Biomedical subjects

Annette McWilliams

Publications and source records attributed to Annette McWilliams.

12 recordsLinked to original sources

PubMed2006

Bronchial thermoplasty for asthma.

RATIONALE: Bronchial thermoplasty (BT) reduces the potential for smooth muscle-mediated bronchoconstriction by reducing the mass of smooth muscle in the walls of conducting airways. OBJECTIVES: This study was conducted to examine the safety and impact on lung function and airway responsiveness of BT over 2 yr. METHODS: The safety of BT was studied in 16 subjects with mild to moderate asthma. Baseline and 12-wk post-treatment measurements included spirometry, methacholine challenge, daily diary recordings of peak flow, symptoms, and medication usage. Subjects completed follow-up evaluations at 12 wk, 1 yr, and 2 yr. MEASUREMENTS AND MAIN RESULTS: The procedure was well tolerated; side effects were transient and typical of what is commonly observed after bronchoscopy. All subjects demonstrated improvement in airway responsiveness. The mean PC(20) increased by 2.37 +/- 1.72 (p < 0.001), 2.77 +/- 1.53 (p = 0.007), and 2.64 +/- 1.52 doublings (p < 0.001), at 12 wk, 1 yr, and 2 yr post-procedure, respectively. Data from daily diaries collected for 12 wk indicated significant improvements over baseline in symptom-free days (p = 0.015), morning peak flow (p = 0.01), and evening peak flow (p < or = 0.007). Spirometry measurements remained stable throughout the study period. CONCLUSIONS: BT is well tolerated in patients with asthma and results in decreased airway hyperresponsiveness that persists for at least 2 yr.

Adult↗

PubMed2006

Early detection and chemoprevention of lung cancer.

Lung cancer is the most common cause of cancer death worldwide with more than 1.3 million people dying of the disease annually. While antitobacco initiatives in young people are important in preventing lung cancer in the long term, additional measures such as early detection and chemoprevention are needed for individuals already at risk due to past exposure to tobacco smoke. This review highlights the potential use of sputum, exhaled breath and blood biomarkers as well as thoracic CT and autofluorescence bronchoscopy for early detection. The current status of chemoprevention is summarized. The case for using a two-step screening strategy is also discussed.

Anticarcinogenic Agents↗

PubMed2006

A phase I study of myo-inositol for lung cancer chemoprevention.

INTRODUCTION: A phase I, open-label, multiple dose, dose-escalation clinical study was conducted to assess the safety, tolerability, maximum tolerated dose, and potential chemopreventive effect of myo-inositol in smokers with bronchial dysplasia. MATERIALS AND METHODS: Smokers between 40 and 74 years of age with >or= 30 pack-years of smoking history and one or more sites of bronchial dysplasia were enrolled. A dose escalation study ranging from 12 to 30 g/d of myo-inositol for a month was first conducted in 16 subjects to determine the maximum tolerated dose. Ten new subjects were then enrolled to take the maximum tolerated dose for 3 months. The potential chemopreventive effect of myo-inositol was estimated by repeat autofluorescence bronchoscopy and biopsy. RESULTS: The maximum tolerated dose was found to be 18 g/d. Side effects, when present, were mild and mainly gastrointestinal in nature. Using the regression rate of the placebo subjects from a recently completed clinical trial with the same inclusion/exclusion criteria as a comparison, a significant increase in the rate of regression of preexisting dysplastic lesions was observed (91% versus 48%; P = 0.014). A statistically significant reduction in the systolic and diastolic blood pressures by an average of 10 mm Hg was observed after taking 18 g/d of myo-inositol for a month or more. CONCLUSION: myo-Inositol in a daily dose of 18 g p.o. for 3 months is safe and well tolerated. The potential chemopreventive effect as well as other health benefits such as reduction in blood pressure should be investigated further.

Adult↗

PubMed2005

Progression of airway dysplasia and C-reactive protein in smokers at high risk of lung cancer.

