Prevention of atopic dermatitis in high-risk neonates via different types of moisturizer application: A randomized, blinded, parallel, three-group, phase II trial (PAF study).

BACKGROUND: The effectiveness of moisturizers in preventing infant atopic dermatitis (AD) remains unclear. We previously showed that using 2e moisturizer of commercial moisturizer (Shiseido Japan Co., Ltd.) at least once a day significantly prevented AD in infants as compared with as-needed petroleum jelly. This trial aimed to determine the effectiveness of twice- or once-daily application of Fam's Baby moisturizer (Fam's Inc.) in preventing AD compared with once-daily 2e moisturizer. METHODS: This trial was a single-centre, three-parallel-group, assessor-blinded, superiority, individually randomized, controlled, phase II trial that was conducted from 25 August 2020 to 28 September 2021. We randomly assigned 60 newborns with at least one parent or sibling who has AD to receive Fam's Baby moisturizer twice daily (Group A) or once daily (Group B), or 2e once daily (Group C) in a 1:1:1 ratio until they were 32 weeks old. The primary outcome was the time of AD onset. RESULTS: Atopic dermatitis was observed in 11/20 (55%), 5/20 (25%) and 10/20 (50%), infants in Groups A, B and C, respectively. Cumulative incidence values for AD according to the Kaplan-Meier method showed that infants in Group B tended to maintain an intact skin for a longer period than those in Group C (median time, not reached [NR] vs. 212 days, log-rank test, p = 0.064). Cox regression analysis showed that the risk of AD tended to be lower in Group B (hazard ratio with group C as control, 0.36; 95% confidential intervals: 0.12-1.06). No serious adverse events occurred in any of the enrolled infants. CONCLUSION: Fam's Baby moisturizer may better prevent AD than 2e. Further large-scale trials should be performed to confirm the efficacy of Fam's Baby moisturizer in preventing AD in infants.

Non-invasive transcriptomic analysis using mRNAs in skin surface lipids obtained from children with mild-to-moderate atopic dermatitis.

BACKGROUND: Specimens for analysing the molecular pathology of skin disease are generally obtained through invasive methods, such as biopsy. However, less burdensome methods are desirable for paediatric patients. We recently established a method that comprehensively analyses RNA present in sebum (skin surface lipid-RNAs: SSL-RNAs) using a next-generation sequencer. Using this method, biological information can be obtained from the skin in a completely non-invasive manner. OBJECTIVES: To verify the applicability of the SSL-RNA method for analysis of paediatric skin and analyse the molecular pathology of mild-to-moderate atopic dermatitis (AD) in children. METHODS: We collected sebum specimens from the whole faces of 23 healthy children and 16 children with mild-to-moderate AD (eczema area and severity index (EASI) score: 5.9 ± 2.6) ranging in age from 6 months to 5 years, using an oil-blotting film. We then extracted SSL-RNAs from the samples and performed an AmpliSeq transcriptomic analysis. RESULTS: The expressions of genes related to keratinization (LCE, PSORS1C2, IVL and KRT17), triglyceride synthesis and storage (PLIN2, DGAT2 and CIDEA), wax synthesis (FAR2), ceramide synthesis (GBA2, SMPD3 and SPTLC3), antimicrobial peptides (DEFB1) and intercellular adhesion (CDSN), all of which are related to the skin barrier, are lower in children with AD than in healthy children. The children with AD also have higher expression of CCL17, a Th2-cytokine and an increased Th2-immune response as demonstrated by a gene set variation analysis. Moreover, KRT17 and CCL17 expression levels are significantly correlated with the EASI score. CONCLUSIONS: Molecular changes associated with abnormal immune responses and the epidermal barrier in children with mild-to-moderate AD can be determined using the SSL-RNA method. This non-invasive method could therefore be a useful means for understanding the molecular pathology of paediatric AD.

Prostaglandin D2 metabolite is not a useful clinical indicator for assessing atopic dermatitis.

Prostaglandin D2 (PGD2 ) plays an important role in atopic dermatitis (AD), and 11,15-dioxo-9α-hydroxy-2,3,4,5-tetranorprostan-1,20-dioicacid (PGDM) is a major metabolite of PGD2 . We investigated the relationship between urinary PGDM levels and severity of paediatric AD. In total, 31 patients with AD and 21 healthy controls (HCs) without AD were recruited, and urinary PGDM levels were measured. Of the 31 patients with AD, 14 were reassessed for urinary PGDM after topical steroid therapy. There was no difference in urinary PGDM levels between patients with AD and HCs. Although there was a significant positive correlation between the SCORing Atopic Dermatitis (SCORAD) index and the serum level of thymus and activation-regulated chemokine (TARC), the urinary PGDM levels did not correlate with either SCORAD or serum TARC. Moreover, both SCORAD and serum TARC were significantly improved by topical steroid therapy; however, urinary PGDM levels were not changed. In conclusion, the level of urinary PGD2 metabolites in children with AD is substantially the same as that in HCs even if the disease is severe.

