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[Purpose] The aim of this study was to evaluate the effects of a self-managed physical activity program using a pedometer and diary on physical function, ADL, and QOL in patients with chronic respiratory disease. [Subjects and Methods] 17 outpatients with chronic respiratory disease were assessed for dyspnea, muscle strength, exercise tolerance, ADL, and QOL at baseline, after 3-, and 6-months after the start of the program. Patients were randomly assigned to "Control" or "Diary" group. In the Diary group, the number of steps was counted with a pedometer and recorded in a diary together with self-evaluation of physical activity, while patients assigned to the Control group did not use a pedometer or keep a diary. [Results] The Diary group showed significant improvement in the daily step count over time. The Diary group showed significant improvement of the dyspnea, muscle strength, and exercise tolerance at 3 months, dyspnea and muscle strength at 6 months. Significant differences found between two groups with regard to the extent of change in the muscle strength, exercise tolerance, and QOL at 3 months. [Conclusion] This study suggests that a self-managed physical activity program using a pedometer and diary can increase the level of physical activity.

Background:Increased severity of asthma is contributed by airway tissue remodeling, which may be associated with chronic allergic inflammation. A recent study revealed the potential capacity of repeated bronchoconstriction, e.g. induced by a muscarine agonist, methacholine(Mch)challenge, to involve in airway remodeling, even though allergic inflammation is not implicated. We have evaluated the influence of repeated bronchoconstriction induced by Mch inhalation on airway remodeling in a murine model of asthma and have examined its machanisms. Methods:Mice were immunized with ovalbumin(OVA), and consequently, challenged by either daily OVA inhalation(the OVA group;a model of asthma with allergic inflammation)or daily Mch inhalation(the Mch group;a model of asthma without allergic inflammation). Lung tissues were obtained and were evaluated histologically after 5, 10, and 15 consecutive inhalation challenges of both OVA and Mch.Results:Eosinophilia in the airway observed only on the OVA group. Subepithelial collagen-band thickness increased also in the OVA group(p

Purpose This study was designed to confirm the efficacy and safety of amrubicin, a new anthracycline agent, in patients with previously treated non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Methods Eligible patients were required to have recurrent or refractory NSCLC and SCLC after one or two previous chemotherapy regimens. All patients received intravenous amrubicin 35mg/m 2 on days 1–3 every 3 weeks. Overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated. Results Sixty-six patients (37 NSCLC and 29 SCLC) were assessable for efficacy and safety evaluation. Grade 3 or 4 neutropenia was observed in 39.4% of all patients (NSCLC, 37.8%; SCLC, 41.4%). Nonhematological toxicities were mild. No treatment-related death was observed. The ORRs were 13.5% (95% CI, 4.5–28.8%) in NSCLC and 44.8% (95% CI, 26.4–64.3%) in SCLC. In SCLC, ORRs were 60.0% in the sensitive relapse and 36.8% in the refractory relapse ( p =0.2332). In NSCLC, the PFS, OS, and 1-year survival were 3.3 months, 12.0 months, and 35.3%, respectively. In SCLC, the PFS, OS, and 1-year survival were 4.0 months, 12.0 months, and 46.7%, respectively. Conclusions Amrubicin is an active and well-tolerated regimen in patients with previously treated lung cancer. Amrubicin 35mg/m 2 seems to achieve similar efficacy with less toxicity than amrubicin 40mg/m 2 in this patient population. These results warrant further evaluation in previously treated lung cancer.

