Impaired interferon response in plasmacytoid dendritic cells from children with persistent wheeze.

BACKGROUND: Impaired interferon response and allergic sensitization may contribute to virus-induced wheeze and asthma development in young children. Plasmacytoid dendritic cells (pDCs) play a key role in antiviral immunity as critical producers of type I interferons. pDCs also express the high-affinity IgE receptor through which type I interferon production may be negatively regulated. Whether antiviral function of pDCs is associated with recurrent episodes of wheeze in young children is not well understood. OBJECTIVE: We sought to evaluate the phenotype and function of circulating pDCs in children with a longitudinally defined wheezing phenotype. METHODS: We performed multiparameter flow cytometry on PBMCs from 38 children presenting to the emergency department with an acute episode of respiratory wheeze and 19 controls. RNA sequencing on isolated pDCs from the same individuals was also performed. For each subject, their longitudinal exacerbation phenotype was determined using the Western Australia public hospital database. RESULTS: We observed a significant depletion of circulating pDCs in young children with a persistent phenotype of wheeze. The same individuals also displayed upregulation of the FcεRI on their pDCs. Based on transcriptomic analysis, pDCs from these individuals did not mount a robust systemic antiviral response as observed in children who displayed a nonrecurrent wheezing phenotype. CONCLUSIONS: Our data suggest that circulating pDC phenotype and function are altered in young children with a persistent longitudinal exacerbation phenotype. Expression of high-affinity IgE receptor is increased and their function as major interferon producers is impaired during acute exacerbations of wheeze.

Recommendations for asthma monitoring in children: A PeARL document endorsed by APAPARI, EAACI, INTERASMA, REG, and WAO.

Monitoring is a major component of asthma management in children. Regular monitoring allows for diagnosis confirmation, treatment optimization, and natural history review. Numerous factors that may affect disease activity and patient well-being need to be monitored: response and adherence to treatment, disease control, disease progression, comorbidities, quality of life, medication side-effects, allergen and irritant exposures, diet and more. However, the prioritization of such factors and the selection of relevant assessment tools is an unmet need. Furthermore, rapidly developing technologies promise new opportunities for closer, or even "real-time," monitoring between visits. Following an approach that included needs assessment, evidence appraisal, and Delphi consensus, the PeARL Think Tank, in collaboration with major international professional and patient organizations, has developed a set of 24 recommendations on pediatric asthma monitoring, to support healthcare professionals in decision-making and care pathway design.

Rhinoviruses A and C elicit long-lasting antibody responses with limited cross-neutralization.

Rhinoviruses (RVs) can cause severe wheezing illnesses in young children and patients with asthma. Vaccine development has been hampered by the multitude of RV types with little information about cross-neutralization. We previously showed that neutralizing antibody (nAb) responses to RV-C are detected twofold to threefold more often than those to RV-A throughout childhood. Based on those findings, we hypothesized that RV-C infections are more likely to induce either cross-neutralizing or longer-lasting antibody responses compared with RV-A infections. We pooled RV diagnostic data from multiple studies of children with respiratory illnesses and compared the expected versus observed frequencies of sequential infections with RV-A or RV-C types using log-linear regression models. We tested longitudinally collected plasma samples from children to compare the duration of RV-A versus RV-C nAb responses. Our models identified limited reciprocal cross-neutralizing relationships for RV-A (A12-A75, A12-A78, A20-A78, and A75-A78) and only one for RV-C (C2-C40). Serologic analysis using reference mouse sera and banked human plasma samples confirmed that C40 infections induced nAb responses with modest heterotypic activity against RV-C2. Mixed-effects regression modeling of longitudinal human plasma samples collected from ages 2 to 18 years demonstrated that RV-A and RV-C illnesses induced nAb responses of similar duration. These results indicate that both RV-A and RV-C nAb responses have only modest cross-reactivity that is limited to genetically similar types. Contrary to our initial hypothesis, RV-C species may include even fewer cross-neutralizing types than RV-A, whereas the duration of nAb responses during childhood is similar between the two species. The modest heterotypic responses suggest that RV vaccines must have a broad representation of prevalent types.

