Lung clearance index predicts persistence of preschool wheeze.

BACKGROUND: The lung clearance index (LCI) is a measure of pulmonary function. Variable feasibility (50->80%) in preschool children has been reported. There are limited studies exploring its relationship to respiratory symptoms and how it predicts persistent wheeze. We aimed to assess the association with respiratory symptoms in preschool-aged children with LCI and determine its utility in predicting persistent wheeze. METHODS: LCI was measured in a subcohort of the CHILD Cohort Study at age 3 years using SF6  multiple breath washout test mass spectrometry. Respiratory symptom phenotypes at age 3 were derived from children's respiratory symptoms reported by their parents. Responses were used to categorize children into 4 symptom groups: recurrent wheeze (3RW), recurrent cough (3RC), infrequent symptoms (IS), and no current symptoms (NCS). At age 5 years, these children were seen by a specialist clinician and assessed for persistent wheeze (PW). RESULTS: At age 3 years, 69% (234/340) had feasible LCI. Excluding two children with missing data, 232 participants were categorized as follows: 33 (14%) 3RW; 28 (12%) 3RC; 17 (7%) IS; and 154 (66%) NCS. LCI z-score at age 3 years was highest in children with 3RW compared to 3RC (mean (SD): 1.14 (1.56) vs. 0.09 (0.95), p < .01), IS (mean (SD): -0.14 (0.59), p < .01), and NCS (mean (SD): -0.08 (1.06), p < .01). LCI z-score at age 3 was predictive of persistent wheeze at age 5 (PW) (AUROC: 0.87). CONCLUSIONS: LCI at age 3 was strongly associated with recurrent wheeze at age 3, and predictive of its persistence to age 5.

Co-infection in critically ill patients with COVID-19: an observational cohort study from England.

Introduction. During previous viral pandemics, reported co-infection rates and implicated pathogens have varied. In the 1918 influenza pandemic, a large proportion of severe illness and death was complicated by bacterial co-infection, predominantly Streptococcus pneumoniae and Staphylococcus aureus.Gap statement. A better understanding of the incidence of co-infection in patients with COVID-19 infection and the pathogens involved is necessary for effective antimicrobial stewardship.Aim. To describe the incidence and nature of co-infection in critically ill adults with COVID-19 infection in England.Methodology. A retrospective cohort study of adults with COVID-19 admitted to seven intensive care units (ICUs) in England up to 18 May 2020, was performed. Patients with completed ICU stays were included. The proportion and type of organisms were determined at <48 and >48 h following hospital admission, corresponding to community and hospital-acquired co-infections.Results. Of 254 patients studied (median age 59 years (IQR 49-69); 64.6 % male), 139 clinically significant organisms were identified from 83 (32.7 %) patients. Bacterial co-infections/ co-colonisation were identified within 48 h of admission in 14 (5.5 %) patients; the commonest pathogens were Staphylococcus aureus (four patients) and Streptococcus pneumoniae (two patients). The proportion of pathogens detected increased with duration of ICU stay, consisting largely of Gram-negative bacteria, particularly Klebsiella pneumoniae and Escherichia coli. The co-infection/ co-colonisation rate >48 h after admission was 27/1000 person-days (95 % CI 21.3-34.1). Patients with co-infections/ co-colonisation were more likely to die in ICU (crude OR 1.78,95 % CI 1.03-3.08, P=0.04) compared to those without co-infections/ co-colonisation.Conclusion. We found limited evidence for community-acquired bacterial co-infection in hospitalised adults with COVID-19, but a high rate of Gram-negative infection acquired during ICU stay.

Evaluating post-bronchodilator response in well-controlled paediatric severe asthma using hyperpolarised 129Xe-MRI: A pilot study.

