological courses and pathological findings of unilateral upper-PF.

Methods: All the consecutive patients diagnosed as having unilateral upper-PF between March 2012 and April 2018 were included. Radiological images and clinical courses before and after the diagnosis were thoroughly reviewed.

Results: Fourteen patients were included. Unilateral upper-PF was diagnosed after a median of 4.8 years from the open thoracotomy or video-assisted thoracic surgery for treating lung or esophageal cancer, or bronchiectasis. Before or at diagnosis, 12 (85.7%) of 14 patients developed aberrant intrathoracic/extrathoracic air suggestive of pleural fistula, although the degree was slight. Of note, the upper-PF lesion apparently deteriorated once aberrant air emerged in all the patients. After diagnosis, the upper-PF lesion transformed into cystic lesion in 9 patients, 4 of whom eventually developed pulmonary aspergillosis. The prognosis was poor, with a median overall survival of 49.3 months. The autopsy in one patient demonstrated findings consistent with PPFE and chronic pleuritis.

Conclusions: Unilateral upper-PF developed after thoracic surgeries and had many clinical, radiological, and pathological characteristics in common with idiopathic PPFE. Our results indicate that the commonly observed aberrant air may be correlated with disease development and progression.
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http://dx.doi.org/10.1016/j.resinv.2020.05.001DOI Listing
July 2020

Miliary lung metastases from ROS1-rearranged lung adenocarcinoma: A case report.

Mol Clin Oncol 2020 Jul 4;13(1):80-82. Epub 2020 May 4.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Kanagawa 236-0051, Japan.

Miliary lung metastases are a rare form of metastasis of non-small-cell lung carcinoma. Miliary lung metastases commonly develop in lung adenocarcinoma with epidermal growth factor receptor mutation. In the present study, we present a case of miliary lung metastases from lung adenocarcinoma with ROS1 rearrangement. The patient, who had a history of surgery for stage IIIA lung adenocarcinoma, presented to our hospital with cough, dyspnea, and severe hypoxia. Chest computed tomography showed numerous tiny, randomly distributed nodules throughout both lungs. No metastases were observed in other organs. Molecular profiling of the surgical specimens was positive for ROS1 rearrangement. The results suggest that chest physicians should be aware that miliary lung metastases can develop in patients with lung adenocarcinoma with ROS1 rearrangement.
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http://dx.doi.org/10.3892/mco.2020.2040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241238PMC
July 2020

Effectiveness and Safety of Bronchial Thermoplasty in the Treatment of Severe Asthma with Smoking History: A Single-Center Experience.

Int Arch Allergy Immunol 2020 19;181(7):522-528. Epub 2020 May 19.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan.

Introduction: Bronchial thermoplasty (BT) improves asthma-related quality of life and decreases the number of asthma exacerbations. However, the effectiveness of BT in the treatment of severe asthma with smoking history is unclear because previous studies have excluded patients with smoking history of more than 10 pack-years.

Objective: The aim of the study was to clarify the effectiveness and safety of BT for severe asthma with smoking history.

Methods: We retrospectively reviewed patients who received BT and compared its effectiveness and safety with and without smoking history.

Results: Seven patients were assigned to the smoking group and 9 to the nonsmoking group. Before BT, despite Global Initiative for Asthma step 4 or 5 treatment including oral corticosteroids (OCS) or monoclonal antibody drugs, most patients in both groups had asthma-related symptoms every day (85.7 vs. 77.8%; p = 0.475) and frequent asthma exacerbations. After BT, in the smoking group, 3 patients could discontinue or reduce OCS and all 3 patients treated with monoclonal antibody drugs could discontinue them. In the smoking group, 6 patients (85.7%) experienced a reduction in the rate of symptoms, of which 3 patients (42.9%) had a disappearance of symptoms, similar to the nonsmoking group. BT was effective in 5 patients (83.3%) in the smoking group and 6 patients (75.0%) in the nonsmoking group. There were no severe complications.

