Clinical impact of episodic nocturnal hypercapnia and its treatment with noninvasive positive pressure ventilation in patients with stable advanced COPD.

Purpose: Episodic nocturnal hypercapnia (eNH) caused by rapid eye movement (REM) sleep-related hypoventilation is often noted in patients with advanced COPD. The purpose of this study was to clarify the clinical significance of eNH and the effectiveness of eNH-targeted noninvasive positive pressure ventilation (NPPV). Patients and methods: We enrolled patients with stable, severe, or very severe COPD with daytime arterial partial oxygen pressure PaO2 ≥55 mmHg and daytime arterial partial carbon dioxide pressure PaCO2 <55 mmHg, who underwent overnight transcutaneous carbon dioxide pressure (PtcCO2) monitoring from April 2013 to April 2016. We retrospectively compared clinical characteristics, daytime blood gas analysis, frequency of exacerbation, serum albumin levels, and ratio of pulmonary artery to aorta diameter (PA:A ratio), between patients with COPD with and without eNH. For those with eNH, we applied NPPV and compared these clinical characteristics before and after NPPV. Results: Twenty-one patients were finally included in this study. Ten patients (47.6%) were evaluated to have eNH. These patients had lower albumin levels (p=0.027), larger PA:A ratio (p=0.019), and higher frequency of exacerbations during the last year (p=0.036). NPPV for the patients with eNH improved daytime PaCO2 compared with that 12 months after NPPV (p=0.011). The frequency of exacerbations 1 year before NPPV decreased 1 year after NPPV (p=0.030). Serum albumin levels improved 1 year after NPPV (p=0.001). Conclusion: In patients with stable severe or very severe COPD, eNH may be a risk factor of exacerbations, hypoalbuminemia, and pulmonary hypertension. NPPV may be effective against hypoalbuminemia and acute exacerbations. However, further study is necessary to validate these findings.

Effectiveness of Shin'iseihaito in Asthmatic Patients with Upper Airway Diseases: A Retrospective Cohort Study.

BACKGROUND: Severe asthma is often associated with sinonasal diseases. Shin'iseihaito is a Japanese traditional herbal medicine, which is used to treat rhinosinusitis. However, its effectiveness in the treatment of asthma has not been elucidated. OBJECTIVE: The aims of this study were to examine the effectiveness of Shin'iseihaito in asthmatic patients with upper airway disease and to identify the characteristics of responders. METHODS: The medical records were retrospectively analyzed of asthmatic patients concomitant with upper airway disease in the outpatient department who had been administered Shin'iseihaito at least once from September 2011 to February 2015. They were classified into responders and non-responders, and the differences in characteristics were compared between the two groups. RESULTS: Shin'iseihaito was effective in 21/40 (52.5%) patients. There was no significant difference between responders and non-responders with regard to age, sex, or age of asthma onset. However, the frequency of aspirin intolerance, the treatment step of asthma, and serum immunoglobulin E levels were significantly higher in responders than they were in non-responders (p = 0.022, p = 0.017, and p = 0.017, respectively). The frequency of occurrence of concomitant eosinophilic chronic rhinosinusitis was not significantly different in both groups. CONCLUSION: Shin'iseihaito could be a potential alternative for the treatment of asthma in patients with upper airway diseases.

Co-existence and seasonal variation in rhinitis and asthma symptoms in patients with asthma.

