Modelling trajectories of parentally reported and physician-confirmed atopic dermatitis in a birth cohort study.

BACKGROUND: In a population-based birth cohort, we aimed to identify longitudinal trajectories of atopic dermatitis (AD) during childhood using data from different sources (validated questionnaires and healthcare records). We investigated the impact of different AD definitions on such trajectories and their relationships with various risk factors. METHODS: Of the 1184 children born into the study, 1083 had information on current AD for at least three follow-ups from birth to age 11 years and were included in the analysis for parentally reported AD (PRAD). Data were transcribed from healthcare records for 916 of 1184 children for the analysis of doctor-diagnosed AD (DDAD). We also derived a composite definition of AD (CDAD) (at least two of the following: PRAD, DDAD, current use of AD treatment). Using latent class analysis (LCA), we determined longitudinal profiles of AD using the three definitions. Filaggrin (FLG) genotype data were available for 803 white participants. RESULTS: For PRAD, LCA identified four AD classes ('no AD', 'persistent', 'early-onset remitting' and 'late-onset'). For DDAD and CDAD, the optimal number of phenotypes was three ('no AD', 'persistent' and 'early-onset remitting'). Although AD classes at population level appeared similar in different models, a considerable proportion of children (n = 485, 45%) moved between classes. The association with FLG genotype, atopic diseases and early-life risk factors was inconsistent across different definitions, but the association with oral food challenge-confirmed peanut allergy was similar, with a nine- to 11-fold increase among children in the persistent AD class. In a CDAD model, compared with the early-onset remitting class, those with persistent AD were significantly more likely to have (at age 3 years) moderate/severe AD, polysensitization and current wheeze, and were less likely to have been breastfed. CONCLUSIONS: Standardized composite definitions of AD may help to define AD cases with more precision and identify more consistent long-term trajectories.

Acidification and hypoxia interactively affect metabolism in embryos, but not larvae, of the coastal forage fish Menidia menidia.

Ocean acidification is occurring in conjunction with warming and deoxygenation as a result of anthropogenic greenhouse gas emissions. Multistressor experiments are critically needed to better understand the sensitivity of marine organisms to these concurrent changes. Growth and survival responses to acidification have been documented for many marine species, but studies that explore underlying physiological mechanisms of carbon dioxide (CO2) sensitivity are less common. We investigated oxygen consumption rates as proxies for metabolic responses in embryos and newly hatched larvae of an estuarine forage fish (Atlantic silverside, Menidia menidia) to factorial combinations of CO2×temperature or CO2×oxygen. Metabolic rates of embryos and larvae significantly increased with temperature, but partial pressure of CO2 (PCO2 ) alone did not affect metabolic rates in any experiment. However, there was a significant interaction between PCO2  and partial pressure of oxygen (PO2 ) in embryos, because metabolic rates were unaffected by PO2  level at ambient PCO2 , but decreased with declining PO2  under elevated PCO2 For larvae, however, PCO2  and PO2  had no significant effect on metabolic rates. Our findings suggest high individual variability in metabolic responses to high PCO2 , perhaps owing to parental effects and time of spawning. We conclude that early life metabolism is largely resilient to elevated PCO2  in this species, but that acidification likely influences energetic responses and thus vulnerability to hypoxia.

Different definitions of atopic dermatitis: impact on prevalence estimates and associated risk factors.

