Methacholine reactivity predicts changes in lung function over time in smokers with early chronic obstructive pulmonary disease. The Lung Health Study Research Group.

As part of a clinical trial of early intervention in chronic obstructive pulmonary disease (COPD) (the Lung Health Study), 5,733 smokers with mild to moderate airflow obstruction underwent methacholine challenge tests at baseline. All participants were randomized to receive either usual care (no intervention) or special intervention, consisting of intensive smoking cessation counseling and the prescription of a metered-dose inhaler containing either ipratropium bromide or placebo (two inhalations three times daily). For this report, we analyzed the relationship between baseline methacholine reactivity and subsequent change in lung function.

The one-year surgical outcome after prism adaptation for the management of acquired esotropia.

Purpose: To report the 1-year motor and sensory outcomes for patients with acquired comitant esotropia managed with preoperative prism adaptation.

Methods: Patients entered a multicenter randomized prospective evaluation of prism adaptation before strabismus surgery. Prism responders were randomized to surgery with the target angle based on either the entry angle or the adapted angle of esotropia.

Safety of nicotine polacrilex gum used by 3,094 participants in the Lung Health Study. Lung Health Study Research Group.

Study Objective: To assess cardiovascular conditions and other side effects associated with the use of nicotine polacrilex (NP), 2 mg.

Design: A multicentered randomized control trial of early intervention for the prevention of COPD.

Setting: Ten university medical centers in the United States and Canada.

Dosimetry of copper-64-labeled monoclonal antibody 1A3 as determined by PET imaging of the torso.

Unlabelled: We present biodistribution and dosimetry results for 64Cu-benzyl-TETA-MAb 1A3 from 15 human subjects injected with this tracer as determined by serial PET imaging of the torso.

Methods: PET imaging was used to quantify in vivo tracer biodistribution at two time points after injection. Absorbed dosimetry calculated using MIRD-11 and the updated MIRDOSE3 was compared with estimates obtained using rat biodistribution data.

Identification of metabolites of 111In-diethylenetriaminepentaacetic acid-monoclonal antibodies and antibody fragments in vivo.

The in vivo fate of various 111In-labeled polypeptides has been the subject of many investigations. Intracellular metabolism has been studied through the use of 111In-labeled glycoproteins that are concentrated in the lysosome by receptor-mediated endocytosis. These studies have indicated that the main lysosomal metabolite is 111In-chelate-epsilon-lysine, both in vitro and in vivo (Y.

Impact of pneumoperitoneum on trocar site implantation of colon cancer in hamster model.

Background: Numerous anecdotal reports have documented the spread of colon cancer to trocar sites after laparoscopic-assisted colectomy. We hypothesized that the pneumoperitoneum of laparoscopy potentiated tumor adherence to trocar sites.

Purpose: This study was designed to determine the effect of CO2 pneumoperitoneum on the rate of tumor implantation at trocar sites.

RadioimmunoPET: detection of colorectal carcinoma with positron-emitting copper-64-labeled monoclonal antibody.

Unlabelled: Detection of tumor foci may be improved by combining the selective tumor-targeting properties of a monoclonal antibody with the superior sensitivity and contrast resolution of PET.

Methods: An anti-colorectal carcinoma monoclonal antibody (MAb 1A3) was labeled with 64Cu, a positron-emitting radionuclide, by use of a bifunctional chelate (bromoacetamidobenzyl-TETA) and evaluated in 36 patients with suspected advanced primary or metastatic colorectal cancer. After radiopharmaceutical injection (5-20 mg protein, 10 mCi 64Cu), PET was performed once or twice, 4 to 36 hr later.

Long-term metered-dose inhaler adherence in a clinical trial. The Lung Health Study Research Group.

Poor adherence to medication regimens is a well-documented phenomenon in clinical practice and an ever-present concern in clinical trials. Little is known about adherence to inhaled medication regimens over extended periods. The present paper describes the 2-yr results of the Lung Health Study (LHS) program, which was developed to maintain long-term adherence to an inhaled medication regimen in 3,923 special intervention participants (as measured by self-report and medication canister weight).

