Sudden atelectasis and respiratory failure in a neutropenic patient: atypical presentation of pseudomembranous necrotizing bronchial aspergillosis.

Pseudomembranous necrotizing bronchial aspergillosis (PNBA) is a rare form of invasive aspergillosis with a very poor prognosis. The symptoms are non-specific, and the necrotizing plugs cause airway obstruction. Atelectasis and respiratory failure can be the initial manifestations. Recently, we treated an immunocompromised patient with PNBA, who presented with a sudden onset of atelectasis and acute respiratory failure. There were no preceding signs except for a mild cough and one febrile episode. Bronchoscopy revealed PNBA, and Aspergillus nidulans was cultured from the bronchial wash.

Ubiquitous-severance hospital project: implementation and results.

OBJECTIVES: The purpose of this study was to review an implementation of u-Severance information system with focus on electronic hospital records (EHR) and to suggest future improvements. METHODS: Clinical Data Repository (CDR) of u-Severance involved implementing electronic medical records (EMR) as the basis of EHR and the management of individual health records. EHR were implemented with service enhancements extending to the clinical decision support system (CDSS) and expanding the knowledge base for research with a repository for clinical data and medical care information. RESULTS: The EMR system of Yonsei University Health Systems (YUHS) consists of HP integrity superdome servers using MS SQL as a database management system and MS Windows as its operating system. CONCLUSIONS: YUHS is a high-performing medical institution with regards to efficient management and customer satisfaction; however, after 5 years of implementation of u-Severance system, several limitations with regards to expandability and security have been identified.

Unilateral ureteral obstruction caused by Aspergillus, subgenus Nidulantes in a patient on steroid therapy: a case report and review of the literature.

Urinary tract obstructions caused by Aspergillus bezoars has been reported on rare occasions. We describe in this paper an unusual case caused by an isolate of the Aspergillus nidulantes subgenus, and review the literature on 13 additional cases of ureteral obstruction due to renoureteric aspergillosis so as to provide the characteristics of this disease entity. Our case presented with a unilateral ureteral obstruction and acute renal failure due to Aspergillus bezoars. The patient was immunocompromised having received corticosteroid therapy for chronic obstructive lung disease and bronchiectasis. She was treated successfully with antifungal chemotherapy, including amphotericin B followed by oral voriconazole for about two months and had a percutaneous nephrostomy for one month. The patient's renal function completely recovered after hemodialysis maintenance for six months.

Asthma-like symptoms are increased in the metabolic syndrome.

BACKGROUND: The prevalence of obesity and asthma has been increasing during the last several decades. Obesity has been reported to be associated with asthma. Obesity, especially abdominal obesity, is the main component of the metabolic syndrome. OBJECTIVES: We thus hypothesized that metabolic syndrome is an important contributing factor for the development of asthma-like symptoms. METHODS: The Korean Health and Genome Study started in 2001 as an ongoing population-based study of Korean adults 40 to 69 years of age. The prevalence of asthma-like symptoms in the previous 12 months was obtained by a questionnaire, and spirometric testing was conducted. RESULTS: Among the 10,038 participants, the data from 9,942 individuals (4,716 men and 5,226 women) was available. Asthma-like symptoms (wheeze [p = 0.0006], resting dyspnea [p = 0.0062], and post-exercise dyspnea [p < 0.0001]) were increased in the subjects of the metabolic syndrome group. Subjects with asthma-like symptoms had a decreased lung function compared to subjects without asthma-like symptoms. Among the components of the metabolic syndrome, abdominal obesity and hypertension were the risk factors for asthma-like symptoms. CONCLUSIONS: Metabolic syndrome is associated with asthma-like symptoms. Among the components of metabolic syndrome, abdominal obesity and hypertension are the risk factors for asthma-like symptoms.

Inflammatory and transcriptional roles of poly (ADP-ribose) polymerase in ventilator-induced lung injury.

