Positive Bronchoalveolar Lavage Research Articles

Post-operative antifungal prophylaxis in lung transplant recipients: Unprecedented evidence

Introduction/objectives Despite recent advances in lung transplantation, Aspergillus infections are still a major concern in lung transplant (LT) recipients. The genus Aspergillus may manifest as colonization or infection forms. The latter being associated with significant mortality and morbidity. Colonization, defined as bronchoalveolar lavage or bronchial aspirate, or positive bronchoalveolar lavage galactomannan test, or at least two positive sputum cultures, or tracheal aspirate for Aspergillus spp. in asymptomatic patients with normal-appearing respiratory mucosa or absence of endobronchial lesions, usually precedes infectious forms and complicates transplantation course. While several antifungal prophylactic strategies have been used to limit this deadly disease that mess with this complex endeavor, evidence from retrospective or prospective studies is lacking. In a recent international survey, only 50% of lung transplants’ centers use antifungal prophylaxis, yet, substantial differences regarding the duration and the modality of antifungal prophylaxis exist among centers and, hence, increase the unmet need for clear recommendations. Since airways’ colonization usually precedes Aspergillus infections and LT recipients are most vulnerable, in particular, during the early post-operative period due to anastomotic ischemia, Aspergillus’ eradication seems to be a plausible solution to prevent or minimize Aspergillus colonization/infections post-transplantation. Consequently, all patients who underwent single or double lung transplantation in our center after 2014 received antifungal prophylaxis started on day 1 post-transplantation and carried on till healing of bronchial anastomosis. We report our 4-year experience with antifungal prophylaxis in LT recipients. Methods A retrospective analysis was conducted and compared LT recipients who systematically received inhaled amphotericin B deoxycholate (6 mg twice daily) and 200 mg twice daily oral voriconazole (2014–2017) to those who did not (2008–2013). Only non-cystic fibrosis LT recipients were included in the analysis given that cystic fibrosis patients usually harbor aspergillus species in their sino-nasal/respiratory tract, a fact that may underestimate such therapeutic strategy benefit and Aspergillus’ eradication may not be achieved. The data showed in this analysis was traced till hospital discharge. Results A total of 142 non-cystic fibrosis patients had undergone single/double lung transplantation. Between 2014 and 2017, 59 LT recipients received antifungal prophylaxis and Aspergillus spp. was found in 20 patients (incidence of 33%), while in the control group (n = 83) Aspergillus spp. was recovered from 42 patients (incidence of 50%). The difference between these 2 groups was statistically significant (P = 0.04) suggesting a potential beneficial effect of prompt post-operative antifungal prophylaxis in reducing Aspergillus colonization. Aspergillus fumigatus, A. niger, and A. flavus were most commonly found. Conclusions Immediate post-operative antifungal prophylaxis using amphotericin B deoxycholate and oral voriconazole significantly reduced nosocomial Aspergillus colonization in non-cystic fibrosis LT recipients. A finding that might decrease subsequent Aspergillus related complications and reduce unnecessary morbidity. However, prospective controlled randomized trials with long-term follow-up are eagerly awaited.

The clinical significance of oropharyngeal cultures in young children with cystic fibrosis.

In children with cystic fibrosis (CF) the associations between oropharyngeal swabs (OPSs) for detection of Pseudomonas and lung disease have not been evaluated.OPS and bronchoalveolar lavage (BAL) samples were obtained annually in children with CF from 2005 to 2017. OPS test characteristics were calculated using BAL as "gold standard". Results were related to lung inflammation (BAL neutrophil elastase and interleukin-8), structural lung disease (chest computed tomography PRAGMA-CF (Perth-Rotterdam Annotated Grid Morphometric Analysis for CF) scores), respiratory exacerbations and future detection of Pseudomonas on BAL.From 181 patients, 690 paired OPS-BAL cultures were obtained. Prevalence of Pseudomonas in BAL was 7.4%. OPS sensitivity was 23.0% and specificity was 91.4%, reducing the post-test probability for a positive BAL following a negative OPS to 6.3%. Pseudomonas on OPS was not associated with lung inflammation or respiratory exacerbations, but was weakly associated with current PRAGMA-CF %Disease score (p=0.043). Pseudomonas on BAL was associated with positive neutrophil elastase (OR 4.17, 95% CI 2.04-8.53; p<0.001), increased interleukin-8 (p<0.001), increased all baseline PRAGMA computed tomography scores (p<0.001), progression of PRAGMA computed tomography scores (p<0.05) and increased risk of respiratory exacerbations (incidence rate ratio 2.11, 95% CI 1.15-3.87; p=0.017).In children with CF OPSs only marginally change the probability of detecting lower airway Pseudomonas and are not associated with lung disease indices nor exacerbations risk.

Positive Pneumocystis jirovecii Sputum PCR Results with Negative Bronchoscopic PCR Results in Suspected Pneumocystis Pneumonia.

