Application of metagenomic next-generation sequencing for bronchoalveolar lavage diagnostics in critically ill patients.

The purpose of this study was to assess the value of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) for the diagnosis of severe respiratory diseases based on interpretation of sequencing results. BALF samples were harvested and used for mNGS as well as microbiological detection. Infectious bacteria or fungi were defined according to relative abundance and number of unique reads. We performed mNGS on 35 BALF samples from 32 patients. The positive rate reached 100% in the mNGS analysis of nine immunocompromised patients. Compared with the culture method, mNGS had a diagnostic sensitivity of 88.89% and a specificity of 74.07% with an agreement rate of 77.78% between these two methods. Compared with the smear method and PCR, mNGS had a diagnostic sensitivity of 77.78% and a specificity of 70.00%. In 13 cases, detection results were positive by mNGS but negative by culture/smear and PCR. The mNGS findings in 11/32 (34.4%) cases led to changes in treatment strategies. Linear regression analysis showed that diversity was significantly correlated with interval between disease onset and sampling. Dynamic changes in reads could indirectly reflect therapeutic effectiveness. BALF mNGS improves sensitivity of pathogen detection and provides guidance in clinical practice. Potential pathogens can be identified based on relative abundance and number of unique reads.

Should we initiate vasopressors earlier in patients with septic shock: A mini systemic review.

Septic shock treatment remains a major challenge for intensive care units, despite the recent prominent advances in both management and outcomes. Vasopressors serve as a cornerstone of septic shock therapy, but there is still controversy over the timing of administration. Specifically, it remains unclear whether vasopressors should be used early in the course of treatment. Here, we provide a systematic review of the literature on the timing of vasopressor administration. Research was systematically identified through PubMed, Embase and Cochrane searching according to PRISMA guidelines. Fourteen studies met the eligibility criteria and were included in the review. The pathophysiological basis for early vasopressor use was classified, with the exploration on indications for the early administration of mono-vasopressors or their combination with vasopressin or angiotensinII. We found that mortality was 28.1%-47.7% in the early vasopressors group, and 33.6%-54.5% in the control group. We also investigated the issue of vasopressor responsiveness. Furthermore, we acknowledged the subsequent challenge of administration of high-dose norepinephrine via peripheral veins with early vasopressor use. Based on the literature review, we propose a possible protocol for the early initiation of vasopressors in septic shock resuscitation.

[The experience of extracorporeal membrane oxygenation for severe acute respiratory failure in adults].

OBJECTIVE: To summarize the experience of extracorporeal membrane oxygenation (ECMO) for patients with severe acute respiratory failure in adults and to investigate the factors associated with death. METHODS: The clinical data of patients with severe acute respiratory failure supported with ECMO in respiratory intensive care unit of Beijing Chaoyang Hospital from November 2009 to December 2011 were prospectively collected and analyzed. The data included general condition before EMCO, blood gas analysis, hemodynamics, ventilator settings of mechanical ventilation and complications during ECMO. The primary outcome was death or severe disability within 3 months. Statistical software of SPSS (version 16.0) was used for data analysis. RESULTS: Twenty-five patients with severe respiratory failure received ECMO treatment, of which 16 patients were analyzed. The mean age was (45 ± 14) years old (range, 22 - 64 years old). Thirteen patients were male. Before ECMO, all of the patients were treated with invasive positive pressure ventilation for (72 ± 64) hours. Eight patients had been treated with noninvasive ventilation for a median of 55(10-114) hours. Patients had severe respiratory failure despite advanced mechanical ventilator support. The mean PaO2/fraction of inspired oxygenation (FiO2) ratio was (54 ± 18) mm Hg (1 mm Hg = 0.133 kPa), positive end-expiratory pressure (PEEP) was (11 ± 6) cm H2O(1 cm H2O = 0.098 kPa), Murray lung injury score was 3.6 ± 0.5, serum lactate was (2.5 ± 2.0) mmol/L, serum white blood cell count was (16 ± 6)×10(9)/L, and APACHEII score was 17 ± 8. All of the patients were treated with venous-venous ECMO (VV-ECMO). The change of mechanical ventilation settings were (pre-ECMO vs 2 hours post-ECMO): FiO2 1.0 vs 0.55 ± 0.21, PEEP (11 ± 6) vs (9 ± 6) cm H2O, V(T) (6.8 ± 2.2) vs (4.4 ± 2.0) ml/kg PBW, peak airway pressure (27 ± 8) vs (24 ± 7) cm H2O, respiratory rate (37 ± 10) vs (23 ± 10) breaths/min. Arterial blood gas, including pH, PaO2 and PaCO2 were significantly improved after ECMO running 24 and 48 hours (P < 0.05). The mean VV-ECMO support interval was (9.7 ± 9.6) days (range, 2 - 41 days). Ten patients were successfully weaned from ECMO, of whom 2 died in ICU. Three patients died during ECMO, while another 3 patients died after withdrawal of further treatment. Eight patients survived to 3 months without severe disability. In a multi-variate Cox regression model, pre-ECMO factors including lower PaO2/FiO2 and increasing white blood cell count were associated with increased risks of death (RR was 0.733, 1.701 respectively, both P values < 0.05). CONCLUSIONS: VV-ECMO is a potentially effective approach for severe acute respiratory failure. PaO2/FiO2 and white blood cell count pre-ECMO may be the risk factors for poor outcome.

