scholarly journals Major Neutrophil-Derived Soluble Mediators Associate With Baseline Lung Pathology and Post-Treatment Recovery in Tuberculosis Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Caleb Nwongbouwoh Muefong ◽  
Olumuyiwa Owolabi ◽  
Simon Donkor ◽  
Salome Charalambous ◽  
Joseph Mendy ◽  
...  
Keyword(s):  
Bacterial Load ◽  
Lung Damage ◽  
Lung Pathology ◽  
Therapeutic Approaches ◽  
Gm Csf ◽  
Whole Cell Lysate ◽  
Tb Treatment ◽  
Chest X Ray ◽  
Multiplex Cytokine ◽  
Severe Lung

BackgroundThe inflammatory response to Mycobacterium tuberculosis results in variable degrees of lung pathology during active TB (ATB) with central involvement of neutrophils. Little is known about neutrophil-derived mediators and their role in disease severity at baseline and recovery upon TB treatment initiation.Methods107 adults with confirmed pulmonary TB were categorised based on lung pathology at baseline and following successful therapy using chest X-ray scores (Ralph scores) and GeneXpert bacterial load (Ct values). Plasma, sputum, and antigen-stimulated levels of MMP1, MMP3, MMP8, MMP9, MPO, S100A8/9, IL8, IL10, IL12/23(p40), GM-CSF, IFNγ, and TNF were analysed using multiplex cytokine arrays.ResultsAt baseline, neutrophil counts correlated with plasma levels of MMP8 (rho = 0.45, p = 2.80E−06), S100A8 (rho = 0.52, p = 3.00E−08) and GM-CSF (rho = 0.43, p = 7.90E−06). Levels of MMP8 (p = 3.00E−03), MMP1 (p = 1.40E−02), S100A8 (p = 1.80E−02) and IL12/23(p40) (p = 1.00E−02) were associated with severe lung damage, while sputum MPO levels were directly linked to lung damage (p = 1.80E−03), Mtb load (p = 2.10E−02) and lung recovery (p = 2.40E−02). Six months of TB therapy significantly decreased levels of major neutrophil-derived pro-inflammatory mediators: MMP1 (p = 4.90E−12 and p = 2.20E−07), MMP8 (p = 3.40E−14 and p = 1.30E−05) and MMP9 (p = 1.60E−04 and p = 1.50E−03) in plasma and sputum, respectively. Interestingly, following H37Rv whole cell lysate stimulation, S100A8 (p = 2.80E−02), MMP9 (p = 3.60E−02) and MPO (p = 9.10E−03) levels at month 6 were significantly higher compared to baseline. Sputum MMP1 (p = 1.50E−03), MMP3 (p = 7.58E−04), MMP9 (p = 2.60E−02) and TNF (p = 3.80E−02) levels were lower at month 6 compared to baseline in patients with good lung recovery.ConclusionIn this study, patients with severe lung pathology at baseline and persistent lung damage after treatment were associated with higher plasma and sputum levels of major pro-inflammatory neutrophil-derived mediators. Interestingly, low sputum MPO levels were associated with severe lung damage, higher Mtb burden and low recovery. Our data suggest that therapeutic agents which target these mediators should be considered for future studies on biomarkers and host-directed therapeutic approaches against TB-related lung pathology and/or lung recovery.

scholarly journals Neutrophils contribute to severity of tuberculosis pathology and recovery from lung damage pre- and post-treatment

2021 ◽  
Author(s):  
Caleb Nwongbouwoh Muefong ◽  
Olumuyiwa Owolabi ◽  
Simon Donkor ◽  
Salome Charalambous ◽  
Abhishek Bakuli ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Bacterial Load ◽  
Load Flow ◽  
Lung Damage ◽  
Ros Generation ◽  
Lung Pathology ◽  
X Rays ◽  
Whole Cell Lysate ◽  
Specific Antigens ◽  
And Function

