Asthma now affects one child in seven in the United Kingdom. Most cases (95%) of childhood asthma are associated with atopy, the immunoglobulin E (IgE)-mediated familial syndrome of allergic asthma, eczema and rhinitis. Segregation analysis has consistently suggested the presence of major genes influencing atopy and IgE levels, with the expectation that these genes may be identified by positional cloning or the examination of candidate genes. Here we report the results of a genome-wide search for linkage to one qualitative and four quantitative traits associated with allergic (atopic) asthma. We have identified six potential linkages (P<0.001), five of which are to quantitative traits. Monte Carlo simulations show that 1.6 false-positive linkages at this level of significance would be expected from the data. One linkage, to chromosome 11q13, has been established previously. Three of the new loci show evidence of linkage to a second panel of families, in which maternal effects and pleiotropy of linked phenotypes are seen. The results demonstrate the extent and the complexity of the genetic predisposition to asthma.

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The relationship between reduced pulmonary function in early life and persistent wheeze (PW) in school-aged children remains uncertain. In this study, VmaxFRC was assessed at 1 month of age, and the presence of wheeze up to 11 years of age was prospectively identified. At 11 years of age, airway responsiveness (AR) to inhaled histamine and atopy were assessed. Recent wheeze at 11 years of age was associated with a reduced mean z score for VmaxFRC at 1 month of age (-0.41 [SD 0.91], n = 31) compared with no recent wheeze (0.04 [SD 1.00], n = 153, p = 0.03). Wheeze between 4 and 6 years that persisted at 11 years (PW) was most prevalent among those with reduced VmaxFRC at 1 month and atopy aged 11 years (p = 0.002) or reduced VmaxFRC and increased AR aged 11 years (p = 0.015). When all factors were considered, reduced VmaxFRC at 1 month (p = 0.03) and increased AR aged 11 years (p < 0.001) were independently associated with PW (n = 17) compared with other outcomes (n = 129). Reduced airway function present in early infancy is associated with PW at 11 years of age, and this relationship is independent of the effect of increased AR and atopy in childhood.

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...