Comparative Study of Dissolution for Cannabidiol in EU and US Hemp Oil Products by HPLC.

For the first time, a simple and robust HPLC method has been developed for dissolution studies for cannabidiol (CBD) in hemp oil products. An isocratic elution of samples performed on SOLAS™ C18 150 mm x 4.6 mm, 5 µm column with a mobile phase consisting of 75:25 acetonitrile-water v/v, delivered at a flow rate 1.5 mL/minutes to variable wavelength detector using 214 nm. An in-house validated assay test was executed for calculating the purity of hemp oil products and also for considering the dissolution medium to be used. For dissolution studies, equivalent of 5 mg and/or 10 mg of the active was introduced into 500 mL of simulated gastric and intestinal fluids separately, and dissolution was performed at 50 rpm using paddles for 180 min. Dissolution profiles for hemp oil products purchased from the United States and Europe were compared. Additionally, dissolution testing was conducted to study the effect of percentage CBD release on increased agitation speed of 75 and 100 rpm and also, on extended dissolution runtime of 240 min.

Preoperative gastric residual volumes in fasted patients measured by bedside ultrasound: a prospective observational study.

The purpose of this prospective observational study was to measure gastric volumes in fasted patients using bedside gastric ultrasound. Patients presenting for non-emergency surgery underwent a gastric antrum assessment, using the two-diameter and free-trace methods to determine antral cross-sectional area (CSA). Gastric residual volume (GRV) was calculated using a validated formula. Univariate and multivariable analyses were performed to examine any potential relationships between 'at risk' GRVs (>100 ml) and patient factors. Two hundred and twenty-two successful scans were performed; of these 110 patients (49.5%) had an empty stomach, nine patients (4.1%) had a GRV >100 ml, and a further six patients (2.7%) had a GRV >1.5 ml/kg. There was no significant relationship between at risk GRV and obesity, diabetes mellitus, gastro-oesophageal reflux disease or opioid use, although our study had insufficient power to exclude an influence of one or more of these factors. Our results indicate that despite compliance with fasting guidelines, a small percentage of patients still have GRVs that pose a pulmonary aspiration risk. Anaesthetists should consider this background incidence when choosing anaesthesia techniques for their patients. While future observational studies are required to determine the role of preoperative bedside gastric ultrasound, it is possible that this technique may assist anaesthetists in identifying patients with 'at risk' GRVs.

A polymorphism in the thyroid hormone receptor gene is associated with bronchodilator response in asthmatics.

A pro-asthmatic culture milieu and ß2-agonist (isoproterenol) were previously shown to regulate the expression of select transcription factors (TFs) within human airway epithelial and smooth muscle cells. This study tests 1116 single-nucleotide polymorphisms (SNPs) across 98 of these TF genes for association with bronchodilator response (BDR) in asthma patients. Genotyping was conducted using the Illumina HumanHap550v3 Beadchip in 403 non-Hispanic White asthmatic children and their parents. SNPs were evaluated for association with BDR using family and population-based analyses. Forty-two SNPs providing P-values <0.1 in both analyses were then genotyped in three adult asthma trials. One SNP 5' of the thyroid hormone receptor-ß gene was associated with BDR in the childhood population and two adult populations (P-value=0.0012). This investigation identified a novel locus for inter-individual variability in BDR and represents a translation of a cellular drug-response study to potential personalization of clinical asthma management.

Screening for the presence of nematophagous fungi collected from Irish sheep pastures.

With worldwide development of anthelmintic resistance, alternative approaches to the chemotherapeutic dominant approach for the control of parasitic nematodes in sheep are urgently required. As natural enemies of nematodes, nematophagous fungi offer the exciting possibility of an alternative to the dominant anthelmintic approach for parasite control in ruminants. Permanent sheep pasture harbor a promising array of nematophagous fungi and merits further investigation. One hundred and fifty samples of soil, old and fresh faeces were collected from 10 Irish sheep pastures. The three methods employed for the isolation of nematophagous fungi include the Baermann technique, flotation method and the sprinkling-baiting technique. Twenty-nine nematophagous fungi were observed of which 12 were predacious and 17 were endoparasitic. The most prevalent fungi were Cystopage lateralis, Stylopage hadra, Drechmeria coniospora and Meristacrum asterosperum. Permanent sheep pasture is a good source of nematophagous fungi and hence may harbor potential biological control agents. Monacrosporium cionopaga, Duddingtonia flagrans, D. coniospora and Hirsutella rhoissilensis were detected in fresh faecal samples indicating they may have survived the gastrointestinal tract and therefore a viable option as a biological control agent.