Report from the fifth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative).

This is the report from the fifth meeting of the Harmonising Outcome Measures for Eczema initiative (HOME V). The meeting was held on 12-14 June 2017 in Nantes, France, with 81 participants. The main aims of the meeting were (i) to achieve consensus over the definition of the core domain of long-term control and how to measure it and (ii) to prioritize future areas of research for the measurement of the core domain of quality of life (QoL) in children. Moderated whole-group and small-group consensus discussions were informed by presentations of qualitative studies, systematic reviews and validation studies. Small-group allocations were performed a priori to ensure that each group included different stakeholders from a variety of geographical regions. Anonymous whole-group voting was carried out using handheld electronic voting pads according to predefined consensus rules. It was agreed by consensus that the long-term control domain should include signs, symptoms, quality of life and a patient global instrument. The group agreed that itch intensity should be measured when assessing long-term control of eczema in addition to the frequency of itch captured by the symptoms domain. There was no recommendation of an instrument for the core outcome domain of quality of life in children, but existing instruments were assessed for face validity and feasibility, and future work that will facilitate the recommendation of an instrument was agreed upon.

Report from the fourth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative).

This article is a report of the fourth meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in Malmö, Sweden on 23-24 April 2015 (HOME IV). The aim of the meeting was to achieve consensus over the preferred outcome instruments for measuring patient-reported symptoms and quality of life for the HOME core outcome set for atopic eczema (AE). Following presentations, which included data from systematic reviews, consensus discussions were held in a mixture of whole group and small group discussions. Small groups were allocated a priori to ensure representation of different stakeholders and countries. Decisions were voted on using electronic keypads. For the patient-reported symptoms, the group agreed by vote that itch, sleep loss, dryness, redness/inflamed skin and irritated skin were all considered essential aspects of AE symptoms. Many instruments for capturing patient-reported symptoms were discussed [including the Patient-Oriented SCOring Atopic Dermatitis index, Patient-Oriented Eczema Measure (POEM), Self-Administered Eczema Area and Severity Index, Itch Severity Scale, Atopic Dermatitis Quickscore and the Nottingham Eczema Severity Score] and, by consensus, POEM was selected as the preferred instrument to measure patient-reported symptoms. Further work is needed to determine the reliability and measurement error of POEM. Further work is also required to establish the importance of pain/soreness and the importance of collecting information regarding the intensity of symptoms in addition to their frequency. Much of the discussion on quality of life concerned the Dermatology Life Quality Index and Quality of Life Index for Atopic Dermatitis; however, consensus on a preferred instrument for measuring this domain could not be reached. In summary, POEM is recommended as the HOME core outcome instrument for measuring AE symptoms.

Total serum IgE level influences oral food challenge tests for IgE-mediated food allergies.

Probability curves predicting oral food challenge test (OFC) results based on specific IgE levels are widely used to prevent serious allergic reactions. Although several confounding factors are known to affect probability curves, the main factors that affect OFC outcomes are currently unclear. We hypothesized that an increased total IgE level would reduce allergic reactivity. Medical records of 337 and 266 patients who underwent OFCs for 3.5 g boiled hen's egg white and 3.1 ml raw cow's milk, respectively, were examined retrospectively. We subdivided the patients into three groups based on total IgE levels and age by percentile (<25th, 25-75th, and >75th percentiles), and logistic regression analyses were performed on each group. Patients with higher total IgE levels were significantly less responsive. In addition, age did not significantly affect the OFC results. Therefore, total IgE levels should be taken into account when predicting OFC results based on food-specific IgE levels.

Report from the third international consensus meeting to harmonise core outcome measures for atopic eczema/dermatitis clinical trials (HOME).