BACKGROUND: Asthma and rhinitis are common diseases that often occur concomitantly. However, in patients with asthma, the concurrent assessment of seasonal variation in rhinitis and asthma symptoms has not been comprehensively addressed. We prospectively evaluated seasonal changes in rhinitis and asthma symptoms over one year. METHODS: Fifty-six patients with asthma were enrolled. Asthma and rhinitis symptoms were assessed by using the State of the Impact of Allergic Rhinitis on Asthma Control (SACRA) questionnaire, developed and validated in Japan by the committee　of Global Initiative for Asthma and the committee of Allergic Rhinitis for asthma and its impact on Asthma. RESULTS: Fifty-three patients completed the study. Forty-five patients (85%) had nasal symptoms during at least one or more seasons and 15 patients (28%) had perennial rhinitis. The association between asthma symptoms and rhinitis symptoms, assessed by a visual analogue scale (VAS), was significant during each season; seasonal variations of symptoms were synchronous. Uncontrolled asthma was more prevalent in patients with moderate-to-severe rhinitis compared to those with mild rhinitis. The VAS score of asthma symptoms in patients with asthma and perennial rhinitis was significantly higher than that in patients with non-perennial rhinitis or without rhinitis, across every season, except for spring. Correlations were more significantn patients less than 65 years of age than in older patients. CONCLUSION: Rhinitis is common in patients with asthma. Symptoms of rhinitis and asthma often co-exist, and the association between these symptoms may be stronger n younger patients with asthma than older.

The relationship between perioperative administration of inhaled corticosteroid and postoperative respiratory complications after pulmonary resection for non-small-cell lung cancer in patients with chronic obstructive pulmonary disease.

OBJECTIVES: Inhaled corticosteroid (ICS) treatment has been shown to increase the risk of respiratory complications in patients with stable chronic obstructive pulmonary disease (COPD). However, the effects of perioperative ICS treatment on postoperative respiratory complications after lung cancer surgery have not been elucidated. The aim of this study was to investigate whether perioperative ICS treatment would increase the risk of postoperative respiratory complications after lung cancer surgery in patients with COPD. METHODS: We retrospectively analyzed 174 consecutive COPD patients with non-small-cell lung cancer (NSCLC) who underwent lobectomy or segmentectomy between January 2007 and December 2014. Subjects were grouped based on whether or not they were administered perioperative ICS treatment. Postoperative cardiopulmonary complications were compared between the groups. RESULTS: There were no statistically significant differences in the incidence of postoperative respiratory complications (P = 0.573) between the perioperative ICS treatment group (n = 16) and the control group (n = 158). Perioperative ICS treatment was not significantly associated with postoperative respiratory complications in the univariate or multivariate analysis (odds ratio [OR] = 0.553, 95% confidence interval [CI] = 0.069-4.452, P = 0.578; OR = 0.635, 95% CI = 0.065-6.158, P = 0.695, respectively). Kaplan-Meier analysis showed that there were no statistically significant differences in the postoperative respiratory complications-free durations between the groups (P = 0.566), even after propensity score matching (P = 0.551). CONCLUSION: There was no relationship between perioperative ICS administration and the incidences of postoperative respiratory complications after surgical resection for NSCLC in COPD patients.

Severe drug-induced interstitial lung disease successfully treated with corticosteroid plus recombinant human soluble thrombomodulin.

There is no established therapeutic option for corticosteroid (CS) refractory drug-induced interstitial lung disease (DILD). We report a case of CS refractory severe DILD successfully treated with recombinant human soluble thrombomodulin (rhTM). A 64-year-old Japanese man was admitted with symptoms of fever, dry cough and dyspnoea. A chest radiograph showed bilateral infiltrations. DILD from Nijutsutou, a Chinese medicine, was suspected based on a history of similar interstitial lung disease after its administration 4 years prior and a positive drug-induced lymphocyte stimulation test. Nijutsutou was promptly discontinued and high doses of CS administered, but the patient's bilateral infiltrations remained unimproved. Since coagulation tests also indicated a rapid aggravation of coagulopathy, rhTM was added to the CS therapy. The patient's lung infiltration ameliorated and plasma levels of D-dimer and high morbidity group box 1 (HMGB1) decreased. rhTM may be an alternative agent for CS refractory DILD. Further study is necessary to confirm this.

A pleomorphic carcinoma of the lung producing multiple cytokines and forming a rapidly progressive mass-like opacity.

