Headache in Multiple Sclerosis: A Narrative Review.

Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system characterized by autoimmune-mediated damage to oligodendrocytes and subsequent myelin destruction. Clinical implications: Clinically, the disease presents with many symptoms, often evolving over time. The insidious onset of MS often manifests with non-specific symptoms (prodromal phase), which may precede a clinical diagnosis by several years. Among them, headache is a prominent early indicator, affecting a significant number of MS patients (50-60%). Results: Headache manifests as migraine or tension-type headache with a clear female predilection (female-male ratio 2-3:1). Additionally, some disease-modifying therapies in MS can also induce headache. For instance, teriflunomide, interferons, ponesimod, alemtuzumab and cladribine are associated with an increased incidence of headache. Conclusions: The present review analyzed the literature data on the relationship between headache and MS to provide clinicians with valuable insights for optimized patient management and the therapeutic decision-making process.

Body weight and quality of life among adolescents in Krakow.

AIM: The aim of this study was to assess the relationship between body weight and the quality of life among adolescents in Krakow, Poland. MATERIAL AND METHODS: The study comprised 1291 pupils - 632 girls and 659 boys from 17 Krakow middle schools. Their quality of life (QoL) was assessed by means of the Polish version of the KIDSCREEN-27 questionnaire. Five dimensions of QoL were analyzed as low, average and high QoL according to Polish cut-off points. The body mass index (BMI) of the adolescents was classified as underweight, normal weight, or excessive weight according to Polish growth charts. RESULTS: Low QoL was observed significantly more often in girls than in boys. Excessive weight among both girls and boys was found to be a risk factor for low QoL in the "Physical Well-being" dimension as compared to normal weight adolescents. Additionally, boys with excessive weight had a two-fold higher risk of low QoL in the "Social Support % Peers" dimension (OR=2.00; 95%CI:1.14-3.50). Underweight was associated with higher risk of low QoL in the "Physical Well-being", "Autonomy & Parents", and "Social Support % Peers" dimensions, but only among boys. CONCLUSIONS: Both, underweight and excessive weight were associated with low QoL. Excessive weight in youth was linked mainly with lower physical well-being. Underweight was a predictor of low QoL only among boys in the dimensions related to physical health, as well as relations with family and peers.

Lung function growth trajectories in non-asthmatic children aged 4-9 in relation to prenatal exposure to airborne particulate matter and polycyclic aromatic hydrocarbons - Krakow birth cohort study.

BACKGROUND: Patterns of lung function development during childhood can be helpful in understanding the pathogenesis of respiratory diseases. A variety of environmental and lifestyle factors, present from the prenatal period to adulthood, may affect or modulate lung function growth. The aim of this study was to investigate, the associations between individual growth trajectories of children's lung function during childhood and prenatal exposure to airborne fine particulate matter (PM2.5) and polycyclic aromatic hydrocarbons (PAH), which were hypothesized to adversely affect spirometry parameters. MATERIAL AND METHODS: The study group comprised 294 non-asthmatic, full term children from the Krakow birth cohort, who underwent annual spirometry testing at the ages of 4-9 years. Individual personal air monitoring of PM2.5 and PAH were performed over 48 h in the second trimester of pregnancy. Possible confounders or modifiers such as child's gender, height, atopic status and exposure to environmental tobacco smoke (ETS) were considered. Polynomial multilevel mixed models were used to assess the growth rates of children's lung functions. RESULTS: Lung function trajectories differed significantly for boys and girls for FVC, FEV1 and FEF25-75. Girls had lower rates of increase than boys: - 20.5 (95%CI: - 32.4; - 8.6) ml/year (FVC); - 19.9 (95%CI: -30.7;-9.0) ml/year (FEV1); and - 32.5 (95%CI: - 56.9; - 8.2) ml/year (FEF25-75). Spirometry functions increased with age; however the growth rate decelerated over time. Significant lung function impairment (lower FVC and FEV1 levels) was observed from 4 to 9 years among subjects prenatally exposed to higher levels of PM2.5 as well as PAH, but not in the case of FEF25-75. No significant differences were observed in the rates of increase over time in relation to prenatal PM2.5 and PAH exposure. CONCLUSION: Our results indicate that in non-asthmatic children high prenatal exposure to airborne PM2.5 and PAH is associated with lower trajectories of FVC and FEV1, but not the rate of increase over time, suggesting that the initial effect is not diminishing in time.

Urinary polycyclic aromatic hydrocarbon metabolites among 3-year-old children from Krakow, Poland.

