Association between episodes of upper respiratory infection and exacerbations in adult patients with asthma.

BACKGROUND: Asthma has several phenotypical features, including recurrent exacerbations and recurrent episodes of upper respiratory infection (URI). PURPOSE: A retrospective study was performed to identify the characteristics of adult patients with recurrent exacerbations of asthma, especially in association with recurrent episodes of URI. METHODS: Information was collected using a self-administered questionnaire given to 7070 patients in autumn-winter 2006, 4859 patients in spring-summer 2007, and 4452 patients in autumn-winter 2007. The patients reported the degree of symptoms and the frequency of febrile episodes of URI and exacerbations. Severe exacerbations were defined as a self-report of asthma-related hospitalization, an emergency department visit, or a requirement for systemic corticosteroids. Recurrent febrile URI and exacerbations were defined as two or more episodes within the previous 6 months. A Poisson regression model was used to identify the factors that were predictors of a risk for exacerbations. RESULTS: Of the 6266 patients who completed the questionnaire, the frequencies of febrile URI and episodes of severe exacerbations were 1.54 and 0.54 per subject per year, respectively. Logistic regression analysis showed that an older age [odds ratio (OR): 1.57; 95% confidence interval (CI): 1.15-2.13], female sex (OR: 1.58; 95% CI: 1.20-2.08), recurrent febrile episodes of URI (OR: 2.68; 95% CI: 1.47-4.91), a history of previous exacerbation within 1 year (OR: 1.74; 95% CI: 1.28-2.34), disuse of inhaled corticosteroids (ICSs) (OR: 2.63; 95% CI: 1.68-4.12), and disuse of add-on leukotriene receptor antagonists (LTRAs) (OR: 1.42; 95% CI: 1.06-1.74) were independently associated with moderate to severe symptom-severity. Poisson regression analysis showed that the independent factors that contributed to the frequency of recurrent severe exacerbations were female sex (regression coefficient ß = 0.62, p < .01), an episode of sputum with coughing (ß = 1.23, p < .01), nocturnal awakening (ß = 1.22, p < .01), and severe exacerbation (ß = 0.78, p < .01) within the previous 6 months. CONCLUSION: Symptom-severity of asthma and the frequency of severe exacerbations were associated with previous exacerbations and susceptibility to URI.

Therapeutic effect of direct hemoperfusion with a polymyxin B-immobilized fiber column in the treatment of HIV-negative severe pneumocystis pneumonia.

BACKGROUND: Direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP) has been shown to improve oxygenation in cases of diffuse alveolar damage, but little is known about its effectiveness in treating pneumocystis pneumonia (PCP) in HIV-negative immunosuppressed patients. OBJECTIVES: This study was aimed at investigating the effect of PMX-DHP in treating non-HIV-related PCP. METHODS: Between October 2005 and September 2008, 6 patients with non-HIV-related PCP were treated with 2 sessions of PMX-DHP at an attending physician's discretion when severe hypoxemia developed despite conventional treatments including high-dose corticosteroid, whereas 9 patients in a similar condition were treated without PMX-DHP. Changes in oxygenation and radiographic findings in the PMX-DHP group and adverse events associated with PMX-DHP were investigated retrospectively, as were the outcomes for both treatment groups. RESULTS: There was an improvement in PaO(2)/FiO(2) during each PMX-DHP session, from 148.8 ± 52.5 to 188.2 ± 79.3 mm Hg (p = 0.02). After 2 sessions of PMX-DHP, an improvement in PaO(2)/FiO(2), from 131.8 ± 37.4 to 213.3 ± 87.3 mm Hg, was observed (p = 0.04), but no significantly different improvement was detected on the following day. The radiographic findings improved in 4 patients during PMX-DHP. The in-hospital mortality was similarly high in both groups (50% in the PMX-DHP group vs. 67% in the non-PMX-DHP group). No significant adverse events associated with PMX-DHP were observed except for advanced thrombocytopenia in 1 patient. CONCLUSION: PMX-DHP may serve as an adjunct in the treatment of non-HIV-related PCP, temporarily alleviating severe hypoxemia even in cases refractory to conventional treatments.

The use of non-invasive ventilation for life-threatening asthma attacks: Changes in the need for intubation.