BACKGROUND: There is no objective test that can unequivocally confirm the diagnosis of atopic dermatitis (AD), and no uniform clinical definition. OBJECTIVES: To investigate to what extent operational definitions of AD cause fluctuation in the prevalence estimates and the associated risk factors. METHODS: We first reviewed the operational definitions of AD used in the literature. We then tested the impact of the choice of the most common definitions of 'cases' and 'controls' on AD prevalence estimates and associated risk factors (including filaggrin mutations) among children aged 5 years in two population-based birth cohorts: the Manchester Asthma and Allergy Study (MAAS) and Asthma in Ashford. Model performance was measured by the percentage of children within an area of clinical indecision (defined as having a posterior probability of AD between 25% and 60%). RESULTS: We identified 59 different definitions of AD across 45 reviewed studies. Of those, we chose four common 'case' definitions and two definitions of 'controls'. The prevalence estimates using different case definitions ranged between 22% and 33% in MAAS, and between 12% and 22% in Ashford. The area of clinical indecision ranged from 32% to 44% in MAAS and from 9% to 29% in Ashford. Depending on the case definition used, the associations with filaggrin mutations varied, with odds ratios (95% confidence intervals) ranging from 1·8 (1·1-2·9) to 2·2 (1·3-3·7) in MAAS and 1·7 (0·8-3·7) to 2·3 (1·2-4·5) in Ashford. Associations with filaggrin mutations also differed when using the same 'case' definition but different definitions of 'controls'. CONCLUSIONS: Use of different definitions of AD results in substantial differences in prevalence estimates, the performance of prediction models and association with risk factors. What's already known about this topic? There is no objective test that can unequivocally confirm the diagnosis of atopic dermatitis (AD) and no uniform clinical definition. This results in different definitions utilized in AD studies, raising concerns on the generalizability of the results and comparability across different studies. What does this study add? This study has shown that different definitions of 'cases' and 'controls' have major impacts upon prevalence estimates and associations with risk factors, including genetics, in two population-based birth cohorts. These findings suggest the importance of developing a consensus on AD definitions of both 'controls' and 'cases' to minimize biases in studies.

Blood eosinophils as a marker of likely corticosteroid response in children with preschool wheeze: time for an eosinophil guided clinical trial?

Childhood wheezing is common particularly in children under the age of 6 years and in this age group is generally referred to as preschool wheezing. Particular diagnostic and treatment uncertainties exist in these young children due to the difficulty in obtaining objective evidence of reversible airways narrowing and inflammation. A diagnosis of asthma depends on the presence of relevant clinical signs and symptoms and the demonstration of reversible airways narrowing on lung function testing, which is difficult to perform in young children. Few treatments are available and inhaled corticosteroids are the recommended preventer treatment in most international asthma guidelines. There is, however, considerable controversy about its effectiveness in children with preschool wheeze and a corticosteroid responder phenotype has not been established. These diagnostic and treatment uncertainties in conjunction with the knowledge of corticosteroid side effects, in particular the reduction of growth velocity, have resulted in a variable approach to inhaled corticosteroid prescribing by medical practitioners and a reluctance in carers to regularly administer the treatment. Identifying children who are likely responders to corticosteroid therapy would be a major benefit in the management of this condition. Eosinophils have emerged as a promising biomarker of corticosteroid responsive airways disease, and evaluation of this biomarker in sputum has successfully been employed to direct management in adults with asthma. Obtaining sputum from young children is time consuming and difficult, and it is hard to justify more invasive procedures such as a bronchoscopy in young children routinely. Recently, in children, interest has shifted to assessing the value of less invasive biomarkers of likely corticosteroid response and the biomarker 'blood eosinophils' has emerged as an attractive candidate. The aim of this review was to summarize the evidence for blood eosinophils as a predictive biomarker for corticosteroid responsive disease with a particular focus on the difficult area of preschool wheeze.

Impact of rhinitis on asthma severity in school-age children.

BACKGROUND: In a population-based sample of school-age children, we investigated factors associated with rhinitis, and differences between allergic and nonallergic rhinitis. Amongst children with asthma, we explored the association between rhinitis and asthma severity. METHODS: Children participating in a birth cohort study (n = 906) were reviewed at age 8 years. Asthma was defined as at least two of the following three features: physician-diagnosed asthma, currently using asthma medication and current wheeze. We measured lung function (plethysmography and spirometry) and airway hyper-reactivity (AHR; methacholine challenge). RESULTS: In the analysis adjusted for the presence of asthma, children with rhinitis had significantly higher AHR (P = 0.001). Maternal smoking and absence of breastfeeding were stronger predictors of nonallergic rhinitis, whereas current wheeze and eczema were stronger predictors of allergic rhinitis. Amongst asthmatics (n = 159), when compared to 76 children without rhinitis, those with rhinitis (n = 83) were 2.89-fold (95% CI 1.41-5.91) more likely to experience frequent attacks of wheezing, 3.44-fold (1.19-9.94) more likely to experience severe attacks of wheezing limiting speech, 10.14-fold (1.27-81.21) more likely to have frequent visits to their doctor because of asthma and nine-fold (1.11-72.83) more likely to miss school. Reported use of intranasal corticosteroids resulted in a numerically small, but consistent reduction in risk, rendering the associations between rhinitis and asthma severity nonsignificant. CONCLUSION: We observed differences in risk factors and severity between allergic and nonallergic rhinitis. In children with asthma, rhinitis had adverse impact on asthma severity. The use of intranasal corticosteroids resulted in a small, but consistent reduction in the risk.

