Explore the vast range of titles available.

Background: Stroke-associated pneumonia (SAP) has been implicated in the morbidity, mortality and increased medical cost after acute ischemic stroke. The annual cost of SAP during hospitalization in the United States approaches USD 459 million. The incidence and prognosis of SAP among intensive care unit (ICU) patients have not been thoroughly investigated. We reviewed the pathophysiology, microbiology, incidence, risk factors, outcomes and prophylaxis of SAP with special attention to ICU studies. Methods: To determine the incidence, risk factors and prognosis of acute SAP, PubMed was searched using the terms ‘pneumonia' AND ‘neurology intensive unit' and the MeSH terms ‘stroke' AND ‘pneumonia'. Non-English literature, case reports and chronic SAP studies were excluded. Studies were classified into 5 categories according to the setting they were performed in: neurological intensive care units (NICUs), medical intensive care units (MICUs), stroke units, mixed studies combining more than one setting or when the settings were not specified and rehabilitation studies. Results: The incidences of SAP in the following settings were: NICUs 4.1-56.6%, MICUs 17-50%, stroke units 3.9-44%, mixed studies 3.9-23.8% and rehabilitation 3.2-11%. The majority of NICU and MICU studies were heterogeneous including different neurovascular diseases, which partly explains the wide range of SAP incidence. The higher incidence in the majority of ICU studies compared to stroke units or acute floor studies is likely explained by the presence of mechanical ventilation, higher stroke severity causing higher rates of aspiration and stroke-induced immunodepression among ICU patients. The short-term mortality of SAP was increased among the mixed and stroke unit studies ranging between 10.1 and 37.3%. SAP was associated with worse functional outcome in the majority of stroke unit and floor studies. Mortality was less consistent among NICU and MICU studies. This difference could be due to the heterogeneity of ICU studies and the effect of small sample size or other independent risk factors for mortality such as the larger neurological deficit, mechanical ventilation, and age, which may simultaneously increase the risk of SAP and mortality confounding the outcomes of SAP itself. The pathophysiology of SAP is likely explained by aspiration combined with stroke-induced immunodepression through complex humeral and neural pathways that include the hypothalamic-pituitary-adrenal axis, parasympathetic and sympathetic systems. Conclusions: A unified definition of SAP, strict inclusion criteria, and the presence of a long-term follow-up need to be applied to the future prospective studies to better identify the incidence and prognosis of SAP, especially among ICU patients.

species are frequently found in the lower respiratory tract (LRT) of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), but the clinical significance is uncertain. This study compared the clinical differences between AECOPD patients with and without in their LRT and assessed the impact on disease outcomes. We conducted a retrospective case-control study on AECOPD patients hospitalized at the First Affiliated Hospital of Guangxi Medical University. Demographic characteristics, clinical data, and follow-up data were compared between AECOPD patients with and without isolated from their LRT. Univariate and multivariate logistic regression analyses were performed to identify risk factors for AECOPD. Survival curves for the patients with and without -positive LRT samples were calculated using the Kaplan-Meier method. A total of 225 hospitalized AECOPD patients were included in the study, 88 of whom had isolated from their LRT, while 137 did not. The -positive group had a greater pack-year history and higher COPD Assessment Test (CAT) scores compared to the -negative group. The proportion of patients with Modified Medical Research Council (mMRC) grade 4, Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) grade 4 and hospitalizations for AECOPD in the past year were higher in the -positive group. Peripheral blood lymphocytes, CD8 T-lymphocytes and percent predicted forced expiratory volume in 1 s (FEV ) were significantly lower in the -positive group ( < 0.05). Patients without survived significantly longer than those with ( < 0.001). The presence of and mMRC grade 4 were independent risk factors for both acute exacerbation and hospitalization in the past year. Positive C isolation and mMRC grade 4 are independent risk factors for AECOPD. in the LRT of COPD patients may predict more severe clinical symptoms, greater airflow limitation, and poorer survival outcomes.