Conclusions: BT was found to be effective and safe for treatment of severe asthma with smoking history. Our results suggest that BT may be a therapeutic option for asthma-chronic obstructive pulmonary disease overlap.
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http://dx.doi.org/10.1159/000507446DOI Listing
November 2020

Five cases of V600E-mutant lung adenocarcinoma with high expression of programmed death ligand 1.

Respir Med Case Rep 2020 1;30:101071. Epub 2020 May 1.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan.

We reported consecutive five patients with V600E-mutant recurrent or advanced non-small cell lung cancer who were identified between April 2016 and June 2019. All five patients had high programmed death ligand 1 (PD-L1) tumor proportion scores (50, 55, 75, 95 and 100%). Four of the five patients received regimens including pembrolizumab. Of them, one patient experienced a partial response, but two patients experienced progressive disease and one patient was not evaluable. Three of the four patients received regimens including pemetrexed were able to continue long-term treatment. The presence of a mutation may be associated with higher levels of PD-L1 expression. The effect of immune checkpoint inhibitors therapy in patients with mutation was similar to the previous reports in patients with previously treated advanced non-small cell lung cancer with PD-L1 tumor proportion score ≥50%. Chemotherapy regimens including pemetrexed may have a positive effect in patients with V600E-mutant lung adenocarcinoma. Accumulation of additional Case series is necessary to confirm our results.
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http://dx.doi.org/10.1016/j.rmcr.2020.101071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218153PMC
May 2020

Pulmonary Malignant Ameloblastoma without Local Recurrence 31 Years after Primary Resection: A Case Report and Literature Review.

Intern Med 2020 Jun 5;59(11):1423-1426. Epub 2020 Mar 5.

Respiratory Medicine, Tokyo Metropolitan Toshima Hospital, Japan.

A 78-year-old man with a history of surgical resection for ameloblastoma 31 years earlier visited our hospital for prolonged cough. Chest computed tomography showed multiple nodules in both lungs. Although there was no local recurrence in the mandible, the specimen taken from a transbronchoscopic bronchial biopsy showed recurrent ameloblastoma. Despite receiving no treatment, the disease in our patient remained clinically stable for 8.4 years. Chest physicians should be aware that pulmonary malignant ameloblastoma can first relapse several decades after curative surgery. In addition, pulmonary malignant ameloblastoma without local recurrence may be associated with a good prognosis.
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http://dx.doi.org/10.2169/internalmedicine.3716-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332631PMC
June 2020

Promising Effects of Benralizumab on Chronic Eosinophilic Pneumonia.

Intern Med 2020 May 1;59(9):1195-1198. Epub 2020 Feb 1.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Japan.

We herein report a case of refractory chronic eosinophilic pneumonia (CEP) complicated with uncontrolled bronchial asthma, in which remission was successfully induced with single dose of benralizumab, a monoclonal antibody against the alpha-chain of the interleukin-5 receptor. Resolution of the patient's symptoms and consolidation on chest X-ray were observed at 2 weeks and lasted for 8 weeks after the administration of benralizumab. Benralizumab would be a novel alternative choice of treatment for CEP patients who are at risk of potential toxicity due to long-term corticosteroid therapy.
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http://dx.doi.org/10.2169/internalmedicine.3606-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270749PMC
May 2020

Transbronchial lung cryobiopsy in idiopathic acute fibrinous and organizing pneumonia.

Respir Med Case Rep 2019 18;28:100888. Epub 2019 Jun 18.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan.