気管支喘息の基本的病態は慢性の気道炎症として認識され,その機序が徐々に解明されてきている.特に重症・難治化には気道リモデリングがその要因として注目されている.今回,我々は神経原性炎症に深く関与している神経ペプチド(サブスタンスP,ニューロキニンA)が気道リモデリング,特に線維化サイトカインTGF-βのシグナル伝達機構に関与するTIEG, smad 7遺伝子発現に与える影響について検討した.これら神経ペプチドは線維化サイトカインTGF-βの発現を誘導し,さらにTGF-βの抑制型シグナル伝達分子smad 7の遺伝子発現を低下させた.これらの結果より神経ペプチドはTGF-βのシグナル伝達分子smad 7発現を抑制することによりリモデリング形成に関与している可能性が示唆された.持続するTh2型気道炎症はTGF-β産生増加へ傾きTIEG発現を誘導し,その結果smad 7の発現を抑制する事が知られている.我々は,気道平滑筋におけるサブスタンスP刺激によりTIEG遺伝子発現が誘導される事を見出した.また, TGF-β前処置後サブスタンスPで刺激することによりその効果は増強される事も確認した.これらの結果より,アレルギー性炎症により惹起された神経原性炎症はTIEG発現を誘導し,結果としてsmad 7発現が抑制され気道の線維化・リモデリング形成を促進している可能性が示唆された., Airway remodeling is a typical issue of asthma. Transforming growth factor (TGF)-β plays an important role for the regulation of airway inflammation and remodeling in asthma. The expression of TGF-β in the asthmatic airways was predominantly detected in eosinophils and fibroblasts and it was significantly correlated with the severity of the disease, basement membrane thickness, and submucosal fibroblast number, thus suggesting that TGF-β is involved in airway remodeling in adult asthma. TGF-β-inducible early gene (TIEG) is a Kruppel-like transcription factor that is rapidly induced upon TGF-β treatment TIEG promotes TGF-β/smad signaling by down-regulating negative feedback through the inhibitory smad 7. Among numerous peptide mediators such as tachykinin, calcitonin gene-related peptide, substance P or neurokinin A is one of the most abundant molecules found in the respiratory tract. Neurogenic inflammation might contribute to selective upregulation of TIEG through unknown mechanisms. We therefore examine whether neuropeptides modulate TGF-β and TIEG expression. In this study, we found that TIEG was significantly increased in the cultured smooth muscle cells stimulating with substance P. Furthermore, we found the synergistic effect on TIEG expression in cultured smooth muscle cells stimulating with substance P and pretreatment of TGF-β. These results suggest that increased TIEG expression in airway epithelial and smooth muscle cells might result in increased substance P, TGF-β activity and contribute to the development of airway inflammation seen in chronic asthma.

気管支喘息の基本病態は好酸球,T細胞(特にTh2細胞),肥満細胞,などの炎症細胞を中心とする慢性の気道炎症と気道リモデリングによって矛盾なく説明できる.気道リモデリングの分子レベルでの形成機序は未だ不明な部分が多く,最近線維化サイトカインTGF-βの役割が注目されている.特にシグナル伝達分子Smadの制御機構の不均衡により起こって来ることも解明されつつある.今回我々はTh2サイトカインIL-5,GM-CSFおよび調節性サイトカインIL-10が気道上皮細胞における抑制型Smad7発現に与える影響についてReal time RT-PCR法を用いて検討した.IL-10刺激は,コントロールに比較して,Smad7の発現が増強し,一方でIL-5,GM-CSFはその発現は誘導されなかった.また,その発現はIL-10との混合培養にて増強した.更に,IL-10はSmad7発現を減弱させることが知られている遺伝子TIEG発現に関しても抑制することを見出し,IL-10が制御性サイトカインとして気道炎症の抑制に関与していることが示唆された, Transforming growth factor-β (TGF-β) is an important pro-fibrogenic growth factor implicated in airway remodeling and pulmonary fibrosis. TGF-β signals from membrane to nucleus by using Smad proteins. Recently, Smad7 has been identified as an intracellular antagonist for TGF-β signaling and it inhibits TGF-β-induced transcriptional responses. And InterleukinlO (IL-10) is general inhibitor of proliferative and cytokine responses in T cells and is produced by mononuclear phagocytes, natural killer cells and by both Th1 and Th2 type lymphocytes. Therefore, we examined the relationship between expression of smad7 in cultured epithelial cells (Beads 2B) stimulated with IL-10. We thought to determine the relationships between Smad7 expression in human bronchial cell line, BEAS-2B cells stimulated with Th2 type cytokine and regulatory cytokine IL-10. Expression levels of Smad7 was expressed in cultured epithelial cells. Interestingly, Th2 cytokines IL-5, GM-CSF exhibited less Smad7 expression in BEAS-2B cells than IL-10 stimulation. In addition, combination with IL-10 and IL-5 stimulation inhibited decreased Smad7 expression. TGF-β induced TIEG expression in BRAS-2B cells were also decreased in a IL-10 stimulation. These findings suggest that Smad7 in a key molecule that defines the susceptibility of bronchial epithelial cells to TGF-β action and regulation of Smad7 expression in bronchial epithelial cells may be related to the development of airway remodeling.