INTRODUCTION: Poly (ADP-ribose) polymerase (PARP) participates in inflammation by cellular necrosis and the nuclear factor-kappa-B (NF-kappaB)-dependent transcription. The purpose of this study was to examine the roles of PARP in ventilator-induced lung injury (VILI) in normal mice lung. METHODS: Male C57BL/6 mice were divided into four groups: sham tracheostomized (sham), lung-protective ventilation (LPV), VILI, and VILI with PARP inhibitor PJ34 pretreatment (PJ34+VILI) groups. Mechanical ventilation (MV) settings were peak inspiratory pressure (PIP) 15 cm H2O + positive end-expiratory pressure (PEEP) 3 cm H2O + 90 breaths per minute for the LPV group and PIP 40 cm H2O + PEEP 0 cm H2O + 90 breaths per minute for the VILI and PJ34+VILI groups. After 2 hours of MV, acute lung injury (ALI) score, wet-to-dry (W/D) weight ratio, PARP activity, and dynamic compliance (CD) were recorded. Tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), myeloperoxidase (MPO) activity, and nitrite/nitrate (NOX) in the bronchoalveolar lavage fluid and NF-kappaB DNA-binding activity in tissue homogenates were measured. RESULTS: The VILI group showed higher ALI score, W/D weight ratio, MPO activity, NOX, and concentrations of TNF-alpha and IL-6 along with lower CD than the sham and LPV groups (P < 0.05). In the PJ34+VILI group, PJ34 pretreatment improved all histopathologic ALI, inflammatory profiles, and pulmonary dynamics (P < 0.05). NF-kappaB activity was increased in the VILI group as compared with the sham and LPV groups (P < 0.05) and was decreased in the PJ34+VILI group as compared with the VILI group (P = 0.009). Changes in all parameters were closely correlated with the PARP activity (P < 0.05). CONCLUSION: Overactivation of PARP plays an important role in the inflammatory and transcriptional pathogenesis of VILI, and PARP inhibition has potentially beneficial effects on the prevention and treatment of VILI.

Atypical radiological manifestation of pulmonary metastatic calcification.

Metastatic pulmonary calcification refers to calcium deposition in the normal pulmonary parenchyma and this deposition is secondary to abnormal calcium metabolism. The most common radiologic manifestation consists of poorly-defined nodular opacities that are mainly seen in the upper lung zone. We present here a case of metastatic pulmonary calcification that manifested as atypical, dense, calcium deposition in airspaces within the previously existing consolidation in the bilateral lower lobes, and this process was accelerated by pneumonia-complicated sepsis in a patient with hypercalcemia that was due to hyperparathyroidism.

Characteristics of mechanical ventilation employed in intensive care units: a multicenter survey of hospitals.

A 1D point-prevalence study was performed to describe the characteristics of conventional mechanical ventilation in intensive care units (ICUs). In addition, a survey was conducted to determine the characteristics of ICUs. A prospective, multicenter study was performed in ICUs at 24 university hospitals. The study population consisted of 223 patients who were receiving mechanical ventilation or had been weaned off mechanical ventilation within the past 24 hr. Common indications for the initiation of mechanical ventilation included acute respiratory failure (66%), acute exacerbation of chronic respiratory failure (15%) (including tuberculosis-destroyed lung [5%]), coma (13%), and neuromuscular disorders (6%). Mechanical ventilation was delivered via an endotracheal tube in 68% of the patients, tracheostomy in 28% and facial mask with noninvasive ventilation (NIV) in 4%. NIV was used in 2 centers. In patients who had undergone tracheostomy, the procedure had been performed 16.9+/-8.1 days after intubation. Intensivists treated 29% of the patients. A need for additional educational programs regarding clinical practice in the ICU was expressed by 62% of the staff and 42% of the nurses. Tuberculosis-destroyed lung is a common indication for mechanical ventilation in acute exacerbation of chronic respiratory failure, and noninvasive ventilation was used in a limited number of ICUs.

Potential use of an anticancer drug gefinitib, an EGFR inhibitor, on allergic airway inflammation.