Genetic variants of TLR4, including the novel variant, rs5030719, and related genes are associated with susceptibility to clinical malaria in African children.

BACKGROUND: Malaria is a deadly disease caused by Plasmodium spp. Several blood phenotypes have been associated with malarial resistance, which suggests a genetic component to immune protection. METHODS: One hundred and eighty-seven single nucleotide polymorphisms (SNPs) in 37 candidate genes were genotyped and investigated for associations with clinical malaria in a longitudinal cohort of 349 infants from Manhiça, Mozambique, in a randomized controlled clinical trial (RCT) (AgeMal, NCT00231452). Malaria candidate genes were selected according to involvement in known malarial haemoglobinopathies, immune, and pathogenesis pathways. RESULTS: Statistically significant evidence was found for the association of TLR4 and related genes with the incidence of clinical malaria (p = 0.0005). These additional genes include ABO, CAT, CD14, CD36, CR1, G6PD, GCLM, HP, IFNG, IFNGR1, IL13, IL1A, IL1B, IL4R, IL4, IL6, IL13, MBL, MNSOD, and TLR2. Of specific interest, the previously identified TLR4 SNP rs4986790 and the novel finding of TRL4 SNP rs5030719 were associated with primary cases of clinical malaria. CONCLUSIONS: These findings highlight a potential central role of TLR4 in clinical malarial pathogenesis. This supports the current literature and suggests that further research into the role of TLR4, as well as associated genes, in clinical malaria may provide insight into treatment and drug development.

Enhanced Neutralizing Antibody Responses to Rhinovirus C and Age-Dependent Patterns of Infection.

Rationale: Rhinovirus (RV) C can cause asymptomatic infection and respiratory illnesses ranging from the common cold to severe wheezing.Objectives: To identify how age and other individual-level factors are associated with susceptibility to RV-C illnesses.Methods: Longitudinal data from the COAST (Childhood Origins of Asthma) birth cohort study were analyzed to determine relationships between age and RV-C infections. Neutralizing antibodies specific for RV-A and RV-C (three types each) were determined using a novel PCR-based assay. Data were pooled from 14 study cohorts in the United States, Finland, and Australia, and mixed-effects logistic regression was used to identify factors related to the proportion of RV-C versus RV-A detection.Measurements and Main Results: In COAST, RV-A and RV-C infections were similarly common in infancy, whereas RV-C was detected much less often than RV-A during both respiratory illnesses and scheduled surveillance visits (P < 0.001, χ2) in older children. The prevalence of neutralizing antibodies to RV-A or RV-C types was low (5-27%) at the age of 2 years, but by the age of 16 years, RV-C seropositivity was more prevalent (78% vs. 18% for RV-A; P < 0.0001). In the pooled analysis, the RV-C to RV-A detection ratio during illnesses was significantly related to age (P < 0.0001), CDHR3 genotype (P < 0.05), and wheezing illnesses (P < 0.05). Furthermore, certain RV types (e.g., C2, C11, A78, and A12) were consistently more virulent and prevalent over time.Conclusions: Knowledge of prevalent RV types, antibody responses, and populations at risk based on age and genetics may guide the development of vaccines or other novel therapies against this important respiratory pathogen.

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.

Upper Airway Cell Transcriptomics Identify a Major New Immunological Phenotype with Strong Clinical Correlates in Young Children with Acute Wheezing.

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 IRF7hi versus IRF7lo 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 IRF7lo 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 IRF7hi versus IRF7lo phenotypes with associated differences in clinical phenotypes.

Spatially explicit analyses of environmental and health data to determine past, emerging and future threats to child health.