Background. Pulmonary zygomycosis (PZ), an emerging mycosis among patients with cancer, has a clinical manifestation similar to that of invasive pulmonary aspergillosis (IPA). Most cases of PZ in such patients develop as breakthrough infections if treatment with antifungal agents effective against Aspergillus species is administered. However, clinical criteria to differentiate PZ from IPA are lacking. Methods. We retrospectively reviewed the clinical characteristics and computed tomography (CT) findings for 16 patients with cancer and PZ and for 29 contemporaneous patients with cancer and IPA at the time of infection onset (2002–2004). Patients with mixed infections were excluded. Parameters predictive of PZ by univariate analysis were included in a logistic regression model. Results. Almost all patients with PZ (15 of 16) and IPA (28 of 29) had underlying hematological malignancies and typical risk factors for invasive mold infections. In logistic regression analysis of clinical characteristics, concomitant sinusitis (odds ratio [OR], 25.7; 95% confidence interval [CI], 1.47–448.15; P = .026) and voriconazole prophylaxis (OR, 7.76; 95% CI, 1.32–45.53; P = .023) were significantly associated with PZ. The presence of multiple (⩾10) nodules (OR, 19.8; 95% CI, 1.94–202.29; P = .012) and pleural effusion (OR, 5.07; 95% CI, 1.06–24.23; P = .042) at the time that the patient underwent the initial CT were both independent predictors of PZ in the logistic regression analysis of radiological parameters. No difference occurred in the frequency of other CT findings suggestive of pulmonary mold infections (e.g., masses, cavities, halo sign, or air-crescent sign) between the 2 patient groups. Conclusions. PZ in immunocompromised patients with cancer could potentially be distinguished from IPA on the basis of clinical and radiological parameters; prospective validation is needed.

Background: After lung transplantation (LTx), inhaled corticosteroids may be prescribed and at the same time prophylaxis against fungal infections with itraconazole is common. In our center, the addition of inhaled fluticasone propionate to systemic immunosuppression resulted in clinical Cushing’s syndrome in 4 lung transplant recipients on itraconazole comedication. Objectives: The current study was undertaken to compare systemic levels of inhaled fluticasone in patients with and without concomitant itraconazole therapy. Methods: The single-center, prospective controlled study was performed in the LTx program in Zurich, Switzerland. Twenty stable recipients, 1–7 years after LTx, on a prednisone maintenance dose (5–7.5 mg/day) gave informed consent and were assigned to 2 groups: (A) without itraconazole comedication and (B) currently on itraconazole, being continued during the study period. The patients of both groups started inhalation of 1 mg fluticasone propionate twice daily for 14 days with a powder disc inhaler. Plasma fluticasone levels were measured before the start of the study and on day 14. Results: Fluticasone levels before starting the treatment were below the detection limit in all 17 patients (7 in group A and 10 in group B) adhering to the study protocol. Baseline characteristics (underlying disease, age at LTx, time since LTx, FEV 1 ) were comparable between the 2 groups. On study day 14, plasma fluticasone levels had increased to detectable levels in all patients (A: 273 ± 124 pg/ml, B: 701 ± 131 pg/ml), i.e. to significantly higher (p = 0.038) concentrations in patients on itraconazole. Conclusions: Itraconazole comedication substantially increases systemic levels of inhaled fluticasone, most likely by inhibiting the cytochrome P450 3A4 enzyme system and thus the clearance of fluticasone. Accumulation of fluticasone can result in increased systemic effects and therefore comedication has to be taken into consideration when inhaled fluticasone is prescribed.

