Rostrum Editor’s note: Ths diagnoaia and tmatment of chronic sinusitis conti13uee to be frequently unsatisfactory. In this Restrum attiM, two highly expwi6naed inwstigators in this area of study give their pragmatic approa~has to diagnosis and therapy.
Sinusitis:
A critical need for further
study
Howard M. Druce, MD, and Raymond G. Slavin, MD St. Louis, MO.
In the Ilast few years, we have observed a renaissance of interest in diseases of the paranasal sinuses. The widespread popularity of functional endoscopic sinus surgery, the promotion of over-the-counter sinus remedies, and our understanding and recognition of the connection between sinusitis and asthma have led to increased lay and professional attention. Few, if any, of the novel treatment modalities have been submitted to rigorous prospective study under doubleblind conditions. Thus, their application is largely empirical. In this brief article, we present our clinical approach to sinusitis in a more logical framework for discussion. IS SINUSCTIS OVERDIAGNOSED OR UNfJERDlAGNOSED?
Everyb’ody complains of “sinus.” Patients frequently note chronic nasal congestion, postnasal drip, feelings of facial fullness and headache. Many such patients are given the diagnostic label of “sinusitis.” Although no evidence of infection or inflammation to justify the “sinusitis” is ever documented, brief 7- to lo-day c1oursesof broad-spectrum antibiotics cause resolution of symptoms, but recurrence is frequent. Some Iof these patients are observed after visiting an ear, nose, and throat surgeon, and have undergone minor nasal or sinus surgery (e.g., antral windows or correction of a deviated nasal septum) that again lead only to temporary relief. Alternatively, they may have consulted an allergist who prescribed a course of immunotherapy, again without clear relief. A primary care practitioner may have prescribed frequent 7-day courses of antibiotics.
From the Division of Allergy and Immunology, St. Louis University School of Medicine, St. Louis, MO. Reprint requests: Howard M. Druce, MD, Division of Allergy & Immunology, St. Louis University School of Medicine, 1402 South Grand Blvd., Room R209, St. Louis, MO 63104-1028.
l/1/30598
What is the pathophysiology in these difficult and frustrating patients? In our experience, it is rare for such patients to have received a full evaluation to detect sinus pathology. The typical patient may have had a series of conventional sinus radiographs or a battery of skin tests to detect IgE-mediated allergic sensitivity. WHO MERITS A DIAGNOSTIC
WORKUP?
Patients who complain of recurrent episodes of sinus-associated symptoms deserve a more detailed evaluation under the following circumstances: 1. Symptoms are interfering with activities of daily living (e.g., work or leisure pursuits) 2. Symptoms are recurrent, for example, more than 3 to 4 severe episodes per year 3. Symptoms are not adequately controlled by nonpharmacologic measures (e.g., steam inhalations or saline sprays) or over-the-counter medications 4. Symptoms affect more than one anatomic site, for example, sinus and ears, sinus and teeth, sinus and eye, and sinus and brain 5. Sinus disease associated with distal problems, for example, exacerbations of asthma or chest symptoms perceived by the patient as “bronchitis” or “pneumonia” We plan the workup for such patients (1) to detect the presence of pathology in sinus cavities, (2) to detect anatomic abnormalities that would predispose to this pathology, (3) to detect physiologic changes (e.g., prolonged nasal obstruction) that might predispose to sinus pathology, and (4) to differentiate nasal, sinus, eustachian tube, middle ear, and brain processes. How extensive should the workup
be?
