Respiratory follow-up pre- and post-engineering controls or cessation of added diacetyl at four microwave popcorn facilities.

In a 7-year study at 4 microwave popcorn facilities, mixing room employees exposed to diacetyl prior to the introduction of respirators showed significant loss of lung function but did not continue to decline longitudinally faster than other job categories http://bit.ly/2xwWRiw.

A 30-year mortality and respiratory morbidity study of refractory ceramic fiber workers.

AIM: Report mortality (n = 1119), cancer incidence (n = 1207) and radiographic (n = 1451) findings from a 30-year investigation of current and former refractory ceramic fiber (RCF) workers. METHODS: Cause of death, health and work histories, radiographs and spirometry were collected. Mortality and cancer incidence were analyzed. Logistic regression analysis investigated the associations of latency and cumulative fiber exposure (CFE) on radiographic changes. RESULTS: The mortality study showed no increase in standardized mortality rates (SMR) for lung cancer, but urinary cancers were significantly elevated in the higher exposed group (SMR = 3.62, 95% CI: 1.33-7.88) and leukemia in the total cohort (SMR = 2.51, 95% CI: 1.08-4.94). One death attributed to mesothelioma was identified (SMR = 2.86, 95% CI: 0.07-15.93) in a worker reporting some asbestos exposure. The overall rate of pleural changes was 6.1%, attaining 21.4% in the highest CFE category for all subjects (adjusted odds ratio (aOR) = 6.9, 95% CI: 3.6-13.4), and 13.0% for those with no reported asbestos exposure (OR= 9.1, 95% CI: 2.5-33.6). Prevalence for recent hires (≥1985) was similar to the background. Interstitial changes were not elevated. Localized pleural thickening was associated with small decreases in spirometry results. CONCLUSION: Increases in leukemia and urinary cancer but not lung cancer mortality were found. One death attributed to mesothelioma was observed in a worker with self-reported asbestos exposure and a work history where occupational asbestos exposure may have occurred, rendering uncertainties in assigning causation. Radiographic analyses indicated RCF exposure alone is associated with increased pleural but not interstitial changes. Reductions in RCF exposure should continue. The mortality study is ongoing.

Clinical characteristics of chronic rhinitis patients with high vs low irritant trigger burdens.

BACKGROUND: Patients with chronic allergic rhinitis (AR) and nonallergic rhinitis (NAR) often experience irritant-induced symptoms. The clinical relevance of the magnitude of their symptoms in response to these nonspecific stimuli remains unclear. OBJECTIVE: To determine the internal consistency and validity of an irritant index questionnaire (IIQ) and whether reclassification of physician-diagnosed rhinitis subtypes based on IIQ scores results in rhinitis subtypes with different clinical characteristics. METHODS: Patients 18 to 65 years old with physician-diagnosed AR (n = 404), mixed rhinitis (MR; n = 129), or NAR (n = 123) completed an IIQ that rated rhinitis symptom severity in response to 21 nonallergic irritant triggers on a 1- to 10-point scale. Multistage sex-specific statistical analyses were performed using IIQ responses to reclassify physician-diagnosed AR, MR, and NAR into categories with high and low irritant burdens. RESULTS: The IIQ demonstrated good internal consistency and cross-validation. After reclassification, 48% and 52% of patients with physician-diagnosed AR patients (n = 533) were categorized as having low-burden AR and high-burden AR, respectively, whereas 64% and 36% of NAR (n = 123) patients were categorized as having low-burden NAR and high-burden NAR, respectively. Reclassified high-burden AR and high-burden NAR patients were more likely to have a physician diagnosis of asthma and a greater number of self-reported rhinitis symptoms and perennial symptoms with seasonal exacerbations than reclassified low-burden AR and low-burden NAR patients, respectively (P < .01). CONCLUSION: The IIQ resulted in significant reclassification of physician-diagnosed rhinitis patients into different diagnostic categories with unique clinical characteristics. Further studies are necessary to confirm the IIQ's utility as a tool for characterizing rhinitis patients in clinical practice and research.

Biopersistence of refractory ceramic fiber in human lung tissue and a 20-year follow-up of radiographic pleural changes in workers.

