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Treatment of Acute and Chronic Rhinosinusitis
in the United States, 1999-2002
Hadley J. Sharp, BS; David Denman, MD; Susan Puumala, MS; Donald A. Leopold, MD Objective: To generalize the prescribing trends of a sta-
nasal decongestants; corticosteroids; and antitussive, ex- tistically defined sample of patient visits because of acute pectorant, and mucolytic agents, respectively. In addi- or chronic rhinosinusitis in the United States, using re- tion, corticosteroids are used for the treatment of chronic ported diagnostic codes from the International Classifi- cation of Diseases, Ninth Revision, Clinical Modification.
Conclusions: The use of prescription antibiotics far out-
Design: Four-year prospective study.
weighs the predicted incidence of bacterial causes of acuteand chronic rhinosinusitis. Frequency of antibiotic class Setting: Public use data from the National Ambulatory
used was not congruent with reported antimicrobial effi- Medical Care Survey and the National Hospital Ambu- cacy of the respective classes. Despite contradictory effi- latory Medical Care Survey collected by the National Cen- cacies reported in the literature, inhaled corticosteroids were frequently used to treat acute rhinosinusitis. Antibiotics andinhaled nasal corticosteroids are being used more often than Results: The most frequently recommended medica-
their published efficacies would encourage.
tions for treatment of both acute and chronic rhinosinu-sitis are antibiotic agents, followed by antihistamines; Arch Otolaryngol Head Neck Surg. 2007;133:260-265 RHINOSINUSITISISANIMPOR- recentlyfavoredasadiagnosisbecauseof
the combined nasal and paranasal sinus in- consistent with the current guidelines and to avoid confusion, we use the term “rhino- chronic rhinosinusitis based on time line sinusitis” throughout this article. Physi- cian-generated clinical information about tion added clarity, there is still much con- patient visits because of rhinosinusitis was collected. Using reported International Classification of Diseases, Ninth Revision, stitute rhinosinusitis and within the medi- Clinical Modification (ICD-9-CM) codes cal field about how to treat the different subgroups. Until recently, most studies of ize the prescribing trends of a statisti- cally defined sample of visits in the UnitedStates that resulted in a primary diagno-sis of acute or chronic rhinosinusitis.
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cial burden for the US health care sys-tem. In 1992, direct medical costs of rhino- conservative estimates. With direct and in- Author Affiliations:
ment, these results were difficult to inter- direct costs calculated, the total expendi- sive disorders experienced by the US popu- lation.3 Proof can also be found in the num- were used to evaluate patient visits to sta- ber of prescriptions written for antibiotic tistically selected ambulatory care facili- ties. Although rhinosinusitis has been more (REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 133, MAR 2007 2007 American Medical Association. All rights reserved.
scriptions for antibiotics in children and 21% in adults.4 antimicrobial use in the past 4 to 6 weeks.4 This order Not only cost, but also the effect that rhinosinusitis has will be compared with the descending order of antimi- on quality of life, makes it a major medical concern.5 With- crobial prescribing frequency by physicians in the United out standard protocols, treatment of this varied disor- States. The effects of antibiotic therapy on chronic rhino- der can be inconsistent between providers and among sinusitis are questionable, but if an acute infection oc- curs in the inflamed nasal or sinus cavities, use of a short- In this article the various medical treatments used for term regimen can provide relief.4 Decongestants are often chronic and acute rhinosinusitis are tabulated. The cur- used in treatment plans to increase sinus drainage and rent classification of rhinosinusitis in adults, from the ventilation and to thin mucosa and mucous secretions, Sinus and Allergy Health Partnership (SAHP) and the and result in decreasing mucous stasis.13 American Rhinologic Society, is as follows: acute rhino- For acute rhinosinusitis, and especially for acute bac- sinusitis is manifested with symptoms for up to 4 weeks, terial rhinosinusitis, there are guidelines for treatment.
