Early improvement in serial echocardiographic studies in heart failure patients predicts long term survival-a pilot study.

BACKGROUND: Several echocardiographic measures have prognostic value in heart failure (HF). However, no definitive data exist on how changes in these parameters with treatment affect survival in this patient population. We hypothesized that early improvement on echocardiography could predict long-term survival. METHODS AND RESULTS: We conducted a retrospective review of 404 patients seen in the HF clinic from 2002 to 2008 (6.5 years). Patients had one echocardiogram ≤1 year before and another ≥1 month (10 ± 7 months) after treatment onset. We studied changes in standard echocardiographic parameters, including left (LV) and right (RV) ventricular size and/or function (systolic and/or diastolic), valvular (mitral and tricuspid) function, and pulmonary artery pressure. Survival curves and hazard ratios were generated for patients showing improvement on the 2nd echocardiogram versus those who did not. Multivariable analyses were performed adjusting for age, sex, ischemic etiology, and significant baseline echocardiographic parameters. Average follow-up was 2.9 ± 1.5 years. Improvement in LV end-systolic dimension, RV function, and mitral regurgitation were independent predictors of 5-year survival (P < .05) and, importantly, more predictive than baseline values of these parameters alone (higher hazard ratios). CONCLUSIONS: Early echocardiographic improvement is strongly associated with 5-year survival in patients with HF. Serial echocardiography may aid in stratifying patient care.

Incidence and determinants of sudden infant death syndrome: a population-based study on 37 million births.

BACKGROUND: The objective of our study is to measure the incidence of sudden infant death syndrome (SIDS), estimate the birth to death interval, and identify associated maternal and infant risk factors. METHODS: We carried out a population-based cohort study on 37 418 280 births using data from the Centers for Disease Control and Prevention's "Linked Birth-Infant Death" and "Fetal Death" data files from 1995 to 2004. Descriptive statistics and cox-proportional hazard models were used to estimate the adjusted effect of maternal and newborn characteristics on the risk of SIDS. RESULTS: There were 24 101 cases of SIDS identified for an overall 10-year incidence of 6.4 cases per 10 000 births. Over the study period, the incidence decreased from 8.1 to 5.6 per 10 000 and appeared to be most common among infants aged 2-4 months. Risk factors included maternal age <20 years, black, non-Hispanic race, smoking, increasing parity, inadequate prenatal care, prematurity and growth restriction. CONCLUSIONS: While the incidence of SIDS in the US has declined, it currently remains the leading cause of post-neonatal mortality, highlighting an important public health priority. Educational campaigns should be targeted towards mothers at increased risk in order to raise their awareness of modifiable risk factors for SIDS such as maternal smoking and inadequate prenatal care.

Incidence, risk factors, and obstetrical outcomes of women with breast cancer in pregnancy.

Breast cancer in pregnancy is a rare condition. The objective of our study was to describe the incidence, risk factors, and obstetrical outcomes of breast cancer in pregnancy. We conducted a population-based cohort study on 8.8 million births using data from the Healthcare Cost and Utilization Project - Nationwide Inpatient Sample from 1999-2008. The incidence of breast cancer was calculated and logistic regression analysis was used to evaluate the independent effects of demographic determinants on the diagnosis of breast cancer and to estimate the adjusted effect of breast cancer on obstetrical outcomes. There were 8,826,137 births in our cohort of which 573 cases of breast cancer were identified for an overall 10-year incidence of 6.5 cases per 100,000 births with the incidence slightly increasing over the 10-year period. Breast cancer appeared to be more common among women >35 years of age, odds ratio (OR)=3.36 (2.84-3.97); women with private insurance plans, OR=1.39 (1.10-1.76); and women who delivered in an urban teaching hospital, OR=2.10 (1.44-3.06). After adjusting for baseline characteristics, women with pregnancy-associated breast cancer were more likely to have an induction of labor, OR=2.25 (1.88, 2.70), but similar rates of gestational diabetes, preeclampsia, instrumental deliveries, and placental abruption. The incidence of breast cancer in pregnancy appears higher than previously reported with women over 35 being at greatest risk. Aside from an increased risk for induction of labor, women with breast cancer in pregnancy have similar obstetrical outcomes.

Inadequate prenatal care utilization and risks of infant mortality and poor birth outcome: a retrospective analysis of 28,729,765 U.S. deliveries over 8 years.