Hormonal relationships during the periovulatory period among ewe breeds known to differ in fertility after cervical artificial insemination with frozen thawed semen.

Our previous work indicates that ewe breed differences in fertility following cervical AI with frozen-thawed semen are due to failure of normal sperm transport and/or early embryo development. Here we examined differences in hormone concentrations about the time of ovulation among more (Finnish Landrace and Belclare) and less (Suffolk and Texel) fertile ewes after AI with frozen thawed semen. In Experiment 1, oestradiol concentrations were measured in samples collected frequently from 12h before to 18h after the LH surge and progesterone was measured in samples collected from 9 to 27h after the LH surge in Suffolk (n=24), Texel (n=20) and Finnish Landrace (n=27) ewes. In Experiment 2, oestradiol concentrations were measured in samples collected frequently from 24h before to 6h after the LH surge and progesterone was measured in samples collected from 6h to 6 days after the LH surge in Suffolk (n=35) and Belclare (n=30) ewes. In Experiment 1, there was an effect of breed, time and their interaction (P<0.001) on oestradiol concentrations between -12 and +6h but only breed differences at +12 and +18h (P<0.01). Progesterone concentrations increased over time (P<0.001) and the rate of increase was significantly greater in Finnish Landrace than in the other two breeds. In Experiment 2, oestradiol concentrations were unaffected by breed. There was an interaction between breed and time with the rate of increase of progesterone being greater in Belclare than Suffolk ewes (P<0.001). In conclusion, differences in hormone concentrations in the periovulatory period are not consistent with ewe breed differences in fertility; however, we have showed that progesterone concentrations rise earlier in the more prolific breeds and suggest that this may explain reported ewe breed differences in embryo development.

The difference in embryo quality between Belclare and Suffolk ewes is not due to differences in oocyte quality.

We have previously reported that the percentage of fertilized oocytes which reached the blastocyst stage by Day 6 after AI with frozen-thawed semen was higher for Belclare (94%) than Suffolk (59%) ewes. This may reflect differences in the timing of fertilization (Experiment 1) or differences in oocyte quality (Experiments 2 and 3). In Experiment 1, oocytes recovered from slaughterhouse ovaries were matured in vitro for 18, 20, 24, 28 or 30 h prior to fertilization and were then cultured in vitro. In Experiment 2, Belclare (n = 69) and Suffolk (n = 71) ewes were laparoscopically inseminated using frozen-thawed semen. Presumptive zygotes were recovered between 23 and 47 h post-insemination and cultured in vitro (grouped by breed). In Experiment 3, immature oocytes from Suffolk and Belclare ewes, were matured, fertilized and cultured in vitro (grouped by breed). Cleavage rate and blastocyst development was assessed. There was no effect of time of fertilization on cleavage rate, however, a lower proportion of cleaved oocytes reached the blastocyst stage after insemination at 30h compared to 24 h (P < 0.001). Ewe breed did not affect cleavage rate of oocytes matured and fertilized in vivo (41+/-9.6 and 47+/-10.1) or in vitro (47+/-9.4 and 52+/-9.4) for Belclare and Suffolk ewes, respectively (P > 0.05; %+/-S.E.). Likewise, ewe breed had no effect on the percentage (+/-S.E.) of cleaved oocytes developing to the blastocyst stage for in vivo (29+/-7.2 and 25+/-7.9) or in vitro matured and fertilized oocytes (29+/-6.1 and 36+/-5.9) from Belclare and Suffolk ewes, respectively (P>0.05). Based on this study oocyte quality does not differ between the breeds and in addition a 4h difference in the timing of fertilization, reflective of the breed difference in the timing of the LH surge in vivo, would not affect early embryo development.

Differences between Belclare and Suffolk ewes in fertilization rate, embryo quality and accessory sperm number after cervical or laparoscopic artificial insemination.