with the presence of at least 2 major symptoms, or 1 ma- Chronic disorders are not so categorical and are much jor and at least 2 minor symptoms or purulence; and more complex. This may be why there is no consensus chronic rhinosinusitis is defined as the duration of symp- in the medical community about algorithms or proto- toms for 12 weeks or longer, with the same symptom pro- cols for treatment. The goal of resolution of chronic rhino- sinusitis is to resolve predisposing factors, but many treat- Acute rhinosinusitis is most often thought to be caused ments effective in acute episodes do not have the same by an infectious agent. Watchful waiting, lavage with sa- efficacy in chronic disorders.4 In this article, we exam- line solution, and use of a decongestant or proper anti- ine the national trends in treatment and how they com- microbial agents are the treatments of choice.6 Despite the 32 million cases of chronic rhinosinusitis occurringannually in the United States, the causes are not so clearas for acute rhinosinusitis.7 It is assumed that the chronic process is multifactorial and possibly different inchildren than in adults. Repeated acute upper respira-tory tract infections can lead to mucosal swelling, Public use data from the NAMCS and NHAMCS for 1999 through2002 were combined and used in this analysis. These years were obstruction of sinus outflow, and, eventually, chronic in- chosen because data were collected similarly during all 4 years.
fection. A number of conditions predispose to rhino- The NAMCS and NHAMCS prospectively collect data from a na- sinusitis, including smoking, swimming, decongestant tional probability sample of visits for ambulatory medical care to spray abuse (rhinosinusitis medicamentosa), immuno- a physician’s office and to hospital outpatient departments and globulin deficiencies, disorders of mucociliary trans- emergency departments. These surveys are conducted annually port, and changes in glandular secretions.8 Allergies, via by the National Center for Health Statistics.
antigen-antibody reactions and release of vasodilators and Both surveys use a multistage probability design. The NAMCS mediators of inflammation, can cause mucosal swelling uses a 3-stage design that starts with a probability sample of and obstruction.9 In addition, anatomical factors such as primary sampling units, then samples physician practices within septal spurs or deviations, hypertrophic middle turbi- primary sampling units, and finally samples patient visits withinpractices. Patient visits are randomly selected from a 1-week nates, and concha bullosa can affect nasal cavity and si- reporting period. Physicians are identified through member- nus ostia airflow.10 All of these conditions can lead to an ship lists from the American Medical Association and the environment that is suitable for mucous stasis, bacterial American Osteopathic Association. Only nonfederally em- or fungal overgrowth, and chronic inflammation.11 Other ployed physicians are included. Physicians with a specialty of proposed causes include hormonal effects, and further anesthesiology, pathology, or radiology are excluded from the research should elucidate a better understanding of these survey. The NHAMCS uses a 4-stage design that also starts with a probability sample of primary sampling units, then samples With a demonstration of the complexity of acute and hospitals within primary sampling units; outpatient clinics and chronic rhinosinusitis, it is understandable why the ap- emergency services areas within hospitals; and visits in the out- proach to treatment has remained controversial. Inas- patient and emergency clinic area. Patient visits are randomlysampled during a 4-week reporting period. Hospitals included much as viruses frequently cause acute rhinosinusitis, are noninstitutional general and short-stay hospitals; federal, many advocate no antibiotic treatment if the symptoms military, and Veterans Administration hospitals and hospital are not severe, wane in 5 to 7 days, and resolve in 10 days.6 When antibiotics are used, there are recommendations Data are collected on a patient record form that includes pa- from the SAHP12 for calculated clinical efficacy and bac- tient demographic data and visit information. Visit informa- teriologic efficacy, as well as when to change therapy. In tion includes up to 3 reasons for the visit, a primary diagnosis 2000 and again in 2004, the SAHP reported the clinical and 1 or 2 secondary diagnoses, projected visit payment type, and bacteriologic efficacy of a number of antimicrobial and a list of medications ordered, supplied, administered, or agents, including, in descending order, amoxicillin– continued at the visit. As many as 6 medications can be listed clavulanate potassium, amoxicillin, cefpodoxime prox- on the survey, and each drug is referred to as a drug mention.