It is not generally feasible to obtain biopsy specimens of sinus tissue, especially from the ethmoid and sphenoid sinuses. Thus, we cannot usually confirm a 675
676
Druce and Slavin
J. ALLERGY
TABLE I. A sample regimen to treat chronic sinus-related symptoms in the absence of concomitant allergic disease
1. Amoxicillin, 500 mg t.i.d. or trimethoprim/sulfamethoxazoleDS, b.i.d., for 21 days 2. Beclomethasone aqueousnasalspray,two sprays b.i.d. for 30 days 3. Guaifenesin,600mg/pseudoephedrine, 120mg, combinationtablets,b.i.d. for 30 days 4. Steaminhalationsb.i.d. for 30 days 5. Nasalsalinespraysor irrigations t.i.d.,
Three times a day; DS, double
strength;
b.i.d.,
twice daily.
diagnosisof sinusitis made by an imaging test. Even when biopsy is feasible, as in the more accessible maxillary sinuses,biopsy specimenstudieshave demonstrated pathologic changesto be patchy. The use of plain sinus radiographshas been questioned. Maxillary sinus mucosal thickening >6 mm hasbeen well demonstratedto correlate with recovery of a high titer of pathogenic organismsfrom a maxillary sinus aspirate.’ The significance of ethmoidal mucosal thickening is less clear. Yet, it is probably more critical in that obstruction in the ethmoid region, especially in the area of the ostiomeatal complex, predisposesto both ethmoid and maxillary disease.’ Computed tomography scanning is currently the diagnostic test of choice to define the anatomy of this region.3*4 Computed tomography scansare required before surgery and after an adequatecourseof medical therapy has not produced complete symptom resolution. In this way, the anatomy of residual untreated diseaseis visualized. It is critical that the physician requestcoronal sectionswith bone-window settings.5 Zinreich et al.5have clearly demonstratedthat mucosal thickening can simply melt away from view with incorrect technical settings of the scanner.Limited series, for example, with cuts every 5 mm in the ethmoid region, are available in many centersfor $100 to $200. This provides a more cost-effective screen than the conventional sinusradiograph series.There was a recent surgeof interest in the useof A-mode ultrasound in the diagnosis of sinusitis.6This interest declined for several reasons. Studies have demonstratedthat this technique is reliable only to detect the presence of maxillary sinus-cavity fluid.’ Since ultrasounddoes not observe maxillary mucosal thickening and ethmoid disease,the limitations are too great. Fiberoptic rhinoscopy can reveal a variety of pathology more posterior in the nasal passagesand nasopharynx.’ Nasal polyposis and lymphoid tissuenot visible on anterior rhinoscopy with the speculumare
CLIN. IMMUNOL. OCTOBER 1991
well displayed. However, the findings areoften subtle. Skill is required not only in merely passingthe endoscopebut alsoin differentiating variations in normal anatomy from pathologic lesions. Perhapsthis investigation should be left in the hands of a practitioner well versedin the procedure. Even the fiberoptic scope does not reveal the maxillary sinus ostia. Rigid endoscopy, after more extensive topical anesthesia,is a techniquewell suitedfor this purpose.’ We order other tests, such as allergy skin testing, only if the history justifies the possiblity of concomitant allergic disease. A history of seasonalexacerbations, exacerbationson specific environmental exposures, or worsening asthmamay prompt such tests.
HOW SHOULD
WE TREAT SINUSITIS?