OBJECTIVE: To evaluate the association between adequacy of prenatal care utilization and risk of fetal and neonatal mortality and adverse outcomes. METHODS: We conducted a population-based cohort study using the Center for Disease Control and Prevention's Linked Birth-Infant Death and Fetal Death data on all deliveries in the United States between 1995 and 2002. Inclusion criteria were singleton births ≥22 weeks of gestation with no known congenital malformation. Inadequate prenatal care was defined according to the Adequacy of Prenatal Care Utilization Index, and its effect on fetal and neonatal death was estimated using unconditional logistic regression analysis adjusting for maternal age, race, education, and other confounding variables. RESULTS: During our 8-year study period, 32,206,417 births occurred, 28,729,765 (89.2%) of which met inclusion criteria. Inadequate prenatal care utilization occurred in 11.2% of expectant mothers, more commonly among women ≤20 years, black non-Hispanic and Hispanic women, and those without high school education. Relative to adequate care, inadequate care was associated with increased risk of prematurity 3.75 (3.73 to 3.77), stillbirth 1.94 (1.89 to 1.99), early neonatal dearth 2.03 (1.97 to 2.09), late neonatal death 1.67 (1.59 to 1.76), and infant death 1.79 (1.76 to 1.82). CONCLUSION: Risk of prematurity, stillbirth, early and late neonatal death, and infant death increased linearly with decreasing care. Given the population effect of this association, public health initiatives should target program expansion to ensure timely and adequate access, particularly for women ≤20 years, Black non-Hispanic and Hispanic women, and those without high school education.

Combination of serum biomarkers to differentiate malignant from benign ovarian tumours.

OBJECTIVE: To investigate biomarkers and clinical parameters to distinguish ovarian cancers from benign ovarian tumours. METHODS: Serum biomarkers (CA 125, human epididymis protein 4 [HE 4], interleukin-18 [IL-18], leptin, macrophage migration inhibitory factor [MIF], fibroblast growth factor 2 [FGF-2], insulin-like growth factor, osteopontin, prolactin) and the risk of malignancy indexes I and II (RMI-I and RMI-II) scores were obtained prior to surgery in 52 patients with ovarian tumours (37 malignant and 15 benign). ROC curves were built for each individual marker, for logistic regression models using all markers, and for models combining both biomarkers and RMI scores. RESULTS: The model with nine biomarkers performed well (specificity 93%, sensitivity 84%) and was more reliable than the RMI-I or RMI-II alone. A regression model combining RMI-II and six of the biomarkers (CA 125, HE  4, IL-18, leptin, MIF, and FGF-2) allowed differentiation between the cancer and non-cancer cases in this pilot study. CONCLUSION: The regression models using biomarkers combined with clinical scoring systems warrant further investigation to improve triage of patients with ovarian tumours to enhance utilization of resources and optimize patient care.

Human papillomavirus vaccination intentions and uptake in college women.

OBJECTIVE: Using the health belief model (HBM) and theory of planned behavior (TPB) as theoretical frameworks, the objectives of this study were: (a) to identify correlates of human papillomavirus (HPV) vaccination intentions and (b) to explore differences between correlates of HPV vaccination intentions and uptake. METHODS: Undergraduate women (N = 447) who did not intend to receive (n = 223), intended to receive (n = 102), or had received (n = 122) the HPV vaccine were surveyed. Logistic regressions were conducted to examine the correlates of vaccination intentions and uptake. RESULTS: Negative health consequences of the vaccine, physician's recommendation, positive attitudes toward the vaccine, and subjective norms were significant correlates of vaccination intentions. When comparing correlates of vaccination intentions to correlates of vaccination uptake, physician's recommendation, subjective norms, and perceived susceptibility to HPV were unique correlates of uptake. CONCLUSION: Differences between correlates of vaccination intentions and uptake suggest that social influences of liked and trusted individuals may make an important and unique contribution in motivating young women to receive the HPV vaccine beyond other variables from the HBM and TPB. Future utilization of longitudinal designs is needed to understand which factors may cause individuals to decide to receive the HPV vaccine.

The effect of catastrophizing and depression on chronic pain--a prospective cohort study of temporomandibular muscle and joint pain disorders.

