Search

Background Early diagnosis of invasive fungal disease is essential for optimizing management. Although the clinical utility of fungal polymerase chain reaction (PCR) testing on plasma and bronchoalveolar lavage (BAL) has been established, the role of follow-up testing remains unclear. Methods This was a retrospective single-center study. The yield of follow-up PCR for Aspergillus species, Mucorales agents, Fusarium species, Scedosporium species, dimorphic fungi, Pneumocystis jirovecii , and Candida species on plasma and/or BAL was measured at intervals of 1, 2, 3, and 4 weeks following a negative result. Results A total of 1389 follow-up tests on 406 plasma specimens from 264 patients and 983 BAL specimens from 431 patients were evaluated. Overall, the positivity rate at 1, 2, 3, and 4 weeks was 2.7% (4/148), 3.3% (4/123), 5.1% (4/78), and 3.5% (2/57), respectively, on plasma, and 0% (0/333), 0.3% (1/288), 0.4% (1/228), and 0.7% (1/134), respectively, on BAL. Conversions occurred with Aspergillus species, Mucorales agents, and Fusarium species PCR on plasma and Aspergillus species and P jirovecii PCR on BAL. All patients who converted were immunocompromised. Within 1 week of a prior negative test, 2 Aspergillus and 2 Mucorales PCRs were positive on plasma, and zero tests were positive on BAL. In week 1, only 1 Aspergillus species that was positive on day 7 was classified as probable fungal disease. Conclusions Fungal PCR follow-up testing on plasma and BAL within 4 weeks of a prior negative result was of low yield and rarely generated a positive result considered clinically significant in the first week. [ABSTRACT FROM AUTHOR]

Background In burn patients, skin barrier disruption and immune dysfunctions increase susceptibility to invasive fungal diseases (IFDs) like invasive candidiasis (IC) and invasive mold infections (IMI). We provide an in-depth analysis of IFD-related factors and outcomes in a 10-year cohort of severe burn patients. Methods This retrospective cohort study includes adult patients admitted to the burn intensive care unit (BICU) between April 2014 and May 2023 with total burn surface area (TBSA) ≥15%. Patients were classified as proven IFD according to EORTC/MSGERC criteria applicable for IC. Putative IMIs were defined with: ≥2 positive cultures from a skin biopsy/bronchoalveolar lavage or ≥2 positive blood specific-quantitative polymerase chain reactions (qPCRs) or a combination of both. Results Among 1381 patients admitted, 276 consecutive patients with TBSA ≥15% were included. Eighty-seven (31.5%; IC n = 30; IMI n = 43; both n = 14) patients fulfilled the criteria for probable/putative IFD. At Day 30 after the burn injury, the estimated cumulative incidence proven/putative (pr/pu) IFD was 26.4% (95% confidence interval [CI], 21.4%–31.8%). Factors independently associated with IFDs were TBSA, severity scores and indoor burn injury (ie, from confined space fire). Overall mortality was 15.3% and 36.8% in the no IFD, pr/pu IFD groups respectively (P <.0001). IFD was independently associated with a risk of death (hazard ratio [HR]: 1.94 for pr/pu IFD; 95% CI, 1.12–3.36; P =.019). Conclusions This study describes twenty-first-century characteristics of IFDs in severe burn patients confirming known risk factors with thresholds and identifying the indoor injury as an independent factor associated to IFDs. This suggests a link to contamination caused by fire damage, which is highly susceptible to aerosolizing spores. [ABSTRACT FROM AUTHOR]

Background This meta-analysis examines the comparative diagnostic performance of polymerase chain reaction (PCR) for the diagnosis of Pneumocystis pneumonia (PCP) on different respiratory tract samples, in both human immunodeficiency virus (HIV) and non-HIV populations. Methods A total of 55 articles met inclusion criteria, including 11 434 PCR assays on respiratory specimens from 7835 patients at risk of PCP. QUADAS-2 tool indicated low risk of bias across all studies. Using a bivariate and random-effects meta-regression analysis, the diagnostic performance of PCR against the European Organisation for Research and Treatment of Cancer–Mycoses Study Group definition of proven PCP was examined. Results Quantitative PCR (qPCR) on bronchoalveolar lavage fluid provided the highest pooled sensitivity of 98.7% (95% confidence interval [CI], 96.8%–99.5%), adequate specificity of 89.3% (95% CI, 84.4%–92.7%), negative likelihood ratio (LR−) of 0.014, and positive likelihood ratio (LR+) of 9.19. qPCR on induced sputum provided similarly high sensitivity of 99.0% (95% CI, 94.4%–99.3%) but a reduced specificity of 81.5% (95% CI, 72.1%–88.3%), LR− of 0.024, and LR+ of 5.30. qPCR on upper respiratory tract samples provided lower sensitivity of 89.2% (95% CI, 71.0%–96.5%), high specificity of 90.5% (95% CI, 80.9%–95.5%), LR− of 0.120, and LR+ of 9.34. There was no significant difference in sensitivity and specificity of PCR according to HIV status of patients. Conclusions On deeper respiratory tract specimens, PCR negativity can be used to confidently exclude PCP, but PCR positivity will likely require clinical interpretation to distinguish between colonization and active infection, partially dependent on the strength of the PCR signal (indicative of fungal burden), the specimen type, and patient population tested. [ABSTRACT FROM AUTHOR]

Objective To explore whether cytokines could be potential biomarkers to predict the occurrence of the progressive fibrosis (PF) phenotype among patients with interstitial pneumonia with autoimmune features (IPAF). Methods This study prospectively collected 51 IPAF and 15 idiopathic pulmonary fibrosis (IPF) patients who were diagnosed at the First Affiliated Hospital of Guangzhou Medical University from July 2020 to June 2021. All IPAF patients were followed up for 1 year to assess the development of PF phenotype. Paired bronchoalveolar lavage fluid (BALF) and serum samples were collected at enrolment and analysed for differences in 39 cytokines expression. Principal component analysis (PCA) and cluster analysis were conducted to identify a subgroup of IPAF patients at high risk for developing the PF phenotype. Finally, cytokine differences were compared between subgroups to identify potential biomarkers for PF-IPAF occurrence. Results According to the PCA analysis, 81.25% of PF-IPAF patients share overlapped BALF cytokine profiles with IPF. Cluster analysis indicated that IPAF patients in subtype 2 had a higher risk of developing the PF phenotype within 1 year (P  = 0.048), characterized by higher levels of CCL2 and CXCL12, and lower lymphocyte proportion (LYM%) in BALF. Elevated levels of BALF CCL2 (>299.16 pg/ml) or CXCL12 (>660.115 pg/ml) were associated with a significantly higher risk of developing PF phenotype within the 1-year follow-up period (P  = 0.009, 0.001, respectively). Conclusion PF-IPAF phenotype exhibits similar inflammatory cytokine profiles to IPF. Cytokine CCL2 and CXCL12, and LYM% in BALF serve as potential biomarkers for predicting the PF phenotype in IPAF patients. Clinical Trial Registration Register: Qian Han, Website: http://www.chictr.org.cn/showproj.aspx?proj=61619 , Registration number: ChiCTR2000040998. [ABSTRACT FROM AUTHOR]

We studied patients diagnosed with aspergillosis based on positive bronchoalveolar lavage (BAL) Aspergillus galactomannan (GM) who had follow-up BAL sampling within 180 days. GM trend and clinical outcome were concordant in only 60% (30/50). While useful for the initial diagnosis, BAL GM trending does not always correlate with treatment response. [ABSTRACT FROM AUTHOR]

The article describes the case of a 32-year-old Japanese woman of inborn good health who experienced fever and EBV viremia. Topics discussed include findings on laboratory tests, the hospital admission of the patient at the age of 35 years becuase of dyspnea and pancytopenia, and her death 68 days after admission, despite intensive care.

