Asthmatic individuals are more susceptible to respiratory viral infection. It has been proposed that this is due to an impaired antiviral response of the airway epithelial cells (AECs), in particular a reduced interferon (IFN)-β and –λ response to infection with Rhinovirus. However, this has not been investigated for the common paediatric respiratory viruses; respiratory syncytial virus (RSV) or human metapneumovirus (hMPV). Here we established submerged cultures of nasal (N) and tracheal (T) AECs from children undergoing elective surgery. Respiratory health was determined by questionnaire and atopic status from measurement of specific IgE to locally common aeroallergens. Submerged primary cultures of NECs and TECs were infected with RSV or hMPV at both high and low viral doses. IFN production, inflammatory cytokine expression and viral replication were quantified. NECs, but not TECs, from children with wheeze and/or atopy produced less IFN-β, but not IFN-λ, in response to RSV infection; this was associated with higher viral shedding. However, IFN regulated factors IRF-7, Mx-1 and CXCL-10, and inflammatory cytokines were not differentially regulated. NECs and TECs from children with wheeze and/or atopy demonstrated no impairment of the IFN response (β or λ) to hMPV infection. However, more hMPV was shed from these cells. From these data we can conclude that AECs from children with wheeze and/or atopy do not have an intrinsic defect in the production of IFN-β or –λ in response to viral infection. Rather, virus-specific differences are important in determining risk for asthma. Higher viral shedding associated with wheeze and/or atopy was not necessarily influenced by the production of IFNs, suggesting that IFN-independent mechanisms are important in viral defense.