Ewe breed has been shown to have a major effect on pregnancy rates following cervical AI using frozen-thawed semen. The main objective of this study was to examine the differences between purebred Belclare and Suffolk ewes (multiparous) in fertilization rate, number of accessory sperm and stage of embryo development on day 6 after cervical or laparoscopic AI with frozen-thawed semen. In experiment 1, Belclare and Suffolk ewes were synchronized for 12 days and were either cervically inseminated (year 1: n=28 and 31; year 2: n=16 and 15, respectively) or laparoscopically inseminated (year 2: n=13 and 14). In experiment 2, superovulated Belclare (n=4) and Suffolk (n=13) ewes were laparoscopically inseminated. All ewes were slaughtered 6 days after AI; oocytes/embryos were recovered, morphologically graded and stained to assess the number of cells and accessory spermatozoa. Data from both experiments were combined for statistical analysis. The proportion of ewes with fertilized oocytes was significantly higher following laparoscopic AI compared with cervical AI (54% versus 19%). More Belclare than Suffolk ewes yielded fertilized oocyte(s) after cervical AI (34% versus 10%, P<0.02) but there was no difference after laparoscopic AI (62% versus 60%). From the ewes that yielded at least one fertilized oocyte the proportion of Belclare ewes with embryos at the morula/blastocyst stage was significantly greater than for Suffolk ewes (94% versus 59%, P<0.02). A higher proportion of Belclare than Suffolk ewes had evidence of sperm reaching the site of fertilization following cervical AI (39% versus 15%, P<0.02) but there was no difference after laparoscopic AI (62% versus 64%, P>0.8). Amongst the ewes with evidence of sperm at the site of fertilization, laparoscopic AI resulted in a higher number of sperm per oocyte/embryo or per ewe than cervical AI (P<0.01). These results suggested that the difference in pregnancy rate between Suffolk and Belclare ewes following cervical AI was due to: (i) sperm traversing the cervix and uterus in a higher proportion of Belclare than Suffolk ewes, leading to a higher incidence of fertilization and (ii) the lower developmental competence of fertilized oocytes from Suffolk ewes.

Risk factors for lack of asthma self-management knowledge among ED patients not on inhaled steroids.

The study objective was to estimate the level of asthma knowledge and self-management skills among asthmatic patients who are not on inhaled corticosteroids and who present with acute asthma to the emergency department (ED). The design was to interview of patients by telephone at 90 to 100 days after enrollment in the Fourth Multicenter Airways Research Collaboration (MARC-4), a randomized trial comparing inhaled fluticasone versus placebo in addition to standard post-ED therapy. The setting was a multicenter trial involving 41 US urban EDs. Persons aged 12 to 54, not on inhaled steroids, who presented to the ED with acute asthma were studied. Of the 617 patients enrolled on MARC-4 405 (66%) were contacted. Mean (+/-SD) age was 30 (+/-11); 54% were women; acute asthma severity was 44% moderate and 56% severe; and 9% had prior intubation. Twenty percent (95% CI 16%-24%) responded that asthma could not be monitored and 40% (95% CI 35%-44%) scored low on a hypothetical acute asthma attack scenario. Predictors for lack of asthma knowledge and self-management skills were: less than a high school education; current smoking; lower median household income; and no history of steroid use. These data suggest that many ED patients with asthma have poor knowledge of asthma monitoring and poor self-management skills and that a "high risk" group is also identifiable. Efforts to design and implement an ED-based educational program should be tailored to better meet the needs of this high risk group.

Effect of freezing rate of ram spermatozoa on subsequent fertility in vivo and in vitro.

Ram spermatozoa are most susceptible to damage during freezing between the temperatures of -10 degrees C and -25 degrees C. The objectives of the present study were to examine how freezing rate through this critical temperature zone affected the fertility of spermatozoa as assessed in vivo and in vitro. Semen from six adult rams was frozen at two different rates ("fast": 5 degrees C/min from +5 to -25 degrees C; "slow": 0.5 degrees C/min from +5 to -25 degrees C). In Experiment 1, semen from the fast and slow treatments was used to fertilize ovine oocytes that had been matured in vitro. Semen from the fast treatment yielded a higher cleavage rate (57% vs. 26%; P<0.001) and more blastocysts per oocyte (28% vs. 13%, P<0. 001) than slow-frozen. No correlation was found between fertilizing ability and viability as assessed by fluorescent probes. Experiment 2 was designed to establish the conception rates following both cervical and intrauterine insemination of frozen-thawed semen from the same bank of semen as used in Experiment 1. Ewes were superovulated with FSH and inseminated by laparoscopy with frozen semen. A significant difference was found in the number of fertilized ova following embryo recovery (81.4% vs. 39.3%; P<0.001). In a further study, 119 mature cull ewes were inseminated following a 12-day synchronization treatment with frozen semen by either intrauterine (laparoscopic) or cervical insemination. Insemination with fast-frozen semen resulted in a significantly higher pregnancy rate (P<0.05) irrespective of method of insemination. The data show that freezing rate affects the proportion of spermatozoa that retain their fertilizing ability post-thawing. However, once fertilization has occurred, development to the blastocyst stage is independent of freezing rate.