RATIONALE: Chronic inflammation has been implicated in the development of airway dysplasia and lung cancer. It is unclear whether circulating biomarkers of inflammation could be used to predict progression of airway dysplasia. OBJECTIVE: We determined whether circulating levels of C-reactive protein (CRP) or other inflammatory biomarkers could predict progression of bronchial dysplasia in smokers over 6 mo. METHODS: The plasma levels of CRP, interleukins 6 and 8, and monocyte chemoattractant protein 1 were measured at baseline in 65 ex- and current smokers who had at least one site of bronchial dysplasia > 1.2 mm in size. Additional bronchial biopsies were taken after 6 mo from the same sites where dysplastic lesions were discovered at baseline. Progressive dysplastic lesions were defined as worsening of the dysplastic lesion by at least two grades or development of new dysplastic lesions. RESULTS: Half of the participants developed progressive dysplastic lesions after 6 mo. The baseline CRP levels in these participants were 64% higher than those without progressive disease (p = 0.027). Only one of eight (13%) participants with CRP < or = 0.5 mg/L developed progressive disease, whereas 31 of 57 (54%) participants with CRP > 0.5 mg/L developed progressive disease (p = 0.011). The odds of developing progressive disease were 9.6-fold higher in the latter than in the former group. CONCLUSION: Plasma CRP, in concert with lung function and pack-years of smoking, appears to have excellent predictive powers in identifying participants with bronchial dyplastic lesions whose lesions progress to more advanced stages of dysplasia.

Biomarkers↗

PubMed2005

Lung cancer screening.

PURPOSE OF REVIEW: Advances in imaging technologies and biomarker research offer hope that the incidence and mortality of lung cancer can be reduced by screening similar to what have been achieved for cancer of the cervix, breast, and colon. RECENT FINDINGS: Spiral computed tomography with multitrack scanners and autofluorescence bronchoscopy offer unprecedented sensitivity to detect lung cancer even during the preinvasive stage. The high sensitivity of these tests, however, is associated with a low specificity. Better selection of individuals at highest risk of lung cancer using biomarkers in sputum, blood, or exhaled breath, as well as a better understanding of genetic susceptibility, may improve their positive predictive values, minimize unnecessary downstream investigations or treatment, as well as reduce screening costs. SUMMARY: Improvement in the performance of sputum, exhaled breath, or blood biomarkers holds promise as the first screening step to identify individuals at highest risk of lung cancer beyond what age and smoking could predict to select those who would obtain the most benefits from spiral computed tomography or autofluorescence bronchoscopy as localization tools.

Biomarkers↗

PubMed2004

A randomized phase IIb trial of pulmicort turbuhaler (budesonide) in people with dysplasia of the bronchial epithelium.

PURPOSE: Preclinical studies suggest that inhaled budesonide may be an effective chemopreventive agent for lung cancer. We conducted a phase IIb study to determine the effects of inhaled budesonide in smokers with bronchial dysplasia. EXPERIMENTAL DESIGN: A total of 112 smokers with more than or equal to one site of bronchial dysplasia > 1.2 mm in size identified by autofluorescence bronchoscopy-directed biopsy was randomly assigned to receive placebo or budesonide (Pulmicort Turbuhaler) 800 microg twice daily inhalation for 6 months. The primary end point was change in the histopathologic grade on repeat biopsy of the same sites at the end of 6 months. RESULTS: There were no significant differences in the regression or progression rates of bronchial dysplasia between the two groups. There was a statistically significant but modest decrease in p53 and BclII expression in the bronchial biopsies after 6 months of Pulmicort Turbuhaler versus placebo (P = 0.01 and P = 0.001, respectively). There was a small but statistically significant decrease in the proportion of computed tomography-detected lung nodules after Pulmicort Turbuhaler compared with placebo (P = 0.024). CONCLUSIONS: Our results suggest that in smokers, inhaled budesonide in the dose of 1600 microg daily for 6 months had no effect in regression of bronchial dysplastic lesions or prevention of new lesions. Budesonide treatment resulted in a modest decrease in p53 and BclII protein expression in bronchial biopsies and a slightly higher rate of resolution of computed tomography-detected lung nodules. Whether budesonide truly has an effect in preneoplastic lesions in the peripheral airways and alveoli requires additional investigation.