How to manage isolated tension non-surgical pneumoperitonium during bronchoscopy? A case report.

BACKGROUND: Tension pneumoperitonium is a rare complication during bronchoscopy that can cause acute respiratory and hemodynamic failure, with fatal consequences. Isolated pneumoperitonium during bronchoscopy usually results from ruptures of the abdominal viscera that need surgical repair. Non-surgical pneumoperitoneum (NSP) refers to some pneumoperitoneum that could be relieved without surgery and only by conservative therapy. However, the clinical experience of managing tension pneumoperitonium during bronchoscopy is limited and controversial. CASE SUMMARY: A 51-year-old female was admitted to our hospital for cough with bloody sputum of seven days. On the 8th day of her admission, a bronchoscopy was arranged for bronchial-alveolar lavage to detect possible pathogens in the lower respiratory tract, as oxygen was delivered via a 12 F nasopharyngeal cannula, approximately 5-6 cm from the tip of the catheter, with a flow rate of 5-10 L/min. After four minutes of bronchoscopy, the patient suddenly vomited 20 mL of water, followed by severe abdominal pain, while physical examination revealed obvious abdominal distension, as well as hardness and tenderness of the whole abdomen, which was considered pneumoperitonium, and the bronchoscopy was terminated immediately. A computer tomography scan indicated isolated tension pneumoperitonium, and abdominal decompression was performed with a drainage tube, after which her symptoms were relieved. A multidisciplinary expert consultation discussed her situation and a laparotomy was suggested, but finally refused by her family. She had no signs of peritonitis and was finally discharged 5 d after bronchoscopy with a good recovery. CONCLUSION: The possibility of tension pneumoperitonium during bronchoscopy should be guarded against, and given its serious clinical consequences, cardiopulmonary instability should be treated immediately. Varied strategies could be adopted according to whether it is complicated with pneumothorax or pneumomediastinum, and the presence of peritonitis. When considering NSP, conservative therapy maybe a reasonable option with good recovery. An algorithm for the management of pneumoperitonium during bronchoscopy is proposed, based on the features of the case series reviewed and our case reported.

Th17 cells are involved in mouse chronic obstructive pulmonary disease complicated with invasive pulmonary aspergillosis.

BACKGROUND: The incidence of chronic obstructive pulmonary disease (COPD) complicated with invasive pulmonary aspergillosis (IPA) has increased in the last two decades. The mechanism underpinning susceptibility to and high mortality of COPD complicated with IPA is unclear, and the role of T helper cells 17 (Th17 cells) in the compound disease remains unknown. Therefore, this study aimed to assess the function of Th17 cells in COPD combined with IPA. METHODS: COPD, IPA, and COPD+IPA mouse models were established in male wild type C57/BL6 mice. The amounts of Th17 cells and retinoic acid-related orphan receptors γt (RORγt) were tested by flow cytometry. Then, serum interleukin (IL)-17 and IL-23 levels were detected by enzyme-linked immunosorbent assay (ELISA) in the control, COPD, IPA and COPD+IPA groups. In addition, COPD+IPA was induced in IL-17 knockout (KO) mice, for determining the role of Th17 cells in COPD+IPA. RESULTS: Compared with the COPD group, the COPD+IPA group showed higher amounts of blood RORγt ([35.09 ±â€Š16.12]% vs. [17.92 ±â€Š4.91]%, P = 0.02) and serum IL-17 (17.96 ±â€Š9.59 pg/mL vs. 8.05 ±â€Š4.44 pg/mL, P = 0.02), but blood ([5.18 ±â€Š1.09]% vs. [4.15 ±â€Š0.87]%, P = 0.28) and lung levels of Th17 cells ([1.98 ±â€Š0.83]% vs. [2.03 ±â€Š0.98]%, P = 0.91), lung levels of RORγt ([9.58 ±â€Š6.93]% vs. [9.63 ±â€Š5.98]%, P = 0.49) and serum IL-23 (51.55 ±â€Š27.82 pg/mL vs. 68.70 ±â€Š15.20 pg/mL, P = 0.15) showed no significant differences. Compared with the IPA group, the COPD+IPA group displayed lower amounts of blood ([5.18 ±â€Š1.09]% vs. [9.21 ±â€Š3.56]%, P = 0.01) and lung Th17 cells ([1.98 ±â€Š0.83]% vs. [6.29 ±â€Š1.11]%, P = 0.01) and serum IL-23 (51.55 ±â€Š27.82 pg/mL vs. 154.90 ±â€Š64.60 pg/mL, P = 0.01) and IL-17 (17.96 ±â€Š9.59 pg/mL vs. 39.81 ±â€Š22.37 pg/mL, P = 0.02), while comparable blood ([35.09 ±â€Š16.12]% vs. [29.86 ±â€Š15.42]%, P = 0.25) and lung levels of RORγt ([9.58 ±â€Š6.93]% vs. [15.10 ±â€Š2.95]%, P = 0.18) were found in these two groups. Finally, Aspergillus load in IL-17 KO COPD+IPA mice was almost 2 times that of COPD+IPA mice (1,851,687.69 ±â€Š944,480.43 vs. 892,958.10 ±â€Š686,808.80, t = 2.32, P = 0.02). CONCLUSION: These findings indicate that Th17 cells might be involved in the pathogenesis of COPD combined with IPA, with IL-17 likely playing an antifungal role.