BACKGROUND AND OBJECTIVE: Although non-invasive ventilation (NIV) has been shown to be effective in a wide variety of respiratory diseases, its role in severe asthma attacks remains uncertain. The aim of this study was to clarify the effectiveness of NIV in patients experiencing severe attacks of asthma. METHODS: A retrospective cohort study was performed, comparing the periods November 1999-October 2003 (pre-introduction of NIV) and November 2004-October 2008 (post-introduction of NIV). The data and clinical outcomes for patients who experienced severe attacks of asthma, and who fulfilled the inclusion criteria, were retrieved and compared. RESULTS: Fifty events (48 patients) from the pre-NIV period and 57 events (54 patients) from the post-NIV period, which required hospitalization, were included in the analysis. Nine of the 50 pre-NIV events (mean PaO(2)/fraction of inspired O(2) (FiO(2)) 241 +/- 161; PaCO(2) 79 +/- 40) were treated primarily by endotracheal intubation (ETI), while 17 of the 57 post-NIV events (PaO(2)/FiO(2) 197 +/- 132, P = 0.39; PaCO(2) 77 +/- 30, P = 0.95) were treated primarily by NIV. The rate of ETI decreased in the post-NIV period (2/57 (3.5%) vs 9/50 (18%), P = 0.01). NIV was started earlier than mechanical ventilation (MV) with ETI (mean time interval between arrival and start of MV 171.7 +/- 217.9 min vs 38.5 +/- 113.8 min for NIV, P < 0.05). In the post-NIV cohort, there was a trend towards a reduction in the duration of MV with ETI or NIV (36.9 +/- 38.4 h vs 20.3 +/- 35.8 h, P = 0.09), and hospital stay was shortened (12.6 +/- 4.2 vs 8.4 +/- 2.8 days, P < 0.01). No deaths occurred during this period as a consequence of asthma attacks. CONCLUSIONS: The need for ETI in patients with severe attacks of asthma was decreased after introduction of NIV. The ready availability of NIV enabled the rapid commencement of MV and may decrease the need for ETI. NIV is an acceptable and useful method of stabilizing patients experiencing severe attacks of asthma.

[Case of rapidly progressing primary pulmonary rhabdomyosarcoma with bloody pleural effusion].

A 64-year-old man, complaining of dyspnea from the beginning of May 2006, was admitted to a local hospital because of bloody pleural effusion. After a drainage procedure of the right thoracic cavity was performed, he was referred to our hospital on May 15. Approximately one liter of bloody pleural effusion was drained every day. Computed tomography (CT) on admission showed right pleural effusion, a collapsed right lung and a large marginally enhanced low-density mass in the right lung field. We could not make a specific diagnosis even with a cytological examination of the pleural effusion and thoracoscopic pleural biopsy. Accordingly, open thoracotomy was performed and rhabdomyosarcoma was finally diagnosed. The tumor grew rapidly in a short period, and the patient died only one month after the onset of his complaint. Autopsy revealed primary pulmonary rhabdomyosarcoma occupying most of the right thoracic cavity, but no metastasis. Initially we could not identify the tumor by CT scan, mainly because it had the same density as muscle, nearly the same density as the pleural effusion and lower density than other lung cancers. Primary pulmonary rhabdomyosarcoma is rare. As this tumor could show unexpectedly fast growth, rapid diagnosis is essential. Therefore, we should include thoracic sarcoma in the list of differential diagnosis of rapidly growing lung tumors and bloody pleural effusion.

[A case of lung cancer combined with pregnancy; dramatically deteriorating condition after caesarian section].

A 34-year-old pregnant woman was diagnosed with pneumonia at another hospital in her 26th week of pregnancy. Antibiotics were administered, but they were not effective. She was then introduced and admitted to our hospital. Lung cancer was suspected from her chest-CT scan on admission. Caesarian section was performed on the day after admission at 33 weeks of gestation. Adenocarcinoma of the lung was diagnosed based on the results of a right-axillary lymph node biopsy performed simultaneously with the caesarian section. On the 8th day after admission, we began to administer gefitinib. We expected positive results from gefitinib, because the patient fitted the optimal profile: female, never smoker, adenocarcinoma histology. Her respiratory condition had worsened dramatically after her caesarian section, so she was given noninvasive positive pressure ventilation from the 13th day after admission. Disseminated intravascular coagulation progressed, and her chest X-ray showed bilateral extensive infiltration. Moreover, tests showed that her tumor was negative for epidermal growth factor recepter mutation, so we judged that gefitinib was not effective for her. Although her performance status was very poor, she and her family strongly desired further chemotherapy. We thus began to administer gemcitabine, but her respiratory condition deteriorated further, and she died on the 17th day after admission. Lung cancer combined with pregnancy is a very rare situation, so we report this case with some references.