Background Coronavirus disease 2019 (COVID-19)–associated pulmonary aspergillosis (CAPA) is a frequent superinfection in critically ill patients with COVID-19 and is associated with increased mortality rates. The increasing proportion of severely immunocompromised patients with COVID-19 who require mechanical ventilation warrants research into the incidence and impact of CAPA during the vaccination era. Methods We performed a retrospective, monocentric, observational study. We collected data from adult patients with severe COVID-19 requiring mechanical ventilation who were admitted to the intensive care unit (ICU) of University Hospitals Leuven, a tertiary referral center, between 1 March 2020 and 14 November 2022. Probable or proven CAPA was diagnosed according to the 2020 European Confederation for Medical Mycology/International Society for Human and Animal Mycology (ECMM/ISHAM) criteria. Results We included 335 patients. Bronchoalveolar lavage sampling was performed in 300 (90%), and CAPA was diagnosed in 112 (33%). The incidence of CAPA was 62% (50 of 81 patients) in European Organisation for Research and Treatment of Cancer (EORTC)/Mycosis Study Group Education and Research Consortium (MSGERC) host factor–positive patients, compared with 24% (62 of 254) in host factor–negative patients. The incidence of CAPA was significantly higher in the vaccination era, increasing from 24% (57 of 241) in patients admitted to the ICU before October 2021 to 59% (55 of 94) in those admitted since then. Both EORTC/MSGERC host factors and ICU admission in the vaccination era were independently associated with CAPA development. CAPA remained an independent risk factor associated with mortality risk during the vaccination era. Conclusions The presence of EORTC/MSGERC host factors for invasive mold disease is associated with increased CAPA incidence and worse outcome parameters, and it is the main driver for the significantly higher incidence of CAPA in the vaccination era. Our findings warrant investigation of antifungal prophylaxis in critically ill patients with COVID-19. [ABSTRACT FROM AUTHOR]

Background The impact of metagenomic next-generation sequencing (mNGS) on antimicrobial stewardship in patients with lower respiratory tract infections (LRTIs) is still unknown. Methods This retrospective cohort study included patients who had LRTIs diagnosed and underwent bronchoalveolar lavage between September 2019 and December 2020. Patients who underwent both mNGS and conventional microbiologic tests were classified as the mNGS group, while those with conventional tests only were included as a control group. A 1:1 propensity score match for baseline variables was conducted, after which changes in antimicrobial stewardship between the 2 groups were assessed. Results A total of 681 patients who had an initial diagnosis of LRTIs and underwent bronchoalveolar lavage were evaluated; 306 patients were finally included, with 153 in each group. mNGS was associated with lower rates of antibiotic escalation than in the control group (adjusted odds ratio, 0.466 [95% confidence interval,.237–.919]; P =.02), but there was no association with antibiotic de-escalation. Compared with the control group, more patients discontinued the use of antivirals in the mNGS group. Conclusions The use of mNGS was associated with lower rates of antibiotic escalation and may facilitate the cessation of antivirals, but not contribute to antibiotic de-escalation in patients with LRTIs. [ABSTRACT FROM AUTHOR]

Background Metagenomic next-generation sequencing (mNGS) provides innovative solutions for predicting complex infections. A comprehensive understanding of its strengths and limitations in real-world clinical settings is necessary to ensure that it is not overused or misinterpreted. Methods Two hundred nine cases with suspected pneumonia were recruited to compare the capabilities of 2 available mNGS assays (bronchoalveolar lavage fluid [BALF] mNGS and plasma mNGS) to identify pneumonia-associated DNA/RNA pathogens and predict antibiotic resistance. Results Compared to clinical diagnosis, BALF mNGS demonstrated a high positive percent agreement (95.3%) but a low negative percent agreement (63.1%). Plasma mNGS revealed a low proportion of true negatives (30%) in predicting pulmonary infection. BALF mNGS independently diagnosed 65.6% (61/93) of coinfections and had a remarkable advantage in detecting caustic, rare, or atypical pathogens. Pathogens susceptible to invasive infection or bloodstream transmission, such as Aspergillus spp, Rhizopus spp, Chlamydia psittaci , and human herpesviruses, are prone to be detected by plasma mNGS. BALF mNGS tests provided a positive impact on the diagnosis and treatment of 128 (61.2%) patients. Plasma mNGS, on the other hand, turned out to be more suitable for diagnosing patients who received mechanical ventilation, developed severe pneumonia, or developed sepsis (all P <.01). BALF mNGS was able to identify resistance genes that matched the phenotypic resistance of 69.4% (25/36) of multidrug-resistant pathogens. Conclusions Our data reveal new insights into the advantages and disadvantages of 2 different sequencing modalities in pathogen identification and antibiotic resistance prediction for patients with suspected pneumonia. [ABSTRACT FROM AUTHOR]

In 2019, nearly 3000 U.S. residents developed severe lung injury associated with recent use of e-cigarette or vaping products. The Centers for Disease Control and Prevention responded to the outbreak, which was formally defined as e-cigarette, or vaping, product use-associated lung injury (EVALI). Centers for Disease Control and Prevention Laboratory rapidly developed assays to analyze potentially harmful and addictive substances in bronchoalveolar lavage (BAL) fluid collected from EVALI case patients. This report describes the development and validation of a high-throughput isotope-dilution high performance liquid chromatography–tandem mass spectrometry method for measuring two nicotine biomarkers, cotinine (COT) and trans-3′-hydroxycotinine (HCT), in bronchoalveolar lavage fluid samples. COT and HCT are the major metabolites of nicotine, the addictive alkaloid presents in tobacco products. This method had good specificity and sensitivity. The limit of detection is 0.033 and 0.0165 ng/mL for COT and HCT, respectively, using only 200 µL of sample volume. The within-run and between-run precision were 2–10%. The overall accuracy, calculated from recovery in three different sample matrices spiked at three concentrations, was 94.8% and 93.6% for COT and HCT, respectively. This novel HPLC–MS-MS method was utilized to characterize recent tobacco exposure in EVALI case patients. This method is useful for characterizing tobacco exposure that may be related to acute and chronic lung injury. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to compare metagenomic next-generation sequencing (mNGS) with other methods, including Xpert MTB/RIF, Mycobacterium tuberculosis (MTB) culture, and acid-fast bacillus (AFB) staining in the diagnosis of pulmonary tuberculosis (PTB) using bronchoalveolar lavage fluid (BALF). Methods The data of 186 patients with suspected PTB were retrospectively collected from January 2020 to May 2021 at Tongji Hospital. BALF samples were collected from all patients and analyzed using AFB staining, MTB culture, Xpert MTB/RIF, and mNGS. Results Of the 186 patients, 38 patients were ultimately diagnosed as PTB. Metagenomic next-generation sequencing exhibited a sensitivity of 78.95%, which was higher than AFB staining (27.59%) and MTB culture (44.12%) but similar to Xpert MTB/RIF (72.73%). Utilization of combined methods demonstrates improvement for PTB diagnosis. In support of this, the area under the receiver operating characteristic curve for the combination of mNGS and MTB culture (0.933, 95% CI: 0.871, 0.995) was larger than those of mNGS, Xpert MTB/RIF, MTB culture, and the combination of Xpert MTB/RIF and MTB culture. Conclusion The sensitivity of mNGS in the diagnosis of PTB using BALF specimen is similar to Xpert MTB/RIF. Metagenomic next-generation sequencing in combination with MTB culture may further improve the diagnosis of pulmonary tuberculosis. [ABSTRACT FROM AUTHOR]

