Biomedical subjects

Stephen Lam

Publications and source records attributed to Stephen Lam.

At least 19 recordsLinked to original sources

PubMed2026

Plasma signals of lung tumor promotion for molecular cancer prevention.

Predicting lung cancer risk would enhance prevention trials. Although the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) trial demonstrated reduced lung cancer incidence with interleukin (IL)-1β inhibition, the high number needed to treat (NNT) to prevent lung cancer limits its use in unselected populations. Using machine learning, we identified a 14-protein plasma signature predicting lung cancer more than 5 years before diagnosis. The signature, validated across eight cohorts, was elevated in current smokers and individuals exposed to particulate matter (PM) and linked to lung myeloid and alveolar cells. In epidermal growth factor receptor (EGFR)-driven lung adenocarcinoma, diverse epithelial lineages converged on a keratin8+/claudin4+ alveolar transitional state (KAC), whose transcriptional programs correlated with signature emergence. Components of the signature were induced by PM, oncogenic EGFR, or IL-1β, whereas IL-1β inhibition restrained PM-driven KAC expansion and early tumorigenesis. In CANTOS, the signature identified individuals who seemed to benefit more from anti-IL-1β therapy, lowering the NNT threshold and nominating circulating signals of tumor promotion for prevention.

Humans↗

PubMed2006

Expression profiling and mutant analysis reveals complex regulatory networks involved in Arabidopsis response to Botrytis infection.

The expression profiles of Botrytis-inoculated Arabidopsis plants were studied to determine the nature of the defense transcriptome and to identify genes involved in host responses to the pathogen. Normally resistant Arabidopsis wild-type plants were compared with coi1, ein2, and nahG plants that are defective in various defense responses and/or show increased susceptibility to Botrytis. In wild-type plants, the expression of 621 genes representing approximately 0.48% of the Arabidopsis transcriptome was induced greater than or equal to twofold after infection. Of these 621 Botrytis-induced genes (BIGs), 462 were induced at or before 36 h post-inoculation, and may be involved in resistance to the pathogen. The expression of 181 BIGs was dependent on a functional COI1 gene required for jasmonate signaling, whereas the expression of 63 and 80 BIGs were dependent on ethylene (ET) signaling or salicylic acid accumulation, respectively, based on results from ein2 and nahG plants. BIGs encode diverse regulatory and structural proteins implicated in pathogen defense and abiotic and oxidative-stress responses. Thirty BIGs encode putative DNA-binding proteins that belong to ET response, zinc-finger, MYB, WRKY, and HD-ZIP family transcription-factor proteins. Fourteen BIGs were studied in detail to determine their role in resistance to Botrytis. T-DNA insertion alleles of ZFAR1 (At2G40140), the gene encoding a putative zinc-finger protein with ankyrin-repeat domains, showed increased local susceptibility to Botrytis and sensitivity to germination in the presence of abscisic acid (ABA), supporting the role of ABA in mediating responses to Botrytis infection. In addition, two independent T-DNA insertion alleles in the WRKY70 gene showed increased susceptibility to Botrytis. The transcriptional activation of genes involved in plant hormone signaling and synthesis, removal of reactive oxygen species, and defense and abiotic-stress responses, coupled with the susceptibility of the wrky70 and zfar1 mutants, highlights the complex genetic network underlying defense responses to Botrytis in Arabidopsis.

Ankyrin Repeat↗

PubMed2006

Establishment in severe combined immunodeficiency mice of subrenal capsule xenografts and transplantable tumor lines from a variety of primary human lung cancers: potential models for studying tumor progression-related changes.

PURPOSE: Lung cancer is a biologically diverse disease and relevant models reflecting its diversity would facilitate the improvement of existing therapies. With a view to establishing such models, we developed and evaluated xenografts of a variety of human lung cancers. EXPERIMENTAL DESIGN: Using nonobese diabetic/severe combined immunodeficiency mice, subrenal capsule xenografts were generated from primary lung cancer tissue, including moderately and poorly differentiated squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, small cell carcinoma, large cell undifferentiated carcinoma, and carcinosarcoma. After 4 to 12 weeks, xenografts were harvested for serial transplantation and comparison with the original tissue via histologic, chromosomal, and cytogenetic analyses. RESULTS: Xenografts were successfully established. H&E staining showed that xenografts retained major histologic features of the original cancers. Immunohistochemistry and fluorescence in situ hybridization confirmed the human origin of the tumor cells and development in xenografts of murine supportive stroma. Four transplantable lines were developed from rapidly growing tumors (>5 generations), i.e., a small cell lung carcinoma, large cell undifferentiated carcinoma, pulmonary carcinosarcoma, and squamous cell carcinoma. Analyses including spectral karyotyping, comparative genomic hybridization, and fluorescence in situ hybridization, revealed that the xenografts were genetically similar to the original tumors, showing chromosomal abnormalities consistent with karyotypic changes reported for lung cancer. CONCLUSIONS: The subrenal capsule xenograft approach essentially provides a living tumor bank derived from patient material and a means for isolating and expanding specific cell populations. The transplantable tumor lines seem to provide good models for studying various aspects of tumor progression and a platform for developing novel therapeutic regimens, with the possibility of patient-tailored therapies.

