47 research outputs found

    Human Immunodeficiency Virus-Associated Chronic Lung Disease in Children and Adolescents in Zimbabwe: Chest Radiographic and High-Resolution Computed Tomographic Findings.

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    Background: Chronic respiratory symptoms are common among children living with human immunodeficiency virus (HIV). We investigated the radiological features of chronic lung disease in children aged 6-16 years receiving antiretroviral therapy for ≥6 months in Harare, Zimbabwe. Methods: Consecutive participants from a HIV clinic underwent clinical assessment and chest radiography. Participants with an abnormal chest radiograph (assessed by a clinician) and/or those meeting a clinical case definition for chronic lung disease underwent high-resolution computed tomography (HRCT). Radiological studies were scored independently and blindly by 2 thoracic radiologists. Relationships between radiological abnormalities and lung function were examined. Results: Among 193 participants (46% female; median age, 11.2 years; interquartile range, 9.0-12.8 years), the median CD4 cell count was 720/µL (473-947/µL), and 79% had a human immunodeficiency virus (HIV) load of <400 copies/mL. The most common chest radiographic finding was ring/tramline opacities (55 of 193 participants; 29%). HRCT scans were evaluated in 84 participants (69%); decreased attenuation (present in 43%) was the dominant abnormality seen. The extent of decreased attenuation was strongly correlated with both the severity and extent of bronchiectasis (rs = 0.68 and P < .001 for both). The extent of decreased attenuation was also negatively correlated with forced expiratory volume in first second of expiration (rs = -0.52), forced vital capacity (rs = -0.42), and forced expiratory flow, midexpiratory phase (rs = -0.42) (P < .001 for all). Conclusions: The HRCT findings strongly suggest that obliterative bronchiolitis may be the major cause of chronic lung disease in our cohort. Further studies to understand the pathogenesis and natural history are urgently needed

    A persistent neutrophil-associated immune signature characterizes post-COVID-19 pulmonary sequelae

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    Interstitial lung disease and associated fibrosis occur in a proportion of individuals who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through unknown mechanisms. We studied individuals with severe coronavirus disease 2019 (COVID-19) after recovery from acute illness. Individuals with evidence of interstitial lung changes at 3 to 6 months after recovery had an up-regulated neutrophil-associated immune signature including increased chemokines, proteases, and markers of neutrophil extracellular traps that were detectable in the blood. Similar pathways were enriched in the upper airway with a concomitant increase in antiviral type I interferon signaling. Interaction analysis of the peripheral phosphoproteome identified enriched kinases critical for neutrophil inflammatory pathways. Evaluation of these individuals at 12 months after recovery indicated that a subset of the individuals had not yet achieved full normalization of radiological and functional changes. These data provide insight into mechanisms driving development of pulmonary sequelae during and after COVID-19 and provide a rational basis for development of targeted approaches to prevent long-term complications

    Oral abstracts 3: RA Treatment and outcomesO13. Validation of jadas in all subtypes of juvenile idiopathic arthritis in a clinical setting