This report provides a summary of the third meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in San Diego, CA, U.S.A., 6-7 April 2013 (HOME III). The meeting addressed the four domains that had previously been agreed should be measured in every eczema clinical trial: clinical signs, patient-reported symptoms, long-term control and quality of life. Formal presentations and nominal group techniques were used at this working meeting, attended by 56 voting participants (31 of whom were dermatologists). Significant progress was made on the domain of clinical signs. Without reference to any named scales, it was agreed that the intensity and extent of erythema, excoriation, oedema/papulation and lichenification should be included in the core outcome measure for the scale to have content validity. The group then discussed a systematic review of all scales measuring the clinical signs of eczema and their measurement properties, followed by a consensus vote on which scale to recommend for inclusion in the core outcome set. Research into the remaining three domains was presented, followed by discussions. The symptoms group and quality of life groups need to systematically identify all available tools and rate the quality of the tools. A definition of long-term control is needed before progress can be made towards recommending a core outcome measure.

Cedar and cypress pollen counts are associated with the prevalence of allergic diseases in Japanese schoolchildren.

BACKGROUND: Patients allergic to pollen have been known to become more symptomatic during pollen season compared with the nonpollen season. However, there are few studies regarding whether higher exposure to pollen might increase the prevalence of allergic diseases. METHODS: An ecological analysis was conducted to evaluate whether pollen exposure is associated with the prevalence of allergic diseases in schoolchildren. Pollen count data of Japanese cedar (Cryptomeria japonica) and Japanese cypress (Chamaecyparis obtusa), which are the major pollen allergens in Japan, were obtained from each prefecture. The prevalence of allergic diseases in schoolchildren in each prefecture was based on a nationwide cross-sectional survey using the International Study of Asthma and Allergies in Childhood questionnaire. RESULTS: After omitting three prefectures where pollen data were not available, data of 44 prefectures were analysed. The prevalence of allergic rhinoconjunctivitis in children aged 6-7 years was positively associated with both cedar and cypress pollen counts (P = 0.01, both), whereas the prevalence of allergic rhinoconjunctivitis in children aged 13-14 years was positively associated with only cypress pollen counts (P = 0.003). Furthermore, the prevalence of asthma was positively associated with cedar pollen counts in 6- to 7-year-old children (P = 0.003) but not cypress pollen counts in either age group. CONCLUSIONS: There are ecological associations between pollen counts and the prevalence of allergic diseases in Japanese schoolchildren. Further studies are needed to determine whether the difference between the effects of cedar and cypress pollens is attributable to pollen counts or allergenicity.

Resistance exercise enhances cognitive function in mouse.

Physical exercise has been shown to increase adult neurogenesis in the hippocampus and to enhance synaptic plasticity. It has been demonstrated that these neuroprotective effects can be observed following aerobic exercise. However, it remains unknown whether plasticity molecules, such as brain-derived neurotrophic factor (BDNF) and cyclic AMP response element-binding protein (CREB), are expressed in the hippocampus following resistance exercise. We applied voluntary progressive-resistance wheel exercise (RE) for 14 days, and measured BDNF and CREB in the hippocampus. The Morris water maze was also performed to estimate learning and memory. Furthermore, we measured RE effects on mammalian target of rapamycin (mTOR) and 70-kDa ribosomal protein S6 kinase (p70S6K) mediating muscle protein synthesis in the soleus. As a result, we found that RE enhanced cognition and elevated BDNF and CREB expressions in the hippocampus. Also, RE activated the mTOR-p70S6K signaling pathway in the soleus. We found that phosphorylated mTOR and p70S6K were significantly positively correlated with BDNF expression. Our results indicated that resistance exercise drove the protein synthesis signaling pathway in the soleus and enhanced hippocampal synaptic plasticity-related molecules. These results suggest the beneficial effects of resistance exercise on cognitive function.

Combination of heat-killed Lactiplantibacillus plantarum YIT 0132 (LP0132) and oral immunotherapy in cow's milk allergy: a randomised controlled trial.