OBJECTIVE: The biopersistence of refractory ceramic fiber (RCF) in human lung tissue is unknown and may contribute to an association between cumulative fiber exposure and radiographic changes. METHODS: Lung tissue fiber was analyzed for a case series of 10 RCF workers and a 20-year longitudinal chest radiograph study of 1323 workers was conducted. RESULTS: Within lung tissue, RCF comprised 14% to 100% of fibers 5 µm or more in length and was identified up to 20 years after RCF employment. Among workers with no reported asbestos exposure, cumulative exposure of more than 63 to 110 and more than 110 fiber-months/cm was associated with radiographic pleural changes of 8.5% (odds ratio, 7.2; 95% confidence interval, 1.4 to 36.8) and 11.6% (odds ratio, 10.3; 95% confidence interval, 2.1 to 49.9), respectively. CONCLUSIONS: Refractory ceramic fiber can persist in human lung tissue for up to 20 years and may contribute to the significant association between cumulative fiber exposure and radiographic pleural changes.

Poor asthma control and exposure to traffic pollutants and obesity in older adults.

BACKGROUND: Environmental and host predictors of asthma control in older asthmatic patients (>65 years old) are poorly understood. OBJECTIVE: To examine the effects of residential exposure to traffic exhaust and other environmental and host predictors on asthma control in older adults. METHODS: One hundred four asthmatic patients 65 years of age or older from allergy and pulmonary clinics in greater Cincinnati, Ohio, completed the validated Asthma Control Questionnaire (ACQ), pulmonary function testing, and skin prick testing to 10 common aeroallergens. Patients had a physician's diagnosis of asthma, had significant reversibility in forced expiratory volume in 1 second or a positive methacholine challenge test result, and did not have chronic obstructive pulmonary disease. The mean daily residential exposure to elemental carbon attributable to traffic (ECAT) was estimated using a land-use regression model. Regression models were used to evaluate associations among independent variables, ACQ scores, and the number of asthma exacerbations, defined as acute worsening of asthma symptoms requiring prednisone use, in the past year. RESULTS: In the adjusted model, mean daily residential exposure to ECAT greater than 0.39 µg/m(3) was significantly associated with poorer asthma control based on ACQ scores (adjusted ß = 2.85; 95% confidence interval [CI], 0.58-5.12; P = .02). High ECAT levels were also significantly associated with increased risk of asthma exacerbations (adjusted odds ratio, 3.24; 95% CI, 1.01-10.37; P = .05). A significant association was found between higher body mass index and worse ACQ scores (adjusted ß = 1.15; 95% CI, 0.53-1.76; P < .001). Atopic patients (skin prick test positive) had significantly better ACQ scores than nonatopic patients (adjusted ß = -0.39; 95% CI, -0.67 to -0.11; P < .01). CONCLUSION: Higher mean daily residential exposure to traffic exhaust, obesity, and nonatopic status are associated with poorer asthma control among older asthmatic patients.

Asking the right questions to ascertain early childhood secondhand smoke exposures.

Secondhand smoke is associated with a myriad of adverse health outcomes. Therefore, it is essential for clinicians to ask precise questions about exposures, particularly for children. We present 4 questions that incorporate several locations of exposure and provide a more comprehensive account of children's smoke exposures than maternal smoking alone.

A randomized, double-blind, parallel trial comparing capsaicin nasal spray with placebo in subjects with a significant component of nonallergic rhinitis.

OBJECTIVE: To investigate the efficacy and safety of ICX72 or Sinus Buster, a proprietary homeopathic preparation of Capsicum annum and Eucalyptol, versus placebo administered continuously over 2 weeks in subjects with a significant component of nonallergic rhinitis (NAR). METHODS: Forty-two consented subjects meeting inclusion/exclusion criteria were randomized to ICX72 (n = 20) or control (n = 22) administered twice daily over 2 weeks. The primary endpoint was change in total nasal symptom scores (TNSS) from baseline to end of study. Secondary endpoints included changes in individual symptom scores (ISS) over 2 weeks and average time to first relief. Mean TNSS and ISS were recorded after single dosing at different intervals over 60 minutes. Rhinitis quality-of-life, rescue medication, and safety endpoints were analyzed. RESULTS: ICX72 versus placebo subjects exhibited significant differences in changes from baseline to end of study for TNSS and each ISS (P < .01), had an average time to first relief of 52.6 seconds (P < .01), and improvement in nasal congestion, sinus pain, sinus pressure, and headache at 5, 10, 15, and 30 minutes, persisting at 60 minutes for nasal congestion and sinus pain (P < .05). No difference between groups in adverse events or rescue medication was observed. ICX72 versus placebo subjects experienced no rebound congestion or impaired olfaction at the end of the study. CONCLUSION: This is the first controlled trial demonstrating intranasal capsaicin, when used continuously over 2 weeks, rapidly and safely improves symptoms in rhinitis subjects with a significant NAR component.

