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Use of ipratropium bromide nasal spray in chronic treatment of nonallergic perennial rhinitis, alone and in combination with other perennial rhinitis medications
Use of ipratropium bromide nasal spray in chronic treatment of nonallergic perennial rhinitis, alone and in combination with other perennial rhinitis medications Jay Grossman, MD, Charles Banov, MD, Peter Boggs, MD, Edwin A. Bronsky, MD, Robert J. Dockhorn, MD, Howard Druce, MD, Steven R. Findlay, MD, John W. Georgitis, MD, Frank C. Hampel, MD, Harold Kaiser, MD, Paul Ratner, MD, David G. Tinkelman, MD, Martin D. Valentine, MD, Paul Roszko, RPh," Elena Zegarelli, PhD," and Chester Wood, MD a Albany, N.Y., Charleston, S.C., Shreveport, La., Salt Lake City, Utah, Prairie Village, Kan., St. Louis, Mo., Austin, Texas, WinstonSalem, AT.C., New Braunfels, Texas, Minneapolis, Minn., San Antonio, Texas, Atlanta, Ga., Baltimore, Md., and Ridgefield, Conn. ~ To study the long-term safety and effectiveness of ipratropium bromide nasal spray 0.03% in the treatment of nonallergic perennial rhinitis, we administered this medication for 1 year in an open-label trial involving 285 patients. Our intention was to maintain the highest protocol dose possible to gain a clearer picture of the long-term side effect profile of the compound. Ipratropium bromide was well tolerated with no serious side effects in this patient population. It provided a significant improvement in rhinorrhea throughout the year-long tria# only 17 of 285 patients (6%) were considered treatment failures. There was an improvement in patient quality of life, as well as a substantial reduction in the need for other medications (antihistamines, decongestants, and nasal steroids) used to treat perennial rhinitis symptoms. (J ALLERGY CLIN IMMUNOL1995;95:1123-7.) Key words: Nonallergic rhinitis, ipratropium, nasal spray, safety, efficacy, chronic
Perennial nonallergic rhinitis (PNAR) is an enigmatic disorder that affects millions of Americans every year, with no known specific etiology. The diagnosis of PNAR is usually one of exclusion after ruling out identifiable causes such as atopy and infection. Clinically, PNAR can include rhinorrhea associated with eosinophilia, "vasomotor" rhinitis (sometimes equated with PNAR), rhinitis medicamentosa, and miscellaneous other disorders. Mygind et al. 1 propose that the term be used for any chronic, nonpurulent rhinorrhea of "unknown etiology." To add to the confusion surrounding terminology and diagnosis, PNAR does not always coincide with obvious inflammation in spite of the "rhinitis" designation. Reprint requests: Jay Grossman, MD, Allergy Care Consultants, 3395 N. CampbellAve., Tucson, AZ 85719. Copyright © 1995 by Mosby-Year Book, Inc. 0091-6749/95 $3.00 + 0 1/0/63458
Abbreviation used PNAR: Perennial nonallergic rhinitis
If we use the definition of Mygind et al., it soon becomes apparent that a significant proportion of the population suffers from PNAR, no matter how poorly the etiology of the disease is understood. In evaluating the differences between allergic and nonallergic rhinitis in 142 patients, Mullarkey et al? determined that 52% could be classified as having nonallergic rhinitis either with eosinophilia (15%) or without (37%). If 10% to 20% of the population has allergic rhinitis and roughly 50% of all rhinitis sufferers are nonallergic, then the incidence of PNAR may well extend into the tens of millions in the United States alone. Physician Drug and Diagnosis Audit data 3 indicate that as many as
1123
1124
Grossman
e t al.