Abstract Background Despite microbiological cure, about 50% of TB patients have poor lung recovery. Neutrophils are associated with lung pathology, however, CD16|CD62L-defined subsets have not been studied in TB. Using flow cytometry, we monitored frequencies, phenotype and function of neutrophils following stimulation with Mtb whole cell lysate (WCL) and ESAT-6/CFP-10 fusion protein (EC)) in relation to lung pathology. Methods Fresh blood from 42 adult, HIV-negative TB patients were analysed pre- and post-therapy, with disease severity determined using Chest X-Rays and bacterial load. Flow cytometry was used to monitor frequencies, phenotype and function (generation of ROS, together with CD11b, TNF and IL10 expression) of neutrophils following 2-hour stimulation with Mtb-specific antigens. Results We show that total neutrophils decrease by treatment completion compared to baseline (p=0.0059); however, CD16 brCD62L br (segmented) neutrophils increase (p=0.0031) and CD16 dimCD62L br (banded) neutrophils decrease (p=0.038). Moreover, banded neutrophils are lower in patients with severe lung damage at baseline (p=0.035). Furthermore, we demonstrate that following WCL stimulation, ROS from segmented neutrophils is higher in patients with low Mtb loads even after adjusting for sex (p=0.038) while IL-10-expressing CD16 dimCD62L lo are higher in patients with mild damage (p=0.0397) at baseline. Patients showing good recovery from lung damage possess higher baseline granulocyte frequencies following WCL (p=0.042) and EC stimulation (p=0.011). Conclusion Hence, our results suggest that high ROS generation, low levels of banded neutrophils and high levels of IL10-expressing CD16 dimCD62L lo neutrophils are associated with reduced lung pathology at TB diagnosis. Hence, neutrophils are potential early indicators of TB severity and promising targets for TB host-directed therapy.

scholarly journals GI-19007, a Novel Saccharomyces cerevisiae-Based Therapeutic Vaccine against Tuberculosis

2017 ◽  
Vol 24 (12) ◽  
Author(s):  
Thomas H. King ◽  
Crystal A. Shanley ◽  
Zhimin Guo ◽  
Donald Bellgrau ◽  
Timothy Rodell ◽  
...  
Keyword(s):  
Bacterial Load ◽  
Therapeutic Vaccine ◽  
Lung Damage ◽  
Clinical Strain ◽  
Interleukin 17 ◽  
Lung Pathology ◽  
Content Type ◽  
Secondary Lesion ◽  
Ifn Γ ◽  
Class Ii Antigen

ABSTRACT As yet, very few vaccine candidates with activity in animals against Mycobacterium tuberculosis infection have been tested as therapeutic postexposure vaccines. We recently described two pools of mycobacterial proteins with this activity, and here we describe further studies in which four of these proteins (Rv1738, Rv2032, Rv3130, and Rv3841) were generated as a fusion polypeptide and then delivered in a novel yeast-based platform (Tarmogen) which itself has immunostimulatory properties, including activation of Toll-like receptors. This platform can deliver antigens into both the class I and class II antigen presentation pathways and stimulate strong Th1 and Th17 responses. In mice this fusion vaccine, designated GI-19007, was immunogenic and elicited strong gamma interferon (IFN-γ) and interleukin-17 (IL-17) responses; despite this, they displayed minimal prophylactic activity in mice that were subsequently infected with a virulent clinical strain. In contrast, in a therapeutic model in the guinea pig, GI-19007 significantly reduced the lung bacterial load and reduced lung pathology, particularly in terms of secondary lesion development, while significantly improving survival in one-third of these animals. In further studies in which guinea pigs were vaccinated with BCG before challenge, therapeutic vaccination with GI-19007 initially improved survival versus that of animals given BCG alone, although this protective effect was gradually lost at around 400 days after challenge. Given its apparent ability to substantially limit bacterial dissemination within and from the lungs, GI-19007 potentially can be used to limit lung damage as well as facilitating chemotherapeutic regimens in infected individuals.

scholarly journals Clonal expansion and activation of tissue-resident memory-like Th17 cells expressing GM-CSF in the lungs of severe COVID-19 patients

2021 ◽  
Vol 6 (56) ◽  
pp. eabf6692
Author(s):  
Yu Zhao ◽  
Christoph Kilian ◽  
Jan-Eric Turner ◽  
Lidia Bosurgi ◽  
Kevin Roedl ◽  
...  
Keyword(s):  
Th17 Cells ◽  
Severe Disease ◽  
Lavage Fluid ◽  
Lung Damage ◽  
Lung Pathology ◽  
Gm Csf ◽  
Protein Levels ◽  
Cytokine Expression Profile ◽  
Cell Clones ◽  
Underlying Mechanisms