The EGFR plays an essential role in goblet cell hyperplasia and mucus hypersecretion. EGFR has an intrinsic tyrosine kinase activity that, when activated, induces the production of MUC5AC through the signaling kinase cascade in the airway epithelium. We have investigated the effects of an EGFR tyrosine kinase inhibitor, gefitinib, on ovalbumin (OVA)-induced, allergic inflammation in airway epithelia of mice. OVA-sensitized mice were pretreated with gefitinib at two different doses (12.5 and 50 mg/kg) and then challenged with OVA. The OVA challenge increased the total cell count and eosinophil count in bronchoalveolar lavage fluid (BALF), as well as the concentrations of T-helper2 (Th2) cytokines, such as IL-4 and IL-13, overall eosinophil recruitment in the lung tissue and airway hyperresponsiveness (AHR). Pretreatment with gefitinib reduced the inflammatory cell counts and released cytokine concentrations (IL-4 and IL-13) in BALF, as well as eosinophil recruitment in the lungs and AHR, in a dose-dependent manner. This was associated with decreased EGFR and Akt phosphorylation. We showed that gefinitib inhibits EGFR and phosphoinositol 3'-kinase (PI3K)/Akt activation which were activated in OVA sensitized mice. These findings suggest that inhibitors of the EGFR cascade may have a role in the treatment of asthma.

Basal serum cortisol levels are not predictive of response to corticotropin but have prognostic significance in patients with septic shock.

Because high levels of cortisol are frequently observed in patients with septic shock, low levels of serum cortisol are considered indicative of relative adrenal insufficiency (RAI). This study was performed to investigate whether pretest clinical characteristics, including basal serum cortisol levels, are predictive of serum cortisol response to corticotropin and whether basal cortisol levels have a prognostic significance in patients with septic shock. We performed a retrospective analysis of 68 patients with septic shock who underwent short corticotropin stimulation testing. RAI was defined as an increase in cortisol level <9 microgram/dL from baseline, and results showed that 48 patients (70.6%) had this insufficiency. According to the univariate analysis, the RAI group had significantly higher simplified acute physiology score II (SAPS II) and sequential organ failure assessment (SOFA) scores than the non-RAI group. The incidence of RAI was the same regardless of the basal serum cortisol level (p=0.447). The hospital mortality rate was 58.8% and was not significantly different between the RAI and non-RAI groups. However, a high basal serum cortisol level (> or =30 microgram/dL) was significantly associated with in-hospital mortality. In conclusion, our data suggest that basal serum cortisol levels are not predictive of serum cortisol response to corticotropin but have a significant prognostic value in patients with septic shock.

Prognostic factors in pulmonary tuberculosis requiring mechanical ventilation for acute respiratory failure.

BACKGROUND AND OBJECTIVE: The prognosis in patients with pulmonary tuberculosis and acute respiratory failure requiring mechanical ventilation is believed to be poor. The aim of this study was to identify factors contributing to in-hospital mortality in these patients. METHODS: The medical records of 32 patients with active pulmonary tuberculosis as a primary cause of acute respiratory failure requiring mechanical ventilation in the medical intensive care unit (ICU) of a tertiary referral hospital over a 10-year period were reviewed retrospectively, and predictors of mortality were assessed. RESULTS: The patients' median age was 69 years (range 25-88 years). The median length of intensive care unit stay was 11 days (range 2-88 days), and the median duration of mechanical ventilation was 9 days (range 2-86 days). Overall in-hospital mortality was 59% (19/32). Independent predictive factors of in-hospital mortality included tuberculous-destroyed lungs (hazard ratio 6.61, 95% CI: 1.21-36.04, P = 0.029), Acute Physiology and Chronic Health Evaluation II scores > or =20 (hazard ratio 4.90, 95% CI: 1.43-16.80, P = 0.012) and sepsis (hazard ratio 5.84, 95% CI: 1.63-20.95, P = 0.007). CONCLUSION: Acute respiratory failure caused by pulmonary tuberculosis necessitating mechanical ventilation has a high mortality rate and poor prognosis, particularly in patients with tuberculous-destroyed lungs, high Acute Physiology and Chronic Health Evaluation II scores and sepsis.

