The impact of cytokine levels in young South African children with and without HIV-associated acute lower respiratory infections.

Altered host immune responses are considered to play a key role in the pathogenesis of acute lower respiratory infections (ALRI). The existing literature on cytokine responses in ALRI is largely focussed on adults from developed countries and there are few reports describing the role of cytokines in childhood ALRI, particularly in African or human immunodeficiency virus (HIV)-infected populations. To measure systemic cytokine levels in blood plasma from young South African children with and without ALRI and with and without HIV to determine associations between cytokine responses and disease status and respiratory viral identification. Blood plasma samples were collected from 106 hospitalized ALRI cases and 54 non-ALRI controls less than 2 years of age. HIV status was determined. Blood plasma concentrations of 19 cytokines, 7 chemokines, and 4 growth factors (epidermal growth factor, fibroblast growth factor-basic, hepatocyte growth factor, and vascular endothelial) were measured using The Human Cytokine 30-Plex Panel. Common respiratory viruses were identified by PCR. Mean cytokine concentrations for G-CSF, interferon (IFN)-γ, interleukin (IL)-5, and MCP-1 were significantly higher in ALRI cases than in nonrespiratory controls. Within the ALRI cases, several cytokines were higher in children with a virus compared with children without a virus. Mean cytokine concentrations for IFN-α, IFN-γ, IL-4, IL-5, IL-13, tumour necrosis factor-α, and MIP-1α were significantly lower in HIV-infected cases than in HIV-uninfected cases, while IP-10 and monokine induced by interferon-γ were significantly higher in HIV-infected cases than in HIV-uninfected cases. Certain cytokines are likely to play an important role in the host immune response to ALRI. HIV-infected children have impaired inflammatory responses to respiratory infections compared with HIV-uninfected children.

The lung microbiome in children with HIV-bronchiectasis: a cross-sectional pilot study.

BACKGROUND: Data on the lung microbiome in HIV-infected children is limited. The current study sought to determine the lung microbiome in HIV-associated bronchiectasis and to assess its association with pulmonary exacerbations. METHODS: A cross-sectional pilot study of 22 children (68% male; mean age 10.8 years) with HIV-associated bronchiectasis and a control group of 5 children with cystic fibrosis (CF). Thirty-one samples were collected, with 11 during exacerbations. Sputum samples were processed with 16S rRNA pyrosequencing. RESULTS: The average number of operational taxonomy units (OTUs) was 298 ± 67 vs. 434 ± 90, for HIV-bronchiectasis and CF, respectively. The relative abundance of Proteobacteria was higher in HIV-bronchiectasis (72.3%), with only 22.2% Firmicutes. There was no correlation between lung functions (FEV1% and FEF25/75%) and bacterial community (r = 0.154; p = 0.470 and r = 0.178; p = 0.403), respectively. Bacterial assemblage of exacerbation and non-exacerbation samples in HIV-bronchiectasis was not significantly different (ANOSIM, RHIV-bronchiectasis = 0.08; p = 0.14 and RCF = 0.08, p = 0.50). Higher within-community heterogeneity and lower evenness was associated with CF (Shannon-Weiner (H') = 5.39 ± 0.38 and Pielou's evenness (J) 0.79 ± 0.10 vs. HIV-bronchiectasis (Shannon-Weiner (H') = 4.45 ± 0.49 and Pielou's (J) 0.89 ± 0.03. CONCLUSION: The microbiome in children with HIV-associated bronchiectasis seems to be less rich, diverse and heterogeneous with predominance of Proteobacteria when compared to cystic fibrosis.

Positron emission tomography in the prediction of inflammation in children with human immunodeficiency virus related bronchiectasis.

There is a lack of objective tools to reliably diagnose exacerbations in bronchiectasis. The primary aim of this study was to assess the ability of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (¹8F-FDG PET/CT) to detect sites of active inflammation in children with human immunodeficiency virus (HIV)-related bronchiectasis with or without exacerbations. The secondary aim was to assess whether ¹8F-FDG-PET/CT results are in agreement with local and systemic inflammatory markers and markers of HIV disease activity. Forty-one children with HIV-related bronchiectasis underwent ¹8F-FDG PET/CT. Data on the presence of a clinical exacerbation were recorded. Serum was collected for CD4 count, HIV viral load, C-reactive protein (CRP) and cytokines IL-8, INF-γ and TNF-α. Induced sputum samples were processed for microbiological culture and for IL-8, INF-γ and TNF-α.Mean age of all children was 8.2 ± 2.2 years. Twelve subjects showed F-FDG lung uptake while six of them had an exacerbation. There was no difference in the ¹8F-FDG uptake in participants with or without an exacerbation (P=0.613). Fluorine- 18-FDG-PET had a good correlation with the presence of consolidation (P=0.01, OR=6.67). The mean CRP was higher in the subjects with (18)F-FDG uptake when compared to those without uptake (51.96 ± 95.12 vs. 13.26 ± 19.87), although this difference was not significant (P=0.09). In conclusion, the ¹8F-FDG-PET lung uptake technique could not reliably predict the presence of an exacerbation in children with HIV and bronchiectasis, and its diagnostic value was limited to identifying disease activity on the scan in acute pneumonia cases. Fluorine-18-FDG-PET had no significant correlation with CRP or with other inflammatory biomarkers and markers of HIV disease activity.