Use of Swedish smokeless tobacco during pregnancy: A systematic review of pregnancy and early life health risk.

BACKGROUND AND AIMS: Smokeless tobacco is a heterogeneous product group with diverse composition and prevalence globally. Tobacco use during pregnancy is concerning due to the risk of adverse pregnancy outcomes and effects on child health. Nicotine may mediate several of these effects. This systematic review measured health outcomes from Swedish smokeless tobacco (snus) use during pregnancy. METHOD: Literature search was conducted by an information specialist in May 2022. We included human studies of snus use during pregnancy compared with no tobacco use, assessed risk of bias, conducted a meta-analysis and assessed confidence in effect-estimates using Grading of Recommendations, Assessment, Development and Evaluations (GRADE). RESULTS: We included 18 cohort studies (42 to 1 006 398 participants). Snus use during pregnancy probably (moderate confidence in risk estimates) increase the risk of neonatal apnea, adjusted odds ratio 95% confidence interval [aOR (95% CI)] 1.96 (1.30 to 2.96). Snus use during pregnancy possibly (low confidence in risk estimates) increase the risk of stillbirths aOR 1.43 (1.02 to 1.99), extremely premature births aOR 1.69 (1.17 to 2.45), moderately premature birth aOR 1.26 (1.15 to 1.38), SGA aOR 1.26 (1.09 to 1.46), reduced birth weight mean difference of 72.47 g (110.58 g to 34.35 g reduction) and oral cleft malformations aOR 1.48 (1.00 to 2.21). It is uncertain (low confidence in risk estimates, CI crossing 1) whether snus use during pregnancy affects risk of preeclampsia aOR 1.11 (0.97 to 1.28), antenatal bleeding aOR 1.15 (0.92 to 1.44) and very premature birth aOR 1.26 (0.95 to 1.66). Risk of early neonatal mortality and altered heart rate variability is uncertain, very low confidence. Snus using mothers had increased prevalence of caesarean sections, low confidence. CONCLUSIONS: This systematic review reveals that use of smokeless tobacco (snus) during pregnancy may adversely impact the developing child.

Maternal use of nicotine products and breastfeeding 3 months postpartum.

AIM: We aimed to determine the prevalence of and factors associated with maternal use of nicotine products in relation to breastfeeding. METHODS: Nicotine use 3 months postpartum was determined in the Scandinavian PreventADALL mother-child birth cohort study recruiting 1837 women from 2014 to 2016. Electronic questionnaires at 18 weeks pregnancy and 3 months postpartum provided information on snus use, smoking or other nicotine use, infant feeding and socio-economic factors. The risk of nicotine use in relation to breastfeeding was analysed with logistic regression. RESULTS: Overall, 5.6% of women used snus (2.9%), smoked (2.7%) or both (n = 2) 3 months postpartum, while one used other nicotine products. Among the 1717 breastfeeding women, 95.1% reported no nicotine use, while 2.4% used snus, 2.5% smoked and one dual user. Compared to 3.7% nicotine use in exclusively breastfeeding women (n = 1242), the risk of nicotine use increased by partly (OR 2.26, 95% CI 1.45-3.52) and no breastfeeding (OR 4.58, 95% CI 2.57-8.21). Nicotine use before (14.5% snus, 16.4% smoking) or in pregnancy (0.2% snus, 0.4% smoking) significantly increased the risk of using nicotine during breastfeeding. CONCLUSION: Few breastfeeding women used snus or smoked 3 months postpartum, with increased risk by nicotine use before or during pregnancy.

Parental severity assessment predicts supportive care in infant bronchiolitis.