Safer and more effective cow milk (CM)-oral immunotherapy that does not induce allergic reactions has not yet been standardised. We sought to explore the efficacy and feasibility of a combination of heat-killed Lactiplantibacillus plantarum YIT 0132 (LP0132) and oral immunotherapy for treating IgE-mediated cow milk allergy (CMA). We conducted a 24-week, double-blind, randomised (1:1), two-arm, parallel-group, placebo-controlled, phase 2 trial of LP0132 intervention for treating IgE-mediated CMA in children aged 1-18 years (n=60) from January 29, 2018 to July 12, 2019 in Tokyo, Japan. Participants were randomly assigned to the LP0132 group receiving citrus juice fermented with LP0132 or to the control group receiving citrus juice without. Both groups received low-dose slow oral immunotherapy with CM. The primary outcome was improved tolerance to CM, proven by the CM challenge test at 24 weeks. Secondary outcomes were changes in serum biomarkers of serum-specific ß-lactoglobulin-IgE (sIgE) and ß-lactoglobulin-IgG4 (sIgG4). Exploratory outcomes included changes in serum cytokine levels and gut microbiota composition. A total of 61 participants were included. Finally, 31 children were assigned to the LP0132 group and 30 to the control group, respectively. After the intervention, 41.4 and 37.9% of the participants in the LP0132 and control groups, respectively, showed improved tolerance to CM. In serum biomarkers after the intervention, the sIgG4 level was significantly higher, and interleukin (IL)-5 and IL-9 were significantly lower, in the LP0132 group than in the control group. In the gut microbiome, the α-diversity and Lachnospiraceae increased significantly in the LP0132 group, and Lachnospiraceae after the intervention was significantly higher in the LP0132 group than in the control group. In conclusion, low-dose oral immunotherapy with modulating gut microbiota might be a safer and more effective approach for treating cow's milk allergy.

A role for the Pkc1p/Mpk1p kinase cascade in the morphogenesis checkpoint.

In many cells the timing of entry into mitosis is controlled by the balance between the activity of inhibitory Wee1-related kinases (Swe1p in budding yeast) and the opposing effect of Cdc25-related phosphatases (Mih1p in budding yeast) that act on the cyclin-dependent kinase Cdc2 (Cdc28p in budding yeast). Wee1 and Cdc25 are key elements in the G2 arrest mediated by diverse checkpoint controls. In budding yeast, a 'morphogenesis checkpoint' that involves Swe1p and Mih1p delays mitotic activation of Cdc28p. Many environmental stresses (such as shifts in temperature or osmolarity) provoke transient depolarization of the actin cytoskeleton, during which bud construction is delayed while cells adapt to environmental conditions. During this delay, the morphogenesis checkpoint halts the cell cycle in G2 phase until actin can repolarize and complete bud construction, thus preventing the generation of binucleate cells. A similar G2 delay can be triggered by mutations or drugs that specifically impair actin organization, indicating that it is probably actin disorganization itself, rather than specific environmental stresses, that triggers the delay. The G2 delay involves stabilization of Swe1p in response to various actin perturbations, although this alone is insufficient to produce a long G2 delay.

Sequentially addressable dielectrophoretic array for high-throughput sorting of large-volume biological compartments.

Droplet microfluidics has become a powerful tool in precision medicine, green biotechnology, and cell therapy for single-cell analysis and selection by virtue of its ability to effectively confine cells. However, there remains a fundamental trade-off between droplet volume and sorting throughput, limiting the advantages of droplet microfluidics to small droplets (<10 pl) that are incompatible with long-term maintenance and growth of most cells. We present a sequentially addressable dielectrophoretic array (SADA) sorter to overcome this problem. The SADA sorter uses an on-chip array of electrodes activated and deactivated in a sequence synchronized to the speed and position of a passing target droplet to deliver an accumulated dielectrophoretic force and gently pull it in the direction of sorting in a high-speed flow. We use it to demonstrate large-droplet sorting with ~20-fold higher throughputs than conventional techniques and apply it to long-term single-cell analysis of Saccharomyces cerevisiae based on their growth rate.

Mutations in yeast calmodulin cause defects in spindle pole body functions and nuclear integrity.

Yeast calmodulin (CaM) is required for the progression of nuclear division (Ohya, Y. and Y. Anraku. 1989. Curr. Genet. 15:113-120), although the precise mechanism and physiological role of CaM in this process are unclear. In this paper we have characterized the phenotype caused by a temperature-sensitive lethal mutation (cmdl-101) in the yeast CaM. The cmdl-101 mutation expresses a carboxyl-terminal half of the yeast CaM (Met72-Cys147) under the control of an inducible GAL1 promoter. Incubation of the cmdl-101 cells at a nonpermissive temperature causes a severe defect in chromosome segregation. The rate of chromosome loss in the cmdl-101 mutant is higher than wild-type cell even at permissive temperature. The primary visible defect observed by immunofluorescence and electron microscopic analyses is that the organization of spindle microtubules is abnormal in the cmdl-101 cells grown at nonpermissive temperature. Majority of budded cells arrested at the high temperature contain only one spindle pole body (SPB), which forms monopolar spindle, whereas the budded cells of the same strain incubated at permissive temperature all contain two SPBs. Using the freeze-substituted fixation method, we found that the integrity of the nuclear morphology of the cmdl-101 mutant cell is significantly disturbed. The nucleus in wild-type cells is round with smooth contours of nuclear envelope. However, the nuclear envelope in the mutant cells appears to be very flexible and forms irregular projections and invaginations that are never seen in wild-type cells. The deformation of the nuclear becomes much more severe as the incubation at nonpermissive temperature continues. The single SPB frequently localizes on the projections or the invaginations of the nuclear envelope. These observations suggest that CaM is required for the functions of SPB and spindle, and the integrity of nucleus.