Polycyclic aromatic hydrocarbons (PAHs) are widespread in the environment and can adversely affect human health. The aim of the present study is to describe the level of PAHs exposure in children living in Kraków, one of the most polluted cities in Poland, and to determine the relationship of urinary biomarkers with environmental PAHsexposure. Urinary monohydroxy metabolites (OH-PAHs) of 20 PAHs were assessed in 218 three-year old children, of which only 10 were present in nearly all the samples: monohydroxy metabolites of naphthalene, fluorene, phenantrene and pyrene. Of the metabolites analyzed, hydroxynaphthalenes were predominant and constituted almost 73% of total excreted OH-PAHs, while 1-OH-PYRene was the least abundant (2.3% of total OH-PAHs). All measured urinary OH-PAHs were statistically significantly correlated with each other (R = 0.165-0.880) but the highest correlation coefficients with other individual OH-PAHs and with total OH-PAHs were observed for 2-OH-FLUOR. Children exposed at home to environmental tobacco smoke (ETS) had higher concentrations of fluorene and pyrene urinary metabolites compared to those without ETS exposure; and those exposed to gas-based appliances used for cooking or heating water had higher levels of fluorene and phenanthrene metabolites than children not exposed. The use of coal, wood or oil for heating was associated with elevated levels of 1-OH-PYRene. Urinary PAHs metabolites only modestly reflect high molecular weight carcinogenic PAHs exposures such as those monitored in air in the present study. None of the measured PAHs metabolites was correlated with airborne PM2.5 and only two were slightly correlated with measured higher molecular mass airborne PAHs. The average concentrations of these specific metabolites in Polish children were much higher than observed in other pediatric populations living in developed countries. Our findings suggest that to capture various sources of PAHs, in addition to 1-OH-PYRene, biomonitoring of PAHs exposure should include 2-OH-NAP and 2-OH-FLUOR.

The quality of life among middle-school adolescents in Krakow.

AIM: The aim of the study was to describe the quality of life of Polish adolescents living in a big city and to investigate whether there are differences in this respect between girls and boys. Moreover, we would like to compare the results concerning the quality of life of the screened adolescents from Krakow with those of their European peers. MATERIAL AND METHODS: The survey was carried out in 2013-2015 in 17 middle schools in Krakow based on anonymous auditorium questionnaires. The analysis included the responses of 1387 pupils - 686 girls and 701 boys. In order to assess the quality of life, the Polish version of the international KIDSCREEN-27 questionnaire was used. Five dimensions of the quality of life (Qol) were analyzed. The specific dimensions of Qol were analyzed using 0-100 point scales, as well as T-scores standardized for the European population. RESULTS: The mean values for five dimensions of quality of life assessed by the KIDSCREEN-27 questionnaire ranged from 54 pts. to 65 pts. (maximum score 100 pts.). However, the results for the Polish adolescents were lower when compared to their European peers. The greatest differences in the level of Qol between Polish adolescents and their European peers involved the following dimensions: Psychological Well-being and School Environment. On average, girls scored their Qol lower than boys in three out of five dimensions (Physical Well-being, Psychological Well-being, Autonomy & Parents; p<0.001). Additionally, using the norm data for the Polish population (sex and age specific), more girls than boys were classified as having low Qol regarding the School Environment (23.5%vs 14.8%; p<0.001). CONCLUSIONS: Polish adolescents scored their Qol lower than their European peers. The quality of life for girls was significantly lower than of boys, except for the relation with their friends and peers (Social Support & Peers).

Depressed height gain of children associated with intrauterine exposure to polycyclic aromatic hydrocarbons (PAH) and heavy metals: the cohort prospective study.

Fetal exposure to environmental toxicants may program the development of children and have long-lasting health impacts. The study tested the hypothesis that depressed height gain in childhood is associated with prenatal exposure to airborne polycyclic aromatic hydrocarbons (PAH) and heavy metals (lead and mercury). The study sample comprised 379 children born to non-smoking mothers among whom a total of 2011 height measurements were carried out over the 9-year follow-up period. Prenatal airborne PAH exposure was assessed by personal air monitoring of the mother in the second trimester of pregnancy and heavy metals were measured in cord blood. At the age of 3 residential air monitoring was done to evaluate the level of airborne PAH, and at the age 5 the levels of heavy metals were measured in capillary blood. The effect estimates of prenatal PAH exposure on height growth over the follow-up were adjusted in the General Estimated Equation (GEE) models for a wide set of relevant covariates. Prenatal exposure to airborne PAH showed a significant negative association with height growth, which was significantly decreased by 1.1cm at PAH level above 34.7 ng/m(3) (coeff.=-1.07, p=0.040). While prenatal lead exposure was not significantly associated with height restriction, the effect of mercury was inversely related to cord blood mercury concentration above 1.2 µg/L (coeff.=-1.21, p=0.020), The observed negative impact of prenatal PAH exposure on height gain in childhood was mainly mediated by shorter birth length related to maternal PAH exposure during pregnancy. The height gain deficit associated with prenatal mercury exposure was not seen at birth, but the height growth was significantly slower at later age.

