Inhaled fosamprenavir for laryngopharyngeal reflux: Toxicology and fluid dynamics modeling.

Objectives: Approximately 25% of Americans suffer from laryngopharyngeal reflux (LPR), a disease for which no effective medical therapy exists. Pepsin is a predominant source of damage during LPR and a key therapeutic target. Fosamprenavir (FOS) inhibits pepsin and prevents damage in an LPR mouse model. Inhaled FOS protects at a lower dose than oral; however, the safety of inhaled FOS is unknown and there are no inhalers for laryngopharyngeal delivery. A pre-Good Lab Practice (GLP) study of inhaled FOS was performed to assess safety and computational fluid dynamics (CFD) modeling used to predict the optimal particle size for a laryngopharyngeal dry powder inhaler (DPI). Methods: Aerosolized FOS, amprenavir (APR), or air (control) were provided 5 days/week for 4 weeks (n = 6) in an LPR mouse model. Organs (nasal cavity, larynx, esophagus, trachea, lung, liver, heart, and kidney) were assessed by a pathologist and bronchoalveolar lavage cytokines and plasma cardiotoxicity markers were assessed by Luminex assay. CFD simulations were conducted in a model of a healthy 49-year-old female. Results: No significant increase was observed in histologic lesions, cytokines, or cardiotoxicity markers in FOS or APR groups relative to the control. CFD predicted that laryngopharyngeal deposition was maximized with aerodynamic diameters of 8.1-11.5 µm for inhalation rates of 30-60 L/min. Conclusions: A 4-week pre-GLP study supports the safety of inhaled FOS. A formal GLP assessment is underway to support a phase I clinical trial of an FOS DPI for LPR. Level of Evidence: NA.

Attentional bias toward personally relevant health-threat words.

Conflicting findings have emerged regarding the presence of attentional biases (ABs) in health anxiety, probably due to methodological limitations in the stimuli used in cognitive tasks and the assessment of health anxiety-relevant factors. The current study sought to examine ABs toward health-related threats using idiographically chosen health-threat words in a non-clinical sample. A modified dot-probe task using idiographically selected health-threat words was administered to an undergraduate sample. Self-report measures were administered to assess somatic, cognitive, and behavioral aspects of health anxiety, in addition to assessing negative affect, anxiety sensitivity, and experience of actual medical conditions. Results showed that behavioral and somatic aspects of health anxiety were significantly associated with AB toward personally relevant threat words, even after controlling for negative affect, anxiety sensitivity, and experience of actual medical conditions. Additional analyses revealed that these biases reflected difficulty disengaging attention from threat rather than a facilitated detection of threat. In contrast, illness-related cognitions were found to be unrelated to ABs. These findings suggest an association between threat-related ABs and excessive health-care seeking efforts.