James N. Baraniuk

Rhinosinusitis: Establishing definitions for clinical research and patient care

Background There is a need for more research on all forms of rhinosinusitis. Progress in this area has been hampered by a lack of consensus definitions and the limited number of published clinical trials. Objectives To develop consensus definitions for rhinosinusitis and outline strategies useful in clinical trials. Methods Five national societies, The American Academy of Allergy, Asthma and Immunology; The American Academy of Otolaryngic Allergy; The American Academy of Otolaryngology Head and Neck Surgery; The American College of Allergy, Asthma and Immunology; and the American Rhinologic Society formed an expert panel from multiple disciplines. Over two days, the panel developed definitions for rhinosinusitis and outlined strategies for design of clinical trials. Results Committee members agreed to adopt the term “rhinosinusitis” and reached consensus on definitions and strategies for clinical research on acute presumed bacterial rhinosinusitis, chronic rhinosinusitis without polyposis, chronic rhinosinusitis with polyposis, and classic allergic fungal rhinosinusitis. Symptom and objective criteria, measures for monitoring research progress, and use of symptom scoring tools, quality-of-life instruments, radiologic studies, and rhinoscopic assessment were outlined for each condition. Conclusion The recommendations from this conference should improve accuracy of clinical diagnosis and serve as a starting point for design of rhinosinusitis clinical trials.

Healthcare expenditures for sinusitis in 1996: Contributions of asthma, rhinitis, and other airway disorders

BACKGROUND There have been no recent assessments of the economic burden of sinusitis in the peer-reviewed literature. OBJECTIVE We sought to estimate the 1996 total direct health care expenditures for the treatment of sinusitis. METHODS This study determined (1) direct expenditures of medical and surgical encounters in which sinusitis was the primary diagnosis and (2) attributable expenditures when related airway diseases were the primary diagnosis and sinusitis was a comorbid condition. An expert panel used the Delphi consensus-building technique to determine the proportions for the latter. RESULTS Overall health care expenditures attributable to sinusitis in 1996 were estimated at

Pathogenesis of allergic rhinitis

5.8 billion, of which

Pathophysiology of rhinitis. Lactoferrin and lysozyme in nasal secretions.

1.8 billion (30.6%) was for children 12 years or younger. A primary diagnosis of acute or chronic sinusitis accounted for 58.7% of all expenditures (

Cerebrospinal fluid levels of opioid peptides in fibromyalgia and chronic low back pain

3.5 billion). About 12% each of the costs for asthma and chronic otitis media and eustachian tube disorders were attributed to diagnosis and treatment of comorbid sinusitis. Nearly 90% of all expenditures (

Vasoactive intestinal peptide in human nasal mucosa.

5.1 billion) were associated with ambulatory or emergency department services. CONCLUSION The economic burden of sinusitis in the United States is significant. However, the limitations of this type of evaluation suggest the

Development and validation of a rhinoconjunctivitis and asthma symptom score for use as an outcome measure in clinical trials

5.8 billion amount may be an underestimate of the true direct costs.

Aspartame and susceptibility to headache.

Allergic rhinitis is an increasing problem for which new and exciting therapies are being developed. These can be understood through an appreciation of the newer concepts of pathogenesis of allergic rhinitis. Allergen induces Th2 lymphocyte proliferation in persons with allergies with the release of their characteristic combination of cytokines including IL-3, IL-4, IL-5, IL-9, IL-10, and IL-13. These substances promote IgE and mast cell production. Mucosal mast cells that produce IL-4, IL-5, IL-6, and tryptase proliferate in the allergic epithelium. Inflammatory mediators and cytokines upregulate endothelial cell adhesion markers, such as vascular cell adhesion molecule-1. Chemoattractants, including eotaxin, IL-5, and RANTES, lead to characteristic infiltration by eosinophils, basophils, Th2 lymphocytes, and mast cells in chronic allergic rhinitis. As our understanding of the basic pathophysiologic features of allergic rhinitis continues to increase, the development of new diagnostic and treatment strategies may allow more effective modulation of the immune system, the atopic disease process, and the associated morbidity.

Cerebrospinal Fluid Corticotropin-Releasing Factor Concentration is Associated with Pain but not Fatigue Symptoms in Patients with Fibromyalgia

The antimicrobial proteins lactoferrin (Lf) and lysozyme (Ly) are invariably found in nasal secretions. To investigate the cellular sources and the secretory control of these nasal proteins in vivo, 34 adult subjects underwent nasal provocation tests with methacholine (MC), histamine (H), and gustatory stimuli. Nasal lavages were collected and analyzed for total protein (TP), albumin (Alb), Lf, and Ly. MC (25 mg), H (1 mg), and gustatory stimuli (spicy foods) all increased the concentrations of TP, Alb, Lf, and Ly. However, when each protein was assessed as a percentage of TP (i.e., Alb% = Alb/TP; Lf% = Lf/TP; Ly% = Ly/TP), MC and gustatory stimuli, which both induce glandular secretion, selectively augmented Lf% and Ly% without changing Alb%, while H, which primarily increases vascular permeability, increased Alb% without significantly affecting Lf% or Ly%. Gel electrophoresis and immunoblotting analysis of nasal secretions demonstrated both Lf and Ly in cholinergically induced secretions. Furthermore, histochemical analyses of nasal turbinate tissue revealed Lf and Ly colocalization within the serous cells of submucosal glands, providing evidence that both proteins are strictly glandular products within the nasal mucosa. Therefore, both Lf and Ly are produced and secreted from the glands, and their secretion may be pharmacologically regulated in attempts to improve host defenses.

Neuropeptides and nasal secretion.

BackgroundThe mechanism(s) of nociceptive dysfunction and potential roles of opioid neurotransmitters are unresolved in the chronic pain syndromes of fibromyalgia and chronic low back pain.MethodsHistory and physical examinations, tender point examinations, and questionnaires were used to identify 14 fibromyalgia, 10 chronic low back pain and 6 normal control subjects. Lumbar punctures were performed. Met-enkephalin-Arg6-Phe7 (MEAP) and nociceptin immunoreactive materials were measured in the cerebrospinal fluid by radioimmunoassays.ResultsFibromyalgia (117.6 pg/ml; 85.9 to 149.4; mean, 95% C.I.; p = 0.009) and low back pain (92.3 pg/ml; 56.9 to 127.7; p = 0.049) groups had significantly higher MEAP than the normal control group (35.7 pg/ml; 15.0 to 56.5). MEAP was inversely correlated to systemic pain thresholds. Nociceptin was not different between groups. Systemic Complaints questionnaire responses were significantly ranked as fibromyalgia > back pain > normal. SF-36 domains demonstrated severe disability for the low back pain group, intermediate results in fibromyalgia, and high function in the normal group.ConclusionsFibromyalgia was distinguished by higher cerebrospinal fluid MEAP, systemic complaints, and manual tender points; intermediate SF-36 scores; and lower pain thresholds compared to the low back pain and normal groups. MEAP and systemic pain thresholds were inversely correlated in low back pain subjects. Central nervous system opioid dysfunction may contribute to pain in fibromyalgia.