BACKGROUND: Dire forecasts predict that an increasingly hostile environment globally will increase the threats to human health. Infants and young children are especially at risk because children are particularly vulnerable to climate-related stressors. The childhood diseases most affected, the breadth and magnitude of future health problems and the time frame over which these problems will manifest remain largely unknown. OBJECTIVES: To review the possibility that spacially explicit analyses can be used to determine how climate change has affected children's health to date and whether these analyses can be used for future projections. METHODS: As an example of whether these objectives can be achieved, all available Australian environmental and health databases were reviewed. RESULTS: Environmental and health data in Australia have been collected for up to 30 years for the same spatial areas at 'Statistical Area level 1' (SA1) scale. SA1s are defined as having a population of between 200 and 800 people and collectively they cover the whole of Australia without gaps or overlap. Although the SA1 environmental and health data have been collected separately, they can be merged to allow detailed statistical analyses that can determine how climate change has affected the health of children. CONCLUSIONS: The availability of environmental and health datasets that share the same precise spatial coordinates provides a pathway whereby past and emerging effects on child health can be measured and predicted into the future. Given that the future health and well-being of children is one of society's greatest concerns, this information is urgently needed.

Glutathione S-Transferase Genotype Protects against In Utero Tobacco-linked Lung Function Deficits.

Rationale:In utero tobacco exposure is associated with reduced lung function from infancy. Antioxidant enzymes from the glutathione S-transferase (GST) family may protect against these lung function deficits.Objectives: To assess the long-term effect of in utero smoke exposure on lung function into adulthood, and to assess whether GSTT1 and GSTM1 active genotypes have long-term protective effects on lung function.Methods: In this longitudinal study based on a general population (n = 253), lung function was measured during infancy and at 6, 11, 18, and 24 years. GSTM1 and GSTT1 genotype was analyzed in a subgroup (n = 179). Lung function was assessed longitudinally from 6 to 24 years (n = 199).Measurements and Main Results: Exposure to maternal in utero tobacco was associated with lower FEV1 and FVC longitudinally from 6 to 24 years (mean difference, -3.87% predicted, P = 0.021; -3.35% predicted, P = 0.035, respectively). Among those homozygous for the GSTM1-null genotype, in utero tobacco exposure was associated with lower FEV1 and FVC compared with those with no in utero tobacco exposure (mean difference, -6.2% predicted, P = 0.01; -4.7% predicted, P = 0.043, respectively). For those with GSTM1 active genotype, there was no difference in lung function whether exposed to maternal in utero tobacco or not. In utero tobacco exposure was associated with deficits in lung function among those with both GSTT1-null and GSTT1-active genotypes.Conclusions: Certain GST genotypes may have protective effects against the long-term deficits in lung function associated with in utero tobacco exposure. This offers potential preventative targets in antioxidant pathways for at-risk infants of smoking mothers.

Progressive increase of FcεRI expression across several PBMC subsets is associated with atopy and atopic asthma within school-aged children.

BACKGROUND: Antigen-specific IgE binds the Fcε receptor I (FcεRI) expressed on several types of immune cells, including dendritic cells (DCs). Activation of FcεRI on DCs in atopics has been shown to modulate immune responses that potentially contribute to asthma development. However, the extent to which DC subsets differ in FcεRI expression between atopic children with or without asthma is currently not clear. This study aimed to analyse the expression of FcεRI on peripheral blood mononuclear cells (PBMCs) from atopic children with and without asthma, and non-atopic/non-asthmatic age-matched healthy controls. METHODS: We performed multiparameter flow cytometry on PBMC from 391 children across three community cohorts and one clinical cohort based in Western Australia. RESULTS: We confirmed expression of FcεRI on basophils, monocytes, plasmacytoid and conventional DCs, with higher proportions of all cell populations expressing FcεRI in atopic compared to non-atopic children. Further, we observed that levels of FcεRI expression were elevated across plasmacytoid and conventional DC as well as basophils in atopic asthmatic compared to atopic non-asthmatic children also after adjusting for serum IgE levels. CONCLUSION: Our data suggest that the expression pattern of FcεRI on DC and basophils differentiates asthmatic from non-asthmatic atopic children. Given the significant immune modulatory effects observed as a consequence of FcεRI expression, this altered expression pattern is likely to contribute to asthma pathology in children.

