Modified MRC assessment and FEV1.0 can predict frequent acute exacerbation of COPD: An observational prospective cohort study at a single-center in Japan.

INTRODUCTION: Acute exacerbation (AE) of chronic obstructive pulmonary disease (COPD) is a fatal event, leading to poor outcomes among COPD patients. However, exact frequency and poor prognostic factors are not well known in Japan. METHODS: and patients, To assess the frequency and risk factors of AE, we performed this prospective cohort study at the Kameda Medical Center in Japan between during 2011 and 2013. AE was defined as an acute worsening of respiratory symptoms according to the GOLD guideline. Furthermore, we compared the exacerbation-free time between the groups. RESULTS: A total of 330 patients (230 COPD patients and 100 smoking controls) were enrolled in the study. The mean age in the study was 73 years, and 94% of the patients were male. As for the frequency of AE, 0.17 times/patients/year was found in all patients. The frequency of AE increased as the COPD disease severity (p = 0.042 by Jonch-Heere terpla test). GOLD I patients had longer exacerbation-free time than GOLD II, and GOLD II grade COPD patients had longer exacerbation-free time than GOLD III grade COPD patients. In terms of risk factors for AE, logistic regression analysis showed that Modified Medical Research Council (mMRC) scale ≥3 and FEV1.0% <50% were independent poor prognostic factors for moderate grade of AE events, and mMRC scale ≥3 was independent poor prognostic factor for severe AE events. CONCLUSION: The frequency of AE increases as the disease severity becomes more severe. We found mMRC scale >3 and FEV1 <50% were risk factors for AE-COPD.

Clinical Manifestations and Prognostic Factors of Pneumocystis jirovecii Pneumonia without HIV.

INTRODUCTION: Pneumocystis jirovecii pneumonia (PCP) can occur in HIV patients but also in those without HIV (non-HIV PCP) but with other causes of immunodeficiency including malignancy or rheumatic diseases. OBJECTIVE AND METHODS: To evaluate the clinical presentation and prognostic factors of non-HIV PCP, we retrospectively reviewed all patients diagnosed as having PCP without HIV at Kameda Medical Center, Chiba, Japan, from January 2005 until June 2012. For the purpose of examining a prognostic factor for non-HIV PCP with 30-day mortality, we compared the characteristics of patients, clinical symptoms, radiological images, Eastern Cooperative Oncology Group performance status (PS), and the time from the onset of respiratory symptoms to the start of therapy, in both survival and fatality groups. RESULTS: A total of 38 patients were eligible in this study. Twenty-five survived and 13 had died. The non-HIV PCP patients in the survivor group had a better PS and received anti-PCP therapy earlier than those in the nonsurvivor group. Rales upon auscultation and respiratory failure at initial visits were seen more frequently in the nonsurvivor group than in the survivor group. Lactate dehydrogenase and C-reactive protein values tended to be higher in the nonsurvivor group, but this was not statistically significant. Multivariate analyses using 5 variables showed that a poor PS of 2-4 was an independent risk factor for non-HIV PCP patients and resulted in death (odds ratio 15.24; 95% confidence interval 1.72-135.21). CONCLUSION: We suggest that poor PS is an independent risk factor in non-HIV PCP, and a patient's PS and disease activity may correlate with outcome.

Successful treatment of non-small cell lung cancer with gefitinib after erlotinib-induced severe eyelid erosion: Two case reports.

Gefitinib and erlotinib are first-generation, small, molecular inhibitors of the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Even as these drugs have led to a paradigm shift in the treatment of advanced non-small cell lung cancer (NSCLC), drug-induced adverse effects are commonly seen. We experienced two cases of NSCLC patients who developed erlotinib-induced eyelid erosion and were then successfully treated with gefitinib, without recurrence of toxicity or disease progression. As far as we had investigated, this is the first report documenting the successful cases treated with gefitinib after erlotinib-related severe eyelid erosion.

Relapsed small cell lung cancer: treatment options and latest developments.

According to recent analyses, there was a modest yet significant improvement in median survival time and 5-year survival rate of limited stage small cell lung cancer (SCLC) in North America, Europe, Japan and other countries over the last 30 years. The median survival time of limited stage SCLC is 15-20 months and 5-year survival rate is 15% or less. In terms of extensive stage SCLC, a median survival time of 9.4-12.8 months and 2-year survival of 5.2-19.5% are still disappointing. Despite being highly sensitive to first-line chemotherapy and radiotherapy treatments, most patients with SCLC experience relapse within 2 years and die from systemic metastasis. While several clinical trials of cytotoxic chemotherapies and molecular targeting agents have been investigated in the treatment of relapsed SCLC, none showed a significant clinical activity to be able to exceed topotecan as second-line chemotherapy. There are problematic issues to address for relapsed SCLC, such as standardizing the treatment for third-line chemotherapy. Topotecan alone was the first approved therapy for second-line treatment for relapsed SCLC. Amrubicin is a promising drug and a variety of trials evaluating its efficacy have been carried out. Amrubicin has shown superiority to topotecan in a Japanese population, but was not superior in a study of western patients. There are some controversial issues for relapsed SCLC, such as treatment for older patients, third-line chemotherapy and efficacy of molecular targeting therapy. This article reviews current standard treatment, recent clinical trials and other topics on relapsed SCLC.