Introduction The diagnostic standard for Pneumocystis jirovecii pneumonia (PCP) is direct microscopic identification; however, in recent years, polymerase chain reaction (PCR) from bronchoalveolar lavage (BAL) samples to detect Pneumocystis nucleic acids has proven to be more sensitive and specific. Sputum samples have been presumed inferior to bronchoscopic samples secondary to variability and adequacy of sample collection. We observed several cases of positive sputum PCP-PCR results with negative PCP-PCR BAL results. The aim of the current study was to further characterize the clinical setting and outcomes in patients with positive sputum PCP-PCR samples and negative BAL PCP-PCR samples. Methods We identified all patients who underwent P. jirovecii-PCR testing at Mayo Clinic between 2011 and 2016. Patients with a positive sputum and negative BAL sample collected within a 14-day time frame were identified and underwent further chart review for demographics, immunocompromised state, and clinical outcome. Results From 2011 to 2016, 4431 respiratory samples from 3021 unique patients were tested for the presence of P. jirovecii by PCR. Fifty-five samples (1.2% of all samples collected) belonging to 24 unique patients (0.79% of patients tested) were identified as having a positive and negative sample collected within 14 days. Of these 24 patients, 10 (46%) patients had a positive sputum or tracheal secretion sample with negative BAL or bronchial washings. Out of these 10 patients, 8 were immunocompromised and 9 underwent treatment for PCP with 6 patients improving. Conclusion Our results suggest that discordant P. jirovecii-PCR testing results from sputum and bronchoscopic specimens are an infrequent occurrence. Patients with positive P. jirovecii-PCR sputum/tracheal secretion samples and negative bronchoscopic samples appear to be clinically infected and respond to PCP treatment. Sputum P. jirovecii-PCR testing may be a viable alternative to invasive testing.

Effect of aerosolized antipseudomonals on Pseudomonas positivity and bronchiolitis obliterans syndrome after lung transplantation.

To describe the effects of aerosolized antipseudomonals (AAPs) on Pseudomonas (PS) culture positivity, bronchiolitis obliterans syndrome (BOS), and acute cellular rejection (ACR) in lung transplant recipients (LTRs). Single-center, retrospective cohort study was performed of adult LTRs treated with either AAP for ≥28days vs no AAP therapy or AAP therapy <28days, indexed to a matched median date post lung transplantation (LT). Primary outcome was freedom from PS positivity by positive bronchoalveolar lavage or bronchial wash at 1year. Secondary outcomes were freedom from BOS or BOS progression and ACR burden (defined by the novel composite rejection standardized score. Normality was assessed, and univariate and multivariate parametric and non-parametric statistical tests were used to assess baseline characteristics and outcomes, where appropriate. Freedom from events was compared using the Kaplan-Meier method with log-rank conversion and risk was assigned using multivariable Cox proportional hazards (PH) modeling. In total, 293 LTRs (105 with AAP, 188 with no AAP) were included. Median ages in AAP and control cohorts were 51 (30-63) and 62 (54-67) years (P<.01). Median AAP duration was 198 (interquartile range 94-395) days. Time to median positive PS culture was similar between AAP (median 1.02 [95% confidence interval {CI} 0.74-1.22] years) and control (median 0.96 [95% CI 0.72-1.21] years). Log-rank test for time-to-PS positivity was similar for both groups (log-rank P=.26). Incidence of PS culture positivity at 1year was similar in APP vs controls (59.0% vs 54.8%, P=.48). In the non-cystic fibrosis (CF) subgroup, AAP use was protective against PS recurrence on univariate Cox PH model (hazard ratio [HR] 0.55, 95% CI 0.38-0.83) and on multivariate Cox PH adjusting for age and induction (HR 0.56, 95% CI 0.38-0.83). Incidence of new-onset BOS or BOS progression in APP vs control at 1 (17.1% vs 14.9%, P=.61) and 3 (38.1% vs 37.8%, P=.96) years was similar. CRSS was similar in APP vs control group at 1year (0.42 vs 0.33, P=.41). AAP use was not associated with less PS positivity, BOS, or ACR in all LTRs. In the non-CF subgroup analysis, treatment with AAPS was associated with protection against recurrent PS. Limitations include retrospective design, heterogeneous AAP therapy among LTRs, and potential convenience sampling of LTRs receiving AAPs for >28days at our center. Larger assessments and better controlled analyses are required to further define efficacy of AAPs after LT.

Nasopharyngeal viral PCR in immunosuppressed patients and its association with virus detection in bronchoalveolar lavage by PCR.

ABSTRACTBackground and objectivePulmonary infiltrates are common in immunosuppressed patients. Bronchoscopy with bronchoalveolar lavage (BAL) is often used to evaluate their aetiology. However, it may not always be easily performed. Thus, alternative diagnostic strategies may be needed. There is limited data on the correlation of nasopharyngeal (NP) respiratory viral panel (RVP)‐PCR testing compared with BAL. We aimed to identify the predictive value of NP RVP‐PCR samples compared with samples obtained from BAL in immunosuppressed patients with pulmonary infiltrates.MethodsWe conducted an observational retrospective study of immunosuppressed adults who underwent bronchoscopy in the Pulmonary Department at the University of Rochester Medical Center between January 2011 and June 2016. We compared the positive and negative predictive values, sensitivity, specificity and false negative rate of NP RVP‐PCR and BAL RVP‐PCR, as well as identified clinical predictors of positive viral BAL RVP‐PCR.ResultsEighty‐nine immunosuppressed patients had both NP and bronchoalveolar RVP‐PCR testing. Twenty‐one patients had NP(+)BAL(+) RVP‐PCR testing. Seven patients had false negative (NP(−)BAL(+)) RVP‐PCR testing. Three patients had NP(+)BAL(−) RVP‐PCR testing. The positive and negative predictive values of NP RVP‐PCR testing were 88% and 89%, respectively. Allogeneic bone marrow transplantation and testing performed in the winter and spring months were significantly associated with positive BAL RVP‐PCR (OR = 3.3 (1.19–9.12); OR = 4.62 (1.64–12.99), respectively).Conclusion NP RVP‐PCR testing has high concordance with testing performed on BAL samples. Repeat testing through BAL is beneficial when there is high concern for viral infection after initial NP RVP‐PCR testing is negative.