Administration, Inhalation↗

PubMed2004

Integrated endoscopy system for simultaneous imaging and spectroscopy for early lung cancer detection.

An integrated endoscopy system for simultaneous imaging and spectroscopy was developed to facilitate more accurate and convenient detection of early lung cancers. A specially designed three-CCD camera in combination with a dedicated light source permits capture of both white-light color images and tissue autofluorescence images without the need to switch between two different cameras. A mirror with an optical fiber at its center, placed at an interim imaging plane inside the camera unit, facilitates simultaneous imaging and spectroscopy measurements in either white-light reflectance mode or fluorescence mode. The system has been successfully tested in a clinic, demonstrating a practical approach to improve both diagnostic sensitivity and specificity at the same time.

Early Diagnosis↗

PubMed2003

Near-infrared Raman spectroscopy for optical diagnosis of lung cancer.

Raman spectroscopy is a vibrational spectroscopic technique that can be used to optically probe the molecular changes associated with diseased tissues. The objective of our study was to explore near-infrared (NIR) Raman spectroscopy for distinguishing tumor from normal bronchial tissue. Bronchial tissue specimens (12 normal, 10 squamous cell carcinoma (SCC) and 6 adenocarcinoma) were obtained from 10 patients with known or suspected malignancies of the lung. A rapid-acquisition dispersive-type NIR Raman spectroscopy system was used for tissue Raman studies at 785 nm excitation. High-quality Raman spectra in the 700-1,800 cm(-1) range from human bronchial tissues in vitro could be obtained within 5 sec. Raman spectra differed significantly between normal and malignant tumor tissue, with tumors showing higher percentage signals for nucleic acid, tryptophan and phenylalanine and lower percentage signals for phospholipids, proline and valine, compared to normal tissue. Raman spectral shape differences between normal and tumor tissue were also observed particularly in the spectral ranges of 1,000-1,100, 1,200-1,400 and 1,500-1,700 cm(-1), which contain signals related to protein and lipid conformations and nucleic acid's CH stretching modes. The ratio of Raman intensities at 1,445 to 1,655 cm(-1) provided good differentiation between normal and malignant bronchial tissue (p < 0.0001). The results of this exploratory study indicate that NIR Raman spectroscopy provides significant potential for the noninvasive diagnosis of lung cancers in vivo based on the optic evaluation of biomolecules.

Aged↗

PubMed2003

Lung cancer screening: a different paradigm.

Thoracic computed tomography (CT) is a sensitive method for detecting early lung cancer but has a high false-positive rate and is not sensitive for detecting central preinvasive and microinvasive cancer. Our hypothesis was that automated quantitative image cytometry (AQC) of sputum cells as the first screening method may improve detection rate by identifying individuals at highest risk for lung cancer. A total of 561 volunteer current or former smokers 50 years of age or older, with a smoking history of more than or equal to 30 pack/years, were studied. Among these, 423 were found to have sputum atypia defined as five cells or more with abnormal DNA content using AQC. Noncalcified pulmonary nodules were found in 46% (259/561). Of the 14 detected cancers, 13 were detected in subjects with sputum atypia-nine by CT and four carcinoma in situ/microinvasive cancers by autofluorescence bronchoscopy. One cancer was detected by CT alone. AQC of sputum cells improved the detection rate of lung cancer from 1.8 to 3.1%. CT scan alone would have missed 29% of the cancers. This screening paradigm shift has the additional potential of reducing the number of initial CT scans by at least 25% with further savings in follow-up investigations and treatment.