Cyanobacteria: an unrecognized ubiquitous sensitizing allergen?

This study was designed to investigate the prevalence of skin sensitization using detoxified cyanobacterial reagents in a chronic rhinitis population. Subjects ≥6 years of age who presented for allergy consultation to a community allergy practice and required skin-prick testing (SPT) to common seasonal and perennial aeroallergens were enrolled after signing an informed consent. Detoxified cyanobacteria species were used for skin testing. Skin testing of unexposed, nonsensitized control subjects using these detoxified cyanobacterial skin test reagents was performed to identify irritant threshold responses. All subjects signed an Institutional Review Board-approved informed consent before participation. Two hundred fifty-nine patients ranging in age between 7 and 78 years old underwent testing. The majority were white female patients and over two-thirds (73.4%) were atopic. Seventy-four (28.6% of the population) patients were SPT(+) to at least one of the cyanobacteria species. Positive SPTs were present in 86% of patients to Microcystis aeruginosa and 12% of patients to Aphanizomenon-flos aquae. There was a strong association between severity of atopy (number of positive SPTs), having allergic rhinitis and sensitization to one or more cyanobacteria species (p < 0.001). This is the first study to show that cyanobacterial allergenicity resides in nontoxin-containing components of this organism.

A long term study of pulmonary function among US refractory ceramic fibre workers.

BACKGROUND: Cross-sectional studies have shown declines in lung function among refractory ceramic fibre (RCF) workers with increasing fibre exposure. This study followed current and former workers (n=1396) for up to 17 years and collected 5243 pulmonary function tests. METHODS: Cumulative fibre exposure and production years were categorised into exposure levels at five manufacturing locations. Conventional longitudinal models did not adequately partition age-related changes from other time-dependent variables. Therefore, a restricted cubic spline model was developed to account for the non-linear decline with age. RESULTS: Cumulative fibre >60 fibre-months/cc showed a significant loss in lung function at the first test. When results were examined longitudinally, cumulative exposure was confounded with age as workers with the highest cumulative exposure were generally older. A longitudinal model adjusted by age groups was implemented to control for this confounding. No consistent longitudinal loss in lung function was observed with RCF exposure. Smoking, initial weight and weight increase were significant factors. CONCLUSION: No consistent decline was observed longitudinally with exposure to RCF, although cross-sectional and longitudinal findings were discordant. Confounding and accelerated lung function declines with ageing and the correlation of multiple time-dependent variables should be considered in order to minimise error and maximise precision. An innovative statistical methodology for these types of data is described.

Redefining spirometry hesitating start criteria based on the ratio of extrapolated volume to timed FEVs.

BACKGROUND: The primary purpose of this study was to investigate alternative hesitating start criteria for spirometry maneuvers that do not achieve an acceptable plateau. The current hesitating start criterion that has been in use for 30 years is based on clinical opinion from expert users; it was not established based on information from peer-reviewed scientific studies. METHODS: A total of 1,719 workers met the eligibility criteria for this study and contributed 24,945 trials. The fitted lines obtained from linear regressions of each dependent variable, volume of air calculated at time zero using the back extrapolation method (extrapolated volume [EV])/FEV(1), EV/FEV in 3 s (FEV(3)), and EV/FEV in 6 s (FEV(6)) on EV/FVC were determined. The 95th percentile of the prediction interval of each dependent variable corresponding to EV/FVC = 5% was calculated. RESULTS: The values for EV/FEV(1), EV/FEV(3), and EV/FEV(6) corresponding to the 5% EV/FVC value were determined to be 6.62%, 5.59%, and 5.25%, respectively. CONCLUSIONS: A new hesitating start criterion using EV/FEV(6) of 5.25% is recommended for tracings that do not achieve a plateau or when an FEV(6) is performed. An EV/FEV(3) of 5.59% could be incorporated into spirometry software as an early warning signal that could help operators identify trials with potential hesitating starts.

Assessing dietary variety in children: development and validation of a predictive equation.

