Associations between fatigue and medication use in chronic rhinosinusitis

Ear, Nose & Throat Journal, August, 2006 by Neil Bhattacharyya, Lynn J. Kepnes

Abstract

We conducted a prospective study of 586 adults to determine if associations exist between fatigue symptom scores and three classes of medications prescribed for the treatment of chronic rhinosinusitis (CRS): prescription nonsedating antihistamines, topical nasal steroids, and antibiotics. Patients were assessed with the assistance of the Rhinosinusitis Symptom Inventory and Likert-scale fatigue symptom scores. On multivariate analysis and correcting for disease severity, we found that significantly higher fatigue symptom scores were associated with the use of nonsedating antihistamines (mean Likert score: 2.75 vs. 2.27 for patients not taking a nonsedating antihistamine; p = 0.029). Higher fatigue scores were also associated with a greater number of antibiotic courses and more total weeks of antibiotic use (p < 0.001 in both cases). No association was seen between fatigue scores and the use of topical nasal steroids (mean Likert score: 2.65 vs. 2.24; p = 0.658). We recommend that long-term use of a nonsedating antihistamine be scrutinized in CRS patients who report symptoms of fatigue.

Introduction

Fatigue is a common symptom associated with the diagnosis of chronic rhinosinusitis (CRS). In fact, it is one of the criteria used to establish a diagnosis of CRS. Chronic fatigue places a significant quality-of-life burden on patients, (1,2) and it has attracted a significant amount of research effort because it is associated with many other chronic disease processes, such as infections, obstructive sleep apnea, and chronic fatigue syndrome itself. (3) We have often been struck by the frequency and degree of fatigue symptoms reported by our own patients who undergo evaluation for CRS. (4) Not infrequently, chronic fatigue is a significant factor that motivates patients to seek diagnosis and therapy for CRS.

The cause of fatigue in the CRS syndrome complex remains unknown. Symptoms of fatigue may be associated with the pathogenesis of CRS itself, with the psychological nature of the disease burden in CRS, and/or with the medication regimen often used to treat CRS. Many patients correlate their fatigue with the number of antibiotic courses they have taken. Other patients correlate fatigue with the use of nonsedating antihistamines, and others still with the use of topical nasal steroid sprays. In this article, we describe our study of the relationships between fatigue and medication use in CRS.

Patients and methods

We obtained data at the initial assessment of all adults who presented to our institution for evaluation of CRS. Patients were asked to complete the Rhinosinusitis Symptom Inventory to arrive at scores for major and minor CRS symptoms. (4,5) Patients were also asked to rate their fatigue symptomatology averaged over the previous 12 weeks on a 6-point Likert scale, ranging from 0 (no symptoms of chronic fatigue) to 5 (severe fatigue) in the form of an embedded question. For control purposes, patients were also asked to rate the severity of fever symptoms on the same 6-point scale. Fever is not a major symptom associated with chronic rhinosinusitis, and therefore it served as a good control comparator.

Embedded questions were used to ascertain past and current use of prescription nonsedating antihistamines, topical nasal steroids, and antibiotics. Antibiotic use was quantified as the number of courses and the number of weeks of oral antibiotic therapy during the preceding calendar year. Because over-the-counter antihistamines are well known to cause fatigue, these medications were excluded from this analysis (this study was conducted before loratadine became available as an over-the-counter preparation, and therefore use of this drug was included in the analysis). Patients were blinded as to the specific purpose of this study.

Data on symptoms and medication use were entered into a Microsoft Excel spreadsheet and analyzed for accuracy on a case-by-case basis. Data were then imported into SPSS version 10.0 software for statistical analysis. Standard demographic information with respect to gender, age, symptom scores, and medication use was computed. Next, one-way analysis of variance (ANOVA) was conducted with fatigue as the dependent variable and medication use as the factor variable influencing fatigue. A multivariate ANOVA model was then constructed with fatigue score as the dependent variable; current use of a nonsedating antihistamine and current use of a topical steroid were independent variables; the number of antibiotic courses was entered as a covariate. To control for the probability that increasing disease severity would make multiple medication use more likely (i.e., patients with more severe CRS are more likely to take both a nonsedating antihistamine and a topical nasal steroid), the combined nasal symptom score domain was also entered as a covariate. The nasal symptom domain score is an unweighted average of Likert scores for severity of symptoms for nasal obstruction, rhinorrhea, and dysosmia. A second statistical model was also run with the number of weeks of antibiotics (rather than the simple number of courses of antibiotics) as a covariate. Statistical significance was set at p < 0.05. A similar statistical analysis was conducted for fever symptom severity as the dependent variable in the multivariate model for purposes of control comparison.