Preparation, biodistribution and dosimetry of copper-64-labeled anti-colorectal carcinoma monoclonal antibody fragments 1A3-F(ab')2.

Unlabelled: Antibody fragments labeled with a radiometal using bifunctional chelates generally undergo renal clearance followed by trapping of the metabolites, leading to high radiation doses to the kidneys. Copper-64-labeled BAT-2IT-1A3-F(ab')2 was recently reported to accumulate in colorectal tumors in an animal model, however, kidney uptake was also high. In this study, the preparation of 64Cu-BAT-2IT-1A3-F(ab')2 was optimized to reduce the renal uptake.

Selection of spirometric measurements in a clinical trial, the Lung Health Study.

Although current recommendations for spirometry require that the largest value of FEV1 and FVC should be taken from the largest values of different maneuvers, the validity of this approach was recently questioned. It has been suggested that selection of the maneuver with the largest peak flow or the maneuver with the largest FVC should be used for measurement of spirometric indices. The present analysis was therefore undertaken to determine which method of selection of spirometric maneuvers would give the least short-term variability in a clinical trial population.

Predictors of initial smoking cessation and relapse through the first 2 years of the Lung Health Study.

Analyses were made separately for men and women of the predictors of end-of-treatment (4 months) smoking cessation and subsequent relapse at 12 and 24 months among 3,923 participants enrolled in the Lung Health Study's 12-week cognitive-behavioral group smoking cessation program. Nicotine gum (2 mg) was available to all participants. Men were more likely than women to quit smoking initially, but relapse rates were similar for both genders.

Gender differences in smoking cessation after 3 years in the Lung Health Study.

Objectives: An analysis of gender differences in smoking cessation was conducted among 3923 participants in the Special Intervention group of the Lung Health Study. This report focuses on gender differences in sustained quit rates at 12 and 36 months.

Methods: Special Intervention participants were offered a 12-session, 12-week smoking cessation program using nicotine gum and were followed for 3 years.

Spirometry in the Lung Health Study: II. Determinants of short-term intraindividual variability.

The Lung Health Study (LHS) is a randomized clinical trial designed to determine whether a smoking intervention program and use of an inhaled bronchodilator (BD) can reduce the rate of decline of FEV1 in cigarette smokers with airflow limitation. During recruitment, spirometry was performed at second and third screening visits, a mean of 21 d apart. A total of 5,887 smokers, 35 to 60 yr of age and of whom 63% were men, met the study eligibility requirements.

Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1. The Lung Health Study.

Objective: To determine whether a program incorporating smoking intervention and use of an inhaled bronchodilator can slow the rate of decline in forced expiratory volume in 1 second (FEV1) in smokers aged 35 to 60 years who have mild obstructive pulmonary disease.

Design: Randomized clinical trial. Participants randomized with equal probability to one of the following groups: (1) smoking intervention plus bronchodilator, (2) smoking intervention plus placebo, or (3) no intervention.

Gender difference in airway hyperresponsiveness in smokers with mild COPD. The Lung Health Study.

Methacholine bronchoprovocation challenge testing was successfully completed in 5,662 participants (3,556 men and 2,106 women) at the time they were randomized into the Lung Health Study, a multicenter trial designed to evaluate early intervention in chronic obstructive pulmonary disease (COPD). All participants were smokers between the ages of 35 and 60 yr who had mild COPD. The male:female prevalence of a positive challenge (PC20FEV1) was 25%:48% and 63%:87% at a PC20FEV1 of < or = 5 mg/ml (AHR5) and < or = 25 mg/ml (AHR25), respectively.

Effect of glycemic control on early diabetic renal lesions. A 5-year randomized controlled clinical trial of insulin-dependent diabetic kidney transplant recipients.

Objective: To determine whether optimized glycemic control in type I diabetic recipients of renal allografts will prevent or delay diabetic renal lesions in the allograft.

Design: Prospective, controlled, and randomized trial of glycemic control in an inception cohort of type I diabetic renal allograft recipients. The experimental group underwent maximized glycemic control, and the standard group was treated in the same way as other patients in the transplant clinic.