Aged↗

PubMed2006

Identification of novel lung genes in bronchial epithelium by serial analysis of gene expression.

A description of the transcriptome of human bronchial epithelium should provide a basis for studying lung diseases, including cancer. We have deduced global gene expression profiles of bronchial epithelium and lung parenchyma, based on a vast dataset of nearly two million sequence tags from 21 serial analysis of gene expression (SAGE) libraries from individuals with a history of smoking. Our analysis suggests that the transcriptome of the bronchial epithelium is distinct from that of lung parenchyma and other tissue types. Moreover, our analysis has identified novel bronchial-enriched genes such as MS4A8B, and has demonstrated the use of SAGE for the discovery of novel transcript variants. Significantly, gene expression associated with ciliogenesis is evident in bronchial epithelium, and includes the expression of transcripts specifying axonemal proteins DNAI2, SPAG6, ASP, and FOXJ1 transcription factor. Moreover, expression of potential regulators of ciliogenesis such as MDAC1, NYD-SP29, ARMC3, and ARMC4 were also identified. This study represents a comprehensive delineation of the bronchial and parenchyma transcriptomes, identifying more than 20,000 known and hypothetical genes expressed in the human lung, and constitutes one of the largest human SAGE studies reported to date.

Aged↗

PubMed2006

Progress in chemoprevention drug development: the promise of molecular biomarkers for prevention of intraepithelial neoplasia and cancer--a plan to move forward.

This article reviews progress in chemopreventive drug development, especially data and concepts that are new since the 2002 AACR report on treatment and prevention of intraepithelial neoplasia. Molecular biomarker expressions involved in mechanisms of carcinogenesis and genetic progression models of intraepithelial neoplasia are discussed and analyzed for how they can inform mechanism-based, molecularly targeted drug development as well as risk stratification, cohort selection, and end-point selection for clinical trials. We outline the concept of augmenting the risk, mechanistic, and disease data from histopathologic intraepithelial neoplasia assessments with molecular biomarker data. Updates of work in 10 clinical target organ sites include new data on molecular progression, significant completed trials, new agents of interest, and promising directions for future clinical studies. This overview concludes with strategies for accelerating chemopreventive drug development, such as integrating the best science into chemopreventive strategies and regulatory policy, providing incentives for industry to accelerate preventive drugs, fostering multisector cooperation in sharing clinical samples and data, and creating public-private partnerships to foster new regulatory policies and public education.

Biomarkers, Tumor↗

PubMed2006

High resolution analysis of non-small cell lung cancer cell lines by whole genome tiling path array CGH.

Chromosomal regions harboring tumor suppressors and oncogenes are often deleted or amplified. Array comparative genomic hybridization detects segmental DNA copy number alterations in tumor DNA relative to a normal control. The recent development of a bacterial artificial chromosome array, which spans the human genome in a tiling path manner with >32,000 clones, has facilitated whole genome profiling at an unprecedented resolution. Using this technology, we comprehensively describe and compare the genomes of 28 commonly used non-small cell lung carcinoma (NSCLC) cell models, derived from 18 adenocarcinomas (AC), 9 squamous cell carcinomas and 1 large cell carcinoma. Analysis at such resolution not only provided a detailed genomic alteration template for each of these model cell lines, but revealed novel regions of frequent duplication and deletion. Significantly, a detailed analysis of chromosome 7 identified 6 distinct regions of alterations across this chromosome, implicating the presence of multiple novel oncogene loci on this chromosome. As well, a comparison between the squamous and AC cells revealed alterations common to both subtypes, such as the loss of 3p and gain of 5p, in addition to multiple hotspots more frequently associated with only 1 subtype. Interestingly, chromosome 3q, which is known to be amplified in both subtypes, showed 2 distinct regions of alteration, 1 frequently altered in squamous and 1 more frequently altered in AC. In summary, our data demonstrate the unique information generated by high resolution analysis of NSCLC genomes and uncover the presence of genetic alterations prevalent in the different NSCLC subtypes.