Prognostic factors in patients with terminal stage lung cancer.

BACKGROUND: Lung cancer is the leading cause of cancer-related death.(1) Accurate prediction of survival in the terminal stage is important, because it may help patients make a rational decision. Although several prognostic scores have been described as effective indicators of outcome, these scores were intended for patients with other types of cancers. There is no prognostic score for patients with terminal-stage lung cancer. OBJECTIVE: The aim of this study was to determine prognostic factors for patients with terminal-stage lung cancer. SETTING/SUBJECTS: Patients in our palliative care unit (PCU) were selected retrospectively and divided into two independent groups, training and testing. Univariate and multivariate analyses were performed on data from the training group to detect independent prognostic factors, while data from patients in the testing group were analyzed to validate whether these prognostic factors predicted near-term death. RESULTS: Ninety-three patients (69 in the training group and 24 in the testing group) were included in the analyses. Multivariate analysis showed that fatigue, anorexia, desaturation, hyponatremia, and hypoalbuminemia were independent prognostic factors in the training group. Mean survival time in patients who had more than three of these five factors was 9.2±2.6 days (p=0.012). In the testing group, the presence of more than three of these five factors predicted death within two weeks, with a sensitivity of 100% and specificity of 75%. CONCLUSIONS: This study revealed that fatigue, anorexia, desaturation, hyponatremia, and hypoalbuminemia may be short-term prognostic factors in terminally ill lung cancer patients. In particular, the presence of more than three of these factors predicted death within two weeks.

Clinical manifestations and prognostic factor of iliopsoas abscess.

INTRODUCTION: Iliopsoas abscess (IPA) is a collection of pus in the iliopsoas compartment, which is considered rare in Japan. However, the number of patients with IPA has recently increased among the elderly or compromised hosts. SUBJECTS AND METHODS: This retrospective study aims to examine the clinical pictures, pathological findings, and the prognostic factor of IPA. We analyzed all patients with IPA who were admitted to our hospital from April 2006 to July 2011. Patients' characteristics, treatment, clinical outcome, radiological findings, bacteria isolated, and comorbidities were evaluated. The comorbidities were evaluated by the Charlson comorbidity index (CCI). We compared the survival and non-survival groups to assess the prognostic factors of IPA. RESULTS: A total of 33 patients were enrolled in this study, which included 14 males and 19 females. The mean age of the patients was 71.5 years (range 32-92 years). The most common underlying disease was spinal disease (16 of 33, 48.5%). Twenty-nine patients (87.9%) were cured and four patients (12.1%) died. While 12 patients (36.4%) were initially treated conservatively with antibiotics alone, percutaneous drainage was performed initially in 19 patients (57.6%). Two patients (6%) directly underwent exploratory surgery and open drainage. In terms of patients' characteristics, there were no significant differences in either group. The score of CCI in non-survivors was higher than that in survivors (1.38 vs. 5.5, P < 0.001). CONCLUSIONS: The epidemiology of IPA is quite different from what it used to be. CCI appears to be useful in evaluating the patients' prognosis with IPA.

Is emphysema a risk factor for pneumothorax in CT-guided lung biopsy?

INTRODUCTION: Computed tomography (CT)-guided lung biopsy is commonly used to make a histological diagnosis for pulmonary lesions. Its most common complication is pneumothorax. While it is thought that CT-guided lung biopsy should be avoided in patients with emphysema, however, there is no scientific report documenting the relationship the occurrence of pneumothorax and the severity of emphysema. PURPOSE AND METHODS: To investigate the relationship between the severity of emphysema and the frequency of pneumothorax, we retrospectively reviewed all the patients who received CT-guided lung biopsy. Severity of emphysema is evaluated by Goddard classification, a visual scale by which areas of vascular disruption and low attenuation value were scored for each lung field of high resolution CT. Patients' characteristics, prognostic accuracy of this method, size and location of the lesion, length of intrapulmonary biopsy paths, and frequency of complications such as pneumothorax or intrapulmonary hemorrhage were evaluated. RESULTS: One hundred-two patients (69 males and 33 females) received 102 procedures. Diagnostic accuracy was 90.2%. Pneumothorax occurred in 41 of 102 biopsies (40.2%). Chest tube placement was required in 3 out of the 41 cases (7.3%) complicated by pneumothorax (2.9% of all the biopsies). The longer lesion depths from pleura were, the more frequently pneumothorax occurred (6.67 vs 3.66 mm, p=0.019). No correlation was found between location of lesions and frequency of pneumothorax. No significant differences of COPD staging or LAA score were seen between the patients with and without pneumothorax (5.73 vs 4.32 points, p=0.339). CONCLUSION: We suggest that severity of emphysema such as stage I or II COPD may not be related to the frequency of pneumothorax.