Antenatal interventions in childhood asthma.

The occurrence of asthma in most young children is likely to result from altered or disrupted immune maturation. The persistence of Th2-like lymphocyte responses to common allergens rather than the extinction of immune response (immune tolerance) or the deflection of response to a Th1 pattern (immune deviation) may underlie the development of asthma and the atopic phenotype. It is likely that this failure of normal immune maturation begins early in life, and that both genetic predisposition and environmental factors operating at critical times act jointly to cause it. There is clear evidence that the development of immune response capability begins in utero, and that maternal allergic and other exposures can affect this process before birth. While there is some evidence that the onset of atopy or atopic symptoms can be ameliorated or delayed in early life by reducing maternal prenatal allergen exposure (either food or inhaled allergens), there is currently no convincing evidence that prenatal maternal allergen avoidance will diminish asthma incidence in children. There are similarly no data available to evaluate if dietary antioxidants, postulated but unproven to have a protective role on airway reactivity and asthma incidence and severity in adults, have any protective role in utero. In contrast, maternal smoking during pregnancy has been shown in several studies to be associated with reductions in pulmonary function measures (flows at low lung volumes) in both infants and older children that are consistent with abnormalities seen in asthmatics. This finding, coupled with the clear association of postnatal environmental tobacco smoke exposure with increased wheezing and asthma risk in children, make maternal smoking cessation the prenatal intervention most likely to be effective in reducing asthma risk in children.

Exposure of young infants to environmental tobacco smoke: breast-feeding among smoking mothers.

OBJECTIVES: This study examined the degree to which breast-feeding and cigarette smoking by mothers and smoking by other household members contribute to the exposure of infants to the products of tobacco smoke. METHODS: The subjects were 330 mother-infant pairs derived from a cohort of 1000 pairs enrolled in a longitudinal study of the pulmonary effects of prenatal and postnatal smoking. The main outcome measure was corrected urinary cotinine levels. RESULTS: Urinary cotinine levels were 10-fold higher in breast-fed infants of smoking mothers than among bottle-fed infants of smoking mothers. Among infants of nonsmoking mothers, urine cotinine levels were significantly increased in infants living in homes with other smokers; in this group there was no significant difference between bottle-fed and breast-fed infants. Infants whose mothers smoked in the same room as the infant had only nonsignificant increases in cotinine levels compared with infants whose mothers restricted their smoking to other rooms. CONCLUSIONS: Breast-fed infants of smoking mothers have urine cotinine levels 10-fold higher than bottle-fed infants whose mothers smoke, suggesting that breast-feeding, rather than direct inhalation of environmental tobacco smoke, is the primary determinant of cotinine levels in infants whose mothers smoke.

Maternal smoking during pregnancy, urine cotinine concentrations, and birth outcomes. A prospective cohort study.

BACKGROUND: Most studies of the reproductive consequences of cigarette smoking base exposure on self-reported smoking habits. This study examines the relationship of birth outcomes to the timing and intensity of maternal active and passive smoking estimated both from self-reports and from cotinine concentration in maternal urine during early, middle, and late gestation. METHOD: This cohort study included 740 white and Hispanic women who obtained antenatal care at the East Boston Neighborhood Health Center between 1986 and 1992. At each antenatal visit, information on maternal active and passive smoking was obtained by a detailed questionnaire, and by measurement of urine cotinine concentrations. Infant birth outcomes were obtained from hospital records. Multiple linear regression was used to evaluate antenatal smoking variables on birth outcomes, with adjustment for maternal demographic characteristics, reproductive history, alcohol use, maternal weight and height, and infant gender. RESULTS: The percentage of mothers who ever smoked cigarettes during pregnancy was 55.5% for white and 10.2% for Hispanic women. A significant inverse exposure-response relationship between cotinine concentration in maternal urine and infant size at birth was demonstrated. However, the relationship was less clear between maternal self-reported smoking status and these outcomes. For the entire gestation, a 1000 ng increase in mean urine cotinine concentration was associated with a 59 +/- 9 g reduction in birthweight, a 0.25 +/- 0.05 cm reduction in length, and a 0.12 +/- 0.03 cm reduction in head circumference, respectively. For maternal passive smoking, the much smaller magnitude of effect precludes firm conclusions. CONCLUSIONS: These data suggest that preventing and reducing active maternal smoking during pregnancy may have a beneficial impact on infant size at birth.