Pneumocystis jiroveci pneumonia (PJP) in non-HIV immunocompromised individuals

Objectives: PJP is a major cause of morbidity and mortality in immunocompromised individuals. Diagnosing PJP is often difficult because respiratory signs might be minimal or absent and the sensitivity of a chest X-ray (CXR) is low. We studied the clinical risk factors in order to increase awareness and facilitate the diagnosis.Methods: We studied a prospective case series over a one year period (from 1 January 2015 to 1 January 2016) and did a retrospective analysis (from 2013 to 2016) of all PJP positive bronchoalveolar lavage (BAL) analysis.Results: Seven patients with metastatic solid tumors were diagnosed with symptomatic PJP (based on positive polymerase chain reaction) over a one year period. The median age was 61 years. Three patients had brain metastasis. Four of them were on steroids, the median dose was 16 mg methylprednisolone with three of them at a tapered dose. Respiratory failure developed in four cases and prompted intensive care monitoring. Two patients needed non-invasive ventilation and the third patient was intubated and mechanically ventilated. No patient died of PJP. A retrospective analysis on microbiological results obtained from BAL in our hospital from 2013 to 2016 shows a striking high percentage PJP positivity in cancer patients (including hematologic cancers) of nearly 22% (15/69) as opposed to the overall number of PJP-positives 7.3% (59/803).Discussion: The incidence of clinical PJP in patients treated for metastatic cancer is substantial. A high index of suspicion, especially in cases with unexplained respiratory symptoms, concurrent or recent use of steroids, a normal CXR and otherwise unexplained increased lactate dehydrogenase levels, is critical. The threshold for performing a CT-scan must be low and the diagnosis needs to be confirmed microbiologically.

Diagnostic yield of bronchoalveolar lavage in immunocompromised children with malignant and non-malignant disorders.

SummaryBackgroundThe diagnostic yield of bronchoalveolar lavage (BAL) in the Immunocompromised pediatric population has ranged from 28% to 68%. We hypothesized that the diagnostic yield of BALs would be higher in more recent years due to new diagnostic assays.MethodsA retrospective case series was performed among immunocompromised children ≤18 years old who underwent BALs from 2001 to 2012, to assess the yield of microbiologic diagnostic studies and to determine the impact of BAL findings on antimicrobial management.ResultsIn all, 123 subjects underwent 174 BALs (mean age 9.9 years). Underlying diagnoses included both malignant (n = 79) and non‐malignant (n = 44) disorders, and 75 (61.0%) subjects were hematopoietic stem cell transplant (HSCT) recipients. Fifty‐four (31.0%) of 174 BAL were positive for ≥1 potential pathogen (n = 58 microorganisms). The diagnostic yield of BALs performed from 2001 to 2006 versus2007–2012 was similar (40.5% vs. 26.6%, respectively, P = 0.07). Most subjects (86.2%) were on ≥1 antimicrobial at the time of BAL. Most (65.8%) negative BALs were associated with narrowing antimicrobial therapy, while most (74.1%) positive BALs were associated with continuing or changing to targeted antimicrobial therapy.ConclusionsIn this study population, the diagnostic yield of BAL was similar to that previously described and unchanged in more recent years. Both negative and positive BALs were associated with changes in antimicrobial management.SummaryA 10‐year retrospective review of bronchoalveolar lavage in 123 immunocompromised children determined that the rate of isolation of potential pathogens was 31% in this population. The majority of BAL was associated with a change in antimicrobial therapy. Pediatr Pulmonol. 2017;52:820–826. © 2017 Wiley Periodicals, Inc.

Mechanism of Injury May Influence Infection Risk from Early Blood Transfusion.

Blood transfusion is a known risk factor for infection in trauma patients. Differences based on mechanism of injury have not been well described. We hypothesize that infection risk in trauma patients with early blood transfusion is different based on blunt or penetrating mechanism of injury. Adults admitted to the trauma intensive care unit from January 2010 through January 2015 were reviewed retrospectively. Those receiving transfusion after 24 h were excluded. Infections were defined as positive bronchoalveolar lavage, blood, urine, wound, or abdominal cultures. Logistic regression identified independent predictors of infection. Significance was considered at p ≤ 0.05. With blunt trauma (n = 625), the transfusion rate was 36% (n = 223), with 30% (n = 186) infections. Those with an infection were more severely injured, had a higher operation rate, lower Glasgow Coma Score (GCS), longer hospital stay, and higher transfusion rate (all p < 0.001). With penetrating trauma (n = 292), the transfusion rate was 54% (n = 159), with 26% (n = 77) infections. Those with an infection were older, more severely injured, had a higher operation rate, lower GCS, longer length of stay, and higher transfusion rate (all p < 0.01). Controlling for age, injury severity score (ISS), revised trauma score (RTS), GCS, and hospital stay, transfusion was an independent predictor of infection in patients with blunt (odds ratio: 2.1, 95% confidence intervals: 1.272-3.393, p = 0.003) but not penetrating trauma. Early blood transfusion increases infection risk in blunt but not penetrating trauma.