Hyperinflammation contributes to lung injury and subsequent acute respiratory distress syndrome (ARDS) with high mortality in patients with severe coronavirus disease 2019 (COVID-19). To understand the underlying mechanisms involved in lung pathology, we investigated the role of the lung-specific immune response. We profiled immune cells in bronchoalveolar lavage fluid and blood collected from COVID-19 patients with severe disease and bacterial pneumonia patients not associated with viral infection. By tracking T cell clones across tissues, we identified clonally expanded tissue-resident memory-like Th17 cells (Trm17 cells) in the lungs even after viral clearance. These Trm17 cells were characterized by a a potentially pathogenic cytokine expression profile of IL17A and CSF2 (GM-CSF). Interactome analysis suggests that Trm17 cells can interact with lung macrophages and cytotoxic CD8+ T cells, which have been associated with disease severity and lung damage. High IL-17A and GM-CSF protein levels in the serum of COVID-19 patients were associated with a more severe clinical course. Collectively, our study suggests that pulmonary Trm17 cells are one potential orchestrator of the hyperinflammation in severe COVID-19.

scholarly journals A blunted GPR183/oxysterol axis during dysglycemia results in delayed recruitment of macrophages to the lung during M. tuberculosis infection

2022 ◽  
Author(s):  
Minh Dao Ngo ◽  
Stacey Bartlett ◽  
Helle Bielefeldt-Ohmann ◽  
Cheng Xiang Foo ◽  
Roma Sinha ◽  
...  
Keyword(s):  
Mechanistic Explanation ◽  
Early Infection ◽  
Tuberculosis Infection ◽  
Lung Pathology ◽  
Patients With Diabetes ◽  
Chest X Ray ◽  
Cytochrome P450 Family ◽  
Deficient Mice ◽  
Severe Lung

We previously reported that the oxidised cholesterol-sensing receptor GPR183 is significantly downregulated in blood from tuberculosis (TB) patients with diabetes compared to TB patients without co-morbidities and that lower GPR183 expression in blood is associated with more severe pulmonary TB on chest-x-ray consistent with observations in dysglycemic mice. To further elucidate the role of this receptor and its endogenous high affinity agonist 7α,25-dihydroxycholesterol (7α,25-OHC) in the lung, we studied high fat diet (HFD)-induced 28 dysglycemic mice infected with M.tuberculosis. We found that the 7α,25-OHC-producing enzymes cholesterol 25-hydroxylase (CH25H) and cytochrome P450 family 7 subfamily member B1 (CYP7B1) were highly upregulated upon M.tuberculosis infection in the lungs of normoglycemic mice, and this was associated with increased expression of GPR183 indicative of effective recruitment of GPR183-expressing immune cells to the site of infection. We demonstrated that CYP7B1 was predominantly expressed by macrophages in the centre of TB granulomas. Expression of CYP7B1 was significantly blunted in lungs from HFD-fed dysglycemic animals and this coincided with 36 delayed recruitment of macrophages to the lung during early infection and more severe lung pathology. GPR183 deficient mice similarly had reduced macrophage recruitment during early infection demonstrating a requirement of the GPR183/oxysterol axis for macrophage infiltration into the lung in TB. Together our data demonstrate that oxidised cholesterols and GPR183 play an important role in positioning macrophages to the site of M. tuberculosis infection and that this is impaired by HFD-induced dysglycemia, adding a mechanistic explanation to the poorer TB outcomes in patients with diabetes.

scholarly journals Regulation of Eosinophilia in Asthma—New Therapeutic Approaches for Asthma Treatment

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 817
Author(s):  
Ruth P. Cusack ◽  
Christiane E. Whetstone ◽  
Yanqing Xie ◽  
Maral Ranjbar ◽  
Gail M. Gauvreau
Keyword(s):  
Drug Targets ◽  
Airflow Obstruction ◽  
Chronic Inflammatory Disease ◽  
Therapeutic Approaches ◽  
Eosinophilic Asthma ◽  
Airway Eosinophilia ◽  
Gm Csf ◽  
New Therapeutic Approaches ◽  
Cellular Apoptosis ◽  
Reversible Airflow Obstruction