Objective We aimed to compare the cellular composition of bronchoalveolar lavage (BAL) fluids in children with chronic unexplained cough (group 1) and severely neurologically impaired children with chronic or recurrent respiratory problems (group 2) with the BAL cytology of children without pulmonary or systemic diseases (group 3). Methods Bronchoscopy with BAL fluid analysis was performed in all subjects. Children with respiratory symptoms underwent 24-hour multichannel intraluminal impedance monitoring. Results A significant difference was found between the groups in the total number of cells in BAL fluid cytology (191 [range, 24–12,747], 747 [range, 53–13,000], and 105 [range, 41–233] cells/μL, P =.015), in the percentage of neutrophils (21.2 [SD = 32.4], 49.4 [SD = 36.6], and 3.6 [SD = 2.4], P <.001), and in the percentage of lipid-laden macrophages (10.3 [SD = 11.4], 13.7 [SD = 15.8] and 0.44 [SD = 1.0], P <.001). Conclusion The BAL fluid cytology provides useful data for determining the cause of chronic unexplained cough and chronic or recurrent respiratory problems in severely neurologically impaired children. [ABSTRACT FROM AUTHOR]

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) on nasopharyngeal swab (NPS), remains the most reliable and practical test to diagnose coronavirus disease 2019 (COVID-19). Current literature is sparse regarding the rates of discordance between NPS and bronchoalveolar lavage (BAL) in patients with cancer. Methods We conducted a retrospective cohort study of adult patients with cancer who had BAL samples tested for SARS-CoV-2 at a comprehensive cancer center. Patients without NPS PCR for SARS-CoV-2 before BAL were excluded. Results In a cohort of 345 patients, 12% and 17% tested positive for SARS-CoV-2 on NPS and BAL, respectively. There was a 6.3% NPS−/BAL+ discordance rate and a 9.5% NPS+/BAL− discordance rate. Patients with lymphoma (adjusted odds ratio [aOR] = 4.06; P =.007) and Hispanic patients (aOR = 3.76; P =.009) were more likely to have NPS−/BAL+ discordance on multivariate analysis. Among patients with NPS− /BAL− for SARS-CoV-2, an alternate infectious (23%) and a noninfectious etiology (16%) were identified in BAL. Conclusions Our discordance rates between NPS and BAL were sufficient to recommend BAL in certain patients with cancer with a high clinical suspicion of COVID-19. BAL has value in identifying alternative etiologies of illness in patients with suspected or confirmed COVID-19. [ABSTRACT FROM AUTHOR]

The performance of lateral flow assay (LFA) in diagnosing invasive pulmonary aspergillosis (IPA) has not been well demonstrated. To address this, we conducted a meta-analysis assessing the overall accuracy of LFA in diagnosing IPA using bronchoalveolar lavage fluid (BALF). Over a systematical search and assessment of bias risk, we calculated the pooled specificity, sensitivity, and area under the receiver operating curve (AUC) to assess the diagnostic performance. Our meta-analysis included 11 studies. The combined total sensitivity and specificity for diagnosing IPA were 0.78 (95% confidence interval (CI): 0.71, 0.83) and 0.87 (95% CI: 0.81, 0.91), respectively. The AUC was 0.86 (95% CI: 0.82, 0.89). Our results demonstrate that LFA using galactomannan in BALF exhibits high sensitivity and specificity for diagnosing IPA. [ABSTRACT FROM AUTHOR]

Different human leukocyte antigen (HLA) alleles associate with disease phenotypes in sarcoidosis. Peripheral blood (PB) lymphopenia is reported as more common in sarcoidosis patients with worse prognosis. The mechanisms behind are unrecognized but a PB depletion due to lymphocytes migrating to lung and/or extra pulmonary organs has been suggested. Insights into associations between HLA alleles, lung immune cells, clinical phenotype including extra pulmonary manifestations (EPM), and PB lymphopenia may provide mechanistic clues and enable adequate intervention in this patient group. In this situdy,141 treatment naïve, newly diagnosed patients were retrospectively identified in a Swedish cohort of sarcoidosis patients. Data on HLA-DRB1 alleles, lung immune cells from bronchoalveolar lavage fluid (BALF), PB lymphocytes and clinical parameters including treatment and disease course (chronic vs. resolving) were collected. The patients were followed for 2 years. PB lymphopenia associated with male sex, development of non-resolving disease, a need for first- and second-line systemic immunosuppressant treatment and HLA- DRB1*07. No correlation between BALF and PB lymphocytes, and no difference in EPM was detected between patients with and without PB lymphopenia. In conclusion, PB lymphopenia is associated with a more severe disease phenotype and carriage of the HLA-DRB1*07 allele. The results do not lend support to the hypothesis about sarcoidosis PB lymphopenia being due to a migration of PB lymphocytes to other organs. Rather, they provide a basis for future studies on the connection between HLA-DRB1*07 and PB lymphopenia mechanisms. [ABSTRACT FROM AUTHOR]

Background Bronchiectasis is a chronic inflammatory respiratory disease mainly caused by pathogenic infections. However, standard methods of pathogen detection show prolonged cycle durations and unsatisfactory sensitivity and detection rates. Macrogenomic next-generation sequencing (mNGS) emerges as a promising technique for swift, effective, and unbiased pathogen detection and subsequent data interpretation. Methods Here, a retrospective analysis of 93 patients with suspected bronchiectasis was performed to assess the clinical applicability of mNGS. Bronchoalveolar alveolar lavage fluid (BALF) samples were collected from these subjects, followed by standard assays and mNGS separately. The turnaround time, detection rate, and pathogen identification using mNGS were compared with those of standard methods. Results mNGS identified a greater number of bacteria (72 vs 16), fungi (26 vs 19), and viruses (14 vs 0) than standard methods. Specifically, the commonly identified bacteria were Haemophilus , Mycobacterium intracellulare , Pseudomonas , and Streptococcus pneumoniae , while the most detected fungi were Aspergillus and the most prevalent viruses were human herpesviruses. Of note, 29 out of 30 patients (96.67%) who received optimized treatment strategies based on mNGS results experienced recovery. Conclusions Collectively, these findings suggest that mNGS has the potential to improve the diagnosis and treatment of bronchiectasis patients by enabling rapid and precise pathogen detection, which can lead to timely and effective treatment strategies. [ABSTRACT FROM AUTHOR]

Background Missing or undiagnosed patients with tuberculosis (TB) or coronavirus disease 2019 (COVID-19) are of concern. Identifying both infections in patients with no diagnosis prior to death contributes to understanding the burden of disease. To confirm reports of global reduction in TB incidence, a 2012 autopsy study of adults dying at home of natural causes in a high-TB-burden setting was repeated, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assessments after the first COVID-19 surge in South Africa. Methods Adult decedents who died at home with insufficient information to determine cause of death, no recent hospitalization, and no current antemortem TB or COVID-19 diagnosis were identified between March 2019 and October 2020 with a 4-month halt during lockdown. A standardized verbal autopsy followed by minimally invasive needle autopsy (MIA) was performed. Biopsies were taken for histopathology from liver, bilateral brain and lung; bronchoalveolar lavage fluid was collected for Xpert (MTB/RIF) and mycobacterial culture, and blood for human immunodeficiency virus (HIV) polymerase chain reaction (PCR) testing. After the start of the COVID-19 pandemic, a nasopharyngeal swab and lung tissue were subjected to SARS-CoV-2 PCR testing. Results Sixty-six MIAs were completed in 25 men and 41 women (median age, 60 years); 68.2% had antemortem respiratory symptoms and 30.3% were people with HIV. Overall, TB was diagnosed in 11 of 66 (16.7%) decedents, and 14 of 41 (34.1%) in the COVID-19 pandemic were SARS-CoV-2 positive. Conclusions Undiagnosed TB in adults dying at home has decreased but remains unacceptably high. Forty percent of decedents had undiagnosed COVID-19, suggesting that estimates of excess deaths may underestimate the impact of SARS-CoV-2 on mortality. [ABSTRACT FROM AUTHOR]