BACKGROUND: Lung cancer cells have been reported to produce cytokines, resulting in systemic reactions. There have been few reports showing that these cytokines induced the formation of an inflammatory mass around lung cancers. CASE PRESENTATION: We encountered a patient with a pleomorphic carcinoma of the lung. This tumor produced interleukin (IL)-8, granulocyte colony-stimulating factor and IL-6, which in turn recruited inflammatory cells, such as CD8 positive lymphocytes, around the tumor, resulting in a rapidly growing tumor shadow. CONCLUSION: 18 F-fluoro-deoxy-glucose positron emission tomography, in addition to a conventional radiological approach such as computed tomography, may detect immunological responses around a tumor.

Prognostic impact of preoperative monocyte counts in patients with resected lung adenocarcinoma.

OBJECTIVES: Increasing evidence suggests that an elevated peripheral monocyte count at presentation predicts a poor prognosis in various types of malignancy, including malignant lymphoma. In lung adenocarcinoma, tumor-associated macrophages (TAMs) were reported to be associated with a poor prognosis. However, it is unknown if an elevated peripheral monocyte count is associated with a poor prognosis in lung adenocarcinoma. This study assessed the prognostic impact of the preoperative peripheral monocyte count in lung adenocarcinoma. MATERIALS AND METHODS: We retrospectively analyzed 302 consecutive patients with lung adenocarcinoma who received curative resection at Kitano Hospital. The receiver operating characteristic (ROC) curve for the peripheral monocyte count was used to determine the cut-off value. The relations between peripheral monocyte counts and clinicopathological factors were assessed. We also evaluated the impacts of possible prognostic factors including the preoperative peripheral monocyte count on survival, using the two-tailed log-rank test and Cox proportional hazards model. In addition, immunohistochemical staining for CD68 was performed to evaluate the monocytes in primary tumors. RESULTS: A peripheral monocyte count of 430mm(-3) was the optimal cut-off value for prognosis. An elevated peripheral monocyte count was significantly associated with sex, performance status, smoking history, chronic obstructive pulmonary disease and interstitial lung disease. The two-tailed log-rank test demonstrated that patients with an elevated peripheral monocyte count experienced a poorer recurrence-free survival (RFS) and overall survival (OS) (P=0.0063, P<0.0001, respectively). In the multivariate analysis an elevated peripheral monocyte count was shown to be an independent prognostic factor for the RFS and OS (HR: 1.765; 95% CI: 1.071-2.910; P=0.0258, HR: 4.339; 95% CI: 2.032-9.263; P=0.0001, respectively). Furthermore, numbers of the monocytes in primary tumors significantly correlated with peripheral monocyte counts (r=0.627, P<0.0001). CONCLUSION: The preoperative peripheral monocyte count is an important prognostic factor for patients with lung adenocarcinoma after curative resection.

Effect of a network system for providing proper inhalation technique by community pharmacists on clinical outcomes in COPD patients.

INTRODUCTION: Nonadherence to inhalation therapy is very common in patients with chronic obstructive pulmonary disease (COPD). Few data are available to support the role of community pharmacists in optimizing inhalation therapy in COPD patients. Since 2007, the Kitano Hospital and the Kita-ku Pharmaceutical Association have provided a network system for delivering correct inhalation techniques through certified community pharmacists. The effects of this network system on clinical outcomes in COPD patients were examined. METHODS: A total of 88 consecutive outpatients with COPD at baseline and 82 of those 4 years later were recruited from the respiratory clinic of Kitano Hospital Medical Research Institute. Measurements included the frequency of COPD exacerbations, patients' adherence to inhalation therapy using a five-point Likert scale questionnaire, and patients' health status both prior to this system and 4 years later. RESULTS: Usable information was obtained from 55 patients with COPD at baseline, and from 51 patients 4 years later. Compared with baseline values, a significant decrease was observed in the frequency of COPD exacerbations (1.5 ± 1.6 versus 0.8 ± 1.4 times/year, P = 0.017). Adherence to the inhalation regimen increased significantly (4.1 ± 0.7 versus 4.4 ± 0.8, P = 0.024), but health status was unchanged. At 4 years, of 51 COPD patients, 39 (76%) patients who visited the certified pharmacies showed significantly higher medication adherence than those who did not (4.6 ± 0.6 versus 3.9 ± 1.0, P = 0.022). CONCLUSION: The network system may improve COPD control and adherence to inhalation regimens.

