Recent advances in understanding lung function development

Recent years have witnessed critical contributions to our understanding of the determinants and long-term implications of lung function development. In this article, we review studies that have contributed to advances in understanding lung function development and its critical importance for lung health into adult life. In particular, we have focused on early life determinants that include genetic factors, perinatal events, environmental exposures, lifestyle, infancy lower respiratory tract infections, and persistent asthma phenotypes. Longitudinal studies have conclusively demonstrated that lung function deficits that are established by school age may track into adult life and increase the risk of adult lung obstructive diseases, such as chronic obstructive pulmonary disease. Furthermore, these contributions have provided initial evidence in support of a direct influence by early life events on an accelerated decline of lung function and an increased susceptibility to its environmental determinants well into adult life. As such, we argue that future health-care programs based on precision medicine approaches that integrate deep phenotyping with tailored medication and advice to patients should also foster optimal lung function growth to be fully effective

Climate change and respiratory disease: clinical guidance for healthcare professionals.

UNLABELLED Climate change is one of the major public health emergencies with already unprecedented impacts on our planet, environment and health. Climate change has already resulted in substantial increases in temperatures globally and more frequent and extreme weather in terms of heatwaves, droughts, dust storms, wildfires, rainstorms and flooding, with prolonged and altered allergen and microbial exposure as well as the introduction of new allergens to certain areas. All these exposures may have a major burden on patients with respiratory conditions, which will pose increasing challenges for respiratory clinicians and other healthcare providers. In addition, complex interactions between these different factors, along with other major environmental risk factors (e.g. air pollution), will exacerbate adverse health effects on the lung. For example, an increase in heat and sunlight in urban areas will lead to increases in ozone exposure among urban populations; effects of very high exposure to smoke and pollution from wildfires will be exacerbated by the accompanying heat and drought; and extreme precipitation events and flooding will increase exposure to humidity and mould indoors. This review aims to bring respiratory healthcare providers up to date with the newest research on the impacts of climate change on respiratory health. Respiratory clinicians and other healthcare providers need to be continually educated about the challenges of this emerging and growing public health problem and be equipped to be the key players in solutions to mitigate the impacts of climate change on patients with respiratory conditions. EDUCATIONAL AIMS To define climate change and describe major related environmental factors that pose a threat to patients with respiratory conditions.To provide an overview of the epidemiological evidence on climate change and respiratory diseases.To explain how climate change interacts with air pollution and other related environmental hazards to pose additional challenges for patients.To outline recommendations to protect the health of patients with respiratory conditions from climate-related environmental hazards in clinical practice.To outline recommendations to clinicians and patients with respiratory conditions on how to contribute to mitigating climate change

Cesarean delivery, preterm birth and risk of food allergy : nationwide Swedish cohort study of over 1 million children

Background & Objectives: Little is known about early life risk factors for food allergy in children. We examined the association between perinatal characteristics and future risk of food allergy in offspring. Methods: This nationwide Swedish cohort study of 1,086,378 children born in Sweden in 2001-2012 used prospectively recorded data from health care registers. Using Cox regression, we estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for the association between perinatal characteristics (e.g. caesarean delivery, preterm birth) and food allergy as defined by diagnoses in the National Patient Register, adjusting for infant sex and maternal factors (age at delivery, country of birth, parity, smoking, body mass index and asthma/pulmonary disease). Results: During the 13-year follow-up, 26,732 children (2.5%) were diagnosed with food allergy. Food allergy was positively associated with caesarean delivery (HR=1.21; 95%CI=1.18-1.25), large for gestational age (HR=1.15; 95%CI=1.10-1.19) and low 5-minute Apgar score (HR=1.22, 95CI=1.10-1.36) but negatively associated with very preterm birth (<32 weeks of gestation: HR=0.74; 95%CI=0.56-0.98). No association was found between food allergy and moderately preterm birth, low birth weight or small for gestational age. Risk estimates were similar when the outcome was restricted to two records of diagnosed food allergy. In 1,000 children undergoing caesarean delivery, an extra 5 developed food allergy compared with the reference group, suggesting that 17% of food allergy in children born with caesarean delivery can be explained by this exposure (attributable fraction). Conclusions: Caesarean delivery was associated with increased risk of food allergy, whereas very preterm birth with decreased risk.NoneAccepte

Allergies to food and airborne allergens in children and adolescents:role of epigenetics in a changing environment

Allergic diseases affect millions of children and adolescents worldwide. In this Review, we focus on allergies to food and airborne allergens and provide examples of prevalence trends during a time when climate change is of increasing concern. Profound environmental changes have affected natural systems in terms of biodiversity loss, air pollution, and climate. We discuss the potential links between these changes and allergic diseases in children, and the clinical implications. Several exposures of relevance for allergic disease also correlate with epigenetic changes such as DNA methylation. We propose that epigenetics could be a promising tool by which exposures and hazards related to a changing environment can be captured. Epigenetics might also provide promising biomarkers and help to elucidate the mechanisms related to allergic disease initiation and progress.</p

Allergies to food and airborne allergens in children and adolescents : role of epigenetics in a changing environment