BACKGROUND: Research indicates that the length of time needed to describe dietary diversity is approximately 2 weeks. This is the first study conducted to develop a dietary variety measurement tool that is sensitive to the effect of time on dietary variety without the burden of gathering data for 2 weeks. OBJECTIVE: To determine whether 3 days of 24-hour dietary recall logs collected during a 15-day period would predict food variety as well as 15 consecutive days. The study also determined which set of 3 days (consecutive vs interval days) within a 15-day period would better predict 15-day food variety. DESIGN: Prospective survey of the dietary practices of children. SUBJECTS/SETTING: Seventy-two children aged 9 to 12 years attending fourth and fifth grades in a public elementary school in a Midwestern town in the fall of 2005. MAIN OUTCOME MEASURES: Predicted 15-day cumulative dietary variety score from 3 consecutive days and 3 interval days of dietary data. STATISTICAL ANALYSIS PERFORMED: Two prediction models were obtained from multiple linear regression analyses in which natural log-transformed (log(e)) 15-day variety scores were regressed on log(e) 3-day variety scores (consecutive and interval days). The ability of each model to predict the 15-day cumulative variety score was assessed by comparisons of mean bias, mean-squared error, coefficient of determination (R(2)), and Pearson product-moment correlation coefficients. RESULTS: Three days of dietary data accurately estimated dietary variety over time for this sample of 9- to 12-year-old children using the predictive equation generated in this study. Three interval days predicted 15-day food variety more precisely than 3 consecutive days. CONCLUSIONS: The predictive equation is accurate in estimating food variety over time for this population and, if validated in independent samples, could be applied to similar populations.

Spinal deformity: a new classification derived from neutral upright spinal alignment measurements in asymptomatic juvenile, adolescent, adult, and geriatric individuals.

OBJECTIVE: In this literature review, the authors analyze data from previously published studies that evaluated neutral upright spinal alignment (NUSA) from the occiput to the pelvis in asymptomatic individuals. Based on the data for NUSA in asymptomatic volunteers, a new classification is proposed for spinal deformity. METHODS: A review of the English literature was conducted to identify studies evaluating NUSA from the occiput to the pelvis in asymptomatic juvenile, adolescent, adult, and geriatric volunteers. From the literature review, 17 angles and displacements were selected to depict neutral upright coronal and axial spinal alignment, and 21 angles and displacements were selected to depict neutral upright sagittal spinal alignment. Pooled estimates of the mean and variance were calculated for the angles and displacements from the articles that met inclusion criteria. A new classification of spinal deformity was then developed based on age-dependent NUSA; spinal abnormality; deformity curve location, pattern, magnitude, and flexibility; and global spinal alignment. RESULTS: Despite a wide variation in the regional curves from the occiput to the pelvis in asymptomatic volunteers, global spinal alignment is maintained in a narrow range for preservation of horizontal gaze and balance of the spine over the pelvis and femoral heads. CONCLUSION: A new classification of spinal deformity is proposed that provides a structure for defining deformity of all patient ages and spinal abnormalities.

Neutral upright sagittal spinal alignment from the occiput to the pelvis in asymptomatic adults: a review and resynthesis of the literature.

OBJECT: An increasing emphasis is being placed on the preservation or restoration of neutral upright sagittal spinal alignment in both deformity surgery and routine spinal operations. Sagittal spinal alignment is becoming recognized as an important predictor of a patient's outcome after spinal surgery. In this literature review, the authors analyze data obtained from previously published studies conducted to evaluate neutral upright sagittal spinal alignment from the occiput to the pelvis in asymptomatic adults. METHODS: A review of the English-language literature was conducted to identify studies conducted to evaluate neutral upright sagittal spinal (occiput-pelvis) alignment in asymptomatic adult volunteers with no spinal disease. The authors identified 12 articles that met the strict primary inclusion criteria of the current study. From these articles, 23 angles and displacements were selected to depict neutral upright sagittal occiput-pelvis alignment. Pooled estimates of the mean and variance were calculated for angles and displacements that met secondary inclusion criteria. The greatest variation in the regional spinal curves occurred in the cervical spine from C-2 to C-7, whereas the greatest focal angulation in the spine occurred from L-4 to S-1. Sagittal spinal balance was maintained in a narrow range for alignment of the spine over the pelvis and femoral heads. CONCLUSIONS: Neutral upright sagittal occiput-pelvis alignment in asymptomatic adults has been well studied regionally. Despite a wide variation in the undulating lordotic and kyphotic regional curves from the occiput to the pelvis, sagittal spinal balance is maintained in a narrower range for alignment of the spine over the pelvis and femoral heads.

