Associations between APOE-, COMT Val108/158Met- and BDNF Val66Met polymorphisms and variations in depressive and anxiety symptoms, sense of coherence and vital exhaustion in the real-life setting of mandatory basic military training.

Apolipoprotein E (APOE) ε, catechol-O-methytranferase (COMT) Val108/158Met and brain-derived neurotrophic factor (BDNF) Val66Met single nucleotide polymorphisms (SNPs) were shown to affect stress perception and response. The present study explored possible associations between these SNPs and changes in subclinical anxiety- and depressive symptoms, sense of coherence (SOC) and vital exhaustion (VE) during compulsory basic military training. The study encompassed 179 conscripts of a training base in Greece. The neuropsychiatric assessment was based on the Beck Depression Inventory, the State-Trait Anxiety Inventory, the Antonovsky SOC scale and the Maastricht Questionnaire. It was conducted at three time points of the 19-day basic military training: on day one (baseline), day six (follow-up I) and day 13 (follow-up II). Statistical analyses included Mann-Whitney test, Chi-square test and cross-sectional time series regression models based on the Skillings-Mack statistic. APOE ε4 non-carriers encountered significant changes in anxiety- and depressive symptoms and SOC (in all cases P < 0.001) over the observation period, whilst ε4 carriers did not. The changes in anxiety, depressive symptoms and SOC attained statistical significance in both BDNF Met66 carriers (in all cases P < 0.001) and non-carriers (P = 0.036; < 0.001; < 0.001, respectively) as well as in COMT Met108/158 carriers (P = 0.004; < 0.001; < 0.001, respectively) and non-carriers (P = 0.02; 0.01; 0.021, respectively. Changes over time in VE were not significant (P > 0.05). The observed resistance of APOE ε4 carriers vs non-carriers to changes in anxiety- and depressive symptoms and SOC when exposed to a stressful environment may point to superior coping capacities of healthy young men carrying the ε4 allele.

Nutritional status and pulmonary outcome in children and young people with cystic fibrosis.

BACKGROUND: Nutrition is closely related to mortality and pulmonary and respiratory muscle function in cystic fibrosis (CF) patients. We initially validated results from a bioelectrical impedance device against dual energy x-ray absorptiometry (DEXA). We then determined whether fat free mass assessed by a portable impedance device rather than body mass index (BMI) better correlated with pulmonary function, respiratory muscle strength and exercise capacity in CF patients. METHODS: Eighteen young people and adults (median age 19, range 12-39 years) with CF had dual energy X-ray absorptiometry and direct segmental multi-frequency impedance analysis. Body composition, pulmonary function, respiratory muscle function and exercise tolerance using the impedance device were measured in 29 young people with CF with median age 15 (range 12-19) years. MAIN FINDINGS: There was a significant correlation between impedance and absorptiometry results (r2 = 0.947). Fat free mass correlated with the forced vital capacity z-score (r = 0.442, p = 0.016), maximal inspiratory pressure (r = 0.451, p = 0.014) and exercise tolerance (r = 0. 707, p < 0.001). BMI z-scores did not significantly correlate with pulmonary or respiratory muscle function. Subjects with a fat free mass z-score of ≤2 had a lower forced expiratory volume in 1 s z-score (p = 0.007), lower forced vital capacity z-score (p = 0.001), higher residual volume z-score (p = 0.042), lower maximal inspiratory pressure (p = 0.039), more days of intravenous antibiotics per year (p = 0.016) and a higher rate of chronic infections (p = 0.006). PRINCIPAL CONCLUSIONS: Fat-free mass measured by impedance correlated better with pulmonary and respiratory muscle function and exercise capacity than BMI.

Chronic Pseudomonas aeruginosa infection and respiratory muscle impairment in cystic fibrosis.

BACKGROUND: Chronic infection with Pseudomonas aeruginosa in patients with cystic fibrosis (CF) is associated with increased morbidity. Chronic infection can cause limb and respiratory muscle compromise. Respiratory muscle function can be assessed via maximal inspiratory pressure (PImax), maximal expiratory pressure (PEmax), and the pressure-time index of the respiratory muscles (PTImus). We studied the effect of chronic P. aeruginosa infection on respiratory muscle function in patients with CF. METHODS: This cross-sectional study assessed PImax, PEmax, PTImus, FEV1, FVC, maximum expiratory flow during the middle half of the FVC maneuver, body mass index, and upper arm muscle area in 122 subjects with CF, in 4 subgroups matched for age and sex at different stages of P. aeruginosa infection, according to the Leeds criteria. We compared respiratory muscle function in the subgroups according to P. aeruginosa infection state. RESULTS: Median PImax was significantly lower in CF subjects with chronic P. aeruginosa infection (PImax = 62 cm H2O), compared to subjects who were never infected (PImax = 86 cm H2O, P = .02), free of infection (PImax = 74 cm H2O, P = .01), or intermittently infected (PImax = 72 cm H2O, P = .02). Median PTImus was significantly increased in CF subjects with chronic P. aeruginosa infection (PTImus = .142), compared to subjects who were free of infection (PTImus = .102, P = .006). Median upper-arm muscle area was significantly lower in CF subjects with chronic P. aeruginosa infection (upper-arm muscle area = 2,219 mm(2)), compared to subjects who were never infected (2,754 mm(2), P = .03), free of infection (2,678 mm(2), P = .01), or intermittently infected (2,603 mm(2), P = .04). Multivariate logistic regression revealed P. aeruginosa state of infection as a significant determinant of PTImus (P = .03) independently of sex, upper-arm muscle area, and FEV1. CONCLUSIONS: CF subjects with chronic P. aeruginosa infection exhibited impaired respiratory muscle function and decreased inspiratory muscle strength, and chronic P. aeruginosa infection independently impacts respiratory muscle function in subjects with CF.

