Kai-Håkon Carlsen

Dietary prevention of allergic diseases in infants and small children.

Because of scientific fraud four trials have been excluded from the original Cochrane meta‐analysis on formulas containing hydrolyzed protein for prevention of allergy and food intolerance in infants. Unlike the conclusions of the revised Cochrane review the export group set up by the Section on Paediatrics, European Academy of Allergology and Clinical Immunology (SP‐EAACI) do not find that the exclusion of the four trials demands a change of the previous recommendations regarding primary dietary prevention of allergic diseases. Ideally, recommendations on primary dietary prevention should be based only on the results of randomized and quasi‐randomized trials (selection criteria in the Cochrane review). However, regarding breastfeeding randomization is unethical, Therefore, in the development of recommendations on dietary primary prevention, high‐quality systematic reviews of high‐quality cohort studies should be included in the evidence base. The study type combined with assessment of the methodological quality determines the level of evidence. In view of some methodological concerns in the Cochrane meta‐analysis, particularly regarding definitions and diagnostic criteria for outcome measures and inclusion of non peer‐reviewed studies/reports, a revision of the Cochrane analysis may seem warranted. Based on analysis of published peer‐reviewed observational and interventional studies the results still indicate that breastfeeding is highly recommended for all infants irrespective of atopic heredity. A dietary regimen is effective in the prevention of allergic diseases in high‐risk infants, particularly in early infancy regarding food allergy and eczema. The most effective dietary regimen is exclusively breastfeeding for at least 4–6 months or, in absence of breast milk, formulas with documented reduced allergenicity for at least the first 4 months, combined with avoidance of solid food and cows milk for the first 4 months.The role of primary prevention of allergic diseases has been a matter of debate for the last 40 years. In order to shed some light on this issue, a group of experts of the Section of Pediatrics EAACI reviewed critically the existing literature on the subject. An analysis of published peer-reviewed observational and interventional studies was performed following the statements of evidence as defined by WHO. The results of the analysis indicate that breastfeeding is highly recommended for all infants irrespective of atopic heredity. A dietary regimen is unequivocally effective in the prevention of allergic diseases in high-risk children. In these patients breastfeeding combined with avoidance of solid food and cows milk for at least 4-6 months is the most effective preventive regimen. In the absence of breast milk, formulas with documented reduced allergenicity for at least 4-6 months should be used.

Practical guide to skin prick tests in allergy to aeroallergens

To cite this article: Bousquet J, Heinzerling L, Bachert C, Papadopoulos NG, Bousquet PJ, Burney PG, Canonica GW, Carlsen KH, Cox L, Haahtela T, Lodrup Carlsen KC, Price D, Samolinski B, Simons FER, Wickman M, Annesi‐Maesano I, Baena‐Cagnani CE, Bergmann KC, Bindslev‐Jensen C, Casale TB, Chiriac A, Cruz AA, Dubakiene R, Durham SR, Fokkens WJ, Gerth‐van‐Wijk R, Kalayci O, Kowalski ML, Mari A, Mullol J, Nazamova‐Baranova L, O’Hehir RE, Ohta K, Panzner P, Passalacqua G, Ring J, Rogala B, Romano A, Ryan D, Schmid‐Grendelmeier P, Todo‐Bom A, Valenta R, Woehrl S, Yusuf OM, Zuberbier T, Demoly P. Practical guide to skin prick tests in allergy to aeroallergens. Allergy 2012; 67: 18–24.

Dietary prevention of allergic diseases in infants and small children. Part III: Critical review of published peer-reviewed observational and interventional studies and final recommendations

The role of primary prevention of allergic diseases has been a matter of debate for the last 40 years. In order to shed some light on this issue, a group of experts of the Section of Pediatrics EAACI reviewed critically the existing literature on the subject. An analysis of published peer‐reviewed observational and interventional studies was performed following the statements of evidence as defined by WHO. The results of the analysis indicate that breastfeeding is highly recommended for all infants irrespective of atopic heredity. A dietary regimen is unequivocally effective in the prevention of allergic diseases in high‐risk children. In these patients breastfeeding combined with avoidance of solid food and cows milk for at least 4–6 months is the most effective preventive regimen. In the absence of breast milk, formulas with documented reduced allergenicity for at least 4–6 months should be used.