Although most cases of temporomandibular muscle and joint disorders (TMJD) are mild and self-limiting, about 10% of TMJD patients develop severe disorders associated with chronic pain and disability. It has been suggested that depression and catastrophizing contributes to TMJD chronicity. This article assesses the effects of catastrophizing and depression on clinically significant TMJD pain (Graded Chronic Pain Scale [GCPS] II-IV). Four hundred eighty participants, recruited from the Minneapolis/St. Paul area through media advertisements and local dentists, received examinations and completed the GCPS at baseline and at 18-month follow-up. In a multivariable analysis including gender, age, and worst pain intensity, baseline catastrophizing (ß 3.79, P<0.0001) and pain intensity at baseline (ß 0.39, P<0.0001) were positively associated with characteristic of pain intensity at the 18th month. Disability at the 18-month follow-up was positively related to catastrophizing (ß 0.38, P<0.0001) and depression (ß 0.17, P=0.02). In addition, in the multivariable analysis adjusted by the same covariates previously described, the onset of clinically significant pain (GCPS II-IV) at the 18-month follow-up was associated with catastrophizing (odds ratio [OR] 1.72, P=0.02). Progression of clinically significant pain was related to catastrophizing (OR 2.16, P<0.0001) and widespread pain at baseline (OR 1.78, P=0.048). Results indicate that catastrophizing and depression contribute to the progression of chronic TMJD pain and disability, and therefore should be considered as important factors when evaluating and developing treatment plans for patients with TMJD.

Infliximab therapy for moderately severe Crohn's disease and ulcerative colitis: a retrospective comparison over 6 years.

BACKGROUND: Infliximab has shown benefit in Crohn's disease (CD) and ulcerative colitis (UC). OBJECTIVE: Evaluation of long-term outcome of therapy for both diseases. METHODS: We analyzed retrospectively patients treated at infusion centers from one institution. Demographic, laboratory parameters leading up to biologic therapy and the subsequent pattern of outcomes in either disease were established as a database. Initial failure, subsequent need to change therapy, or need to adjust therapy were evaluated. Kruskal-Wallis (nonparametric) tests to compare two groups and Kaplan-Meier survival curve analysis were used to compare outcomes. RESULTS: Over approximately 6 years, 71 CD and 26 UC patients received 999 and 215 infusions, respectively, for a median of 62 months. Of these, 17% for CD and 19% for UC patients were primary failures. Following the start of infliximab, 18% of CD and 11% of UC patients required stoppage and switching to another type of therapy. In either CD or UC patients, 54% or 62%, respectively, continued therapy without the need to change to other treatments. Few serious side effects were noted. No important statistically significant differences in treatment patterns or outcome were observed between the groups. DISCUSSION: Long-term treatment of both inflammatory bowel diseases reflects outcomes of clinical trials. CONCLUSIONS: This study emphasizes similarities between CD and UC and reports therapeutic success for an extended time.

Elevated plasma gas6 levels are associated with venous thromboembolic disease.

Growth arrest-specific 6 (gas6), a novel vitamin K-dependent protein, has been demonstrated to have a role in thrombus stabilization as gas6 null mice are resistant to lethal venous and arterial thrombosis. However, the association between gas6 and venous thromboembolism has not been elucidated in humans. The present study aims to assess the role of gas6 in human venous thromboembolic (VTE) disease. Using a highly specific ELISA method, we measured plasma levels of gas6 in plasma samples obtained from 279 patients with VTE and 79 healthy volunteers. Medication history, comorbid conditions and VTE characteristics were documented. Mean gas6 levels were higher in patients with VTE as compared to healthy volunteers, being 46 ±11 ng/ml and 35 ±6.4 ng/ml respectively (P < 0.001). Odds ratios (OR) for VTE given elevated (≥90th percentile of healthy volunteers) gas6 levels were estimated in regression models in the whole study population. After adjustment for age, sex, medications and comorbidity, subjects with elevated gas6 had an increased risk of VTE (OR of 16.3 (95% CI 5.8-45.7, P < 0.001) compared to those with lower levels of gas6. This association remains significant even among patients with a comparable age distribution. Among patients with VTE, mean gas levels showed a trend of higher levels in those with more extensive thrombi. There was no correlation between elevated gas6 levels and recurrent VTE. In conclusion, we demonstrate an association between VTE and elevated gas6 levels consistent with in vivo murine models of thrombosis. This constitutes a potential novel mechanism for thrombosis in humans and may aid in the understanding of the pathophysiology of VTE.

Serum thyroglobulin predicts thyroid remnant ablation failure with 30 mCi iodine-131 treatment in patients with papillary thyroid carcinoma.