Asthma is a complex and chronic inflammatory disease of the airways, characterized by variable and recurring symptoms, reversible airflow obstruction, bronchospasm, and airway eosinophilia. As the pathophysiology of asthma is becoming clearer, the identification of new valuable drug targets is emerging. IL-5 is one of these such targets because it is the major cytokine supporting eosinophilia and is responsible for terminal differentiation of human eosinophils, regulating eosinophil proliferation, differentiation, maturation, migration, and prevention of cellular apoptosis. Blockade of the IL-5 pathway has been shown to be efficacious for the treatment of eosinophilic asthma. However, several other inflammatory pathways have been shown to support eosinophilia, including IL-13, the alarmin cytokines TSLP and IL-33, and the IL-3/5/GM-CSF axis. These and other alternate pathways leading to airway eosinophilia will be described, and the efficacy of therapeutics that have been developed to block these pathways will be evaluated.

scholarly journals Baseline Xpert MTB/RIF ct values predict sputum conversion during the intensive phase of anti-TB treatment in HIV infected patients in Kampala, Uganda: a retrospective study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Juliet Namugenyi ◽  
Joseph Musaazi ◽  
Achilles Katamba ◽  
Joan Kalyango ◽  
Emmanuel Sendaula ◽  
...  
Keyword(s):  
Bacterial Load ◽  
Sputum Smear ◽  
People Living With Hiv ◽  
Cd4 Cell Count ◽  
Cut Point ◽  
Ct Value ◽  
Tb Treatment ◽  
Drug Concentrations ◽  
Unit Increase ◽  
Sputum Conversion

Abstract Background In resource-limited settings, sputum smear conversion is used to document treatment response. Many People living with HIV (PLHIV) are smear-negative at baseline. The Xpert MTB/RIF test can indirectly measure bacterial load through cycle threshold (ct) values. This study aimed to determine if baseline Xpert MTB/RIF could predict time to culture negativity in PLHIV with newly diagnosed TB. Methods A subset of 138 PLHIV from the ‘SOUTH’ study on outcomes related to TB and antiretroviral drug concentrations were included. Bacterial load was estimated by Mycobacterium Growth Indicator Tubes (MGIT) culture time-to-positivity (TTP) and Lowenstein Jensen (LJ) colony counts. Changes in TTP and colony counts were analyzed with Poisson Generalised Estimating Equations (GEE) and multilevel ordered logistic regression models, respectively, while time to culture negativity analysed with Cox proportional hazard models. ROC curves were used to explore the accuracy of the ct value in predicting culture negativity. Results A total of 81 patients (58.7%) were males, median age 34 (IQR 29  ̶ 40) years, median CD4 cell count of 180 (IQR 68  ̶ 345) cells/μL and 77.5% were ART naive. The median baseline ct value was 25.1 (IQR 21.0  ̶ 30.1). A unit Increase in the ct value was associated with a 5% (IRR = 1.05 95% CI 1.04  ̶ 1.06) and 3% (IRR = 1.03 95% CI 1.03  ̶ 1.04) increase in TTP at week 2 and 4 respectively. With LJ culture, a patient’s colony grade was reduced by 0.86 times (0R = 0.86 95% CI 0.74  ̶ 0.97) at week 2 and 0.84 times (OR = 0.84 95% CI 0.79  ̶ 0.95 P = 0.002) at week 4 for every unit increase in the baseline ct value. There was a 3% higher likelihood of earlier conversion to negativity for every unit increase in the ct value. A ct cut point ≥28 best predicted culture negativity at week 4 with a sensitivity of 91. 7% & specificity 53.7% while a cut point ≥23 best predicted culture negativity at week 8. Conclusion Baseline Xpert MTB/RIF ct values predict sputum conversion in PLHIV on anti-TB treatment. Surrogate biomarkers for sputum conversion in PLHIV are still a research priority.

scholarly journals LUNG ULTRASOUND DURING COVID-19 PANDEMICS: WHY, HOW AND WHEN?

2021 ◽  
Vol 74 (8) ◽  
pp. 1783-1788
Author(s):  
Khrystyna O. Pronyuk ◽  
Liudmyla O. Kondratiuk ◽  
Andrii D. Vysotskyi ◽  
Olga A. Golubovska ◽  
Iryna M. Nikitina
Keyword(s):  
Hospital Stay ◽  
Clinical Decision Making ◽  
Lung Ultrasound ◽  
Limited Resource ◽  
Clinical Decision ◽  
Lung Damage ◽  
Dynamic Monitoring ◽  
Initial Assessment ◽  
X Ray ◽  
Chest X Ray