[Clinical features of invasive pulmonary aspergillosis in critically ill patients with chronic respiratory diseases].

OBJECTIVE: To describe the clinical features of invasive pulmonary aspergillosis (IPA) in critically ill patients with chronic respiratory diseases (CRD) and to estimate its value for early diagnosis and treatment. METHODS: Retrospective study of critically ill CRD patients with positive Aspergillus from sputum or bronchial alveolar lavage fluid in a respiratory ICU of a teaching hospital. RESULTS: There were 149 CRD patients admitted between October 2004 and February 2007. Among these patients, 16 cases of IPA (11 COPD,4 COPD with asthma, 1 bronchiectasis ) were collected. Three cases fulfilled the criteria of proven IPA, 10 of probable and 3 of possible IPA. Corticosteroids and multiple broad-spectrum antibiotics had been administered to 12 and 15 patients respectively. Fifteen patients experienced worsening of bronchospasm leading to acute respiratory failure. Nine patients failed to improve on noninvasive ventilation, and 14 patients required invasive ventilation. Twelve patients had infiltrates on chest X-ray. Before the appearance of infiltrates, bronchoscopy showed tracheobronchial inflammatory changes with severe bronchospasm. With the rapid progression of infiltrates, bronchial pseudomembrane was observed, with increased white blood cell count and exacerbated radiology findings. The rate of positive isolation of Aspergillus from airway samples during early stage was lower than late stage (2/12 vs 10/12). Early treatment was started before the appearance of infiltrates in 4 patients, all of whom survived. Although antifungal treatment was started when IPA was suspected after the appearance of infiltrates, 11 of 12 patients died in septic shock or multiple-organ failure. CONCLUSIONS: IPA occurring in critically ill CRD patients is not rare and has a poor prognosis. Early diagnosis and empirical antifungal treatment based on certain clinical features may improve the outcome.

A follow-up study on acute respiratory distress syndrome survivors after extracorporeal membrane oxygenation by pulmonary high-resolution CT.

OBJECTIVE: This study aims to identify morphological changes in the lung parenchyma of acute respiratory distress syndrome (ARDS) survivors after extracorporeal membrane oxygenation  (ECMO) by high-resolution computed tomography (HRCT) follow-up. Factors influencing these changes are also examined. METHODS: Information and lung HRCT scans were collected and studied 1, 3, 6, and 12 months after the withdrawal of severe ARDS survivors rescued by ECMO in the Respiratory Care Unit of Beijing Chaoyang Hospital from November 2009 to August 2012. The observation endpoint was set as the time when the lung lesions were basically absorbed or 12 months after withdrawal. RESULTS: Among nine survivors, one survivor was lost to follow-up. The lesions of two patients, which were attributed to bacterial pneumonia and pneumocystis pneumonia, were basically absorbed 1 month after surgery. Six patients completed the 12 month follow-up. Although initial morphological changes varied, different degrees of absorption improvement were observed in later stages of treatment. Lung HRCT analysis on the sixth month indicated that the degree of involvement of the ventral region was greater than that of the dorsal area. No significant difference was observed in patients in terms of ECMO support time, pre-ECMO Murray score, and APACHE II score, among others. CONCLUSION: Lung HRCT of severe ARDS survivors after ECMO treatment showed various degrees of morphological changes in the lung parenchyma. The severity of these changes may be associated with the disease duration.