Treatment and secondary prevention effects of the probiotics Lactobacillus paracasei or Bifidobacterium lactis on early infant eczema: randomized controlled trial with follow-up until age 3 years.

BACKGROUND: Allergic disease has been associated with altered intestinal microbiota. Therefore, probiotics have been suggested as a potential treatment for eczema. OBJECTIVE: We investigated whether dietary supplementation of infants with eczema at age 3-6 months with Lactobacillus paracasei CNCM I-2116 or Bifidobacterium lactis CNCM I-3446 had a treatment effect or altered allergic disease progression. METHODS: Primary outcome included eczema severity (SCORing Atopic Dermatitis, SCORAD) 3 months post-randomization. Secondary: SCORAD (other visits); infant dermatitis quality of life (IDQoL); gastrointestinal permeability; urinary eosinophilic protein X; allergen-sensitization; allergic symptoms (age 12, 18, 36 months). A total of 208 infants aged 3-6 months with physician-diagnosed eczema were recruited; 137/208 (SCORAD ≥ 10, consuming ≥ 200 mL standard formula/day) were randomized to daily supplements containing L. paracasei or B. lactis or placebo for a 3-month period, while receiving extensively hydrolysed whey-formula (dairy-free diet). There were two open observational groups, one group exclusively breastfed (n = 22) and the other, standard formula-fed (n = 49). TRIAL NUMBER: ISRCTN41490500. RESULTS: Eczema severity decreased significantly over time in all groups. No significant difference was observed between randomized groups after 12-week treatment-period (SCORAD-score pre-/post-intervention: B. lactis 25.9 [95% CI: 22.8-29.2] to 12.8 [9.4-16.6]; L. paracasei 25.4 [22.1-29] to 12.5 [9.2-16.4]; placebo 26.9 [23.4-30.6] to 11.8 [9.6-14.3]; P = 0.7). Results were similar when analysis was controlled for allergen-sensitization, or when only sensitized infants were analysed. No differences were found for secondary outcomes. No difference was observed in SCORAD-score between randomized and observational groups. CONCLUSION AND CLINICAL RELEVANCE: We found no benefit from supplementation with B. lactis or L. paracasei in the treatment of eczema, when given as an adjunct to basic topical treatment, and no effect on the progression of allergic disease from age 1 to 3 years.

Body mass index in young children and allergic disease: gender differences in a longitudinal study.

BACKGROUND: The increase in allergic diseases has occurred in parallel with the obesity epidemic, suggesting a possible association. OBJECTIVE: We investigated the relationship of body mass index (BMI) up to age 8 years with allergic disease within a birth cohort. METHODS: Children were followed from birth and were reviewed at age 3, 5 and 8 years (n=731; male 406). Parents completed questionnaires; children were weighed, measured, skin prick tested and examined. RESULTS: Increasing BMI at 3, 5 and 8 years increased the risk of current wheezing at the corresponding age (odds ratio [95% confidence interval] per standardized deviation score: age 3, 1.26 [1.04-1.53], P=0.02; age 5, 1.33 [1.06-1.67], P=0.02; age 8, 1.27 [1.0-1.62], P=0.05). The effect of BMI on wheeze at age 8 years differed between boys and girls, with a significant positive association in girls, but not in boys (P=0.04 for interaction). The effect of BMI at earlier ages on current or subsequent wheezing did not differ significantly between genders. Increasing BMI significantly increased the risk of physician-diagnosed eczema at age 5 (1.23 [1.04-1.47], P=0.02) and 8 (1.23 [1.03-1.45], P=0.02), with a significant interaction between gender and BMI at age 5 (P=0.04). There was no association between BMI and sensitization. Being overweight at age 3 years was significantly associated with late-onset wheeze (3.83 [1.51-9.75], P=0.005), persistent wheeze (4.15 [2.07-8.32], P<0.001) and persistent eczema (1.79 [1.03-3.13], P=0.04) in both boys and girls. CONCLUSIONS: Being overweight is associated with an increased risk of allergic disease in childhood. However, the strength of the association varies with the gender, age and atopic phenotype.