Long term effects of prenatal and postnatal airborne PAH exposures on ventilatory lung function of non-asthmatic preadolescent children. Prospective birth cohort study in Krakow.

The main goal of the study was to test the hypothesis that prenatal and postnatal exposures to polycyclic aromatic hydrocarbons (PAH) are associated with depressed lung function in non-asthmatic children. The study sample comprises 195 non-asthmatic children of non-smoking mothers, among whom the prenatal PAH exposure was assessed by personal air monitoring in pregnancy. At the age of 3, residential air monitoring was carried out to evaluate the residential PAH exposure indoors and outdoors. At the age of 5 to 8, children were given allergic skin tests for indoor allergens; and between 5 and 9 years lung function testing (FVC, FEV05, FEV1 and FEF25-75) was performed. The effects of prenatal PAH exposure on lung function tests repeated over the follow-up were adjusted in the General Estimated Equation (GEE) model for the relevant covariates. No association between FVC with prenatal PAH exposure was found; however for the FEV1 deficit associated with higher prenatal PAH exposure (above 37 ng/m(3)) amounted to 53 mL (p=0.050) and the deficit of FEF25-75 reached 164 mL (p=0.013). The corresponding deficits related to postnatal residential indoor PAH level (above 42 ng/m(3)) were 59 mL of FEV1 (p=0.028) and 140 mL of FEF25-75 (p=0.031). At the higher residential outdoor PAH level (above 90 ng/m(3)) slightly greater deficit of FEV1 (71 mL, p=0.009) was observed. The results of the study suggest that transplacental exposure to PAH compromises the normal developmental process of respiratory airways and that this effect is compounded by postnatal PAH exposure.

Prenatal exposure to polycyclic aromatic hydrocarbons and cognitive dysfunction in children.

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants produced by combustion of fossil fuel and other organic materials. Both experimental animal and human studies have reported the harmful impacts of PAH compounds on fetal growth and neurodevelopment, including verbal IQ of children. Here, we have assessed the association between cognitive function of children and prenatal PAH exposures. The study is part of an ongoing, longitudinal investigation of the health effects of prenatal exposure to air pollution on infants and children in Krakow, Poland. The subjects in this report included 170 children whose mothers were enrolled to the study in the first or second trimester of pregnancy whose cord blood were tested for PAH-DNA adducts and who were assessed at age 7 using the Wechsler Intelligence Scale for Children-Revised (WISC-R). The outcome of a priori interest was depressed verbal IQ index (DepVIQ), which is the difference between WISC-R performance and verbal IQ scores. Prenatal PAH exposure was measured by cord blood PAH-DNA adducts, an individual dosimeter, integrating exposure from various sources of exposure over the gestational period. The estimated effect of prenatal PAH exposure on cognitive function was adjusted in multivariable regression for a set of potential confounders (child's gender, parity, maternal education, breastfeeding practice, environmental tobacco smoke (ETS), and postnatal PAH exposure). The prevalence of DepVIQ was significantly higher in children with detectable PAH-DNA adducts compared to those with undetectable adducts (13.7 vs. 4.4 %,). Binary multivariable regression documented that the relative risk of DepVIQ increased threefold with a ln-unit increase in cord blood adducts (relative risk (RR) = 3.0, 95 % confidence interval (CI) 1.3-6.8). Postnatal PAH exposure also increased the risk of DepVIQ (RR = 1.6, 95 % CI 1.1-2.5). Long-term exclusive breastfeeding (at least 6 months) showed a protective effect (RR = 0.3, 95 % CI 0.1-0.9). In conclusion, these results provide further evidence that PAHs are harmful to the developing fetal brain with effects extending through childhood, with implications for the academic success of the children.

[The influence of tocolytic drugs usage in the third trimester of pregnancy on obstetric and neonatal outcomes]. / Wplyw stosowania Ieków zapobiegajacych porodowi przedwczesnemu w III trymestrze ciazy na wyniki poloznicze oraz neonatologiczne.