Development and validation of a questionnaire measuring quality of life in primary caregivers of children with atopic dermatitis (QPCAD).

BACKGROUND: Disease-specific health-related quality of life (HRQoL) instruments for primary caregivers of children with atopic dermatitis are useful in evaluating the efficacy of treatment in clinical practice and study. However, no such scale has been available in Japan. OBJECTIVES: To develop and validate a self-administered instrument specifically designed to measure quality of life in primary caregivers of children with atopic dermatitis (QPCAD). METHODS: This study consisted of three successive phases: the item generation phase, pilot test phase and validation phase. In the item generation phase, questionnaire items were derived from 33 qualitative interviews with primary caregivers. In the pilot test phase, the face and content validity of the preliminary scale were assessed (n = 33). In the validation phase, the questionnaire was finalized and assessed in terms of statistical performance (n = 416). RESULTS: The QPCAD included 19 items in the following categories: 'exhaustion', 'worry about atopic dermatitis', 'family cooperation' and 'achievement'. The reliability of internal consistency was fair (Cronbach's alpha coefficients 0.66-0.87). The QPCAD subscales and total score were significantly correlated with psychological health, physical health, anxiety, depression and severity score, with mild to moderate correlation coefficients. Test-retest reliability and responsiveness to change in severity were also satisfactory. CONCLUSIONS: The QPCAD is an appropriate tool for assessing HRQoL of primary caregivers of children with atopic dermatitis in clinical practice and clinical trials.

Diverse essential functions revealed by complementing yeast calmodulin mutants.

Calmodulin, a cytoplasmic calcium-binding protein, is indispensable for eukaryotic cell growth. Examination of 14 temperature-sensitive yeast mutants bearing one or more phenylalanine to alanine substitutions in the single essential calmodulin gene of yeast (CMD1) revealed diverse essential functions. Mutations could be classified into four intragenic complementation groups. Each group showed different characteristic functional defects in actin organization, calmodulin localization, nuclear division, or bud emergence. Phenylalanine residues implicated in calmodulin localization and nuclear division are located in the amino-terminal half of the protein, whereas those implicated in actin organization and bud emergence are located in the carboxyl-terminal half.

Identification of yeast Rho1p GTPase as a regulatory subunit of 1,3-beta-glucan synthase.

1,3-beta-D-glucan synthase [also known as beta(1-->3) glucan synthase] is a multi-enzyme complex that catalyzes the synthesis of 1,3-beta-linked glucan, a major structural component of the yeast cell wall. Temperature-sensitive mutants in the essential Rho-type guanosine triphosphatase (GTPase), Rho1p, displayed thermolabile glucan synthase activity, which was restored by the addition of recombinant Rho1p. Glucan synthase from mutants expressing constitutively active Rho1p did not require exogenous guanosine triphosphate for activity. Rho1p copurified with beta(1-->3)glucan synthase and associated with the Fks1p subunit of this complex in vivo. Both proteins were localized predominantly at sites of cell wall remodeling. Therefore, it appears that Rho1p is a regulatory subunit of beta(1-->3)glucan synthase.

The crystal polymorphism of calcium carbonate is determined by the matrix structure in quail eggs.

Two calcified structures, the eggshell and sperm-associated body (SB), are present in the eggs of the Japanese quail, Coturnix japonica. X-ray diffractometry showed that calcium carbonates take the form of calcite in the eggshell and aragonite in the SB. The aim of the present study was to identify the factors that determine the morphology of calcium carbonate crystals. The matrix of EDTA-treated eggshell was a meshwork of vesicles, 200 to 500 nm in diameter, connected by fine fibers or fibrous sheets. The matrix of SB cortex was a radiation of rod-shaped projections approximately 130 nm in width. In vitro crystal formation was achieved by adding dissociated matrix substances to test solutions. When eggshell matrix material was added, formation of calcite crystals, which had many vesicular holes on their surface, was observed. When SB matrix material dissociated by sonication was added, rhombohedral calcite crystals formed at protein concentrations of 100 microg/mL or lower, and elongated and bundled crystals formed at concentrations of 150 microg/mL or higher. When SB matrix material dissociated by pipetting was added, aragonite crystals formed. These observations indicate that the matrix structure is the principal factor in determining the crystal polymorphism of calcium carbonate.