BACKGROUND: Most patients with differentiated thyroid cancer are treated with radioiodine (131-I) after thyroidectomy. The characteristics predictive of successful remnant ablation with low activities of 131-I are ill defined and could help stratify patients into those who should receive higher activities. METHODS: In a case series of 193 consecutive patients with papillary thyroid cancer who underwent total thyroidectomy and received 30 mCi (1110 MBq) of 131-I, we assessed the percentage of successful radioremnant ablation as defined by a composite of scintigraphic and biochemical endpoints. Clinical, histological, scintigraphic, and biochemical covariables were analyzed to identify associations with treatment failure. RESULTS: Successful radioremnant ablation with low-activity 131-I was obtained in 78% of the entire cohort of patients. The presence of limited microscopic extrathyroidal extension, nodal micrometastases, or an elevated stimulated ablation was associated with failure to ablate the remnant. While accounting for other factors in a multivariable analysis, patients with an ablation thyroglobulin of at least 6 µg/l were at a more than five times greater risk (P<0.001) to fail 30 mCi 131-I remnant ablation. CONCLUSION: The majority of patients with papillary thyroid carcinoma experienced successful ablation. However, elevated-stimulated ablation thyroglobulin levels were strongly predictive of ablation failure, suggesting that this biochemical marker correlates with a more aggressive tumor profile and identifies those patients who might benefit from additional therapy.

The effect of fibromyalgia and widespread pain on the clinically significant temporomandibular muscle and joint pain disorders--a prospective 18-month cohort study.

UNLABELLED: Although most cases of temporomandibular muscle and joint disorders (TMJD) are mild and self-limiting, about 10% of TMJD patients develop severe disorders associated with chronic pain and disability. It has been suggested that fibromyalgia and widespread pain play a significant role in TMJD chronicity. This paper assessed the effects of fibromyalgia and widespread pain on clinically significant TMJD pain (GCPS II-IV). Four hundred eighty-five participants recruited from the Minneapolis/St. Paul area through media advertisements and local dentists received examinations and completed the Graded Chronic Pain Scale (GCPS) at baseline and at 18 months. Baseline widespread pain (OR: 2.53, P = .04) and depression (OR: 5.30, P = .005) were associated with onset of clinically significant pain (GCPS II-IV) within 18 months after baseline. The risk associated with baseline fibromyalgia was moderate, but not significant (OR: 2.74, P = .09). Persistence of clinically significant pain was related to fibromyalgia (OR: 2.48, P = .02) and depression (OR: 2.48, P = .02). These results indicate that these centrally generated pain conditions play a role in the onset and persistence of clinically significant TMJD. PERSPECTIVE: Fibromyalgia and widespread pain should receive important consideration when evaluating and developing a treatment plan for patients with TMJD.

Work environment risk factors for injuries in wood processing.

PROBLEM: The reported injury rate for wood product manufacturing in Maine, 1987-2004, was almost twice the state-wide average for all jobs. METHOD: A case-control study was conducted in wood processing plants to determine preventable risk factors for injury. A total of 157 cases with injuries reported to workers' compensation and 251 controls were interviewed. RESULTS: In multivariable analyses, variables associated with injury risk were high physical workload, machine-paced work or inability to take a break, lack of training, absence of a lockout/tagout program, low seniority, and male gender. Different subsets of these variables were significant when acute incidents and overexertions were analyzed separately and when all injuries were stratified by industry sub-sector. IMPACT ON INDUSTRY: Generalizability may be limited somewhat by non-representative participation of workplaces and individuals. Nevertheless, these findings provide evidence that many workplace injuries occurring in wood processing could be prevented by application of ergonomics principles and improved work organization.

Brain sterol dysregulation in sporadic AD and MCI: relationship to heme oxygenase-1.

The objective of this study was to ascertain the impact of aging and Alzheimer's disease (AD) on brain cholesterol (CH), CH precursors, and oxysterol homeostasis. Altered CH metabolism and up-regulation of heme oxygenase-1 (HO-1) are characteristic of AD-affected neural tissues. We recently determined that HO-1 over-expression suppresses total CH levels by augmenting liver X receptor-mediated CH efflux and enhances oxysterol formation in cultured astroglia. Lipids and proteins were extracted from postmortem human frontal cortex derived from subjects with sporadic AD, mild cognitive impairment (MCI), and no cognitive impairment (n = 17 per group) enrolled in the Religious Orders Study, an ongoing clinical-pathologic study of aging and AD. ELISA was used to quantify human HO-1 protein expression from brain tissue and gas chromatography-mass spectrometry to quantify total CH, CH precursors, and relevant oxysterols. The relationships of sterol/oxysterol levels to HO-1 protein expression and clinical/demographic variables were determined by multivariable regression and non-parametric statistical analyses. Decreased CH, increased oxysterol and increased CH precursors concentrations in the cortex correlated significantly with HO-1 levels in MCI and AD, but not no cognitive impairment. Specific oxysterols correlated with disease state, increasing neuropathological burden, neuropsychological impairment, and age. A model featuring compensated and de-compensated states of altered sterol homeostasis in MCI and AD is presented based on the current data set and our earlier in vitro work.