Maternal smoking during pregnancy and birth outcomes with weight gain adjustments via varying-coefficient models.

There is considerable interest in the impact of maternal exposures during pregnancy on birth outcomes. Clearly, exposures associated with poor birth outcomes need modification or avoidance. However, arriving at such estimates of association is made challenging by a number of features characteristic of the relevant data. First, exposures may be time varying (for example, cigarette and alcohol consumption) so that, to relate them to birth outcomes, one needs to model them and then extract derived parameters. Secondly, there are likely to be unequal numbers and spacings of exposure determinations during pregnancy. Thirdly, one needs to account for a variety of additional covariates. Finally, the variability and non-linearities inherent in birth outcomes mandate flexible modelling approaches. Here we use data from a cohort of East Boston mothers to assess the impact of smoking during pregnancy on birth weights. We emphasize modelling of, and then adjusting for, maternal weight gain during pregnancy and a proxy measure for pre-pregnancy weight, so as to obtain better estimates of the smoking effect. Throughout, our analysis is guided by appropriate graphics. The adjustment features an interesting application of varying-coefficient models. Results indicate that smoking related deficits in birth weights depend on the mode of adjustment, and that previously observed deficits of approximately 200 g are best recaptured with use of varying-coefficient models.

Passive respiratory mechanics in healthy infants. Effects of growth, gender, and smoking.

This investigation characterizes the normal growth, variability, and effects of gender and smoking on passive respiratory mechanics in healthy infants. Passive respiratory mechanics were assessed at 193 test sessions on 127 infants (55 boys, 72 girls) between 2 wk and 18 mo of age using the single-occlusion passive flow-volume technique. Respiratory compliance (Crs) increased significantly with increasing infant length, whereas respiratory resistance (Rrs) declined. No significant gender differences were apparent for Crs, although there was a tendency for this measure to be both lower at birth and increase at a slower rate in girls than in boys. Rrs was significantly higher at birth in infant boys than in infant girls, but the rate of the normal decline in Rrs during the first 18 mo also occurred at a significantly greater rate in boys. The passive respiratory time constant (Trs) overall showed little change over this age range, but it was both lower near birth and increased at a significantly greater rate versus infant length in girls than in boys. Maternal smoking during pregnancy was associated with lower levels of Rrs at birth, as well as with significantly slower growth of Crs and natural decline of Rrs in the first 18 mo of life. These data suggest that infant girls may have more mature respiratory mechanics at birth, but that postnatal growth/maturation may be faster in boys.

Respiratory symptoms in urban Hispanic and non-Hispanic white women.

The prevalence and predictors of wheeze syndromes, including asthma, were examined among 475 non-Hispanic (NH) white and 371 Hispanic pregnant women enrolled in a population-based study in East Boston, Massachusetts. Respiratory symptoms and risk factors were ascertained by questionnaire early in pregnancy. Hispanic and NH white women were of similar age (mean +/- SD, 26 +/- 5 yr), but Hispanics reported less schooling (30 versus 50% completed high school), a lower frequency of household pets (4 versus 47%), and a lower frequency of parental asthma (6 versus 12%). Hispanics smoked significantly less than NH whites did, both in prevalence (8 versus 50%) and number of cigarettes per day among current smokers (12 +/- 9 versus 22 +/- 10; p < 0.0001). Hispanics reported a lower frequency than NH whites did of doctor-diagnosed asthma (6 versus 12%), persistent wheeze (5 versus 19%), and either persistent wheeze or asthma (11 versus 30%). In multivariate analysis, active cigarette smoking and parental history of asthma were associated most strongly with wheeze syndromes. When these two factors as well as educational level, presence of household pets, and height2-adjusted FEV1 were controlled, Hispanics remained at lower risk of asthma (odds ratio [OR] 0.71; 95% confidence interval [CI], 0.37-1.37) and persistent wheeze (OR 0.48; 95% CI, 0.25-0.95) than NH whites. These results suggest that chronic wheeze syndromes are common among young urban women and are associated with both active smoking and a parental history of asthma. Hispanic women from Central and South America living in urban environments in the United States may be at less risk for these conditions than NH white women, in contrast to those from Puerto Rico.