If the imaging tests imply chronic pathology, appropriate therapy is needed. In all patients that have not had an adequatetrial of multimodal medical therapy, we start a l-month long regimen designedto: 1. Treat any bacterial infection present in the sinus cavities 2. Reduceswelling at the sinusostia, which is usually inflammatory in nature (whether initially provoked by an allergy, infection, or irritation) 3. Institute drainageof sinussecretionsand abnormal contents 4. Promote continued sinusdrainage after resolution of symptoms Welist such a regimen in Table I. Admittedly, such a regimen is empiric but is based on the following rationale: We use a broad-spectrumantibiotic to treat any infection present. Seven- or lo-day antibiotic coursessterilize infected maxillary sinusfluid asdemonstratedin well-controlled studiesin acute sinusitis.lo Yet, in most chronic cases,ethmoid diseaseis present and is recalcitrant to this brief treatment. We thus prescribe antibiotics for a minimum of 2 1 days. In most adults, who would reveal mixed flora on maxillary sinus aspiration, drugs, such as amoxicillin or sulfa trimethoprim generally suffice if they are adminisfered at adequatedoses.” In children and resistant adult casesin which Moraxellu cuturrhalis is the predominant pathogen, amoxicillin/ clavulanate is currently the antibiotic of choice.” The temptation to treat recurrent episodeswith successiveshort courses of increasingly potent, and expensive, agents alone shouldbe vigorously resisted.Persistenceof frank pus should prompt the need for aerobic, anaerobic, and perhapsfungal cultures. We usea variety of adjunctive therapiesat the same time as the antibiotics. l3 Topical corticosteroids (beclomethasone, flunisolide, or budesonide) may theo-
VOLUME NUMBER
Sinusitis
BE 4
retically increase sinus ostial diameter by reducing inflamma.tion in the area of the sinus ostia. We have not observed evidence that they may induce superinfection or encourage development of resistant organisms. Data clearly demonstrating their clinical efficacy as adjunctive therapy have not yet been produced. Several large clinical trials are in progress. We use high-dose guaifenesin for its theoretical ability to thin tenacious respiratory secretions, based on data derived from its effects on sputum. Oral aadrenerg:lc agonists have a documented ability to increase ostial patency.14 There has been a concern that a-sympathomimetics may cause ciliary stasis that might counteract any beneficial effect. However, the presence of pus in active infection inhibits ciliary activity; therefore, the clinical effects are not apparent. Steam and saline prevent crusting of secretions in the nasal cavity and especially in the region of the ostiomeatal complex. By liquefying secretions, they also help mucociliary clearance. Repetitive saline applications also act as a mild vasoconstrictor of nasal blood flow. I5 Antihistamines and other “allergy” medications are generally withheld unless the patient has a history of concomitant allergic disease, supported by appropriate positive laboratory tests. There is yet no clear evidence that the use of these adjunctive agents prolongs the symptom-free period or reduces the eventual need for surgery. In chronic cases with anatomic reasons to prevent sinus drainage, surgery is the ultimate mode of therapy. Because patients present with a variety of symptoms, it is hard to conceive a scientifically valid study based on objective parameters. A “sham” surgical procedure to ensure blinding would be unethical. Since the use of adjunctive agents has become the accepted “standard of care,” tt is difficult to withhold these agents. WHAT QUESTIONS UNANSWERED?
REMAIN
We recognize sinusitis and nasal disease as the most prevalent of the chronic diseases. I6 They cause morbidity and widespread economic hardship. Yet, our current research leaves many questions unanswered. We half jokingly believe that we need an Institute of Nonaller,gy and Noninfectious Diseases to champion research on these diseases, which reflect the pathologic consequences of chronic inflammation. The relationship between sinus symptoms and allergic disease, sinus symptoms in the absence of infection, fungal sinusitis, and sinusitis and asthma need additional elucidation. For the present, it is important that
677
we do not accept uncritically the diagnosis of sinusitis. We should investigate those patients who suffer from chronic symptoms, attempt to localize disease, and provide a treatment program based on rational principles. In the future, we hope we can support this empirical action with studies that provide scientific validity. We thank
Maria
J. Weingartner
for excellent
secretarial
support.