These medications were assigned therapeutic classifications from etil, cefuroxime axetil, cefdinir, trimethoprim- the National Drug Code Directory, 1995 edition. An overall an- sulfamethoxasole, doxycycline, azithromycin or tibiotic category was created by combining the following thera- clarithromycin or erythromycin, and telithromycin. The peutic classes: penicillins; cephalosporins; erythromycins, lin- SAHP recommended antibiotic therapy for adults with cosamides, and macrolides; tetracyclines; sulfonamides and acute bacterial rhinosinusitis with mild disease and no trimethoprim; and quinolones and their derivatives.
(REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 133, MAR 2007 2007 American Medical Association. All rights reserved.
Table 1. ICD-9-CM Codes Used to Evaluate Frequency of Chronic and Acute Rhinosinusitis Visits in the United States, 1999-2002*
Chronic Rhinosinusitis
Acute Rhinosinusitis
ICD-9-CM Code
No. of Visits in Database
ICD-9-CM Code
No. of Visits in Database
Abbreviation: ICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical Modification.
*Of the codes included, any one listed as the primary diagnosis qualified the visit for the respective category of diagnosis, chronic or acute rhinosinusitis.
Table 2. Medication Classes With Frequency per Visit*
Medication Class†
Chronic Rhinosinusitis
Acute Rhinosinusitis
Erythromycins, lincosamides, and macrolides Antitussives, expectorants, and mucolytics Abbreviation: NE, not reliably estimable because of fewer than 30 observations or a relative standard error greater than 30%.
*Data are given as number of visits (95% confidence interval).
†Up to 6 medications could be listed per visit. Medication classes of interest that met the requirement of 30 subjects and less than 30% relative standard error for either chronic or acute rhinosinusitis are given in Table 3.
STUDY SAMPLE SELECTION
than 30 visits in the database or if their relative standard errorwas greater than 30%.14 In this study, we selected only those visits that resulted in aprimary diagnosis of chronic or acute rhinosinusitis. As manyas 3 diagnoses could be listed at each visit. The first diagnosis was considered primary and the other diagnoses were consid-ered secondary.
If a visit included 1 of the ICD-9-CM codes given in Table 1
Extrapolations of data from the NAMCS and NHAMCS for the primary diagnosis, it was selected as a visit because of show that in 1999 through 2002 in the United States chronic or acute rhinosinusitis. We excluded those visits with there were an estimated 14 277 026 visits annually a diagnosis of both chronic and acute rhinosinusitis because because of chronic rhinosinusitis and an estimated there were fewer than 30 such visits in the database.
3 116 142 visits annually because of acute rhinosinusi-tis. These visits represented 1.39% (95% CI, 1.26-1.52) STATISTICAL ANALYSIS
and 0.30% (95% CI, 0.22-0.38), respectively, of all vis-its for ambulatory care.
Sample weights from the National Center for Health Statistics Antibiotic agents were mentioned in visits because of were used for each visit in both the NAMCS and NHAMCS data both acute and chronic rhinosinusitis. Penicillins were to obtain unbiased national estimates based on various patient the most frequently recommended class of antibiotics characteristics and to adjust for nonresponse. Standard errors mentioned (Table 2), and in this group, most men-
were calculated using an ultimate cluster variance estimationdesign using Survey Data Analysis software (SUDAAN, ver- tions were specifically for amoxicillin or amoxicillin– sion 8.0; Research Triangle Institute, Cary, NC). This ac- clavulanate potassium (Table 3). The grouping of eryth-
counts for the multistage sampling design to estimate unbi- romycin, lincosamides, and macrolides was the second ased standard errors and 95% confidence intervals (CIs).
most frequent class of antibiotics mentioned at visits be- Estimates were considered unreliable if they were based on fewer (REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 133, MAR 2007 2007 American Medical Association. All rights reserved.
Among other drug classes, inhaled or nasal cortico- steroidal agents and antihistamines were mentioned in Table 3. Frequency of Amoxicillin vs
visits because of both acute and chronic rhinosinusitis.
Amoxicillin–Clavulanate Potassium for Treatment
of Both Chronic and Acute Rhinosinusitis*
Additional drug class uses are given in Table 2.