A clinical-based intervention improves diet in patients with head and neck cancer at risk for second primary cancer.

A diet rich in fruits and vegetables is associated with a reduced risk of head and neck cancer. This study was designed to assess the efficacy of an intervention to increase fruit and vegetable consumption and improve overall diet quality in patients with early stage head and neck cancer at risk for second primary cancer. The study was a crossover-controlled design with each patient being his or her own control. Patients received usual care during the control period followed by a clinical-based intervention grounded in the Social Learning Theory for 3 months. Measurements were taken at baseline, 6 months, and 12 months. The intervention consisted of a face-to-face counseling session, a phone call, and three mailings. Findings from this study indicate that these patients increased their intake of fruits (number of servings and variety), vegetables (number of servings), and improved overall diet quality while exposed to the intervention as compared with usual care.

Exposures to refractory ceramic fibers in manufacturing and related operations: a 10-year update.

Refractory ceramic fiber (RCF) is a man-made vitreous fiber used for its insulating properties. Since 1987, the work environment of approximately 800 persons employed in fiber manufacture or production operations directly related to manufacturing has been monitored to evaluate exposure levels. Samples were collected quarterly from the breathing zones of randomly selected workers. The measurements from those working in areas of similar activities and exposure controls (dust zones or homogeneous exposure groups) were used to calculate a mean exposure during identified time periods. Persons who spent all of their work time in one zone/group were assigned this mean exposure; those with responsibilities in more than one area were assigned an exposure based on a time-weighted formula. A total of 3213 measurements were used to estimate exposure for 130 job titles; because of the mobile jobs, many samples contribute to the estimates of exposure for multiple job titles. The majority of exposure estimates (53%) have remained stable over the operational history of the plant reported here. For 32 job titles (25%) exposures have decreased, and for 28 job titles (22%) exposures have increased. Of the 122 job titles active in 2001, 97 (79%) exposures were estimated to be at 0.25 f/cc or lower; 8 (7%) had an exposure exceeding 0.5 f/cc (range 0.51-0.80) and 17 (14%) of these exposure estimates were in the range of > 0.25 f/cc to 0.5 f/cc. The continuing program to measure exposure supports a respiratory health surveillance program in these facilities.

Functional effect of the R110Q IL13 genetic variant alone and in combination with IL4RA genetic variants.

BACKGROUND: IL-13 is a key mediator of allergic asthma. IL-13 mediates its effects via its receptor, a heterodimer composed of IL-4R alpha and IL-13R alpha1. Polymorphic variants of both IL-13 and IL-4R alpha have been shown to be associated with atopy. OBJECTIVE: We examined the functional consequences of the Q110 IL-13 variant in vitro and in vivo to determine whether it displays enhanced functional activity compared with R110 IL-13, both in the context of I50Q551 IL-4R alpha and of the atopy-associated variant V50R551 IL-4R alpha. METHODS: We used a mouse cell line stably expressing human IL-4R alpha and IL-13R alpha1 that readily responds to human IL-4 and IL-13. For in vivo analyses, we used BALB/c mice. RESULTS: The Q110 IL-13 variant displayed significantly increased activity compared with R110 IL-13. Furthermore, mice treated with Q110 IL-13 variant displayed increased airways hyperresponsiveness relative to R110 IL-13. We then examined the functional consequences of Q110 IL-13 variant in combination with an atopy-associated variant of its receptor, IL-4R alpha (V50R551). Q110 IL-13 variant had increased activity on these cells as well, and, strikingly, the effect was greater than that observed in cells expressing I50Q551 IL-4R alpha. CONCLUSION: Either Q110 IL-13 variant or V50R551 IL-4R alpha variant has enhanced function alone, but the 2 together have a synergistic effect on IL-13-dependent gene induction. Our data demonstrate the importance of relatively small individual differences in gene products from common single nucleotide polymorphisms that may result in larger combined differences. Furthermore, a relatively modest change in function from a single nucleotide polymorphism can result in an important biological difference in vivo.

Evolution of the mdx mouse cardiomyopathy: physiological and morphological findings.