REFERENCES I. Evans FO Jr, Sydnor JB, Moore WEC, et al. Sinusitis of the maxillary antrum. N Engl J Med 197$293:735-g. 2. McAlister WH, Lusk R, Muntz HR. Comparison of plain radiographs and coronal CT scans in infants and children with recurrent sinusitis. Am J Radio1 1989;153:1259-64. 3. Carter BL, Runge VS. Imaging modalities for the study of the paranasal sinuses and nasopharynx. Otolatyngol Clin North Am 1988;21:395-417. 4. Zinreich SJ. Paranasal sinus imaging. Otolaryngol Head Neck Surg 1990;103:863-9. 5. Zinreich SJ, Kennedy DW, Rosenbaum AE, Gayler BW, Kumar AI, Stammberger H. Paransal sinuses: CT imaging requirements for endoscopic surgery. Radiology 1987;163: 769-5. 6. Druce HM. Emerging techniques in the diagnosis of sinusitis. Ann Allergy 1991;66;132-6. I. Rohr AS, Spector SL, Siegel SC, Katz RM, Rachelefsky GS. Correlation between A-mode ultrasound and radiography in the diagnosis of maxillary sinusitis. J ALLERGY CLIN IMMUNOL 1986;78:58-61. 8. Selner JC, Koepke JW. Rhinolaryngoscopy in the allergy office. Ann Allergy 1985;54:479-82. 9. Stammberger H. Nasal and paranasal sinus endoscopy: a diagnostic and surgical approach to recurrent sinusitis. Endoscopy 1986;18:213-8. 10. Winther B, Gwaltney JM. Therapeutic approach to sinusitis: antiinfectious therapy as the baseline of management. Otolaryngology Head Neck Surg 1990;103:876-9. 11. Druce HM. Diagnosis and management of chronic sinusitis and its complications. Immunol Allergy Clin N Am 1987;7;117-31. 12. Goldenhersh MJ, Rachelefsky GS, Dudley J, et al. The microbiology of chronic sinus disease in children with respiratory allergy. J ALLERGY CLIN IMMUNOL 1990;85: 1030-9. 13 Druce HM. Adjuncts to medical management of sinusitis. Otolaryngol Head Neck Surg 1990;103:880-3. 14. Melen I, Friberg B, Andreasson L, Ivarsson A, Jannert M. Johansson C-J. Effects of phenolpropanolamine on ostial and nasal patency in patients treated for chronic maxillary sinusitis. Acta Otolaryngol 1986;101:494-500. 15 Druce HM, Bonner RF, Patow C, Choo P, Summers RJ, Kaliner MA. Response of nasal blood flow to nemohormones as measured by laser-Doppler velocimetry. J Appl Physiol: Respirat Environ Exercise Physiol 1984;57(4): 1276-83. 16 NIH data book 1990, table 44, page 76. National Institutes of Health publication 90-1261, Bethesda, Md.: Department of Health and Human Services.
Sinusitis:
A critical need for further
study
Howard M. Druce, MD, and Raymond G. Slavin, MD St. Louis, MO.
In the Ilast few years, we have observed a renaissance of interest in diseases of the paranasal sinuses. The widespread popularity of functional endoscopic sinus surgery, the promotion of over-the-counter sinus remedies, and our understanding and recognition of the connection between sinusitis and asthma have led to increased lay and professional attention. Few, if any, of the novel treatment modalities have been submitted to rigorous prospective study under doubleblind conditions. Thus, their application is largely empirical. In this brief article, we present our clinical approach to sinusitis in a more logical framework for discussion. IS SINUSCTIS OVERDIAGNOSED OR UNfJERDlAGNOSED?
Everyb’ody complains of “sinus.” Patients frequently note chronic nasal congestion, postnasal drip, feelings of facial fullness and headache. Many such patients are given the diagnostic label of “sinusitis.” Although no evidence of infection or inflammation to justify the “sinusitis” is ever documented, brief 7- to lo-day c1oursesof broad-spectrum antibiotics cause resolution of symptoms, but recurrence is frequent. Some Iof these patients are observed after visiting an ear, nose, and throat surgeon, and have undergone minor nasal or sinus surgery (e.g., antral windows or correction of a deviated nasal septum) that again lead only to temporary relief. Alternatively, they may have consulted an allergist who prescribed a course of immunotherapy, again without clear relief. A primary care practitioner may have prescribed frequent 7-day courses of antibiotics.
From the Division of Allergy and Immunology, St. Louis University School of Medicine, St. Louis, MO. Reprint requests: Howard M. Druce, MD, Division of Allergy & Immunology, St. Louis University School of Medicine, 1402 South Grand Blvd., Room R209, St. Louis, MO 63104-1028.
l/1/30598
What is the pathophysiology in these difficult and frustrating patients? In our experience, it is rare for such patients to have received a full evaluation to detect sinus pathology. The typical patient may have had a series of conventional sinus radiographs or a battery of skin tests to detect IgE-mediated allergic sensitivity. WHO MERITS A DIAGNOSTIC
WORKUP?
