Yuichi Tambo

Transformation to small-cell lung cancer following treatment with EGFR tyrosine kinase inhibitors in a patient with lung adenocarcinoma.

We report the case of a 52-year-old woman with lung adenocarcinoma treated with EGFR tyrosine kinase inhibitor (TKI) therapy. After disease progression, histological examination of a secondary biopsy specimen revealed small-cell lung cancer (SCLC) that was sensitive to standard SCLC treatment. Tumor markers, including ProGRP and NSE, were elevated. Transformation to SCLC is a mechanism for acquired resistance to EGFR-TKI therapy. Secondary biopsy is important for evaluation of genetic and histological changes and selection of appropriate treatment. Furthermore, ProGRP and NSE may be useful for early detection of SCLC transformation in cases resistant to EGFR-TKI therapy.

Sputum Eosinophilia, Airway Hyperresponsiveness and Airway Narrowing in Young Adults with Former Asthma

BACKGROUND 30-80% of outgrown asthma subjects develop symptoms again later in life. We investigated inflammation and function of lower airway in adolescents with former asthma. METHODS 326 never-smoking young adults (mean age 24.0 years) were interviewed with special emphasis on history of asthma. Diagnosis of asthma was based on GINA guidelines. Former asthma subjects consisted of ones with a history of physician-diagnosed childhood asthma, who had been free of asthma symptoms without the use of medication for at least 10 years prior to the study. Provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second (FEV(1))(PC(20)) and eosinophil percentage in induced sputum were measured. RESULTS 31 subjects were former asthma subjects (FBA), 11 subjects were current asthma subjects (CBA) and 284 subjects had no history of asthma (non-BA). PC(20) and FEV(1)/FVC ratio were significantly lower in the FBA group than in the non-BA group (P < 0.01). Maximal mid-expiratory flow (MMF) was significantly lower in the FBA group than in the non-BA group (P < 0.05). Sputum eosinophil percentage was significantly increased in the FBA group compared with the non-BA group (P < 0.01). PC(20) was significantly lower in the CBA group than in the FBA and non-BA groups (P < 0.01). FEV(1), FEV(1)/FVC ratio and MMF were significantly lower in the CBA group than in the FBA group (P < 0.05, P < 0.05 and P < 0.05, respectively) and the non-BA group (P < 0.01, P < 0.01 and P < 0.05, respectively). Sputum eosinophils were significantly higher in the CBA group than in the FBA and non-BA groups (P < 0.01). CONCLUSIONS This study shows that subjects with long-term outgrown asthma continue to have airway eosinophilic inflammation, airway hyperresponsiveness and airway narrowing.

Pneumothorax as a first manifestation of SS

William Tillett, Gavin Shaddick, Eleanor Korendowych, Corinne S. de Vries and Neil McHugh Department of Rheumatology, Royal National Hospital for Rheumatic Diseases, Bath, Department of Mathematics and Department of Pharmacy and Pharmacology, University of Bath, Bath, UK. Accepted 20 March 2012 Correspondence to: William Tillett, Department of Rheumatology, Royal National Hospital for Rheumatic Diseases, Upper Borough Walls, Bath BA1 1RL, UK. E-mail: w.tillett@nhs.net

Remission of psoriasis with nintedanib for the treatment of idiopathic pulmonary fibrosis