Alterations in follicular function associated with selection on ovulation rate in Finn ewes.

Finn ewes have been selected on ovulation rate to produce three lines with approximate ovulation rates of 5 (High), 3 (Control), and 2.5 (Low). The associated alterations in follicular function were investigated in three experiments. The function of large estrogenic follicles (Exp. 1) was assessed by measuring in vitro output of steroids and inhibin after a 1-h culture period. Follicles from High line ewes contained fewer (P < .01) granulosa cells than follicles from Low line ewes. Estradiol output per granulosa cell and testosterone output per thecal cell were greater for High than for Low line follicles (P < .01 and < .05, respectively). In contrast, inhibin output, expressed per follicle or per granulosa cell, did not differ between lines. In Exp. 2, cell proliferation in small follicles from the three lines was assessed after incubation of follicles in the presence of [3H]thymidine and in the presence or absence of FSH. The slope of the linear regression relating labeling index of the granulosa cells and follicle size differed significantly between High and Low lines with a significant negative coefficient for High line and a nonsignificant positive slope in the Low line. In Exp. 3, follicular fluid and serum proteins were compared between High and Low lines with 2D PAGE. A line difference was detected for a serum protein (40 kDa, pI = 6). High line had one spot, whereas Low line had three spots on 2D PAGE. This protein was not apolipoprotein E. Furthermore, the pattern of lipoproteins (high-density and low-density lipoproteins) in serum was similar between High and Low line sheep. The results indicate that selection for High ovulation rate was associated with smaller follicles that contained fewer granulosa cells per thecal cell. Aspects of function of estrogenic follicles (estradiol but not inhibin production) were also changed by selection.

Maternal smoking during pregnancy. Effects on lung function during the first 18 months of life.

The present investigation evaluated the effects of maternal smoking during pregnancy on the growth of lung function during the first 18 mo of life in 159 infants who were part of a longitudinal study of the effects of maternal smoking on respiratory health. Infant pulmonary function was assessed at 2 to 6 wk of age and at 4 to 6, 9 to 12, and 15 to 18 mo of age by partial expiratory flow-volume curves and helium dilution FRC. Maternal smoking was assessed by standard questionnaire and urine cotinine measurements. Maternal smoking during pregnancy was associated with a reduction of 9.4 +/- 4.3 ml (p = 0.029) for FRC and 33 +/- 12.3 ml/s (p = 0.008) reduction for flow at FRC (VFRC) after controlling for the effects of growth (length). The effect of maternal smoking was greater for female infants than for male infants. At 1 yr female infants exposed in utero were predicted to have a 16% reduction in VFRC compared with 5% for male infants. No sex difference was seen for FRC or VFRC/FRC. Exposure to environmental tobacco smoke in the postnatal period was not significantly related to reduced FRC or VFRC. These data provide further evidence that maternal smoking during pregnancy may play a greater role than postnatal and childhood exposure on the observed effects on lung function in children.

Relationship between an index of tidal flow and lower respiratory illness in the first year of life.

The ratio of time to tidal peak flow (Tme) to total tidal expiratory time (Te) has been reported to be decreased in infants who later develop wheezing lower respiratory tract illness (LRI) in the first year of life. The relationship between Tme/Te to the subsequent occurrence of LRI was studied in 98 infants in whom the first measurement of pulmonary function (PFT) was made before the age of 6 months and before the occurrence of any LRI. Occurrence of LRI was evaluated by standardized questionnaires at well-baby visits, through biweekly telephone calls to mothers, and review of all visits to physicians. Tme/Te was derived from 10 tidal breathing loops during stable respiration. Partial expiratory flow-volume curves were obtained with the rapid compression technique, and passive respiratory mechanics were evaluated by the single breath occlusion technique. Analysis of Tme/Te was stratified by age (< or = 10 weeks, > 10 weeks to 6 months) to take into account the age-related decline in Tme/Te. Among 80 infants first tested at < or = 10 weeks, Tme/Te was 12.4% shorter in those who developed a LRI vs. those who did not (P = 0.46); for 18 infants tested after 10 weeks, the difference was 1.9% (P = 0.39). Among male infants, the decrease in Tme/Te was observed only for those studied at < or = 10 weeks (16%, P = 0.16). For females, decreases were observed for those tested at < or = 10 weeks (11%, P = 0.83) and those tested after 10 weeks (17.5%, P = 0.09). Poisson regression analysis which included data for multiple measurements of Tme/Te over the first year of life and adjusted for age-at-test and maternal smoking during pregnancy also demonstrated a greater decrease in Tme/Te in female infants who subsequently develop an LRI (P = 0.08). Level of Tme/Te was not consistently related to level of respiratory system resistance (RRS) or flow at functional residual capacity (VFRC). Level of VFRC has been shown previously to be related to the occurrence of LRI and in this study to RRS(P = 0.007). The results indicate (1) a shortened Tme/Te is only weakly associated with the development of LRI in the first year of life; (2) this ratio is a less precise and an epidemiologically less useful measure than is VFRC to investigate groups of infants with and without LRI and without clinically significant underlying lung disease.

