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.

An investigation into biomarkers for the diagnosis of ABPA and aspergillus disease in cystic fibrosis.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease due to Aspergillus fumigatus (Af) which occurs in 10% of patients with cystic fibrosis (CF). ABPA is associated with increased morbidity and accelerated lung function decline; however, existing diagnostic criteria are nonspecific and diagnosis remains challenging. As ABPA is driven by Th2 inflammation, the aim of this study was to evaluate exhaled nitric oxide (FE NO ), eosinophilic cationic protein (ECP), peripheral eosinophil count, and bronchodilator response (BDR) in patients with CF. METHODS: A prospective observational cohort study of pediatric CF patients in a tertiary center. Patients had a clinical and serologic ABPA assessment, FENO , serum ECP, peripheral eosinophil count, and assessment of BDR. Patients were stratified into three groups; ABPA, Af sensitized (AFS), and non-ABPA non-Af-sensitized (non-AFS). RESULTS: A total of 62 patients were included in the study: 13% ABPA, 19% AFS, and 68% non-AFS. Mean FENO was higher in the ABPA group at 37.8 ppb compared to AFS 15.1 ppb (P = .05) and non-AFS 13.7 ppb (P = .04). Mean peripheral eosinophil count in ABPA group was also higher at 1000 cells/uL, compared to AFS 221 cells/uL (P = .03) and non-AFS 220 cells/uL (P = .03). Mean BDR in ABPA group was 13% compared to 5.5% in non-AFS (P = .01). Serum ECP was higher in patients with ABPA positive compared to the other groups, although this was not statistically significant. CONCLUSION: In children with cystic fibrosis, FENO and peripheral eosinophil counts are elevated in ABPA compared to those that are just sensitized to Aspergillus and may serve as useful diagnostic tests.