A case of obstructive sleep apnea syndrome caused by malignant melanoma in the nasal cavity and paranasal sinus.

A 71 year-old obese woman complained of obstructive sleep apnea syndrome (OSAS) related symptoms. The apnea-hypopnea index (AHI) was 73.5/hour. She presented with nasal bleeding to an ENT doctor. A mass on the nasal septum was seen and biopsy was performed. Histological confirmation showed malignant melanoma. The tumor stage proved to be cT4aN2M1 (stage IV) due to multiple metastatic lesions. After palliative irradiation, the nasal tumor was reduced in size and her symptoms of OSAS were improved. The second AHI revealed 13.5/hour. This case was considered to be OSAS caused by a tumor obstructing the nasal cavity. This might suggest the necessity of routine work-up of the upper airway in cases of patients with sleep disorder. Otherwise, OSAS caused by such obstruction might be missed. We report a very rare case with secondary OSAS caused by malignant melanoma in the nasal cavity and paranasal sinus.

Non-HIV Pneumocystis pneumonia: do conventional community-acquired pneumonia guidelines under estimate its severity?

BACKGROUND: Non-HIV Pneumocystis pneumonia (PCP) can occur in immunosuppressed patients having malignancy or on immunosuppressive agents. To classify severity, the A-DROP scale proposed by the Japanese Respiratory Society (JRS), the CURB-65 score of the British Respiratory Society (BTS) and the Pneumonia Severity Index (PSI) of the Infectious Diseases Society of America (IDSA) are widely used in patients with community-acquired pneumonia (CAP) in Japan. To evaluate how correctly these conventional prognostic guidelines for CAP reflect the severity of non-HIV PCP, we retrospectively analyzed 21 patients with non-HIV PCP. METHODS: A total of 21 patients were diagnosed by conventional staining and polymerase chain reaction (PCR) for respiratory samples with chest x-ray and computed tomography (CT) findings. We compared the severity of 21 patients with PCP classified by A-DROP, CURB-65, and PSI. Also, patients' characteristics, clinical pictures, laboratory results at first visit or admission and intervals from diagnosis to start of specific-PCP therapy were evaluated in both survivor and non-survivor groups. RESULTS: Based on A-DROP, 18 patients were classified as mild or moderate; respiratory failure developed in 15 of these 18 (83.3%), and 7/15 (46.7%) died. Based on CURB-65, 19 patients were classified as mild or moderate; respiratory failure developed in 16/19 (84.2%), and 8 of the 16 (50%) died. In contrast, PSI classified 14 as severe or extremely severe; all of the 14 (100%) developed respiratory failure and 8/14 (57.1%) died. There were no significant differences in laboratory results in these groups. The time between the initial visit and diagnosis, and the time between the initial visit and starting of specific-PCP therapy were statistically shorter in the survivor group than in the non-survivor group. CONCLUSIONS: Conventional prognostic guidelines for CAP could underestimate the severity of non-HIV PCP, resulting in a therapeutic delay resulting in high mortality. The most important factor to improve the mortality of non-HIV PCP is early diagnosis and starting of specific-PCP therapy as soon as possible.

Efficacy and safety of amurubicin for the elderly patients with refractory relapsed small cell lung cancer as third-line chemotherapy.

BACKGROUND: While more elderly patients are being diagnosed with lung cancer every year, no anti-lung cancer therapy designed specifically for the elderly has been established yet. This is the first retrospective study to examine the efficacy and safety of amurubicin (AMR) for elderly patients with refractory relapsed small cell lung cancer (SCLC) as second or third-line chemotherapy. MATERIALS AND METHODS: Thirty-six patients were eligible for analyzing the frequency of hematologic and non-hematologic toxicities and effectiveness of AMR for refractory relapsed SCLC in both elderly (≥ 70 years) and non-elderly (<70 years) groups. RESULTS: Among these patients as third-line chemotherapy, the response rate and the disease control rate of refractory relapsed cases were 44.4 and 55.6%, respectively. The median of progression-free survival time was 3.0 months and the median of overall survival time was 5.1 months. There were no significant differences in the frequency of the grade 3-5 hematologic or non-hematologic toxicity between the elderly (≥ 70 years) and non-elderly (<70 years) patients or second and third-line chemotherapies. CONCLUSIONS: AMR could be one of the effective tools in the treatment of elderly patients with refractory relapsed SCLC as third-line chemotherapy, and the recommended dose is 30 mg/m 2 for three consecutive days.