Change in Clinical Management Associated with Flexible Bronchoscopy and Bronchoalveolar Lavage in Hematopoietic Stem Cell Transplant Recipients with New Pulmonary Infiltrates

BackgroundPulmonary complications occur in 60% of hematopoietic stem cell transplant (HSCT) recipients with significant morbidity and mortality. Bronchoscopy with bronchoalveolar lavage (BAL) is an important diagnostic tool, but yield can be variable. The aim of this study was to investigate the utility of BAL in HSCT patients with new pulmonary infiltrates and determine factors associated with higher BAL yield.MethodsRetrospective review of BAL results from January 2014 to July 2016. Included first bronchoscopy for HSCT patients over 18 years of age. Positive BAL determined by positive culture (bacterial, fungal, mycobacteria), viral PCR, elevated aspergillus galactomannan antigen (AGA), and cytology. Logistic regression analysis was performed.Results54 HSCT recipients were included: 93% allogeneic, 34% neutropenic, 39% on prednisone, 59% on supplemental oxygen, 8% receiving mechanical ventilation (MV), 85% with multilobar infiltrates, 92% on antimicrobials (antibacterial 83%, antifungal 92%, antiviral 13%). 65% had positive BAL (23/54 bacterial, 16/54 elevated AGA, 6/54 fungal, 14/54 viral PCR, 1/54 mycobacteria). Median time to BAL from HSCT was 7.5 months. Not on levofloxacin prophylaxis (P = 0.004), not on MV (P = 0.037), or unrelated donor were associated with positive BAL results. Positive bacterial BAL culture was predictive of antibacterial escalation (P < 0.001). Elevated BAL AGA was associated with antifungal escalation and antibacterial de-escalation (P = 0.012). Antiviral initiation was more likely with positive BAL PCR (P = 0.002). Antifungal de-escalation (P = 0.047) and steroid initiation (P = 0.010) were more likely with negative BAL. 6 month mortality was 41%, and more likely with positive bacterial BAL culture (P = 0.046). Overall positive BAL was not predictive of mortality.ConclusionBronchoscopy with BAL assisted in making critical management changes: elevated AGA with antifungal escalation and antibacterial de-escalation; and negative BAL with prednisone initiation and antifungal de-escalation. Unrelated donors, patients not on levofloxacin, or not on MV were more likely to have a positive BAL. Antimicrobial use likely reduced diagnostic yield for bacterial pathogens. Overall 6 month mortality was high, especially among those with bacterial infections.Disclosures All authors: No reported disclosures.

Shifted focus of bronchoalveolar lavage in patients with suspected thoracic malignancy: an analysis of 224 patients.

Bronchoscopies are extensively adopted for diagnosing and staging thoracic malignancies, but studies are missing as how to keep the process streamlined and more efficient. To evaluate current role of bronchoalveolar lavage (BAL) for cancer and possible infection diagnosis when practicing comprehensive bronchoscopy for patients suspected with thoracic malignancy, and provide foundation for possible practice modification. We retrospectively analyzed a prospectively kept database of immunocompetent patients undergoing bronchoscopy for suspected non-hematologic malignancies. Clinical, radiographic data, bronchoscopic sampling techniques and diagnostic results were recorded. Initially undiagnostic patients were followed up for 2 years for a definitive diagnosis. Of 224 patients included, 179 (79.9%) were confirmed with active thoracic malignancies. BAL diagnostic yield of cancer based on different radiographic characters of target lesion are as follow: isolated lymphadenopathies 0%, central lesions 45.5%, peripheral masses (diameter ≥3 cm) 21.4%, peripheral large nodules (2≤ diameter <3 cm) 15.8%, and peripheral small nodules (diameter <2 cm) 7.1%, while composite bronchoscopy achieved diagnostic yield of 93.3%, 95.5%, 91.7%, 76.9%, and 66.7% in corresponding lesion types. No cancer was diagnosed solely by BAL-cytology. Proportions of patients with positive BAL culture did not differ significantly between patients with and without pre-test suspicion for infections (P=0.199). In multivariable analysis, infections were associated with age ≥75 (OR 3.0; 95% CI: 1.29-7.06), chronic obstructive pulmonary disease (COPD) (OR 2.7; 95% CI: 1.14-6.26) and diabetes mellitus (DM) (OR 4.5; 95% CI: 1.90-10.44). Omitting BAL cytology in settings of comprehensive bronchoscopy may not compromise cancer diagnosis. For patients primarily suspected with thoracic malignancy, performing BAL culture only based on clinical suspicion could miss important infectious etiology.