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    Background: Juvenile Arthritis Disease Activity Score (JADAS) is a 4 variable composite disease activity (DA) score for JIA (including active 10, 27 or 71 joint count (AJC), physician global (PGA), parent/child global (PGE) and ESR). The validity of JADAS for all ILAR subtypes in the routine clinical setting is unknown. We investigated the construct validity of JADAS in the clinical setting in all subtypes of JIA through application to a prospective inception cohort of UK children presenting with new onset inflammatory arthritis. Methods: JADAS 10, 27 and 71 were determined for all children in the Childhood Arthritis Prospective Study (CAPS) with complete data available at baseline. Correlation of JADAS 10, 27 and 71 with single DA markers was determined for all subtypes. All correlations were calculated using Spearman's rank statistic. Results: 262/1238 visits had sufficient data for calculation of JADAS (1028 (83%) AJC, 744 (60%) PGA, 843 (68%) PGE and 459 (37%) ESR). Median age at disease onset was 6.0 years (IQR 2.6-10.4) and 64% were female. Correlation between JADAS 10, 27 and 71 approached 1 for all subtypes. Median JADAS 71 was 5.3 (IQR 2.2-10.1) with a significant difference between median JADAS scores between subtypes (p < 0.01). Correlation of JADAS 71 with each single marker of DA was moderate to high in the total cohort (see Table 1). Overall, correlation with AJC, PGA and PGE was moderate to high and correlation with ESR, limited JC, parental pain and CHAQ was low to moderate in the individual subtypes. Correlation coefficients in the extended oligoarticular, rheumatoid factor negative and enthesitis related subtypes were interpreted with caution in view of low numbers. Conclusions: This study adds to the body of evidence supporting the construct validity of JADAS. JADAS correlates with other measures of DA in all ILAR subtypes in the routine clinical setting. Given the high frequency of missing ESR data, it would be useful to assess the validity of JADAS without inclusion of the ESR. Disclosure statement: All authors have declared no conflicts of interest. Table 1Spearman's correlation between JADAS 71 and single markers DA by ILAR subtype ILAR Subtype Systemic onset JIA Persistent oligo JIA Extended oligo JIA Rheumatoid factor neg JIA Rheumatoid factor pos JIA Enthesitis related JIA Psoriatic JIA Undifferentiated JIA Unknown subtype Total cohort Number of children 23 111 12 57 7 9 19 7 17 262 AJC 0.54 0.67 0.53 0.75 0.53 0.34 0.59 0.81 0.37 0.59 PGA 0.63 0.69 0.25 0.73 0.14 0.05 0.50 0.83 0.56 0.64 PGE 0.51 0.68 0.83 0.61 0.41 0.69 0.71 0.9 0.48 0.61 ESR 0.28 0.31 0.35 0.4 0.6 0.85 0.43 0.7 0.5 0.53 Limited 71 JC 0.29 0.51 0.23 0.37 0.14 -0.12 0.4 0.81 0.45 0.41 Parental pain 0.23 0.62 0.03 0.57 0.41 0.69 0.7 0.79 0.42 0.53 Childhood health assessment questionnaire 0.25 0.57 -0.07 0.36 -0.47 0.84 0.37 0.8 0.66 0.4

    High-resolution CT phenotypes in pulmonary sarcoidosis: a multinational Delphi consensus study

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    One view of sarcoidosis is that the term covers many different diseases. However, no classification framework exists for the future exploration of pathogenetic pathways, genetic or trigger predilections, patterns of lung function impairment, or treatment separations, or for the development of diagnostic algorithms or relevant outcome measures. We aimed to establish agreement on high-resolution CT (HRCT) phenotypic separations in sarcoidosis to anchor future CT research through a multinational two-round Delphi consensus process. Delphi participants included members of the Fleischner Society and the World Association of Sarcoidosis and other Granulomatous Disorders, as well as members' nominees. 146 individuals (98 chest physicians, 48 thoracic radiologists) from 28 countries took part, 144 of whom completed both Delphi rounds. After rating of 35 Delphi statements on a five-point Likert scale, consensus was achieved for 22 (63%) statements. There was 97% agreement on the existence of distinct HRCT phenotypes, with seven HRCT phenotypes that were categorised by participants as non-fibrotic or likely to be fibrotic. The international consensus reached in this Delphi exercise justifies the formulation of a CT classification as a basis for the possible definition of separate diseases. Further refinement of phenotypes with rapidly achievable CT studies is now needed to underpin the development of a formal classification of sarcoidosis

    Method for minimizing observer variation for the quantitation of high-resolution computed tomographic signs of lung disease.

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    OBJECTIVES: This study aimed to describe a method of reducing interobserver variation associated with the visual quantitation of high-resolution computed tomographic (HRCT) signs of airways and interstitial lung disease (ILD). METHODS: The HRCT scans of 2 cohorts of patients with airways disease (n = 144) and ILD (n = 109) were evaluated by 2 observers. Selected signs of airways disease were evaluated: (1) bronchial wall thickness and (2) the extent of the decreased attenuation. In the ILD group, the total extent of disease was scored. These 3 HRCT signs were scored by 2 observers independently using a standard method. The observers rescored the CT scans with a new scoring system (continuous learning method, CLM). RESULTS: Observer agreement for CT signs was superior for CLM: bronchial wall thickness κw increased from 0.51 to 0.76; for decreased attenuation, κw increased from 0.34 to 0.81; and for ILD extent, κw increased from 0.53 to 0.87. CONCLUSIONS: The CLM reduces noise from observer variation in studies that require visual quantitation of HRCT signs of lung disease
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