Background: The Scandinavian Diverticulitis (SCANDIV) trial and the LOLA arm of the LADIES trial randomized patients with Hinchey III perforated diverticulitis to laparoscopic peritoneal lavage or sigmoid resection. The aim of this analysis was to identify risk factors for treatment failure in patients with Hinchey III perforated diverticulitis. Methods: This was a post hoc analysis of the SCANDIV trial and LOLA arm. Treatment failure was defined as morbidity requiring general anaesthesia (Clavien-Dindo grade IIIb or higher) within 90 days. Age, sex, BMI, ASA fitness grade, smoking status, previous episodes of diverticulitis, previous abdominal surgery, time to surgery, and surgical competence were all tested in univariable and multivariable logistic regression analyses using an interaction variable. Results: The pooled analysis included 222 patients randomized to laparoscopic lavage and primary resection (116 and 106 patients respectively). Univariable analysis found ASA grade to be associated with advanced morbidity in both groups, and the following factors in the laparoscopic lavage group: smoking, corticosteroid use, and BMI. Significant factors for laparoscopic lavage morbidity in multivariable analysis were smoking (OR 7.05, 95 per cent c.i. 2.07 to 23.98; P = 0.002) and corticosteroid use (OR 6.02, 1.54 to 23.51; P = 0.010). Conclusion: Active smoking status and corticosteroid use were risk factors for laparoscopic lavage treatment failure (advanced morbidity) in patients with perforated diverticulitis. [ABSTRACT FROM AUTHOR]

Aims To perform a prospective diagnostic study exploring the clinical utility of metagenomic next-generation sequencing (mNGS) in diagnosing community-acquired pneumonia (CAP), and revealing resistome differences in bronchoalveolar lavage fluid (BALF) from CAP patients with varying severity of admission base on Pneumonia Patient Outcomes Research Team (PORT) risk classes. Methods and results We compared the diagnostic performances of mNGS and conventional testing for the detection of pathogens in BALF from 59 CAP patients, and performed resistome differences analysis of metagenomic data from 59 BALF samples, namely, 25 from CAP patients with PORT score I (I group), 14 from CAP patients with PORT score II (II group), 12 from CAP patients with PORT score III (III group), and 8 from CAP patients with PORT score IV (IV group). The diagnostic sensitivities of mNGS and conventional testing for the detection of pathogens in BALF in patients with CAP were 96.6% (57/59) and 30.5% (18/59), respectively. There was a significant difference in the overall relative abundance of resistance genes between the four groups (P  = 0.014). The results of principal coordinate analysis based on Bray–Curtis dissimilarities showed that there were significant differences in the composition of resistance genes among the I, II, III, and IV groups (P  = 0.007). A large number of antibiotic resistance genes, such as those affiliated with multidrug, tetracycline, aminoglycoside, and fosfomycin resistance, were enriched in the IV group. Conclusions In conclusion, mNGS has a high diagnostic value in CAP. There were significant differences present in microbiota resistance to antibiotics in BALF from CAP patients in different PORT risk classes, which should attract enough attention. [ABSTRACT FROM AUTHOR]

Background Early and accurate recognition of respiratory pathogens is crucial to prevent increased risk of mortality in critically ill patients. Microbial-derived volatile organic compounds (mVOCs) in exhaled breath could be used as noninvasive biomarkers of infection to support clinical diagnosis. Methods In this study, we investigated the diagnostic potential of in vitro – confirmed mVOCs in the exhaled breath of patients under mechanical ventilation from the BreathDx study. Samples were analyzed by thermal desorption–gas chromatography–mass spectrometry. Results Pathogens from bronchoalveolar lavage (BAL) cultures were identified in 45 of 89 patients and Staphylococcus aureus was the most commonly identified pathogen (n = 15). Of 19 mVOCs detected in the in vitro culture headspace of 4 common respiratory pathogens (S. aureus , Pseudomonas aeruginosa , Klebsiella pneumoniae , and Escherichia coli), 14 were found in exhaled breath samples. Higher concentrations of 2 mVOCs were found in the exhaled breath of patients infected with S. aureus compared to those without (3-methylbutanal: P <.01, area under the receiver operating characteristic curve [AUROC] = 0.81–0.87; and 3-methylbutanoic acid: P =.01, AUROC = 0.79–0.80). In addition, bacteria identified from BAL cultures that are known to metabolize tryptophan (E. coli , Klebsiella oxytoca , and Haemophilus influenzae) were grouped and found to produce higher concentrations of indole compared to breath samples with culture-negative (P =.034) and other pathogen-positive (P =.049) samples. Conclusions This study demonstrates the capability of using mVOCs to detect the presence of specific pathogen groups with potential to support clinical diagnosis. Although not all mVOCs were found in patient samples within this small pilot study, further targeted and qualitative investigation is warranted using multicenter clinical studies. [ABSTRACT FROM AUTHOR]

Introduction Taniborbactam (formerly VNRX-5133) is an investigational β-lactamase inhibitor in clinical development in combination with cefepime for the treatment of MDR Gram-negative pathogens. Objectives To assess the safety profile and pulmonary disposition of 2–0.5 g cefepime/taniborbactam administered as a 2 h IV infusion every 8 h following three doses in healthy adult subjects. Methods In this Phase 1 trial, open-label study, plasma samples were collected over the last dosing interval, and subjects (n  = 20) were randomized to undergo bronchoalveolar lavage (BAL) at four timepoints after the last dose. Drug concentrations in plasma (total and free as determined by protein binding), BAL fluid and alveolar macrophages (AM) were determined by LC-MS/MS, and the urea correction method was used to calculate epithelial lining fluid (ELF) drug concentrations. Pharmacokinetic parameters were estimated by non-compartmental analysis. Results Mean (±SD) taniborbactam C max and AUC0–8 in plasma were 24.1 ± 4.1 mg/L and 81.9 ± 13.9 mg·h/L, respectively. Corresponding values for cefepime were 118.4 ± 29.7 mg/L and 346.7 ± 71.3 mg·h/L. Protein binding was 0% for taniborbactam and 22.4% for cefepime. Mean taniborbactam concentrations (mg/L) at 2, 4, 6 and 8 h were 3.9, 1.9, 1.0 and 0.3 in ELF and 12.4, 11.5, 14.3 and 14.9 in AM, with corresponding AUC0–8 ELF of 13.8 and AUC0–8 AM of 106.0 mg·h/L. Cefepime AUC0–8 ELF was 77.9 mg·h/L. No serious adverse events were observed. Conclusion The observed bronchopulmonary exposures of taniborbactam and cefepime can be employed to design optimal dosing regimens for clinical trials in patients with pneumonia. [ABSTRACT FROM AUTHOR]

An editorial focuses on two studies regarding the diagnosis of invasive aspergillosis (IA) using polymerase chain reaction (PCR) on plasma and bronchoalveolar lavage (BAL) fluid. It discusses the findings of these studies, emphasizing the improved accuracy of PCR in plasma compared to traditional tests like galactomannan. It also explores the challenges and questions raised by the studies, particularly in the context of the current definitions and classification criteria for IA.