INTRODUCTION: The occurrence of preterm labor is the cause of 75% of preterm births. Prematurity is the leading cause of mortality of children under four weeks of age. Tocolytic drugs are used widely in the treatment of preterm labor. The aim of this study was to assess the impact of the tocolytic therapy on obstetric and neonatal outcomes. MATERIAL AND METHODS: The prospective, cohort study included 499 pregnant women The study enrolled women who met certain criteria of age, with singleton pregnancy, having no chronic diseases. After delivery the following data were obtained: sociodemographic profile (including data on occupational activity), body height and weight before pregnancy, weight gain, duration of pregnancy, mode of delivery, obstetric complications, medications, anthropometric parameters and state of health of newborns. A group of patients treated with tocolytic drugs and a control group were identified. Then obstetric and neonatal outcomes in both groups were subjected to statistical analysis. RESULTS: There was no statistically significant difference between the two groups in terms of the following variables: mother's age, her education, professional activity of mothers in the first and second trimester of pregnancy, weight gain during pregnancy, parity, exposure to passive smoking during pregnancy, method of pregnancy termination. We found a statistically significant difference between the groups with respect to maternal weight before pregnancy (lower in the group using tocolytics), the average duration of pregnancy (lower in the group using tocolytics), the frequency of preterm birth (higher in the group using tocolytics) and neonatal anthropometric parameters and the number of points in the Apgar score at 5 minutes of age (lower in the group using tocolytics). CONCLUSIONS: Low pregestational weight is a risk factor for preterm labor. Term birth rate in pregnant women treated for preterm labor is significantly smaller compared to the general population, which may indicate low efficacy of tocolytic drugs. There was no positive correlation found between the professional activity of pregnant women and the risk of threatening preterm labor.

Dose-dependent relationship between prenatal exposure to fine particulates and exhaled carbon monoxide in non-asthmatic children. A population-based birth cohort study.

OBJECTIVES: The main goal of the study was to assess possible association between fetal exposure to fine particulate matter (PM2.5) and exhaled carbon monoxide (eCO) measured in non-asthmatic children. MATERIAL AND METHODS: The subjects include 118 children taking part in an ongoing population-based birth cohort study in Kraków. Personal samplers of PM2.5 were used to measure fine particle mass in the fetal period and carbon monoxide (CO) in exhaled breath from a single exhalation effort at the age of 7. In the statistical analysis of the effect of prenatal PM2.5 exposure on eCO, a set of potential confounders, such as environmental tobacco smoke (ETS), city residence area, sensitization to house dust allergens and the occurrence of respiratory symptoms monitored over the seven-year follow-up was considered. RESULTS: The level of eCO did not correlate with the self-reported ETS exposure recorded over the follow-up, however, there was a positive significant relationship with the prenatal PM2.5 exposure (non-parametric trend p = 0.042). The eCO mean level was higher in atopic children (geometric mean = 2.06 ppm, 95% CI: 1.58-2.66 ppm) than in non-atopic ones (geometric mean = 1.57 ppm, 95% CI: 1.47-1.73 ppm) and the difference was statistically significant (p = 0.036). As for the respiratory symptoms, eCO values were associated positively only with the cough severity score recorded in the follow-up (nonparametric trend p = 0.057). In the nested multivariable linear regression model, only the effects of prenatal PM2.5 and cough severity recorded in the follow-up were related to eCO level. The prenatal PM2.5 exposure represented 5.1%, while children's cough represented only 2.6% of the eCO variability. CONCLUSION: Our study suggests that elevated eCO in non-asthmatic children may result from oxidative stress experienced in the fetal period and that heme oxygenase (HO) activity in body tissues may be programmed in the fetal period by the exposure to fine particulate matter.

Fractional exhaled nitric oxide in healthy non-asthmatic 7-year olds and prenatal exposure to polycyclic aromatic hydrocarbons: nested regression analysis.

UNLABELLED: The main goal of the study was to assess possible association between transplacental exposure to genotoxic PAH compounds assessed by the cord blood PAH-DNA adducts and fractional exhaled nitric oxide (FeNO) measured in healthy non-asthmatic children at the age of 7 years. The subjects included the subsample of 89 children who took part in the ongoing population based birth cohort study in Krakow and attended FeNO testing. The effect of transplacental PAH exposure was adjusted for potential confounders, such as maternal allergy and children's specific atopy to common domestic allergens. RESULTS: FeNO values were significantly elevated in children with higher prenatal PAH exposure (gmean = 7.7 ppb; 95% CI: 5.8-10.2 ppb) compared with those at low exposure level (gmean = 3.8 ppb; 95% CI: 2.3-6.3) (P = 0.011). Children with maternal allergy had also significantly higher mean FeNO values (gmean = 13.7 ppb, 95% CI: 8.8-21.4 ppb) compared with the subjects whose mothers denied allergy (gmean = 5.6 ppb, 95% CI: 4.3-7.3 ppb) (P = 0.012). Similarly, FeNO values in atopic children were higher (gmean = 11.2 ppb; 95% CI: 3.8-32.8 ppb) than in non-atopic individuals (gmean = 6.0 ppb; 95% CI: 4.7-7.7 ppb, P = 0.079). The results of the nested multivariable linear regression analysis showed that both maternal allergy and sensitization of children to domestic aeroallergens jointly explained 10.4% of FeNO variance, however, the additional 10.9% was determined by prenatal PAH exposure. CONCLUSION: FeNO is more than a marker useful for screening atopy or symptomatic bronchial inflammation and may also be a proxy for cytokine deregulation and "allergic response" phenotype possibly established in fetal period due to transplacental PAH exposure. Preliminary results of our study should encourage more studies on intrauterine PAH exposure and later respiratory symptoms.