Proteomic analysis of peripheral T-lymphocytes in patients with asthma.

BACKGROUND: Asthma is chronic airway inflammation that occurs together with reversible airway obstruction. T-lymphocytes play an important role in the pathogenesis of asthma. Proteomic technology has rapidly developed in the postgenomic era, and it is now widely accepted as a complementary technology to genetic profiling. We investigated the changes of proteins in T-lymphocytes of asthma patients by using standard proteome technology: two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), and a database search. METHODS: The proteins of CD3+ T-lymphocytes were isolated from whole blood of six steroid-naive asthmatic patients and of six healthy volunteers. 2D-PAGE was performed and the silver-stained protein spots were comparatively analyzed between the asthma and control groups using an image analyzer. Some differentially expressed spots were identified by MALDI-TOF-MS and database search. The messenger RNA expressions of some identified proteins were examined by real-time polymerase chain reaction (RT-PCR). RESULTS: Thirteen protein spots in the T-lymphocytes of the asthmatic patients were increased and 12 spots were decreased compared to those of the normal subjects. Among the identified proteins, the increased expression of the messenger RNA of phosphodiesterase 4C and thioredoxin-2 and the decreased expression of the messenger RNA of glutathione S-transferase M3 were confirmed by RT-PCR in the asthmatic patients. CONCLUSIONS: Proteomic examination of the peripheral T-lymphocytes revealed some differentially expressed proteins in the asthmatic patients. The possibility of using the differentially expressed proteins as important biomarkers and therapeutic targets in asthma patients warrants further studies.

Diaphragmatic weakness after transcatheter arterial chemoembolization of inferior phrenic artery for treatment of hepatocellular carcinoma.

PURPOSE: To prospectively assess the diaphragmatic anatomic and functional consequences of transcatheter arterial chemoembolization (TACE) of the inferior phrenic artery in patients with hepatocellular carcinoma. MATERIALS AND METHODS: Informed consent and institutional review board approval were obtained. Fifteen patients (13 men, two women; mean age, 52 years; age range, 22-61 years) who underwent TACE of the inferior phrenic artery for treatment of hepatocellular carcinoma were enrolled. The right inferior phrenic artery was embolized in 14 patients, and the left inferior phrenic artery was embolized in one patient. Chest radiography, fluoroscopy, computed tomography (CT), and pulmonary function tests were performed before and after TACE of the inferior phrenic artery. The post-TACE examinations were performed 2-3 months after TACE, and the results were compared with those of the pre-TACE examinations. A paired t test or the Wilcoxon signed rank test was used for statistical analyses. RESULTS: At chest radiography and fluoroscopy, six of 15 patients (40%) had both elevation and movement abnormality of the ipsilateral hemidiaphragm after TACE of the inferior phrenic artery. The mean (+/- standard deviation) diaphragmatic thickness on CT scans changed from 9.11 mm +/- 3.02 to 7.67 mm +/- 2.27 after TACE (P = .048). The mean vital capacity also was significantly decreased after TACE, from 91.87% +/- 18.52 to 82.27% +/- 16.94 of the predicted value (P = .006). The decreases in diaphragmatic thickness and vital capacity were most pronounced in the patients with abnormal findings at chest radiography and fluoroscopy. CONCLUSION: After TACE of the inferior phrenic artery, a substantial portion of patients showed functional and anatomic evidence of diaphragmatic weakness.

Partial interferon-gamma receptor deficiency and non-tuberculous mycobacterial lung disease.

