Neuropathology in rhinosinusitis

Abstract:

Pathophysiologic differences in neural responses to hypertonic saline (HTS) were investigated in subjects with acute sinusitis (n = 25), subjects with chronic fatigue syndrome (CFS) with nonallergic rhinitis (n = 14), subjects with active allergic rhinitis (AR; n = 17), and normal (n = 20) subjects. Increasing strengths of HTS were sprayed into their nostrils at 5-minute intervals. Sensations of nasal pain, blockage, and drip increased with concentration and were significantly elevated above normal. These parallels suggested activation of similar subsets of afferent neurons.

Urea and lysozyme secretion were dose dependent in all groups, suggesting that serous cell exocytosis was one source of urea after neural stimulation. Only AR and normal groups had mucin dose responses and correlations between symptoms and lysozyme secretion (R(2) = 0.12-0.23). The lysozyme dose responses may represent axon responses in these groups. The neurogenic stimulus did not alter albumin (vascular) exudation in any group. Albumin and mucin concentrations were correlated in sinusitis, suggesting that nonneurogenic factors predominated in sinusitis mucous hypersecretion. CFS had neural hypersensitivity (pain) but reduced serous cell secretion. HTS nasal provocations identified significant, unique patterns of neural and mucosal dysregulation in each rhinosinusitis syndrome.

 

Source: Baraniuk JN, Petrie KN, Le U, Tai CF, Park YJ, Yuta A, Ali M, Vandenbussche CJ, Nelson B. Neuropathology in rhinosinusitis. Am J Respir Crit Care Med. 2005 Jan 1;171(1):5-11. Epub 2004 Oct 11. http://www.ncbi.nlm.nih.gov/pubmed/15477496

 

A tender sinus does not always mean rhinosinusitis

Abstract:

BACKGROUND: Sinus tenderness has not been quantitatively assessed.

OBJECTIVE: We sought to compare sinus and systemic tenderness in rhinosinusitis, allergic rhinitis, and chronic fatigue syndrome (CFS), and healthy (non-CFS) groups.

METHODS: Cutaneous pressures (kg/cm(2)) causing pain at 5 sinus and 18 systemic sites were measured in acute and chronic rhinosinusitis, active allergic rhinitis, healthy non-CFS/no rhinosinusitis, and CFS subjects.

RESULTS: Sinus thresholds differed significantly (P </= 10(-11), ANOVA) between non-CFS/no rhinosinusitis (1.59 +/- 0.14 kg/cm(2), mean +/- 95% CI, n = 117), allergic rhinitis (1.19 +/- 0.31, n = 30), exacerbations of chronic rhinosinusitis (1.25 +/- 0.26, n = 25), non-CFS/chronic rhinosinusitis (1.23 +/- 0.27, n = 23), acute rhinosinusitis (1.10 +/- 0.20, n = 22), CFS/no rhinosinusitis (0.98 +/- 0.15, n = 70), and CFS/chronic rhinosinusitis (0.78 +/- 0.12, n = 56). Systemic pressure thresholds were lower for CFS (1.46 +/- 0.15) than for non-CFS (2.67 +/- 0.22, P </= 10(-11)).

CONCLUSIONS: The lower sinus thresholds of rhinosinusitis groups validated the sign of sinus tenderness. Sinus and systemic thresholds were both 44% lower in CFS than in non-CFS subjects, suggesting that systemic hyperalgesia contributed to CFS sinus tenderness and “rhinosinusitis” complaints.

 

Source: Naranch K, Park YJ, Repka-Ramirez MS, Velarde A, Clauw D, Baraniuk JN. A tender sinus does not always mean rhinosinusitis. Otolaryngol Head Neck Surg. 2002 Nov;127(5):387-97. http://www.ncbi.nlm.nih.gov/pubmed/12447232

 

Cytokines in nasal lavage fluids from acute sinusitis, allergic rhinitis, and chronic fatigue syndrome subjects

Abstract:

The aim of this study was to compare the degree of inflammation present in acute sinusitis, allergic rhinitis, chronic Fatigue Syndrome (CFS), and non-CFS control subjects by measuring cytokine concentrations in nasal lavage fluids. The concentrations of total protein (TP; Lowry assay), nerve growth factor (NGF), tumor necrosis factor (TNF) alpha, and interleukin (IL)-8 were measured by ELISA in nasal lavage fluids from acute sinusitis (n = 13), active allergic rhinitis (n = 16), CFS (n = 95), and non-CFS (n = 89) subjects. CFS and non-CFS groups were subdivided further using allergy skin test and rhinitis score results. Acute sinusitis subjects had significantly higher TP (p = 0.011, ANOVA), TNF-alpha (p = 0.00071), and IL-8 (p = 0.0000027) concentrations and IL-8/TP ratios (p = 0.0030) than the other three patient groups. There were no differences based on skin test or rhinitis score severity within either the CFS or non-CFS groups. The mucopurulent discharge of acute sinusitis contained significantly higher TNF-alpha and IL-8. Neutrophils were a likely source for these cytokines. There were no differences between CFS and non-CFS subjects, making it unlikely that the rhinitis of CFS has an inflammatory component.

 

Source: Repka-Ramirez S, Naranch K, Park YJ, Clauw D, Baraniuk JN. Cytokines in nasal lavage fluids from acute sinusitis, allergic rhinitis, and chronic fatigue syndrome subjects. Allergy Asthma Proc. 2002 May-Jun;23(3):185-90. http://www.ncbi.nlm.nih.gov/pubmed/12125506

 

IgE levels are the same in chronic fatigue syndrome (CFS) and control subjects when stratified by allergy skin test results and rhinitis types

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) has an uncertain pathogenesis. Allergies have been suggested as one cause.