Prohypertensive effect of gestational personal exposure to fine particulate matter. Prospective cohort study in non-smoking and non-obese pregnant women.

Exposure to fine particulate matter (PM) is a recognized risk factor for elevated blood pressure (BP) and cardiovascular disease in adults, and this prospective cohort study was undertaken to evaluate whether gestational exposure to PM(2.5) has a prohypertensive effect. We measured personal exposure to fine particulate matter (PM(2.5)) by personal air monitoring in the second trimester of pregnancy among 431 women, and BP values in the third trimester were obtained from medical records of prenatal care clinics. In the general estimating equation model, the effect of PM(2.5) on BP was adjusted for relevant covariates such as maternal age, education, parity, gestational weight gain (GWG), prepregnancy BMI, environmental tobacco smoke (ETS), and blood lead level. Systolic blood pressure (SBP) increased in a linear fashion across a dosage of PM(2.5) and on average augmented by 6.1 mm Hg (95% CI, 0.6-11.6) with log unit of PM(2.5) concentration. Effects of age, maternal education, prepregnancy BMI, blood lead level, and ETS were insignificant. Women with excessive gestational weight gain (>18 kg) had higher mean SBP parameters by 5.5 mmHg (95% CI, 2.7-8.3). In contrast, multiparous women had significantly lower SBP values (coeff. = -4.2 mm Hg; 95% CI, -6.8 to -1.6). Similar analysis performed for diastolic blood pressure (DBP) has demonstrated that PM(2.5) also affected DBP parameters (coeff. = 4.1; 95% CI, -0.02 to 8.2), but at the border significance level. DBP values were positively associated with the excessive GWG (coeff. = 2.3; 95% CI, 0.3-4.4) but were inversely related to parity (coeff. = -2.7; 95% CI, -4.6 to -0.73). In the observed cohort, the exposure to fine particulate matter during pregnancy was associated with increased maternal blood pressure.

Effect of exclusive breastfeeding on the development of children's cognitive function in the Krakow prospective birth cohort study.

The main goal of the study was to assess the effect of exclusive breastfeeding on the neurodevelopment of children over a 7-year follow-up period and to test the hypothesis that the observed cognitive gain in breastfed children in the first years of life is a strong predictor of their cognitive development trajectory, which may be continued in later life. The analysis is based on data from the 7-year follow-up of 468 term babies (>36 weeks of gestation) born to non-smoking mothers participating in an ongoing prospective cohort study. The cognitive function of children was assessed by psychometric tests performed five times at regular intervals from infancy through the preschool age. The study included valid neurodevelopmental assessment of the children-443 participants were evaluated least twice; 425, three times; and 307, five times in the follow-up period. The association between the cognitive achievements of preschool age children and exclusive breastfeeding of various durations was performed using the generalized estimating equation longitudinal model, adjusted for major confounders such as maternal education, gender, parity, and weight gain in pregnancy. Children breastfed exclusively for up to 3 months had intelligence quotients (IQs) that were on average 2.1 points higher compared to the others (95% confidence interval (CI), 0.24-3.9); children breastfed for 4-6 months scored higher by 2.6 points (95% CI, 0.87-4.27); and the benefit for children breastfed even longer (>6 months) increased by 3.8 points (95% CI, 2.11-5.45). Other predictors were maternal education, gender of the child, having an older sibling, and weight gain during pregnancy. The results of the study support the WHO expert recommendations on exclusive breastfeeding for 6 months; moreover, they provide evidence that even a shorter duration of exclusive breastfeeding in early infancy produces beneficial effects on the cognitive development of children. The breastfeeding-related IQ gain observed already at the age of 1 was sustained through preschool age, and the difference in terms of IQ score between breastfed children and the reference group (mixed breastfeeding) held constant over the whole preschool period.