Pediatric asthma: An unmet need for more effective, focused treatments.

BACKGROUND: Despite remarkable advances in our understanding of asthma, there are still several unmet needs associated with the management of pediatric asthma. METHODS: A two-day, face-to-face meeting was held in London, United Kingdom, on October 28 and 29, 2017, involving a group of international expert clinicians and scientists in asthma management to discuss the challenges and unmet needs that remain to be addressed in pediatric asthma. RESULTS: These unmet needs include a lack of clinical efficacy and safety evidence, and limited availability of non-steroid-based alternative therapies in patients <6 years of age. An increased focus on children is needed in the context of clinical practice guidelines for asthma; current pediatric practice relies mostly on extrapolations from adult recommendations. Furthermore, no uniform definition of pediatric asthma exists, which hampers timely and robust diagnosis of the condition in affected patients. CONCLUSIONS: There is a need for a uniform definition of pediatric asthma, clearly distinguishable from adult asthma. Furthermore, guidelines which provide specific treatment recommendations for the management of pediatric asthma are also needed. Clinical trials and real-world evidence studies assessing anti-immunoglobulin E (IgE) therapies and other monoclonal antibodies in children <6 years of age with asthma may provide further information regarding the most appropriate treatment options in these vulnerable patients. Early intervention with anti-IgE and non-steroid-based alternative therapies may delay disease progression, leading to improved clinical outcomes.

Association between pro-inflammatory alleles and allergic phenotypes in Xhosa adolescents.

BACKGROUND: Significant differences exist in the prevalence, spectrum, and severity of allergic diseases between developing and developed countries and between subpopulations within single countries. These discrepancies likely result from a complex interaction between genetic and environmental factors. However, the precise nature of the contribution of ethnicity to genetic differences in the predisposition to allergic disease is not yet fully understood. In particular, there is a paucity of literature regarding the genetic determinants of allergic disease in people of black African origin with little or no genetic admixture. OBJECTIVE: We aimed to analyze associations between 27 single nucleotide polymorphisms (SNPs) and allergy phenotypes in the local Xhosa population. METHODS: A convenience sample of 213 Xhosa teenagers was enrolled at a local high school. Phenotypic data were collected in the form of a symptom questionnaire, skin prick tests for common food and aeroallergens, total serum IgE, and IgE to Ascaris lumbricoides. In addition, genotyping was performed to establish the prevalence of putative pro-inflammatory alleles. RESULTS: We demonstrated several significant associations between polymorphisms and allergy phenotypes. In particular, 2 polymorphisms in the IL-10 gene (IL10 -592A>C and IL10 -1082A>G) and 1 in the IL-4 gene (IL4 -589C>T) showed multiple associations with allergic sensitization and asthma phenotypes. Other polymorphisms, across a multitude of genes with discrepant functions, showed less consistent associations. CONCLUSION: This study represents an important first step in genotype/phenotype association in this population. Further research is required to confirm or refute our findings.

Gene-based analysis of regulatory variants identifies 4 putative novel asthma risk genes related to nucleotide synthesis and signaling.