Septic pulmonary embolism due to periodontal disease.

BACKGROUND AND OBJECTIVE: Septic pulmonary embolism due to periodontal disease (SPE-PD) is rarely reported and little is known about its clinical features. The purpose of this study was to evaluate the clinical and radiological features, as well as outcome, in SPE-PD. METHODS: Patients' records were retrospectively reviewed and 12 patients with SPE-PD were identified (10 men, mean age 60.5 years). The patients' demographic features, laboratory data, physical and radiological findings, and clinical outcomes were evaluated. RESULTS: All but one patient were smokers. Eight of the 12 patients had comorbidities including hypertension (58%) and/or diabetes mellitus (17%). Prevalent symptoms were fever (67%) and chest pain (58%). Only two patients fulfilled the criteria of systemic inflammatory response syndrome; most of the subjects were not clinically severely ill. Blood cultures were negative in all cases. Contrast-enhanced chest computed tomography (CT) showed multiple peripheral nodules in all 12 patients, wedge-shaped peripheral lesions abutting on the pleura in 10 (83%) and a feeding-vessel sign in 9 (75%). All patients recovered from their illness after antimicrobial therapy concomitant with tooth extraction or periodontal care. The median duration of antibiotic administration was 51 days. CONCLUSIONS: Most patients with SPE-PD were not seriously ill. Contrast-enhanced chest CT appeared to be useful to diagnose SPE-PD.

Impact of a network system for providing proper inhalation technique by community pharmacists.

OBJECTIVE: The availability of many types of inhalers in the treatment of asthma has resulted in a wide range of prescription choices for clinicians. With so many devices available, however, there is some confusion regarding their proper use among both medical staff and patients. Since 2007, Kitano Hospital and Kita-ku Pharmaceutical Association, Osaka, Japan, have provided a network system for delivering instruction on correct inhalation technique through community pharmacists. We examined the clinical effects of this network system. METHODS: Our measurements included the manner in which community pharmacists instruct patients with asthma, the frequency of asthma exacerbations, patients' adherence to inhalation therapy using a 5-point Likert scale questionnaire, and patients' health status both prior to this system and at 4 years after. RESULTS: Usable information was obtained from 53 community pharmacists and 146 patients with asthma at baseline and from 60 community pharmacists and 148 patients at 4 years. When compared with baseline values, significant improvement was found in pharmacists' instruction and significant decreases were observed in the frequency of asthma exacerbations (1.4 ± 1.6 vs. 1.0 ± 1.4 times/yr, p = .042) and emergency room visits (0.5 ± 1.0 vs. 0.2 ± 0.5 times/yr, p = .004). Adherence to the inhalation regimen significantly increased (4.0 ± 0.7 vs. 4.2 ± 0.8, p = .041), but health status was unchanged. CONCLUSIONS: Our network system may improve asthma control and adherence to inhalation regimens.

[Effectiveness of the HighFO novel oxygen nebulizer for respiratory failure patients with severe hypoxia].

Optimal oxygen delivery is an essential component of therapy for patients with respiratory failure. Reservoir masks or air entrainment nebulizers have often been used for patients who require highly concentrated oxygen, but these may not actually deliver a sufficient fraction of inspired oxygen if there is a marked increase in the patient's ventilatory demands, or if oxygen flow becomes limited due to high resistance in the nebulizer nozzles. The HighFO nebulizer is a novel air entrainment nebulizer equipped with unique structures which reduce nozzle resistance, and as a result, it is possible to supply a sufficient flow of highly concentrated-oxygen. The purpose of this study was to evaluate the effectiveness and usefulness of the HighFO nebulizer in 10 respiratory failure patients with severe hypoxemia who used a reservoir mask and required more than 10 L/min of oxygen supply. In each case, the reservoir mask was replaced with the HighFO nebulizer, and changes in percutaneous oxygen saturation (SpO2) were monitored using pulse oximetry. Oxygenation improved promptly after the reservoir mask was substituted for the HighFO nebulizer (SpO2 : 83.7% +/- 8.5%-94.2% +/- 3.2%, p = 0.007). This finding suggests that the HighFO nebulizer was reasonably effective in delivering highly concentrated oxygen, sufficient for patient demands. The HighFO nebulizer may be the beginning of a new strategy for oxygen therapy.

