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Aim: The individual effects of climate and soil properties on functional trait distributions have become increasingly clear with recent syntheses of large datasets. However, the distribution of traits in a given climate may depend on the fertility of the soil. Our aim was to quantify how soil-climate interactions explain community-level variation in functional traits from every plant organ to improve predictions of plant community responses to environmental change. Location: Temperate forests throughout New Zealand. Methods: We measured traits of foliar, stem, root and reproductive tissue for 64 species and calculated abundance-weighted mean trait values on 324 forest plots. Multiple linear regression was used to model the variation in each of the traits as functions of mean annual temperature (MAT), vapour pressure deficit (VPD), soil pH, soil total phosphorus (P) and their interactions. Results: Soil-climate interactions explained significant variation in functional traits. For example, specific leaf area (SLA) was highest in high-P soil within a wet and warm climate; however, strong interactions indicate that SLA was lowest in wet and warm climates in low-P soil. Root tissue density was lowest in warm climates and high-P soil, but it was high in warm climates and low-P soil and in cold climates and high-P soil. According to model predictions, the largest potential responses of vegetation to warming may occur in fertile and wet environments. Main conclusions: Pervasive soil-climate interactions demonstrate that interpreting simple bivariate relationships between traits and climate must be done with caution because the adaptive value of traits in a given climate depends on the fertility of the soil. Predictions of vegetation responses to climate change will improve significantly by incorporating local-scale soil properties into modelling frameworks. Rising global temperatures may shift community-level trait values in opposite directions depending on whether the soil is fertile or infertile.

Abstract Rationale Allergen exposure in sensitized individuals with asthma interacts with viruses to increase the risk of asthma exacerbation. Objectives To evaluate the use of house dust mite–impermeable bedding and its impact on severe asthma exacerbations in children. Methods We randomized mite-sensitized children with asthma (ages 3–17 yr) after an emergency hospital attendance with an asthma exacerbation to receive mite-impermeable (active group) or control (placebo group) bed encasings. Measurements and Main Results Over a 12-month intervention period, the occurrence of severe asthma exacerbations was investigated. Of 434 children with asthma who consented, 286 (mean age, 7.7 yr; male sex, 65.8%) were mite sensitized, and 284 were randomized (146 to the active group and 138 to the placebo group). At 12 months, significantly fewer children in the active group than in the placebo group had attended the hospital with an exacerbation (36 [29.3%] of 123 vs. 49 [41.5%] of 118; P = 0.047). In the multivariable analysis, the risk of emergency hospital attendance was 45% lower in the active group (hazard ratio, 0.55; 95% confidence interval [CI], 0.36–0.85; P = 0.006) than in the placebo group. The annual rate of emergency hospital attendance with exacerbations was 27% lower in the active group than in the placebo group, but this did not reach significance (estimated marginal mean [95% CI], active, 0.38 [0.26–0.56] vs. placebo, 0.52 [0.35–0.76]; P = 0.18). No difference between the groups in the risk of prednisolone use for exacerbation was found (hazard ratio, 0.82; 95% CI, 0.58–1.17; P = 0.28). Conclusions Mite-impermeable encasings are effective in reducing the number of mite-sensitized children with asthma attending the hospital with asthma exacerbations but not the number requiring oral prednisolone. This simple measure may reduce the health care burden of asthma exacerbations in children. Clinical trial registered with www.isrctn.com (ISRCTN 69543196).