In utero exposure to cigarette smoking influences lung function at birth

To avoid the possible confounding effects of postnatal exposure to tobacco smoke, we investigated possible effects of uterine tobacco smoke (UTS) exposure upon infant lung function shortly after birth. Infants with no major disease, in one maternity ward in Oslo, Norway, participating in a cohort study established in 1992/1993, were included in the present study (n=803). Exposure information, assessed as maternal active and passive smoking during pregnancy and other personal and environmental factors, was obtained by questionnaire. Tidal flow-volume (TFV) loops (n=802) and compliance (Crs) and resistance (Rrs) of the respiratory system (n=663) were measured at a mean age of 2.7 days. In girls, the TFV ratio (time to reach peak expiratory flow to total expiratory time (tPEF/tE)), and Crs were significantly lower with active as well as passive maternal smoking compared to nonexposure to UTS. Respiratory rate and Rrs were not significantly influenced by UTS exposure. However, in linear regression analysis adjusted for confounding factors (including respiratory rate), tPEF/tE and Crs, but not Rrs, were related to maternal active but not passive daily smoking. One daily cigarette corresponded to a change in tPEF/tE of -0.0021 (95% confidence interval (95% CI) -0.0040 to -0.0002) and a change in Crs of -0.026 mL x cmH2O (95% CI -0.045 to -0.007 mL x cmH2O). The decrease was 0.023 and 0.29, respectively, in infants of an average smoker. Maternal smoking during pregnancy adversely affected tidal flow-volume ratios in healthy newborn babies, as well as the compliance of the respiratory system in girls, independently of the reduced body size also resulting from maternal smoking.

Does Pet Ownership in Infancy Lead to Asthma or Allergy at School Age? Pooled Analysis of Individual Participant Data from 11 European Birth Cohorts

Objective To examine the associations between pet keeping in early childhood and asthma and allergies in children aged 6–10 years. Design Pooled analysis of individual participant data of 11 prospective European birth cohorts that recruited a total of over 22,000 children in the 1990s. Exposure definition Ownership of only cats, dogs, birds, rodents, or cats/dogs combined during the first 2 years of life. Outcome definition Current asthma (primary outcome), allergic asthma, allergic rhinitis and allergic sensitization during 6–10 years of age. Data synthesis Three-step approach: (i) Common definition of outcome and exposure variables across cohorts; (ii) calculation of adjusted effect estimates for each cohort; (iii) pooling of effect estimates by using random effects meta-analysis models. Results We found no association between furry and feathered pet keeping early in life and asthma in school age. For example, the odds ratio for asthma comparing cat ownership with “no pets” (10 studies, 11489 participants) was 1.00 (95% confidence interval 0.78 to 1.28) (I2 = 9%; p = 0.36). The odds ratio for asthma comparing dog ownership with “no pets” (9 studies, 11433 participants) was 0.77 (0.58 to 1.03) (I2 = 0%, p = 0.89). Owning both cat(s) and dog(s) compared to “no pets” resulted in an odds ratio of 1.04 (0.59 to 1.84) (I2 = 33%, p = 0.18). Similarly, for allergic asthma and for allergic rhinitis we did not find associations regarding any type of pet ownership early in life. However, we found some evidence for an association between ownership of furry pets during the first 2 years of life and reduced likelihood of becoming sensitized to aero-allergens. Conclusions Pet ownership in early life did not appear to either increase or reduce the risk of asthma or allergic rhinitis symptoms in children aged 6–10. Advice from health care practitioners to avoid or to specifically acquire pets for primary prevention of asthma or allergic rhinitis in children should not be given.

Validity of physical activity monitors in adults participating in free-living activities

Background For a given subject, time in moderate to very vigorous intensity physical activity (MVPA) varies substantially among physical activity monitors. Objective In the present study, the primary objective, whether time in MVPA recorded with SenseWear Pro2 Armband (Armband; BodyMedia, Pittsburgh, Pennsylvania, USA), ActiGraph (7164, LLC, Fort Walton Beach, Florida, USA), ikcal (Teltronic AG, Biberist, Switzerland) and ActiReg (PreMed AS, Oslo, Norway) is different compared with indirect calorimetry, was determined. The secondary objective, whether these activity monitors estimate energy expenditure differently compared with indirect calorimetry, was also determined. Material and methods The activity monitors and a portable oxygen analyser were worn by 14 men and 6 women for 120 min doing a variety of activities of different intensities. Resting metabolic rate was measured with indirect calorimetry. The cutoff points defining moderate, vigorous and very vigorous intensity were three, six and nine times resting metabolic rate. Results Time in MVPA was overestimated by 2.9% and 2.5% by Armband and ActiGraph, respectively, and was underestimated by 11.6% and 98.7% by ikcal and ActiReg, respectively. ActiReg (p = 0.004) and ActiGraph (p = 0.007) underestimated energy expenditure in MVPA, and all monitors underestimated total energy expenditure (by 5% to 21%). Conclusions Recorded time in MVPA and energy expenditure varies substantially among physical activity monitors. Thus, when comparing physical activity level among studies, it is essential to know the type of physical activity monitor being used.

