A Retrospective Study of Pneumococcal Pneumonia in Hospitalized Patients Aged ≥65 Years in Izumo, Japan: 2010 to 2014.

Purpose: In Japan, both a 23-valent pneumococcal polysaccharide vaccine (PPSV23) and a 13-valent pneumococcal conjugate vaccine (PCV13) are available. Although randomized controlled trials have examined the effects of pneumococcal vaccines, few epidemiological studies have investigated the onset of pneumococcal pneumonia in general practice. In Izumo, Shimane Prefecture, Japan, a public subsidy for PPSV23 inoculation began in November 2012. Patients and Methods: The subjects were pneumonia patients aged 65 and over who were admitted to a hospital in Izumo. This retrospective study analyzed the following data extracted from medical records: pneumococcal pneumonia prevalence, pneumonia severity, mortality rate, PPSV23 vaccination rate, and length of hospital stay. The 2 years before the start of the public subsidy were defined as the early phase, and the 2 years after the subsidy initiation were defined as the late phase. We compared the two phases in terms of PPSV23 vaccination rate, prevalence and severity of pneumococcal pneumonia, and mortality rate. Results: We investigated data from a total of 1188 and 1086 patients in the early and late phases, respectively. The prevalence of pneumococcal pneumonia was 21.0% and 21.3% in the early and late phases, respectively. The mortality rate from pneumococcal pneumonia was 10.4% and 5.4% in the early and late phases, respectively (p = 0.080), indicating a 50% reduction. The PPSV23 vaccination rate (p < 0.001) and the comorbidity rates of chronic respiratory disease (p = 0.022) and chronic renal disease (p < 0.001) were significantly different between the early and late phases. Conclusion: This study showed that the rate of in-hospital deaths due to pneumococcal pneumonia was halved after the PPSV23 vaccine was subsidized. The causal relationship between the pneumococcal vaccination rate and the mortality rate of pneumococcal disease was unclear. Further investigation is deemed necessary.

Efficacy of erlotinib and its effects on the quality of life of older patients with epidermal growth factor receptor-mutant non-small cell lung cancer: A prospective, multicenter, dose-modification study.

AIM: Gefitinib and erlotinib are efficacious and safe for older patients with epidermal growth factor receptor-mutant non-small cell lung cancer. However, prolonged use of epidermal growth factor receptor-tyrosine kinase inhibitors in older patients is difficult, owing to potential adverse events. Hence, dose reduction or treatment discontinuation is often required. We investigated the efficacy of low-dose first-line erlotinib and its effects on the quality of life of older patients with lung cancer. METHODS: A prospective, multicenter, phase II clinical trial was carried out in patients aged ≥75 years with epidermal growth factor receptor-mutant non-small cell lung cancer. Initially, 100 mg/day erlotinib was administered orally; if well tolerated, it was increased to 150 mg/day. The primary end-point was progression-free survival, and secondary end-points were the response rate, overall survival and change in quality of life ("Care Notebook" questionnaire). RESULTS: The median progression-free survival was 17.8 months, response rate was 63.6% and median overall survival was 27.8 months. The change in the quality of life after 6 weeks was assessed in 72.7% of the patients. Fatigue, pain, anxiety and deterioration in daily activities were found in at least 40% of the patients. Despite the therapeutic effect of 100 mg/day erlotinib, many patients required dose reduction, and in some, the quality of life could not be maintained. CONCLUSIONS: Many older patients with epidermal growth factor receptor-mutant non-small cell lung cancer might require treatment dose reduction. Further studies are required to develop individualized treatments for older patients with lung cancer. Geriatr Gerontol Int 2021; 21: 881-886.

Clinical Management of Asthma by Respiratory Specialists versus General Practitioners: Questionnaire Survey Results Over 6 Years.