Aged↗

PubMed2003

Effect of formalin fixation on the near-infrared Raman spectroscopy of normal and cancerous human bronchial tissues.

Raman spectroscopy is a vibrational spectroscopic technique that can be used to probe molecular changes associated with tissue malignancy. In this report, the effect of formalin fixation on human bronchial tissues was studied by near-infrared (NIR) Raman spectroscopy to determine if the variations of Raman spectra caused by formalin fixation would affect the potential diagnostic ability for lung cancer detection. A rapid dispersive-type NIR Raman system with an excitation wavelength of 785 nm was used for this study. Bronchial tissue samples were obtained from six patients with known or suspected malignancies of the lung. Raman spectra of fresh normal and tumor tissue were compared with spectra of formalin-fixed normal and tumor tissue. Changes of the ratios of Raman intensities at 1445 to 1655 cm(-1) and 1302 to 1265 cm(-1) versus formalin fixing times varying from 2 to 24 h were also examined. The major tissue Raman peaks at 1265, 1302, 1445, and 1655 cm(-1) were found in both fresh and fixed bronchial tissues. However, bronchial tissue preserved in formalin showed a progressive decrease in overall intensities of these Raman peaks. Raman contaminations due to formalin were also found in the 980-1100, and 1480-1650 cm(-1) ranges with notable formalin peaks (1041 and 1492 cm(-1)) appearing in the fixed normal and tumor tissues. The results showed that NIR Raman spectra of human bronchial tissues were significantly affected by formalin fixing and tissue hydration. Diagnostic markers at the 980-1100, and 1500-1650 cm(-1) regions derived from fixed tissues do not appear to be applicable for in vivo lung cancer detection. To yield valid Raman diagnostic information for in vivo applications, fresh tissue should be used. If only fixed tissue is available, thorough rinsing of specimens in phosphate-buffered saline (PBS) before spectral measurements may help reduce the formalin fixation artifacts on tissue Raman spectra.

Adenocarcinoma↗

PubMed2002

Innovative molecular and imaging approaches for the detection of lung cancer and its precursor lesions.

Current approaches for the therapy of lung cancer, the majority of which being advanced cancers, have failed to impact on long term survival. The key to improvement lies in the combination of early diagnosis and the introduction of novel targeted therapies. In this article we review some of the innovative approaches, both imaging and molecular, that are currently under investigation for early detection. Because lung cancers may arise in the central or peripheral compartments of the lung, newer approaches must target tumours arising in both of these compartments. Specimens available for analysis include sputa and blood. Detection of genetic changes in peripheral blood is a promising avenue being explored by several groups. Molecular techniques discussed include gene mutations, detection of nuclear riboprotein, methylation related silencing of genes and malignancy associated changes. Newer imaging technologies include autofluorescence bronchoscopy, virtual bronchoscopy, optical coherent tomography and confocal microscopy. Although the impact of these new technologies on survival has not been determined, they offer a wide range of exciting new approaches. In time they may completely revamp the present highly conservative and unsuccessful approaches to early diagnosis.

Diagnostic Imaging↗

PubMed2002

New approaches to lung cancer prevention.

Lung cancer is the most common cause of cancer death worldwide. The overall 5-year survival rate remains disappointing at 14% or less. Several clinician- and community-based interventions show promise for reducing lung cancer incidence through prevention and smoking cessation. However, long-term heavy smokers retain a significant lung cancer risk despite smoking cessation. Half of newly diagnosed lung cancers are now found in former smokers. An additional strategy of lung cancer control through chemoprevention needs to be developed. Advances in optical imaging technologies and genome science will continue to improve our ability to identify individuals with the highest risk of lung cancer for chemoprevention. More accurate surrogate endpoint biomarkers are becoming available for phase II trials of new agents. A number of promising agents are currently being tested in phase II and III trials for prevention of lung cancer.

Animals↗