Asthma drug adherence in a long term clinical trial

AIM To measure drug adherence in children with mild asthma receiving long term prophylactic treatment. METHODS Double blind randomised placebo controlled trial. Patients received inhaled budesonide 100 μg or 200 μg daily, or placebo for 27 months. All participants were asked to inhale medication or placebo from two different Turbuhalers (morning and evening) during the study. A total of 122 children (80 boys, 42 girls) aged 7–16 years with mild asthma (mean FEV1 103.7% of predicted) were included in the trial. Drug adherence was assessed by counting the number of remaining doses in the inhaler when study medication was returned at six month intervals. RESULTS A statistically significant and continuing decrease in measured drug adherence was found from three to nine months and then to 27 months, reaching mean values of 40.6% and 46.9% for inhaled morning and evening medication respectively. Drug adherence declined more rapidly in the placebo group (compared to active treatment); this difference became significant after two years of treatment. Children aged 9 years or less had better drug adherence during the entire study period, but the difference was only significant for the first three months of the study. Measured drug adherence was significantly higher for evening medication compared to morning medication for all study intervals after nine months. CONCLUSION Measured drug adherence diminishes significantly when treating children with mild asthma in a long term trial. This emphasises the importance of monitoring compliance in clinical trials.

Asthma in every fifth child in Oslo, Norway: a 10‐year follow up of a birth cohort study*

Background:  The western worlds increase in childhood asthma is suggested to level off. We aimed to investigate asthma prevalence in 10‐year‐old children within the prospective birth cohort Environment and Childhood Asthma (ECA) Study in Oslo established in 1992/1993.

Viruses and bacteria in acute asthma exacerbations--a GA² LEN-DARE systematic review

To cite this article: Papadopoulos NG, Christodoulou I, Rohde G, Agache I, Almqvist C, Bruno A, Bonini S, Bont L, Bossios A, Bousquet J, Braido F, Brusselle G, Canonica GW, Carlsen KH, Chanez P, Fokkens WJ, Garcia‐Garcia M, Gjomarkaj M, Haahtela T, Holgate ST, Johnston SL, Konstantinou G, Kowalski M, Lewandowska‐Polak A, Lødrup‐Carlsen K, Mäkelä M, Malkusova I, Mullol J, Nieto A, Eller E, Ozdemir C, Panzner P, Popov T, Psarras S, Roumpedaki E, Rukhadze M, Stipic‐Markovic A, Todo Bom A, Toskala E, van Cauwenberge P, van Drunen C, Watelet JB, Xatzipsalti M, Xepapadaki P, Zuberbier T. Viruses and bacteria in acute asthma exacerbations – A GA2LEN‐DARE systematic review. Allergy 2011; 66: 458–468.

Severity of obstructive airways disease by age 2 years predicts asthma at 10 years of age

Background: Predicting school-age asthma from obstructive airways disease (OAD) in early life is difficult, even when parental and children’s atopic manifestations are taken into consideration. Objective: To assess if the severity of OAD in the first 2 years of life predicts asthma at 10 years of age. Methods: From a nested case control study within the Environment and Childhood Asthma study, 233 2-year-old subjects with recurrent (⩾2 episodes) bronchial obstruction (rBO+) and 216 subjects without bronchial obstruction (rBO−) underwent clinical examination, parental interview, treadmill test and metacholine bronchial hyperresponsiveness (BHR) measurement at 10 years. A severity score at 2 years was calculated by frequency, persistence of bronchial obstruction and hospital admissions because of OAD. Main outcomes: Current asthma at 10 years (asthma with symptoms and/or asthma medication during the past year and/or positive treadmill test). Secondary outcome was metacholine BHR at 10 years. Results: Compared with rBO− subjects, adjusted odds ratio (95% CI) of current asthma among rBO+ was 7.9 (4.1, 15.3), and among rBO+ with a severity score of >5, 20.2 (9.9, 41.3). In receiver operated characteristic analysis, positive and negative predictive values demonstrated the applicability and value of the score, with an optimal cut-off at severity score 5. Children with severity score >5 had severe BHR more often (PD20 metacholine <1 μmol) than children with a lower or 0 score (p = 0.0041). Conclusion: Using a simple scoring system, a high severity score of OAD by 2 years of age is a strong risk factor for, and may predict, current asthma at 10 years of age.