INTRODUCTION: Pulmonary function tests (PFTs) are the main objective measures used to assess asthma in children. However, PFTs provide a global measure of lung function. Hyperpolarised xenon-129 magnetic resonance imaging (129Xe-MRI) can assess lung function spatially. This cross-sectional cohort study aimed to evaluate the use of 129Xe-MRI in detecting ventilation abnormalities in children with well-controlled severe asthma pre- and post-bronchodilator (BD). METHOD: Six healthy children (aged 11 ± 3) and six with well-controlled severe asthma (14 ± 1) underwent spirometry, multiple breath washout (MBW), and 129Xe-MRI. These tests were repeated post-BD in the asthma cohort. Image analysis was performed in MATLAB. Wilcoxon signed-rank test, repeated measures analysis of variance (ANOVA), and Spearman's rank correlation coefficient were used for statistical analysis. RESULTS: A significantly higher number of ventilation defects were found in the asthma cohort pre-BD compared to the healthy participants and post-BD within the asthma cohort (p = 0.02 and 0.01). A greater number of wedge-shaped defects were detected in the asthma cohort pre-BD compared to healthy participants and post-BD within the asthma cohort (p = 0.01 and 0.008, respectively). 129Xe ventilation defect percentage (VDP) and coefficient of variation (CoV) were significantly higher in the asthma cohort pre-BD compared to the healthy cohort (p = 0.006 for both). VDP and CoV were reduced significantly post-BD in the asthma cohort, to a level where there was no longer a significant difference between the two cohorts. CONCLUSION: 129Xe-MRI is a sensitive marker of ventilation inhomogeneity in paediatric severe asthma and may potentially be used as a biomarker to assess disease progression and therapeutic response.

Assessing the impact of posture on diaphragm morphology and function using an open upright MRI system-A pilot study.

PURPOSE: The diaphragm is the most important muscle of respiration. Disorders of the diaphragm can have a deleterious impact on respiratory function. We aimed to evaluate the use of an open-configuration upright low-field MRI system to assess diaphragm morphology and function in patients with bilateral diaphragm weakness (BDW) and chronic obstructive pulmonary disease (COPD) with hyperinflation. METHOD: The study was approved by the National Research Ethics Committee, and written consent was obtained. We recruited 20 healthy adult volunteers, six subjects with BDW, and five subjects with COPD with hyperinflation. We measured their vital capacity in the upright and supine position, after which they were scanned on the 0.5 T MRI system during 10-s breath-holds at end-expiration and end-inspiration in both positions. We developed and applied image analysis methods to measure the volume under the dome, maximum excursion of hemidiaphragms, and anterior-posterior and left-right extension of the diaphragm. RESULTS: All participants were able to complete the scanning protocol. The patients found scanning in the upright position more comfortable than the supine position. All differences in the supine inspiratory-expiratory parameters, excluding left-right extension, were significantly smaller in the BDW and COPD groups compared with healthy volunteers. No significant correlation was found between the postural change in diaphragm morphology and vital capacity in either group. CONCLUSION: Our combined upright-supine MR imaging approach facilitates the assessment of the impact of posture on diaphragm morphology and function in patients with BDW and those with COPD with hyperinflation.

Persistent ventilation inhomogeneity after an acute exacerbation in preschool children with recurrent wheezing.

BACKGROUND: Preschool children with recurrent wheezing suffer high morbidity. It is unclear whether objective measures of asthma control, such as pulmonary function tests (PFTs), provide additional information to the clinical assessment. METHODS: We recruited children between 3 and 6 years old, with a history of recurrent wheezing in the preceding year and treated for acute wheezing exacerbation in the emergency department (ED) into an observational cohort study. Children attended two outpatient visits: the first study visit within five days of discharge from the ED and the second study visit 12 weeks after the ED visit. We performed standardized symptom score (test for respiratory and asthma control in kids (TRACK)), multiple breath washout (MBW), spirometry, and clinical assessment at both visits. RESULTS: Seventy-four children, mean (standard deviation (SD)) age of 4.32 years (0.84), attended both visits. Paired FEV0.75 and lung clearance index (LCI) measurements at both time points were obtained in 37 and 34 subjects, respectively. Feasibility for all tests improved at visit 2 and was not age-dependent. At the second study visit, a third had controlled asthma based on the TRACK score, and the mean lung clearance index (LCI) improved from 9.86 to 8.31 (P = .003); however, 46% had an LCI in the abnormal range. FEV0.75 z-score improved from -1.66 to -1.17 (P = .05) but remained in the abnormal range in 24%. LCI was abnormal in more than half of the children with "well-controlled" asthma based on the TRACK score. There was no correlation between PFT measures and TRACK scores at either visit. CONCLUSIONS: Lung clearance index demonstrates a persistent deficit post-exacerbation in a large proportion of preschoolers with recurrent wheezing, highlighting that symptom scores alone may not suffice for monitoring these children.