Successful chemotherapy for small-cell lung cancer in an elderly patient undergoing continuous ambulatory peritoneal dialysis.

A standard treatment has not yet been established for elderly small-cell lung cancer patients, especially when they have end-stage renal disease. We report the first case of successful chemoradiotherapy in an elderly small-cell lung cancer patient undergoing continuous ambulatory peritoneal dialysis. A 77-year-old Japanese man on continuous ambulatory peritoneal dialysis was diagnosed as having limited disease small-cell lung cancer. He received four monthly cycles of chemotherapy consisting of carboplatin at 240 mg/m(2) on day 1 and etoposide at 40 mg/m(2) on days 1 and 3. He underwent additional hemodialysis on days 1 and 3, while continuous ambulatory peritoneal dialysis continued as usual on the other days. Following chemotherapy, he underwent hyperfractionated radiotherapy to a total dose of 45 Grey, resulting in complete remission of the disease. A pharmacokinetic study showed an area under the concentration-time curve of carboplatin of 3.41 to 4.88 mg.min/mL, increasing gradually over the first three cycles, while etoposide did not show this gradual increase. The increased area under the concentration-time curve of carboplatin may have reflected a worsened renal function during chemotherapy. Despite dose reductions and favorable areas under the concentration-ime curve of carboplatin, the patient suffered grade 3-4 hematological toxicities, necessitating transfusions and a further dose reduction. The patient died of recurrent small-cell lung cancer 19 months after diagnosis.

Massive eosinophilic pleural effusion preceding vasculitic symptoms in Churg-Strauss syndrome.

We report a case of Churg-Strauss syndrome (CSS) presenting as a massive pleural effusion. A 52-year-old asthmatic Japanese woman presented with progressive dyspnea caused by an eosinophilic pleural effusion (EPE). She also had chronic sinusitis, skin lesions and blood eosinophilia, but no antineutrophil cytoplasmic antibodies. Skin biopsy and the late onset of mononeuritis multiplex led to the diagnosis of CSS. The pleural effusion resolved soon after corticosteroid treatment was started. CSS is rare as a cause of EPE, but should be included in the differential diagnosis of EPE in asthmatic patients. This is the first report showing that EPE can precede other vasculitic symptoms in CSS.

Pulmonary thrombosis with transient antiphospholipid syndrome after mononucleosis-like illness.

Antiphospholipid antibodies (aPL) have been reported to occur in numerous viral infections. We report a 24-year-old Japanese woman, who developed multiple venous thrombosis associated with the elevation of anticardiolipin IgM after acute viral infection presenting a mononucleosis-like illness. Two months later, aPL and thromboses disappeared. In this case both parvovirus B19 and cytomegalovirus antibodies IgM were elevated, which indicated the possibility of cross-reaction.

[A case of drug-induced pleuritis, possibly due to Hochuekkito].

We report a case of drug-induced pleuritis possibly due to Hochuekkito. Hochuekkito, a Chinese-Japanese herbal medicine, was prescribed for a 33-year-old woman with panic disorder and depressive state. About 10 weeks after the first administration, she was admitted complaining of chest pain and cough. Chest X-ray and computed tomography showed the right pleural effusion. Thoracocentesis revealed eosinophilic pleuritis. Discontinuation of Hochuekkito resulted in improvement of the clinical findings. Based on the clinical course, we considered this case to be Hochuekkito-induced pleuritis.

[A case of pulmonary adenocarcinoma accompanied by minimal change nephrotic syndrome, antiphospholipid syndrome and warm-type autoimmune hemolytic anemia].