OBJECTIVE: The aim of this study was to compare serum immunoglobulin (Ig)E in CFS and control subjects to determine whether IgE levels were elevated in CFS. This would be suggestive of increased atopy in CFS.

METHODS: IgE was measured by quantitative ELISA (sandwich) immunoassay in 95 CFS and 109 non-CFS control subjects. Subjects were classified by positive or negative allergy skin tests (AST) and rhinitis questionnaires (rhinitis score, RhSc) into four rhinitis types: nonallergic rhinitis (NAR with positive RhSc and negative AST); allergic rhinitis (AR with positive AST and RhSc); atopic/no rhinitis (AST positive/RhSc negative); and nonatopic/no rhinitis (both AST and RhSc negative) subjects.

RESULTS: IgE was not significantly different between control (128 +/- 18 IU/mL, mean +/- SEM) and CFS (133 +/- 43 IU/mL) groups, or between control and CFS groups classified into the four rhinitis types. IgE was significantly higher in subjects with positive AST whether or not they had positive RhSc or CFS symptoms.

CONCLUSIONS: Elevated IgE and positive AST indicate allergen sensitization, but are not necessarily indicators of symptomatic allergic diseases. There was no association between IgE levels and CFS, indicating that atopy was probably not more prevalent in CFS. Therefore, TH2-lymphocyte and IgE-mast cell mechanisms are unlikely causes of CFS.

 

Source: Repka-Ramirez MS, Naranch K, Park YJ, Velarde A, Clauw D, Baraniuk JN. IgE levels are the same in chronic fatigue syndrome (CFS) and control subjects when stratified by allergy skin test results and rhinitis types. Ann Allergy Asthma Immunol. 2001 Sep;87(3):218-21. http://www.ncbi.nlm.nih.gov/pubmed/11570618

 

Nasal secretion analysis in allergic rhinitis, cystic fibrosis, and nonallergic fibromyalgia/chronic fatigue syndrome subjects

Abstract:

Rhinitis symptoms are present in approximately 70% of subjects with fibromyalgia and chronic fatigue syndrome (FM/CFS). Because only 35% to 50% have positive allergy skin tests, nonallergic mechanisms may also play a role.

To better understand the mechanisms of nonallergic rhinitis in FM/CFS, nasal lavages were performed, and markers of vascular permeability, glandular secretion, and neutrophil and eosinophil infiltration measured in 27 nonallergic FM/CFS, 7 allergic rhinitis, 7 cystic fibrosis, and 9 normal subjects. Allergic rhinitis subjects had significantly increased vascular permeability (IgG) and ECP levels.

Cystic fibrosis subjects had significantly higher elastase and total protein levels. There were no significant differences between FM/CFS and normal lavage fluids. Analysis of the constituents of nasal mucus provides information about ongoing secretory processes in rhinitis.

There were no differences in the basal secretion of these markers of vascular permeability, submucosal gland serous cell secretion, eosinophil and neutrophil degranulation in nonallergic FM/CFS subjects. This suggests that constitutively active secretory processes that regulate continuous production of nasal secretions are not altered in FM/CFS. Future studies should examine alternative mechanisms such as inducible, irritant-activated, or reflex-mediated effects.

 

Source: Baraniuk JN, Clauw D, Yuta A, Ali M, Gaumond E, Upadhyayula N, Fujita K, Shimizu T. Nasal secretion analysis in allergic rhinitis, cystic fibrosis, and nonallergic fibromyalgia/chronic fatigue syndrome subjects. Am J Rhinol. 1998 Nov-Dec;12(6):435-40. http://www.ncbi.nlm.nih.gov/pubmed/9883301

 

Rhinitis symptoms in chronic fatigue syndrome

Abstract:

BACKGROUND: Atopy and allergic rhinitis are thought to be increased in prevalence in chronic fatigue syndrome (CFS).

METHODS: To investigate this hypothesis, 51 CFS (CFS), 34 normal (N), 27 allergic rhinitis (AR), and 17 patients with other rheumatologic diseases filled out an Airway Symptom Severity self-report questionnaire to determine the frequencies of nasal, sinus, and chest symptoms, and a Systemic Complaints self-report questionnaire to determine the frequencies of complaints referable to neurologic, rheumatologic, gastrointestinal, and other systems. All subjects received a standard set of allergy skin tests, and were subdivided into those with positive and negative results.

RESULTS: Allergy skin tests were positive in 35% of CFS and 44% of N subjects (difference not significant by Chi2). Significant rhinitis complaints were present in 83% of skin test positive CFS, 76% of skin test negative CFS, 74% of AR, and 23% of N subjects. Systemic Complaints scores were significantly elevated in skin test positive (94%) and negative (94%) CFS groups compared with AR (35%) and N (6%) groups. This score could significantly discriminate between CFS and N subjects.

CONCLUSIONS: These data indicate that in this CFS population, 24% had no significant rhinitis complaints, 30% had positive skin tests suggesting the potential for allergic rhinitis complaints, and 46% had nonallergic rhinitis. The mechanism of the nonallergic component may offer insights into the pathogenesis of CFS.

 

Source: Baraniuk JN, Clauw DJ, Gaumond E. Rhinitis symptoms in chronic fatigue syndrome. Ann Allergy Asthma Immunol. 1998 Oct;81(4):359-65. http://www.ncbi.nlm.nih.gov/pubmed/9809501