The term \"atopic march\" has been used to imply a natural progression of a cascade of symptoms from eczema to asthma and rhinitis through childhood. We hypothesize that this expression does not adequately describe the natural history of eczema, wheeze, and rhinitis during childhood. We propose that this paradigm arose from cross-sectional analyses of longitudinal studies, and may reflect a population pattern that may not predominate at the individual level. Data from 9,801 children in two population-based birth cohorts were used to determine individual profiles of eczema, wheeze, and rhinitis and whether the manifestations of these symptoms followed an atopic march pattern. Children were assessed at ages 1, 3, 5, 8, and 11 y. We used Bayesian machine learning methods to identify distinct latent classes based on individual profiles of eczema, wheeze, and rhinitis. This approach allowed us to identify groups of children with similar patterns of eczema, wheeze, and rhinitis over time. Using a latent disease profile model, the data were best described by eight latent classes: no disease (51.3%), atopic march (3.1%), persistent eczema and wheeze (2.7%), persistent eczema with later-onset rhinitis (4.7%), persistent wheeze with later-onset rhinitis (5.7%), transient wheeze (7.7%), eczema only (15.3%), and rhinitis only (9.6%). When latent variable modelling was carried out separately for the two cohorts, similar results were obtained. Highly concordant patterns of sensitisation were associated with different profiles of eczema, rhinitis, and wheeze. The main limitation of this study was the difference in wording of the questions used to ascertain the presence of eczema, wheeze, and rhinitis in the two cohorts. The developmental profiles of eczema, wheeze, and rhinitis are heterogeneous; only a small proportion of children (∼ 7% of those with symptoms) follow trajectory profiles resembling the atopic march. Please see later in the article for the Editors' Summary.

Abstract Rationale Developmental patterns of lung function during childhood may have major implications for our understanding of the pathogenesis of respiratory disease throughout life. Objectives To explore longitudinal trajectories of lung function during childhood and factors associated with lung function decline. Methods In a population-based birth cohort, specific airway resistance (sRaw) was assessed at age 3 (n = 560), 5 (n = 829), 8 (n = 786), and 11 years (n = 644). Based on prospective data (questionnaires, skin tests, IgE), children were assigned to wheeze phenotypes (no wheezing, transient, late-onset, and persistent) and atopy phenotypes (no atopy, dust mite, non–dust mite, multiple early, and multiple late). We used longitudinal linear mixed models to determine predictors of change in sRaw over time. Measurements and Main Results Contrary to the assumption that sRaw is independent of age and sex, boys had higher sRaw than girls (mean difference, 0.080; 95% confidence interval [CI], 0.049–0.111; P < 0.001) and a higher rate of increase over time. For girls, sRaw increased by 0.017 kPa ⋅ s−1 per year (95% CI, 0.011–0.023). In boys this increase was significantly greater (P = 0.012; mean between-sex difference, 0.011 kPa ⋅ s−1; 95% CI, 0.003–0.019). Children with persistent wheeze (but not other wheeze phenotypes) had a significantly greater rate of deterioration in sRaw over time compared with never wheezers (P = 0.009). Similarly, children with multiple early, but not other atopy phenotypes had significantly poorer lung function than those without atopy (mean difference, 0.116 kPa ⋅ s−1; 95% CI, 0.065–0.168; P < 0.001). sRaw increased progressively with the increasing number of asthma exacerbations. Conclusions Children with persistent wheeze, frequent asthma exacerbations, and multiple early atopy have diminished lung function throughout childhood, and are at risk of a progressive loss of lung function from age 3 to 11 years. These effects are more marked in boys.

There is evidence for adverse effects of outdoor air pollution on lung function of children. Quantitative summaries of the effects of air pollution on lung function, however, are lacking due to large differences among studies. We aimed to study the association between residential exposure to air pollution and lung function in five European birth cohorts with a standardized exposure assessment following a common protocol. As part of the European Study of Cohorts for Air Pollution Effects (ESCAPE) we analyzed data from birth cohort studies situated in Germany, Sweden, the Netherlands, and the United Kingdom that measured lung function at 6-8 years of age (n = 5,921). Annual average exposure to air pollution [nitrogen oxides (NO2, NOx), mass concentrations of particulate matter with diameters < 2.5, < 10, and 2.5-10 μm (PM2.5, PM10, and PMcoarse), and PM2.5 absorbance] at the birth address and current address was estimated by land-use regression models. Associations of lung function with estimated air pollution levels and traffic indicators were estimated for each cohort using linear regression analysis, and then combined by random effects meta-analysis. Estimated levels of NO2, NOx, PM2.5 absorbance, and PM2.5 at the current address, but not at the birth address, were associated with small decreases in lung function. For example, changes in forced expiratory volume in 1 sec (FEV1) ranged from -0.86% (95% CI: -1.48, -0.24%) for a 20-μg/m3 increase in NOx to -1.77% (95% CI: -3.34, -0.18%) for a 5-μg/m3 increase in PM2.5. Exposure to air pollution may result in reduced lung function in schoolchildren.