BACKGROUND: Hundreds of genetic variants are thought to contribute to variation in asthma risk by modulating gene expression. Methods that increase the power of genome-wide association studies (GWASs) to identify risk-associated variants are needed. OBJECTIVE: We sought to develop a method that aggregates the evidence for association with disease risk across expression quantitative trait loci (eQTLs) of a gene and use this approach to identify asthma risk genes. METHODS: We developed a gene-based test and software package called EUGENE that (1) is applicable to GWAS summary statistics; (2) considers both cis- and trans-eQTLs; (3) incorporates eQTLs identified in different tissues; and (4) uses simulations to account for multiple testing. We applied this approach to 2 published asthma GWASs (combined n = 46,044) and used mouse studies to provide initial functional insights into 2 genes with novel genetic associations. RESULTS: We tested the association between asthma and 17,190 genes that were found to have cis- and/or trans-eQTLs across 16 published eQTL studies. At an empirical FDR of 5%, 48 genes were associated with asthma risk. Of these, for 37, the association was driven by eQTLs located in established risk loci for allergic disease, including 6 genes not previously implicated in disease cause (eg, LIMS1, TINF2, and SAFB). The remaining 11 significant genes represent potential novel genetic associations with asthma. The association with 4 of these replicated in an independent GWAS: B4GALT3, USMG5, P2RY13, and P2RY14, which are genes involved in nucleotide synthesis or nucleotide-dependent cell activation. In mouse studies, P2ry13 and P2ry14-purinergic receptors activated by adenosine 5-diphosphate and UDP-sugars, respectively-were upregulated after allergen challenge, notably in airway epithelial cells, eosinophils, and neutrophils. Intranasal exposure with receptor agonists induced the release of IL-33 and subsequent eosinophil infiltration into the lungs. CONCLUSION: We identified novel associations between asthma and eQTLs for 4 genes related to nucleotide synthesis/signaling and demonstrated the power of gene-based analyses of GWASs.

Immunodominant T-Cell Epitopes in the VP1 Capsid Protein of Rhinovirus Species A and C.

Rhinovirus (RV) species A and C are the most frequent cause of respiratory viral illness worldwide, and RV-C has been linked to more severe exacerbations of asthma in young children. Little is known about the immune responses to the different RV species, although studies comparing IgG1 antibody titers found impaired antibody responses to RV-C. Therefore, the aim of this study was to assess whether T-cell immunity to RV-C is similarly impaired. We measured T-cell proliferation to overlapping synthetic peptides covering the entire VP1 capsid protein of an RV-A and RV-C genotype for 20 healthy adult donors. Human leukocyte antigen (HLA) was typed in all the donors in order to investigate possible associations between the HLA type and RV peptide recognition. Total and specific IgG1 antibody titers to the VP1 proteins of both RV-A and RV-C were also measured to examine associations between the antibody and T-cell responses. We identified T-cell epitopes that are specific to and representative of each RV-A and RV-C species. These epitopes stimulated CD4+-specific T-cell proliferation, with similar magnitudes of response for both RV species. All the donors, independent of their HLA-DR or -DQ type, were able to recognize the immunodominant RV-A and -C regions of VP1. Furthermore, the presence or absence of specific antibody titers was not related to changes in T-cell recognition. Our results indicate a dissociation between the antibody and T-cell responses to rhinoviruses. The species-representative T-cell epitopes identified in this study are valuable tools for future studies investigating T-cell responses to the different RV species. IMPORTANCE: Rhinoviruses (RVs) are mostly associated with the common cold and asthma exacerbations, although their contributions to most upper and lower respiratory tract diseases have increasingly been reported. Species C (RV-C) has been associated with more frequent and severe asthma exacerbations in young children and, along with RV-A, is the most clinically relevant species. Little is known about how our immune system responds to rhinoviruses, and there are limited tools to study specific adaptive immunity against each rhinovirus species. In this study, we identified immunodominant T-cell epitopes of the VP1 proteins of RV-A and RV-C, which are representative of each species. The study found that T-cell responses to RV-A and RV-C were of similar magnitudes, in contrast with previous findings showing RV-C-specific antibody responses were low. These findings will provide the basis for future studies on the immune response to rhinoviruses and can help elucidate the mechanisms of severity of rhinovirus-induced infections.

Rhinovirus C is associated with wheezing and rhinovirus A is associated with pneumonia in hospitalized children in Morocco.