A 53-year-old Japanese female was admitted to our hospital with 3-week history of cough and worsening dyspnea. Chest computed tomography revealed unilateral focal consolidation in the right lower lobe. She underwent transbronchial lung cryobiopsy (TBLC) and histology showed acute fibrinous and organizing pneumonia (AFOP). High-dose methylprednisolone treatment improved her respiratory condition and radiological findings. AFOP is a rare histologic interstitial pneumonia pattern and has been diagnosed by surgical lung biopsy or autopsy in most cases. To our knowledge, this is the first detailed report of AFOP diagnosed by TBLC. TBLC can be performed safely with less invasion and be a useful diagnostic technique for rapidly progressive diffuse lung disease such as AFOP.
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http://dx.doi.org/10.1016/j.rmcr.2019.100888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597736PMC
June 2019

Safety of pyrazinamide-including regimen in late elderly patients with pulmonary tuberculosis: A prospective randomized open-label study.

J Infect Chemother 2019 Dec 19;25(12):1026-1030. Epub 2019 Jun 19.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, 6-16-1 Tomioka-higashi, Kanazawa-ku, Yokohama, 236-0051, Japan.

Pyrazinamide (PZA) -including regimen had not been fully recommended for late elderly patients with tuberculosis (TB) by Japanese Society for Tuberculosis until 2018. Studies on the safety of adding PZA to other first-line TB drugs for late elderly patients are limited. In this prospective randomized open-label study, we aimed to assess the safety of regimen including PZA for patients aged 80 or older. Patients in their eighties with smear-positive pulmonary TB without any liver diseases were randomly assigned to HRE (isoniazid, rifampicin, ethambutol) group or HREZ (HRE and PZA) group. The primary endpoint was discontinuation or interruption rate of treatment due to liver injury. Other endpoint included overall rate of liver injury, time to culture conversion, and overall mortality. Eighty-nine patients were assigned to either HRE group (n = 45) or HREZ group (n = 44). Clinical background was not different in two groups including age, smear grade, body weight, serum albumin, and activity degree. Discontinuation of treatment due to liver injury occurred in 15.6% of HRE group and 9.1% of HREZ group, which showed no statistical difference. Incidence of liver injury was also comparable between two groups. Overall mortality was statistically higher in HREZ group (3 in HRE vs. 10 in HREZ), although all deaths seemed to be irrelevant to PZA use. Time to culture conversion was significantly shorter in HREZ group (43.6 days vs. 30.2 days). In conclusion, regimen including PZA seems to be safe for late elderly patients with pulmonary TB.
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http://dx.doi.org/10.1016/j.jiac.2019.05.030DOI Listing
December 2019

Nivolumab for advanced non-small cell lung cancer patients with mild idiopathic interstitial pneumonia: A multicenter, open-label single-arm phase II trial.

Lung Cancer 2019 08 3;134:274-278. Epub 2019 Jun 3.

Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan.

Objectives: The efficacy of nivolumab against metastatic non-small cell lung cancer (NSCLC) has been demonstrated; however, pneumonitis is relatively common and is a potentially life-threatening immune-related adverse event. Patients with idiopathic interstitial pneumonia (IIP) have a higher risk of pneumonitis and are generally excluded from clinical trials. Additionally, to date, a multicenter prospective trial for previously-treated NSCLC patients with IIP has not been performed. To fulfill this unmet medical need, we conducted a multicenter, open-label single-arm phase II trial to evaluate the efficacy and safety of nivolumab in NSCLC patients with mild IIP.

Materials And Methods: Eligible patients had previously-treated, inoperable NSCLC with mild IIPs. Mild IIP was defined as a predicted vital capacity of at least 80% and possible usual interstitial pneumonia (UIP) or inconsistent with UIP pattern by chest high-resolution computed tomography. Primary end point was the 6 months PFS rate and secondary end point was the safety of this therapy.

Results: Eighteen patients were enrolled in this trial. Six months PFS rate was 56%, response rate was 39%, and disease control rate was 72%. There were no treatment-related deaths. One drug-related grade 3/4 nonhematologic event (grade 3 neurotoxicity) was observed. Two patients had grade 2 pneumonitis which improved by corticosteroid therapy.