Heart failure is a major cause of death in boys with Duchenne muscular dystrophy. In order to determine if the cardiac function of the mdx mouse is similarly disturbed, we performed murine echocardiograms and left heart catheterization studies, along with morphometric analysis of cardiac fibrosis. Serial echocardiograms in mdx mice revealed the evolution from normal cardiac function in young mice to a dilated cardiomyopathy in adult mice. Very old mdx mice exhibited a widespread but patchy increase in ventricular wall fibrosis. These results show that the mdx cardiac function is more impaired than was previously thought and shares important clinical features with the cardiomyopathy of Duchenne muscular dystrophy.

Induction of centrosome amplification and chromosome instability in human bladder cancer cells by p53 mutation and cyclin E overexpression.

Centrosome amplification frequently occurs in human cancers and is a major cause of chromosome instability (CIN). In mouse cells, centrosome amplification can be readily induced by loss or mutational inactivation of p53. In human cells, however, silencing of endogenous p53 alone does not induce centrosome amplification or CIN, although high degrees of correlation between p53 mutation and CIN/centrosome amplification in human cancer can be detected, suggesting the presence of additional regulatory mechanism(s) in human cells that ensures the numeral integrity of centrosomes and genomic integrity. Cyclin E, a regulatory subunit for CDK2 that plays a key role in centrosome duplication, frequently is overexpressed in human cancers. We found that cyclin E overexpression, together with loss of p53, efficiently induces centrosome amplification and CIN in human bladder cancer cells but not by either cyclin E overexpression or loss of p53 alone. We extended these findings to bladder cancer specimens and found that centrosome amplification is strongly correlated with concomitant occurrence of cyclin E overexpression and p53 inactivation but not with either cyclin E overexpression or p53 inactivation alone. Because cyclin E expression is strictly controlled in human cells compared with mouse cells, our findings suggest that this stringent regulation of cyclin E expression plays an additional role underlying numeral homeostasis of centrosomes in human cells and that deregulation of cyclin E expression, together with inactivation of p53, results in centrosome amplification.

Mortality of workers occupationally exposed to refractory ceramic fibers.

This study was prompted by refractory ceramic fibers (RCF) inhalation studies at high dose levels in animals that demonstrated positive effects for lung fibrosis, mesothelioma, and lung cancer. Current and former male workers employed between 1952 and 2000 at two RCF manufacturing facilities were followed to investigate a possible excess in mortality. The mortality analytic methods included: (1) standardized mortality ratios comparing this cohort to the general and state populations, and (2) a proportional hazards model that relates risk of death to the lifetime cumulative fiber-months/cc exposure among the RCF cohort, adjusted for age at hire and for race. There was no excess mortality related to all deaths, all cancers, or malignancies or diseases of the respiratory system including mesothelioma, but there was a statistically significant association with cancers of the urinary organs SMR = 344.8 (95% CL of 111.6, 805.4). The quality of the data for job history, exposure, and smoking history were very high. Although the cohort was relatively small and young with an average age of 51, the mean latency period was over 21 years. Because of these limitations, the preliminary findings warrant the continuation of this mortality registry for future analyses.

Pregnancy hormone metabolite patterns, pregnancy symptoms, and coffee consumption.

Because of contradictory reports of pregnancy outcomes and coffee intake, this study was designed to determine how hormone metabolite levels, symptoms, and coffee consumption patterns are related. Eligible subjects were recruited in Cincinnati, Ohio, from 1996 to 1998, aged 18-40 years, and nonsmokers; drank at least 18 ounces (1 ounce = 29.6 ml) of coffee per week (including decaffeinated) at the last menstrual period; and were enrolled by 9 weeks from the last menstrual period. Beverage consumption and pregnancy symptoms were recorded daily. Weekly, first-morning urine samples were collected to assess human chorionic gonadotropin, estrone-3-glucuronide, and pregnanediol-3-glucuronide. A time-dependent, repeated measures analysis was performed to test several associations. Data from 92 subjects were analyzed with the following results. 1) Coffee consumption was significantly, inversely associated with weekly levels of estrone-3-glucuronide and human chorionic gonadotropin. 2) Weekly hours of nausea were significantly, directly associated with human chorionic gonadotropin and inversely with estrone-3-glucuronide and pregnanediol-3-glucuronide. 3) Weekly coffee consumption was significantly associated with vomiting but not with nausea or appetite loss. 4) Weekly levels of pregnanediol-3-glucuronide were 32.2% lower in subjects who drank at least 8 ounces of coffee/day at the last menstrual period, though above what was necessary to maintain those pregnancies. This study shows the significance of these important variables to be considered in future research.