Human rhinovirus (RV) is commonly associated with severe acute lower respiratory infections (ALRI) in children. We aimed to describe the distribution of RV species and associations between RV species and clinical features in children hospitalized with clinically severe pneumonia (CSP) in Morocco. Nasopharyngeal aspirates (NPAs) were collected from 700 children, 2-59 months of age, admitted with CSP to the Hôpital d'Enfants de Rabat in Morocco. At least one respiratory virus was identified in 92% of children, of which RV was the most common (53%). PCR assays, sequencing, and phylogenetic tree analyses were carried out on 183 RV-positive NPAs to determine RV species and genotypes. Of 157 successfully genotyped NPAs, 60 (38.2%) were RV-A, 8 (5.1%) were RV-B, and 89 (56.7%) were RV-C. Wheezing and cyanosis were more common in RV-C-positive than RV-A-positive children (80.9% vs. 56.7%; P = 0.001 for wheezing and 10.1% vs. 0%; P = 0.011 for cyanosis). Physician's discharge diagnosis of pneumonia was more frequent among RV-A-positive (40.0%) than RV-C-positive children (20.2%; P = 0.009). RV-A and RV-C showed distinct seasonal patterns. Our findings suggest that RV-C is associated with wheezing illness while RV-A is associated with pneumonia. J. Med. Virol. 89:582-588, 2017. © 2016 Wiley Periodicals, Inc.

Infant lung function predicts asthma persistence and remission in young adults.

BACKGROUND AND OBJECTIVE: Asthma in adults is associated with a persistent reduction in lung function from childhood, but this link has not been assessed back to infancy. Reduced infant lung function (ILF), a measure of antenatal and infant lung growth, is associated with asthma into adolescence. Our aim was to assess whether this link persists into adulthood and whether ILF can predict the remission of asthma symptoms in young adults. METHODS: The study cohort was an unselected full-term birth cohort of 253 subjects enrolled antenatally with lung function assessments at 1, 6 and 12 months (maximum expiratory flow at functional residual capacity, V'maxFRC), and 6, 11, 18 and 24 years (spirometry) of age. RESULTS: Infants with V'maxFRC in the lowest quartile at 1 month had an OR of 5.1 (95% CI: 2-13, P = 0.001) for asthma at 24 years. Subjects with asthma at 24 years had a mean V'maxFRC at 1 month of 69% predicted (95% CI: 48-90%) versus 110% (95% CI: 101-119%) in non-asthmatic patients (P = 0.001). Subjects with current versus resolved asthma symptoms at 24 years had a mean V'maxFRC at 1 month of 69% predicted (95% CI: 53-84%) versus 105% (88-123%), respectively (P = 0.003). Subjects with current asthma at 24 years had persistently lower lung function from infancy with a mean reduction of 16.2% (95% CI: 8.1-24.3%, P < 0.0001). CONCLUSION: Reduced lung function in early infancy is predictive of persistent asthma in young adults and a persistent reduction in lung function, suggesting abnormal lung development and growth in utero or very early in life.

Clinical characteristics of eosinophilic asthma exacerbations.