Dietary antioxidant intake, allergic sensitization and allergic diseases in young children.

BACKGROUND: Allergic diseases have risen in prevalence over recent decades. The aetiology remains unclear but is likely to be a result of changing lifestyle and/or environment. A reduction in antioxidant intake, consequent to reduced intake of fresh fruits and vegetables, has been suggested as a possible cause. OBJECTIVE: To investigate whether dietary antioxidant intake at age 5 was related to atopy at 5 and 8 years of age amongst children in an unselected birth cohort. METHODS: Children were followed from birth. Parents completed a validated respiratory questionnaire and children were skin prick tested at 5 and 8 years of age. Serum IgE levels were measured at age 5. At age 5, antioxidant intake was assessed using a semi-quantitative food frequency questionnaire (FFQ). A nutrient analysis program computed nutrient intake, and frequency counts of foods high in the antioxidant vitamins A, C and E were assessed. RESULTS: Eight hundred and sixty-one children completed both the respiratory and FFQ. Beta-carotene intake was associated with reduced risk of allergic sensitization at age 5 [0.80 (0.68-0.93)] and 8 [0.81 (0.70-0.94)]. In addition, beta-carotene intake was negatively associated with total IgE levels (P = 0.002). Vitamin E intake was associated with an increased risk of allergic sensitization [1.19 (1.02-1.39)], only at age 5. There was no association between antioxidant intakes and wheeze or eczema. CONCLUSION: Increased beta-carotene intake was associated with a reduced risk of allergic sensitization and lower IgE levels, in 5- and 8-year-old children. Dietary antioxidants may play a role in the development of allergic sensitization.

Finding protein-protein interaction patterns by contact map matching.

We propose a novel method for defining patterns of contacts present in protein-protein complexes. A new use of the traditional contact maps (more frequently used for representation of the intra-chain contacts) is presented for analysis of inter-chain contacts. Using an algorithm based on image processing techniques, we can compare protein-protein interaction maps and also obtain a dissimilarity score between them. The same algorithm used to compare the maps can align the contacts of all the complexes and be helpful in the determination of a pattern of conserved interactions at the interfaces. We present an example for the application of this method by analyzing the pattern of interaction of bovine pancreatic trypsin inhibitors and trypsins, chymotrypsins, a thrombin, a matriptase, and a kallikrein - all classified as serine proteases. We found 20 contacts conserved in trypsins and chymotrypsins and 3 specific ones are present in all the serine protease complexes studied. The method was able to identify important contacts for the protein family studied and the results are in agreement with the literature.

Finding protein-protein interaction patterns by contact map matching

We propose a novel method for defining patterns of contacts present in protein-protein complexes. A new use of the traditional contact maps (more frequently used for representation of the intra-chain contacts) is presented for analysis of inter-chain contacts. Using an algorithm based on image processing techniques, we can compare protein-protein interaction maps and also obtain a dissimilarity score between them. The same algorithm used to compare the maps can align the contacts of all the complexes and be helpful in the determination of a pattern of conserved interactions at the interfaces. We present an example for the application of this method by analyzing the pattern of interaction of bovine pancreatic trypsin inhibitors and trypsins, chymotrypsins, a thrombin, a matriptase, and a kallikrein - all classified as serine proteases. We found 20 contacts conserved in trypsins and chymotrypsins and 3 specific ones are present in all the serine protease complexes studied. The method was able to identify important contacts for the protein family studied and the results are in agreement with the literature.

Dietary intake in sensitized children with recurrent wheeze and healthy controls: a nested case-control study.