[An autopsy case of racemose hemangioma of bronchial arteries associated with neovascularization from the chest wall after ligation and frequent embolizations].

We report an autopsied 33 year old pregnant woman with racemose hemangioma of the bronchial arteries. She was first given a diagnosis of racemose hemangioma of the bronchial arteries at age 19 and underwent surgical ligation. Nevertheless, she had to be admitted to the hospital for bronchial artery embolizations every time hemoptysis recurred. In her 21st gestational week, she was admitted to our hospital because of her 9th recurrent massive hemoptysis and dyspnea. Bronchial artery embolizations were repeatedly performed under intubation to ventilate the healthy left lung separately. We succeeded in temporarily stopping the hemoptysis, but her case was complicated by bacterial pneumonia and septic shock. Her baby was born dead on day 11 and she died on day 12. The autopsy revealed abnormal convoluted and dilated arteries branching from the right intercostal and subclavian arteries and intruding into the lung parenchyma through adhesion caused by her previous thoracostomy. The connections of these abnormal arteries with pulmonary arteries and veins, which had been shown by angiography, were confirmed by autopsy. The autopsy findings suggest that temporal surgical procedures with thoracostomy in this condition can induce abnormal neovascularization via pleural adhesion.

[A case of cavitating pneumococcal pneumonia developed during the treatment with etanercept for rheumatoid arthritis].

A 54-year-old woman who had been treated for rheumatoid arthritis (RA) with the anti-TNF-alpha drug, etanercept, was referred to our department on 27 April 2006 because of dyspnea and shock. Chest X-ray and computed tomography on admission indicated bilateral pneumonia which was proved to be caused by Streptococcus pneumoniae with positive blood culture results. The patient had recovered from multiple organ failure with intensive treatments such as NIPPV and cardiovascular support with cathecolamines, however, the left upper lobe of her lung had developed a large cavity that had been producing viable pneumococci on sputum culture for more than one month. As the development of lung necrosis and subsequent formation of a cavity is rare in patients with pneumococcal pneumonia, this case should be noted in terms of the relevance of both the fulminating pathogenecity of Streptococcus pneumoniae and the anti TNF-alpha drug treatment.

[Pulmonary eosinophilic granuloma presenting as a solitary pulmonary nodule].

A symptomless 60 year old man with a heavy smoking history presented with a nodule in the right lung, which was found by an annual chest X-ray. Chest CT showed a 1 cm speculated nodule in the right S8. Bronchoscopic transbronchial biopsy to the nodule yielded no definite diagnosis. Since the nodule was highly suggestive of lung cancer, wedge resection was performed by video-assisted thoracoscopic surgery. Pathological findings of the specimen showed that the nodule consisted of a mixed population of histiocytoid cells with eosinophils. The nuclei and cytoplasms of the histiocytoid cells were stained positively for S-100 protein. Pulmonary eosinophilic granuloma (PEG) was diagnosed. Common radiographic findings of PEG should present with a mixture of multiple nodular shadows and cystic lesions. PEG presenting as a solitary nodule is rare.

Frequency of EGFR and KRAS mutations in Japanese patients with lung adenocarcinoma with features of the mucinous subtype of bronchioloalveolar carcinoma.