Intraepithelial neutrophils in pediatric severe asthma are associated with better lung function

BackgroundNeutrophils and IL-17A have been linked mechanistically in models of allergic airways disease and have been associated with asthma severity. However, their role in pediatric asthma is unknown.ObjectivesWe sought to investigate the role of neutrophils and the IL-17A pathway in mediating pediatric severe therapy-resistant asthma (STRA).MethodsChildren with STRA (n = 51; age, 12.6 years; range, 6-16.3 years) and controls without asthma (n = 15; age, 4.75 years; range, 1.6-16 years) underwent clinically indicated fiberoptic bronchoscopy, bronchoalveolar lavage (BAL), endobronchial brushings, and biopsy. Neutrophils, IL-17A, and IL-17RA–expressing cells and levels of IL-17A and IL-22 were quantified in BAL and biopsies and related to clinical features. Primary bronchial epithelial cells were stimulated with IL-17A and/or IL-22, with and without budesonide.ResultsChildren with STRA had increased intraepithelial neutrophils, which positively correlated with FEV1 %predicted (r = 0.43; P = .008). Neutrophilhigh patients also had better symptom control, despite lower dose maintenance inhaled steroids. Submucosal neutrophils were not increased in children with STRA. Submucosal and epithelial IL-17A–positive cells and BAL IL-17A and IL-22 levels were similar in children with STRA and controls. However, there were significantly more IL-17RA–positive cells in the submucosa and epithelium in children with STRA compared with controls (P = .001). Stimulation of primary bronchial epithelial cells with IL-17A enhanced mRNA expression of IL-17RA and increased release of IL-8, even in the presence of budesonide.ConclusionsA proportion of children with STRA exhibit increased intraepithelial airway neutrophilia that correlated with better lung function. STRA was also characterized by increased airway IL-17RA expression. These data suggest a potential beneficial rather than adverse role for neutrophils in pediatric severe asthma pathophysiology.

Pseudooutbreak of rapidly growing mycobacteria due to Mycobacterium abscessus subsp bolletii in a digestive and respiratory endoscopy unit caused by the same clone as that of a countrywide outbreak.

The nontuberculous mycobacteria (NTM) are widely spread. In Brazil, 2,520 cases of rapidly growing mycobacteria (RGM) infections after medical procedures were reported, with 5.4% of cases related to nonsurgical invasive procedures and with an occurrence of 1 clone (BRA100) of Mycobacterium abscessus subsp bolletii. To describe a pseudooutbreak of M abscessus subsp bolletii in an endoscopy and bronchoscopy unit. The alert for a pseudooutbreak was given when 3 patients, in the same week, had a positive bronchoalveolar lavage culture for M abscessus subsp bolletii. The patients had no symptoms/signs of mycobacterial infection; thus, contamination of bronchoscopes was suspected. Samples for culturing were collected from bronchoscopes, digestive endoscopes, automated disinfection machines, and the water supply. Clinical samples were identified by polymerase chain reaction restriction-enzyme analysis (PRA) of the hsp65 gene and their pulsed-field gel electrophoresis pattern was compared with environmental samples. The investigation demonstrated a contamination of bronchoscopes, digestive endoscopes, and disinfection machines. Molecular typing demonstrated that all strains belonged to the same clone (MAB01), identical to clone BRA100. Cross-transmission due to poor disinfection as well as resistance to glutaraldehyde may play roles in the spread of MAB01 M abscessus subsp bolletii, which may have a unique resistance to the environment and adaption to human hosts. However the water supply may have played a role. Attention is needed to ensure the quality of water used to rinse disinfected equipment.

The Significance of Bronchoalveolar Lavage Fluid Cytology in Diagnosing Lung Infiltrates in Children.

Aim:The aim of this research is to show why is it important in diagnosing children with lung infiltrates.Methods:Our study included 50 children with lung infiltrates during period 2005-2012, and was conducted on Pediatric Clinic of the University Clinical Center Sarajevo. We sent all cytological BAL analyses to the University Clinical Center Sarajevo. Cytology was performed by direct microscopy. BAL cytology was performed by the principle of sending samples for centrifuging, 12000 revolutions during a 10 min Shandon-cyto spin. Then the centrifuged sample is dried in the air during 1-2 hours, and is then dyed under the May-Grünwald-Giemsa staining, and analyzed under the Olympus BX41 microscope.Results:Nosocomial pneumonia has occurred in 32% children, acquired pneumonia in 38%, and 30% children had a lung infiltrates. 6 (12%) of children were younger then 1 year old, 23 (46%) children were between 1 to 5 years, 14 (28%) of children were between 5 to 10 ages, and 7 (14%) of children were between 10-15 ages. The most of the changes in observed children took place on the right lung, 34%, while 26% occurred on the left side, 22% were normal and 18% changes have affected both lungs, right and left. Percentage of cells in cytological smear in children with BAL were: cylindrical cells 28%, lung macrophage 26%, lymphocytes 17%, detritus 17% and phlegm 12%. Erythrocyte sedimentation rate (ESR) in children with BAL was up to 10-52%, to 50-30%, while ESR after first hour was above 50-18 %.Conclusion:Clinical parameters and local inflammation of the affected lobe are associated with positive bronchoalveolar cytology lavage findings.

The efficiency of routine endotracheal aspirate cultures compared to bronchoalveolar lavage cultures in ventilator-associated pneumonia diagnosis.

Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in İntensive Care Units (ICUs) and its mortality rate varies from 24% to 50%. The most important factor in decreasing the mortality is administering adequate antibiotics as early as possible. In this study, we investigate the efficiency of routine endotracheal aspirate (EA) cultures to identify the etiology of VAP earlier. Fifty-nine patients who were accepted to our ICU with acute cerebrovascular disease with mechanical ventilation (MV) requirement were chosen for this study over a 12-month period. The patients intubated in our ICU were included in the study to exclude prior colonization. Upon ICU admission, the patient's; age, sex, comorbidities, diagnosis, acute physiology and chronic health evaluation II score, and sequential organ failure assessment (SOFA) score were recorded. When bronchoalveolar lavage (BAL) was performed, the SOFA score, temperature, leukocyte count, C-reactive protein levels, PaO2/FiO2ratio, PCO2, clinical pulmonary infection score value, length of MV, and presence of antimicrobiological treatments were recorded. Routine microbiological analysis was performed by EA (pre-VAP EA) twice weekly in all patients until the endotracheal tube was removed. When VAP was suspected, fiberoptic bronchoscopy examination with BAL was performed. A diagnosis of VAP was established when the BAL quantitative culture grew at least one microorganism at a concentration ≥104 cfu/mL. VAP was diagnosed in 41 (69%) of the 59 patients based on BAL culture results. Among 41 positive BAL cultures, pre-VAP EA identified the same microorganism with the same antibiotics resistance pattern in 23 (56%) patients. Regarding only late-onset VAP, pre-VAP EA identified the same microorganisms found by BAL culture in 17 (63%) of the 27 cases. Among 18 BAL culture negative patients, 7 (39%) patients had negative prior pre-VAP EA culture results. Acinetobacter baumannii was the most frequently isolated microorganism from BAL cultures (n = 21, 51%). The diagnostic value of pre-VAP EA results in predicting A. baumannii VAP documented with the following values (sensitivity: 62%; specificity: 95%, positive predictive value: 87%, negative predictive value: 82%). VAP patients should be treated with international guidelines, but if pre-VAP EA cultures identify multidrug resistant pathogens, the initial antibiotic therapy should cover these microorganisms. Thus, quantitative EA cultures are a useful noninvasive diagnostic tool in critically ill patients suspected of having pneumonia especially in the case of VAP.

Infection and inflammation in induced sputum from preschool children with chronic airways diseases.

We hypothesized airway inflammation can be detected non-invasively by induced sputum (IS) or peripheral blood eosinophilia, and IS can detect bacterial and viral infection in preschool children with airway disease, with results comparable to broncho-alveolar lavage (BAL). Preschool children with cystic fibrosis, recurrent wheeze, or wet cough underwent IS with nebulized hypertonic saline, chest physiotherapy, and oropharyngeal suction. Samples were analyzed for inflammation by cytology and bacterial culture, viral detection by PCR. Results were compared to BAL and blood in a sub-group undergoing clinically indicated bronchoscopy. 64 children (median age 33 [7-76] months) underwent IS without adverse events. IS was obtained from 61/64. Twenty out of sixty-four underwent BAL and IS, no IS was obtained in 2/23. Thirteen out of twenty-one (62%) had matching bacteria and viruses, 4/21 had positive BAL bacterial growth with negative IS, and 3/21 had negative BAL growth with positive IS. 67% of sputum samples were processed for cytology, 46% had <80% squamous cells; the proportion of squamous cells reduced with increasing age (r = -0.55, P < 0.01). IS was significantly more neutrophilic and less eosinophilic than BAL; 2/21 IS samples contained eosinophils compared to 17/23 BAL. There was a positive correlation between blood and BAL eosinophilia (r = 0.75, P < 0.01). IS from preschool children can be used to assess infection. BAL and IS culture concurred in approximately two-thirds. However, inflammation was measureable in only one-third of IS samples and the cell differential was predominantly neutrophilic compared to BAL. Blood eosinophils may provide a better reflection of lower airway eosinophilia in this age group. Pediatr Pulmonol. 2016;51:778-786. © 2015 WileyPeriodicals, Inc.

Biomarkers for Idiopathic Pneumonia Syndrome after Hematopoietic Cell Transplantation: Comparison with Viral Infectious Pneumonia