Background This study was performed to evaluate the efficacy of using a thin bronchoscope for the diagnosis of pulmonary tuberculosis (PTB). Methods Between March 2019 and November 2021, we prospectively enrolled participants with suspected PTB whose sputum acid-fast bacilli (AFB) smear and tuberculosis (TB) polymerase chain reaction (PCR) tests were negative or who could not produce self-expectorated sputum. Participants were randomized to a control group (bronchial washing [BW] using a 5.9-mm conventional bronchoscope guided by chest computed tomography) or an investigational group (BW using a 4.0-mm thin bronchoscope under virtual bronchoscopic navigation guidance). The primary outcome was detection of TB in BW fluid, defined as a positive result in the Xpert MTB/RIF assay. The secondary outcomes included AFB smear and Mycobacterium tuberculosis culture positivity, time to treatment initiation, and bronchoscopy-related complications. Results In total, 85 participants were included in the final analysis (43 in the control group and 42 in the investigational group). Twenty-three and 29, respectively, were finally diagnosed with PTB. The TB detection rate in BW fluid was higher in the investigational group (72.4% vs 43.5%, P =.035). Mycobacterium tuberculosis culture positivity was also higher in the investigational group (79.3% vs 52.2%, P =.038). No participants required premature bronchoscopy termination because of complications. Of the participants with PTB, the time to treatment initiation was shorter in the investigational group (median, 2.0 days vs 4.0 days, P =.001). Conclusions BW using a thin bronchoscope increases the TB detection rate in patients with PTB compared to conventional bronchoscopy. Clinical Trials Registration. ȃNCT03802812. [ABSTRACT FROM AUTHOR]

Computational cell type deconvolution on bulk transcriptomics data can reveal cell type proportion heterogeneity across samples. One critical factor for accurate deconvolution is the reference signature matrix for different cell types. Compared with inferring reference signature matrices from cell lines, rapidly accumulating single-cell RNA-sequencing (scRNA-seq) data provide a richer and less biased resource. However, deriving cell type signature from scRNA-seq data is challenging due to high biological and technical noises. In this article, we introduce a novel Bayesian framework, tranSig, to improve signature matrix inference from scRNA-seq by leveraging shared cell type-specific expression patterns across different tissues and studies. Our simulations show that tranSig is robust to the number of signature genes and tissues specified in the model. Applications of tranSig to bulk RNA sequencing data from peripheral blood, bronchoalveolar lavage and aorta demonstrate its accuracy and power to characterize biological heterogeneity across groups. In summary, tranSig offers an accurate and robust approach to defining gene expression signatures of different cell types, facilitating improved in silico cell type deconvolutions. [ABSTRACT FROM AUTHOR]

Background Nontuberculous Mycobacterium infections, particularly Mycobacterium abscessus , are increasingly common among patients with cystic fibrosis and chronic bronchiectatic lung diseases. Treatment is challenging due to intrinsic antibiotic resistance. Bacteriophage therapy represents a potentially novel approach. Relatively few active lytic phages are available and there is great variation in phage susceptibilities among M. abscessus isolates, requiring personalized phage identification. Methods Mycobacterium isolates from 200 culture-positive patients with symptomatic disease were screened for phage susceptibilities. One or more lytic phages were identified for 55 isolates. Phages were administered intravenously, by aerosolization, or both to 20 patients on a compassionate use basis and patients were monitored for adverse reactions, clinical and microbiologic responses, the emergence of phage resistance, and phage neutralization in serum, sputum, or bronchoalveolar lavage fluid. Results No adverse reactions attributed to therapy were seen in any patient regardless of the pathogen, phages administered, or the route of delivery. Favorable clinical or microbiological responses were observed in 11 patients. Neutralizing antibodies were identified in serum after initiation of phage delivery intravenously in 8 patients, potentially contributing to lack of treatment response in 4 cases, but were not consistently associated with unfavorable responses in others. Eleven patients were treated with only a single phage, and no phage resistance was observed in any of these. Conclusions Phage treatment of Mycobacterium infections is challenging due to the limited repertoire of therapeutically useful phages, but favorable clinical outcomes in patients lacking any other treatment options support continued development of adjunctive phage therapy for some mycobacterial infections. [ABSTRACT FROM AUTHOR]

Objectives: Oil Red O (ORO) positivity in bronchoalveolar lavage (BAL) fluid macrophages in the setting of e-cigarette, or vaping, product use-associated acute lung injury (EVALI) has been frequently requested by clinicians based on rare reports and subsequent US Centers for Disease Control and Prevention guidelines. The aim of this study was to determine the specificity of ORO staining in BAL specimens with disease states other than EVALI.Methods: Consecutive BAL specimens (October-December 2019) were stained with ORO. The lipid-laden macrophage index (LLMI) was calculated for each case.Results: We studied BAL samples from 50 patients. Indications for BAL were surveillance bronchoscopy for lung transplantation (27/50), suspected infection (12/50), sarcoidosis/suspected sarcoidosis (3/50), nodules or ground-glass opacities (3/50), hemoptysis (2/50), asthma or eosinophilic pneumonia (2/50), and idiopathic pulmonary fibrosis (1/50). ORO staining was seen in BAL fluid macrophages in 45 of 50 cases (focal in 18, moderate in 23, diffuse in 4); LLMI ranged from 0 to 218. Using a threshold of LLMI of 85 or higher as positive, ORO was positive in 7 of 50 (14%) cases (range, 85-218).Conclusions: ORO staining in BAL fluid macrophages is not specific for EVALI. Even when an LLMI of 85 or higher is used as a threshold for positivity, ORO positivity occurs in a significant subset of non-vaping-related cases. [ABSTRACT FROM AUTHOR]

Chronic lower respiratory tract infections are a leading contributor to morbidity and mortality in persons with cystic fibrosis (pwCF). Traditional respiratory tract surveillance culturing has focused on a limited range of classic pathogens; however, comprehensive culture and culture-independent molecular approaches have demonstrated complex communities highly unique to each individual. Microbial community structure evolves through the lifetime of pwCF and is associated with baseline disease state and rates of disease progression including occurrence of pulmonary exacerbations. While molecular analysis of the airway microbiome has provided insight into these dynamics, challenges remain including discerning not only "who is there" but "what they are doing" in relation to disease progression. Moreover, the microbiome can be leveraged as a multi-modal biomarker for both disease activity and prognostication. In this article, we review our evolving understanding of the role these communities play in pwCF and identify challenges in translating microbiome data to clinical practice. [ABSTRACT FROM AUTHOR]

The article discusses a study which reported a close relationship between Anti-Melanoma Differentiation-Associated gene 5 (anti-MDA5)-positive dermatomyositis (DM) and infection. Topics include function of metagenomic next-generation sequencing (mNGS), general information of 22 anti-MDA5-positive DM patients, and conclusions of the study.

Objectives: The cytomorphologic findings of bronchoalveolar lavage (BAL) in pediatrics were correlated with clinical symptoms.Methods: Patient demographics, clinical symptoms/history, cytomorphologic findings, and oil red O (ORO) staining of 100 pediatric patients who underwent BAL between 2014 and 2016 were reviewed at a large academic institution.Results: Of the 100 patients (males/females, 62:38), the most common conditions for BAL included cough (46/100), reflux (39/100), pneumonia (30/100), dysphagia (22/100), asthma (19/100), and cystic fibrosis (15/100). Sixteen of 100 patients were admitted with pulmonary symptoms from the emergency department. Cytomorphologic findings showed acute inflammation in 37 BALs and chronic inflammation in 9. Abundant thick mucin was present in 3 cytology cases from patients with cystic fibrosis. Fungal elements were detected in 3 cases (Candida, Aspergillus, and Pneumocystis jirovecii) and viral effects (rhinovirus) in one. Thirty-seven of 100 had rare ORO-positive lipid-laden macrophages (LLMs), 7 of 100 had moderate LLMs, 11 of 100 had numerous LLMs, 18 of 100 had positive staining without the degree of staining, 25 of 100 had negative ORO staining, and 2 of 100 had noncontributory ORO staining. An iron stain was done on 15 BALs (2 positive, 9 negative, and 4 noncontributory).Conclusions: BAL cytology is a useful tool in pediatrics to discriminate underlying causes of aerodigestive system conditions, while ORO staining may occasionally help. [ABSTRACT FROM AUTHOR]