INTRODUCTION: Adenocarcinoma of the lung, especially bronchioloalveolar carcinoma (BAC) and adenocarcinoma with BAC features (AWBF), is potentially sensitive to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs); however, the efficacy seems to differ between the histologic subtypes. Mucinous BAC and AWBF (MBAC/AWBF) are not particularly responsive to EGFR-TKIs compared with nonmucinous BAC/AWBF (N-MBAC/AWBF). This may be due to the rarity of EGFR mutations and high frequency of KRAS mutations in MBAC/AWBF in contrast to N-MBAC/AWBF. METHODS: One hundred ninety-one patients with adenocarcinoma of the lung underwent surgery at our institution. There were 59 patients (30%) diagnosed with BAC/AWBF; 20 had MBAC/AWBF (10%) and 39 had N-MBAC/AWBF (20%). We isolated 44 tissue specimens from these patients (20 consecutive cases of MBAC/AWBFs and 24 randomly chosen cases of N-MBAC/AWBFs as the control group), and we analyzed them for EGFR and KRAS mutations. We used the peptide nucleic acid-locked nucleic acid polymerase chain reaction clump method to detect EGFR mutations and conventional DNA sequencing to identify KRAS mutations. RESULTS: EGFR mutations were found in three of the 20 MBAC/AWBFs (15%) and in 14 of the 24 N-MBAC/AWBFs (58%) (p = 0.005). In addition, there were 14 KRAS mutations identified in the 20 MBAC/AWBFs (70%) and seven in the 24 N-MBAC/AWBFs (29%) (p = 0.0144). CONCLUSIONS: The incidence of EGFR mutation is low and that of KRAS mutation is frequent in MBAC/AWBFs. Conversely, the incidence of EGFR mutation is high and KRAS mutation is low in N-MBAC/AWBFs. Based on these findings, EGFR-TKIs may not be effective in patients with MBAC/AWBF.

Role of non-invasive ventilation in managing life-threatening acute exacerbation of interstitial pneumonia.

INTRODUCTION: Invasive mechanical ventilation (IMV) is not effective for acute exacerbation of interstitial pneumonia (AE-IP); however, the role of non-invasive ventilation (NIV) for this condition remains unknown. METHODS: Comparisons were made for two periods: before (October 2001 - September 2003) and after (October 2004 - September 2006) the introduction of NIV as the primary method of mechanical ventilation for AE-IP. We retrospectively screened emergent admissions and enrolled consecutively those patients with AE-IP who had acutely worsening hypoxemia with new infiltrates, background chronic interstitial CT changes, and no findings suggestive of other diseases. The two periods were compared primarily for 60-day survival and secondarily for other outcomes associated with mechanical ventilation. RESULTS: Medical records were retrieved for 11 episodes in 11 patients identified from 485 pre-NIV records and 27 episodes in 22 patients from 859 post-NIV records. Five patients required IMV in the earlier cohort and 9 patients received NIV in the later cohort. Although there was no difference in the PaO(2)/FiO(2) ratio on admission (167 vs. 139), the 60-day survival rate for all episodes in the later cohort was better than in the earlier cohort (27% vs. 65%, p=0.02). Moreover, the NIV-administered group had a better 60-day survival rate (0% vs. 44%, p=0.03), shorter high-care unit stay (17 vs. 6 days, p=0.03) and better-preserved verbal communication (0 vs., 89%) than the IMV-administered group. CONCLUSION: Use of NIV in place of IMV for the management of life-threatening AE-IP appears to result in a better 60-day survival rate, lower high-care unit use and better patient tolerability.

Impact of noninvasive ventilation (NIV) trial for various types of acute respiratory failure in the emergency department; decreased mortality and use of the ICU.

BACKGROUND: Trial of noninvasive ventilation (NIV) in the emergency department (ED) for heterogeneous acute respiratory failure (ARF) has been optional and its clinical benefit unclear. METHODS: We conducted a retrospective cohort study comparing between two periods, October 2001-September 2003 and October 2004-September 2006, i.e., before and after adopting an NIV-trial strategy in which NIV was applied in the ED to any noncontraindicated ARF patients needing ventilatory support and was then continued in the intermediate-care-unit. During these two periods, we retrieved cases of ARF treated either invasively or with NIV, and compared the patients' in-hospital mortalities and the length of ICU and intermediate-care-unit stay. RESULTS: Compared were 73 (invasive 56, NIV 17) and 125 cases (invasive 31, NIV 94) retrieved from 271 and 415 emergent admissions with proper pulmonary etiologies for mechanical ventilation, respectively. Of their respiratory failures, type (hypercapnic/non-hypercapnic, 0.97 vs. 0.98) and severity (pH 7.23 vs. 7.21 for hypercapnic; PaO(2)/FiO(2) 133 vs. 137 for non-hypercapnic) were similar, and the rate of predisposing etiologies was not significantly different. However, excluding those with recurrent aspiration pneumonia for whom NIV was mostly used as "ceiling" treatment, significant reductions in both overall in-hospital mortality (38%-19%, risk ratio 0.51, 95% CI 0.31-0.84), and median length of ICU and intermediate-care-unit stay (12 vs. 5 days, P<0.0001) were found. CONCLUSIONS: NIV-trial in the ED for all possible patients with ARF of pulmonary etiologies, excluding those with recurrent aspiration pneumonia, may reduce overall in-hospital mortality and ICU stays.

