Editor’s ChoiceThe Editor takes a closer look at some of this month’s articles

Risk factors for allergic disease: one new, one old.Whenever there is a public discussion about allergy one of the first questions is what has caused the dramaticincrease in the incidence of allergic disease in the last five decades? The community of allergy epidemiologistshas come up with many suggestions, although no definitive answers. In this issue a new twist is given to theparacetamol story; intrauterine ingestion, and a new risk factor is introduced; lack of sleep. We have reportedbefore on the increasing interest in the link between paracetamol ingestion in infancy and the development ofallergic disease [1, 2]. In this issue Eyers et al (pp. 481–488), have undertaken a meta-analysis of studies thathave investigated the relationship between paracetamol exposure during pregnancy and the development ofallergic disease in the offspring. They have found a modest (1.21), but significant increase in risk. This adds tothe weight of evidence implicating paracetamol in causing allergic disease and there is now an imperative needfor a large prospective study to provide a definitive answer to whether this association is causal. Theimplications of this study are further explored in an excellent editorial by Shyamali Dharmage.

An intriguing and novel observation has come out of a largeepidemiological study of sleep patterns in children in China.Zhang and colleagues (pp. 547–555), have for the first timeinvestigated the relationship between sleep duration andallergic sensitization in a large population of normal bodyweight twins. They found a striking association between shortsleep duration and sensitization with a good dose responseeffect. This observation needs to be replicated and explainedalthough the trivial explanation of sleep disturbance as aresult of having allergic disease was excluded.

Exhaled nitric oxide (eNO): a good negative predictor?Exhaled nitric oxide has the great advantage for a biomarker in being relativelyeasy to measure and has been promoted as a useful tool to guide management,although the evidence that eNO can fulfil this role has so far not been supportedin real life studies [3]. Further light is shed on the potential role of eNO in thediagnosis and management of allergic disease in a population based study by Yaoet al (pp. 556–564). They related the eNO concentration to clinical andimmunological characteristics of 1717 children aged 5–18 years. eNO was ageand weight dependent. They found a strong link between raised eNO and allergicsensitization (not necessarily with symptoms of allergic disease). When theyadjusted for sensitization there was a link between raised eNO and rhinitis, but notasthma consistent with its lack of specificity and sensitivity for this condition.Nonetheless an eNO of less than 28ppb was associated with a 97.7% negative predictive value for asthma, supporting other evidence thatin mild to moderate asthma a low eNO suggests the diagnosis of asthma is unlikely. Whether this is robust enough to be helpful in theclinic requires an appropriately designed prospective study.

New pathways in asthma: pituitary adenylate cyclase-activating-polypeptide (PACAP).PACAP was identified over twenty years and has been shown to have a wide array of pharmacologicalactions [4]. However its role in asthma has not been studied in any detail. PACAP is a member of thevasoactive intestinal peptide (VIP)-secretin-growth hormone releasing hormone-glucagon superfamily ofneurogenic mediators. There are three receptors for PACAP, two shared with VIP and one, PAC1-R, specificto the peptide. In a novel study Lauenstein et al (pp. 592–601), have investigated the potential role of thispathway in the mouse ovalbumin challenge asthma model using gene deletion of the receptor and a specificagonist. They found that the pathway was anti-inflammatory, but had no effect on lung function. When thereceptor was deleted the inflammation in response to allergen challenge was more florid and the receptoragonist maxadilan had anti-inflammatory effects. These effects were possibly mediated by modulatingdendritic cell function. Perhaps this pathway could explain the link between sleep and allergy noted above!

References1 Farquhar H, Stewart A, Mitchell E et al. The role of paracetamol in the pathogenesis of asthma. Clin Exp Allergy 2010; 40:32–41.2 Wickens K, Beasley R, Town I et al. The effects of early and late paracetamol exposure on asthma and atopy: a birth cohort. Clin Exp Allergy 2011;

41:399–408.3 Gibson PG. Using fractional exhaled nitric oxide to guide asthma therapy: design and methodological issues for ASthma TReatment ALgorithm

studies. Clin Exp Allergy 2009; 39:478–90.4 Vaudry D, Falluel-Morel A, Bourgault S et al. Pituitary adenylate cyclase-activating polypeptide and its receptors: 20 years after the discovery.

Pharmacol Rev 2009; 61:283–357.

Cover illustration: Asthma in the elderly is understudied. This aspect of asthma is addressed in the April issue by an original article by Pereira Vale et al, acommentary by Olivenstein and Hamid and a review article by Jones et al. (Photo: r Serena Corporate Photography).

�EC This logo highlights the Editor’s Choice articles on the cover and the first page of each of the articles.

Shanchun Zhang (author)

Clinical & Experimental Allergy Volume 41, April 2011

Sally Eyers (author)

Tsung-Chieh Yao (author)

Hans Lauenstein (author)