AIM: In infants with acute bronchiolitis, the precision of parental disease severity assessment is unclear. We aimed to determine if parental assessment at the time of hospitalisation predicted the use of supportive care, and subsequently determine the likelihood that the infant with acute bronchiolitis would receive supportive care. METHODS: From the Bronchiolitis ALL south-east Norway study, we included all 267, 0-12 month old, infants with acute bronchiolitis whose parents at the time of hospitalisation completed a three-item visual analogue scale (VAS) concerning Activity, Feeding and Illness. Respiratory rate, oxygen saturation (SpO2 ) and use of supportive care were recorded daily. By multivariate logistic regression analyses we included significant predictors available at hospital admission to predict the use of supportive care. RESULTS: The parental Activity, Feeding and Illness VAS scores significantly predicted supportive care with odds ratios of 1.23, 1.26 and 1.36, respectively. The prediction algorithm included parental Feeding and Illness scores, SpO2 , gender and age, with an area under the curve of 0.76 (95% CI 0.69, 0.81). A positive likelihood ratio of 2.1 gave the highest combined sensitivity of 81% and specificity of 61%. CONCLUSION: Parental assessment at hospital admission moderately predicted supportive care treatment in infants with acute bronchiolitis.

Recommendations for the Appropriate Structure, Communication, and Investigation of Tobacco Harm Reduction Claims. An Official American Thoracic Society Policy Statement.

RATIONALE: The tobacco harm reduction literature is replete with vague language, far-reaching claims, and unwarranted certainty. The American Thoracic Society has increasingly recognized the need for a framework for reliably making such claims. Evidence-based standards improving the scientific value and transparency of harm reduction claims are expected to improve their trustworthiness, clarity, and consistency. METHODS: Experts from relevant American Thoracic Society committees identified key topic areas for discussion. Literature search strategy included English language articles across Medline, Google Scholar, and the Cochrane Collaborative databases, with expanded search terms including tobacco, addiction, smoking, cigarettes, nicotine, and harm reduction. Workgroup members synthesized their evidentiary summaries into a list of candidate topics suitable for inclusion in the final report. Breakout groups developed detailed content maps of each topic area, including points to be considered for suggested recommendations. Successive draft recommendations were modified using an iterative consensus process until unanimous approval was achieved. Patient representatives ensured the document's relevance to the lay public. RESULTS: Fifteen recommendations were identified, organized into four framework elements dealing with: estimating harm reduction among individuals, making claims on the basis of population impact, appropriately careful use of language, and ethical considerations in harm reduction. DISCUSSION: This statement clarifies important principles guiding valid direct and inferential harm reduction claims. Ideals for effective communication with the lay public and attention to unique ethical concerns are also delineated. The authors call for formal systems of grading harm reduction evidence and regulatory assurances of longitudinal surveillance systems to document the impact of harm reduction policies.

ERS technical standard on bronchial challenge testing: pathophysiology and methodology of indirect airway challenge testing.

Recently, this international task force reported the general considerations for bronchial challenge testing and the performance of the methacholine challenge test, a "direct" airway challenge test. Here, the task force provides an updated description of the pathophysiology and the methods to conduct indirect challenge tests. Because indirect challenge tests trigger airway narrowing through the activation of endogenous pathways that are involved in asthma, indirect challenge tests tend to be specific for asthma and reveal much about the biology of asthma, but may be less sensitive than direct tests for the detection of airway hyperresponsiveness. We provide recommendations for the conduct and interpretation of hyperpnoea challenge tests such as dry air exercise challenge and eucapnic voluntary hyperpnoea that provide a single strong stimulus for airway narrowing. This technical standard expands the recommendations to additional indirect tests such as hypertonic saline, mannitol and adenosine challenge that are incremental tests, but still retain characteristics of other indirect challenges. Assessment of airway hyperresponsiveness, with direct and indirect tests, are valuable tools to understand and to monitor airway function and to characterise the underlying asthma phenotype to guide therapy. The tests should be interpreted within the context of the clinical features of asthma.

The toxicity of E-cigarettes and children's respiratory health.