Conclusions: Nivolumab could be an effective therapy for NSCLC patients with mild IIPs.
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http://dx.doi.org/10.1016/j.lungcan.2019.06.001DOI Listing
August 2019

Pemetrexed-induced Interstitial Lung Disease Mimicking Hypersensitivity Pneumonia: A Pathologically Proven Case.

Intern Med 2019 Sep 7;58(18):2679-2682. Epub 2019 Jun 7.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Japan.

We herein report a 45-year-old woman with lung adenocarcinoma stage IV (cT4N3M1a). She was treated with pemetrexed (PEM) monotherapy following four cycles of first-line treatment with carboplatin, paclitaxel, and veliparib. After three cycles of PEM treatment, she presented with dyspnea, and chest computed tomography showed diffuse ground-glass attenuation (GGA), suggesting hypersensitivity pneumonia (HP). Bronchoalveolar lavage revealed a marked increase in lymphocytes (90.5%), and a transbronchial lung biopsy confirmed lymphocytic alveolitis with granuloma. Because her symptoms and diffuse GGA were spontaneously resolved with PEM discontinuation alone, PEM-induced interstitial lung disease was diagnosed. Chest physicians should be aware that PEM can induce HP-type interstitial lung disease.
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http://dx.doi.org/10.2169/internalmedicine.2548-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6794179PMC
September 2019

Interstitial Lung Disease with Anti-melanoma Differentiation-associated Protein 5 Antibody: Rapidly Progressive Perilobular Opacity.

Intern Med 2019 Sep 7;58(18):2605-2613. Epub 2019 Jun 7.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Japan.

Objective Rapidly progressive interstitial lung disease (RP-ILD) with anti-melanoma differentiation-associated protein 5 (MDA5) antibody potentially presents with a fatal clinical course and requires early intensive treatment. Recently, perilobular opacity was reported to pathologically correspond to the acute phase of diffuse alveolar damage in RP-ILD with anti-MDA5 antibody. We aimed to investigate whether or not perilobular opacity was a common radiological finding in RP-ILD patients with anti-MDA5 antibody. Methods We conducted a retrospective review of the medical records of eight consecutive patients with RP-ILD with anti-MDA5 antibody. The clinical features and radiological findings of follow-up computed tomography (CT) during the course of their disease were evaluated. Results Among eight RP-ILD patients with anti-MDA-5 antibody, six showed perilobular opacity in the lower lobes, and the remaining two had only consolidation on high-resolution CT. Of note, the perilobular opacity in all six patients thickened and progressed to consolidation with a loss of lung volume in a short period. Despite intensive treatment, 6 patients (75%) died within 100 days after the first visit. Notably, the two patients with consolidation presented with a very rapid clinical course and died in 13 days each. In the two survivors, the perilobular opacity and consolidation recovered with improvement in the loss of lung volume. Conclusion Rapidly progressive perilobular opacity that thickens and progresses to consolidation is characteristic of RP-ILD with anti-MDA5 antibody. Chest physicians should immediately check the status of anti-MDA-5 antibody in order to initiate early aggressive therapy in RP-ILD patients with rapidly progressive perilobular opacity.
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http://dx.doi.org/10.2169/internalmedicine.2328-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6794190PMC
September 2019

Evaluation of changes in the serum levels of Krebs von den Lungen-6 and surfactant protein-D over time as important biomarkers in idiopathic fibrotic nonspecific interstitial pneumonia.

Respir Investig 2019 Sep 16;57(5):422-429. Epub 2019 Apr 16.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, 6-16-1 Tomioka-higashi, Kanazawa-ku, Yokohama 236-0051, Japan. Electronic address:

Background: Some cases of idiopathic fibrotic nonspecific interstitial pneumonia (f-NSIP) show a progressive course that is similar to that of idiopathic pulmonary fibrosis. However, it is difficult to predict poor patient outcomes. This study aimed to evaluate whether serial changes in serum levels of Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D) can predict disease progression.