Effect of maternal smoking during pregnancy on passive respiratory mechanics in early infancy.

We studied the effect of prenatal maternal cigarette smoking on passive expiratory mechanics in 53 healthy infants tested early in infancy (mean +/- SD, 5.1 +/- 1.5 weeks). Maternal smoking was measured by: 1) questionnaire reports of the number of cigarettes smoked per day; and 2) urine cotinine concentrations (corrected for creatinine) at each visit. Respiratory system mechanics were assessed by the single-breath occlusion-passive-flow-volume maneuver. In ten infants born to smoking mothers the time constant of the respiratory system was 23% reduced [0.34 vs. 0.44 s; 95% confidence interval (CI), -45% + 1%; P = 0.06]. This was related to an estimated 13% decrease in respiratory system compliance (4.86 vs. 5.62 mL/cmH2O; 95%CI, -33% + 6%; P = 0.18) and a 10% reduction in respiratory system resistance (0.073 vs. 0.081 cm H2O/mL/s; 95%CI, -42% + 22%; P = 0.56). Functional residual capacity (FRC), measured by helium-dilution, was also decreased by 13% (78 vs. 90 mL; 95%CI, -27% + 0.3%; P = 0.06) in smoke-exposed infants. Forced expiratory flow rates at FRC obtained by thoraco-abdominal compression were reduced by 28% in infants of smoking mothers (VFRC, 99 vs. 138 mL/s; 95%CI, -54% + 2%; P = 0.04) as reported previously in a larger sample from this population. This study was limited by small numbers of infants exposed to smoking during pregnancy and by ethnic imbalance among the smoking-exposed and unexposed groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Lung function, pre- and post-natal smoke exposure, and wheezing in the first year of life.

The relationship between initial level of lung function and subsequent wheezing, lower respiratory illness (LRI) was studied in 97 infants in whom the first measurement of pulmonary function (PFT) was made before 6 months of age. Occurrence of LRI was evaluated by standardized questionnaires at each well-baby visit, biweekly telephone calls to mothers, and review of all visits to physicians. Infant PFT was assessed by partial expiratory flow-volume curves and helium-dilution measurement of functional residual capacity (FRC). Maternal, prenatal smoking was assessed by urine cotinine and standard questionnaires. Infants who developed an LRI during the first year of life had lower preillness length-corrected forced expiratory flow at FRC (VFRC) than those who did not experience an LRI (males, 2.06 +/- 0.20 versus 2.32 +/- 0.29 ml/s/cm; females, 2.38 +/- 0.20 versus 2.91 +/- 0.26 ml/s/cm). Similar results were observed with FRC-corrected VFRC. No differences were observed for FRC. Differences in lung function were greatest in female infants whose mothers did not smoke during pregnancy (VFRC 2.67 +/- 0.25 versus 3.49 +/- 0.26 ml/s/cm for those with and without LRI, respectively; p = 0.03). History of maternal wheezing was more common in infants who experience an LRI, independent of maternal smoking. The results were not influenced by exposure to nonmaternal sources of environmental tobacco smoke in the postnatal period. Regression analyses that included data for multiple measurements of VFRC over the first year and took account of duration of follow-up demonstrated that lower levels of VFRC were associated with an increased frequency of LRI, especially in female infants.(ABSTRACT TRUNCATED AT 250 WORDS)