J ALLERGY CLIN IMMUNOL MAY 1995
TABLE III. incidence of selected adverse events in 1-year open-label trials
TABLE I. Baseline demographics and site of nasal discharge
No. of patients entered Sex Males Females Age Range Mean Race White Black Other Weight (Mean) Site of nasal discharge Anterior Posterior Anterior/posterior
285
Ipratropium bromide 0.03% 42 ~g/nostril tid
87 (31%) 198 (69%)
First 6 mo Second 6 mo
21-74 yr 44.3 -+ 13.6 yr 267 (94%) 7 (2%) 11 (4%) 155.2 + 35.6 lb 84 (29.5%) 23 (8.1%) 178 (62.5%)
TABLE II. Patient dose status in 1-year trial of ipratropium bromide nasal spray No. of patients
Total treated* Ipratropium bromide 0.03% dose 2 sprays/tid 1 spray/tid 2 sprays/bid 1 spray/bid 2 sprays/qd 1 spray/qd
3mo
6mo
9mo
12mo
232
200
179
159
223 3 3 2 1 0
179 14 6 1 0 0
155 15 6 1 0 2
138 11 7 2 1 0
Source Data: Case Report form Tabulations. t/d, Three times daily; bid, Twice daily; qd, every day. *Fifty-three patients were discontinued before completion of 3 months of open-label treatment. 4 million visits to the doctor's office per year may be attributable to PNAR. This is probably an underestimate. To date there has been no specific, effective therapy for the rhinorrhea associated with PNAR. Corticosteroids reduce the inflammation associated with rhinitis, but their effects are not specific to rhinorrhea, and many P N A R sufferers do not have detectable inflammation. The other available therapies--antihistamines, decongestants, and crom o l y n - - a r e even less specific than the corticosteroids and are generally known to be less effective in P N A R than in allergic rhinitis. Ipratropium bromide, an anticholinergic agent that blocks the action of acetylcholine, has been shown to reduce
Total treated Total any adverse event Total any nasal adverse event Upper respiratory tract infection Sinusitis Headache Pharyngitis Epistaxis Nasal dryness Nasal irritation Other nasal symptoms Nasal congestion
(%)
(%)
285 198 (69.5) 59 (20.7) 64 (22.5)
200 128 (64.0) 40 (20.0) 50 (25.0)
34 (11.9) 24 (8.4) 23 (8.1) 12 (4.2) 23 (8.1) 14 (4.9) 25 (8.8) 21 (7.4)
18 (9.0) 10 (5.0) 9 (4.5) 5 (2.5) 7 (3.5) 7 (3.5) 24 (12.0) 15 (7.5)
significantly the rhinorrhea associated with P N A R 4 with few adverse effects. These results are not inconsistent with the theory that P N A R is, in most cases, a "vasomotor" or hyperreactive cholinergic disorder? The short-term safety and efficacy of ipratropium nasal spray in P N A R have been assessed in a large, multicenter, double-blind study (see Bronsky et al. in this supplement). The purpose of our open-label trial was to study the effects of long-term ipratropium therapy in these P N A R patients for 1 full year, to establish a clearer safety profile of the drug and to evaluate its long-term efficacy. MATERIAL
AND
METHODS
Two hundred eighty-five patients with PNAR were followed for up to 1 year; 198 were women (see Table I for a summary of demographics). The mean age of patients was 44 years, (range, 21 to 74 years). The mean duration of disease was 17 years. All patients had year-round nasal symptoms with negative skin tests to perennial allergens. During the first 6 months, patients were maintained on the highest dose permitted by the protocol--two sprays per nostril of ipratropium bromide nasal spray 0.03% administered three times daily. Exceptions were made only if they were unable to tolerate this dose. In the last 6 months of the study, the dose could be decreased at the discretion of the physician to the lowest amount required to control rhinorrhea. Two hundred patients were treated for more than 6 months; 159 were treated for more than 1 year. Most patients (>80%) were maintained on the original dose of two sprays (42 ~g per nostril) three times daily throughout the study (Table II). A nasal examination was performed at each visit.
J ALLERGY CLIN IMMUNOL VOLUME 95, NUMBER 5, PART 2
Grossman
SNEEZING ,,z, .l
RHINORRHEA
Physician
90-
~ 90-
J
w
80-
tll
1125
100 -
100 I-
et al,
Physician
_ _......-.0
80-
Patient 70-
~70O
O
8 6o-
8 60-
50
50 8
16
24
32
4;
&
1;
5;
90-
o
80-
31
4'o
&
5;
28
56
NASAL CONGESTION
POSTNASAL DRIP 100-
~
21
WEEKSTREATED
WEEKSTREATED
9 00 ]
1 Patient
..t- ....