Methods: We retrospectively analyzed the medical records of 75 patients with idiopathic f-NSIP. Disease behavior was categorized into two groups depending on long-term change of pulmonary function: progressive type (≥5%/year relative decline in the slope of forced vital capacity [FVC] and/or ≥7.5%/year relative decline in the slope of %diffusing capacity of the lung for carbon monoxide [%D]) and stable type. Levels of KL-6 and SP-D and results of pulmonary function tests, which were performed parallelly, were reviewed and analyzed using a linear mixed-effects model.

Results: The study subjects comprised 62 patients with stable type and 13 patients with progressive type disease behavior. Among these subjects, 50 patients fulfilled the diagnostic criteria of interstitial pneumonia with autoimmune features (IPAF). Serum levels of both KL-6 and SP-D at baseline showed a negative correlation with %D, but not with FVC, and these biomarkers were not related to disease progression. Persistently high levels of KL-6 and SP-D correlated with progressive type disease behavior in idiopathic (non-IPAF) f-NSIP.

Conclusions: Changes in serum KL-6 and SP-D levels over time may provide useful predictive information on disease behavior during treatment in patients with idiopathic f-NSIP and especially in those with non-IPAF f-NSIP.
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http://dx.doi.org/10.1016/j.resinv.2019.03.006DOI Listing
September 2019

Negative impact of anorexia and weight loss during prior pirfenidone administration on subsequent nintedanib treatment in patients with idiopathic pulmonary fibrosis.

BMC Pulm Med 2019 Apr 11;19(1):78. Epub 2019 Apr 11.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Tomioka-Higashi 6-16-1, Kanazawa-ku, Yokohama, 236-0051, Japan.

Background: Current clinical practice guidelines for idiopathic pulmonary fibrosis (IPF) conditionally recommend use of pirfenidone and nintedanib. However, an optimal treatment sequence has not been established, and the data of treatment sequence from pirfenidone to nintedanib are limited. This study aimed to evaluate safety, tolerability and efficacy of nintedanib switched from pirfenidone in patients with IPF.

Methods: Thirty consecutive IPF cases, which discontinued pirfenidone because of a decline in forced vital capacity (FVC) or intolerable adverse event (AE), and newly started nintedanib (150 mg twice daily) from September 2015 to August 2017 (switch-group) were retrospectively reviewed. Subsequently, we compared the characteristics, treatment status, and AEs between the switch-group and other 64 IPF patients newly started nintedanib during the same period without any prior anti-fibrotic treatment (pirfenidone-naïve group).

Results: In the switch group, median age, body weight, body mass index (BMI), and %FVC were 72 years old, 54.9 kg, 21.0 kg/m, and 52.9%, respectively. Most common AE of nintedanib was aspartate aminotransferase/alanine aminotransferase elevation (71.9%), followed by anorexia (46.7%) and diarrhea (46.7%); whereas, anorexia (63.3%) and ≥ 5% weight loss from baseline (56.7%) were common during pirfenidone administration. Sixteen patients (53.3%) discontinued nintedanib within 6 months (early termination). Multivariate logistic regression analysis revealed a significant association between low BMI and early nintedanib termination in the switch-group (p = 0.0239). Nintedanib suppressed FVC decline as compared with that during administration period of pirfenidone in 70% of the patients who could undergo lung function before and after switching to nintedanib. The incidence of early termination of nintedanib was higher in the switch-group than in the pirfenidone-naïve group, whereas body-weight, BMI, absolute FVC values, and %FVC were significantly lower in the switch-group (just before nintedanib initiation) than in the pirfenidone-naïve group. Nintedanib-induced anorexia was more frequent and severer in the switch-group than in the pirfenidone-naïve group, but no significant differences were observed in terms of other AEs.

Conclusions: A high incidence of early termination of nintedanib was noted when patients were switched from pirfenidone. Anorexia and weight loss during prior pirfenidone administration may increase the rate of the early termination of subsequent nintedanib treatment.
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http://dx.doi.org/10.1186/s12890-019-0841-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458823PMC
April 2019
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