Medication†
Chronic Rhinosinusitis
Acute Rhinosinusitis
The use of prescription antibiotics to treat acute rhino-sinusitis far outweighs the predicted incidence of bacte- *Data are given as number of visits (95% confidence interval).
rial causes. The literature repeatedly shows that viruses are †Some visits listed both medications. While this is unlikely accurate and by far the most frequent cause of acute rhinosinusitis. How- more likely a mistake in reporting, the data must be evaluated.
‡Includes amoxicillin, Amoxil (SmithKline Beecham Pharmaceuticals, ever, in practice, physicians ordered, supplied, adminis- Philadelphia, Pa), Polymox (Apothecon, a Bristol-Myers Squibb Co, Shawnee tered, or continued at least 1 prescription antibiotic in Mission, Kan), and Trimox (Apothecon).
82.74% of visits because of acute rhinosinusitis. With eti- §Includes Augmentin, Augmentin 125, Augmentin 250, Augmentin 500, and ologies less understood for chronic rhinosinusitis, a com- Augmentin ES (all produced by SmithKline Beecham Pharmaceuticals).
parison cannot be made between research and practice.
However, with inflammation the most likely cause, the useof at least 1 antibiotic in 69.95% of visits because of chronic tertain the secondary efficacy of these drugs. Perhaps these rhinosinusitis is a surprising number.
physicians were treating a secondary infection or using Penicillins, mainly amoxicillin and amoxicillin– the anti-inflammatory effects of antibiotic treatments.
clavulanate potassium, were the most commonly used While keeping the goals of treatment in mind, there are medication class for both chronic and acute rhinosinu- concerns about the overuse of antibiotics and the resul- sitis. A penicillin drug was mentioned in 30.35% of all tant problems, including drug resistance and increas- visits with a primary diagnosis of chronic rhinosinusitis ingly virulent bacteria. When two thirds of patients with and in 27.18% visits with a primary diagnosis of acute sinus symptoms expect or receive an antibiotic and as rhinosinusitis. This is intuitive, inasmuch as recent stud- many as one fifth of antibiotic prescriptions for adults ies have shown penicillins to be highly effective against are written for a drug to treat rhinosinusitis, these dis- the bacteria in nasal and sinus areas. Amoxicillin– orders hold special pertinence on the topic.
clavulanate potassium (875/125 mg twice a day for 14 Inhaled or nasal corticosteroids were mentioned in days) has a 95% clinical response rate in acute bacterial 15.05% of visits because of acute rhinosinusitis. Pre- rhinosinusitis and acute exacerbations of chronic rhino- scribed in a significant number of visits, it is important to discuss what has previously been reported about the Penicillins are mentioned more often in visits be- role of corticosteroids in rhinosinusitis. Dolor et al17 cause of chronic rhinosinusitis compared with acute showed that the concomitant use of cefuroxime and in- rhinosinusitis. When the SAHP published antimicrobial tranasal fluticasone for 21 days had a higher clinical suc- guidelines for acute bacterial rhinosinusitis in 2004, they cess rate than use of cefuroxime with placebo (93.5% and discussed all antimicrobial agents with ␤-lactam activ- 73.9%, respectively; P = .009). Lack of objective criteria ity en bloc. This class topped the list of efficacious agents, for measuring improvement, data based on patient re- and, when subdivided, amoxicillin–clavulanate potas- ports of improvement, and funding of the study by the sium had the highest calculated clinical efficacy in both manufacturer of fluticasone all proved limitations of the groups that had or had not recently received antimi- that publication. In a different double-blind, placebo- controlled trial,2 the use of flunisolide as an adjunct to The group including erythromycins, lincosamides, and amoxicillin–clavunate potassium therapy was studied. De- macrolides was second in frequency of antibiotic men- spite use of flunisolide vs placebo 3 times daily for 3 weeks, tions in visits because of acute rhinosinusitis. A men- many patients continued to have symptoms and recur- tion in 24.32% of visits puts the use of this class of an- rences were common in both groups.2 As our data show tibiotics ahead of cephalosporins, sulfonamides and and as many practicing clinicians can report, the use of trimethoprim, and tetracyclines, in that order. The Acute inhaled corticosteroids as adjunctive treatment in acute Bacterial Rhinosinusitis protocol issued by the SAHP in rhinosinusitis is not rare but is of undetermined benefit.
