Background: Regular use of inhaled beta(2)-agonists has been associated with a paradoxical loss of asthma control and a deterioration of airway hyper-responsiveness, but the underlying mechanism is unknown. The neurotrophin brain-derived neurotrophic factor (BDNF) has recently been identified as a mediator of airway hyper-responsiveness in asthma.Methods: Eighteen patients with mild allergic asthma who did not use any regular antiasthmatic therapy inhaled the long-acting beta(2)-agonist salmeterol for 2 weeks followed by 2 weeks of combination therapy with salmeterol and the corticosteroid fluticasone. Airway responsiveness to histamine and BDNF concentrations in blood were assessed prior to entry, after 14 days of salmeterol therapy and after 14 days of combination therapy. In a separate experiment, salmeterol effects on BDNF release by human peripheral blood mononuclear cells were assessed.Results: Monotherapy with salmeterol significantly increased BDNF concentrations in serum and platelets. This increase was abolished by the addition of fluticasone to the treatment. The findings were confirmed in vitro: salmeterol increased the release of BDNF by mononuclear cells, and this was inhibited by co-incubation with fluticasone. Increased BDNF concentrations in serum and platelets correlated with the deterioration of airway hyper-responsiveness following salmeterol monotherapy. In contrast, there was no association between beta(2)-receptor polymorphisms and changes in airway responsiveness.Conclusion: Increased BDNF concentrations may underly the adverse effects of salmeterol monotherapy on airway responsiveness in asthma.Trial registration number: NCT00736801.

Neonatal lupus erythematosus (NLE) develops in foetuses of mothers with Ro/SSA and La/SSB antibodies and may include foetal atrioventricular block and dermatologic manifestations. In this study, we investigated postnatal Ro and La IgG, IgA and IgM antibody levels up to 1 year of age in 32 children born to Ro/SSA positive mothers. Antibody levels were correlated with NLE manifestations, and the role of breast feeding in transfer of autoantibodies from mother to child was evaluated. Ro52, Ro60 and La IgG antibodies all transferred from the mothers to their foetus in utero and were present in the infant at birth as detected by enzyme-linked immunosorbent assay using recombinant antigens and a synthetic peptide. A significant decrease in Ro52, Ro60 and La IgG autoantibody levels of the infants was observed from birth to 4–5 weeks of age (P < 0.05, P < 0.05 and P < 0.01). Ro- and La-specific IgA and IgM antibodies were detected in the serum from a subset of mothers. However, Ro- and La-specific IgA and IgM antibody levels were low or non-detectable in children raised both with and without breastfeeding. Furthermore, NLE skin lesions developed independently of breastfeeding. Our findings support a role for placental materno-foetal transfer of IgG autoantibodies in the pathogenesis of NLE and indicate that refraining from breastfeeding does not protect from NLE skin involvement.

Aim: To determine instantaneous cardiac variability responses to increased carbon dioxide (CO2) during quiet sleep in infants who may be at risk for the Sudden Infant Death syndrome (SIDS). Methods: The cardiac rate variability before, during and after a CO2 challenge was examined in 41 infants who had experienced an apparent life-threatening event (ALTE) and 41 gender- and age-matched control infants. Results: The ALTE infants responded to CO2 breathing with a significant increase in R-R intervals, i.e. decreases in heart rate, compared to the controls (45.1% increase in R-R intervals vs. 41.4%; p=0.005). The differences between ALTE infants and controls depended primarily on the boys' responses.Conclusion: ALTE infants, particularly ALTE boys, have an autonomic dysfunction-lower sympathetic stimulation and/or inhibited vagal withdrawal when stressed with CO2. The outcome might provide clues to the mechanisms underlying the cardiovascular processes contributing to the terminal event in SIDS.

Heart rate variability (HRV) is often used as an index of sympatho‐vagal balance. A decreased HRV has been observed in patients with central hypoventilation and in infants who have later succumbed to sudden infant death syndrome (SIDS). The aim of the present study was to investigate whether HRV is altered in infants with apparent life‐threatening events (ALTE), a group with an increased risk of SIDS. Fifty infants with ALTE were compared with 50 age‐ and sex‐matched controls. ECG was recorded overnight in all infants. Two sequences of RR intervals free of artefacts were selected from each sleep state and spectral analysis of RR variability was performed. The mean and SD of RR and the low (LFPow) and high (HFPow) frequency power were analysed. In active sleep (AS) the LF/HF ratio was lower in ALTE infants, but no differences were seen in either the LFPow or the HFPow. In quiet sleep (QS), however, ALTE infants had higher SD‐RR (p= 0.006), greater HFPow (p= 0.02) and VLFPow (very low frequency power, p= 0.02) than the control infants. The same results were seen when the two sleep states were combined for analysis, ALTE infants had higher SD‐RR (p= 0.004), HFPow (p= 0.006) and VLFPow (p= 0.04). Conclusion: The different HRV pattern in ALTE infants compared to healthy controls suggests an altered autonomic control.

Sympatheticovagal imbalance causing episodes of severe bradycardia has been suggested as a cause of apparent life threatening events (ALTEs). The autonomic control of the heart rate in 18 infants with ALTEs and 12 controls was evaluated by the head upright tilt test. Five different heart rate response profiles (compared with the baseline) were observed during the tilt: (1) increase followed by a decrease and return to baseline; (2) sustained increase; (3) decrease followed by an increase and return to baseline; (4) sustained decrease; (5) no change. Eighty eight per cent of controls responded with heart rate increase followed by decrease or sustained increase compared with 55% of infants with an ALTE; a significantly greater proportion of infants with ALTEs than controls responded with heart rate decrease or no change in rate (45% v 8%). This altered reaction during a head upright tilt test may be an expression of an underlying autonomic dysfunction in infants who have experienced an ALTE.