BACKGROUND: The rising prevalence of asthma and allergic disease remains unexplained. Several risk factors have been implicated including diet, in particular poly-unsaturated fats and antioxidant intake. METHODS: A nested case-control study comparing the dietary intake of sensitized children with recurrent wheeze (age 3-5 years) and nonsensitized children who had never wheezed was carried out within an unselected population-based cohort. Cases and controls were matched for age, sex, parental atopy, indoor allergen exposure and pet ownership. Dietary intake was assessed using a validated semi-quantitative food frequency questionnaire and nutrient analysis program. RESULTS: Thirty-seven case-control pairs (23 male, mean age 4.4 years) participated. Daily total polyunsaturated fat intake was significantly higher in sensitized wheezers (g/day, geometric mean, 95% confidence intervals: 7.1, 6.4-7.9) compared with nonsensitized nonwheezy children (5.6, 5.0-6.3, P = 0.003). Daily omega-3 and omega-6 fat intakes were not significantly different between the two groups. No significant differences were found in intake of any antioxidant or antioxidant cofactors between the groups. CONCLUSIONS: Young sensitized wheezy children had a significantly higher total polyunsaturated fat intake compared with nonsensitized nonwheezy children. However, we were unable to distinguish a significant difference in specific poly-unsaturated fat intakes. Otherwise the children in both groups had a very similar nutritional intake.

Effect of childhood eczema and asthma on parental sleep and well-being: a prospective comparative study.

BACKGROUND: The psychological impact of childhood atopic eczema on parents and carers is poorly quantified. Objectives To compare the impact of caring for a child with atopic eczema vs. asthma on parents' sleep and well-being. METHODS: Ninety-two parents of 55 children who had moderate to severe atopic eczema or asthma took part in this prospective, questionnaire-based study. It was conducted at regional eczema and asthma outpatient clinics within a U.K. tertiary paediatric hospital. The main outcome measures were the number and duration of parents' sleep disturbances, as well as their anxiety and depression scores. RESULTS: Mothers caring for children with atopic eczema lost a median of 39 min of sleep per night and fathers lost 45 min sleep per night. This compared with a median of 0 min sleep lost by parents who had children with asthma (P < 0.001). These differences were independent of the age of the children, and whether the child came from a single-parent or two-parent family. There was a direct correlation between the severity of sleep disturbance and the level of maternal anxiety (rho = 0.58; P = 0.002) and depression (rho = 0.73; P < 0.001), as well as the level of paternal anxiety (rho = 0.59; P = 0.01). CONCLUSIONS: Compared with looking after a child with chronic asthma, caring for a child with chronic atopic eczema was associated with greater parental sleep disturbances. Disruption to parental sleep correlated with anxiety levels and, in the case of mothers, depression scores.

Study of modifiable risk factors for asthma exacerbations: virus infection and allergen exposure increase the risk of asthma hospital admissions in children.

BACKGROUND: Asthma exacerbation is the most common cause of hospital admission in children. A study was undertaken to investigate the importance of allergen exposure in sensitised individuals in combination with viral infections and other potentially modifiable risk factors precipitating asthma hospital admission in children. METHODS: Eighty four children aged 3-17 years admitted to hospital over a 1 year period with an acute asthma exacerbation (AA) were matched for age and sex with two control groups: stable asthmatics (SA) and children admitted to hospital with non-respiratory conditions (IC). Risk factors were assessed by questionnaires and determination of allergen sensitisation, home allergen exposure, pollen exposure, and respiratory virus infection. RESULTS: Several non-modifiable factors (atopy, duration of asthma) were associated with increased risk. Among the modifiable factors, pet ownership, housing characteristics, and parental smoking did not differ between the groups. Regular inhaled corticosteroid treatment was significantly less common in the AA group than in the SA group (OR 0.2, 95% CI 0.1 to 0.6; p = 0.002). A significantly higher proportion of the AA group were virus infected (44%) and sensitised and highly exposed to sensitising allergen (76%) compared with the SA (18% and 48%) and IC groups (17% and 28%; both p<0.001). In a multiple conditional logistic regression (AA v SA), allergen sensitisation and exposure or virus detection alone were no longer independently associated with hospital admission. However, the combination of virus detection and sensitisation with high allergen exposure substantially increased the risk of admission to hospital (OR 19.4, 95% CI 3.7 to 101.5, p<0.001). CONCLUSIONS: Natural virus infection and real life allergen exposure in allergic asthmatic children increase the risk of hospital admission. Strategies for preventing exacerbations will need to address these factors.

Itching for progress.

The study of itch remains a neglected field, with a number of barriers limiting satisfactory therapy in the majority of instances. We review recent advances, focusing on the identification of the neural pathways, distinct from pain, that signal itch; methods to measure itch as scratch in humans; and the identification of a role for H4 receptors in mediating itch (in the mouse).