Patients who complain of recurrent episodes of sinus-associated symptoms deserve a more detailed evaluation under the following circumstances: 1. Symptoms are interfering with activities of daily living (e.g., work or leisure pursuits) 2. Symptoms are recurrent, for example, more than 3 to 4 severe episodes per year 3. Symptoms are not adequately controlled by nonpharmacologic measures (e.g., steam inhalations or saline sprays) or over-the-counter medications 4. Symptoms affect more than one anatomic site, for example, sinus and ears, sinus and teeth, sinus and eye, and sinus and brain 5. Sinus disease associated with distal problems, for example, exacerbations of asthma or chest symptoms perceived by the patient as “bronchitis” or “pneumonia” We plan the workup for such patients (1) to detect the presence of pathology in sinus cavities, (2) to detect anatomic abnormalities that would predispose to this pathology, (3) to detect physiologic changes (e.g., prolonged nasal obstruction) that might predispose to sinus pathology, and (4) to differentiate nasal, sinus, eustachian tube, middle ear, and brain processes. How extensive should the workup
be?
It is not generally feasible to obtain biopsy specimens of sinus tissue, especially from the ethmoid and sphenoid sinuses. Thus, we cannot usually confirm a 675
676
Druce and Slavin
J. ALLERGY
TABLE I. A sample regimen to treat chronic sinus-related symptoms in the absence of concomitant allergic disease
1. Amoxicillin, 500 mg t.i.d. or trimethoprim/sulfamethoxazoleDS, b.i.d., for 21 days 2. Beclomethasone aqueousnasalspray,two sprays b.i.d. for 30 days 3. Guaifenesin,600mg/pseudoephedrine, 120mg, combinationtablets,b.i.d. for 30 days 4. Steaminhalationsb.i.d. for 30 days 5. Nasalsalinespraysor irrigations t.i.d.,
Three times a day; DS, double
strength;
b.i.d.,
twice daily.
diagnosisof sinusitis made by an imaging test. Even when biopsy is feasible, as in the more accessible maxillary sinuses,biopsy specimenstudieshave demonstrated pathologic changesto be patchy. The use of plain sinus radiographshas been questioned. Maxillary sinus mucosal thickening >6 mm hasbeen well demonstratedto correlate with recovery of a high titer of pathogenic organismsfrom a maxillary sinus aspirate.’ The significance of ethmoidal mucosal thickening is less clear. Yet, it is probably more critical in that obstruction in the ethmoid region, especially in the area of the ostiomeatal complex, predisposesto both ethmoid and maxillary disease.’ Computed tomography scanning is currently the diagnostic test of choice to define the anatomy of this region.3*4 Computed tomography scansare required before surgery and after an adequatecourseof medical therapy has not produced complete symptom resolution. In this way, the anatomy of residual untreated diseaseis visualized. It is critical that the physician requestcoronal sectionswith bone-window settings.5 Zinreich et al.5have clearly demonstratedthat mucosal thickening can simply melt away from view with incorrect technical settings of the scanner.Limited series, for example, with cuts every 5 mm in the ethmoid region, are available in many centersfor $100 to $200. This provides a more cost-effective screen than the conventional sinusradiograph series.There was a recent surgeof interest in the useof A-mode ultrasound in the diagnosis of sinusitis.6This interest declined for several reasons. Studies have demonstratedthat this technique is reliable only to detect the presence of maxillary sinus-cavity fluid.’ Since ultrasounddoes not observe maxillary mucosal thickening and ethmoid disease,the limitations are too great. Fiberoptic rhinoscopy can reveal a variety of pathology more posterior in the nasal passagesand nasopharynx.’ Nasal polyposis and lymphoid tissuenot visible on anterior rhinoscopy with the speculumare
CLIN. IMMUNOL. OCTOBER 1991
well displayed. However, the findings areoften subtle. Skill is required not only in merely passingthe endoscopebut alsoin differentiating variations in normal anatomy from pathologic lesions. Perhapsthis investigation should be left in the hands of a practitioner well versedin the procedure. Even the fiberoptic scope does not reveal the maxillary sinus ostia. Rigid endoscopy, after more extensive topical anesthesia,is a techniquewell suitedfor this purpose.’ We order other tests, such as allergy skin testing, only if the history justifies the possiblity of concomitant allergic disease. A history of seasonalexacerbations, exacerbationson specific environmental exposures, or worsening asthmamay prompt such tests.