Objective To investigate the role of bronchoalveolar lavage (BAL) in DM-associated interstitial lung disease (ILD). Methods We retrospectively reviewed the medical records of patients with DM-ILD who underwent bronchoscopy between October 2015 and September 2019. We then collated clinical features, laboratory data and bronchoscopy findings. The follow-up study was terminated on the 1 May 2020. Results A total of 113 DM-ILD patients were included in this study, including 27 patients with acute/subacute interstitial pneumonia (A/SIP) and 86 patients with chronic interstitial pneumonia (CIP). The A/SIP group had significantly lower proportions of lymphocytes and eosinophils in the bronchoalveolar lavage fluid (BALF) than the CIP group, but had a significantly higher proportion of neutrophils. Pathogens were discovered in BALF from 28 (24.8%) patients. Twenty-five (22.1%) patients commenced or changed antibiotic therapy on the basis of their bronchoscopy results. Lymphopenia and intensive care unit care were significantly associated with pathogen-positive BALF findings. Complications of bronchoscopy occurred in nine (8.0%) patients; fever (5.3%) was the most common complication. Twenty-five deaths (25/106, 23.6%) were observed during a mean follow-up of 22 months. Age, A/SIP and anti-MDA5 antibody were identified as independent predictors of a poor outcome, while mechanic's hands was an independent protective factor. However, cellular and pathogen findings in BALF had no significant influence on 30-day or overall mortality. Conclusion Bronchoscopy is a relatively useful instrument to evaluate ILD in patients with DM, and BAL can improve the diagnosis of infection. However, cellular and pathogen findings from BALF had no significant influence on prognosis. [ABSTRACT FROM AUTHOR]

Invasive aspergillosis (IA) is an acute infection affecting patients who are immunocompromised, as a result of receiving chemotherapy for malignancy, or immunosuppressant agents for transplantation or autoimmune disease. Whilst criteria exist to define the probability of infection for clinical trials, there is little evidence in the literature or clinical guidelines on when to change antifungal treatment in patients who are receiving prophylaxis or treatment for IA. To try and address this significant gap, an advisory board of experts was convened to develop criteria for the management of IA for use in designing clinical trials, which could also be used in clinical practice. For primary treatment failure, a change in antifungal therapy should be made: (i) when mycological susceptibility testing identifies an organism from a confirmed site of infection, which is resistant to the antifungal given for primary therapy, or a resistance mutation is identified by molecular testing; (ii) at, or after, 8 days of primary antifungal treatment if there is increasing serum galactomannan, or galactomannan positivity in serum, or bronchoalveolar lavage fluid when the antigen was previously undetectable, or there is sudden clinical deterioration, or a new clearly distinct site of infection is detected; and (iii) at, or after, 15 days of primary antifungal treatment if the patient is clinically stable but with ≥2 serum galactomannan measurements persistently elevated compared with baseline or increasing, or if the original lesions on CT or other imaging, show progression by >25% in size in the context of no apparent change in immune status. [ABSTRACT FROM AUTHOR]

Objectives: Organic polymers are materials widely used in our daily lives, such as daily necessities, foods, and medicines. There have been reports recently that cross‐linked polyacrylic acid (CL‐PAA) can possibly cause serious lung disease. We investigated whether intratracheal instillation of CL‐PAA causes pulmonary disorder in rats. Methods: Male F344 rats were administered low (0.2 mg/rat) and high (1.0 mg/rat) doses of CL‐PAA intratracheally and were dissected 3 days, 1 week, 1 month, 3 months, and 6 months after exposure to examine inflammatory and fibrotic responses in the lungs. Only the high‐dose specimens were subjected to ultrasonic dispersion treatment of the administered material. Results: There was a dose‐dependent increase in the total cell count, neutrophil count, neutrophil percentage, lactate dehydrogenase (LDH), surfactant protein D (SP‐D), cytokine‐induced neutrophil chemoattractant (CINC)‐1 and CINC‐2 values in bronchoalveolar lavage fluid (BALF) from 3 days to at least 3 months after intratracheal administration of CL‐PAA. Heme oxygenase‐1 (HO‐1) in lung tissue was also persistently elevated from 3 days to 6 months after exposure. Alkaline phosphatase (ALP) in BALF was elevated at 3 days and 1 month after exposure only in the high‐dose group. Histopathological findings in lung tissue showed inflammatory and fibrotic changes from 3 days after administration, and we observed obvious inflammatory changes for up to 3 months and fibrotic changes for up to 6 months. Conclusion: Intratracheal administration of CL‐PAA induced persistent neutrophilic inflammation and fibrosis in the rats' lungs, suggesting that CL‐PAA may have inflammogenic and fibrogenic effects. [ABSTRACT FROM AUTHOR]

Background Limited data exist regarding the impact of human bocavirus (BoV) in hematopoietic cell transplant (HCT) recipients. Methods In a longitudinal surveillance study among allogeneic HCT recipients, pre-HCT and weekly post-HCT nasal washes and symptom surveys were collected through day 100, then at least every 3 months through 1 year post-HCT at the Fred Hutchinson Cancer Research Center (2005–2010). Samples were tested by multiplex semiquantitative polymerase chain reaction (PCR) for 12 viruses. Plasma samples from BoV + subjects were analyzed by PCR. Separately, we conducted a retrospective review of HCT recipients with BoV detected in lower respiratory tract specimens. Results Among 51 children and 420 adults in the prospective cohort, 21 distinct BoV respiratory tract infections (RTIs) were observed by 1 year post-HCT in 19 patients. Younger age and exposure to children were risk factors for BoV acquisition. Univariable models among patients with BoV RTI showed higher peak viral load in nasal samples (P  = .04) and presence of respiratory copathogens (P  = .03) were associated with presence of respiratory symptoms, but BoV plasma detection was not. Only watery eyes and rhinorrhea were associated with BoV RTI in adjusted models. With additional chart review, we identified 6 HCT recipients with BoV detected in lower respiratory tract specimens (incidence rate of 0.4% [9/2509] per sample tested). Although all cases presented with hypoxemia, 4 had respiratory copathogens or concomitant conditions that contributed to respiratory compromise. Conclusions BoV RTI is infrequent in transplant recipients and associated with mild symptoms. Our studies did not demonstrate convincing evidence that BoV is a serious respiratory pathogen. [ABSTRACT FROM AUTHOR]

Microbial cultivation is the current gold standard for the clinical diagnosis of bacterial infections. However, this method sometimes produces false negative results. We present a case study of multisite Pseudomonas aeruginosa infections detected by metagenomic next-generation sequencing in a child with aplastic anemia, highlighting the rapid and accurate advantages of this technique. [ABSTRACT FROM AUTHOR]

The article presents a case study of 79-year-old male presented to the pulmonary service in April 2021 complaining of persistent, productive cough for 2 months, with fatigue and night sweats. His relevant past medical history included asbestos exposure in the 1980s, chronic obstructive pulmonary disease, emphysema requiring ambulatory oxygen, obstructive sleep apnea, a pulmonary right upper lobe cavitary lesion, hypertension, and an aortic aneurysm.