BACKGROUND: In Japan, the Ministry of Health, Labour and Welfare population dynamics investigation showed a decrease in the number of deaths related to asthma in recent years. In 2016, the mortality rate was 1.2 deaths per 100,000 population. There were regional differences; Shimane Prefecture had a higher mortality rate (1.6 deaths per 100,000 population in 2016) than other prefectures. In this study, to clarify problems in asthma treatment, we evaluated the status of asthma treatment in Shimane Prefecture. METHODS: We performed three cross-sectional questionnaire surveys, in October 2006, February 2009, and February 2012. We received responses from 78 clinics and hospitals. Subjects were patients with bronchial asthma over 14 years of age who regularly visited an outpatient clinic. Survey items included smoking status, control status assessed using the Asthma Control Test (ACT), treatment, and medication adherence. Doctors board-certified by the Japanese Respiratory Society were defined as respiratory specialists (RSs) and other doctors were defined as general practitioners (GPs). We compared various factors between the RS and GP groups. RESULTS: Clinical data of 2159 patients were available for analysis. The proportion of patients with ACT score ≥ 20 points increased significantly between 2006 and 2012 in the GP group. The rate of inhaled corticosteroid use increased in the GP group from 63.6% to 76.4%. CONCLUSION: It was suggested that asthma control and the rate of inhaled corticosteroid use were related. We should continue educating GPs about asthma treatment.

Antibiotic-induced reduction of abnormal lung shadow in pulmonary nodular lymphoid hyperplasia.

Pulmonary nodular lymphoid hyperplasia (PNLH) involves proliferative lymphatic tissues and is reportedly associated with inflammatory disease or autoimmune disorders. Herein, we describe a case of PNLH with difficult diagnosis because of antibiotics therapy-induced reduction in the abnormal tumour shadow. An 86-year-old man was admitted for persistent cough and bloody sputum. Computed tomography (CT) revealed a mass in the right middle lobe, which got smaller on treatment with tosufloxacin for pneumonia. Unexpectedly, the tumour shadow remained one month later. Positron emission tomography depicted fluorodeoxyglucose uptake at the site. Although lung cancer was suspected, the mass was non-diagnostic on transbronchial and CT-guided biopsies. He was eventually diagnosed with PNLH on post-surgical histological analysis of the lung mass. Neutrophil accumulation and bacterial lumps were present, indicating Actinomyces infection in the pulmonary alveolus, suggesting that PNLH was associated with pneumonia. Histopathological examination helped identify the aetiology of this rare case of PNLH.

Pleuroparenchymal fibroelastosis after haematopoietic stem cell transplantation without graft-versus-host disease findings.

Although rare, pleuroparenchymal fibroelastosis (PPFE) is a serious late-onset complication of haematopoietic stem cell transplantation (HSCT). It remains unclear whether graft-versus-host disease (GVHD) is involved in the development of PPFE. We report the case of a patient with PPFE after HSCT. The patient experienced pneumothorax repeatedly despite surgical treatment. A surgical specimen demonstrated PPFE findings, without evidence of GVHD. In this case, development of PPFE was not associated with GVHD, and immunosuppressive therapy did not improve pulmonary function. Surgical biopsy is recommended for precise treatment and elucidation of pathogenesis in each suspected PPFE patient.

Up-regulated integrinα4ß1 on systemic lymphocytes and serum IL-17A in interstitial pneumonia.

BACKGROUND AND AIMS: In interstitial pneumonia (IP), lymphocytes play an important role in lung injury and the involvement of integrinα4ß1 on leukocytes has previously been reported in animal models. Although the integrinα4ß1 expression level is known to be up-regulated by inflammatory cytokines, the involvement of interleukin (IL)-17A is unclear. The purpose of this study is to address the possible involvement of integrinα4ß1 on circulating lymphocytes and its correlation with serum IL-17A in interstitial lung diseases (ILDs). METHODS: We measured the expression levels of integrinα4ß1 on peripheral lymphocytes and the serum concentration of IL-17A and IL-23 in subjects with ILDs (n = 27; 14 males and 13 females, 66.7 ± 7.8 years old) and control subjects (n = 10; 5 males and 5 females, 66.6 ± 4.6 years old). RESULTS: Recombinant IL-17A up-regulated expression levels of integrinα4ß1 on healthy human lymphocytes in an in vitro experiment. Expression levels of integrinα4ß1 were significantly higher in those with acute hypersensitivity pneumonitis (HP) and non-specific IP (NSIP) compared with control. Serum IL-17A concentration was also significantly increased in acute HP and NSIP subjects compared with control. And IL-17A concentration positively correlated with integrinα4ß1 expression level (P < 0.05). Serum IL-23 was below the minimal detectable level in all subjects. CONCLUSIONS: These findings suggest that up-regulated levels of integrinα4ß1 on systemic lymphocytes and elevated serum IL-17A might be involved in the extravasation of lymphocytes in IP.