気管支喘息は気道への好酸球を中心とする慢性アレルギー性炎症性疾患として認識され,その患者は各種IgE抗体を発現し,対応するアレルゲン暴露により気道にIgEを介するアレルギー性炎症が惹起される.一方,CD40LigandはTリンパ球,肥満細胞などに発現し,CD40との伝達を介してBリンパ球のIgE産生細胞への分化,増殖に働いており,IgE産生において重要な働きをしている.しかし好酸球におけるCD40Ligand発現とIgE産生へ役割は明確ではない.我々は気管支喘息患者末梢血好酸球のCD40Ligand発現とそれがBリンパ球IgE産生誘導に与える影響について検討した.(方法)気管支喘息患者末梢血より好酸球を分離精製し,各種サイトカインで刺激しCD40L発現を検討した.また精製Bリンパ球と混合培養し上清中のIgEを測定した,(結果)気管支喘息患者群の末梢血好酸球は健常者群に比較し優位にCD40Ligandを発現し,またBリンパ球は好酸球との混合培養によりIL-4,IL-13存在下にIgEを産生した.(考案)気管支喘息患者好酸球はTリンパ球とは別個に独立してBリンパ球のIgE産生に関与する可能性が示唆された., Bronchial asthma is a chronic inflammatory disease of the airway.The accumulation of eosinophils in the airway is one of characteristic seen in patients with bronchial asthma. Asthmatic patients have a large number of IgE antibodies to environmental allergens. The exposure of these allergens induces IgE mediated allergic inflammation in the airway. Allergic reaction is a most important aspect of airway inflammation of the bronchial asthma. It is well known that CD40/CD40-Ligand interaction is a key factor for IgE production. CD40-Ligand, a surface molecule which can be expressed by T cells, mast cells and basophils has been shown to be involved in the control of B cell proliferation. We have observed following in vitro study. It have been shown that freshly isolated eosinophils from asthmatic subjects can be induced to express CD40-Ligand but not from normal controls. IgE synthesis can be induced by the interaction of B cells with eosinophils in the presence of exogenous IL-13. These result suggest that eosinophils can induce the production of IgE, independently of T cells.

A study to evaluate the efficacy of cisplatin, doxorubicin, and etoposide chemotherapy with combined radiotherapy was undertaken in 26 patients with limited disease-small-cell lung cancer. Patients were treated with cisplatin (80 mg/m 2 ) intravenously (i.v.) on day 1, doxorubicin (30 mg/m 2 ) i.v. on day I, and etoposide (80 mg/m 2 ) i.v. on days 1, 3, and 5, every 4 weeks for four cycles. Thoracic irradiation of 40 Gy in 20 fractions was delivered during 4 weeks to the primary site starting on day 8 of the second cycle of chemotherapy. The objective response rate was 100%. A complete response was observed in 10 patients (38%). The median survival time was 23 months, and the 3-year survival rate was 42%. Seven patients (27%) continued to survive at least 8 years and remain free from disease. Grade III/IV leukopenia was observed in 25 patients (96%). Grade III/IV thrombocytopenia developed in 19 patients (73%). Grade III/IV esophagitis was not seen. Interstitial pneumonitis occurred in two patients. This regimen is effective and has acceptable toxicity for use in the treatment of limited disease-small-cell lung cancer.