The aim: To optimize diagnostic of pathological processes in lungs affected by COVID-19, dynamic monitoring and clinical decision making using lung ultrasound in limited resources settings. Materials and methods: Between the onset of pandemics and January 2021, approximately 9000 patients have been treated for confirmed COVID-19 in the Olexandrivska Clinical Hospital. Assessment of all hospitalized patients included hematology, chemistries and proinflammatory cytokines – IL-6, CRP, procalcitonin, ferritin. Diagnosis was confirmed by PCR for SARS-CoV-2 RNA. Chest X-ray was performed in all hospitalized cases, while CT was available approximately in 30% of cases during hospital stay. Lung ultrasound was proactively utilized to assess the type and extent of lung damage and to monitor the progress of disease in patients hospitalized into the ICU and Infection Unit (n=135). Ultrasound findings were recorded numerically based on scales. Results: In the setting of СOVID-19, bedside lung ultrasound has been promptly recognized as a tool to diagnose and monitor the nature and extent of lung injury. Lung ultrasound is a real time assessment, which helps determine the nature of a pathologic process affecting lungs. In this paper the accuracy of bedside LUS, chest X-ray and computer tomography are compared based on clinical cases, typical for COVID-19 lung ultrasound appearance is evaluated. Described in article data is collected in one of the biggest facility that deals with COVID-19. Chest X-ray was performed in all hospitalized cases, while CT was available approximately in 30% of cases during hospital stay. The cases presented in the paper indicate potential advantages to the use of ultrasound in limited resource healthcare settings, especially when the risk of transportation to CT outweighs the value of information obtained. Conclusions: Grading of ultrasonographic findings in the lungs was sufficient for both initial assessment with identification of high risk patients, and routine daily monitoring. Hence, lung ultrsound may be used to predict deterioration, stratify risks and make clinical decisions.

scholarly journals Respiratory symptoms and lung function in patients treated for pulmonary tuberculosis in Malawi: a prospective cohort study

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2021-217190
Author(s):  
Rebecca Nightingale ◽  
Beatrice Chinoko ◽  
Maia Lesosky ◽  
Sarah J Rylance ◽  
Bright Mnesa ◽  
...  
Keyword(s):  
Lung Function ◽  
Pulmonary Tuberculosis ◽  
Respiratory Symptoms ◽  
Treatment Completion ◽  
First Year ◽  
Tb Treatment ◽  
Effective Interventions ◽  
Hiv Coinfection ◽  
History Of ◽  
Chest X Ray

RationalePulmonary tuberculosis (PTB) can cause post-TB lung disease (PTLD) associated with respiratory symptoms, spirometric and radiological abnormalities. Understanding of the predictors and natural history of PTLD is limited.ObjectivesTo describe the symptoms and lung function of Malawian adults up to 3 years following PTB-treatment completion, and to determine the evolution of PTLD over this period.MethodsAdults successfully completing PTB treatment in Blantyre, Malawi were followed up for 3 years and assessed using questionnaires, post-bronchodilator spirometry, 6 min walk tests, chest X-ray and high-resolution CT. Predictors of lung function at 3 years were identified by mixed effects regression modelling.Measurement and main resultsWe recruited 405 participants of whom 301 completed 3 years follow-up (mean (SD) age 35 years (10.2); 66.6% males; 60.4% HIV-positive). At 3 years, 59/301 (19.6%) reported respiratory symptoms and 76/272 (27.9%) had abnormal spirometry. The proportions with low FVC fell from 57/285 (20.0%) at TB treatment completion to 33/272 (12.1%), while obstruction increased from and 41/285 (14.4%) to 43/272 (15.8%) at 3 years. Absolute FEV1 and FVC increased by mean 0.03 L and 0.1 L over this period, but FEV1 decline of more than 0.1 L was seen in 73/246 (29.7%). Higher spirometry values at 3 years were associated with higher body mass index and HIV coinfection at TB-treatment completion.ConclusionSpirometric measures improved over the 3 years following treatment, mostly in the first year. However, a third of PTB survivors experienced ongoing respiratory symptoms and abnormal spirometry (with accelerated FEV1 decline). Effective interventions are needed to improve the care of this group of patients.

scholarly journals Inflammatory phenotyping predicts clinical outcome in COVID-19