Significance of Aspergillus spp. isolation from lower respiratory tract samples for the diagnosis and prognosis of invasive pulmonary aspergillosis in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary diseases (COPD) is an emerging population at risk for invasive infection of Aspergillus. Isolation of Aspergillus from lower respiratory tract (LRT) samples is important for the diagnosis of invasive pulmonary aspergillosis (IPA). The purpose of this study was to investigate the value of Aspergillus isolation from LRT samples for the diagnosis and prognosis of IPA in COPD population. METHODS: Clinical record with Aspergillus spp. isolation in COPD and immunocompromised patients was reviewed in a retrospective study. Patients were categorized and compared according to their severity of illness (admitted to general ward or ICU) and immunological function (COPD or immunocompromised). RESULTS: Multivariate statistical analysis showed that, combined with Aspergillus spp. isolation, APACHE II scores > 18, high cumulative doses of corticosteroids (> 350 mg prednisone or equivalent dose) and more than four kinds of broad-spectrum antibiotics received in hospital may be predictors of IPA in COPD (OR = 9.076, P = 0.001; OR = 4.073, P = 0.026; OR = 4.448, P = 0.021, respectively). The incidence of IPA, overall mortality, mortality of patients with IPA and mortality of patients with Aspergillus spp. colonization were higher in COPD patients in ICU than in general ward, but were similar between COPD and immunocompromised patients. CONCLUSIONS: Aspergillus spp. isolation from LRT in COPD may be of similar importance as in immunocompromised patients, and may indicate an increased diagnosis possibility of IPA and worse prognosis when these patients received corticosteroids, antibiotics, and need to admit to ICU. Aspergillus spp. isolation from LRT samples combined with certain risk factors may be useful in differentiating colonization from IPA and evaluating the prognosis of IPA in COPD patients.

Effects of activated protein C on coagulation and fibrinolysis in rabbits with endotoxin induced acute lung injury.

BACKGROUND: Sepsis induced acute lung injury (ALI) as a common syndrome in clinical practice has a high mortality. Recombinant human activated protein C (APC) can significantly reduce the mortality of patients with severe sepsis. Several studies have implicated that APC may be protective in ALI. METHODS: Twenty-one rabbits were operatively prepared and randomly divided into sham, control, or APC groups (n = 7 in each group). After a tracheotomy had been performed, ALI was produced in the control and APC groups by infusion of Escherichia coli endotoxin 100 microg/kg per hour intravenously for 1 hour. The sham group received only the vehicle, infusion of 20 ml of 0.9% saline. The rabbits were studied under anesthesia for 6 hours and were ventilated with 40% oxygen. Bovine APC (25 microg x kg(-1) x h(-1)) was intravenously administered. The infusion was initiated half an hour post-injury and lasted for 4 hours. The animals were resuscitated with Ringer's lactate solution. RESULTS: In comparison with nontreatment in the control group, the infusion of APC significantly reduced the increase of thrombomodulin level (TM; control group was (0.68 +/- 0.06) ng/ml, vs APC group of (0.62 +/- 0.07) ng/ml at 6 hours, P < 0.05), and significantly attenuated the fall in protein S (PS; control group was (2.32 +/- 0.03) microg/ml at 2 hours, (2.24 +/- 0.06) microg/ml at 4 hours and (2.21 +/- 0.09) microg/ml at 6 hours, vs APC group (2.46 +/- 0.04) microg/ml at 2 hours, (2.40 +/- 0.05) microg/ml at 4 hours and (2.39 +/- 0.07) microg/ml at 6 hours, P < 0.01). In addition, APC limited the increase in plasminogen activator inhibitor-1 (PAI-1) both in plasma (control group was (0.68 +/- 0.12) ng/ml at 1 hour, (0.84 +/- 0.06) ng/ml at 2 hours, (0.87 +/- 0.08) ng/ml at 4 hours and (0.91 +/- 0.05) ng/ml at 6 hours, vs APC group (0.42 +/- 0.16) ng/ml at 1 hour, (0.43 +/- 0.04) ng/ml at 2 hours, (0.45 +/- 0.09) ng/ml at 4 hours and (0.45 +/- 0.14) ng/ml at 6 hours, P < 0.01) and in bronchoalveolar lavage fluid (at 6 hours: sham, (1.05 +/- 0.05) ng/ml; control, (1.13 +/- 0.06) ng/ml; APC, (1.06 +/- 0.06) ng/ml; P < 0.05). However, APC failed to prevent the decrease in PaO(2)/FiO(2) ratio. APC-treated rabbits showed no significant difference in platelet count and antithrombin but exhibited less D-dimer production than did the controls. Moreover, APC limited the histopathological score of lung injury (2.6 +/- 0.8 in control, vs 1.4 +/- 0.6 in APC group, P < 0.01). CONCLUSION: Anti-coagulation and pro-fibrinolysis activity may be two of the possible mechanisms by which activated protein C attenuated endotoxin-induced ALI.