70O
O
8 6o50
8
1;
24
32
40
48
5;
WEEKSTREATED
6°1 5o I 0
1;
24
32
4;
WEEKSTREATED
FIG. 1. Patient and physician long-term global assessments of effectiveness of ipratropium bromide nasal spray in PNAR.
Physical examinations and laboratory tests were performed on the final visit or the visit at which the patient was discontinued from the trial. At each visit, patients and physicians separately recorded their impressions of the effectiveness of ipratropium bromide against rhinorrhea, postnasal drip, congestion, and sneezing. Efficacy evaluations included treatment failures, quality of life assessments of the degree of interference with daily activities and moods caused by rhinorrhea and congestion, and the need for concomitant perennial rhinitis medications. Safety was assessed by reviewing adverse events, laboratory results, and physician evaluations. RESULTS
The long-term use of ipratropium bromide nasal spray by patients with P N A R was well tolerated in this trial and was not associated with any serious or systemic drug-related adverse effects. Only 10% of patients were discontinued during the year-long study because of adverse events; half of these were considered potentially drug related by the investigators. The most common non-nasal adverse events were upper respiratory tract infections, sinusitis, headache, and pharyngitis. None of these appeared to be attributable to treatment with
TABLE IV. Use of standard perennial rhinitis medications concomitantly with ipratropium bromide (n = 219)
Baseline During long-term
Any use 161 (56%) Long-term use (>3 mo) 74 (26%)
97 (34%) 37 (13%)
ipratropium bromide. The two most frequent nasal adverse events were nasal dryness (10%) and epistaxis (4%). The incidence of these events was higher in the first than in the second 6 months of t r e a t m e n t - - 8 % versus 4% and 4% versus 3%, respectively. The decrease in incidence was not due to discontinuation; improvement in adverse effects was attributable to better tolerance with continued treatment, dose reduction, or both. Table Ill summarizes selected adverse events. Patient and physician global assessments suggested that long-term treatment with ipratropium bromide nasal spray offers sustained efficacy for controlling rhinorrhea in PNAR. There was no decrease in effectiveness during the 1-year trial
1126
Grossman et al.
100 90 I.tl 80 Z 70 Lkl rr 60 W r~ 50 40 I-_z 30 20 10 0
Physical Activity (n=215)
J ALLERGYCLIN IMMUNOL MAY 1995
Mental Work (n=217)
Tired (n=182
Irritable (n=183)
Sleeping (n=221)
[ ] Baseline
Reading (n=218)
Depressed (n=140)
Anxious (n=159)
[ ] End of Treatment
FIG. 2. A s s e s s m e n t of quality of life after 1 year of long-term t r e a t m e n t with i p r a t r o p i u m b r o m i d e in patients with PNAR.
TABLE V. Change in nasal examination after 1 year of treatment with ipratropium bromide nasal spray No. of patients (%) Baseline
Total treated Degree of mucosal edema None/mild Moderate/severe Color of nasal mucosa Normal Red Pale Quantity of rhinorrhea None/Scanty Some/profuse Postnasal drip Not present Present
At completion of long-term
273
273
125 (45.8) 148 (54.2)
190 (69.6) 83 (30.4)
75 (27.5) 137 (50.2) 54 (19.8)
110 (40.3) 125 (45.8) 33 (12.1)
140 (51.3) 133 (48.8)
209 (76.9) 63 (23.1)
162 (59.3) 111 (40.7)
197 (72.2) 76 (27.8)
ity of life and a significant reduction in the degree to which rhinorrhea and congestion interfered with the patients' day-to-day activities and moods (Fig.
