Differences in Baseline Nasal Secretions Between Chronic Fatigue Syndrome
(CFS) and Control Subjects

J of Chronic Fatigue Syndrome, Vol. 10(1) 2002, pp. 3-15

K. Naranch, BA; S. M. Repka-Ramirez, MD; Y.-J. Park, MD; A.
Velarde, BA; R. Finnegan, BA; J. Murray, Sgt. Marine Reserve; A.
Pheiffer, BSc; E. Hwang, BSc; D. Clauw, MD; J. N. Baraniuk, MD

Division of Rheumatology, Immunology and Allergy, Georgetown
University, 3800 Reservoir Road, NW, Washington, DC 20007-2197
Address correspondence to: J. N. Baraniuk at the above address (E-mail:
mailto:baraniuj@gunet.georgetown.edu ).


ABSTRACT.
Objective: To assess potential mechanism(s) for the rhinitis found in
Chronic Fatigue Syndrome (CFS) subjects.

Methods: The concentrations of mucus constituents were measured in basal
nasal lavage fluids of 103 CFS and 92 non-CFS control subjects. Subjects
were further characterized by their Rhinitis Score and allergy skin test
results into nonallergic and allergic rhinitis, atopic, and negative
subgroups to determine if differences were related to atopy. Other
questionnaires of irritant sensitivity and medicine use were completed.

Results: Mucin polysaccharide (p = 0.043, ANOVA), free hemoglobin (p =
0.0044), mucin/total protein (p = 0.039) and hemoglobin/total protein (p
= 0.043) were higher in CFS than controls. CFS subjects with positive
Rhinitis Scores (p = 0.023) or skin tests (p = 0.047) had higher mucin
levels than those with negative values. For all subjects, increased mucin
was correlated with total protein (Pearson's r2 = 0.188) and inhaled
corticosteroid use (r2 = 0.091), while hemoglobin was correlated with
total protein (r2 = 0.082) and elevated Tobacco Scores (r2 = 0.061).
Other correlations with demographic, medication, or questionnaire
responses gave r2 < 0.05.

Conclusions: CFS subjects have a higher level of complaints in many
systems including the nose. They appear to have an irritant (nonallergic)
rhinitis with increased mucin production and mucosal friability
(epistaxis of hemoglobin). Nasal and systemic drugs do not explain these
significant baseline changes.


KEYWORDS. Nonallergic rhinitis, allergic rhinitis, fibromyalgia, multiple
chemical sensitivity, chronic sinusitis

ABBREVIATIONS. AR, allergic rhinitis; NAR, nonallergic rhinitis; Atopy,
subjects with positive allergy skin tests and negative rhinitis scores;
Negative, subjects with negative allergy skin tests and rhinitis scores


INTRODUCTION
Approximately 70% of Chronic Fatigue Syndrome (CFS) subjects complain of
chronic rhinitis (1-4). In order to help determine the cause of these
complaints, the baseline concentrations of mucus constituents were
measured. These concentrations represent a "snapshot" of the ongoing
dynamic mucosal functions that respond to the conditions of inhaled air
such as its relative humidity, temperature, particulate and irritant
content. Characteristic changes in baseline secretions have been
identified in chronic sinusitis (5), rhinovirus infections (6), and other
types of rhinosinusitis. These changes offer clues into potentially
specific pathophysiological alterations in mucosal function and the
autonomic nervous system inputs that regulate mucosal secretion (7).

The major source of mucosal secretions comes from glandular exocytosis
(7,8). Submucosal glands are densely packed beneath the superficial,
highly vascular lamina propria of the nasal turbinates. Both serous and
mucous cells are present. The serous cells secrete a diversity of
antimicrobial proteins such as lysozyme and secretory IgA (each
contributes about 15% of the total protein), lactoferrin, proteases and
neutral mucins. The highly acidic sialylyl and sulfated mucins are
secreted from the mucous cells. The protein backbones of the mucins
contribute about 28% of the total protein. Mucins can be quantified by
measuring the total carbohydrate in mucous secretions. Plasma glucose and
saccharides are present in too low a concentration to interfere with
mucin oligosaccharide concentrations (9). Epithelial goblet cells also
secrete the acidic mucins.

Approximately one-third of the total protein is derived from plasma
exudation. Hydrostatic pressures exceeding 5 cm H2O drives plasma through
the very superficial fenestrated capillaries and post-capillary venules
into the interstitial spaces (10). This pressure drives the interstitial
fluid across the basement membrane, between epithelial cells and through
tight junctions into the nasal cavity. When the pressure gradient drops,
the exudation abates and the tight junctions close reversibly. Albumin,
IgG, IgM, fibrinogen and alpha2-macroglobumin have been used as markers
of plasma exudation, with albumin contributing up to 15% of total mucus
protein ( I I ). Urea is thought to freely equilibrate across the
epithelium (12).

Epistaxis leads to plasma and erythrocyte leakage. While epistaxis can be
obvious as bright red blood in nasal lavage fluids, lower levels of
bleeding may occur that are not visibly apparent. Erythrocytes would be
incorporated into the vascular, interstitial, epithelial, or
supraepithelial coagulated plug. Since the erythrocytes will become
permeable and release hemoglobin, we have measured the free hemoglobin in
lavage fluids as an indicator of bleeding (13). Thus, the sources of free
hemoglobin could be extravasated and degenerated erythrocytes or clots
within tissues without epithelial disruption, or degenerating clots over
mucosal abrasions, or freely bleeding mucosal abrasions.

Markers of these secretory processes were measured in baseline nasal
lavage fluids from CFS and non-CFS control subjects. Significant
differences were sought that could offer insights into rhinitis
pathophysiology in CFS.