BACKGROUND AND OBJECTIVE: Airway eosinophilia is associated with an increased risk of asthma exacerbations; however, the impact on the severity of exacerbations is largely unknown. We describe the sputum inflammatory phenotype during asthma exacerbation and correlate it with severity and treatment response. METHODS: Patients presenting to hospital with an asthma exacerbation were recruited during a 12-month period and followed up after 4 weeks. Induced sputum was collected at both visits. Patients underwent spirometry, arterial blood gas analysis, fractional exhaled nitric oxide analysis, white blood cell counts and a screening for common respiratory viruses and bacteria. An eosinophilic exacerbation (EE) was defined as having sputum eosinophils ≥ 3% and a non-eosinophilic exacerbation as < 3% (NEE). RESULTS: A total of 47 patients were enrolled; 37 (79%) had successful sputum induction at baseline, of whom 43% had sputum eosinophils ≥3% (EE). Patients with EE had a significantly lower forced expiratory volume in 1 s (FEV1 ) % predicted (70.8%, P = 0.03) than patients with NEE (83.6%). Furthermore, EE patients were more likely to require supplemental oxygen during admission (63% vs 14%, P = 0.002). The prevalence of respiratory viruses was the same in EE and NEE patients (44% vs 52%, P = 0.60), as was bacterial infection (6% vs 14%, P = 0.44). Fractional expiratory nitric oxide (FeNO) correlated with sputum %-eosinophils (ρ = 0.57, P < 0.001), and predicted airway eosinophilia with a sensitivity of 86% and a specificity of 70%. CONCLUSION: Our findings suggest that eosinophilic asthma exacerbations may be clinically more severe than NEEs, supporting the identification of these higher risk patients for specific interventions.

Knowledge, attitudes and practices regarding tuberculosis care among health workers in Southern Mozambique.

BACKGROUND: Tuberculosis (TB) control is more likely to be achieved if the level of knowledge regarding TB is increased among health workers managing high-risk groups. No formal assessments regarding knowledge, attitudes and practises of health workers about TB have been published for Mozambique, a country facing challenges in the fight against TB, with a fragile health system and considerable work overload of health personnel. The main objective of the study was to determine the level of knowledge, identify attitudes and assess practices regarding TB care and control among health care workers of the district of Manhiça. METHODS: A descriptive cross-sectional study was performed through the use of a specifically designed Knowledge, Attitudes and Practices (KAP) questionnaire in the district of Manhiça, a high tuberculosis and HIV burden rural area in Southern Mozambique. In this district, 14 health care facilities service a population of approximately 160,000 people. The questionnaire took 30-45 min to administer with external assistance not permitted. The survey contained 79 questions pertaining to four different areas: demographics, TB knowledge, attitudes and practices. RESULTS: The study sample included 170 health care workers. The average knowledge score was 14.89 points (SD = 3.61) out of a total possible 26 points. Less than 30% of respondents had heard of Xpert MTB/RIF®. Seventy per cent agreed there was stigma associated with TB and 48.2% believed this stigma was greater than that associated with HIV. The average practice score was 3.2 out of 9 points (35.6%, SD = 2.4). CONCLUSION: Health care worker's knowledge gaps identified in this study may result in substandard patient care. Specific deficiencies in understanding existed in terms of paediatric TB and Xpert MTB/RIF® testing. The present study provides impetus for tailored TB education among health care workers from a high TB burden rural area in Southern Mozambique.

Rhinovirus-C detection in children presenting with acute respiratory infection to hospital in Brazil.

Human rhinovirus (RV) is a common cause of acute respiratory infection (ARI) in children. We aimed to characterize the clinical and demographic features associated with different RV species detected in children attending hospital with ARI, from low-income families in North-east Brazil. Nasopharyngeal aspirates were collected from 630 children <5 years with ARI. Clinical diagnosis and disease severity were also recorded. Samples were analyzed by multiplex PCR for 18 viral and atypical bacterial pathogens; RV positive samples underwent partial sequencing to determine species and type. RV was the fourth commonest pathogen accounting for 18.7% of pathogens detected. RV was commonly detected in children with bronchiolitis, pneumonia, and asthma/episodic viral wheeze (EVW). Species and type were assigned in 112 cases (73% RV-A; 27% RV-C; 0% RV-B). Generally, there were no differences in clinical or demographic characteristics between those infected with RV-A and RV-C. However, in children with asthma/EVW, RV-C was detected relatively more frequently than RV-A (23% vs. 5%; P = 0.04). Our findings highlight RV as a potentially important pathogen in this setting. Generally, clinical and demographic features were similar in children in whom RV-A and C species were detected. However, RV-C was more frequently found in children with asthma/EVW than RV-A.