HOW SHOULD
WE TREAT SINUSITIS?
If the imaging tests imply chronic pathology, appropriate therapy is needed. In all patients that have not had an adequatetrial of multimodal medical therapy, we start a l-month long regimen designedto: 1. Treat any bacterial infection present in the sinus cavities 2. Reduceswelling at the sinusostia, which is usually inflammatory in nature (whether initially provoked by an allergy, infection, or irritation) 3. Institute drainageof sinussecretionsand abnormal contents 4. Promote continued sinusdrainage after resolution of symptoms Welist such a regimen in Table I. Admittedly, such a regimen is empiric but is based on the following rationale: We use a broad-spectrumantibiotic to treat any infection present. Seven- or lo-day antibiotic coursessterilize infected maxillary sinusfluid asdemonstratedin well-controlled studiesin acute sinusitis.lo Yet, in most chronic cases,ethmoid diseaseis present and is recalcitrant to this brief treatment. We thus prescribe antibiotics for a minimum of 2 1 days. In most adults, who would reveal mixed flora on maxillary sinus aspiration, drugs, such as amoxicillin or sulfa trimethoprim generally suffice if they are adminisfered at adequatedoses.” In children and resistant adult casesin which Moraxellu cuturrhalis is the predominant pathogen, amoxicillin/ clavulanate is currently the antibiotic of choice.” The temptation to treat recurrent episodeswith successiveshort courses of increasingly potent, and expensive, agents alone shouldbe vigorously resisted.Persistenceof frank pus should prompt the need for aerobic, anaerobic, and perhapsfungal cultures. We usea variety of adjunctive therapiesat the same time as the antibiotics. l3 Topical corticosteroids (beclomethasone, flunisolide, or budesonide) may theo-
VOLUME NUMBER
Sinusitis
BE 4
retically increase sinus ostial diameter by reducing inflamma.tion in the area of the sinus ostia. We have not observed evidence that they may induce superinfection or encourage development of resistant organisms. Data clearly demonstrating their clinical efficacy as adjunctive therapy have not yet been produced. Several large clinical trials are in progress. We use high-dose guaifenesin for its theoretical ability to thin tenacious respiratory secretions, based on data derived from its effects on sputum. Oral aadrenerg:lc agonists have a documented ability to increase ostial patency.14 There has been a concern that a-sympathomimetics may cause ciliary stasis that might counteract any beneficial effect. However, the presence of pus in active infection inhibits ciliary activity; therefore, the clinical effects are not apparent. Steam and saline prevent crusting of secretions in the nasal cavity and especially in the region of the ostiomeatal complex. By liquefying secretions, they also help mucociliary clearance. Repetitive saline applications also act as a mild vasoconstrictor of nasal blood flow. I5 Antihistamines and other “allergy” medications are generally withheld unless the patient has a history of concomitant allergic disease, supported by appropriate positive laboratory tests. There is yet no clear evidence that the use of these adjunctive agents prolongs the symptom-free period or reduces the eventual need for surgery. In chronic cases with anatomic reasons to prevent sinus drainage, surgery is the ultimate mode of therapy. Because patients present with a variety of symptoms, it is hard to conceive a scientifically valid study based on objective parameters. A “sham” surgical procedure to ensure blinding would be unethical. Since the use of adjunctive agents has become the accepted “standard of care,” tt is difficult to withhold these agents. WHAT QUESTIONS UNANSWERED?