Electronic cigarettes (E-cig), also referred to as Electronic Nicotine Delivery System (ENDS), were initially developed in 2003 to reduce the harmful effects of tobacco smoking. Since then, E-cig have become widely available in many countries and are used by many young people who would be unlikely to take up cigarette smoking. However, the adverse effects on child health remain largely unknown. E-cigs are available through regulated sale in many countries, but easily accessible by the internet in others. Adverse effects may be ascribed to the nicotine itself, to the accompanying substances in the aerosol (often referred to as vapour) or to temperature modifications of the content. There is a lack of human studies to assess respiratory effects of nicotine exposure to the unborn or young child. Also assessing the effects of the vaping content apart from nicotine is challenging, with the huge variety of exposure by frequency, duration and content, but experimental studies are on the way that may indicate the level of harm by such products. This article will summarize what is currently known about the use of E-cigs in children and in pregnancy, and discuss adverse effects of direct or in utero exposure to E-cig on the respiratory health of children. We thereby hope to provide a background for discussing potential harms to the respiratory system of children by E-cig exposure in pregnancy and early post-natal life, in a setting where an increasing proportion of adolescent and young adults use E-cigs, marketed to be 95% less harmful than conventional cigarettes.

Perceived exercise limitation in asthma: The role of disease severity, overweight, and physical activity in children.

BACKGROUND: Children with asthma may be less physically active than their healthy peers. We aimed to investigate whether perceived exercise limitation (EL) was associated with lung function or bronchial hyper-responsiveness (BHR), socioeconomic factors, prenatal smoking, overweight, allergic disease, asthma severity, or physical activity (PA). METHODS: The 302 children with asthma from the 10-year examination of the Environment and Childhood Asthma birth cohort study underwent a clinical examination including perceived EL (structured interview of child and parent(s)), measure of overweight (body mass index by sex and age passing through 25 kg/m2 or above at 18 years), exercise-induced bronchoconstriction (forced expiratory volume in one-second (FEV1 ) pre- and post-exercise), methacholine bronchial challenge (severe BHR; provocative dose causing ≥20% decrease in FEV1 ≤ 1 µmol), and asthma severity score (dose of controller medication and exacerbations last 12 months). Multivariate logistic regression analyses were conducted to assess associations with perceived EL. RESULTS: In the final model explaining 30.1%, asthma severity score (OR: 1.49, (1.32, 1.67)) and overweight (OR: 2.35 (1.14, 4.82)) only were significantly associated with perceived EL. Excluding asthma severity and allergic disease, severe BHR (OR: 2.82 (1.38, 5.76)) or maximal reduction in FEV1 post-exercise (OR: 1.48 (1.10, 1.98)) and overweight (OR: 2.15 (1.13, 4.08) and 2.53 (1.27, 5.03)) explained 9.7% and 8.4% of perceived EL, respectively. CONCLUSIONS: Perceived EL in children with asthma was independently associated with asthma severity and overweight, the latter doubling the probability of perceived EL irrespectively of asthma severity, allergy status, socioeconomic factors, prenatal smoking, or PA.

An Official American Thoracic Society Research Statement: Current Understanding and Future Research Needs in Tobacco Control and Treatment.

INTRODUCTION: Since the mid-20th century, the scientific community has substantially improved its understanding of the worldwide tobacco epidemic. Although significant progress has been made, the sheer enormity and scope of the global problem put it on track to take a billion lives this century. Curbing the epidemic will require maximizing the impact of proven tools as well as the development of new, breakthrough methods to help interrupt the spread of nicotine addiction and reduce the downstream morbidity. METHODS: Members of the Tobacco Action Committee of the American Thoracic Society queried bibliographic databases, including Medline, Embase, and the Cochrane Collaborative, to identify primary sources and reviews relevant to the epidemic. Exploded search terms were used to identify evidence, including tobacco, addiction, smoking, cigarettes, nicotine, and smoking cessation. Evidence was consolidated into three thematic areas: (1) determinants of risk, (2) maternal-fetal exposure, and (3) current tobacco users. Expert panel consensus regarding current gaps in understanding and recommendations for future research priorities was generated through iterative discussion. RESULTS: Although much has been accomplished, significant gaps in understanding remain. Implementation often lags well behind insight. This report identifies a number of investigative opportunities for significantly reducing the toll of tobacco use, including: (1) the need for novel, nonlinear models of population-based disease control; (2) refinement of "real-world" models of clinical intervention in trial design; and (3) understanding of mechanisms by which intrauterine smoke exposure may lead to persistent, tobacco-related chronic disease. DISCUSSION: In the coming era of tobacco research, pooled talent from multiple disciplines will be required to further illuminate the complex social, environmental and biological codeterminants of tobacco dependence.