Efficacy and safety of once-daily inhaled ciclesonide in adults with mild to moderate asthma: a double-blind, placebo-controlled study.

BACKGROUND AND OBJECTIVE: Inhaled corticosteroids are recommended as first-line therapy for the management of asthma, although side-effects may limit their use. Ciclesonide, a novel pro-drug inhaled corticosteroid, exerts potent and prolonged local anti-inflammatory effects in the lungs, and is considered to have an improved safety and tolerability profile. The aim of this study was to evaluate the efficacy and safety of ciclesonide in adult patients with mild to moderate asthma. METHODS: A placebo-controlled, multicentre, randomized, double-blind, parallel-group study was conducted. During the 4-week baseline period, patients were given 400 microg/day of beclomethasone dipropionate in a chlorofluorocarbon formulation. After the baseline period, 311 patients were given once-daily 100, 200 or 400 microg of ciclesonide or placebo for an 8-week treatment period without the use of a spacer. The primary efficacy variable was morning PEF. RESULTS: Changes in the morning PEF (least squares mean) at the end of the study were 4.23 L/min (P < 0.001) in the 100 microg group, 3.75 L/min (P < 0.001) in the 200 microg group, -0.40 L/min (P < 0.001) in the 400 microg group, as compared with -24.95 L/min in the placebo group. In the ciclesonide groups, the PEF remained at the same level as the baseline period. No large differences were observed between the placebo group and the ciclesonide groups regarding safety. CONCLUSION: Once-daily administration of ciclesonide at doses of 100, 200 or 400 microg was shown to be effective in adult patients with mild to moderate asthma. Ciclesonide is considered to have favourable safety profiles and be well tolerated.

Efficacy and safety of inhaled ciclesonide compared with chlorofluorocarbon beclomethasone dipropionate in adults with moderate to severe persistent asthma.

BACKGROUND AND OBJECTIVE: Inhaled corticosteroids are recognized as first-line therapy in the management of asthma; however, their use may be limited by systemic and local side-effects. Ciclesonide, a novel pro-drug inhaled corticosteroid, is activated in the lungs and is expected to have less systemic and local side-effects. This study evaluated the efficacy and safety of ciclesonide in hydrofluoroalkane (HFA) compared with beclomethasone dipropionate (BDP) in a chlorofluorocarbon (CFC) formulation in adult patients with moderate to severe asthma. METHODS: This was a multicentre, randomized, open-label, parallel-group comparative study. The patients were given 800 microg/day of CFC-BDP in the four-week baseline period. After the baseline period, 319 patients were randomly allocated into three groups which, respectively, received HFA-ciclesonide 400 microg/day (without a spacer), HFA-ciclesonide 800 microg/day (without spacer) and CFC-BDP 800 microg/day (with spacer) for the eight-week treatment period. The primary efficacy variable was morning PEF. RESULTS: The morning PEF increased by 16.02 L/min in the 400 microg HFA-ciclesonide group, 23.98 L/min in the 800 microg HFA-ciclesonide group and 5.91 L/min in the 800 microg CFC-BDP group. Better outcomes were achieved by the use of 800 microg/day of HFA-ciclesonide compared with 800 microg/day of CFC-BDP (P = 0.001). There was no difference in adverse events between the groups. CONCLUSION: In adult patients with moderate to severe asthma, 800 microg/day of HFA-ciclesonide was significantly more effective than 800 microg/day of CFC-BDP. Ciclesonide at doses of 400 microg/day and 800 microg/day was safe and well tolerated.