Cognitive function of 6-year old children exposed to mold-contaminated homes in early postnatal period. Prospective birth cohort study in Poland.

In the last decade, the neurologic effects of various air pollutants have been the focus of increasing attention. The main purpose of this study was to assess the potential impact of early childhood exposure to indoor molds on the subsequent cognitive function of 6-year old children. The results of this study are based on the six-year follow-up of 277 babies born at term to mothers participating in a prospective cohort study in Krakow, Poland. The study participants are all non-smoking pregnant women who were free of chronic diseases such as diabetes and hypertension. The presence of visible mold patches on indoor walls was monitored at regular time intervals over gestation and after birth up to the age of five. The Wechsler Intelligence Scale for Children (WISC-R) was administered to children at age 6. The exposure effect of living in mold-contaminated homes on the IQ scores of children was adjusted for major confounders, known to be important for the cognitive development of children such as maternal education, the child's gender, breastfeeding practices in infancy, the presence of older siblings and the prenatal exposure to lead and environmental tobacco smoke (ETS). The adjusted IQ deficit attributed to longer exposures to indoor molds (>2 years) was significantly lower on the IQ scale (beta coeff.=-9.16, 95%CI: -15.21, -3.10) and tripled the risk of low IQ scoring (OR=3.53; 95%CI: 1.11-11.27) compared with references. While maternal education (beta coeff.=0.61, 95%CI: 0.05, 1.17) and breastfeeding (beta coeff.=4.0; 95%CI: 0.84, 7.17) showed a significant positive impact on cognitive function, prenatal ETS exposure (beta coeff.=-0.41; 95%CI: -0.79, -0.03) and the presence of older siblings (beta coefficient=-3.43; 95%CI: -5.67, -1.20) were associated with poorer cognitive function in children. In conclusion, the results of this study draw attention to the harmful effect of early postnatal exposure to indoor molds on children's cognitive development and provide additional evidence on the role of environmental determinants in human cognitive development.

Early wheeze as reported by mothers and lung function in 4-year-olds. Prospective cohort study in Krakow.

SUMMARY: The purpose of the study was to check the hypothesis that early wheezing as reported by mothers would be associated with reduced lung function in 4-year olds. Study participants were recruited prenatally, as part of a prospective cohort study on the respiratory health of young children exposed to various ambient air pollutants. After delivery, infants were followed over 4 years and the interviewers visited participants at their home to record respiratory symptoms every 3 months in the child's first 2 years of life and every 6 months in the 3rd and 4th years. In the 4th year of follow-up, children were invited for standard lung function testing by spirometry quantified by forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV(1)), and forced expiratory volume in 0.5 sec (FEV(0.5)) levels. Out of 258 children attending spirometry testing 139 performed at least two acceptable exhalation efforts. Cohort children with acceptable spirometric measurements did not differ with respect to wheezing experience and exposure characteristics from those without. The study shows that episodic wheeze was reported in 28.1% of 4-year olds, 6.5% had transient wheeze, and 4.3% had recurrent wheeze. There was an increased frequency of wheezing symptoms and their duration in transient and recurrent wheezers. Adjusted multivariable regression models for gender and height showed that children who reported more than two episodes of wheezing at any point over the follow-up had FVC values lower by 120.5 ml (P = 0.016) and FEV(1) values lower by 98.3 ml (P = 0.034) compared to those who did not report any wheezing; children experiencing more than 10 wheezing days by age 4 showed FVC deficit of 87.4 ml (P = 0.034) and FEV(1) values of 65.7 ml (P = 0.066). The ratios of FEV(1)/FVC%, and FEV(0.5)/FVC% were neither associated with wheezing episodes nor wheezing days. In recurrent wheezers, lung function decrement amounted to 207 ml of FVC, 175 ml of FEV(1), and 104 ml of FEV(0.5). In conclusion, our findings show that wheezing experience during early postnatal life may be associated with lung function deficit of restrictive character in preschool children and detailed history of wheeze in early postnatal life, even though not physician-confirmed, may help define the high risk group of children for poor lung function testing.

Intrauterine exposure to polycyclic aromatic hydrocarbons, fine particulate matter and early wheeze. Prospective birth cohort study in 4-year olds.