REMAIN
We recognize sinusitis and nasal disease as the most prevalent of the chronic diseases. I6 They cause morbidity and widespread economic hardship. Yet, our current research leaves many questions unanswered. We half jokingly believe that we need an Institute of Nonaller,gy and Noninfectious Diseases to champion research on these diseases, which reflect the pathologic consequences of chronic inflammation. The relationship between sinus symptoms and allergic disease, sinus symptoms in the absence of infection, fungal sinusitis, and sinusitis and asthma need additional elucidation. For the present, it is important that
677
we do not accept uncritically the diagnosis of sinusitis. We should investigate those patients who suffer from chronic symptoms, attempt to localize disease, and provide a treatment program based on rational principles. In the future, we hope we can support this empirical action with studies that provide scientific validity. We thank
Maria
J. Weingartner
for excellent
secretarial
support.
REFERENCES I. Evans FO Jr, Sydnor JB, Moore WEC, et al. Sinusitis of the maxillary antrum. N Engl J Med 197$293:735-g. 2. McAlister WH, Lusk R, Muntz HR. Comparison of plain radiographs and coronal CT scans in infants and children with recurrent sinusitis. Am J Radio1 1989;153:1259-64. 3. Carter BL, Runge VS. Imaging modalities for the study of the paranasal sinuses and nasopharynx. Otolatyngol Clin North Am 1988;21:395-417. 4. Zinreich SJ. Paranasal sinus imaging. Otolaryngol Head Neck Surg 1990;103:863-9. 5. Zinreich SJ, Kennedy DW, Rosenbaum AE, Gayler BW, Kumar AI, Stammberger H. Paransal sinuses: CT imaging requirements for endoscopic surgery. Radiology 1987;163: 769-5. 6. Druce HM. Emerging techniques in the diagnosis of sinusitis. Ann Allergy 1991;66;132-6. I. Rohr AS, Spector SL, Siegel SC, Katz RM, Rachelefsky GS. Correlation between A-mode ultrasound and radiography in the diagnosis of maxillary sinusitis. J ALLERGY CLIN IMMUNOL 1986;78:58-61. 8. Selner JC, Koepke JW. Rhinolaryngoscopy in the allergy office. Ann Allergy 1985;54:479-82. 9. Stammberger H. Nasal and paranasal sinus endoscopy: a diagnostic and surgical approach to recurrent sinusitis. Endoscopy 1986;18:213-8. 10. Winther B, Gwaltney JM. Therapeutic approach to sinusitis: antiinfectious therapy as the baseline of management. Otolaryngology Head Neck Surg 1990;103:876-9. 11. Druce HM. Diagnosis and management of chronic sinusitis and its complications. Immunol Allergy Clin N Am 1987;7;117-31. 12. Goldenhersh MJ, Rachelefsky GS, Dudley J, et al. The microbiology of chronic sinus disease in children with respiratory allergy. J ALLERGY CLIN IMMUNOL 1990;85: 1030-9. 13 Druce HM. Adjuncts to medical management of sinusitis. Otolaryngol Head Neck Surg 1990;103:880-3. 14. Melen I, Friberg B, Andreasson L, Ivarsson A, Jannert M. Johansson C-J. Effects of phenolpropanolamine on ostial and nasal patency in patients treated for chronic maxillary sinusitis. Acta Otolaryngol 1986;101:494-500. 15 Druce HM, Bonner RF, Patow C, Choo P, Summers RJ, Kaliner MA. Response of nasal blood flow to nemohormones as measured by laser-Doppler velocimetry. J Appl Physiol: Respirat Environ Exercise Physiol 1984;57(4): 1276-83. 16 NIH data book 1990, table 44, page 76. National Institutes of Health publication 90-1261, Bethesda, Md.: Department of Health and Human Services.