Dear Editor, Psoriasis is a chronic, relapsing skin disease characterized by the hyperproliferation of the keratinocytes in the epidermis. Several biologic therapies have been approved for treating moderate to severe psoriasis. We herein report a case of psoriasis successfully treated with nintedanib. A 75-year-old man with idiopathic pulmonary fibrosis (IPF) presented to our hospital complaining of progressive dyspnea on exertion. He had suffered from moderate psoriasis vulgaris for 21 years and used topical corticosteroids without any improvement. The patient had a history of cerebral infarction 24 years prior and obstructive lower extremity arteriosclerosis 5 years prior. His usual medications included olmesartan medoxomil azelnidipine combination, clopidogrel, allopurinol and ethyl icosapentate. On physical examination, many small plaques of psoriasis were found on his scalp, face, trunk and limbs, and he had a Psoriasis Area and Severity Index (PASI) of 9.2 (Fig. 1a). Because of the progression of IPF, nintedanib was administrated at 150 mg twice daily. Two weeks after starting the treatment, his psoriatic lesions gradually improved, and he achieved PASI-90 after 1 month (Fig. 1b). Two months later, the dose of nintedanib was reduced from 150 to 100 mg twice daily due to drug-induced liver injury. Although his liver function improved immediately, nintedanib was eventually discontinued due to severe diarrhea. The total duration of nintedanib was 4 months. At the 1-year follow up, the patient’s psoriasis had maintained remission (PASI-90) even without any additional treatment. To the best of our knowledge, this is the first reported case of the remission of psoriasis in response to nintedanib therapy. Nintedanib is a tyrosine kinase inhibitor that targets vascular endothelial growth factor (VEGF) receptor, fibroblast growth factor (FGF) receptor and platelet-derived growth factor (PDGF) receptor. It has been widely used for the treatment of IPF. Although our patient could not continue due to its adverse events, nintedanib has a tolerability profile that is acceptable and manageable for the majority of patients. Although the precise mechanisms underlying its effects are unclear, its antiangiogenic effect may have an important role in ameliorating psoriasis. The histological characteristics of psoriatic skin include the infiltration of immune cells, keratinocyte proliferation and increased dermal vascularity. The plasma level of VEGF and the expression of VEGF receptor (VEGFR) in skin lesions are increased in patients with psoriasis. Previous case reports have described improvements in psoriatic lesions after treatment with bevacizumab, a monoclonal antibody against VEGFR, in patients with colon carcinoma or renal cell carcinoma. Therefore, angiogenesis through VEGF signaling may be an important route for the development of psoriasis. In addition, other angiogenic mediators, such as PDGF and FGF, are upregulated in psoriatic development. These growth factors may also contribute to the disease pathogenesis. In conclusion, nintedanib may be a novel targeted therapy for psoriasis. We expect that nintedanib would be an additional treatment option for psoriasis that is severe or resistant to other treatments. Further clinical and experimental studies are needed to evaluate the usefulness of nintedanib for the treatment of psoriasis.

A Single Institution Retrospective Study of the Clinical Efficacy of Tiotropium Respimat in Never-Smoking Elderly Asthmatics with Irreversible Airflow Limitation

OBJECTIVE In Japan, most asthma deaths occur among the elderly. We should improve the control of asthma in elderly patients to reduce the number of deaths due to asthma. This retrospective study aimed to evaluate the efficacy of tiotropium RespimatⓇ (Tio-Res) in symptomatic, never-smoking, elderly asthmatics with irreversible airflow limitation despite the use of high-dose inhaled corticosteroids (ICS) plus long-acting β2-adrenoceptor agonists (LABA). METHODS The Asthma Control Test™ (ACT), pulmonary function tests, morning and evening peak flow (mPEF, ePEF, respectively, evaluated with an ASSESS® peak flow meter), and respiratory impedance (assessed with MostGraph®) were measured before and after a minimum of one year of Tio-Res 5 µg/day administration. Sixteen symptomatic, never-smoking asthmatics, aged 75 or over with irreversible airflow limitation despite the use of high-dose ICS plus LABA, were analyzed. RESULTS All patients were female (mean age, 81.6 years). Tio-Res led to statistically significant improvements in the total ACT score (19.9 to 23.6), FVC and FEV1 (1.97 to 2.14 L and 1.13 to 1.23 L, respectively), and mPEF and ePEF (229.9 to 253.8 L/min and 259.8 to 277.4 L/min, respectively). Tio-Res also resulted in statistically significant improvements in respiratory resistance at 5 Hz (R5), respiratory resistance at 20 Hz (R20), R5-R20, low-frequency reactant indices at 5 Hz (X5), resonant frequency (Fres) and low-frequency reactance area (ALX). CONCLUSIONS Our retrospective study suggests that Tio-Res improves symptoms, pulmonary function, and respiratory impedance in symptomatic asthmatics aged 75 or over with irreversible airflow limitation despite the use of high-dose ICS plus LABA.

Long-lasting shrinkage in tumor mass after discontinuation of nivolumab treatment

We report the case of a 62-year-old man treated with nivolumab as fourth-line therapy for stage IV squamous cell carcinoma of the lung. Because of the onset of nivolumab-induced pneumonitis after 2 doses, nivolumab was discontinued. After discontinuation, the tumor gradually continued to decrease in size without any additional treatment for lung cancer. The patient obtained a long-lasting shrinking of the tumor over 6 subsequent treatment-free months after only 2 administrations of nivolumab. This type of response has not been seen for conventional anticancer drug treatments for NSCLC, and we speculate that a small group of patients with NSCLC will obtain sufficient efficacy from a few doses of nivolumab.

Plasma EGFR and Her2 levels in non-small cell lung cancer patients treated with gefitinib

19007 Background: Although EGFR mutation is a strong predictive factor of EGFR-TKI, it is difficult to obtain tumor tissue which is suitable to examine EGFR mutations in patients (pts) with metasta...