2). Nasal examinations done at each visit by direct anterior rhinoscopy revealed no detrimental effects with long-term use of ipratropium bromide nasal spray. Indeed, some objective improvement was noted, including a normalization of the color of the mucosa, a reduction in mucosal edema and a reduction in rhinorrhea and postnasal drip (Table V). Therefore rhinoscopy was supportive of patient and physician assessments of control of nasal symptoms. DISCUSSION
(Fig. 1). The data indicate that long-term use of ipratropium bromide may also contribute to the control of congestion, postnasal drip and sneezing. Only 17 of 285 patients (6%) were considered to have failed treatment. There was a substantial reduction in the need for concomitant, long-term perennial rhinitis medications, from 26% at the start of the study to 13% during long-term treatment with ipratropium bromide (Table IV). The clinical benefit of long-term treatment was further demonstrated by an improvement in patient qual-
The rhinorrhea associated with PNAR is generally regarded as a nuisance, but it can be severe enough to have a significant negative impact on patient daily moods and activities and require a large number of physician visits. To date there have been no effective treatments specifically for PNAR-induced rhinorrhea. The drugs commonly used to treat PNAR--steroids, antihistamines and decongestants--are not as effective in this hyperreactive condition as in allergic rhinitis; also, none are specific to rhinorrhea. One of the problems physicians face with PNAR is the need for a long-term therapy that does not induce tolerance. Because rhinorrhea is an annoyance and not a life-threatening condition, there is also a need for a therapy that is safe and well tolerated. Our long-term, multicenter experience with ipratropium bromide nasal spray 0.03% indicates
J ALLERGYCLIN IMMUNOL
G r o s s m a n et
al.
1127
VOLUME 95, NUMBER 5, PART 2
that it is a safe and effective treatment for the control of rhinorrhea associated with PNAR. Most of the adverse effects coincident to the use of intranasal ipratropium appear to be mild, and in many cases they are either transient or can be successfully managed by reducing the dosage. In our study ipratropium bromide nasal spray significantly reduced the need for other perennial rhinitis medications. Therefore it would not seem unreasonable to use ipratropium as maintenance therapy for PNAR, adding antihistamines and decongestants only as needed. Many patients with P N A R use more than one medication; there was no evidence during the trial of increased side effects when ipratropium bromide was used with other P N A R treatments. The fact that ipratropium bromide was well tolerated over the year-long study indicates that it will be useful in long-term maintenance therapy. It is also significant that patients with P N A R perceived an improvement in quality of life with
ipratropium use. Finally, the gradual improvement over the course of the year in other PNAR symptoms, such as postnasal drip, sneezing, and congestion, suggests that there may be a significant cholinergic component to this difficult to treat disorder. REFERENCES
1. MygindN, Anggard A, Druce HM. Definition,classification and terminology.In: MygindM, Weeke B, eds. Allergic and vasomotor rhinitis; clinical aspects. Copenhagen: Munksgaard, 1985:17. 2. MullarkeyMF, Hill JS, Webb DR. Allergic and nonallergic rhinitis: their characterizationwith attention to the meaning of nasal eosinophilia. J ALLERGYCLINIMMUNOL1980;65: 122-6. 3. Scott-Levin Physician Drug and Diagnosis Audit, August 1994. Newton, Pa.: Scott Levin Associates, 4. DruceHM, Spector SL, Fireman P, et al. Double-blindstudy of intranasal ipratropium bromide in nonallergic perennial rhinitis. Ann Allergy 1992;69:53-60. 5. Borum P, Mygind N, Scholtz Larsen F. Intranasal ipratropium: a new treatment for perennial rhinitis. Clin Otolaryngol 1979;4:407-11.
Perennial nonallergic rhinitis (PNAR) is an enigmatic disorder that affects millions of Americans every year, with no known specific etiology. The diagnosis of PNAR is usually one of exclusion after ruling out identifiable causes such as atopy and infection. Clinically, PNAR can include rhinorrhea associated with eosinophilia, "vasomotor" rhinitis (sometimes equated with PNAR), rhinitis medicamentosa, and miscellaneous other disorders. Mygind et al. 1 propose that the term be used for any chronic, nonpurulent rhinorrhea of "unknown etiology." To add to the confusion surrounding terminology and diagnosis, PNAR does not always coincide with obvious inflammation in spite of the "rhinitis" designation. Reprint requests: Jay Grossman, MD, Allergy Care Consultants, 3395 N. CampbellAve., Tucson, AZ 85719. Copyright © 1995 by Mosby-Year Book, Inc. 0091-6749/95 $3.00 + 0 1/0/63458
Abbreviation used PNAR: Perennial nonallergic rhinitis
If we use the definition of Mygind et al., it soon becomes apparent that a significant proportion of the population suffers from PNAR, no matter how poorly the etiology of the disease is understood. In evaluating the differences between allergic and nonallergic rhinitis in 142 patients, Mullarkey et al? determined that 52% could be classified as having nonallergic rhinitis either with eosinophilia (15%) or without (37%). If 10% to 20% of the population has allergic rhinitis and roughly 50% of all rhinitis sufferers are nonallergic, then the incidence of PNAR may well extend into the tens of millions in the United States alone. Physician Drug and Diagnosis Audit data 3 indicate that as many as
1123
1124
Grossman
e t al.