Abstract Background: Understanding the relationship between dose, lung exposure, and drug efficacy continues to be a challenging aspect of inhaled drug development. An experimental inhalation platform was developed using mometasone furoate to link rodent lung exposure to its in vivo pharmacodynamic (PD) effects. Methods: We assessed the effect of mometasone delivered directly to the lung in two different rodent PD models of lung inflammation. The data obtained were used to develop and evaluate a mathematical model to estimate drug dissolution, transport, distribution, and efficacy, following inhaled delivery in rodents and humans. Results: Mometasone directly delivered to the lung, in both LPS and Alternaria alternata rat models, resulted in dose dependent inhibition of BALf cellular inflammation. The parameters for our mathematical model were calibrated to describe the observed lung and systemic exposure profiles of mometasone in humans and in animal models. We found that physicochemical properties, such as lung fluid solubility and lipophilicity, strongly influenced compound distribution and lung retention. Conclusions: Presently, we report on a novel and sophisticated mathematical model leading to improvements in a current inhaled drug development practices by providing a quantitative understanding of the relationship between PD effects and drug concentration in lungs.

It is widely held that exposure to pathogens such as fungi can be an agent of comorbidity, such as exacerbation of asthma or chronic obstructive pulmonary disease. Although many studies have examined allergic responses to fungi and their effects on pulmonary function, the possible pathologic implications of the early innate responses to fungal pathogens have not been explored. We examined early responses to the atypical fungus Pneumocystis in two common strains of mice in terms of overall immunological response and related pathology, such as cell damage and airway hyperresponsiveness (AHR). We found a strong strain-specific response in BALB/c mice that included recruitment of neutrophils, NK, NKT, and CD4 T cells. This response was accompanied by elevated indicators of lung damage (bronchoalveolar lavage fluid albumin and LDH) and profound AHR. This early response was absent in C57BL/6 mice, although both strains exhibited a later response associated with the clearance of Pneumocystis. We found that this AHR could not be attributed exclusively to the presence of recruited neutrophils, NKT, NK, or CD4 cells or to the actions of IFN-γ or IL-4. However, in the absence of STAT6 signaling, AHR and inflammatory cell recruitment were virtually absent. Gene expression analysis indicated that this early response included activation of several transcription factors that could be involved in pulmonary remodeling. These results show that exposure to a fungus such as Pneumocystis can elicit pulmonary responses that may contribute to morbidity, even without prior sensitization, in the context of certain genetic backgrounds.

We developed a new quantitative system for diagnosis of invasive pulmonary aspergillosis (IPA) using real-time automated polymerase chain reaction (PCR). Intra-assay and interassay precision rates for in vitro examination were 2.53% and 2.20%, respectively, and the linearity of this assay was obtained when there were >20 copies/well. We examined 323 samples taken from 122 patients with hematological malignancies, including 33 patients with IPA and 89 control patients. Blood samples were subjected to PCR antigen detection methods, using enzyme-linked immunosorbent assay (ELISA) and determination of plasma (1→3)-β-D-glucan (BDG) concentration. The sensitivities of PCR, ELISA, and BDG measurement for diagnosis of IPA were 79%, 58%, and 67%, respectively; the specificities were 92%, 97%, and 84%. Positive findings on PCR preceded those of computed tomography by -0.3 ± 6.6 days, those of BDG measurement by 6.5 ± 4.9 days, and those of ELISA by 2.8 ± 4.1 days. Real-time PCR was sensitive for IPA diagnosis, and quantitation was accurate.

Background: The opportunistic fungus Pneumocystis jiroveci is a common cause of respiratory infection in immunocompromised patients. By contrast, pneumocystis pneumonia (PCP) occurs only rarely in immunocompetent individuals. Asymptomatic colonisation with P jiroveci has recently been described in patients who are either minimally immunosuppressed or who have underlying lung disorders such as bronchiectasis. We sought to determine the prevalence of asymptomatic colonisation by P jiroveci in a cohort of adult patients undergoing diagnostic bronchoscopy. Methods: A prospective observational cohort study was performed in patients who required bronchoscopy and bronchoalveolar lavage (BAL) as part of their routine clinical assessment. All the samples underwent standard microbiological analysis and a Grocott methenamine silver stain was performed where clinically indicated to detect the presence of P jiroveci. Polymerase chain reaction for detection of P jiroveci specific DNA was also performed. Results: Ninety three consecutive BAL fluid samples were analysed, 17 (18%) of which contained P jiroveci DNA. Of the potential predictors examined, only glucocorticoid use was significantly associated with detectable P jiroveci DNA. Eighteen patients were receiving oral glucocorticoids (equivalent to >20 mg/day prednisolone) at the time of bronchoscopy, of whom eight (44%) had detectable P jiroveci DNA. In contrast, P jiroveci was detected in only nine of 75 patients (12%) who were not receiving glucocorticoids (difference between proportions 32%, 95% CI 8 to 57; p=0.004, two tailed Fisher’s exact test). Conclusions:P jiroveci colonisation, as determined by detection of P jiroveci DNA in BAL fluid, is common in HIV negative patients with primary respiratory disorders undergoing bronchoscopy and BAL. The higher prevalence in patients receiving corticosteroids suggests that oral glucocorticoid therapy is an independent risk factor for colonisation. In contrast, underlying lung cancer or COPD did not appear to be risk factors.