January 2004 listed efficacies of these classes in an or- In chronic rhinosinusitis, even more intranasal and oral der different from that reported in our studies. In the SAHP corticosteroid use was reported. Inasmuch as many con- data, the erythromycin, lincosamides, and macrolides sider chronic rhinosinusitis both an infectious and an in- group had the lowest calculated clinical efficacy and bac- flammatory disease, it is understandable that clinicians are, teriologic efficacy, behind the cephalosporins and the in many cases, attempting to treat both. Two studies used sulfonamides and trimethoprim. This higher than ex- to evaluate treatment approaches in chronic rhinosinusi- pected ranking in clinical practice could be owing to an tis have been published. One focused on symptomatic im- anti-inflammatory benefit that macrolides possess.16 Based provement only, while a more recent study coupled symp- on the number of visits with an antibiotic mention tomatic and radiographic changes due to medical treatment.
(69.95% for chronic rhinosinusitis and 82.74% for acute In the earlier study, McNally et al18 showed that treatment rhinosinusitis) and the suspected low number of rhino- with antibiotics, decongestants, and intranasal steroids can sinusitis episodes caused by a bacterium, one must en- decrease symptoms of chronic rhinosinusitis. In that study, (REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 133, MAR 2007 2007 American Medical Association. All rights reserved.
however, patients were not followed up for occurrence of tion antibiotic drugs are being used far more than bac- relapse.16 In a 2002 retrospective study, chronic rhinosinu- terial causes studies would indicate. Within the class of sitis was treated with an antibiotic (most commonly, trova- antibiotics, the penicillins are, appropriately, at the top floxacin, amoxicillin–clavulanate potassium, levofloxa- of the prescription list for both acute and chronic rhino- cin, or metronidazole), oral prednisone for 10 days, sinusitis. Questionable is the frequent use of the class that intranasal steroids, and nasal irrigation with saline solu- includes erythromycins, lincosamides, and macrolides, tion.19 Statistically significant improvement in both symp- with other classes having higher antibacterial efficacy. Na- toms and findings at computed tomography from base- sal and inhaled corticosteroids are prescribed more fre- line to the end of the study were demonstrated.19 However, quently to treat acute rhinosinusitis than published stud- neither of these studies included a concurrent control group.
ies imply is necessary. Despite current theories of causes Based on current understanding of the pathogenesis of of chronic rhinosinusitis, the use of corticosteroids re- chronic rhinosinusitis and these findings, it is understand- mains low in this setting. An area where our findings fit able why some physicians prescribe corticosteroids to treat nicely with current information is use of antihista- mines, which roughly matched the prevalence of their Allergic rhinosinusitis is a common disease that affects major indication, allergic rhinosinusitis.
approximately 20% of the US population.20 Because corti- A limitation of this study is that the databases used costeroids are effective in the treatment of this disorder, only data for medications ordered, supplied, adminis- higher numbers of drug mentions for this chronic class tered, or continued by attending physicians. Because these might be expected. Inasmuch as a patient could have acute data were not based on patient responses, the use of over- or chronic sinus complications from allergies, it further the-counter medicines or home remedies was not re- clouds the assumptions about use of corticosteroids to treat corded. We wonder whether the percentages of medica- tions used would be much smaller when compared with The use of antihistamines demonstrated by our data the number of patients who use hot packs to relieve the seems logical; 20.93% of visits because of chronic rhino- symptoms of chronic rhinosinusitis or whether physi- sinusitis and 25.26% of visits because of acute rhinosinu- cians recommend irrigation with saline solution and sitis is near the prevalence of allergic rhinosinusitis in the steam, as often as antihistamine prescriptions.