Fecal microbiota in sensitized wheezy and non-sensitized non-wheezy children: a nested case-control study.

BACKGROUND: It has been suggested that intestinal microbiota of allergic and non-allergic children differs in composition, and that microbiota-immune system interactions may predispose children to develop sensitization. Previous studies have examined fecal microbiota of allergic children with atopic dermatitis, but little is known about that of atopic wheezy children. OBJECTIVE: To investigate the composition of the fecal microbiota of young sensitized wheezy and non-sensitized non-wheezy children, using molecular methods. METHODS: Within the context of a prospective birth cohort, we carried out a nested case-control study of sensitized wheezy children (cases) and non-sensitized non-wheezy controls. Cases and controls were matched for age, sex, parental atopy, allergen exposure, and pet ownership. We evaluated the composition of fecal microbiota by nucleic acid-based methods (PCR combined with denaturing gradient gel electrophoresis and quantification of bifidobacteria by fluorescent in situ hybridization). RESULTS: Thirty-three case-control pairs (mean age 4.4 years) provided stool samples. Comparison of total bacterial community profiles showed that each child had a unique fecal microbiota (mean Dice's similarity coefficient 22%, range 3.3-60.8%). There was no difference between the groups in prevalence of Lactic Acid bacteria (12/33 vs. 11/33, P=0.8) or bifidobacteria (30/33 vs. 31/33, P=1.00, cases vs. controls). The bifidobacterial species detected were similar in both groups. The percentage of bifidobacteria in total fecal microflora was no different between cases (median 1.7%, range 0-20.8%) and controls (1.9%, 0-18.2%, P=0.7). However, cases with eczema had significantly fewer bifidobacteria (median 1.6%, range 0-4.8%) than their controls (4.0%, 1.9-18.2%, P=0.05). CONCLUSION: We found no differences in fecal microbiota composition between sensitized wheezy and non-sensitized, non-wheezy children aged 3-5 years using nucleic acid-based methods. Differences appear to be isolated to those allergic children with eczema.

Thick melanoma: the challenge persists.

BACKGROUND: Considerable resources have been channelled into primary and secondary prevention of cutaneous melanoma over the past 20 years. These efforts have been associated with a significant increase in the proportion of thin, good prognosis lesions and this is felt to be the principal reason for the current overall improvement in melanoma survival. OBJECTIVES: Analysis of Scottish Melanoma Group (SMG) data was carried out to identify the proportion of thick melanomas presenting over time. SMG data were used to characterize the patients presenting with thick melanoma. METHODS: Using data from the SMG database 915 patients (392 male and 523 female) first diagnosed with invasive melanoma > or = 3.5 mm thick in the two decades between 1979 and 1998, inclusive, were identified. The patients were from regions designated South-east Scotland, Tayside, Grampian and Highland, which together form half of all Scottish cases. RESULTS: The analysis shows that, although the proportion of thick, poor prognosis melanomas has decreased over time, the number presenting per year has not significantly altered. In the first decade, 50.5% of registrations were thick lesions and these fell to 31.0% in the second decade. In the first decade there were 419 cases (173 male), median age 66 years (range 5-99). Fifty-five patients were under the age of 40 years. Two hundred and twelve melanomas were nodular, 116 superficial spreading (SSM), 34 acral and 26 lentigo maligna melanoma. Sixty-nine patients had either lymph node involvement or distant spread at presentation. Despite a 93.3% increase in the total number of melanoma registrations by the end of the second decade, there was relatively little change in the absolute numbers of thick lesions. The total number of thick lesions was 496 (220 male), an increase of 18.4%. Median age was greater, at 70 years (range 1-98), and 31 patients were under the age of 40 years. Nodular was still the commonest type but its proportion had dropped significantly compared with the first decade, with a corresponding increase in SSM and acral types. CONCLUSIONS: Over a 20-year period there was little change in the absolute number of patients presenting with thick melanoma each year, though these form a diminishing proportion of the rising number of total melanomas. This thick melanoma group is characterized by an increasingly older age group and a changing type profile, nodular and SSM being the most common types. This work suggests that the resources currently directed at public and professional education on melanoma are having no effect on this group of patients and that alternative strategies may need to be considered.

Reported versus confirmed wheeze and lung function in early life.