Abstract Rationale The pattern of IgE response (over time or to specific allergens) may reflect different atopic vulnerabilities which are related to the presence of asthma in a fundamentally different way from current definition of atopy. Objectives To redefine the atopic phenotype by identifying latent structure within a complex dataset, taking into account the timing and type of sensitization to specific allergens, and relating these novel phenotypes to asthma. Methods In a population-based birth cohort in which multiple skin and IgE tests have been taken throughout childhood, we used a machine learning approach to cluster children into multiple atopic classes in an unsupervised way. We then investigated the relation between these classes and asthma (symptoms, hospitalizations, lung function and airway reactivity). Measurements and Main Results A five-class model indicated a complex latent structure, in which children with atopic vulnerability were clustered into four distinct classes (Multiple Early [112/1053, 10.6%]; Multiple Late [171/1053, 16.2%]; Dust Mite [47/1053, 4.5%]; and Non-dust Mite [100/1053, 9.5%]), with a fifth class describing children with No Latent Vulnerability (623/1053, 59.2%). The association with asthma was considerably stronger for Multiple Early compared with other classes and conventionally defined atopy (odds ratio [95% CI]: 29.3 [11.1–77.2] versus 12.4 [4.8–32.2] versus 11.6 [4.8–27.9] for Multiple Early class versus Ever Atopic versus Atopic age 8). Lung function and airway reactivity were significantly poorer among children in Multiple Early class. Cox regression demonstrated a highly significant increase in risk of hospital admissions for wheeze/asthma after age 3 yr only among children in the Multiple Early class (HR 9.2 [3.5–24.0], P < 0.001). Conclusions IgE antibody responses do not reflect a single phenotype of atopy, but several different atopic vulnerabilities which differ in their relation with asthma presence and severity. Clinical trial registered with www.controlled-trials.com (ISRCTN72673620).

BackgroundAsthma is misdiagnosed in one-third of patients . Due to its variable nature, international guidelines recommend performing key diagnostic tests during symptomatic periods or in the morning to improve accuracy. Limited access to timely clinic appointments and community-based diagnostics makes this difficult. Handheld spirometry and fractional exhaled nitric oxide (FeNO) are feasible for home use, enabling timely and flexible testing.ObjectiveTo explore patients’ views on performing spirometry and FeNO at home during the asthma diagnostic process.DesignA qualitative study using semistructured interviews. Data were analysed using the framework approach.SettingThis prospective observational study was conducted at a National Institute for Health and Care Research Clinical Research Facility, based within a large National Health Service Trust, as part of the Rapid-Access Diagnostics for Asthma (RADicA) study (ISRCTN11676160).ParticipantsA purposive sample of 15 symptomatic adult patients with general practitioner-suspected asthma who were referred for diagnostic evaluation of the condition; all patients were given home spirometry and FeNO devices during their diagnostic processes.ResultsThree themes emerged from the analysis: ‘Perceived value of, and burdens of home testing’, ‘Views on device usability and acceptability’ and ‘Information and support needs’. Home testing was generally welcomed by patients as a way of improving their understanding of their condition and enabling an accurate diagnosis of their symptoms. Key barriers (eg, testing frequency, lack of privacy) and enablers to improve feasibility (eg, training and support) were also identified.ConclusionThis study provides valuable insights into the barriers and enablers of home-based diagnostic strategies for asthma. Findings can inform service design and implementation approaches to enhance the feasibility and effectiveness of home testing.Trial registration numberISRCTN11676160.