Background: Idiopathic pneumonia syndrome (IPS) is a non-infectious pulmonary complication with diffuse lung injury that develops in 5-10% of patients who undergo hematopoietic cell transplantation (HCT) and the mortality rate remains high at 50-90%. IPS is difficult to distinguish from occult pneumonia after HCT, because it is hard to exclude all infectious etiologies. There are currently no laboratory tests to aid physicians in the early detection of IPS and other pulmonary infections. The aim of this study was to identify prognostic biomarkers of future occurrence of IPS and compare their profiles to that for subjects with infectious pneumonia.Patients and methods: Among patients transplanted between 1988 and 2014 at FHCRC, we identified 42 patients with IPS based on radiographic findings and exclusion of possible pathogens using frozen bronchoalveolar lavage (BAL) samples of occult viral infections as recently reported (Blood 2015: 24: 3789-97). HCT recipients who did not require bronchoscopic examination and who did not grow any bacterial or fungal blood cultures within 100 days after HCT were considered as controls (n=163) and samples were collected at similar timepoints as IPS cases. We examined cases of viral pneumonia confirmed by positive BAL: human rhinovirus (HRV, n=18) and parainfluenza (PIV, n=21). A set of 1129 plasma samples from pre-HCT, day 7, day 14, day 21 post-HCT and at onset of each event was analyzed. The "onset sample" for controls was the sample closest to day 24 (median day of onset for patients with pulmonary symptoms). We measured six proteins by ELISA: Suppressor of tumorigenicity 2 (ST2), tumor necrosis factor receptor 1 (TNFR1), interleukin-6 (IL-6), lymphocyte vessel endothelial receptor (LYVE)-1, endothelial protein C receptor (EPCR), and herpes virus entry mediator (HVEM). TNFR1, LYVE-1, EPCR and HVEM were discovered through a proteomics approach, and ST2 and IL-6 were also measured due to their associations with endothelial processes and IPS (Blood 2015: 15: 2435-44), respectively.Multivariable logistic regression was used to evaluate the association of each protein with IPS vs. controls and IPS vs. HRV+PIV. Protein concentrations were log10 transformed and values below the lower limit of detection were replaced with that value (this occurred in 28% of the IL-6 measurements only). All analyses were adjusted for age, sex, transplant year, and acute GVHD status (grade 0-1 vs 2-4). Odds ratios indicate an increase in the odds of IPS for a tenfold increase in the protein concentration (Table 1). Receiver Operating Characteristic (ROC) curves were generated for each marker and if the area under the ROC (AUC) was greater than 0.7, then the analyte was considered an informative predictor of IPS.Results: Patients' characteristics are detailed in Table 1. Of the six proteins, TNFR1, ST2, LYVE-1, HVEM, and IL-6 were significantly elevated at the onset of IPS compared to controls at similar time point (adjusted, Table 2). ST2 and IL-6 were also elevated in infectious cases, although to a lesser degree. However, the biomarkers were able to distinguish IPS cases from viral infections (HRV and PIV) occurring approximately at the same time post HCT (Figure 1A). We also evaluated the prognostic value of the proteins by analyzing samples measured at day 7 post-HCT. All six proteins were elevated in IPS cases versus controls as early as day 7 with AUC from 0.85 to 0.75 (data not shown), and distinguished IPS from HRV and PIV infections (Figure 1B).Conclusion: Five proteins, TNFR1, ST2, LYVE-, HVEM, and IL-6 were significantly elevated at the onset of respiratory failure in IPS patients as compared to patients without pulmonary injury. Although the markers were also elevated in viral pulmonary infections, they were able to distinguish IPS from HRV and PIV. Importantly, these markers were elevated as early as day 7 after HCT, prior to the clinical signs of IPS. Additional analyses combining proteins together to form a composite panel are currently ongoing. [Display omitted] [Display omitted] [Display omitted] DisclosuresPaczesny:Viracor laboratories: Patents & Royalties: "Methods of detection of graft-versus-host disease" (US- 13/573,766).

Detection of Angiostrongylus vasorum by quantitative PCR in bronchoalveolar lavage fluid in Belgian dogs.

To describe Angiostrongylus vasorum infection in a series of clinical cases over a 12-month period, report the use of quantitative PCR on broncho-alveolar lavage fluid and investigate the -possibility of previously undiagnosed angiostrongylosis in a retrospective cohort of coughing and healthy dogs. Pulmonary angiostrongylosis was diagnosed based on compatible clinical signs and positive quantitative PCR on broncho-alveolar lavage fluid and/or positive Baermann examination. Quantitative PCR was also performed retrospectively on broncho-alveolar lavage fluid from 65 dogs (55 coughing and 10 healthy dogs), examined between 2008 and 2014; results of Baermann examination were also available in 33 dogs. Seven young adult dogs from Southeastern Belgium with respiratory clinical signs were diagnosed with angiostrongylosis between March 2013 and April 2014. Positive broncho-alveolar lavage fluid quantitative PCR results and positive Baermann examination were obtained in 5/5 and 2/5 dogs, respectively. In the remaining two dogs, only Baermann analysis was performed. Among the retrospective cohorts, only one broncho-alveolar lavage fluid from a coughing dog was quantitative PCR-positive whereas all faecal samples were negative. Until recently, canine angiostrongylosis was not reported in Belgium. It should now be included in the differential diagnosis of coughing Belgian dogs. Identification of affected dogs may be aided by quantitative PCR on broncho-alveolar lavage fluid.

Legionellosis in Patients With Cancer

Background Legionella species cause severe pneumonia in the immunocompromised population, especially those with cell-mediated immunodeficiency. However, the varied clinical and radiographic presentation of Legionnaires disease can make diagnosis very difficult, which can result in a delay of appropriate therapy. For that reason, we performed this study to review the characteristics of Legionella pneumonia in immunocompromised patients with underlying cancer. Methods The study was a retrospective chart review of 11 patients with Legionella pneumonia at the Moffitt Cancer Center diagnosed between March 2005 and February 2014. The patients were identified on the basis of a positive bronchoalveolar lavage culture for Legionella and/or a positive Legionella urine antigen. Summarized host characteristics included underlying malignancy, absolute neutrophil count, and absolute lymphocyte count at the time of diagnosis as well as the computed tomographic chest imaging findings. Results Of the 11 patients included, 10 had Legionella pneumophila and 1 had L. feeleii. Nine (81.8%) of the 11 patients had a hematologic malignancy and 2 (18.2%) of the 11 patients had a solid organ tumor. One (9.0%) of the 11 patients had an underlying lung disease. At the time of the diagnosis, 3 (27.2%) of the 11 patients were neutropenic (absolute neutrophil count, <500 cells/mm3) and 8 (72.7%) of the 11 patients were lymphopenic (absolute lymphocyte count, <1500 cells/mm3). Four (36.3%) of the 11 patients had bilateral pneumonia. Three (27.2%) of the 11 patients had nodular consolidation. However, only 2 (18%) of the 11 patients were found to have consolidation along with ground-glass opacity. All patients were treated with levofloxacin. Seven (63.6%) of the 11 patients adequately responded to the therapy, 1 (9.0%) patient died because of pneumonia, and 3 (27.3%) patients died because of the underlying cancer. Conclusions Legionnaire disease remains a life-threatening illness in patients with cancer. Our study found that most patients are lymphopenic, with multifocal consolidation in 2 of 3 patients. In addition, nodular opacities on computed tomographic imaging were described in more than one third of our patients, which resembles a mold pneumonia. All the cases that were thought to be a mold pneumonia were diagnosed as Legionella by bronchoalveolar lavage culture or the Legionella urine antigen, emphasizing the need for heightened awareness and testing for this pathogen.

