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Improved Diagnostic Sensitivity for Lung Cancer Using an Automated Quantitative Cytology System and Uridine 5′-Triphosphate-Induced Sputum Specimens* FREE TO VIEW

Fred L. Johnson, PhD; Bojana Turic, MD; Roger Kemp, PhD; Branko Palcic, PhD; Robert Sussman, MD, FCCP; Kirk G. Voelker, MD, FCCP; Emory Robinette, MD, FCCP
Author and Funding Information

*From Inspire Pharmaceuticals, Inc (Dr. Johnson), Durham, NC; Perceptronix Medical Inc (Drs. Turic, Kemp, and Palcic), Vancouver, BC, Canada; Pulmonary & Allergy Associates (Dr. Sussman), Springfield, NJ; Lung Associates of Sarasota (Dr. Voelker), Sarasota, FL; and Abingdon Internal Medicine (Dr. Robinette), Abingdon, VA.

Correspondence to: Fred L. Johnson, PhD, Inspire Pharmaceuticals, Inc, 4222 Emperor Blvd, Suite 200, Durham, NC 27703-8466; e-mail: fjohnson@inspirepharm.com

Chest. 2004;125(5_suppl):157S-158S. doi:10.1378/chest.125.5_suppl.157S-a
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Sputum cytology is a noninvasive means of diagnosing lung cancer, although the sensitivity has been limited, due in part to the difficulty of consistently obtaining high-quality sputum specimens. In addition, identifying malignant cells in sputum requires a high degree of expertise by experienced personnel. The use of automated high-resolution computer-assisted quantitative image cytometry (AQC) is being developed to more readily detect lung cancers from sputum specimens. Uridine 5′-triphosphate (UTP) is being developed as a novel inhaled agent for acquiring high-quality sputum specimens for diagnostic purposes. UTP activates the P2Y2 receptors on airway epithelial cells and stimulates chloride and water secretion, cilia beat frequency, and mucociliary clearance. The current study examined the potential of AQC to improve the detection sensitivity of sputum specimens, obtained with and without the use of UTP, in which cancer was not identified by conventional cytology.

The current study was part of an ongoing study in subjects highly suspected of having lung cancer. Sputum specimens were collected spontaneously or following induction with UTP or placebo in a blinded fashion. Specimens were collected in Saccomanno preservative, conventional cytospin slides were prepared, and diagnoses were issued by majority rule from a panel of three experienced cytopathologists. In 18 selected specimens in which malignancy was not observed by the panel, Feulgen-Thionin-stained cytospin slides were prepared and evaluated by AQC. Eleven of these specimens were selected because, according to the panel, they contained suspicious, atypical cells. The remaining seven specimens were selected for AQC without knowledge of the panel diagnoses. The diagnostic software of the cytometer had been previously trained using a set of slides compiled from available high-risk negative and true-positive patients, and was set so that its specificity would be 90% in this population.

Nine of the 11 suspicious specimens were positive for malignancy by AQC, and all were subsequently confirmed to have lung cancer. Of the remaining seven specimens, a review by the cytopathologists yielded the diagnoses “benign,” “atypia: not suspicious for malignancy,” or “inadequate cellularity,” and all were determined by AQC to be negative or inadequate specimens.

The AQC system greatly improved the detection sensitivity of sputum cytology for lung cancer in these specimens. Additional data will be required to accurately confirm the specificity of this technology.

Abbreviations: AQC = assisted quantitative image cytometry; UTP = uridine 5′-triphosphate




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