Tuberculin reactivity and allergic disorders in schoolchildren, Okinawa, Japan.

BACKGROUND: Bacillus Calmette-Guérin (BCG) vaccination triggers a T-helper type 1 response. Whether BCG vaccination and positive tuberculin reactivity are preventive against allergic disorders remains controversial. OBJECTIVE: The current cross-sectional study investigated the relationship of BCG vaccination and tuberculin reactivity with the prevalence of allergic disorders using data from the Ryukyus Child Health Study (RYUCHS). METHODS: Subjects were 5717 schoolchildren aged 8-11 years in Okinawa, Japan. The RYUCHS collected information on symptoms of allergic disorders and potential confounding factors. The outcomes were based on diagnostic criteria from the International Study of Asthma and Allergies in Childhood. Data on BCG vaccination and tuberculin tests were obtained from school records. Allowance was made for grade, sex, sibship size, smoking in the household, paternal and maternal history of asthma, atopic eczema, and allergic rhinitis, and paternal and maternal educational level. RESULTS: No measurable relationship was found between BCG vaccination in infants and the prevalence of allergic disorders. Among 5567 BCG-vaccinated children, positive tuberculin reactivity (induration >/=10 mm) in the first grade was independently associated with a decreased prevalence of wheeze, asthma, and atopic eczema: the multivariate odds ratios for wheeze, asthma, and atopic eczema were 0.80 (95% confidence interval [CI], 0.67-0.94), 0.78 (95% CI, 0.64-0.95), and 0.77 (95% CI, 0.62-0.95), respectively. The inverse associations were more pronounced in children with a negative parental allergic history than in those with a positive parental allergic history. There was no significant relationship between tuberculin reactivity and allergic rhinoconjunctivitis. CONCLUSIONS: The findings suggest that positive tuberculin reactivity may be inversely associated with the prevalence of wheeze, asthma, and atopic eczema, but not allergic rhinoconjunctivitis, especially among Japanese children without a parental allergic history.

Fatty acid intake and asthma symptoms in Japanese children: the Ryukyus Child Health Study.

BACKGROUND: It has been hypothesized that increased consumption of n-6 polyunsaturated fatty acids and decreased consumption of n-3 polyunsaturated fatty acids have contributed to the recent increased prevalence of asthma. OBJECTIVES: The present cross-sectional study examined the association of intake of specific types of fatty acids with the prevalence of asthma symptoms using data from the Ryukyus Child Health Study. METHODS: Study subjects were 25,033 schoolchildren aged 6-15 years in Okinawa, Japan. Symptoms of wheeze and asthma were defined according to diagnostic criteria from the International Study of Asthma and Allergies in Childhood. Information on dietary factors was collected using a self-administered brief diet history questionnaire for children. Adjustment was made for age, sex, number of siblings, smoking in the household, body mass index, paternal and maternal history of allergic diseases, and paternal and maternal educational level. RESULTS: Intake of polyunsaturated fatty acids, n-3 and n-6 polyunsaturated fatty acids and linoleic acid (18:2 n-6) was independently associated with an increased prevalence of wheeze--the multivariate odds ratios for the highest quintile were 1.19 (95% confidence interval [CI], 1.05-1.35), 1.17 (95% CI, 1.03-1.34), 1.19 (95% CI, 1.04-1.35), and 1.20 (95% CI, 1.06-1.37), respectively. There was no measurable relationship of consumption of alpha-linolenic (18:3 n-3), eicosapentaenoic (20:5 n-3), docosahexaenoic (22:6 n-3) or arachidonic acid (20:4 n-6) or the ratio of n-3 to n-6 polyunsaturated fatty acids with the prevalence of wheeze. Consumption of total fat, saturated fatty acids, monounsaturated fatty acids and cholesterol were not evidently related to wheeze. No material dose-response association was found between the intake of any of the types of fatty acids considered and the prevalence of asthma. CONCLUSIONS: The findings suggest that consumption of both n-3 and n-6 polyunsaturated fatty acids, especially linoleic acid, may be associated with an increased prevalence of wheeze.