Background Infection with Ureaplasma species (spp) has been linked to fatal hyperammonemia syndrome (HS) in lung transplant recipients. We sought to characterize the epidemiology of Ureaplasma spp in candidates and donors and describe outcomes of antimicrobial therapy in preventing and treating HS. Methods Candidate testing for Ureaplasma spp was performed with urine culture and polymerase chain reaction (PCR) pretransplant. Positive candidates were treated with levofloxacin. Donor testing was performed with bronchoalveolar lavage (BAL) culture and PCR intraoperatively. From 7/2014 to 2/2017 patients were treated according to results; from 2/2017 to 10/2018 recipients received empiric levofloxacin and azithromycin at transplant until testing returned negative. HS was defined as new onset altered mental status after transplant with ammonia > 200 µmol/L. Results In total, 60 patients who underwent lung transplant were included. And 80% (n = 48) of patients had negative screening tests in donor and candidate pre-lung transplant, 8.3% (n = 5) of recipients had positive Ureaplasma spp testing in urine pre-transplant, and 13.3% (n = 8) had positive donor BAL testing at the time of lung transplant. Three patients developed HS a median of 7 days posttransplant; 2 died of HS. Recipients of organs with Ureaplasma spp who received empiric therapy did not develop HS. Donors with Ureaplasma spp were younger and more sexually active. Conclusions Donor-derived Ureaplasma spp in lung transplant was associated with HS. Screening lung donors for Ureaplasma spp might allow for targeted therapy to reduce risk for development of HS, but future confirmatory studies are needed. [ABSTRACT FROM AUTHOR]

Background The Aspergillus Galactomannan Lateral Flow Assay (LFA) is a rapid test for the diagnosis of invasive aspergillosis (IA) that has been almost exclusively evaluated in patients with hematologic malignancies. An automated digital cube reader that allows for quantification of results has recently been added to the test kits. Methods We performed a retrospective multicenter study on bronchoalveolar lavage fluid (BALF) samples obtained from 296 patients with various underlying diseases (65% without underlying hematological malignancy) who had BALF galactomannan (GM) ordered between 2013 and 2019 at the University of California, San Diego, the Medical University of Graz, Austria, and the Mannheim University Hospital, Germany. Results Cases were classified as proven (n = 2), probable (n = 56), putative (n = 30), possible (n = 45), and no IA (n = 162). The LFA showed an area under the curve (AUC) of 0.865 (95% confidence interval [CI].815–.916) for differentiating proven/probable or putative IA versus no IA, with a sensitivity of 74% and a specificity of 83% at an optical density index cutoff of 1.5. After exclusion of GM as mycological criterion for case classification, diagnostic performance of the LFA was highly similar to GM testing (AUC 0.892 vs 0.893, respectively). LFA performance was consistent across different patient cohorts and centers. Conclusions In this multicenter study the LFA assay from BALF demonstrated good diagnostic performance for IA that was consistent across patient cohorts and locations. The LFA may serve a role as a rapid test that may replace conventional GM testing in settings where GM results are not rapidly available. [ABSTRACT FROM AUTHOR]

Sarcoidosis is a multi‐systemic granulomatous disease of unknown origin. Recent research has focused upon the role of autoimmunity in its development and progression. This study aimed to determine and define the disturbance and distribution of T and B cell subsets in the alveolar and peripheral compartments. Thirteen patients were selected for the study [median age, interquartile range (IQR) = 57 years (48–59); 23% were male]. Twelve healthy controls [median age, IQR = 53 years (52–65); 16% male] were also enrolled into the study. Cellular and cytokine patterns were measured using the cytofluorimetric approach. Peripheral CD8 percentages were higher in sarcoidosis patients (SP) than healthy controls (HC) (p = 0.0293), while CD4 percentages were lower (p = 0.0305). SP showed low bronchoalveolar lavage (BAL) percentages of CD19 (p = 0.0004) and CD8 (p = 0.0035), while CD19+CD5+CD27− percentages were higher (p = 0.0213); the same was found for CD4 (p = 0.0396), follicular regulatory T cells (Treg) (p = 0.0078) and Treg (p < 0.0001) cells. Low T helper type 17 (Th17) percentages were observed in BAL (p = 0.0063) of SP. Peripheral CD4+ C‐X‐C chemokine receptor (CXCR)5+CD45RA−) percentages and follicular T helper cells (Tfh)‐like Th1 (Tfh1) percentages (p = 0.0493 and p = 0.0305, respectively) were higher in the SP than HC. Tfh1 percentages and Tfh‐like Th2 percentages were lower in BAL than in peripheral blood (p = 0.0370 and p = 0.0078, respectively), while CD4+ C‐X‐C motif CXCR5+CD45RA− percentages were higher (p = 0.0011). This is the first study, to our knowledge, to demonstrate a link between an imbalance in circulating and alveolar Tfh cells, especially CCR4‐, CXCR3‐ and CXCR5‐expressing Tfh subsets in the development of sarcoidosis. These findings raise questions about the pathogenesis of sarcoidosis and may provide new directions for future clinical studies and treatment strategies. [ABSTRACT FROM AUTHOR]

Upon returning from deployment to Afghanistan, a substantial number of U.S. military personnel report deployment-related lung disease (DRLD) symptoms, including those consistent with an asthma-like airways disease. DRLD is thought to be caused by prolonged inhalation of toxic desert particulate matter, which can persist in the postdeployment setting such as exposure to common household allergens. The goal of this study was to define the transcriptomic responses of lung leukocytes of mice exposed to Afghanistan desert particulate matter (APM) and house dust mite (HDM). C57BL/6 mice (n  = 15/group) were exposed to filtered air or aerosolized APM for 12 days, followed by intranasal PBS or HDM allergen challenges for 24 h. Bronchoalveolar lavage (BAL) cells were collected for single-cell RNA sequencing (scRNAseq), and assessment of inflammation and airway hyper-responsiveness. Unsupervised clustering of BAL cell scRNAseq data revealed a unique monocyte population induced only by both APM and allergen treatments. This population of monocytes is characterized by the expression of genes involved in allergic asthma, including Alox15. We validated Alox15 expression in monocytes via immunostaining of lung tissue. APM pre-exposure, followed by the HDM challenge, led to significantly increased total respiratory system resistance compared with filtered air controls. Using this mouse model to mimic DRLD, we demonstrated that inhalation of airborne PM during deployment may prime airways to be more responsive to allergen exposure after returning home, which may be linked to dysregulated immune responses such as induction of a unique lung monocyte population. [ABSTRACT FROM AUTHOR]

Purpose A case of diffuse alveolar hemorrhage (DAH) occurring as a reaction to ustekinumab therapy is reported. Summary After starting ustekinumab for treatment of psoriatric arthritis, a 46-year-old female presented with flu-like symptoms and cough with blood-tinged sputum that had begun 1 week previously. Her initial computed tomography scan of the chest demonstrated bilateral ground-glass opacities. On bronchoscopy, the bronchoalveolar lavage (BAL) return became bloodier from sample 1 to samples 2 and 3. Her BAL fluid was more than 90% hemosiderin-laden macrophages, a finding consistent with DAH. We ruled out infectious etiologies and other common vasculitis conditions that can cause DAH. A diagnosis of ustekinumab-induced DAH was made due to a temporal relationship between initiation of the drug and the patient's presentation and the absence of infection and other alternate diagnosis. Prior case reports including ustekinumab-induced pneumonitis, interstitial lung disease with a granulomatous component, and lupus syndrome have been reported, with this being the first case of DAH in a patient undergoing treatment of psoriatic arthritis. Conclusion A 46-year-old woman developed DAH during ustekinumab treatment. Symptoms abated after drug discontinuation and supportive treament. Clinicians must remain mindful of this rare complication of ustekinumab use in order to avoid potential delays in appropriate DAH treatment. [ABSTRACT FROM AUTHOR]

Ureaplasma urealyticum has high nutritional requirements for culture, and it requires special tools for identification. Theoretically, metagenomic next generation sequencing (mNGS) can be used to detect many pathogens in clinical specimens, especially for complex infectious diseases with rare and atypical causes. Here, our patient developed severe pneumonia caused by U. urealyticum infection after allogeneic hematopoietic stem cell transplantation, and the etiology is unclear. After continuous negative culture, U. urealyticum was detected in the bronchoalveolar lavage fluid by mNGS, and azithromycin was used. Because of the difficulty in its diagnosis, diagnosis and treatment of extragenital U. urealyticum infection is challenging. In addition, many broad-spectrum antibiotics are ineffective against this pathogen because it lacks a cell wall. Therefore, early diagnosis and treatment are key to preventing further complications and deaths. [ABSTRACT FROM AUTHOR]