Asthma, a family of airway disorders characterized by airway inflammation, has an increasing incidence worldwide. Platelet-activating factor (PAF) may play a role in the pathophysiology of asthma. Its proinflammatory actions are antagonized by PAF acetylhydrolase. A missense mutation (V279F) in the PAF acetylhydrolase gene results in the complete loss of activity, which occurs in 4% of the Japanese population. We asked if PAF acetylhydrolase deficiency correlates with the incidence and severity of asthma in Japan. We found that the prevalence of PAF acetylhydrolase deficiency is higher in Japanese asthmatics than healthy subjects and that the severity of this syndrome is highest in homozygous-deficient subjects. We conclude that the PAF acetylhydrolase gene is a modulating locus for the severity of asthma.

CYFRA 21-1 is a new tumor marker using two different monoclonal antibodies which recognize the divergent epitope on the N- or C-terminal region of domain 2 of cytokeratin 19 fragment, respectively. In this study, we investigated the relationship between levels of CYFRA 21-1 and survival duration, as well as the efficacy of chemotherapy associated with changes in CYFRA 21-1. Serum samples were obtained from 87 patients with nonoperable lung cancer (35 cases with squamous-cell carcinoma, 33 with adenocarcinoma, 3 with large-cell carcinoma, and 16 with small-cell carcinoma). The cutoff point was set at 3.5 ng/ml. In a CYFRA 21-1 assay, significantly more patients with squamous-cell carcinoma and adenocarcinoma were positive compared to patients with small-cell and large-cell carcinomas (p = 0.0017). Following chemotherapy, blood levels of CYFRA 21-1 decreased significantly in responders versus nonresponders (p = 0.0246). A significant correlation was noted between survival periods and pretreatment levels of CYFRA 21-1 (p = 0.0036). The present study suggests that CYFRA 21-1 might be useful as a possible indicator of survival and therapeutic effect for lung cancer.

Background We conducted a phase II study to evaluate the efficacy and safety of S-1 plus cisplatin with bevacizumab followed by maintenance bevacizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC). Patients and methods Chemotherapy-naive patients received S-1 plus cisplatin with bevacizumab. S-1 (80mg/m 2 ) was administered orally twice daily for 14 days, cisplatin (60mg/m 2 ) on day 1, and bevacizumab (15mg/kg) on day 1 and every 3 weeks for 4–6 cycles. Patients with an objective response or stable disease received maintenance bevacizumab every 3 weeks until disease progression. Results Thirty patients were enrolled in this study. The median number of chemotherapy was four (range, 1–6 cycles), and the median number of bevacizumab alone was three (range, 1–31 cycles). The grade 3/4 toxicities were neutropaenia (23%), thrombocytopaenia (10%), febrile neutropaenia (3%), hypertension (17%), pneumonia (7%), and bowel perforation (3%). The objective response rate was 71% (95% CI, 55–88%) for a disease control rate of 100%. The median progression-free and overall survival times were 7.0 months and 20.0 months, respectively. Conclusions S-1 plus cisplatin with bevacizumab is an active and well-tolerated regimen in patients with chemotherapy-naive non-squamous NSCLC.