Comparative analysis of tumor angiogenesis and clinical features of 55 cases of pleomorphic carcinoma and adenocarcinoma of the lung.

BACKGROUND/AIM: Pleomorphic carcinoma (PC) of the lung is a rare tumor that usually has an aggressive clinical course and a poor prognosis. Clinical and pathological features remain unclear. The aim of this study was to determine whether tumor angiogenesis of PC is up-regulated compared to that in adenocarcinoma (AD). MATERIALS AND METHODS: We collected 55 cases of PC and AD in which the patients had undergone either lung resection or autopsy and immunohistochemically examined the expression of vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF)-1α and microvessel density (MVD) in tissue specimens. RESULTS: VEGF was expressed in many cases of both PC and AD with no significant differences between the groups. In contrast, the expression of HIF-1α and MVD were significantly greater in PC than AD. Median survival time of the PC group was 14.7 months and significantly shorter than that of the AD group. CONCLUSION: MVD and expression of HIF-1α are associated with angiogenesis in PC and confer a poorer prognosis. Tumor angiogenesis provides significant prognostic information regarding clinical outcome in patients with PC.

Comparison of clinical management of young and elderly asthmatics by respiratory specialists and general practitioners.

BACKGROUND: Asthmatic death in the elderly is a serious problem worldwide. Differences in clinical skill between respiratory specialists (RS) and general practitioners (GP) are important in asthma control. The aim of this study was to compare asthma management between RS and GP. METHODS: A cross-sectional survey was carried out in Shimane, Japan, in February 2009 using a questionnaire about patient background, treatment, asthma control test (ACT) and adherence to treatment. We secured the cooperation of 48 clinics (39 private clinics and 9 general hospitals). Asthmatics were divided into the elderly and young groups, and also into the RS and GP groups. RESULTS: Clinical data of 779 patients were available for analysis. Elderly patients constituted 464 (RS group: 192, GP group: 272), while those of the young group were 315 (RS group: 207, GP group: 108). RS prescribed inhaled corticosteroids (ICSs) to their elderly and young patients more than GP. The total ACT score was higher in young RS group than in young GP group, but no such difference was noted in the elderly. Despite more asthma-related symptoms, the ACT showed that elderly GP asthmatics used fewer rescue inhalers than elderly RS. Self-assessment was higher in elderly GP than elderly RS asthmatics. Adherence to therapy was better in elderly patients than young patients. CONCLUSIONS: Elderly asthmatics treated by GPs underestimated the severity of their asthma and asthmatics seen by GPs were undertreated. The results stress the need to engage patients in educational activities, to adhere to guidelines, and to improve the coordination between GP and RS.

Association of EPAS1 gene rs4953354 polymorphism with susceptibility to lung adenocarcinoma in female Japanese non-smokers.

INTRODUCTION: Hypoxia-inducible factor-2α (also called endothelial periodic acid-Schiff domain protein 1 [EPAS1]) seems to play an important role in some carcinogenesis, though there is no information on the relationship between single nucleotide polymorphism of EPAS1 and lung cancer development. The aim of this study was to explore a possible association of the EPAS1 gene rs4953354 polymorphism with susceptibility to lung cancer. METHODS: A case-control study of 346 patients with non-small-cell lung carcinoma (adenocarcinoma = 249, squamous cell carcinoma = 97) and 247 healthy control subjects was carried out. A/G polymorphism within an intron 2 of the EPAS1 (rs4953354) was determined by direct sequencing. RESULTS: A frequency of lung adenocarcinoma patients with a minor allele G (A/G or G/G genotype) at the rs4953354 was much higher than that of controls (odds ratio, 1.800; 95% confidence interval, 1.161-2.791; p = 0.008). This association was more evident when analyzed using female never-smokers (odds ratio, 3.31; 95% confidence interval, 1.21-9.01; p = 0.017). Mutations in epidermal growth factor receptor tended to be frequent in patients with G allele at the rs4953354, compared with those with other genotypes. CONCLUSION: The EPAS1 rs4953354 may be a potentially susceptible marker for development of lung adenocarcinoma, especially in female never-smokers.

Immunohistochemical comparison of biomarker expression in biopsy and surgical specimens of non-small cell lung cancer.