Results from early studies in the diagnostic yield of bronchoalveolar lavage (BAL) in immunocompromised adults and children were variable. This prospective study aimed to determine the diagnostic yield of BALs in immunocompromised children over the first 18 months of service at a newly established children's hospital. Relationship between BAL results and changes in antimicrobial management was also studied. Twenty-one bronchoscopic BALs were performed on 18 children; 14 BALs (66.7%) yielded at least 1 pathogen and 7 (33.3%) yielded no pathogen. Two pathogens were found in 2 samples, and 1 pathogen was identified in 12 samples. Bacteria (n = 7 patients), viruses (n = 8 patients) and fungus (Pneumocycstis jirovecii in one patient) were yielded. Of the 21 BALs, 8 (38.1%) were associated with changes in antimicrobial management (Fisher's exact test, p = 0.018). No significant side effects such as pneumothorax or pulmonary hemorrhages were observed in this series. In conclusion, BAL in immunocompromised children is rewarding and has potential to impact on antimicrobial management. [ABSTRACT FROM AUTHOR]

Invasive pulmonary aspergillosis (IPA) is a serious infectious disease with high mortality. However, the rapid diagnosis of IPA remains difficult since the microbiological evidence is difficult to obtain or time-consuming. Thus, we attempted to rapidly diagnose two pediatric cases with respiratory failure due to IPA via bronchoalveolar lavage fluid with Calcofluor White fluorescence staining, which has rarely been used before. [ABSTRACT FROM AUTHOR]

Objectives:In order to cope with the rapid spread of the COVID-19 pandemic, we introduced on our in-house high-throughput molecular diagnostic platform (MDx Platform) a real-time reverse transcriptase PCR (RT-PCR) to detect the SARS-CoV-2 from any clinical specimens. The aim of this study was to compare the RT-PCR results obtain with the MDx Platform and the commercial assay cobas SARS-CoV-2 (Roche) on nasopharyngeal swab and other clinical specimens including sputum, bronchial aspirate, bronchoalveolar lavage and anal swabs. Methods: Samples received in our laboratory from patients suspected of COVID-19 (n = 262) were tested in parallel with our MDx platform SARS-CoV-2 PCR and with the cobas SARS-CoV-2 test. Results: The overall agreement between the two tests for all samples tested was 99.24% (260/262), which corresponded to agreements of 100% (178/178) on nasopharyngeal swabs, 95.45% (42/44) on lower respiratory tract specimen with discordant resultS obtained for very high cycle threshold (Ct) value and 100% (40/40) on anorectal swabs. The Ct values for nasopharyngeal swabs displayed an excellent correlation (R2 > 96%) between both tests. Conclusions: The high agreements between the cobas SARS-CoV-2 test and the MDx platform supports the use of both methods for the diagnostic of COVID-19 on various clinical samples. Very few discrepant results may occur at very low viral load. [ABSTRACT FROM AUTHOR]

Keywords: Strongyloides; COVID-19; steroids; immunosuppression EN Strongyloides COVID-19 steroids immunosuppression 1 3 3 01/24/22 20220101 NES 220101 Certain helminth infections such as strongyloidiasis may be underdiagnosed in non-endemic areas due to the presence of asymptomatic individuals, the lack of awareness of the disease and the poor sensitivity of diagnostic methods. COVID-19 and dexamethasone: a potential strategy to avoid steroid-related strongyloides hyperinfection. Life-threatening complications of these infections may occur especially in patients with altered immune responses.1 Case report A 69-year-old Colombian man presented with abdominal pain and vomiting. [Extracted from the article]

Abstarct: Polyherbal compound (Bronco-T) has been extensively used as a traditional medicine for various therapies. However, very few report studies on anti-inflammatory and lung regeneration properties are evidenced. In the present study, we evaluated the beneficial actions and anti-inflammatory properties of polyherbal medicine, Bronco-T, exhibited by treating the lungs of rats exposed to formaldehyde to evaluate the beneficial properties. For this study, we divided into five groups': i.e. Group-I served as a control and the other four groups such as II, III, IV, and V are experimental. All animals maintained by regular feed and water ad libitum during the study. Formaldehyde vapors exposure at a single period of time (1 hour) daily (40%formaldehyde at room temperature) for 21 days period exposed all groups. The Bronco-T extracts about 50 mg/kg BW administered to experimental groups and group IV rats treated with 500μ grams/Kg BW salbutamol. To understand the impact of formaldehyde exposure on the beneficial effects of Bronco-T, we evaluated hematological parameters, bronchoalveolar lavage (BAL), histamine levels, and histological alterations of lung architecture. Formaldehyde-induced adverse effects in lung and increased histamine levels in BAL compared to Bronco-T-treated rats act as a preventive immunological role in blood toxicity and recovery of lung architecture in Bronco-T-treated rats. This study showed the evaluation of antihistamine levels through HPLC analysis. Bronco-T has antioxidant and anti-histamine properties as the widest therapeutic window, and we continue to evaluate the pharmacological evaluations needed in our further studies. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the efficacy and safety of bronchoalveolar lavage (BAL) in the treatment of neonatal severe pneumonia (NSP).Methods: One hundred patients with severe pneumonia were randomly divided into two groups, the BAL and control groups, with 50 patients in each group. In the BAL group, normal saline was instilled into the endotracheal tube for BAL. Before and after lavage, lung ultrasound (LUS) monitoring was performed to observe the lung pathological changes. Conventional treatment was administered in the control group. The need for and duration of invasive mechanical ventilation, the complication rate, the duration and cost of hospitalization and the mortality rate were compared between the two groups.Results: The results of this study showed that there were 35 (70%) patients who meet the indications of the invasive mechanical ventilation (IMV) at admission in the BAL group, while there were only 15 (30%) patients still requiring IMV after BAL therapy. The duration of IMV was 41.7 ± 7.5 vs. 97.7 ± 12.9 h in BAL and controls, the incidence rate of complications was 8.0% vs. 20.0% in both groups, the length of hospital stay was 9.2 ± 1.9 vs. 14.1 ± 2.1 days in both groups, and the expense of hospital cost was 12 557 ± 832 vs. 19 121 ± 929 Chinese Yuan in both groups. All patients had stable vital signs during lavage, and no significant adverse side effects were observed.Conclusion: BAL was significantly beneficial for NSP with no significant adverse side effects; LUS is a useful tool for the timely detection of BAL effects. [ABSTRACT FROM AUTHOR]

Clinical laboratory testing routinely provides actionable results, which help direct patient care in the inpatient and outpatient settings. Since December 2019, a novel coronavirus (SARS-CoV-2) has been causing disease (COVID-19 [coronavirus disease 2019]) in patients, beginning in China and now extending worldwide. In this context of a novel viral pandemic, clinical laboratories have developed multiple novel assays for SARS-CoV-2 diagnosis and for managing patients afflicted with this illness. These include molecular and serologic-based tests, some with point-of-care testing capabilities. Herein, we present an overview of the types of testing available for managing patients with COVID-19, as well as for screening of potential plasma donors who have recovered from COVID-19. [ABSTRACT FROM AUTHOR]

Uterine lavage is presented as a way to perform aneuploidy screening without IVF. The feasibility of this method was tested in a research study. This study combined a number of highly contentious ethical issues: the creation of embryos for research (very early), abortion and (moderate) payments to research participants. It is concluded that the study largely fulfils the criteria of ethical research but that the researchers should have avoided a number of steps. These steps were the inclusion of infertility patients, the performance of the research in a middle-income country and the double destination of the embryos. The next question then becomes whether it would be acceptable to apply the method in a clinical setting. Two elements complicate the introduction in the clinic: low success rate of embryo collection and risk of unintended pregnancy. The application of the method in the clinic may lead to very complicated ethical and legal situations for which both patients and doctors should be prepared. [ABSTRACT FROM AUTHOR]