An observational study examining the relationship between respiratory symptoms, airway inflammation and bacteriology in children with severe neurodisability.

BackgroundChildren with severe neurodisability (ND) commonly suffer from chronic respiratory symptoms that impact greatly on quality of life, and lead to recurrent hospital admissions. This morbidity (and its causes) is poorly described, despite being well recognised by paediatricians. In this study, we characterised respiratory symptoms in children with ND at times of stability and deterioration. We also assessed the relationship between respiratory symptoms, lower airway inflammatory markers and levels of infection/colonisation.MethodsND children were recruited upon admission for elective surgery (Elective-ND [n = 16]), or acutely upon admission to Intensive Care (PICU-ND [n = 19]), and compared to healthy control children [n = 12]. Parents completed a validated respiratory symptom questionnaire in which symptoms associated with activity were removed (total maximal score of 108). Bronchoalveolar lavage (BAL) was collected, and BAL neutrophil counts, IL-8 and TGFβ-1 levels measured. BAL microbial analysis was performed using a 16S/18S rRNA gene based assay and Pseudomonas aeruginosa PCR.ResultsAll ND children had high levels of respiratory symptoms (median [IQR] symptom score PICU-ND, 55[38-64]; Elective-ND, 26[7-45]; Control, 4[0-7]: p<0.01), which affected their families, particularly at nighttime. Elective-ND patients with a total respiratory symptom score >20 invariably had BAL neutrophilia. Elective patients with 16S/18S microbial rDNA positive BAL had higher neutrophil counts (positive, 33[18-70]%; negative, 8[4-38]%: p<0.05) and generally higher symptom scores (positive, 17[5-32]; negative, 5[0-9]: p = 0.097). Streptococcus mitis was commonly identified in BAL from ND children; Pseudomonas aeruginosa was not identified in any sample.ConclusionsChildren with severe ND often have high levels of chronic respiratory symptoms, which may relate to lower airway inflammation. Bacterial airway colonisation, particularly with oral commensals, may play a role in both symptom generation and inflammation.

The Incidence of Ventilator-Associated Infections in Children Determined Using Bronchoalveolar Lavage.

Hospital-acquired infections are a major contributor to inpatient morbidity, mortality, and health care costs. Ventilator-associated pneumonia (VAP) is among the most common. It is associated with longer duration of mechanical ventilation (MV), longer intensive care unit stays, increase in cost per case of VAP of at least $40 000, and over 2-fold increased risk of mortality.1,2 Hospital rates of VAP are subject to mandated reporting and measured against national benchmarks. However, because the definition of VAP is complex and includes subjective signs and symptoms, the reported incidence in children varies widely from 0.3 to 45.1 cases per 1000 ventilator days.3 VAP may not include all clinically important infections associated with MV.4 Another infection, ventilator-associated tracheobronchitis (VAT), has been described using varying definitions with unclear clinical significance. The incidence of VAT in pediatric intensive care unit (PICU) populations has been reported at 3.4% to 7.3% of ventilated patients, and as high as 21.2% in trauma patients.5-9 VAT has been associated with longer duration of MV and length of stay but not increased mortality.5-7 Variable definitions have been used in studies of VAT, but generally include clinical signs of respiratory infection in the absence of pneumonia on chest radiograph combined with a positive respiratory culture.8,9 Recent studies of VAT in pediatrics have all used a definition based on the Centers for Disease Control and Prevention/National Healthcare Safety Network (CDC/NHSN) definition of “lower respiratory tract infection other than pneumonia” and applied it to children on MV.5-7,10 Definitions of VAT, and those of VAP, are complicated by their reliance on poor interpretability and subjectivity of data including clinical signs and chest radiographs. Microbiologic testing is complicated due to the lack of standard microbiologic methods.3 Respiratory specimens can be obtained by bronchoscopic or non-bronchoscopic bronchoalveolar lavage (BAL), by protected specimen brush, or by endotracheal aspirate (ETA) via new or inline suction catheters. ETA may be preferred due to perceived safety, feasibility, and cost concerns.4 However, validity of cultures obtained by ETA may be questioned due to bacterial colonization of endotracheal tubes. Quantitative bacterial cultures may improve specificity of ETA cultures for infection over colonization, and a threshold of >105 cfu/mL has been suggested.9 Publications on VAT have invariably used ETA as the method to obtain specimens, but have varied in the use of quantitative culture. In our institution, BAL is used for the routine evaluation of ventilator-associated infections including VAP and VAT. Surveillance cultures and ETA are not performed due to concerns of interpretability of results. Because of this, we are in a unique position to provide the first report of BAL results in a large cohort of PICU patients. We hypothesized that VAP represents only a small portion of positive BALs, suggesting that other potentially significant ventilator-associated infections are not well characterized.