Interferon-gamma (IFN-gamma) plays a key role in the host defense response against mycobacterial disease, and a complete or partial deficiency in IFN-gamma receptor 1 (IFN-gammaR1) or IFN-gamma receptor 2 (IFN-gammaR2) has been reported to contribute to susceptibility to disseminated infection with non-tuberculous mycobacteria (NTM). However, IFN-gammaR1 and IFN-gammaR2 deficiencies have not yet been studied in adult patients with isolated NTM lung disease. The purpose of the present study was to evaluate whether partial IFN-gammaR1 and IFN-gammaR2 deficiency are associated with human susceptibility to NTM lung disease. We studied 40 patients with NTM lung disease (Mycobacterium avium complex infection, 20 patients; Mycobacterium abscessus infection, 20 patients) for partial IFN-gammaR1 and IFN-gammaR2 deficiency. Genomic DNA was amplified by polymerase chain reaction and sequenced for revealing mutations of the IFN-gammaR1 and IFN-gammaR2 gene. None of the patients had previously reported homozygous recessive missense mutation causing an amino-acid substitution in the extracellular domain of the receptor (I87T) and hotspot for small deletions (818delT, 818del4) of the IFN-gammaR1 or homozygous missense mutation (R114C) of the IFN-gammaR2. In conclusion, in adult patients with isolated NTM lung disease, there is no evidence for previously known genetic defects of partial deficiencies of IFN-gammaR1 and IFN-gammaR2 to correlate with disease.

Early intervention can improve clinical outcome of acute interstitial pneumonia.

STUDY OBJECTIVES: To report on our experience with acute interstitial pneumonia (AIP) in which patients underwent early diagnostic procedures and received mechanical ventilation with a "lung-protective" strategy and early institution of immunosuppressive therapy. DESIGN: A retrospective chart review. SETTING: A tertiary referral hospital. PARTICIPANTS: Ten patients with AIP who presented with idiopathic ARDS and showed diffuse alveolar damage on surgical lung biopsy specimens from July 1995 to March 2004. MEASUREMENTS AND RESULTS: The median age of patients was 65.5 years (age range, 38 to 73 years). Patients presented with a median duration of severe dyspnea of 9.5 days (range, 2 to 34 days) at the hospital visit. All patients required mechanical ventilation beginning at median time of hospital day 1 (range, hospital day 0 to 5), which continued for a median duration of 9.5 days (range, 4 to 98 days). Patients received ventilation in the pressure assist-control mode with a median tidal volume of 6.97 mL/kg (range, 6.05 to 8.86 mL/kg) and median positive end-expiratory pressure of 11 cm H(2)O (range, 8 to 16 cm H(2)O). An aggressive diagnostic workup for respiratory infection, including BAL at a median time of hospital day 2 (range, hospital day 1 to 5) was performed. High-dose steroid pulse therapy was initiated on median hospital day 3.5 (range, hospital day 1 to 8), while surgical lung biopsy was performed on median hospital day 4 (range, hospital day 2 to 7). Eight patients (80%) survived to hospital discharge. CONCLUSION: Earlier intervention, such as an aggressive diagnostic approach, mechanical ventilation with lung-protective strategy, and the early institution of immunosuppressive may improve clinical outcome in patients with AIP.

Recruitment maneuvers attenuate repeated derecruitment-associated lung injury.

