Our data strengthen the role of rhinovirus-associated wheeze as an important risk factor for recurrent wheezing and asthma in young first-time wheezing children. Prospective randomized trials on the efficacy of corticosteroids in rhinovirus-associated early wheezing are warranted. (ClinicalTrials.gov number, NCT 00494624).

Neuroendocrine cell hyperplasia of infancy (NEHI) has recently been described as an obstructive airway disease that affects infants aged 1-24 months, and presents typically with tachypnoea, crackles and hypoxia. The pathogenesis of the disease is unknown. We describe the clinical course of nine infants with radiologically and histologically confirmed NEHI. Host or environmental factors were not associated with the disease development. All infants with lung function tests demonstrated findings consistent with severe irreversible peripheral airway obstruction, assessed with whole body plethysmography (6/6) or the rapid thoracoabdominal compression technique (5/5). While the symptoms abated in all infants, six infants developed a non-atopic asthma during the follow-up. Systemic or inhaled corticosteroid treatment did not affect the duration of the symptoms. NEHI may mimic severe asthma and thus this entity should be taken into account when evaluating infants with chronic respiratory symptoms.

We read with interest the paper by BERGAUER et al. [1] on innate immune responses to viral infection in paediatric asthma. The paper confirms previous reports on impaired interferon responses in stable asthma [2-4], but describes a hyperactive interferon production during asthma exacerbations associated with rhinovirus infection. The authors conclude that, despite impaired immune condition at stable state, the ability to upregulate type I interferons during the acute phase is preserved in asthmatic children. However, what is lacking from this study is the information on interferon production during acute rhinovirus infection in an age-matched group of non-asthmatics. Thus, how can it be conclusively excluded that the production of interferon is impaired during the rhinovirus-induced acute phase of asthma in the absence of such a comparative control group? A study which examined nasal washes of children during acute episodes of wheezing or rhinitis, reported lower levels of IFN-λ in children with wheezing than in those with acute rhinitis, even if the differences were not statistically significant [5]. The fact that asthmatic patients, once infected, have more severe manifestations of the infectious diseases [6] could possibly suggest an impaired response also in the acute phase, but conclusive data are lacking.

Maternal prenatal psychological symptoms are associated with child health outcomes, e.g., atopic diseases. Altered prenatal functioning of the immune system is a potential mechanism linking maternal symptoms with child health. Research on prenatal distress and cytokines is warranted. The study population comprised consecutive N = 139 women from a general population-based FinnBrain Birth Cohort Study. Standardized questionnaires for depressive, overall anxiety, and pregnancy-related anxiety symptoms were used. Serum concentrations of selected cytokines were analyzed using Multiplex bead arrays from samples drawn at the gestational week 24. The concentrations of T helper (Th)2-related interleukins (IL)-9 and IL-13 and Th1-related IL-12 correlated positively with prenatal depressive and overall anxiety symptom scores (p values, range 0.011-0.029). Higher interferon (IFN)-γ/IL-4 ratio (p = 0.039) and Th2-related IL-5 (p = 0.007) concentration correlated positively with depressive symptoms. Pregnancy-related anxiety score correlated positively with IL-12 (p = 0.041), IL-13 (p = 0.025), and anti-inflammatory IL-10 (p = 0.048) concentrations. IL-6 and TNF-α concentrations were unrelated to prenatal symptoms. As a novel finding, we observed positive correlations between concentrations of potentially proallergenic cytokines and maternal prenatal psychological symptoms. Different symptom measures may yield distinct cytokine responses. This provides hypotheses for studies on mechanisms bridging prenatal stress and child health.

Increased activity of matrix metalloproteinase (MMP)-9 is associated with the development of bronchopulmonary dysplasia (BPD) in newborn infants, but the role of MMP-9 in the pathophysiology of BPD is unclear. We have shown that perinatal expression of interleukin-1 beta (IL-1 beta) in the lung is sufficient to cause a BPD-like illness in infant mice. To study the hypothesis that MMP-9 is an important downstream mediator in IL-1 beta-induced lung injury in the newborn, we compared the effects of IL-1 beta on fetal and postnatal lung inflammation and development in transgenic mice with regulatable pulmonary overexpression of human mature IL-1 beta with wild-type (IL-1 beta/MMP-9(+/+)) or null (IL-1 beta/MMP-9(-/-)) MMP-9 loci. IL-1 beta increased the expression of MMP-9 mRNA and amount of MMP-9 protein in the lungs of MMP-9(+/+) mice. IL-1 beta/MMP-9(-/-) mice had fewer neutrophils but more macrophages in the lungs than did IL-1 beta/MMP-9(+/+) mice. MMP-9 deficiency increased pulmonary cell death and macrophage clearance of dying cells in IL-1 beta-expressing mice. IL-1 beta/MMP-9(-/-) mice had more severe alveolar hypoplasia than IL-1 beta/MMP-9(+/+) mice, implying that IL-1 beta-induced lung disease was worsened in the absence of MMP-9. These results suggest that MMP-9 activity in the inflamed neonatal lung protects the lung against injury.