A combination chemotherapy consisting of a 72-hour continuous infusion of cisplatin (CDDP; 100 mg/m2/72 h) and 5-fluorouracil (5-FU; 3 g/m2/72 h) was conducted for inoperable non-small cell lung cancer (NSCLC). Sixty patients were accepted for this study between June 1988 and December 1990. Forty-seven patients were male (median age 68). Thirty-four patients had stage III and 26 had stage IV disease. The response rate was 25.0% (95% confidence interval, CI, 14.0-36.0%), median survival was 15.7 months. In squamous cell carcinoma, the response rate was 35.5% (95% CI, 18.7-52.3%) and median survival was 15.1 months. In non-squamous cell carcinoma, the response rate was 13.8% (95% CI, 1.2-26.4%) and median survival was 17.7 months. There was a significant difference in response rate (p0.01), but no significant difference in survival (p = 0.36). Grade 3 leukopenia was 11.7%, grade 3 and 4 thrombocytopenia was 13.3%. Grade 3 nausea and vomiting were 8.3%. One patient had grade 4 renal toxicity. However, there was no treatment-related death. This regimen was well tolerated. In multivariate analysis, the significant parameters were CEA, performance status and response. In conclusion, 72-hour continuous infusion of CDDP and 5-FU for treatment of NSCLC provides similar response and toxicity as previously reported regimens using CDDP.

Background In patients with chronic respiratory disease, Pneumocystis jirovecii (P. jirovecii) colonization is observed, and may influence disease progression and systemic inflammation. Pneumocystis pneumonia causes interstitial changes, so making a diagnosis of PCP in patients who have interstitial pneumonia (IP) with P. jirovecii colonization is sometimes difficult based on radiography. Methods This study investigated the prevalence of P. jirovecii colonization in IP patients and assessed pulmonary injury due to P. jirovecii colonization by measurement of serum markers (KL-6, SP-A, SP-D, and (1→3) β-D-glucan (β-D-glucan)) and the peripheral lymphocyte counts, prospectively. A total of 75 patients with idiopathic pulmonary fibrosis (n = 29), collagen vascular-related interstitial pneumonia (n = 19), chronic bronchitis or pneumonia (n = 20), and Pneumocystis pneumonia (n = 7) were enrolled in this prospective study. P. jirovecii DNA was detected in sputum samples, while serum markers and the lymphocyte count were measured in the peripheral blood. Results IP patients (idiopathic pulmonary fibrosis and collagen vascular-related IP) who received oral corticosteroids had a high prevalence of P. jirovecii colonization (23.3%). In IP patients, oral corticosteroid therapy was a significant risk factor for P. jirovecii colonization (P < 0.05). Serum markers did not show differences between IP patients with and without P. jirovecii colonization. The β-D-glucan level and lymphocyte count differed between patients with Pneumocystis pneumonia or P. jirovecii colonization. Conclusion Serum levels of KL-6, SP-A, SP-D, and β-D-glucan were not useful for detecting P. jirovecii colonization in IP patients. However, the serum β-D-glucan level and lymphocyte count were useful for distinguishing P. jirovecii colonization from pneumocystis pneumonia in IP patients.

Background: The basic pathological features of bronchial asthma can be explained on the basis of chronic airway inflammation, involving inflammatory cells such as T cells (particularly type 2 helper T, Th2, cells) and mast cells, and airway remodeling. Many aspects of airway remodeling remain unclear at the molecular level. Recent attention has focused on the role of transforming growth factor (TGF)-β, a fibrogenic cytokine, in airway remodeling. Currently available evidence suggests that airway remodeling is caused by an imbalance in regulatory mechanisms mediated by Smads, a family of signal-transducing molecules. Objectives: We studied the effects of the Th2 cytokines interleukin (IL)-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF), and the regulatory cytokine IL-10 on the expression of inhibitory Smad7 protein in bronchial epithelial cells. Methods: Real-time reverse-transcriptase polymerase chain reaction was employed. Results: Stimulation with IL-10 upregulated the expression of Smad7 compared with control. Neither IL-5 nor GM-CSF induced Smad7 expression. Smad7 expression was upregulated by IL-10 plus either IL-5 or GM-CSF. IL-10 inhibited the expression of TGF-β-inducible early gene, which is known to downregulate Smad7 expression. Conclusions: Our results suggest that IL-10 acts as a regulatory cytokine in the inhibition of airway inflammation.