Childhood lung function and the association with ß2-adrenergic receptor haplotypes.

AIM: To determine associations between ADRB2 polymorphisms and lung function through childhood, and possible modification by gender, pet keeping or tobacco smoke. METHODS: Four ADRB2 single nucleotide polymorphisms (rs1042711, rs1042713, rs1042714 and rs1800888) were genotyped in 953 children from the prospective birth cohort 'Environment and Childhood Asthma' study and analysed for association with flow-volume parameters at birth (tidal breathing) and at 10 years of age (maximally forced), stratified by environmental exposures. RESULTS: The risk of reduced lung function was reduced in 10-year-old children carrying the most common ADRB2 haplotype (CGGC) (OR 0.45 (95% CI 0.25, 0.82)), whereas there was no association between lung function at birth and ADRB2 haplotypes. Tobacco smoke exposure, gender and pet keeping did not significantly interact with the haplotypes in influencing lung function. CONCLUSION: This study demonstrates a possible protective effect by the ADRB2 haplotype I (CGGC) on reduced FEV1 in 10-year-old children, whereas no ADRB2 geno-/haplotypes were significantly associated with neonatal lung function. The ADRB2 gene thus appears to contribute to lung function development in childhood, independently of smoking, pets and gender.

Pet keeping and tobacco exposure influence CD14 methylation in childhood.

BACKGROUND: Several CD14 gene-environment interactions in relation to the development of allergic diseases have been reported, but the underlying biological mechanisms are unclear. We recently showed that CD14 methylation increased during childhood, parallelling a decreased impact of CD14 polymorphisms on soluble CD14 levels. Here, we aim to explore whether environmental stimuli during childhood affects CD14 methylation, thereby providing a biological mechanism through which environment may modulate genetic effect. METHODS: CD14 methylation levels were quantified in 157 children from the prospective Environment and Childhood Asthma birth cohort at ages 2 and 10. Associations between CD14 methylation levels and house dust levels of endotoxin, ß(1,3)-glucans (at 2 yr only), allergens (dog, cat, and house dust mite), pet keeping and tobacco smoke exposure (TSE; questionnaire data) at 2 and 10 yr were explored. RESULTS: Children in homes without pets had larger increases in CD14 methylation through childhood (2-10 yr) compared with children with pets (2.1% increase (p = 0.003) vs. 0.4% decrease (n.s.), global p = 0.04). At 10 yr of age, lower CD14 methylation values were found in children with pets compared with children without pets at both 2 and 10 yr (5.4% vs. 7.5% [p = 0.02]). A similar trend was detected for TSE; children not exposed show larger increases in CD14 methylation, most pronounced in school-age girls exposed vs. not exposed to tobacco (5.5% vs. 7.5% methylation, p = 0.037). CONCLUSION: Pet keeping and TSE appears to limit increase in CD14 methylation from 2 to 10 yr of age. This may partly explain the diverging CD14 allele associations with allergic diseases detected in different environments.

The European Respiratory Society spirometry tent: a unique form of screening for airway obstruction.