BACKGROUND: Single tumors may show heterogeneity, and it is unclear whether biomarker expression in surgical and diagnostic biopsy samples correlates. MATERIALS AND METHODS: We retrospectively identified lung cancer patients who were diagnosed by biopsy and underwent surgery between January 2007 and October 2010 at the Shimane University Hospital, Shimane, Japan. Thirty-two patients were identified. The expression of four predictive biomarkers was assessed, namely excision repair cross-complementing gene 1 (ERCC1), ribonucleotide diphosphate reductase M1 (RRM1), thymidylate synthase (TS), and class III beta-tubulin (BT). We also compared immunohistochemical staining in diagnostic biopsy and corresponding resected surgical samples. RESULTS: Moderate correlation was seen between the expression of ERCC1, RRM1, TS, and BT in the biopsy and surgical specimens, with r values of 0.512 (p=0.003), 0.411 (p=0.020), 0.475 (p=0.006), and 0.404 (p=0.027), respectively. CONCLUSION: Assessment of biopsy samples with immunohistochemical staining is a feasible and reliable method for use in clinical decision making.

Solitary fibrous tumor with rapid progression after 16 years' follow up.

A 79-year-old woman was admitted to our hospital for an investigation of a large 13-cm tumor in the chest and treatment for dyspnea in January 2010. The tumor had been observed on chest X-rays since 1992. It had measured 7 cm in 2008, then started to grow rapidly. Further investigations revealed that it was a malignant solitary fibrous tumor that was strongly suspected to have transformed from a benign to malignant state. Resection was not possible, and the patient died one month later. Benign solitary fibrous tumors of the pleura may become malignant during long-term follow-up. All suspected or proven solitary fibrous tumors of the pleura should be resected.

Nephrotoxicity induced by piperacillin­tazobactam in late elderly Japanese patients with nursing and healthcare associated pneumonia.

This study aimed to clarify the efficacy, safety, and pharmacokinetics of piperacillin­tazobactam (PIPC­ TAZ) in late elderly Japanese patients. This is the first antimicrobial pilot study in late elderly patients with nursing and healthcare associated pneumonia. After PIPC­TAZ administration, PIPC concentrations in plasma were measured chromatographically and the pharmacokinetic parameters were estimated. Efficacy, safety, and bacteriological evaluations were also carried out. The mean age was 85.0 years old and most of the patients were late elderly. Chest X-rays, body temperature, white blood cell count, and C reactive protein all improved significantly, and a high efficacy ratio of 90.9% was observed. Serious nephrotoxicity was observed in 4 cases (18.2%) after administration of PIPC­TAZ. Creatinine clearance (meanS.D.) measured before PIPC­TAZ therapy was significantly lower in the nephrotoxicity group (32.54.4 mL/min) than in the non-nephrotoxicity group (46.116.7 mL/min), although the ages were not different between the 2 groups. In the pharmacokinetic parameters for PIPC, total clearance was slightly lower in the nephrotoxicity group than in the non-nephrotoxicity group. However, no significant difference was observed in plasma PIPC levels between the 2 groups. In patients with renal impairment, especially with a creatinine clearance of <40 mL/ min, renal impairment was found to be an influencing factor for severe nephrotoxicity following PIPC­TAZ administration. In conclusion, the results suggest that physicians should pay close attention in order to avoid possible toxicity, and that deliberate administration planning and careful follow-up are required in late elderly patients with comprised organ dysfunction.

Multiple logistic regression analysis of risk factors in elderly pneumonia patients: QTc interval prolongation as a prognostic factor.

BACKGROUND: Acute pneumonia is a serious problem in the elderly and various risk factors have already been reported, but the involvement of QTc interval prolongation remains uncertain. The aim of this study was to elucidate the prognostic factors for the development of pneumonia in elderly patients and to study the possible involvement of QTc interval prolongation. METHODS: The subjects were 249 hospitalized pneumonia patients more than 65 years old in Aki-Ohta Hospital from January 2010 to December 2013. Community-acquired pneumonia patients and nursing care and healthcare-associated pneumonia patients were included in the study. The pneumonia severity index, vital signs, blood chemistry data and ECG findings were retrospectively compared using multiple logistic regression analysis. RESULTS: 39 patients died within 30 days from onset. The clinical features related to poor prognosis were: advanced age, past history of cerebral vascular disease and/or diabetes mellitus, decreased serum albumin level, higher CURB-65 or PORT index scores and QTc interval prolongation. Patients showing a prolonged QTc interval had a higher mortality than those with a normal QTc interval. A prolonged QTc interval was not related to serum calcium concentration and/or treatment with QTc prolongation drug, clarithromycin or azithromycin, but related to age, lower albumin concentration and past history of diabetes mellitus. CONCLUSIONS: These findings suggest potential prognostic factors for pneumonia in elderly patients, including a prolonged QTc interval (> 0.44 seconds).