The main goal of the study was to determine the relationship between prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) measured by PAH-DNA adducts in umbilical cord blood and early wheeze. The level of PAH-DNA adducts in the cord blood is assumed to reflect the cumulative dose of PAHs absorbed by the foetus over the prenatal period. The effect of prenatal PAH exposure on respiratory health measured by the incidence rate ratio (IRR) for the number of wheezing days in the subsequent 4 yr follow-up was adjusted for potential confounding factors such as personal prenatal exposure to fine particulate matter (PM(2.5)), environmental tobacco smoke (ETS), gender of child, maternal characteristics (age, education and atopy), parity and mould/dampness in the home. The study sample includes 339 newborns of non-smoking mothers 18-35 yr of age and free from chronic diseases, who were recruited from ambulatory prenatal clinics in the first or second trimester of pregnancy. The number of wheezing days during the first 2 yr of life was positively associated with prenatal level of PAH-DNA adducts (IRR = 1.69, 95%CI = 1.52-1.88), prenatal particulate matter (PM(2.5)) level dichotomized by the median (IRR = 1.38; 95%CI: 1.25-1.51), maternal atopy (IRR = 1.43; 95%CI: 1.29-1.58), mouldy/damp house (IRR = 1.43; 95%CI: 1.27-1.61). The level of maternal education and maternal age at delivery was inversely associated with the IRRs for wheeze. The significant association between frequency of wheeze and the level of prenatal environmental hazards (PAHs and PM(2.5)) was not observed at ages 3 or 4 yrs. Although the frequency of wheezing at ages 3 or 4 was no longer associated with prenatal exposure to PAHs and PM(2.5), its occurrence depended on the presence of wheezing in the first 2 yr of life, which nearly tripled the risk of wheezing in later life. In conclusion, the findings may suggest that driving force for early wheezing (<24 months of age) is different to those leading to later onset of wheeze. As we reported no synergistic effects between prenatal PAH (measured by PAH-DNA adducts) and PM(2.5) exposures on early wheeze, this suggests the two exposures may exert independent effects via different biological mechanism on wheeze.

Case-control study on beneficial effect of regular consumption of apples on colorectal cancer risk in a population with relatively low intake of fruits and vegetables.

Laboratory in-vitro studies and animal experiments showing the potential health benefits from apples raises the question to what extent the regular consumption of apples in humans may have a beneficial effect on colorectal cancer risk. A total of 592 incident cases of colorectal cancer have been enrolled in a hospital-based case-control study. The comparison group included 765 controls chosen from the patients of the same hospital without history of cancer and admitted for treatment of nonneoplastic conditions. Interviews of both cases and controls were conducted in the hospital setting by trained interviewers. The median intake of fruits among cases was lower than in controls (9.5 vs. 11 servings/week) and the difference was statistically significant. Apples were the most frequent fruit consumed by the study participants and about 80% of variability in the total fruit consumption resulted from the intake of apples. We did not observe any significant statistical differences in consumption of berries, citrus, or stone fruits and other kinds of fruits across cases and controls. The adjusted estimates of colorectal cancer risk related to the daily consumption of apples (in quintiles) were based on the unconditional multivariate logistic model, which considered the set of potential confounding variables such as demographic characteristics of participants (age, gender, place of residency, marital status, tobacco smoking), total energy intake, intake of vegetables and fruits without apples. The results of the logistic analysis showed that the adjusted risk of colorectal cancer inversely correlated with daily number of apple servings. The reduced risk of colorectal cancer of border significance level was already observed at the consumption of at least one apple a day (odds ratio=0.65, 95% CI: 0.39-1.09), but at the intake of more than one apple a day the risk was reduced by about 50% (odds ratio=0.53, 95% CI: 0.35-0.79). Neither the consumption of vegetables nor other fruits have shown beneficial effects on the risk of colorectal cancer. The observed protective effect of apple consumption on colorectal risk may result from their rich content of flavonoid and other polyphenols, which can inhibit cancer onset and cell proliferation.

Early wheezing phenotypes and severity of respiratory illness in very early childhood: study on intrauterine exposure to fine particle matter.