Allergic diseases today affect millions of children and adolescents worldwide. In this review, we focus on allergies to food and airborne allergens, and provide examples of prevalence trends during a time when climate change is of increasing concern. Profound environmental changes have affected natural systems in terms of biodiversity loss, air pollution levels and climate change. We discuss potential links between these changes and allergic diseases in children, as well as clinical implications. Several exposures of relevance for allergic disease also correlate with epigenetic changes such as DNA-methylation levels. We propose that epigenetics may offer a promising tool by which exposures and hazards related to a changing environment may be captured. Epigenetics may also provide promising biomarkers and help elucidation of mechanisms related to allergic disease initiation and progress. Key messages: • Allergic diseases affect millions of children and adolescents worldwide; between 5 and 30% of adolescents report rhino-conjunctivitis symptoms and up to 10 % report food allergy. • Links between climate change and allergic diseases are of increasing concern, and these include: extended and altered pollen seasons, spread of allergens to new areas along with changing and warmer climate, air pollution exposures changes, increasing exposure to heat events, and altered biodiversity. • These new climate change aspects of allergic diseases have clinical implications for prevention, diagnostics and treatment. • Epigenetic changes, exemplified by DNA methylation, are associated both with environmental exposures and allergic diseases, although causality needs to be explored further. • There is potential in the use of epigenetic signatures and omics profiles to detect and monitor aspects of environmental exposures of relevance for health and disease in children and adolescents.H2020 research program (TRIBAL, No 757919; EXPANSE project, No 874627; Prominent)Swedish Research CouncilSwedish Heart-Lung FoundationRegion StockholmUS National Institutes of Health (R01 AI118833, R01 AI147028, U01 AI160082, and U19 AI136053)ZON-MW (VICI grant)Netherlands Lung FoundationGSKVertexTEVA the NetherlandsNovo Nordisk Foundation Challenge Programme (#NNF17OC0027812)Accepte

Allergies to food and airborne allergens in children and adolescents: role of epigenetics in a changing environment.

Allergic diseases affect millions of children and adolescents worldwide. In this Review, we focus on allergies to food and airborne allergens and provide examples of prevalence trends during a time when climate change is of increasing concern. Profound environmental changes have affected natural systems in terms of biodiversity loss, air pollution, and climate. We discuss the potential links between these changes and allergic diseases in children, and the clinical implications. Several exposures of relevance for allergic disease also correlate with epigenetic changes such as DNA methylation. We propose that epigenetics could be a promising tool by which exposures and hazards related to a changing environment can be captured. Epigenetics might also provide promising biomarkers and help to elucidate the mechanisms related to allergic disease initiation and progress

Effects of inhaled corticosteroids on DNA methylation in peripheral blood cells in children with asthma

Non peer reviewe

Development and comorbidity of eczema, asthma and rhinitis to age 12 : data from the BAMSE birth cohort

BACKGROUND: Allergy-related diseases are a public health issue, but knowledge on development and comorbidity among children is scarce. The aim was to study the development of eczema, asthma and rhinitis in relation to sex and parental allergy, in a population-based cohort, during childhood. METHODS: At 1, 2, 4, 8 and 12 years, parental questionnaires were used to obtain data on allergy-related diseases. Complete data for all five follow-up occasions were available from 2916 children. Odds ratios for the risk of any allergy-related disease in relation to heredity and sex were calculated using generalized estimating equations. RESULTS: At 12 years, 58% of the children had had eczema, asthma and/or rhinitis at some time. Disease turnover was high for all three diseases throughout the study. Comorbidity increased with age, and at 12 years, 7.5% of all the children were affected by at least two allergy-related diseases. Parental allergy was associated with increased comorbidity and more persistent disease and increased the risk of having any allergy-related disease (adjusted OR 1.76; 95% CI 1.57-1.97) up to 12 years. Male sex was associated with an increased risk throughout childhood. Boys and girls did not differ in disease persistence, and for comorbidity, the differences were minor. CONCLUSIONS: Allergy-related diseases may affect a majority of children. Eczema, asthma and rhinitis develop dynamically throughout childhood, and allergic comorbidity is common. These findings indicate that allergy-related diseases should be neither seen nor studied as isolated entities.Stockholm County CouncilHjärt- och LungfondenVetenskapsrådetAstma- och allergiförbundetManuscrip

Neuropeptide S (NPS) variants modify the signaling and risk effects of NPS Receptor 1 (NPSR1) variants in asthma

Single nucleotide polymorphisms (SNPs) close to the gain-of-function substitution, Asn(107) Ile (rs324981, A>T), in Neuropeptide S Receptor 1 (NPSR1) have been associated with asthma. Furthermore, a functional SNP (rs4751440, G>C) in Neuropeptide S (NPS) encodes a Val(6)Leu substitution on the mature peptide that results in reduced bioactivity. We sought to examine the effects of different combinations of these NPS and NPSR1 variants on downstream signaling and genetic risk of asthma. In transfected cells, the magnitude of NPSR1-induced activation of cAMP/PKA signal transduction pathways and downstream gene expression was dependent on the combination of the NPS and NPSR1 variants with NPS-Val(6)/NPSR1-Ile(107) resulting in strongest and NPS-Leu(6)/NPSR1-Asn(107) in weakest effects, respectively. One or two copies of the NPS-Leu(6) (rs4751440) were associated with physician-diagnosed childhood asthma (OR: 0.67, 95% CI 0.49-0.92, p = 0.01) and together with two other linked NPS variants (rs1931704 and rs10830123) formed a protective haplotype (p = 0.008) in the Swedish birth cohort BAMSE (2033 children). NPS rs10830123 showed epistasis with NPSR1 rs324981 encoding Asn(107)Ile (p = 0.009) in BAMSE and with the linked NPSR1 rs17199659 (p = 0.005) in the German MAGIC/ISAAC II cohort (1454 children). In conclusion, NPS variants modify asthma risk and should be considered in genetic association studies of NPSR1 with asthma and other complex diseases.Peer reviewe