Cyclooxygenase 2 1195G > A polymorphism is associated with chronic obstructive pulmonary disease in Japanese and Chinese patients.

BACKGROUND: Cyclooxygenase-2 (COX-2) is overexpressed during airway inflammation in chronic obstructive pulmonary disease (COPD) patients. Single nucleotide polymorphisms (SNPs) in the COX-2 promoter might contribute to differential COX-2 expression and subsequent interindividual variability in susceptibility to COPD. We investigated the association between COX-2 (-765G > C, -1195G > A) polymorphisms and COPD susceptibility in Japanese and Chinese patients. METHODS: COX-2 genotypes were determined by polymerase chain reaction, restriction fragment length polymorphism in 230 COPD patients (103 Japanese and 127 Chinese) and 273 healthy controls (129 Japanese and 144 Chinese). RESULTS: The frequency of -1195AA homozygote was significantly higher than the controls in Chinese COPD (adjusted OR = 2.43, 95%CI 1.14 - 4.19), Japanese COPD (adjusted OR = 2.25, 95%CI 1.06 - 4.76) and combined COPD groups (adjusted OR = 2.26, 95%CI 1.34 - 3.99). There was no difference in COX-2 -765G > C polymorphism between COPD and control groups in either Japanese or Chinese, while more Chinese individuals carried the -765C allele than Japanese in both groups (15.3% vs. 2.9% in COPD, 18.8% vs. 5.5% in control). Chinese individuals with the haplotype -765G:-1195A were at higher risk for COPD (adjusted OR = 1.93, 95%CI 1.05 - 3.55). CONCLUSIONS: The COX-2 -1195AA genotype is associated with increased risk for COPD in both Japanese and Chinese individuals. Although COX-2 -765G > C polymorphism was not associated with COPD in either ethnic group, the -765C allele frequency was higher in Chinese than Japanese and haplotype -765G-1195A may confer susceptibility to COPD in Chinese.

Efficacy and safety of piperacillin/tazobactam versus biapenem in late elderly patients with nursing- and healthcare-associated pneumonia.

Pneumonia is associated with an extremely high mortality rate in patients of late elderly age. Piperacillin/tazobactam and carbapenems are drugs of first choice for hospitalized patients with potentially resistant bacteria. We compared the efficacy and safety of piperacillin/tazobactam and biapenem. Among elderly patients with nursing- and healthcare-associated pneumonia, we extracted 53 patients treated with piperacillin/tazobactam and 53 patients treated with biapenem who were matched for sex, age, and severity of pneumonia. The average age was more than 80 years; most of the patients were middle- to oldest old in age. Although clinical efficacy was equally good, patients in the piperacillin/tazobactam group achieved significantly faster improvements on chest X-ray and body temperature on day 7. However, in the piperacillin/tazobactam group, nephrotoxicity frequently led to a need for a reduction in the dose or complete discontinuation of treatment. The average age of patients who developed significant nephrotoxicity was high, at 83.2 years. The biapenem group exhibited significantly better continuation of treatment than the piperacillin/tazobactam group. Toxicity profiles were different between the two groups. Hepatic toxicity was significantly higher in the biapenem group, whereas nephrotoxicity was significantly more common in the piperacillin/tazobactam group. Rate of decrease in bacteria was equally good between the two groups. Providing careful follow-up and conducting more detailed examinations, including studies to determine optimal dose and timing of administration, are necessary for the treatment of late elderly patients with numerous underlying diseases and potential organ dysfunctions.

Phase I clinical and pharmacokinetic study of bi-weekly carboplatin/paclitaxel chemotherapy in elderly patients with advanced non-small cell lung cancer.