population. Antihistamines are clearly indicated in the treat- The use of antibiotics and corticosteroids, inhaled and ment of allergy-related disease. Some of the older, gener- oral, needs more investigation in the treating of rhino- ally over-the-counter antihistamines are considered detri- sinusitis. Current theories and contradicting evidence in mental to the nose and sinus mucosa because their the literature makes the findings of our study all the more cholinergic effects cause dryness of the mucous secre- compelling. Could their use be more efficacious than tions and resolution of infections can be slowed.22 Most of proved? Can it be assumed that practicing physicians in the antihistamines in this study were prescription drugs, the United States base their decisions on experienced suc- and these newer antihistamines have fewer adverse effects cess? Evidence-based medicine means incorporating the and cause much less drying than their predecessors, which best evidence into treatment decisions. With limited or no literature addressing the efficacy of each drug class Decongestants were mentioned in as many as a fourth with the separate diagnoses, evidence-based medicine of visits because of rhinosinusitis, and more often acute would indicate that it is appropriate to use personal or rhinosinusitis than chronic rhinosinusitis. The high use of this class of drugs (evaluated separately from antihis- The vast use of these agents makes the statement that tamine combination agents) is understandable consid- they seem to be effective in reducing symptoms or pre- ering the efficacy reports in the literature. In reviewing venting relapse, or they would have been abandoned. An- 5 studies, Arroll24 reports a reduction in nasal airway re- other important possibility is that many patients have self- sistance in patients using these drugs compared with pla- limited disease that will resolve regardless of treatment, cebo. The same study stated that mucolytic agents were and their physicians could be prescribing what they think less reported but that such treatment decreased symp- will work. With time, many infectious processes are re- tom scores when compared with placebo.24 The conclu- solved by the patient’s immune system. To attribute ef- sions of this review rely on primary studies of variable ficacy or curative credit to a drug class based solely on quality. The reviewers were clear about the lack of effi- resolution of symptoms without comparison with non- cacy except in the high-quality studies in which global treated control subjects, physicians could be oversatis- improvement in symptoms was noted. With limited quan- fied with their own prescribing habits.
tifiable data and supportive anecdotal evidence, the high Many physicians might use an ICD-9-CM code to en- use of decongestant and mucolytic agents is logical. Fur- sure that a patient’s insurance will pay for a particular ther, both decongestant and mucolytic agents are avail- medication and not necessarily because the code is for able over the counter; thus, it can be assumed that us- the disease they believe they are treating. The coding could age is even higher than reflected by physician reports.
be questioned if the physician, nurse, or billing clerk maysimply be in the habit of using a few ICD-9-CM codes,regardless of the actual findings or symptoms. Fol- low-up studies might reveal how these trends change.
In evaluating the trends of rhinosinusitis treatment in the Submitted for Publication: April 25, 2006; final revision
United States, many points became apparent. Prescrip- received September 22, 2006; accepted October 29, 2006.
(REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 133, MAR 2007 2007 American Medical Association. All rights reserved.
Correspondence: Hadley J. Sharp, BS, Department of
9. Hinni ML, McCaffrey TV, Kasperbauer JL. Early mucosal changes in experimen- Otolaryngology–Head and Neck Surgery, University of tal sinusitis. Otolaryngol Head Neck Surg. 1992;107:537-548.
10. Stammberger H. Endoscopic endonasal surgery: concepts in treatment of re- Nebraska Medical Center, 5226 B St, Omaha, NE 68106 curring rhinosinusitis, part I: anatomic and pathophysiologic considerations. Oto- laryngol Head Neck Surg. 1986;94:143-147.
Author Contributions: Ms Sharp had full access to all
11. Benninger MS, Anon J, Mabry RL. The medical management of rhinosinusitis.
the data in the study and takes responsibility for the in- Otolaryngol Head Neck Surg. 1997;117(3, pt 2):S41-S49.
tegrity of the data and the accuracy of the data analysis.
12. Sinus and Allergy Health Partnership. Antimicrobial treatment guidelines for acute bacterial rhinosinusitis. Otolaryngol Head Neck Surg. 2000;123:5-31.
Study concept and design: Sharp, Denman, and Leopold.