J ALLERGY CLIN IMMUNOL MAY 1995
TABLE III. incidence of selected adverse events in 1-year open-label trials
TABLE I. Baseline demographics and site of nasal discharge
No. of patients entered Sex Males Females Age Range Mean Race White Black Other Weight (Mean) Site of nasal discharge Anterior Posterior Anterior/posterior
285
Ipratropium bromide 0.03% 42 ~g/nostril tid
87 (31%) 198 (69%)
First 6 mo Second 6 mo
21-74 yr 44.3 -+ 13.6 yr 267 (94%) 7 (2%) 11 (4%) 155.2 + 35.6 lb 84 (29.5%) 23 (8.1%) 178 (62.5%)
TABLE II. Patient dose status in 1-year trial of ipratropium bromide nasal spray No. of patients
Total treated* Ipratropium bromide 0.03% dose 2 sprays/tid 1 spray/tid 2 sprays/bid 1 spray/bid 2 sprays/qd 1 spray/qd
3mo
6mo
9mo
12mo
232
200
179
159
223 3 3 2 1 0
179 14 6 1 0 0
155 15 6 1 0 2
138 11 7 2 1 0
Source Data: Case Report form Tabulations. t/d, Three times daily; bid, Twice daily; qd, every day. *Fifty-three patients were discontinued before completion of 3 months of open-label treatment. 4 million visits to the doctor's office per year may be attributable to PNAR. This is probably an underestimate. To date there has been no specific, effective therapy for the rhinorrhea associated with PNAR. Corticosteroids reduce the inflammation associated with rhinitis, but their effects are not specific to rhinorrhea, and many P N A R sufferers do not have detectable inflammation. The other available therapies--antihistamines, decongestants, and crom o l y n - - a r e even less specific than the corticosteroids and are generally known to be less effective in P N A R than in allergic rhinitis. Ipratropium bromide, an anticholinergic agent that blocks the action of acetylcholine, has been shown to reduce
Total treated Total any adverse event Total any nasal adverse event Upper respiratory tract infection Sinusitis Headache Pharyngitis Epistaxis Nasal dryness Nasal irritation Other nasal symptoms Nasal congestion
(%)
(%)
285 198 (69.5) 59 (20.7) 64 (22.5)
200 128 (64.0) 40 (20.0) 50 (25.0)
34 (11.9) 24 (8.4) 23 (8.1) 12 (4.2) 23 (8.1) 14 (4.9) 25 (8.8) 21 (7.4)
18 (9.0) 10 (5.0) 9 (4.5) 5 (2.5) 7 (3.5) 7 (3.5) 24 (12.0) 15 (7.5)
significantly the rhinorrhea associated with P N A R 4 with few adverse effects. These results are not inconsistent with the theory that P N A R is, in most cases, a "vasomotor" or hyperreactive cholinergic disorder? The short-term safety and efficacy of ipratropium nasal spray in P N A R have been assessed in a large, multicenter, double-blind study (see Bronsky et al. in this supplement). The purpose of our open-label trial was to study the effects of long-term ipratropium therapy in these P N A R patients for 1 full year, to establish a clearer safety profile of the drug and to evaluate its long-term efficacy. MATERIAL
AND
METHODS
Two hundred eighty-five patients with PNAR were followed for up to 1 year; 198 were women (see Table I for a summary of demographics). The mean age of patients was 44 years, (range, 21 to 74 years). The mean duration of disease was 17 years. All patients had year-round nasal symptoms with negative skin tests to perennial allergens. During the first 6 months, patients were maintained on the highest dose permitted by the protocol--two sprays per nostril of ipratropium bromide nasal spray 0.03% administered three times daily. Exceptions were made only if they were unable to tolerate this dose. In the last 6 months of the study, the dose could be decreased at the discretion of the physician to the lowest amount required to control rhinorrhea. Two hundred patients were treated for more than 6 months; 159 were treated for more than 1 year. Most patients (>80%) were maintained on the original dose of two sprays (42 ~g per nostril) three times daily throughout the study (Table II). A nasal examination was performed at each visit.