Background Pulmonary cryptococcosis is an uncommon infectious disease that can develop in both immunocompromised and immunocompetent patients. The severity of chronic kidney disease (CKD) was reported to be one of the risk factors for pulmonary cryptococcosis, but its clinical characteristics have not been fully assessed. The purpose of this study was to clarify the clinical characteristics of advanced CKD in patients with pulmonary cryptococcosis. Methods The present study retrospectively investigated 56 patients who had non-human immunodeficiency virus (HIV) pulmonary cryptococcosis and were treated at Saga University Hospital between 2005 and 2018. The clinical characteristics were evaluated and compared between patients with estimated glomerular filtration rate (eGFR) > 45 mL/min/1.73 m 2 ( n  = 42, early CKD) and those with eGFR < 45 mL/min/1.73 m 2 ( n  = 14, advanced CKD. Results Compared with patients with early CKD, those with advanced CKD had significantly higher rate of disseminated cryptococcosis (21.4% vs. 2.4%, p  = 0.03); lower percentage of patients who recovered after treatment (63.6% vs. 92.5%, p  = 0.02); and more frequent clinical features of fever (57.1% vs. 19.0%, p  < 0.01), pleural effusion (21.4% vs. 2.4%, p  = 0.03), high white blood cell count (8550/mL vs. 6150/mL, p  = 0.01) and C-reactive protein (CRP) (2.1 mg/dL vs. 0.2 mg/dL, p  = 0.02), and low level of serum albumin (3.0 g/dL vs. 3.8 g/dL, p  < 0.01). Multivariate analysis adjusted by immunosuppressive drug use indicated the significant factors of fever (odds ratio or β value [95% confidence interval] 6.4 [1.65–20.09], p  < 0.01), high white blood cell count (1293.2 [110.2–2476.2], p  = 0.03), C-reactive protein (0.89 [0.18–1.59], p  = 0.01) and low level of serum albumin (− 0.34 [− 0.54 – − 0.14], p  < 0.01) in patients with eGFR < 45 mL/min/1.73m 2 . Conclusion Advanced CKD was associated with poor clinical characteristics and outcomes in patients with non-HIV pulmonary cryptococcosis. Trial registration The patients in this study were registered retrospectively.

Surveillance for coccidioidomycosis (CM) and a case-control study for risk factors among adults were conducted in Kern County, California. From January 1995 through December 1996, 905 cases of CM were identified, for an annual incidence of 86 cases per 100,000 population. A total of 380 adults were enrolled in the case-control study: 77 had severe pulmonary disease, 33 had disseminated disease, and 270 control patients had mild disease. Independent risk factors for severe pulmonary disease included diabetes, recent history of cigarette smoking, income of <$15,000 per year, and older age. Oral antifungal therapy before hospitalization was associated with a reduced risk of CM pneumonia. Risk factors for disseminated disease were black race, income of <$15,000 per year, and pregnancy. Early treatment of CM with oral antifungal agents may prevent severe pulmonary disease in groups considered to be at high risk, such as elderly individuals, persons with diabetes, and smokers. Persons at risk for severe CM may benefit from vaccination once an effective CM vaccine is available.