We investigated the usefulness of serum pro-gastrin-releasing peptide (Pro-GRP) as a tumor marker for diagnosis, treatment monitoring and the prediction of relapse and prognosis in patients with small-cell lung cancer (SCLC). Serum samples were obtained from 127 patients with primary lung cancer (48 patients with small-cell carcinoma, 31 with adenocarcinoma, 36 with squamous cell carcinoma and 11 with large-cell carcinoma). The cutoff levels of serum Pro-GRP and neuron-specific enolase (NSE) were set at 46 pg/ml and 10 ng/ml, respectively. The specificity of Pro-GRP was significantly higher than that of NSE (Pro-GRP: 93.7%, NSE: 65.8%, p < 0.01). According to the histological type of lung cancer, the positive rates of Pro-GRP were 75% (36/48) in the small-cell carcinomas, 9.7% (3/31) in the adenocarcinomas, 5.6% (2/36) in the squamous cell carcinomas and 0% (0/10) in the large cell carcinomas. The median levels of Pro-GRP in limited disease (LD) and extensive disease (ED) patients were 199 and 295.5 pg/ml, whereas those of NSE were 14.8 and 29.3 ng/ml, respectively. The positive rates of Pro-GRP in LD and ED patients were 80.0% (16/20) and 71.4% (20/28), whereas those of NSE were 70.0% (14/20) and 89.3% (25/28), respectively. The positive rate of NSE tended to elevate with the progression of disease, whereas that of Pro-GRP was already high at an early stage. Among the 29 patients with SCLC who could be followed, the serum Pro-GRP levels of 18 responders were significantly decreased after treatment (p < 0.01), whereas those of the 11 nonresponders were not significantly different between before and after treatment (p = 0.72). In the 9 patients with SCLC who relapsed, the serum Pro-GRP levels were again elevated at the time of relapse. Seventeen patients whose ratio of the Pro-GRP level after treatment to the level before treatment was below 50% (taking the levels before treatment as 100%) survived significantly longer than did the patients whose ratio was over 50% (p < 0.01). The results of the present study suggest that serum Pro-GRP has high specificity and could be a useful marker of SCLC for treatment monitoring and prognosis.

It is reported that the combination of cisplatin (CDDP) and carboplatin (CBDCA) is synergistic in vitro. The objective of this study was to evaluate the therapeutic effect and safety of the two platinum compounds in combination with etoposide in the treatment of non-small-cell lung cancer (NSLC). Forty patients were registered. Based on the results of a phase I study, patients were treated with CDDP (80 mg/m2 i.v. on day 1), CBDCA (280 mg/m2 i.v. on day 1), and etoposide (80 mg/m2 i.v. on days 1-3). Of the 40 patients, 30 were men and 10 women. Histology revealed adenocarcinoma(AC) (n = 20), squamous cell carcinoma(SCC) (n = 18), and large cell carcinoma(LCC) (n = 2). Staging: IIIA (n = 3); IIIB (n = 17); and IV (n = 20). A 32.5% overall response rate [13 of 40; 95% confidence interval (CI) 18-47%] was achieved. The response rates in patients with SCC and AC were 55.6 and 10.0% (p < 0.005), respectively. The median duration of response was 47.1 weeks and the overall median survival time was 57.1 weeks. Leukopenia and thrombocytopenia--World Health Organization (WHO) grade IV--occurred in nine and 11 patients, respectively. Nonhematological toxicities were mainly nausea, vomiting, and alopecia. In conclusion, further investigations of this regimen are warranted in the treatment of NSLC.

