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.

Pathophysiological mechanism of non-HIV Pneumocystis jirovecii pneumonia.

While Pneumocystis jirovecii pneumonia (PCP) can occur in immunocompromised patients with HIV infection, the prognosis of non-HIV PCP is still poor, showing a high mortality rate of 30%-75%. The pathophysiological mechanism of non-HIV PCP is quite different from that of HIV-PCP. Aging, underlying disease, dysbiotic gut microbiome, and Th1 predominance, leads to macrophagic polarization shifting from M2 to M1. These cause dysregulation in the host immunity against P. jirovecii, resulting in severe lung injury and a high mortality rate among non-HIV PCP patients. This review describes poor prognostic factors, an issue of predictive values used for general pneumonia practice, and new aspects, including the dysbiosis of the gut microbiome and macrophagic polarization in the treatment of non-HIV PCP.

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.

Rice-Field Drowning-Associated Pneumonia in which Pseudomonas spp., Aspergillus fumigatus, and Cunninghamella sp. Are Isolated.

We herein report the case of an 84-year-old who developed pneumonia after drowning in a rice field. Besides Aspergillus fumigatus, many pathogens previously not reported in drowning-associated pneumonia (such as Pseudomonas fluorescens, Pseudomonas putida, Nocardia niigatensis, and Cunninghamella sp.) were isolated from his sputum. He received sulbactam/ampicillin, trimethoprim/sulfamethoxazole, voriconazole, levofloxacin and liposomal amphotericin B, but died due to respiratory failure. Because the patient had drowned in a contaminated stagnant rice field and had multiple lung cavities, zygomycosis was suspected. This report provides invaluable information for the consideration of zygomycosis after an individual drowning in a rice field, even in an immunocompetent patient.

Familial Summer-type Hypersensitivity Pneumonitis: A Review of 25 Families and 50 Cases in Japan.

Summer-type hypersensitivity pneumonitis (SHP) is the most common form of pneumonitis in Japan; it accounts for 74% of all cases. It has been reported that 19.5-23.8% of SHP cases occur in families who live in the same house. We present our SHP cases and review 50 familial cases in 23 families that were reported in Japan (including our own) and 48 cases that were previously described in 22 articles published between January 1982 and October 2011. To the best of the authors' knowledge, this is the first review article in English to document the familial occurrence of SHP in Japan.

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.

Loop-mediated isothermal amplification method for diagnosing Pneumocystis pneumonia in HIV-uninfected immunocompromised patients with pulmonary infiltrates.

Loop-mediated isothermal amplification (LAMP) is becoming an established nucleic acid amplification method offering rapid, accurate, and cost-effective diagnosis of infectious diseases. We retrospectively evaluated 78 consecutive HIV-uninfected patients who underwent LAMP method for diagnosing Pneumocystis pneumonia (PCP). Diagnosis of PCP was made by the detection of Pneumocystis jirovecii (P. jirovecii) with positive LAMP or conventional staining (CS) (Grocott methenamine silver staining or Diff-Quick™) on the basis of compatible clinical symptoms and radiologic findings. Additionally, we reviewed HIV-uninfected immunocompromised patients who underwent subcontract PCR as a historical control. LAMP was positive in 10 (90.9%) of 11 positive-CS patients. Among 13 negative-CS patients with positive LAMP, 11 (84.6%) had PCP, and the remaining 2 were categorized as having P. jirovecii colonization. LDH levels in negative-CS PCP were higher than in positive-CS PCP (p = 0.026). (1 → 3)-ß-D-glucan levels in negative-CS PCP were lower than in positive-CS PCP (p = 0.011). The interval from symptom onset to diagnosis as PCP in LAMP group (3.45 ± 1.77 days; n = 22) was shorter than in subcontract PCR group (6.90 ± 2.28 days; n = 10; p < 0.001). As for patients without PCP, duration of unnecessary PCP treatment in LAMP group (2; 2-3 days; n = 10) was shorter than in subcontract PCR group (7; 7-12.25 days; n = 6; p = 0.003). LAMP showed higher sensitivity (95.4%) and positive predictive value (91.3%) than subcontract PCR did. Pneumocystis LAMP method is a sensitive and cost-effective diagnostic method and is easy to administer in general hospitals. In-house LAMP method would realize early diagnosis of PCP, resulting in improving PCP prognosis and reducing unnecessary PCP-specific treatment.

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.

Implementation of do not attempt resuscitate orders in a Japanese nursing home.

OBJECTIVE: To investigate whether do not attempt resuscitation (DNAR) orders can be implemented in a standard nursing home in Japan, where routine DNAR orders are not yet common in many facilities including hospitals. METHOD: Ninety-eight residents in a 100-bed nursing home were evaluated. All of the eligible residents and/or their family members were asked whether they wanted to receive resuscitation, including mechanical ventilation. RESULT: The residents were 54 to 101 years of age (mean 83.3), with 27 males and 71 females. After administering the questionnaire, 92 (94%) patients did not want resuscitation and mechanical ventilation. CONCLUSION: In a nursing home, it was possible to obtain advance directives by which most residents/families rejected resuscitation and mechanical ventilation. This could avoid unnecessary and undesirable resuscitation procedures.

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.

Therapeutic impact of CT-guided percutaneous catheter drainage in treatment of deep tissue abscesses.

Combination therapy of CT-guided percutaneous drainage and antibiotics is the first-line treatment for abscesses. Its effectiveness has been demonstrated. However, the therapeutic impact of this procedure for infection treatment has never been reported. We retrospectively analyzed all 47 patients who received CT-guided percutaneous drainage for infection treatment. Patients' characteristics, pathogens isolated, antibiotics administered, technical and clinical outcomes, complications related to this procedure and therapeutic impacts were investigated. Patients were 26 males and 21 females. The mean age was 63.5 years (±18.7). The diseases targeted were 19 retroperitoneal abscesses, 18 intra-abdominal abscesses, three pelvic abscesses, and seven others. As for technical outcomes, all of the 54 procedures (100%) were successful. As for clinical outcomes, 44 (93.6%) were cured and three patients (6.4%) died. No complications related to this procedure were found in this study. A total of 42 patients (88%) had a change in the management of their infection as a result of CT-guided percutaneous drainage, such as selection and discontinuation of antibiotics. In conclusion, CT-guided percutaneous drainage is a safe and favorable procedure in the treatment of deep tissue abscesses. Therapeutic impact of these procedures helped physicians make a rational decision for antibiotics selection.

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.