In order to raise public awareness of the importance of early detection of airway obstruction and to enable many people who had not been tested previously to have their lung function measured, the European Lung Foundation and the European Respiratory Society (ERS) organised a spirometry testing tent during the annual ERS Congresses in 2004-2009. Spirometry was performed during the ERS Congresses in volunteers; all participants answered a simple, brief questionnaire on their descriptive characteristics, smoking and asthma. Portable spirometers were freely provided by the manufacturer. Nurses and doctors from pulmonary departments of local hospitals/universities gave their service for free. Lower limit of normal (LLN) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for diagnosing and grading airway obstruction were used. Of 12,448 participants in six congress cities, 10,395 (83.5%) performed acceptable spirometry (mean age 51.0 ± 18.4 yrs; 25.5% smokers; 5.5% asthmatic). Airway obstruction was present in 12.4% of investigated subjects according to LLN criteria and 20.3% according to GOLD criteria. Through multinomial logistic regression analysis, age, smoking habits and asthma were significant risk factors for airway obstruction. Relative risk ratio and 95% confidence interval for LLN stage I, for example, was 2.9 (2.0-4.1) for the youngest age (≤ 19 yrs), 1.9 (1.2-3.0) for the oldest age (≥ 80 yrs), 2.4 (2.0-2.9) for current smokers and 2.8 (2.2-3.6) for reported asthma diagnosis. In addition to being a useful advocacy tool, the spirometry tent represents an unusual occasion for early detection of airway obstruction in large numbers of city residents with an important public health perspective.

Alpha-nicotinic acetylcholine receptor and tobacco smoke exposure: effects on bronchial hyperresponsiveness in children.

BACKGROUND: The CHRNA 3 and 5 genes on chromosome 15 encode the alpha subunits of the nicotinic acetylcholine receptor, mediating airway cholinergic activity. Polymorphisms are associated with cigarette smoking, chronic obstructive pulmonary disease, and lung cancer. AIMS: To determine possible associations between CHRNA 3/5 SNP rs8034191 and asthma or lung function in children in one local and one replicate multinational population, and assess if tobacco smoke modified the associations. MATERIALS AND METHODS: The rs8034191 SNP genotyped in 551 children from the environment and childhood asthma (ECA) birth cohort study in Oslo, Norway, and in 516 families from six European centers [the Genetics of Asthma International Network (GAIN) study] was tested for genotypic or allelic associations to current or history of asthma, allergic sensitization (≥ one positive skin prick tests), bronchial hyperresponsiveness (BHR), and lung function (FEV(1%) of predicted and FEV(1) /FVC ratio over/ below the 5th percentile). RESULTS: Although the TT and CT genotypes at SNP rs 8034191 were overall significantly associated with BHR (OR = 3.9, 95% CI 1.5-10.0, p = 0.005), stratified analyses according to exposure to maternal smoking in-utero or indoor smoking at 10 yrs of age showed significant association (OR = 4.4, 95% CI 1.5-12.6, p = 0.006 and OR 5.6, 95% CI 1.7-18.5, p = 0.004, respectively) only in the non-exposed and not in exposed children. The SNP-BHR association was replicated in the non-tobacco-smoke-exposed subjects in one of the GAIN centers (BHR associated with the T allele (p = 0.034)), but not in the collated GAIN populations. Asthma, allergic sensitization, and lung function were not associated with the rs8034191 alleles. CONCLUSION: An interaction between tobacco smoke exposure and a CHRNA3/5 polymorphism was found for BHR in children, but CHRNA3/5 was not associated with asthma or lung function.

Eoxins: a new inflammatory pathway in childhood asthma.