Maximum rate of pressure development and maximal relaxation rate of respiratory muscles in patients with cystic fibrosis.

BACKGROUND: Respiratory muscle function in patients with cystic fibrosis (CF) has been studied by measurement of maximal inspiratory pressure (P(Imax)), maximal expiratory pressure (P(Emax)), and the pressure-time index of the respiratory muscles (PTI(mus)). The maximum rate of pressure development (MRPD) during P(Imax) (MRPD-P(Imax)), MRPD during P(Emax) (MRPD-P(Emax)), maximal relaxation rate (MRR) during P(Imax) (MRR-P(imax)), and MRR during P(Emax) (MRR-P(Emax)) have not been studied in CF. Our aim was to study MRPD and MRR and investigate their possible application as accessory indices of respiratory muscle function in patients with CF. METHODS: FEVY, FVC, and maximal expiratory flow between 25% and 75% of vital capacity, body mass index (BMI), upper arm muscle area, P(imax), P(Emax), PTI(mus), MRPD-P(Imax), MRPD-P(Emax), MRR-P(imax), and MRR-P(Emax) were assessed in 123 CF patients and in a control group of 123 healthy subjects matched for age and sex. RESULTS: MRR-P(Emax) was significantly increased and MRPD-P(Emax) was significantly decreased in the CF patients, compared to the healthy controls. In the CF patients MRR-P(Imax) was significantly related to PTI(mus) (P = .02), FEV1 (P = .03), FVC (P = .001), BMI (P < .001), and upper arm muscle area (P < .001). In the CF patients, MRPD-P(Imax) and MRPD- P(Emax) were significantly related to upper arm muscle area (P < .001), BMI (P < .001 and P = .01, respectively), P(Imax) (P < .001), and P(Emax) (P < .001). CONCLUSIONS: The CF patients exhibited increased MRR and decreased MRPD during maximal respiratory effort, compared to controls. The differences in MRR-P(imax) and MRPD-P(Imax) between the controls and the complete group of CF patients were not significant. MRPD and MRR were significantly related to nutritional and pulmonary function impairment in CF patients. MRPD strongly correlated to maximal respiratory muscle pressures, and MRR strongly correlated to PTI(mus) in patients with CF. These findings suggest that CF patients are at increased risk of respiratory muscle fatigue. Regular determination of MRPD and MRR may be clinically useful in CF patients and help to initiate inspiratory muscle training and noninvasive ventilation.

Periconceptional tobacco smoking and isolated congenital heart defects in the neonatal period.

BACKGROUND: Tobacco use in pregnancy is considered a human developmental toxicant and potential teratogen. The aim of the study was to test for a possible association between periconceptional tobacco smoking and congenital heart disease (CHD) in the neonatal period. METHODS: Maternal and infant characteristics of 157 neonates diagnosed with CHD at the University of Patras Medical School were collected and were compared with 208 normal neonates (aged 1-28 days) that were referred for echocardiography during a specified 3-year period. RESULTS: In neonates with CHD 64 of 157 mothers (40.8%) reported smoking in pregnancy, whereas in the control group 41 of 208 mothers (19.7%) were smokers (p=0.000). Logistic regression analysis with pregestational diabetes, history of influenza-like illness in the first trimester, therapeutic drug exposure in pregnancy, maternal age, parity, family history of CHD, infant gender, prematurity and paternal smoking, as potential confounding factors showed that periconceptional tobacco smoking was associated with increased risk of CHD in the offspring (OR=2.750, 95% CI=1.659-4.476, p=0.00001). The incidence of neonatal heart disease in women who were non-smokers or smoked 1-10 and ≥11 cigarettes per day increased with the level of fetal tobacco exposure (35.8% versus 55.3% versus 64.3%, x2-test=20.303, p=0.000), suggesting a dose effect. CONCLUSIONS: The results of the study are indicative of an association between periconceptional tobacco exposure and increased risk of CHD in the neonatal period. The potential role of gestational smoking as a risk factor for specific heart defect subgroups requires the conduction of large population based epidemiological studies.