Prognostic significance of crazy paving ground grass opacities in non-HIV Pneumocystis jirovecii pneumonia: an observational cohort study.

BACKGROUND: In patients with non-HIV Pneumocystis jirovecii pneumonia (PjP), computed tomography imaging reveals ground grass opacities (GGO). Previous reports show that some patients with non-HIV PjP exhibit GGO with crazy paving. However, there have been no studies on the association between crazy paving GGO and non-HIV PjP clinical outcomes. Here, at the diagnosis of non-HIV PjP, we reviewed high-resolution computed tomography (HRCT) findings that included GGO types and evaluated the prognostic impact of crazy paving GGO on the clinical outcomes of non-HIV PjP immunocompromised patients. METHODS: We retrospectively reviewed the clinical information including the HRCT findings of patients diagnosed with non-HIV PjP from five institutions between 2006 and 2015. The GGO types included those with or without crazy paving. The associations between clinical factors such as HRCT findings and in-hospital mortality were assessed using the Cox regression model. RESULTS: Sixty-one patients were included in our study. Nineteen patients died at a hospital. All patients exhibited GGO on HRCT imaging at diagnosis of non-HIV PjP. The HRCT findings included crazy paving GGO (29 patients, 47.5%), consolidations (23 patients, 37.7%), bronchiectasis (14 patients, 23.0%), and centrilobular small nodules (30 patients, 49.2%). Cysts were not observed in any patient. Multivariate analysis revealed that crazy paving GGO and low serum albumin levels were independent risk factors for mortality. CONCLUSIONS: At the diagnosis of non-HIV PjP, patients with crazy paving GGO on HRCT imaging and low serum albumin levels may have a poor prognosis.

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.

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.

Relationship Between Episodic Nocturnal Hypercapnia and History of Exacerbations in Patients with Advanced Chronic Obstructive Pulmonary Disease.

Purpose: An episodic increase in transcutaneous carbon dioxide pressure (PtcCO2) is often recognized in patients with advanced chronic obstructive pulmonary disease (COPD) by overnight PtcCO2 monitoring. This phenomenon, called episodic nocturnal hypercapnia (eNH), mainly corresponds to rapid eye movement (REM) sleep-related hypoventilation. However, it is unclear whether eNH is associated with the frequency of COPD exacerbation. We aimed to investigate whether a relationship exists between COPD exacerbation and eNH. Patients and Methods: We enrolled consecutive patients with stable, severe, or very severe COPD with a daytime arterial carbon dioxide pressure (PaCO2) <55.0 mmHg who underwent overnight PtcCO2 monitoring from April 2013 to January 2017. We retrospectively analyzed the prevalence of eNH and sleep-associated hypoventilation (SH) as defined by the American Academy of Sleep Medicine. Moreover, we compared the relationship between the frequency of COPD exacerbations in the previous year and eNH or SH. Results: Twenty-four patients were included in this study. The study patients had a mean daytime PaCO2 and nocturnal PtcCO2 of 43.3 ± 6.8 mmHg and 42.9 ± 9.6 mmHg, respectively. Six (25.0%) and 11 (45.9%) of the 24 patients met the SH and eNH criteria, respectively. The odds ratios of SH and eNH for at least one annual exacerbation were 1.0 [95% confidence interval (CI): 0.16-6.00] and 11.1 [95% CI: 1.39-87.7], respectively. The odds ratios of SH and eNH for at least two annual exacerbations were 0.3 [95% CI: 0.04-2.64] and 6.6 [95% CI: 1.06-39.4], respectively. Conclusion: In patients with advanced COPD and a daytime PaCO2 <55.0 mmHg, eNH may be associated with a history of more frequent exacerbations than SH. Further studies are required to validate these findings.

[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.

SARS-CoV-2-related Progressive Brain White Matter Lesion Associated with an Increased Cerebrospinal Fluid Level of IL-6.

We herein report a 49-year-old man with a fever, diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. After two weeks of hospitalization, he suddenly mentioned visual field impairment. Computed tomography and magnetic resonance imaging revealed white matter damage and vasogenic edema. Cerebrospinal fluid showed increased levels of interleukin (IL)-6. His symptoms and white matter lesion deteriorated. After treatment with intravenous methylprednisolone therapy and plasmapheresis, his symptoms and white matter lesion improved gradually. We suspect that our patient was affected by a secondary hyperinflammatory syndrome related to cytokines, alone or in combination with direct viral injury through endothelial cell damage. The IL-6 levels were elevated only in the cerebrospinal fluid, suggesting focal central nervous system inflammation.

Pneumonia Caused by Severe Acute Respiratory Syndrome Coronavirus 2 and Influenza Virus: A Multicenter Comparative Study.