Spiders are commonly found in terrestrial environments and many rely heavily on their silks for fitness related tasks such as reproduction and dispersal. Although rare, a few species occupy aquatic or semi-aquatic habitats and for them, silk-related specializations are also essential to survive in aquatic environments. Most spider silks studied to date are from cob-web and orb-web weaving species, leaving the silks from many other terrestrial spiders as well as water-associated spiders largely undescribed. Here, we characterize silks from three Dictynoidea species: the aquatic spiders Argyroneta aquatica and Desis marina as well as the terrestrial Badumna longinqua . From silk gland RNA-Seq libraries, we report a total of 47 different homologs of the spidroin (spider fibroin) gene family. Some of these 47 spidroins correspond to known spidroin types (aciniform, ampullate, cribellar, pyriform, and tubuliform), while other spidroins represent novel branches of the spidroin gene family. We also report a hydrophobic amino acid motif (GV) that, to date, is found only in the spidroins of aquatic and semi-aquatic spiders. Comparison of spider silk sequences to the silks from other water-associated arthropods, shows that there is a diversity of strategies to function in aquatic environments.

Abstract Rationale Pooling data from multiple cohorts and extending the time frame across childhood should minimize study-specific effects, enabling better characterization of childhood wheezing. Objectives To analyze wheezing patterns from early childhood to adolescence using combined data from five birth cohorts. Methods We used latent class analysis to derive wheeze phenotypes among 7,719 participants from five birth cohorts with complete report of wheeze at five time periods. We tested the associations of derived phenotypes with late asthma outcomes and lung function, and investigated the uncertainty in phenotype assignment. Results We identified five phenotypes: never/infrequent wheeze (52.1%), early onset preschool remitting (23.9%), early onset midchildhood remitting (9%), persistent (7.9%), and late-onset wheeze (7.1%). Compared with the never/infrequent wheeze, all phenotypes had higher odds of asthma and lower forced expiratory volume in 1 second and forced expiratory volume in 1 second/forced vital capacity in adolescence. The association with asthma was strongest for persistent wheeze (adjusted odds ratio, 56.54; 95% confidence interval, 43.75–73.06). We observed considerable within-class heterogeneity at the individual level, with 913 (12%) children having low membership probability (<0.60) of any phenotype. Class membership certainty was highest in persistent and never/infrequent, and lowest in late-onset wheeze (with 51% of participants having membership probabilities <0.80). Individual wheezing patterns were particularly heterogeneous in late-onset wheeze, whereas many children assigned to early onset preschool remitting class reported wheezing at later time points. Conclusions All wheeze phenotypes had significantly diminished lung function in school-age children, suggesting that the notion that early life episodic wheeze has a benign prognosis may not be true for a proportion of transient wheezers. We observed considerable within-phenotype heterogeneity in individual wheezing patterns.

Groups were well matched for age (P = 0.11), body mass index (P = 0.25), FEV1% predicted (P = 0.85), smoking status (P = 0.3), serum total IgE (P = 0.23), fractional exhaled nitric oxide (P = 0.58), blood eosinophil count (P = 0.58), and treatment (intramuscular triamcinolone [P = 0.71], oral prednisolone [P = 0.31], or daily inhaled corticosteroids [beclomethasone dipropionate equivalent]; P = 0.31). H.J.D. is supported by an Asthma UK Senior Clinical Academic Development Award (AuK-SCAD-2013-229), the J P Moulton Charitable Foundation, a North West Lung Centre Charity project grant, and the University of Manchester Dean's Prize for Clinicians. D.W.R. is a Wellcome Trust Investigator (107849/Z/15/Z) and received a Medical Research Council Program grant (MR/P023576/1). A.S. was supported by grants from the Medical Research Council, National Institute for Health Research, EU FP7, and the NIHR Manchester Biomedical Research Centre.