13. Taccariello M, Parikh A, Darby Y, Scadding G. Nasal douching as a valuable ad- Acquisition of data: Sharp, Puumala, and Leopold. Analy- junct in the management of chronic rhinosinusitis. Rhinology. 1999;37: sis and interpretation of data: Sharp, Puumala, and Leopold.
Drafting of the manuscript: Sharp and Puumala. Critical 14. Reliability of survey estimates—2005 Centers for Disease Control and Preven- revision of the manuscript for important intellectual con- tion: National Center for Health Statistics. http://www.cdc.gov/nchs/about/major/ahcd/reliabilityhtm. Accessed May 10, 2005.
tent: Sharp, Denman, Puumala, and Leopold. Statistical 15. Namyslowski G, Misiolek M, Czecior E, et al. Comparison of the efficacy and tol- analysis: Puumala. Administrative, technical, and mate- erability of amoxycillin/clavulanic acid 875 mg b.i.d. with cefuroxime 500 mg bid rial support: Sharp and Leopold. Study supervision: Sharp in the treatment of chronic and acute exacerbation of chronic sinusitis in adults.
J Chemother. 2002;14:508-517.
Financial Disclosure: None reported.
16. Amsden GW. Anti-inflammatory effects of macrolides: an underappreciated ben- efit in the treatment of community-acquired respiratory tract infections and chronicinflammatory pulmonary conditions? J Antimicrob Chemother. 2005;55:10-21.
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for the treatment of rhinosinusitis: the CAFFS Trial, a randomized controlled trial [published correction appears in JAMA. 2004;292:1686]. JAMA. 2001;286: 2. Meltzer EO, Orgel HA, Backhaus JW, et al. Intranasal flunisolide spray as an ad- junct to oral antibiotic therapy for sinusitis. J Allergy Clin Immunol. 1993;92: 18. McNally PA, White MV, Kaliner MA. Sinusitis in an allergist’s office: analysis of 200 consecutive cases. Allergy Asthma Proc. 1997;18:169-175.
3. Benson V, Marano MA. Current estimates from the National Health Interview Sur- 19. Subramanian HN, Schechtman KB, Hamilos DL. A retrospective analysis of treat- vey, 1992. Vital Health Stat. 1994;10:1-269.
ment outcomes and time to relapse after intensive medical treatment for chronic 4. Anon JB, Jacobs MR, Poole MD, et al. Antimicrobial treatment guidelines for acute sinusitis. Am J Rhinol. 2002;16:303-312.
bacterial rhinosinusitis [published correction appears in Otolaryngol Head Neck 20. Meltzer EO, Hamilos DL, Hadley JA, et al. Rhinosinusitis: establishing defini- Surg. 2004;130:794-796]. Otolaryngol Head Neck Surg. 2004;130:1-45.
tions for clinical research and patient care. Otolaryngol Head Neck Surg. 2004; 5. Gliklich RE, Metson R. The health impact of chronic sinusitis in patients seeking otolaryngologic care. Otolaryngol Head Neck Surg. 1995;113:104-109.
21. Becker J. Allergic rhinitis. http://wwwemedicinecom. Accessed April 15, 2006.
6. Snow V, Mottur-Pilson C, Hickner JM. Principles of appropriate antibiotic use 22. Spector SL, Bernstein IL, Li JT, et al. Parameters for the diagnosis and manage- for acute sinusitis in adults. Ann Intern Med. 2001;134:495-497.
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7. Melen I. Chronic sinusitis: clinical and pathophysiological aspects. Acta Oto- 23. Storms WW, Bodman SF, Nathan RA, et al. SCH 434: a new antihistamine/ laryngol Suppl. 1994;515:45-48.
decongestant for seasonal allergic rhinitis. J Allergy Clin Immunol. 1989;83: 8. Benninger MS, Schmidt JL, Crissman JD, Gottlieb C. Mucociliary function fol- lowing sinus mucosal regeneration. Otolaryngol Head Neck Surg. 1991;105: 24. Arroll B. Non-antibiotic treatments for upper-respiratory tract infections (com- mon cold). Respir Med. 2005;99:1477-1484.
(REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 133, MAR 2007 2007 American Medical Association. All rights reserved.

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