BACKGROUND: Detailed differences in clinical information between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia (CP), which is the main phenotype of SARS-CoV-2 disease, and influenza pneumonia (IP) are still unclear. METHODS: A prospective, multicenter cohort study was conducted by including patients with CP who were hospitalized between January and June 2020 and a retrospective cohort of patients with IP hospitalized from 2009 to 2020. We compared the clinical presentations and studied the prognostic factors of CP and IP. RESULTS: Compared with the IP group (n = 66), in the multivariate analysis, the CP group (n = 362) had a lower percentage of patients with underlying asthma or chronic obstructive pulmonary disease (P < .01), lower neutrophil-to-lymphocyte ratio (P < .01), lower systolic blood pressure (P < .01), higher diastolic blood pressure (P < .01), lower aspartate aminotransferase level (P < .05), higher serum sodium level (P < .05), and more frequent multilobar infiltrates (P < .05). The diagnostic scoring system based on these findings showed excellent differentiation between CP and IP (area under the receiver operating characteristic curve, 0.889). Moreover, the prognostic predictors were different between CP and IP. CONCLUSIONS: Comprehensive differences between CP and IP were revealed, highlighting the need for early differentiation between these 2 pneumonias in clinical settings.

The utility of serial procalcitonin measurements in addition to pneumonia severity scores in hospitalised community-acquired pneumonia: A multicentre, prospective study.

OBJECTIVES: The usefulness of serial procalcitonin (PCT) measurements for predicting the prognosis and treatment efficacy for hospitalised community-acquired pneumonia (CAP) patients was investigated. METHODS: This prospective, multicentre, cohort study enrolled consecutive CAP patients who were hospitalised at 10 hospitals in western Japan from September 2013 to September 2016. PCT and C-reactive protein (CRP) were measured on admission (PCT D1 and CRP D1), within 48-72 h after admission (PCT D3 and CRP D3), and within 144-192 h after admission. CURB-65 and the Pneumonia Severity Index (PSI) were assessed on admission. The primary outcome was 30-day mortality; secondary outcomes were early and late treatment failure rates. RESULTS: A total of 710 patients were included. The 30-day mortality rate was 3.1%. On multivariate analysis, only PCT D3/D1 ratio >1 [odds ratio (95% confidence interval): 4.33 (1.46-12.82),P = 0.008] and PSI [odds ratio (95% confidence interval): 2.32 (1.07-5.03), P = 0.03] were significant prognostic factors. Regarding treatment efficacy, PCT D3/D1 >1 was a significant predictor of early treatment failure on multivariate analysis. PCT D3/D1 with the PSI significantly improved the prognostic accuracy over that of the PSI alone. CONCLUSIONS: PCT should be measured consecutively, not only on admission, to predict the prognosis and treatment efficacy in CAP.

Secondary pulmonary alveolar proteinosis during corticosteroid therapy for organising pneumonia associated with myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) is frequently complicated by pulmonary disease. Here, we describe secondary pulmonary alveolar proteinosis (sPAP) that developed during corticosteroid therapy for organising pneumonia (OP) associated with MDS. A 75-year-old woman with MDS complained of cough for 2 weeks. Chest CT showed bilateral patchy consolidations with reversed halo sign. Bronchoalveolar lavage (BAL) examination showed remarkably increased cell density with an increased lymphocyte proportion. Abnormal radiological findings improved rapidly on administration of systemic corticosteroid under the diagnosis of OP; however, they relapsed a few weeks later. Transbronchial lung biopsy showed periodic acid-Schiff stain-positive amorphous materials. Autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) in serum and BAL fluid (BALF) were both negative, while GM-CSF level in BALF was elevated. The patient was diagnosed with sPAP. When chest radiological findings show exacerbation during corticosteroid therapy for OP in a patient with MDS, physicians should consider sPAP complication as a differential diagnosis.

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.

Site-specific cleavage of acetoacetyl-CoA synthetase by legumain.

Acetoacetyl-CoA synthetase (AACS) is a ketone body-utilizing enzyme and is responsible for the synthesis of cholesterol and fatty acids. We have previously shown that AACS is cleaved by legumain, a lysosomal asparaginyl endopeptidase. In this study, we attempted to determine the cleavage site of AACS. Mutagenesis analysis of AACS revealed that Asn547 is the specific cleavage site of AACS in mouse livers. The cleaved form of AACS (1-547) lost the ability to convert acetoacetate to acetoacetyl-CoA. Moreover, hydrodynamics-based gene transduction showed that overexpression of AACS (1-547) increases the protein expression of caveolin-1, the principal component of the caveolae. These results suggest that cleavage of AACS by legumain is critical for the regulation of enzymatic activity and results in gain-of-function changes.

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.

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.