AIM: We evaluated the pharmacokinetics and quality of life of elderly patients with advanced non-small-cell lung cancer (NSCLC) treated with bi-weekly carboplatin and paclitaxel chemotherapy, and determined the maximum tolerated dose (MTD) of this treatment. PATIENTS AND METHODS: Eligible patients had histologically- or cytologically-proven inoperable NSCLC, age of 70 years or older, no prior treatment, and Eastern Cooperative Oncology Group performance status 0-2. Paclitaxel was administered in combination with carboplatin under a bi-weekly schedule. We determined the plasma concentrations of both drugs during therapy. RESULTS: The median patient age was 80 years. Using carboplatin at AUC 3, the MTD of paclitaxel was 100 mg/m(2). Both hematological and non-hematological toxicities were mostly mild and manageable. Although paclitaxel is predominantly metabolized in the liver, clearance was decreased in patients with lower estimated glomerular filtration rate. CONCLUSION: Bi-weekly treatment, as described here, is feasible for elderly patients as a conventional regimen, particularly in the outpatient setting, due to its lower toxicity.

Increased expression levels of integrin α9ß1 and CD11b on circulating neutrophils and elevated serum IL-17A in elderly aspiration pneumonia.

BACKGROUND: Repeated aspiration pneumonia is a serious problem in the elderly. In aspiration pneumonia, neutrophils play an important role in acute lung injury, while CD18-independent neutrophil transmigration pathways have also been reported in acid-aspiration pneumonia animal models. However, the involvement of IL-17A and ß1 integrin still remains unclear. The ß1 integrin subfamily integrin α9ß1 has been shown to be expressed on human neutrophils and to mediate adhesion to extracellular matrix proteins including the vascular cell adhesion molecule-1. OBJECTIVES: To elucidate the possible involvement of ß1 integrin subfamily and IL-17A in aspiration pneumonia. METHODS: We analyzed the expression levels of CD11b, CD18 and integrin α9ß1 in circulating neutrophils and serum concentration of IL-17A, IL-22 and IL-23 in elderly aspiration pneumonia patients (n = 32, 14 males and 18 females, 78.8 ± 3.9 years old) at 2 time points (on the day of admission before starting antibiotics and the day after finishing antibiotics) and compared the results with those of a control group (n = 30, 13 males and 17 females, 76.1 ± 3.4 years old). RESULTS: Recombinant IL-17A stimulated integrin α9ß1 and CD11b expression levels in healthy human neutrophils in vitro. The expression levels of integrin α9ß1 and CD11b in circulating neutrophils were significantly higher in pneumonia patients compared with the controls. In addition, serum IL-17A concentration was significantly increased in pneumonia patients. Integrin α9ß1 levels positively correlated with serum IL-17A and CD18 expression levels. CONCLUSIONS: These findings suggest a potential role of integrin α9ß1 expressed in neutrophils and elevated serum IL-17A in extravasation of neutrophils in cases of aspiration pneumonia.

Tumor angiogenesis in 75 cases of pleomorphic carcinoma of the lung.

BACKGROUND: Pleomorphic carcinoma (PC) of the lung is a rare tumor that usually has an aggressive clinical course and a poor prognosis. In this study, 75 cases of PC were reviewed to identify its clinical features, and we examined the expression of angiogenic factors. PATIENTS AND METHODS: We immunohistochemically examined the expression of angiogenic factors in tissue specimens of PC. RESULTS: 66 males and 9 females were examined. The median survival time was 16.5 months. The stage and symptomatical diagnosis were significantly associated with the survival. In the immunohistochemical analyses, vascular endothelial growth factor (VEGF) was expressed in many cases of PC. A high score for angiogenesis was significantly related to a poorer prognosis. CONCLUSION: We conclude that PC should be considered an aggressive disease, and that the stage and symptomatical diagnosis are strong prognostic factors. Furthermore, tumor angiogenesis provides significant prognostic information about the clinical outcome in PC.

Erlotinib-induced acute interstitial lung disease associated with extreme elevation of the plasma concentration in an elderly non-small-cell lung cancer patient.

We herein describe a case of drug-induced interstitial lung disease (ILD) following treatment with erlotinib. The plasma trough concentration of erlotinib at the time of the ILD diagnosis was extremely elevated compared with the plasma maximum concentration on day 1. We hypothesized that this phenomenon was associated with the pharmacodynamic interaction with a concomitant drug. The present case indicates that erlotinib-induced ILD was associated with a high plasma concentration of erlotinib. Oncologists should be aware of the possibility of ILD induced by erlotinib, especially for patients with co-morbidities.