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Molecular classification of nonsmall-cell lung cancer using a 4-protein quantitative assay.

The importance of definitive histological subclassification has increased as drug trials have shown benefit associated with histology in nonsmall-cell lung cancer (NSCLC). The acuity of this problem is further exacerbated by the use of minimally invasive cytology samples.

Here we describe the development and validation of a 4-protein classifier that differentiates primary lung adenocarcinomas (AC) from squamous cell carcinomas (SCC).

METHODS: Quantitative immunofluorescence (AQUA) was employed to measure proteins differentially expressed between AC and SCC followed by logistic regression analysis. An objective 4-protein classifier was generated to define likelihood of AC in a training set of 343 patients followed by validation in 2 independent cohorts (n = 197 and n = 235). The assay was then tested on 11 cytology specimens.

RESULTS: Statistical modeling selected thyroid transcription factor 1 (TTF1), CK5, CK13, and epidermal growth factor receptor (EGFR) to generate a weighted classifier and to identify the optimal cutpoint for differentiating AC from SCC. Using the pathologist's final diagnosis as the criterion standard, the molecular test showed a sensitivity of 96% and specificity of 93%. Blinded analysis of the validation sets yielded sensitivity and specificity of 96% and 97%, respectively. Our assay classified the cytology specimens with a specificity of 100% and sensitivity of 87.5%.

CONCLUSIONS: Molecular classification of NSCLC using an objective quantitative test can be highly accurate and could be translated into a diagnostic platform for broad clinical application. Cancer 2011;. © 2011 American Cancer Society.

Single-dose dexamethasone for mild-to-moderate asthma exacerbations: Effective, easy, and acceptable.

Question I prescribe oral steroids for children in my community when they suffer asthma exacerbation. How many doses of steroids are recommended? Do all children need to take steroids for 5 days? Answer Traditionally, mild-to-moderate pediatric asthma exacerbations have been treated with a short course of oral steroids-often 5 days of prednisone or prednisolone.

However, recent evidence suggests a similar outcome can be acheived with a single dose of dexamethasone, which has a longer half-life and powerful anti-inflammatory effects, along with easier administration and compliance.

Single-dose dexamethasone offers a simple and reliable treatment for these patients in office, urgent care, and emergency department settings.

Congenital malformations among infants born to women receiving montelukast, inhaled corticosteroids, and other asthma medications.

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Article Outline

Long-term use of fluticasone propionate/salmeterol fixed-dose combination and incidence of cataracts and glaucoma among chronic obstructive pulmonary disease patients in the UK General Practice Research Database.

Some large population-based studies have reported a dose-related increased risk of cataracts and glaucoma associated with use of inhaled corticosteroids (ICS) in patients with asthma or chronic obstructive pulmonary disease (COPD). We evaluated the association between use of ICS-containing products, specifically fluticasone propionate/salmeterol fixed-dose combination (FSC), and incidence of cataracts and glaucoma among patients with COPD in a large electronic medical record database in the United Kingdom.

METHODS: We identified a cohort of patients aged 45 years and over with COPD in the General Practice Research Database (GPRD) between 2003 and 2006. Cases of incident cataracts or glaucoma were defined based on diagnosis and procedure codes and matched to controls from the risk set to estimate odds ratios (OR) and 95% confidence intervals (CI). The association with FSC or ICS exposure was modeled using conditional logistic regression. Medication exposure was assessed with respect to recency, duration, and number of prescriptions prior to the index date. Average daily dose was defined as none, low (1-250 mcg), medium (251-500 mcg), high (501-1000 mcg), or very high (1001+ mcg) using fluticasone propionate (FP) equivalents.

RESULTS: We identified 2941 incident cataract cases and 327 incident glaucoma cases in the COPD cohort (n = 53,191). FSC or ICS prescriptions were not associated with risk of incident cataracts or glaucoma for any exposure category, after adjusting for confounders. We observed a lack of a dose response in all analyses, where low dose was the reference group. The odds of cataracts associated with FSC dose were medium OR: 1.1 (95% CI: 0.9-1.4); high OR: 1.2 (95% CI: 0.9-1.5); and very high OR: 1.2 (95% CI: 0.9-1.7). The odds of glaucoma associated with FSC dose: medium OR: 1.0 (95% CI: 0.5-2.1); high OR: 1.0 (95% CI: 0.5-2.0); and very high OR: 1.0 (95% CI: 0.4-2.8).

CONCLUSIONS: FSC or other ICS exposure was not associated with an increased odds of cataracts or glaucoma, nor was a dose-response relationship observed in this population-based nested case-control study of COPD patients in the United Kingdom.

Comparison of Airway Wall Remodeling in Asthma and Chronic Obstructive Pulmonary Disease. Biopsy Findings.

Bronchial remodeling is currently known to affect not only patients with asthma, but also COPD patients. Some studies have demonstrated that basement membrane thickening and destruction of the bronchial epithelium are also found in COPD.

The aim of the study was to compare the basement membrane thickness (BMT) and epithelial damage in biopsy specimens from patients with asthma and COPD.

METHODS: The study was performed in 20 patients with asthma and 12 patients with COPD, who had not been treated with corticosteroids for at least three months before study enrollment. Patients' characteristics were based on the results of: clinical assessment, allergic skin-prick tests, lung function testing and methacholine bronchial challenge. All patients underwent bronchoscopy with forceps biopsies of bronchial mucosa. Light-microscope and semi-automatic software were used to measure BMT in haematoxylin-eosin stained sections. Total (denudation) and partial epithelial damage were assessed independently by two pathologists.

RESULTS: The mean BMT in patients with asthma was 12.54 ± 2.8 microm, and only 7.81 ± 2.0 microm in COPD patients (p < 0.05). Overall percentage of the BM length lined with damaged epithelium was 45 ± 20% in the asthma group and 47 ± 22% in the COPD group (ns). Total and partial epithelial damage were not different between the groups.

CONCLUSIONS: BMT might be a histopathological parameter helpful in distinguishing asthma and COPD patients whereas the extent and pattern of epithelial damage not.

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