Immunoscintigraphy with a new indium-111-labeled monoclonal antibody (MAb 1A3) in patients with colorectal cancer.

Purpose: This study was designed to evaluate a new anticolorectal carcinoma monoclonal antibody (1A3), conjugated with the bifunctional chelating agent N,N'-bis(2-hydroxybenzyl)1(4-bromoacetamidobenzyl)1,2-ethylenediam ine-N,N'- diacetic acid and labeled with indium-111, in a Phase I/II study involving 38 patients with localized or advanced colorectal cancer.

Methods: Patients were injected with indium-111-N,N'-bis(2-hydroxybenzyl) 1(4-bromoacetamidobenzyl)1,2-ethylenediamine-N,N'-diacetic acid-monoclonal antibody 1A3 (1-50 mg, 1-5 mCi) and imaged at two or three sessions one to five days later. Scintigraphic findings were compared with radiologic, pathologic, surgical, and other clinical findings to assess the accuracy of radioimmunoscintigraphy.

Weight gain as a function of smoking cessation and 2-mg nicotine gum use among middle-aged smokers with mild lung impairment in the first 2 years of the Lung Health Study.

The extent and predictors of weight change were assessed among sustained nonsmoking special intervention participants in the Lung Health Study. The intervention included a 12-session group program and 2-mg nicotine gum. At 12 months, female sustained quitters (SQs; n = 248) had gained a mean of 8.

Use of surrogate information time for monitoring the effect of treatment on the change in a response variable in clinical trials.

We discuss the monitoring of clinical trials data and propose two surrogates for total information for use with the spending function approach where there are repeated measurements and we wish to compare the rates of change in a response variable under different treatments. These surrogates are applied to a setting similar to the Lung Health Study. Although the surrogates do not require estimation of the variance parameters, they do require some knowledge of the ratio R of the within- to the between-individual variances.

Evaluation of a direct method for technetium labeling intact and F(ab')2 1A3, an anticolorectal monoclonal antibody.

A direct method for 99mTc-labeling monoclonal antibodies (MAb) has been evaluated for labeling intact and F(ab')2 1A3, an anticolorectal carcinoma MAb. The method employs ascorbic acid to reduce the MAbs. By altering the reaction conditions for 99mTc-1A3, a maximum radiolabeling yield of 48% was obtained with an immunoreactivity (IR) value of 87%; and for 99mTc-1A3-F(ab')2, a yield of 49% and an IR value of 70% was obtained.

Error in smoking measures: effects of intervention on relations of cotinine and carbon monoxide to self-reported smoking. The Lung Health Study Research Group.

Objectives: Sources of measurement error in assessing smoking status are examined.

Methods: The Lung Health Study, a randomized trial in 10 clinical centers, includes 3923 participants in a smoking cessation program and 1964 usual care participants. Smoking at first annual follow-up was assessed by salivary cotinine, expired air carbon monoxide, and self-report.

Chronic Obstructive Pulmonary Disease Early Intervention Trial (Lung Health Study). Baseline characteristics of randomized participants.

The Chronic Obstructive Pulmonary Disease Early Intervention Trial, or Lung Health Study, is a multicenter randomized clinical trial sponsored by the Division of Lung Diseases of the National Heart, Lung, and Blood Institute. The hypothesis being tested is that over a 5-year period, a comprehensive intervention program can reduce both the rate of decline in pulmonary function and the rates of respiratory morbidity and mortality in middle-aged smokers with mild to moderate airflow obstruction. The primary outcome variable of the trial is the annual rate of decline of maximum postbronchodilator FEV1.

Design and results of the initial intervention program for the Lung Health Study. The Lung Health Study Research Group.

Background: The design and results of the initial intervention program of the Lung Health Study are presented for 3,923 male and female participants. One of the major aims of this clinical trial was to achieve smoking cessation early in the study and to provide intensive follow-up procedures for maintaining abstinence. In addition, compliance with use of aerosolized inhalers (either placebo or active bronchodilator) would be necessary in order to achieve the trial goal of improved pulmonary function.