A new and potentially more pathogenic group of human rhinovirus (HRV), group C (HRVC), has recently been discovered. We hypothesised that HRVC would be present in children with acute asthma and cause more severe attacks than other viruses or HRV groups.Children with acute asthma (n5128; age 2-16 yrs) were recruited on presentation to an emergency department. Asthma exacerbation severity was assessed, and respiratory viruses and HRV strains were identified in a nasal aspirate.The majority of the children studied had moderate-to-severe asthma (85.2%) and 98.9% were admitted to hospital. HRV was detected in 87.5% and other respiratory viruses in 14.8% of children, most of whom also had HRV. HRVC was present in the majority of children with acute asthma (59.4%) and associated with more severe asthma. Children with HRVC (n576) had higher asthma severity scores than children whose HRV infection was HRVA or HRVB only (n534; p50.018), and all other children (n550; p50.016). Of the 19 children with a non-HRV virus, 13 had HRV co-infections, seven of these being HRVC.HRVC accounts for the majority of asthma attacks in children presenting to hospital and causes more severe attacks than previously known HRV groups and other viruses.

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 ¼ 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 ¼ 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 ¼ 0.004) and within 12 months (34.6% vs. 17.0%; P ¼ 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 ¼ 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. Keywords: human rhinovirus; acute wheezing illnesses; hospital admissions; pediatricsNumerous studies have demonstrated that wheezing associated with certain viruses in early childhood is an independent risk factor for subsequent wheezing illnesses and the development of asthma (1-7). Most earlier reports focused on respiratory syncytial virus (RSV) bronchiolitis in infancy and recurrent wheezing (1-3, 8, 9), but more recent research has shown that wheezing episodes due to human rhinovirus (HRV) have a stronger association than RSV with further wheezing episodes and asthma in early childhood (4,5,7,9).Previously, HRV-A and -B (10-12) were the only known HRV species, but improved virological detection methods using polymerase chain reaction (PCR) and sequencing (13-15) have revealed another species of rhinovirus, C (16,17). A number of studies have shown that HRV-C is the most common HRV species associated with acute asthma attacks severe enough to result in children presenting to hospital (18-21), and further studies have shown that it also causes more severe asthma attacks than other rhinoviruses (22) and all other viruses (23).These studies raise the issue of whether HRV-C also influences subsequent acute wheezing e...

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Early recognition of aggressive localised scleroderma and appropriate referral is imperative for a good outcome.

Aim: To review multiorgan involvement and management in children with Down syndrome (DS).

The filamin A gene (FLNA) on Xq28 encodes the filamin A protein. Mutation in FLNA causes a wide spectrum of disease including skeletal dysplasia, neuronal migration abnormality, cardiovascular malformation, intellectual disability and intestinal obstruction. Recently, childhood-onset interstitial lung disease associated with a range of FLNA mutations has been recognised and reported. We document our personal experience of this emerging disorder and compile a comprehensive overview of clinical features and molecular changes in all identifiable published cases. Reviewing the emerging dataset, we underline this unanticipated phenotypic consequence of pathogenic FLNA mutation-associated pulmonary disease. Conclusion: From the emerging data, we suggest that while reviewing complex cases with a sustained oxygen requirement against a clincial background of cardiac concerns or intestinal obstruction to have a high index of suspicion for FLNA related pathology and to instigate early MRI brain scan and FLNA mutation analysis. What is Known: • FLNA gene on Xq28 encodes the filamin A protein and mutation therein is associated with variable phenotypes depending on its nature of mutation. • Loss-of-function mutation of filamin A is associated with X-linked inherited form of periventricular nodular heterotopia with or without epilepsy with most individuals affected being female. There is a recently recognised associated respiratory phenotype. What is New: • The respiratory phenotype in the form of childhood interstitial lung disease is a recently recognised clinical consequence of loss-of-function FLNA mutation. • Rare male patients with loss-of-function FLNA mutation-associated lung disease with residual protein function can survive into infancy with a severe form of the phenotype.

Respiratory virus infections account for a significant proportion of acute admissions to the paediatric intensive care unit (PICU). Recent studies have shown that rhinoviruses (RV) are the most frequent virus detected in severe cases of acute respiratory illnesses (ARI) admitted to a PICU. The aim of this study was to determine the prevalence of different viruses, in particular RV species, in children with ARI admitted to a tertiary PICU. Nasopharyngeal aspirates (NPA) from 229 children admitted to PICU with an ARI were analysed. RV was the most common virus detected, being present in 94 (41.0%) of samples examined, followed by respiratory syncytial virus (RSV) which was identified in 50 (21.8%) samples. A subsection analysis of cases with residual sample available of sufficient quality to allow for RV species typing showed that overall, the percentage of PICU admissions for each RV species was 22.3% for RV-C, 17.5% for RV-A and 1.7% for RV-B. This study demonstrated that RV is the most frequent virus identified in children admitted to a tertiary PICU with an ARI and RV-C is the most common RV species detected. Importantly, in the children admitted to PICU with an ARI, RV-C was by itself as common a pathogen as RSV.

The higher total anti-HRV antibody titers of asthmatic children and their higher anti-HRV-A and -B titers show their development of a heightened antiviral immune response. The low species-specific HRV-C titers found in all groups, even when the virus was found, point to a different and possibly less efficacious immune response to this species.