e18037 Background: Cisplatin combined with S-1 is an active regimen for patients with advanced non-small cell lung cancer (NSCLC). Although the addition of bevacizumab to platinum based regimens significantly improved outcome, it remains unknown about the safety and efficacy of first-line cisplatin plus S-1 with bevacizumab. Therefore, we conducted a phase II study to evaluate the efficacy and tolerability of bevacizumab in combination with S-1 plus cisplatin regimen in patients with advanced non-squamous NSCLC. Methods: Patient with ages ranging from 20 to 74 years, non-squamous NSCLC, no prior systemic therapy, no brain metastases and ECOG PS 0-1 were enrolled. Patients received cisplatin 60mg/m2 and bevacizumab 15mg/kg on day 1 of each cycle, and S-1 80mg/m2 orally twice daily for 14 days every 21 days. After 4-6 courses, patients were continued on bevacizumab until progression disease (PD). Primary end point was response rate (RR). Secondary end points included overall survival (OS), PFS, time to treatment failure (TTF), and safety. Results: Twenty-nine patients were enrolled in this study. Median age was 67 years (range: 42 to 74); male/female=17(58%)/12(42%); ECOG PS 0/ 1 = 18 (62%) / 11(38%); stageIIIB/IV=3(10%)/26(90%); adeno / NSCLC = 26 (90%) / 3 (10%). The median courses of the induction therapy was 4 (range: 2 to 6), and that of the maintenance therapy was 3 courses (range: 1 to 15). Response rate (RR) was 65.5%, and disease control rate (DCR) was 100%. Median PFS was 5.39 months (95%CI, 125-265 days). Hematological adverse events reaching grade 3 or 4 were leukocytopenia (6.8%), neutropenia (20.9%), anemia (3.4%), thrombocytopenia (6.9%), and febrile neutropenia (3.4%). Nonhematological toxicities of grade3/4 were hypertension (17.2%), appetite loss (3.4%), mucositis oral (3.4%), alkaline phosphatase elvation (3.4%), serum amylase elevation (3.4%), and hyponatremia (3.4%). Seven patients delayed the start of next course because of adverse events. Conclusions: Bevacizumab in combination with S-1 plus cisplatin was effective in disease control and well-tolerated regimen for the treatment of patients with advanced non-squamous NSCLC.

脈絡膜転移による視覚異常を主症状とした原発性肺腺癌の2症例を経験した. 1例は54歳の男性, 他の一例は58歳の女性でともに原発性肺腺癌であったが, 原発巣の呼吸器症状よりも, 眼球への転移症状を主訴として医療機関を受診した. 今後肺癌の増加に伴い, このような症例を経験する機会も多くなると思われたので, 文献的考察を加えて報告した.

Theophylline is a bronchodilator that also has an anti-inflammatory effect. In Japan, methylxanthines, including theophylline and aminophylline (theophylline ethylenediamine), have been used widely in the treatment of asthma. In some asthma management guidelines, although methylxanthines are recommend for the treatment of asthma, they are not preferred primarily because of potential serious adverse effects in case of overdose. The present review examines the efficacy and adverse effects of sustained-release theophylline and injectable methylxanthines in the treatment of chronic asthma and acute exacerbation of asthma by evaluating reports of published clinical trials and a prospective survey on the occurrence of serious adverse drug reactions to these agents. A prospective survey on the safety of methylxanthines was administered to adult patients (15–64 years of age), mainly with asthma, in medical centers by physicians certified as specialists by the Japanese Society of Allergology. Review of published clinical trials has shown that methylxanthines are effective in controlling asthma. In the prospective study, in the case of sustained-release theophylline, 3921subjects reported by 66 medical centers and meeting the criteria for inclusion in the survey were selected for analysis. In the case of intravenous methylxanthines, 682 subjects reported by 55 medical centers conforming and meeting the criteria for inclusion in the survey were selected for analysis. None of these subjects exhibited serious adverse drug reaction with sustained-release theophylline or intravenous methylxanthines. In conclusion, methylxanthines are effective for the treatment of asthma and are safe as long as the dose administered accords with the protocols recommended by asthma management guidelines.