BACKGROUND: Increased levels of leukotrienes (LTs) in exhaled breath condensate (EBC) are associated with asthma and bronchial hyperresponsiveness (BHR), whereas eicosanoids generated through the 15-lipoxygenase (LO) pathway (15-hydroxyeicosatetraenoic acid [HETE] and eoxins) have been less studied. OBJECTIVE: We investigated whether metabolites of the 5- and 15-LO pathways in EBC are associated with childhood asthma, asthma severity, and clinical parameters. METHODS: The present study included 131 school-aged children (27 children with problematic severe asthma, 80 children with mild-to-moderate asthma, and 24 healthy children) from the Severe Asthma Recognized in Childhood study and 19 children with other nonasthmatic chronic lung diseases. Clinical work-up included spirometry, fractional exhaled nitric oxide measurements, skin prick testing, and methacholine challenge. Eicosanoids were analyzed in EBC by using mass spectrometry and are reported as concentrations (in picograms per milliliter) and eicosanoid/palmitic acid (PA) ratios. RESULTS: Eoxin C4/PA, eoxin D4/PA, eoxin E4/PA, 15-HETE/PA, and LTC4/PA ratios were significantly increased in asthmatic versus healthy children. Eoxin D4/PA and LTE4/PA ratios were also significantly higher in children with BHR. A nonsignificant trend was observed toward higher eoxin/PA ratios with increasing asthma severity. In contrast to asthma, children with chronic lung disease had the highest 15-HETE/PA, LTC4/PA, LTE4/PA, and LTB4/PA ratios. CONCLUSION: The results point to increased activity of the 15-LO inflammatory pathway in childhood asthma. Mass spectrometric analyses of EBC demonstrate that increased eoxin levels not only accompany the increased 5-LO product LTC4 but are also associated with BHR. These markers might represent a new therapeutic target for asthma treatment.

An official American Thoracic Society workshop report: tobacco control initiatives within the American Thoracic Society.

Cigarette smoking represents the single most preventable cause of premature morbidity and mortality in the United States and the burden of tobacco use is apparent world-wide. Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease, the third leading cause of death in the United States in 2004. The American Thoracic Society (ATS) and its members have contributed significantly to an understanding of the biological and pathophysiologic mechanisms responsible for the development and management of tobacco-attributable disease and disability. The society's active involvement in tobacco control advocacy and policy-related initiatives are central to its mission. Within the ATS, there is also increased interest in accelerating the society's efforts to understand the mechanisms responsible for the uptake, persistence, and cessation of tobacco use. Scientific, clinical, and educational activities that include an examination of these underlying mechanisms are warranted. This paper describes findings from an ATS initiative that developed a preliminary strategy for enhancing scientific, clinical, educational, and policy-related tobacco control efforts that are consistent with the vision of the ATS. The specific aims of this project included the identification of existing mechanisms, as well as the current governance in place within the ATS infrastructure, to address tobacco control issues related to scientific inquiry, policy initiatives, and advocacy for tobacco control. This assessment generated recommendations to inform the ATS leadership with regard to the future development of relevant tobacco control initiatives.

Obese children playing towards an active lifestyle.

AIM: To determine whether five months of guided active play in overweight or obese children and adolescents under multi-disciplinary management for weight reduction leads to increased physical activity levels in leisure time, as well as changes in aerobic fitness and body composition. METHODS: Sixty overweight or obese children and adolescents were randomly assigned to an intervention or control group. All participants received dietary advice and were encouraged to increase physical activity level. The intervention group additionally participated in 60-minute guided active play/physical activity twice a week for 5 months. Physical activity was recorded; aerobic fitness and body composition were measured at inclusion and after cessation of intervention. RESULTS: Physical activity level during weekend days was significantly higher for the intervention group compared with the controls after 5 months intervention (p=0.04). The mean reduction in percentage of body fat was 1.8% (95%CI: 0.6, 3.1) in the intervention group (p=0.04) and not significant among the controls (0.9 [-0.9, 2.7]). There was no change in aerobic fitness. CONCLUSION: Five months of guided active play was associated with increased physical activity levels during weekend days and reduced body fat, although weakly, in overweight and obese children and adolescents participating in multi-disciplinary weight reduction programmes.

Comparison of four nasal sampling methods for the detection of viral pathogens by RT-PCR-A GA(2)LEN project.