Should Blood Cultures be Performed in Terminally Ill Cancer Patients?

BACKGROUND: No evidence-based guidelines or protocols to treat the infection-related symptoms in cancer patients with terminal stages have been established. MATERIALS AND METHODS: We retrospectively analyzed all the patients with terminal stage cancer who died between April 2009 and March 2010. The patients' background, the prevalence of infection and clinical outcomes, pathogens isolated, antibiotics used, and whether blood cultures and some of examinations were performed or not were evaluated. RESULTS: A total of 62 (44 males and 18 females) patients were included in this study. The median age was 73 years (35-98 years). The most common cancer was that of the lung (n =59, 95.2%). A total of 32 patients were diagnosed with the following infections: Infection of respiratory tract in 27 (84.4%), of urinary tract in 4 (12.5%), and cholangitis in 1 (3.1%). Two cases (6.3%) had pneumonia complicated with urinary tract infection. Blood cultures and antibiotic therapies were performed in 28 and 30 cases, respectively. Four (14.3%) positive cultures were isolated from the blood obtained from 28 individual patients. As for clinical course, 3 (10%) of them experienced improved symptoms after antibiotic therapy. Twenty-seven (90%) patients were not confirmed as having any symptom improvement. CONCLUSIONS: Blood cultures and antibiotic therapy were limited, and might not be effective in terminally ill cancer patients with lung cancer. We suggest that administering an antibiotic therapy without performing a blood culture would be one of choices in those with respiratory tract infections if patients' life expectancy is short.

The effect of comorbidity on the prognosis of acute lung injury and acute respiratory distress syndrome.

OBJECTIVE: We conducted a retrospective study assessing the relationship between comorbidity, using the Charlson Comorbidity Index (CCI), and the prognoses of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) patients. METHODS: We analyzed the data of 47 patients with ALI and ARDS who were admitted to our center between April 2004 and July 2009. The patients were classified into 2 groups (survival and non-survival) 3 months after diagnosis, and demographic and clinical characteristics were analyzed. We also evaluated the ROC curve and Akaike's information criterion (AIC) to determine the most appropriate cut-off level for the CCI at 3 months survival. The survival rate was estimated based on the AIC results. RESULTS: The mean age was 71.0 years; 25 (53%) of the patients died within 3 months of the diagnosis. Although age, etiology of ALI and ARDS, and APACHE II score did not differ between the two groups, smoking history, CCI, SOFA score, and steroid use were higher in the non-survival group than in the survival group. Age was not significantly correlated with CCI; however, CCI had weak, but statistically significant correlations with the APACHE II and SOFA scores (r=0.387, p<0.01 and r=0.288, p<0.05, respectively). AIC analysis revealed that a score of 4 on the CCI was the most appropriate cut off level for 3 months survival. The 3-month survival rate was lower in patients with a CCI≥4 than in those with a CCI<4 (9.5% vs. 55.5%, p<0.05). DISCUSSION: This study showed that the prognosis of ALI and ARDS was affected more by comorbidity than by age, and that the CCI was useful for assessing patient comorbidities in ALI and ARDS. We have to consider that patients with a CCI score of 4 or more are at risk of developing multi-organ failure and have a poor prognosis.

A case of novel swine influenza A (H1N1) pneumonia complicated with virus-associated hemophagocytic syndrome.

Influenza related to complications such as pneumonia and encephalitis have sporadically been reported. However, influenza A (H1N1)-virus-associated hemophagocytic syndrome (VAHS) has rarely been reported. A 39-year old woman complained of high fever and was referred to us. Chest infiltrations in both lungs and a positive polymerase chain reaction (PCR) for novel swine origin influenza A (H1N1) in bronchial alveolar lavage fluid (BALF) specimen was confirmed and she was diagnosed with influenza A (H1N1) pneumonia. Pancytopenia was found, and hemophagocytic syndrome (HPS) was diagnosed by bone marrow aspiration. Following intravenous administration of antiflu drug and combination therapy of steroid pulse and erythromycin IV, the patient's respiratory dysfunction and lab data gradually improved and she was discharged on day 21. Whereas secondary HPS related to viral infections such as Epstein­Barr virus, cytomegalovirus, and human herpesvirus type 6 are commonly seen, H1N1 pneumonia complicated with secondary VAHS is rare.