Carcinoma, Non-Small-Cell Lung↗

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

The relationship between stage 1 and 2 non-small cell lung cancer and lung function in men and women.

BACKGROUND: Reduced forced expiratory volume in one second (FEV1) has been linked to non small cell lung cancer (NSCLC). However, it is unclear whether all or only certain histological subtypes of NSCLC are associated with reduced FEV1. Moreover, there is little information on whether gender modifies this relationship. Using a large tissue registry, we sought to determine the relationship between FEV1 and subtypes of NSCLC and determine whether this relationship is modified by gender. METHODS: We used data from patients who underwent tumor resection for NSCLC at a teaching hospital in Vancouver and had various pre-operative clinical measurements including FEV1. We divided the cohort into quartiles of predicted FEV1 and using both logistic and linear regression modeling techniques determined whether FEV1 was related to the occurrence of adeno or squamous cell carcinoma in men and women. RESULTS: There were 610 patients in the study (36% females). On average, women were more likely to have adenocarcinoma than were men (72% of all cases of NSCLC in women versus 40% in men; p < 0.001). In women, there was no significant relationship between FEV1 and the risk of any histological subtypes of NSCLC. In men, however, there was an inverse relationship between the risk of adenocarcinoma and FEV1 such that the lowest quartile of FEV1 was 47% less likely to have adenocarcinoma compared with the highest FEV1 quartile (adjusted odds ratio, 0.52; 0.28 to 0.98; p for trend, 0.028). The reverse was observed for squamous cell carcinoma. CONCLUSION: In individuals undergoing lung resection for NSCLC, the risk of adenocarcinoma and squamous cell carcinoma of the lung varies as a function of FEV1, independent of smoking intensity in men but not in women. CLINICAL IMPLICATIONS: These data indicate that women are much more susceptible to adenocarcinoma than are men especially when they have normal or near normal lung function. It may thus be useful to conduct periodic surveillance chest radiographs in asymptomatic female smokers (or ex-smokers) to ascertain peripheral nodules or masses before distant metastases occur since adenocarcinomas tend to metastasize earlier in the disease course than squamous cell carcinomas.

Adult↗

PubMed2006

Gain of a region on 7p22.3, containing MAD1L1, is the most frequent event in small-cell lung cancer cell lines.

Small-cell lung cancer (SCLC) is a highly aggressive lung neoplasm, which accounts for 20% of yearly lung cancer cases. The lack of knowledge of the progenitor cell type for SCLC precludes the definition of a normal gene expression profile and has hampered the identification of gene expression changes, while the low resolution of conventional genomic screens such as comparative genomic hybridization (CGH) and loss of heterozygosity analysis limit our ability to fine-map genetic alterations. The recent advent of whole genome tiling path array CGH enables profiling of segmental DNA copy number gains and losses at a resolution 100 times that of conventional methods. Here we report the analysis of 14 SCLC cell lines and six matched normal B-lymphocyte lines. We detected 7p22.3 copy number gain in 13 of the 14 SCLC lines and 0 of the 6 matched normal lines. In 4 of the 14 cell lines, this gain is present as a 350 kbp gene specific copy number gain centered at MAD1L1 (the human homologue of the yeast gene MAD1). Fluorescence in situ hybridization validated the array CGH finding. Intriguingly, MAD1L1 has been implicated to have tumor-suppressing functions. Our data suggest a more complex role for this gene, as MAD1L1 is the most frequent copy number gain in SCLC cell lines.

B-Lymphocytes↗

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

Increased staining for phospho-Akt, p65/RELA and cIAP-2 in pre-neoplastic human bronchial biopsies.

BACKGROUND: The development of non-small cell lung carcinoma proceeds through a series of well-defined pathological steps before the appearance of invasive lung carcinoma. The molecular changes that correspond with pathology changes are not well defined and identification of the molecular events may provide clues on the progression of intraepithelial neoplasia in the lung, as well as suggest potential targets for chemoprevention. The acquisition of anti-apoptotic signals is critical for the survival of cancer cells but the pathways involved are incompletely characterized in developing intra-epithelial neoplasia (IEN). METHODS: We used immunohistochemistry to determine the presence, relative levels, and localization of proteins that mediate anti-apoptotic pathways in developing human bronchial neoplasia. RESULTS: Bronchial epithelial protein levels of the phosphorylated (active) form of AKT kinase and the caspase inhibitor cIAP-2 were increased in more advanced grades of bronchial IEN lesions than in normal bronchial epithelium. Additionally, the percentage of biopsies with nuclear localization of p65/RELA in epithelial cells increased with advancing pathology grade, suggesting that NF-kappaB transcriptional activity was induced more frequently in advanced IEN lesions. CONCLUSION: Our results indicate that anti-apoptotic pathways are elevated in bronchial IEN lesions prior to the onset of invasive carcinoma and that targeting these pathways therapeutically may offer promise in prevention of non-small cell lung carcinoma.