The aim of this study was to compare the efficacy and patient discomfort between four techniques for obtaining nasal secretions. Nasal secretions from 58 patients with symptoms of a common cold, from three clinical centers (Amsterdam, Lodz, Oslo), were obtained by four different methods: swab, aspirate, brush, and wash. In each patient all four sampling procedures were performed and patient discomfort was evaluated by a visual discomfort scale (scale 1-5) after each procedure. Single pathogen RT-PCRs for Rhinovirus (RV), Influenza virus and Adenovirus, and multiplex real-time PCR for RV, Enterovirus, Influenza virus, Adenovirus, Respiratory Syncytial Virus (RSV), Parainfluenza virus, Coronavirus, Metapneumovirus, Bocavirus and Parechovirus were performed in all samples. A specific viral cause of respiratory tract infection was determined in 48 patients (83%). In these, the detection rate for any virus was 88% (wash), 79% (aspirate), 77% (swab) and 74% (brush). The degree of discomfort reported was 2.54 for swabs, 2.63 for washes, 2.68 for aspirates and 3.61 for brushings. Nasal washes yielded the highest rate of viral detection without excessive patient discomfort. In contrast, nasal brushes produced the lowest detection rates and demonstrated the highest level of discomfort.

Respiratory effects of tobacco smoking on infants and young children.

Second-hand smoke (SHS) and tobacco smoke products (TSPs) are recognised global risks for human health. The present article reviews the causal role of SHS and TSPs for respiratory disorders in infants and young children. Several studies have shown an effect of TSPs exposure during pregnancy upon lung function in the newborn infant and of SHS on symptoms and lung function after birth. From 1997 to 1999 a set of systematic reviews concerning the relationship between second-hand exposure to tobacco smoke and respiratory health in children was published in Thorax by Cook and Strachan, covering hundreds of published papers. The evidence for a causal relationship between SHS exposure and asthmatic symptoms and reduced lung function is quite strong, whereas the evidence related to the development of allergy is much weaker. There is recent evidence relating to an interaction between TSP exposure and genetic ploymorphisms, demonstrating that certain individuals are more susceptible to the effect of TSP exposure on lung health. In the present review, an overview is given for the effects of TSP exposure and SHS upon lung health in children, with a focus on infants and young children. There is a need for intervention to reduce TSP exposure in young children, by educating parents and adolescents about the health effects of TSP exposure. Recent legislation in many European countries related to smoking in the workplace is of great importance for exposure during pregnancy. Studies are needed to identify possible critical periods for TSPs to induce harmful effects upon lung health in young children and on environment-gene interactions in order to prevent harm.

CFTR gene mutations and asthma in the Norwegian Environment and Childhood Asthma study.

BACKGROUND: Several candidate genes have been implicated in the etiology of asthma, including the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR). Mutations in the CFTR gene result in derangements of mucociliary clearance. Homozygotes for CFTR mutations develop cystic fibrosis (CF), a disorder characterized mainly by lung and pancreas disease. OBJECTIVE: To investigate whether there was an increased frequency of CFTR mutations in asthma patients. METHODS: Seven hundred and three subjects aged 10-11 years from the environment and childhood asthma (ECA) study were included in the present study. Possible associations between asthma, reduced lung function, bronchial hyperresponsiveness (BHR), and increased or decreased nitrogen oxide (NO) levels (based on structural parental interview, spirometry, PD20 methacholine challenge test and exhaled NO measurements), and the five most common CFTR mutations in Norway (DeltaF508, R117H, R117C, 4005+2T-->C, 394delTT), the modulating polymorphisms IVS8(TG)mTn and the IVS8-5T were investigated. RESULTS: No association were found between asthma, reduced lung function, BHR or exhaled NO levels and CF heterozygosity. However, the IVS8(TG)11T7 haplotype was associated with normal lung function. CONCLUSIONS: Our results do not support the hypothesis that CFTR mutations or polymorphisms play a role in the pathogenesis of asthma in children. However, the distribution of Tn(TG)m haplotypes differed between individuals with reduced lung function and individuals with normal lung function.