A 49-year-old man was urgently admitted due to edema in both leg and left toe pain. A chest radiograph revealed a solitary nodule in the right lung field. Detailed investigations including bronchoscopy and renal biopsy led to a simultaneous diagnosis of clinical stage IIIB pulmonary adenocarcinoma, minimal change nephrotic syndrome, antiphospholipid syndrome, and warm-type autoimmune hemolytic anemia. Prednisolone was administered for nephrotic syndrome, antiphospholipid syndrome and warm-type autoimmune hemolytic anemia, and 6 courses of chemotherapy with 70Gy radio-therapy were performed. The pulmonary nodule significantly decreased in size and the other three autoimmune diseases appeared to be well-controlled. Thirteen months after admission, multiple brain metastases developed along with worsening antiphospholipid syndrome symptoms including lupus anticoagulant. Following whole-brain irradiation, the brain metastases decreased in size and antiphospholipid syndrome symptoms improved. Thirty-nine months after the initial visit, the primary lung cancer, its brain metastasis and the 3 other autoimmune diseases appeared to be well-controlled. The temporal correlation of the lung cancer and the three autoimmune diseases suggests the latter may be paraneoplastic syndrome.

[A case of cryptogenic organizing pneumonia accompanied by large bullae].

A 66-year-old man complaining of fever was given intravenous antibiotic therapy, but he did not improve. After subsequent admission, chest X-ray film and computed tomography scans showed large bullae and consolidation in the right lung field. A transbronchial lung biopsy specimen revealed infiltration of mononuclear cells in alveolar septa and organizing lesions in alveolar ducts. We considered this case to be cryptogenic organizing pneumonia (COP) from its clinical course and pathological findings. Treatment with corticosteroid resulted in disappearance of the large bullae and consolidations. COP accompanied by large bullae is very rare. The large bullae may have been caused by check-valve mechanism.

[Pleurodesis using autologous blood plus OK-432 for intractable spontaneous pneumothorax with high surgical risk].

Air leakage persisted from the lung in three cases of spontaneous pneumothorax. Pleurodesis with autologous blood ended in failure. Autologous blood plus OK-432 was instilled into the thoracic cavity from the chest drainage tube. Air leakage was stopped without serious side effects and the chest tube was removed uneventfully. Although the long-term outcome of this treatment is not known, pleurodesis using autologous blood plus OK-432 may be an effective way of treatment for spontaneous pneumothorax in cases with high surgical risk.

[A case of small cell lung cancer with an initial symptom of breast metastasis].

We report a case of small cell lung cancer with an initial symptom of breast metastasis. A 55-year-old woman was admitted complaining of multiple breast masses. Chest computed tomography (CT) and magnetic resonance imaging (MRI) showed a left hilar mass. Specimens obtained from a breast mass and transbronchial biopsy revealed neoplastic cells suggesting small cell carcinoma Small cell lung cancer with breast metastasis was diagnosed. Systemic chemotherapy resulted in partial remission of the primary lesion and breast metastases.

[Three sisters of pulmonary Mycobacterium avium complex disease].

We reported three sisters of pulmonary Mycobacterium avium complex (MAC) disease. The oldest sister was complaining of bloody sputum, and cultures were positive for M. avium. By monotherapy with clarithromycin, symptom and imaging findings had shown no progression for six years. The second sister was complaining of productive cough, and cultures were positive for M. intracellulare. Her symptom and imaging findings had shown no progression for seven years without any treatment. The third sister had rheumatoid arthritis and diabetes mellitus, and cultures were positive for M. intracellulare. Although she received chemotherapy with rifampicin, clarithromycin, ethambutol, and kanamycin, symptom and imaging findings had progressed gradually. She died of respiratory failure four years later. Autopsy findings revealed no disseminated MAC disease. The results which three cases showed different isolate patterns and clinical courses suggest the importance of underlying anti-mycobacterial immunological impairment and defects of local host defense rather than virulence of infected strains as the pathogenesis of pulmonary MAC disease.