Apoptosis↗

PubMed2005

Nuclear morphometry as a biomarker for bronchial intraepithelial neoplasia: correlation with genetic damage and cancer development.

BACKGROUND: Bronchial carcinomas are preceded by epithelial morphologic changes. The variation in interpretation of these grades of intraepithelial neoplasia makes it difficult to determine its natural history and utility of histopathology as a surrogate endpoint biomarker. The objective of this study was to quantitate morphologic changes of intraepitherlial neoplasia and validate its utility through correlation with histopathology, allelic loss, and cancer development. METHODS: Quantitative nuclear morphometry was performed on 47 normal bronchial biopsies and 28 invasive cancer to generate a morphometry index (MI) that was applied to 1,096 bronchial biopsies from 230 volunteers who were current smokers (> or =25 pack-years) and 30 patients who had cancer. In a subset of 631 biopsies, MI was correlated with frequency of loss of heterozygosity at nine chromosomal regions (14 polymorphic markers). RESULTS: A significant correlation was found between MI and allelic loss in six of nine chromosomal regions. As part of patient long-term follow-up, 12 sites that progressed to cancer were identified and had significantly increased MIs relative to nonprogressing sites. Significant overlap in the MIs was found between most grades of intraepithelial neoplasia. CONCLUSIONS: In chemoprevention trials, nuclear morphometry can supplement histopathology as a Surrogate Endpont Biomarker (SEB) because it is quantitative, collelates well with genetic damage, and may predict cancer development.

Biopsy↗

PubMed2005

High-resolution chromosome arm 5p array CGH analysis of small cell lung carcinoma cell lines.

Genomic amplification of regions on chromosome arm 5p has been observed frequently in small cell lung cancer (SCLC), implying the presence of multiple oncogenes on this arm. Although conventional comparative genomic hybridization (CGH) detects gross chromosomal copy number changes, gene discovery requires a higher-resolution approach in order to identify regions of alteration precisely. To identify candidate genes on this chromosome arm, we developed a high-resolution, 10-clone-per-megabase bacterial artificial chromosome CGH array for 5p and examined a panel of 15 SCLC cell lines. Utilization of this CGH array has allowed the fine-mapping of breakpoints to regions as small as 200 kb in a single experiment. In addition to reporting our observations of aberrations at the well-characterized SKP2 and TERT loci, we describe the identification of microdeletions that have escaped detection by conventional screens and the identification TRIO and ANKH as novel putative oncogenes.

Biomarkers, Tumor↗

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

Involvement of multiple developmental genes on chromosome 1p in lung tumorigenesis.

Lung cancer is the leading cause of cancer death in North America. Despite advances in lung cancer treatment, the overall 5 year survival rate for those diagnosed with the disease is bleak presumably due to the late stage of diagnosis. Owing to the difficulty of early detection, preneoplastic specimens are rare. However, studying both preinvasive and invasive stages of disease is necessary to fully understand lung cancer progression. Aberration of chromosome arm 1p is common in lung and other cancers. In this study, we used a genomic array with complete tiling coverage of 1p to profile preinvasive and invasive squamous non-small cell lung carcinoma samples. With this technology, multiple novel submegabase alterations were identified. Three of the 1p alterations harbored genes belonging to gene families known to be involved in cancer development through either the Wnt or the Notch developmental pathways. Our finding of a 0.4 Mb amplified region at 1p36.12 containing WNT4 in preinvasive lung cancer, coupled with the identification of three additional alterations in invasive tumors that also contain genes related to the Notch and Wnt pathways, strongly suggests an intricate role of these pathways in early and late stages of lung cancer development. Furthermore, ectopic expression of DVL1, LRP8 and Notch2 in malignant lung tissue validates the biological impact of these genetic alterations. Importantly, this implication of pathways known only to be activated in fetal lung development lends support to the proposed model of lung cancer ontology whereby tumors arise from dysregulated pleuripotent stem cells.

Adaptor Proteins, Signal Transducing↗

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↗