J ALLERGY CLIN IMMUNOL VOLUME 95, NUMBER 5, PART 2
Grossman
SNEEZING ,,z, .l
RHINORRHEA
Physician
90-
~ 90-
J
w
80-
tll
1125
100 -
100 I-
et al,
Physician
_ _......-.0
80-
Patient 70-
~70O
O
8 6o-
8 60-
50
50 8
16
24
32
4;
&
1;
5;
90-
o
80-
31
4'o
&
5;
28
56
NASAL CONGESTION
POSTNASAL DRIP 100-
~
21
WEEKSTREATED
WEEKSTREATED
9 00 ]
1 Patient
..t- ....
70O
O
8 6o50
8
1;
24
32
40
48
5;
WEEKSTREATED
6°1 5o I 0
1;
24
32
4;
WEEKSTREATED
FIG. 1. Patient and physician long-term global assessments of effectiveness of ipratropium bromide nasal spray in PNAR.
Physical examinations and laboratory tests were performed on the final visit or the visit at which the patient was discontinued from the trial. At each visit, patients and physicians separately recorded their impressions of the effectiveness of ipratropium bromide against rhinorrhea, postnasal drip, congestion, and sneezing. Efficacy evaluations included treatment failures, quality of life assessments of the degree of interference with daily activities and moods caused by rhinorrhea and congestion, and the need for concomitant perennial rhinitis medications. Safety was assessed by reviewing adverse events, laboratory results, and physician evaluations. RESULTS
The long-term use of ipratropium bromide nasal spray by patients with P N A R was well tolerated in this trial and was not associated with any serious or systemic drug-related adverse effects. Only 10% of patients were discontinued during the year-long study because of adverse events; half of these were considered potentially drug related by the investigators. The most common non-nasal adverse events were upper respiratory tract infections, sinusitis, headache, and pharyngitis. None of these appeared to be attributable to treatment with
TABLE IV. Use of standard perennial rhinitis medications concomitantly with ipratropium bromide (n = 219)
Baseline During long-term
Any use 161 (56%) Long-term use (>3 mo) 74 (26%)
97 (34%) 37 (13%)
ipratropium bromide. The two most frequent nasal adverse events were nasal dryness (10%) and epistaxis (4%). The incidence of these events was higher in the first than in the second 6 months of t r e a t m e n t - - 8 % versus 4% and 4% versus 3%, respectively. The decrease in incidence was not due to discontinuation; improvement in adverse effects was attributable to better tolerance with continued treatment, dose reduction, or both. Table Ill summarizes selected adverse events. Patient and physician global assessments suggested that long-term treatment with ipratropium bromide nasal spray offers sustained efficacy for controlling rhinorrhea in PNAR. There was no decrease in effectiveness during the 1-year trial
1126
Grossman et al.
100 90 I.tl 80 Z 70 Lkl rr 60 W r~ 50 40 I-_z 30 20 10 0
Physical Activity (n=215)
J ALLERGYCLIN IMMUNOL MAY 1995
Mental Work (n=217)
Tired (n=182
Irritable (n=183)
Sleeping (n=221)
[ ] Baseline
Reading (n=218)
Depressed (n=140)
Anxious (n=159)
[ ] End of Treatment
FIG. 2. A s s e s s m e n t of quality of life after 1 year of long-term t r e a t m e n t with i p r a t r o p i u m b r o m i d e in patients with PNAR.