Levels of inflammatory markers and the development of the post-thrombotic syndrome.

The post-thrombotic syndrome (PTS) occurs frequently after deep venous thrombosis (DVT) despite appropriate anticoagulant therapy. A close relationship between inflammation and thrombosis exists. While the inflammatory process at the time of DVT appears to improve thrombus resolution, it may promote destruction of venous valves, valvular reflux and subsequent development of PTS. We prospectively evaluated the association between levels of four cytokines (IL-6, IL-8, IL-10 and MCP-1), two adhesion molecules (ICAM-1 and VCAM-1) and the development of PTS in a well-defined cohort of patients with DVT. The study population consisted of 387 patients with objectively diagnosed symptomatic DVT who were followed for two years to determine the incidence of PTS. At the end of followup, plasma samples frozen at the four-month visit in 307 study patients were thawed and analyzed for the above inflammatory markers using the Luminex beads technology. Mean levels of IL-6 were significantly higher in patients with PTS compared to patients without PTS (7.35 pg/ml +/- 14.26 [SD] vs. 4.60 pg/ml +/- 4.90; p = 0.03). Logistic regression analyses showed significant associations between PTS and levels above vs. below the median of IL-6 [odds ratio (OR) 1.66; 95% confidence interval (CI) 1.05, 2.62 (p = 0.03)] and ICAM-1 [OR 1.63; 95% CI 1.03, 2.58 (p = 0.04)]. None of the other markers showed any association with PTS. Our study suggests the presence of significant associations between markers of inflammation such as IL-6 and ICAM-1 and the development of PTS. Further work is needed to evaluate this relationship and to analyse other candidate markers that could be implicated etiologically in the association between DVT and PTS. If confirmed, this could lead to identification of new therapeutic targets for preventing PTS after DVT.

Evaluation of a proposed area equation for improved exothermic process control.

Our understanding of heat transfer and meteorological theories and their applications for engineering control design have been refined since the collective work in ventilation engineering for manufacturing process was published by Hemeon in 1955. These refined theories were reviewed and used to develop a newly proposed equation to estimate buoyant plume area (A). The area is a key parameter in estimating the plume volumetric flow (Q=UA) required for exothermic process control. Subsequent to developing a theoretical equation for plume area (A), plume velocity and area data were collected in the laboratory using a thermal anemometer and a scale-model exothermic process. Laboratory results were compared to solutions provided by the proposed, American Conference of Governmental Industrial Hygienists (ACGIH) and Hemeon plume area equations to determine which equation most closely matched the laboratory data. To make this determination, either t-tests or Wilcoxon signed-rank tests were conducted (based on examination of data normality) to determine the difference between collected data and solutions from the proposed, ACGIH and Hemeon equations. Median differences and P-values from Wilcoxon signed-rank tests (non-parametric) indicate that the ACGIH and Hemeon plume area equations provide significantly lower values than the laboratory data. However, the proposed equation provided solutions that were not significantly different from the collected data. Results indicate that the plume area equations currently recommended by the ACGIH and Hemeon are not as accurate as the proposed equation over the range of parameters investigated.

Evaluation of a proposed velocity equation for improved exothermic process control.