The main goal of the paper was to assess the pattern of risk factors having an impact on the onset of early wheezing phenotypes in the birth cohort of 468 two-year olds and to investigate the severity of respiratory illness in the two-year olds in relation to both wheezing phenotypes, environmental tobacco smoke (ETS) and personal PM(2.5) exposure over pregnancy period (fine particulate matter). The secondary goal of the paper was to assess possible association of early persistent wheezing with the length of the baby at birth. Pregnant women were recruited from ambulatory prenatal clinics in the first and second trimester of pregnancy. Only women 18-35 years of age, who claimed to be non-smokers, with singleton pregnancies, without illicit drug use and HIV infection, free from chronic diseases were eligible for the study. In the statistical analysis of respiratory health of children multinomial logistic regression and zero-inflated Poisson regression models were used. Approximately one third of the children in the study sample experienced wheezing in the first 2 years of life and in about two third of cases (67%) the symptom developed already in the first year of life. The early wheezing was easily reversible and in about 70% of infants with wheezing the symptom receded in the second year of life. The adjusted relative risk ratio (RRR) of persistent wheezing increased with maternal atopy (RRR=3.05; 95%CI: 1.30-7.15), older siblings (RRR=3.05; 95%CI: 1.67-5.58) and prenatal ETS exposure (RRR=1.13; 95%CI: 1.04-1.23), but was inversely associated with the length of baby at birth (RRR=0.88; 95%CI: 0.76-1.01). The adjusted incidence risk ratios (IRR) of coughing, difficult breathing, runny/stuffy nose and pharyngitis/tonsillitis in wheezers were much higher than that observed among non-wheezers and significantly depended on prenatal PM(2.5) exposure, older siblings and maternal atopy. The study shows a clear inverse association between maternal age or maternal education and respiratory illnesses and calls for more research efforts aiming at the explanation of factors hidden behind proxy measures of quality of maternal care of babies. The data support the hypothesis that burden of respiratory symptoms in early childhood and possibly in later life may be programmed already in prenatal period when the respiratory system is completing its growth and maturation.

Fetal exposure to secondhand tobacco smoke assessed by maternal self-reports and cord blood cotinine: prospective cohort study in Krakow.

OBJECTIVES: While the validity of self-reported smoking habits is generally judged as satisfactory, objective markers of secondhand smoke (SHS) exposure may be more useful in validating the causal links between prenatal SHS and health effects. The cohort study in Krakow provided an opportunity for comparative assessment of fetal exposure to SHS based upon questionnaires and cord blood cotinine measurements. METHODS: The study sample included 467 newborns born to women recruited in the first and second trimester of pregnancy. To compare the validity of self-reported SHS and cord blood cotinine levels in assessing the association between fetal passive smoking and health effects of newborns, we separately examined the regression coefficients of birthweight on self-reported number of cigarettes smoked by other household members during the entire pregnancy and cord blood cotinine levels. RESULTS: In the non-exposed newborns the geometric mean of cord blood cotinine was 0.077 ng/ml and was significantly lower than in newborns with a maternal report of SHS. Cord cotinine levels were more highly correlated with a self-reported number of cigarettes smoked daily at home in the third trimester of pregnancy. The two measures of SHS (number of cigarettes and number of hours of daily exposure) were equally well correlated with cord blood cotinine levels. Using cotinine as the exposure variable, overall the association was not significant; but among the subgroup with cord cotinine levels above the median (> or =0.083 ng/ml), the association with birthweight was significant (beta coefficient = -113.65, P = 0.041). CONCLUSION: The study provides evidence that the assessment of fetal SHS exposure based on cord blood cotinine produced better estimates of the association between exposure and birth outcomes.

Risk of wheezing associated with house-dust mite allergens and indoor air quality among three-year-old children. Kraków inner city study.

OBJECTIVES: The aim of the study was to describe the distribution of house-dust mite (HDM) allergens in homes of three-year-old children and to test the hypothesis whether the content of HDM allergens exceeding 2 microg/g of dust may be regarded as a risk level possibly affecting respiratory health in early childhood. MATERIALS AND METHODS: House-dust samples were collected in 275 dwellings from mattresses, children's bedrooms and kitchen floors. In the laboratory, dust samples were analyzed for Der f 1 and Der p 1 using monoclonal antibody enzyme-linked immunosorbent assays (ELISA). At the time of the house-dust collection, mothers were interviewed on the household characteristics and their children's respiratory health. Respiratory outcome variables included wheezing or whistling in the chest irrespective of respiratory infections. The number of the wheezing episodes and their duration in days over the last 6 months were recorded in the questionnaire. In the multivariate Poisson regression analysis on the association between the occurrence of wheezing and exposure, a set of potential confounders, such as child's gender, maternal education, maternal allergy, older siblings, presence of moulds, house dampness, and environmental tobacco smoke (ETS) was taken into account. RESULTS: The adjusted incidence rate ratios (IRR) of wheezing ascribed to a higher HDM level (> 2.0 microg/g dust) were 1.84 (95% CI: 1.45-2.34) for duration of wheezing and 1.56 (95% CI: 0.88-2.75) for episodes. Of the confounders taken into consideration, the presence of moulds had the strongest impact on the risk of wheezing (IRR = 4.24; 95% CI: 3.08-5.84). CONCLUSION: The data support the view that exposure to a higher level of HDM allergens increases the burden of respiratory diseases in the early childhood and the effect is independent of maternal atopy, ETS, and moulds in homes.