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
H. Burke ◽  
◽  
A. Freeman ◽  
D. C. Cellura ◽  
B. L. Stuart ◽  
...  
Keyword(s):  
Adverse Outcome ◽  
Outcome Data ◽  
University Hospital ◽  
Clinical Parameters ◽  
Gm Csf ◽  
Poor Outcome ◽  
Hospitalised Patients ◽  
Cytokine Levels ◽  
Patients At Risk ◽  
Multiplex Cytokine

Abstract Background The COVID-19 pandemic has led to more than 760,000 deaths worldwide (correct as of 16th August 2020). Studies suggest a hyperinflammatory response is a major cause of disease severity and death. Identitfying COVID-19 patients with hyperinflammation may identify subgroups who could benefit from targeted immunomodulatory treatments. Analysis of cytokine levels at the point of diagnosis of SARS-CoV-2 infection can identify patients at risk of deterioration. Methods We used a multiplex cytokine assay to measure serum IL-6, IL-8, TNF, IL-1β, GM-CSF, IL-10, IL-33 and IFN-γ in 100 hospitalised patients with confirmed COVID-19 at admission to University Hospital Southampton (UK). Demographic, clinical and outcome data were collected for analysis. Results Age > 70 years was the strongest predictor of death (OR 28, 95% CI 5.94, 139.45). IL-6, IL-8, TNF, IL-1β and IL-33 were significantly associated with adverse outcome. Clinical parameters were predictive of poor outcome (AUROC 0.71), addition of a combined cytokine panel significantly improved the predictability (AUROC 0.85). In those ≤70 years, IL-33 and TNF were predictive of poor outcome (AUROC 0.83 and 0.84), addition of a combined cytokine panel demonstrated greater predictability of poor outcome than clinical parameters alone (AUROC 0.92 vs 0.77). Conclusions A combined cytokine panel improves the accuracy of the predictive value for adverse outcome beyond standard clinical data alone. Identification of specific cytokines may help to stratify patients towards trials of specific immunomodulatory treatments to improve outcomes in COVID-19.

scholarly journals Ventilator-associated pneumonia in neonates: the role of point of care lung ultrasound

2020 ◽  
Vol 180 (1) ◽  
pp. 137-146
Author(s):  
Nora Tusor ◽  
Angela De Cunto ◽  
Yousef Basma ◽  
John L. Klein ◽  
Virginie Meau-Petit
Keyword(s):  
Lung Disease ◽  
Chronic Lung Disease ◽  
Lung Ultrasound ◽  
Clinical Laboratory ◽  
Control Group ◽  
Ventilator Associated Pneumonia ◽  
Lung Pathology ◽  
Rater Agreement ◽  
X Ray ◽  
Chest X Ray

AbstractNo consensus exists regarding the definition of ventilator-associated pneumonia (VAP) in neonates and reliability of chest X-ray (CXR) is low. Lung ultrasound (LU) is a potential alternative diagnostic tool. The aim was to define characteristics of VAP in our patient population and propose a multiparameter score, incorporating LU, for VAP diagnosis. Between March 25, 2018, and May 25, 2019, infants with VAP were identified. Clinical, laboratory and microbiology data were collected. CXRs and LU scans were reviewed. A multiparameter VAP score, including LU, was calculated on Day 1 and Day 3 for infants with VAP and for a control group and compared with CXR. VAP incidence was 10.47 episodes/1000 ventilator days. LU and CXR were available for 31 episodes in 21 infants with VAP, and for six episodes in five patients without VAP. On Day 1, a VAP score of > 4, and on Day 3 a score of > 5 showed sensitivity of 0.94, and area under the curve of 0.91 and 0.97, respectively. AUC for clinical information only was 0.88 and for clinical and CXR 0.85.Conclusion: The multiparameter VAP score including LU could be useful in diagnosing VAP in neonates with underlying lung pathology. What is Known:• Ventilator associated pneumonia (VAP) is common in infants on the neonatal unit and is associated with increased use of antibiotics, prolonged ventilation and higher incidence of chronic lung disease.• Commonly used definitions of VAP are difficult to apply in neonates and interpretation of chest X-ray is challenging with poor inter-rater agreement in patients with underlying chronic lung disease. What is New:• The multiparameter VAP score combining clinical, microbiology and lung ultrasound (LU) data is predictive for VAP diagnosis in preterm infants with chronic lung disease.• LU findings of VAP in neonates showed high inter-rater agreement and included consolidated lung areas, dynamic bronchograms and pleural effusion.

Sign in / Sign up

Export Citation Format

Share Document