AIMS: To investigate the relation between parentally reported wheeze (unconfirmed), physician confirmed wheeze, and subsequent lung function. METHODS: Children at risk of allergic disease (one parent atopic) were recruited antenatally and followed prospectively from birth. During the first three years of life parents were asked to contact the study team if their child was wheezy. The presence of wheeze was confirmed or not by the primary care or study physician. Respiratory questionnaire and specific airway resistance measurement (sR(aw), body plethysmograph) were completed at age 3 years. RESULTS: A total of 454 children were followed from birth to 3 years of age. One hundred and eighty six (40.9%) of the parents reported their child wheezing in the first three years of life, and in 130 (28.6%) the wheeze was confirmed. A total of 428 children attended the three year clinic review, of whom 274 (64%) successfully carried out lung function tests. There was no significant difference in sR(aw) (kPa.s; geometric mean, 95% CI) between children who had never wheezed (n = 152; 1.03, 1.00 to 1.06) and those with a parentally reported but unconfirmed wheeze (n = 36; 1.02, 0.96 to 1.07, p = 1.00). sR(aw) was significantly higher in children with a physician confirmed wheeze (n = 86; 1.17, 1.11 to 1.22, p < 0.001) compared to those with no history of wheeze or with unconfirmed wheeze. CONCLUSIONS: Children with physician confirmed wheeze have significantly poorer lung function compared to those with parentally reported but unconfirmed and those who have never wheezed. A proportion of parents may have little understanding of what medical professionals mean by the term "wheeze".

Lung function at one month of age as a risk factor for infant respiratory symptoms in a high risk population.

BACKGROUND: Abnormal premorbid lung function is a risk factor for subsequent wheezing in children with one or no atopic parent. This study was undertaken to establish whether early lung function in high risk infants (both parents atopic) was a risk factor for respiratory symptoms in infancy and to examine the influence of maternal asthma, smoking, and allergen exposure during pregnancy on any association. METHODS: Infants were recruited from the NAC Manchester Asthma and Allergy Study cohort at birth. Partial forced expiratory flow volume technique under sedation was carried out to determine maximal flow at FRC (V'maxFRC). Children were followed prospectively and parents completed a standard respiratory questionnaire at one year of age. RESULTS: Sixty nine term infants (34 boys; 88% mothers non-smokers; no household pets) underwent respiratory function testing. Size adjusted V'maxFRC was significantly lower in infants who had recurrent wheeze during the first year of life (mean 1.3 ml/s/cm, 95% CI 0.99 to 1.60) than in those who did not (mean 2.03 ml/s/cm, 95% CI 1.71 to 2.36; p=0.01). V'maxFRC was also significantly lower in infants who had recurrent cough symptoms. In multivariate regression analysis, when adjusted for age at test, sex, maternal asthma, smoking and maternal mattress Der 1 levels, a lower size adjusted V'maxFRC score remained strongly associated with wheezing (OR 0.37, 95% CI 0.18 to 0.77, p=0.007). Maternal smoking also remained an independent risk factor (OR 29.85, 95% CI 2.46 to 362.5, p=0.008). CONCLUSION: Significantly diminished lung function was present in high risk infants who subsequently wheezed and coughed. This was independent of maternal exposure to mite allergen, asthma, and smoking during pregnancy.

The role of indoor allergen exposure in the development of sensitization and asthma.

The role of indoor allergen exposure in the development of sensitization and asthma remains a subject of controversy. From a number of cross-sectional and longitudinal studies we can conclude that there is a very close association between allergen exposure and the sensitization of an individual. The dose-response relationships seem to differ between allergens; house dust mite and cockroach allergens appear to have a positive linear relationship, whereas cat allergens appear to act quite differently, with maximum sensitization developing at moderate exposure levels. Very low levels of cat allergen exposure are likely to induce no response and very high levels are likely to develop a form of tolerance, with a modified T helper cell type 2 response and the production of IgG4 antibodies and but not IgE. The relationship between indoor allergen exposure and asthma is, however, less clear. The proposed mechanism for the development of disease is that allergen exposure causes sensitization, and continued exposure leads to airway responsiveness and inflammation. As yet, the evidence for allergen exposure being a primary cause of asthma remains weak, and the results of ongoing prospective, randomized allergen avoidance trials are awaited to clarify this issue.