TABLE V. Change in nasal examination after 1 year of treatment with ipratropium bromide nasal spray No. of patients (%) Baseline
Total treated Degree of mucosal edema None/mild Moderate/severe Color of nasal mucosa Normal Red Pale Quantity of rhinorrhea None/Scanty Some/profuse Postnasal drip Not present Present
At completion of long-term
273
273
125 (45.8) 148 (54.2)
190 (69.6) 83 (30.4)
75 (27.5) 137 (50.2) 54 (19.8)
110 (40.3) 125 (45.8) 33 (12.1)
140 (51.3) 133 (48.8)
209 (76.9) 63 (23.1)
162 (59.3) 111 (40.7)
197 (72.2) 76 (27.8)
ity of life and a significant reduction in the degree to which rhinorrhea and congestion interfered with the patients' day-to-day activities and moods (Fig.
2). Nasal examinations done at each visit by direct anterior rhinoscopy revealed no detrimental effects with long-term use of ipratropium bromide nasal spray. Indeed, some objective improvement was noted, including a normalization of the color of the mucosa, a reduction in mucosal edema and a reduction in rhinorrhea and postnasal drip (Table V). Therefore rhinoscopy was supportive of patient and physician assessments of control of nasal symptoms. DISCUSSION
(Fig. 1). The data indicate that long-term use of ipratropium bromide may also contribute to the control of congestion, postnasal drip and sneezing. Only 17 of 285 patients (6%) were considered to have failed treatment. There was a substantial reduction in the need for concomitant, long-term perennial rhinitis medications, from 26% at the start of the study to 13% during long-term treatment with ipratropium bromide (Table IV). The clinical benefit of long-term treatment was further demonstrated by an improvement in patient qual-
The rhinorrhea associated with PNAR is generally regarded as a nuisance, but it can be severe enough to have a significant negative impact on patient daily moods and activities and require a large number of physician visits. To date there have been no effective treatments specifically for PNAR-induced rhinorrhea. The drugs commonly used to treat PNAR--steroids, antihistamines and decongestants--are not as effective in this hyperreactive condition as in allergic rhinitis; also, none are specific to rhinorrhea. One of the problems physicians face with PNAR is the need for a long-term therapy that does not induce tolerance. Because rhinorrhea is an annoyance and not a life-threatening condition, there is also a need for a therapy that is safe and well tolerated. Our long-term, multicenter experience with ipratropium bromide nasal spray 0.03% indicates
J ALLERGYCLIN IMMUNOL
G r o s s m a n et
al.
1127
VOLUME 95, NUMBER 5, PART 2
that it is a safe and effective treatment for the control of rhinorrhea associated with PNAR. Most of the adverse effects coincident to the use of intranasal ipratropium appear to be mild, and in many cases they are either transient or can be successfully managed by reducing the dosage. In our study ipratropium bromide nasal spray significantly reduced the need for other perennial rhinitis medications. Therefore it would not seem unreasonable to use ipratropium as maintenance therapy for PNAR, adding antihistamines and decongestants only as needed. Many patients with P N A R use more than one medication; there was no evidence during the trial of increased side effects when ipratropium bromide was used with other P N A R treatments. The fact that ipratropium bromide was well tolerated over the year-long study indicates that it will be useful in long-term maintenance therapy. It is also significant that patients with P N A R perceived an improvement in quality of life with
ipratropium use. Finally, the gradual improvement over the course of the year in other PNAR symptoms, such as postnasal drip, sneezing, and congestion, suggests that there may be a significant cholinergic component to this difficult to treat disorder. REFERENCES
1. MygindN, Anggard A, Druce HM. Definition,classification and terminology.In: MygindM, Weeke B, eds. Allergic and vasomotor rhinitis; clinical aspects. Copenhagen: Munksgaard, 1985:17. 2. MullarkeyMF, Hill JS, Webb DR. Allergic and nonallergic rhinitis: their characterizationwith attention to the meaning of nasal eosinophilia. J ALLERGYCLINIMMUNOL1980;65: 122-6. 3. Scott-Levin Physician Drug and Diagnosis Audit, August 1994. Newton, Pa.: Scott Levin Associates, 4. DruceHM, Spector SL, Fireman P, et al. Double-blindstudy of intranasal ipratropium bromide in nonallergic perennial rhinitis. Ann Allergy 1992;69:53-60. 5. Borum P, Mygind N, Scholtz Larsen F. Intranasal ipratropium: a new treatment for perennial rhinitis. Clin Otolaryngol 1979;4:407-11.