Exothermic or heated processes create potentially unsafe work environments for an estimated 5-10 million American workers each year. Excessive heat and process contaminants have the potential to cause adverse health effects in exposed workers. Owing to the potential hazards, engineering controls are recommended for these processes. Our understanding of heat transfer and meteorological theories, and their applications for engineering controls have evolved since seminal work was published by Hemeon in 1955. These refined theories were reviewed and used to develop a proposed equation to estimate buoyant plume mean velocity. Mean velocity is a key parameter used to estimate the plume volumetric flow required for controlling effluents from exothermic processes. Subsequent to developing the proposed equation, plume velocity data were collected with a thermal anemometer for a model exothermic process in the laboratory, and an actual exothermic process in the field. Laboratory and field results were then compared to solutions provided by the proposed, American Conference of Governmental Industrial Hygienists (ACGIH), and Hemeon mean velocity equations. To determine which equation most closely matched the laboratory and field data, either t-tests or Wilcoxon Signed Rank tests were conducted (based on examination of data normality) to determine the difference between collected data and solutions from the proposed, ACGIH, and Hemeon equations. Median differences and P-values from Wilcoxon Signed Rank tests (nonparametric) indicate that the ACGIH mean velocity equation provides significantly different estimates from the laboratory and the field mean velocity data. However, the proposed and Hemeon equation provided solutions that were not significantly different from the collected data. These results were unexpected due to the similar developmental backgrounds between the ACGIH and Hemeon equations. Findings indicate that radiant heat flux is an important consideration when using horizontal plate heat transfer equations to estimate plume mean velocity over the range of parameters investigated. Results indicate that the mean velocity equation currently recommended by ACGIH is not as accurate as either the proposed or Hemeon equations over the range of parameters investigated.

Phase II study of 5-fluorouracil, doxorubicin, and mitomycin C for metastatic small bowel adenocarcinoma.

BACKGROUND: Small bowel adenocarcinoma is a rare gastrointestinal malignancy that is treated primarily with surgery. Even with optimal resection, however, survival is poor and recurrences are common. Response rates to palliative combination chemotherapy are low, and the median duration of survival for metastatic disease is less than 1 year. This study aimed to document the response rate and survival time for patients with advanced small bowel adenocarcinoma who were not surgically curable and were treated with a regimen of 5-fluorouracil (5-FU), mitomycin C (Mutamycin; Bristol-Myers Squibb; Princeton, NJ), and doxorubicin (Adriamycin; Bedford Laboratories; Bedford, OH), the FAM regimen. METHODS: This multi-institutional study was performed by the Eastern Cooperative Oncology Group (ECOG). Between November, 1983 and December, 1985, 39 patients with advanced or recurrent disease were enrolled. Chemotherapy was given as follows: 5-FU, 600 mg/m(2) on days 1, 8, 29 and 36; mitomycin C, 10 mg/m(2) on day 1; and doxorubicin, 30 mg/m(2) on days 1 and 29. Eligibility criteria included an ECOG performance status score of 0-2, measurable disease, and adequate baseline organ function. Prior chemotherapy was allowed. Response was measured by examination and imaging techniques. Survival time and time to progression were evaluated by the method of Kaplan and Meier, and these outcomes were stratified by clinical and laboratory covariates. RESULTS: Of the 39 evaluated patients, 38 were eligible and 36 were evaluable for response. Grade 3-5 toxicities were experienced by a total of 26 patients (20 grade 3, 5 grade 4, 1 grade 5). The most common adverse events were neutropenia and vomiting. Responses were seen in a total of seven patients (2 complete responses, 5 partial responses), for a response rate of 18.4% (95% confidence interval of 7.8%-34.4%). The median survival time was 8 months. CONCLUSIONS: The FAM regimen was active and tolerable for patients with advanced small bowel adenocarcinoma; however, the results were no better than those seen with other chemotherapy combinations.

Measurement characteristics of peak expiratory flow.

STUDY OBJECTIVES: To evaluate features of the peak expiratory flow (PEF) test protocol, and to characterize patterns of reproducibility in multiple PEF measurements. DESIGN: Cross-sectional study. SETTING: University population. PARTICIPANTS: Two hundred twenty-three healthy adults. INTERVENTIONS: Participants recorded five PEF measurements in each of five sessions per day for 1 week. MEASUREMENTS AND RESULTS: Patterns of within-session variability were characterized using a reproducibility criterion based on a large percentage difference between best trials and evidence of a maneuver-induced bronchospasm (MIB) indicated by successive drops of PEF values in a session. Although the maximum PEF value in a session occurred on the fourth or fifth trial 32% of the time, the change in PEF values was small. Supervision was associated with small improvements in level and reproducibility. Using a cutoff of 5% for defining reproducibility, 15% of all sessions were not reproducible. When averaged over each subject, 9% of the cohort had a mean difference > 5%. Overall, MIB was unusual and observed in 8% of all test sessions; however, MIB was more common among asthmatics and subjects with wheeze, atopy, or allergies than subjects without. By contrast, poor reproducibility was more common among smokers and subjects with cough and phlegm. CONCLUSIONS: These results illustrate that it may be unnecessary to supervise all sessions or collect more than three efforts. Results also suggest that reproducibility reflects smoking-related abnormalities, whereas MIB may reflect airways hyperresponsiveness.