Dana G. Kissner

Barriers to adherence to cystic fibrosis infection control guidelines

In 2003, the American Cystic Fibrosis (CF) Foundation published revised, evidence‐based guidelines for infection control. We sought to assess potential barriers to adherence to these guidelines experienced by health care professionals (HCPs) caring for CF patients.

Management of sinusitis in adult cystic fibrosis.

Until recently, cystic fibrosis was frequently fatal during childhood. However, with current medical management, many patients are living into adulthood. This has created a new population of patients with chronic sinusitis and severe medical problems. In this report, experience with 22 patients, eight of whom have undergone sinus surgery, is presented, and recommendations for management are proposed. Presenting symptoms are typical of sinusitis, but in a few patients, severe debilitating headaches predominate. Oral antibiotics are often of little use due to the numerous courses of high dose intravenous antibiotics used for resistant pulmonary infections. Topical nasal steroids and mucolytics have been of some benefit. Fourteen operative procedures were performed on eight patients. These procedures included 12 endoscopic sphenoethmoidectomies, four Caldwell-Luc procedures, two frontal sinus obliterations, and one transseptal sphenoidotomy (many of these were in combination.) Results from this experience indicate 1) Failure of endoscopic surgery to control frontal and maxillary sinus disease; 2) Delayed healing of the ethmoid cavity with persistent crusting; and 3) Significant, albeit short term, symptomatic relief following surgical intervention. Based on this limited series, we conclude that surgery should be delayed until absolutely necessary and that an aggressive approach should be adopted when surgery is performed. In our hands this included initial endoscopic sphenoethmoidectomy with open surgical techniques used for removal of trapped inspissated secretions. We recommend long term intravenous antibiotics postoperatively and frequent cleaning of the ethmoid cavity after surgery, continuing indefinitely, to optimize the benefit of surgery.

Development of a T7 Phage Display Library to Detect Sarcoidosis and Tuberculosis by a Panel of Novel Antigens.

Sarcoidosis is a granulomatous inflammatory disease, diagnosed through tissue biopsy of involved organs in the absence of other causes such as tuberculosis (TB). No specific serologic test is available to diagnose and differentiate sarcoidosis from TB. Using a high throughput method, we developed a T7 phage display cDNA library derived from mRNA isolated from bronchoalveolar lavage (BAL) cells and leukocytes of sarcoidosis patients. This complex cDNA library was biopanned to obtain 1152 potential sarcoidosis antigens and a microarray was constructed to immunoscreen two different sets of sera from healthy controls and sarcoidosis. Meta-analysis identified 259 discriminating sarcoidosis antigens, and multivariate analysis identified 32 antigens with a sensitivity of 89% and a specificity of 83% to classify sarcoidosis from healthy controls. Additionally, interrogating the same microarray platform with sera from subjects with TB, we identified 50 clones that distinguish between TB, sarcoidosis and healthy controls. The top 10 sarcoidosis and TB specific clones were sequenced and homologies were searched in the public database revealing unique epitopes and mimotopes in each group. Here, we show for the first time that immunoscreenings of a library derived from sarcoidosis tissue differentiates between sarcoidosis and tuberculosis antigens. These novel biomarkers can improve diagnosis of sarcoidosis and TB, and may aid to develop or evaluate a TB vaccine.

CT of unusual mediastinal vascular abnormalities

The previously unreported CT findings of supracardiac anomalous pulmonary venous return and Takayasu arteritis are presented. CT demonstration of a left vertical vein and an enlarged superior vena cava strongly suggests a diagnosis of supracardiac anomalous venous return. Dynamic scanning of the mediastinum following bolus injection of urographic contrast with close attention to vascular enhancement patterns is required to suggest a diagnosis of Takayasu arteritis. CT is not the preferred diagnostic modality for either entity, but may prove definitive in some patients and may serve to triage other patients to the appropriate diagnostic modalities.

Detection of Cystic Fibrosis Serological Biomarkers Using a T7 Phage Display Library

Cystic fibrosis (CF) is an autosomal recessive disorder affecting the cystic fibrosis transmembrane conductance regulator (CFTR). CF is characterized by repeated lung infections leading to respiratory failure. Using a high-throughput method, we developed a T7 phage display cDNA library derived from mRNA isolated from bronchoalveolar lavage (BAL) cells and leukocytes of sarcoidosis patients. This library was biopanned to obtain 1070 potential antigens. A microarray platform was constructed and immunoscreened with sera from healthy (n = 49), lung cancer (LC) (n = 31) and CF (n = 31) subjects. We built 1,000 naïve Bayes models on the training sets. We selected the top 20 frequently significant clones ranked with student t-test discriminating CF antigens from healthy controls and LC at a False Discovery Rate (FDR) < 0.01. The performances of the models were validated on an independent validation set. The mean of the area under the receiver operating characteristic (ROC) curve for the classifiers was 0.973 with a sensitivity of 0.999 and specificity of 0.959. Finally, we identified CF specific clones that correlate highly with sweat chloride test, BMI, and FEV1% predicted values. For the first time, we show that CF specific serological biomarkers can be identified through immunocreenings of a T7 phage display library with high accuracy, which may have utility in development of molecular therapy.