NMR Hyperpolarization Techniques of Gases.

Nuclear spin polarization can be significantly increased through the process of hyperpolarization, leading to an increase in the sensitivity of nuclear magnetic resonance (NMR) experiments by 4-8 orders of magnitude. Hyperpolarized gases, unlike liquids and solids, can often be readily separated and purified from the compounds used to mediate the hyperpolarization processes. These pure hyperpolarized gases enabled many novel MRI applications including the visualization of void spaces, imaging of lung function, and remote detection. Additionally, hyperpolarized gases can be dissolved in liquids and can be used as sensitive molecular probes and reporters. This Minireview covers the fundamentals of the preparation of hyperpolarized gases and focuses on selected applications of interest to biomedicine and materials science.

De novo donor HLA-specific antibodies predict development of bronchiolitis obliterans syndrome after lung transplantation.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the major cause of late graft failure after lung transplantation. The objective was to determine whether de novo donor human leukocyte antigen (HLA)-specific antibodies (DSA) are associated with the development of BOS or patient survival. Data were analyzed from 188 lung transplant recipients with a follow-up period up to 8 years. METHODS: HLA antibody monitoring was performed at 3-month intervals post-transplant at routine outpatient clinic attendances and during the investigation of any acute deterioration. HLA antibody data were available for 148 patients; 66 (45%) had produced HLA antibodies after transplant, of which 38 (26%) were DSA and 28 (19%) non-donor-specific HLA antibodies. RESULTS: De novo DSA was associated with development of BOS Stage 1 (BOS1; hazard ratio [HR] = 2.302, p = 0.0015), BOS2 (HR = 3.627, p < 0.0001) and BOS3 (HR = 5.736, p < 0.0001). De novo persistent DSA correlated strongly with shorter time to onset of BOS3 (HR = 6.506, p = 0.0001). There was a significant reduction in patient survival associated with de novo DSA (HR = 1.886, p = 0.047). In multivariable analyses, de novo DSA was an independent predictor for development of all stages of BOS as well as an independent predictor of poor patient survival. CONCLUSIONS: De novo DSA is a major risk factor for progression to BOS and shorter patient survival. Treatments to remove antibodies or limit antibody-mediated damage could be considered when DSA are first detected. However, a randomized, controlled trial of treatment options would enable a clearer understanding of the benefits, if any, of antibody-removal therapies.

Multi-territory ischaemic strokes and subacute bacterial endocarditis.

We describe an elderly patient presenting with cardio-embolic stroke who was found to have infective endocarditis (IE) affecting the mitral valve. Penicillin-resistant Facklamia hominis was identified as the causative pathogen. Despite initiation of aggressive antibiotic treatment, the patient suffered a fatal myocardial infarction 2 days post-diagnosis of IE. Facklamia spp. have not been previously reported to be associated with IE. Here, we discuss the link between IE and cardio-embolic stroke along with a discussion of various causative pathogens.

Miliary tuberculosis in a young Caucasian adult.

A young Caucasian adult presented to the Accident and Emergency department with small bowel obstruction, which necessitated an exploratory laparotomy. Multiple firm nodules were found with biopsies leading to a diagnosis of peritoneal tuberculosis (TB). Retrospectively, the patient was noted to have classical radiological pulmonary TB findings on a chest radiograph 3 months previously, and 2 weeks later had developed bony infiltration, paravertebral abscesses and likely TB skin lesions. This case illustrates an unusual presentation in a patient with minimal risk factors yet widespread extra-pulmonary disease. It also highlights the importance of attentive reviewing of x-rays.

The bone scan in disseminated BCGitis.

Despite the long history of worldwide use of bacillus Calmette-Guerin (BCG) vaccine, a wide spectrum of adverse reactions has been observed in a small proportion of immunized infants. The most severe complication is disseminated BCGitis, often fatal but extremely rare and considered to be a result of host immunodeficiency. At present, polymerase chain reaction test, CT scan, ultrasound, X-rays and bone marrow aspirations are the investigations used to diagnose this disease. We report a case report of a 6 months old female infant with disseminated BCGitis. This paper aims to highlight the advantages of using bone (99m)Tc-MDP imaging and it's findings in supporting the diagnosis of disseminated BCGitis.