OBJECTIVE: Repeated derecruitments of previously recruited lungs can exacerbate lung injuries during mechanical ventilation. The aim of this study was to assess lung injury associated with repeated derecruitments and to assess whether this type of injury could be attenuated by recruitment maneuvers. DESIGN: Prospective, randomized, experimental animal study. SETTING: University laboratory. SUBJECTS: New Zealand White rabbits. INTERVENTIONS: Twenty-one rabbits were ventilated in pressure-controlled mode with constant tidal volume (10 mL/kg). After lung injury was induced by repeated saline lavage, positive end-expiratory pressure (PEEP) at a lower inflection point was applied for 3 hrs. The control group (n = 7) received ventilation with the same PEEP for 3 hrs without derecruitments. In the derecruitment group (n = 7), derecruitment was repeatedly induced by intentional disconnection of the ventilatory circuit for 1 min every 10 mins for 3 hrs. In the recruitment maneuver group (n = 7), continuous positive airway pressure of 30 cm H2O was applied for 30 secs after each derecruitment. MEASUREMENTS AND MAIN RESULTS: After PEEP levels were increased to lower the inflection point value, Pao2 increased to >500 mm Hg in all groups. Increased Pao2 persisted at >450 mm Hg in the control and recruitment maneuver groups, whereas progressive declines in arterial oxygen levels were observed in the derecruitment group (median, 381.1 mm Hg [interquartile range, 350.1-466.7 mm Hg] at 2 hrs and 318.2 mm Hg [214.3-414.9 mm Hg] at 3 hrs, p < .05 compared with other groups). Histologically, there was significantly increased hyaline membrane formation in alveolar ducts in the derecruitment group compared with the control group (p = .005). Also, significantly more membranous and respiratory bronchiolar injuries were observed in the derecruitment group compared with the control and recruitment maneuver group (p < .005). CONCLUSIONS: These findings suggest that repeated derecruitments could induce lung injuries during mechanical ventilation, and recruitment maneuvers may attenuate derecruitment-associated lung injuries.

Acute respiratory distress syndrome. Computed tomography findings and their applications to mechanical ventilation therapy.

In acute respiratory distress syndrome, computed tomography (CT) typically demonstrates symmetric ground-glass opacity and gravity-dependent consolidation when patients are positioned supine. Moreover, CT findings may vary according to the evolutional stage of the disease over time. The slope of the pressure-volume curve, which is a direct or indirect measure of lung recruitment rather than a measure of the characteristics of the respiratory mechanics of a portion of the aerated lung, indicates the potential for recruitment. The lung recruitment maneuver is performed by maintaining a sustained increase in airway pressure with the goal of opening collapsed alveoli, after which sufficient positive end-expiratory pressure is applied to maintain the alveoli in an open state. Alveolar recruitment resulting from continuous positive airway pressure occurs predominantly in nondependent and cephalic lung regions and is more limited in the diaphragmatic region or even negative (alveolar derecruitment) caudal to the diaphragmatic cupola. By partially relieving cardiac and abdominal compression, positioning patients in prone and semirecumbent positions may reopen dependent and caudal lung regions and improve gas exchange. The mean CT attenuation of a given region is equivalent to its aeration. Computed tomography, especially helical CT, may help to assess alveolar recruitment and lung overinflation by providing information on whole-lung attenuation.

Prone positioning improves oxygenation without adverse hemodynamic effects during partial liquid ventilation in a canine model of acute lung injury.

BACKGROUND: Partial liquid ventilation (PLV) and prone positioning can improve the arterial oxygenation (PaO2) in acute lung injury (ALI). We evaluated the effect of prolonged prone positioning during partial liquid ventilation (PLV) in a canine model of acute lung injury. METHODS: Six mongrel dogs (weighing 17.4 +/- 0.7 kg each) were anesthetized, intubated and mechanically ventilated. After 1 hour of baseline stabilization, the dogs' lungs were instilled with 40 mL/kg perfluorocarbon (PFC). PLV was first performed in the supine position for 1 hour (S1), then in the prone position for 3 hours with hourly measurements (P1, P2, P3), and finally, PLV was performed with the animal turned back to the supine position for 1 hour (S2). RESULTS: After instillation of the PFC, the PaO2 significantly increased from 992 +/- 32.6 mmHg at baseline to 198.1 +/- 59.2 mmHg at S1 (p = 0.001). When the dogs were turned to the prone position, the PaO2 further increased to 288.3 +/- 80.9 mmHg at P1 (p = 0.008 vs. S1): this increase was maintained for 3 hours, but the PaO2 decreased to 129.4 +/- 62.5 mmHg at S2 (p < 0.001 vs. P3). Similar changes were seen in the shunt fraction. There were no significant differences for the systemic hemodynamic parameters between the prone and supine positions. CONCLUSION: Prolonged prone positioning during PLV in an animal model of ALI appears to improve oxygenation without any hemodynamic compromise.