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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., (© 2020 Wiley Periodicals LLC.)

Acute viral wheeze in children is a major cause of hospitalisation and a major risk factor for the development of asthma. However, the role of the respiratory tract microbiome in the development of acute wheeze is unclear. To investigate whether severe wheezing episodes in children are associated with bacterial dysbiosis in the respiratory tract, oropharyngeal swabs were collected from 109 children with acute wheezing attending the only tertiary paediatric hospital in Perth, Australia. The bacterial community from these samples was explored using next generation sequencing and compared to samples from 75 non-wheezing controls. No significant difference in bacterial diversity was observed between samples from those with wheeze and healthy controls. Within the wheezing group, attendance at kindergarten or preschool was however, associated with increased bacterial diversity. Rhinovirus (RV) infection did not have a significant effect on bacterial community composition. A significant difference in bacterial richness was observed between children with RV-A and RV-C infection, however this is likely due to the differences in age group between the patient cohorts. The bacterial community within the oropharynx was found to be diverse and heterogeneous. Age and attendance at day care or kindergarten were important factors in driving bacterial diversity. However, wheeze and viral infection were not found to significantly relate to the bacterial community. Bacterial airway microbiome is highly variable in early life and its role in wheeze remains less clear than viral influences., Competing Interests: The authors have declared that no competing interests exist.

Asthma exacerbations are triggered by rhinovirus infections. We employed a systems biology approach to delineate upper-airway gene network patterns underlying asthma exacerbation phenotypes in children. Cluster analysis unveiled distinct IRF7 hi versus IRF7 lo molecular phenotypes, the former exhibiting robust upregulation of Th1/type I IFN responses and the latter an alternative signature marked by upregulation of cytokine and growth factor signaling and downregulation of IFN-γ. The two phenotypes also produced distinct clinical phenotypes. For IRF7 lo children, symptom duration prior to hospital presentation was more than twice as long from initial symptoms ( p = 0.011) and nearly three times as long for cough ( p < 0.001), the odds ratio of admission to hospital was increased more than 4-fold ( p = 0.018), and time to recurrence was shorter ( p = 0.015). In summary, our findings demonstrate that asthma exacerbations in children can be divided into IRF7 hi versus IRF7 lo phenotypes with associated differences in clinical phenotypes., (Copyright © 2019 by The American Association of Immunologists, Inc.)

Background: Human rhinovirus (RV) is the most common respiratory virus and has been associated with frequent and severe acute lower respiratory infections (ALRI). The prevalence of RV species among HIV-infected children in South Africa is unknown., Objectives: To describe the prevalence of respiratory viruses, including RV species, associated with HIV status and other clinical symptoms in children less than two years of age with and without ALRI in Pretoria, South Africa., Study Design: Nasopharyngeal aspirates were collected from 105 hospitalized ALRI cases and 53 non-ALRI controls less than two years of age. HIV status was determined. Common respiratory viruses were identified by PCR, and RV species and genotypes were identified by semi-nested PCR, sequencing and phylogenetic tree analyses., Results: Respiratory viruses were more common among ALRI cases than controls (83.8% vs. 69.2%; p=0.041). RV was the most commonly identified virus in cases with pneumonia (45.6%) or bronchiolitis (52.1%), regardless of HIV status, as well as in controls (39.6%). RV-A was identified in 26.7% of cases and 15.1% of controls while RV-C was identified in 21.0% of cases and 18.9% of controls. HIV-infected children were more likely to be diagnosed with pneumonia than bronchiolitis (p<0.01). RSV was not identified in any HIV-infected cases (n=15) compared with 30.6% of HIV-uninfected cases (n=85, p=0.013), and was identified more frequently in bronchiolitis than in pneumonia cases (43.8% vs. 12.3%; p<0.01)., Conclusions: RV-A and RV-C are endemic in South African children and HIV infection may be protective against RSV and bronchiolitis., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Rationale: Human rhinovirus species C (HRV-C) is the most common cause of acute wheezing exacerbations in young children presenting to hospital, but its impact on subsequent respiratory illnesses has not been defined., Objectives: To determine whether acute wheezing exacerbations due to HRV-C are associated with increased hospital attendances due to acute respiratory illnesses (ARIs)., Methods: Clinical information and nasal samples were collected prospectively from 197 children less than 5 years of age, presenting to hospital with an acute wheezing episode. Information on hospital attendances with an ARI before and after recruitment was subsequently obtained., Measurements and Main Results: HRV was the most common virus identified at recruitment (n = 135 [68.5%]). From the 120 (88.9%) samples that underwent typing, HRV-C was the most common HRV species identified, present in 81 (67.5%) samples. Children with an HRV-related wheezing illness had an increased risk of readmission with an ARI (relative risk, 3.44; 95% confidence interval, 1.17-10.17; P = 0.03) compared with those infected with any other virus. HRV-C, compared with any other virus, was associated with an increased risk of a respiratory hospital admission before (49.4% vs. 27.3%, respectively; P = 0.004) and within 12 months (34.6% vs. 17.0%; P = 0.01) of recruitment. Risk for subsequent ARI admissions was further increased in atopic subjects (relative risk, 6.82; 95% confidence interval, 2.16-21.55; P = 0.001). Admission risks were not increased for other HRV species., Conclusions: HRV-C-related wheezing illnesses were associated with an increased risk of prior and subsequent hospital respiratory admissions. These associations are consistent with HRV-C causing recurrent severe wheezing illnesses in children who are more susceptible to ARIs.

Objective: To examine the influence of viral respiratory infection (VRI) on treatment response in acute asthma in children., Study Design: A total of 218 children (mean age, 6.6 years) with acute asthma were recruited. Symptoms were recorded, an asthma severity score was determined, and whenever possible, a per-nasal aspirate was obtained for detection of viruses. Each child's response to inhaled β(2)-agonists was assessed after 6, 12, and 24 hours., Results: The 168 children with VRI symptoms received more treatment with inhaled β(2)-agonists after 6 hours (P = .010), 12 hours (P = .002), and 24 hours (P = .0005) compared with the 50 children without such symptoms. Asthma severity did not differ between the 2 groups. A per-nasal aspirate was obtained from 77% of the children. The most frequently identified virus was rhinovirus (61.4%). Among children with symptoms of a VRI, those with rhinovirus had an impaired response to β(2)-agonists at 6 hours (P = .032)., Conclusion: Children with acute asthma and symptoms of VRI respond less effectively to β(2)-agonists after 6, 12, or 24 hours and thus may benefit from more intense therapy and monitoring., (Crown Copyright © 2012. Published by Mosby, Inc. All rights reserved.)