The effect of cromolyn sodium powder as a treatment for ragweed pollinosis

The effect of treating ragweed pollinosis with intranasal cromolyn sodium powder was evaluated in 26 patients in a double-blind clinical study. Thirteen matched patient pairs were treated by either nasal insufflation of cromolyn sodium powder, 20 mg three times daily, or by a placebo powder. Patients were monitored for severity of symptoms by means of daily symptom diaries collected weekly throughout the pollen season. Serum samples were obtained in July prior to the ragweed season and following the ragweed season during the first and fourth weeks of October for the determination of ragweed-specific IgE antibody levels by the radioallergosorbent test. A significant reduction in symptom severity was observed in the treated patients with high preseasonal levels of IgE antibody to ragweed. Initially the levels of IgE antibody to ragweed did not differ between the two groups. IgE antibody levels increased in both groups after pollen exposure, but the treated group showed a significantly greater rise in IgE antibody levels. The results suggest that treatment with cromolyn sodium enhanced IgE antibody response to pollen exposure and significantly reduced the severity of hay fever symptoms in patients with high preseasonal levels of IgE antibody to ragweed.     

Preseasonal IgE ragweed antibody level as a predictor of response to therapy of ragweed hay fever with intranasal cromolyn sodium solution.

Intranasal administration of a 4% solution of cromolyn sodium for the treatment of ragweed hay fever was tested in an 8-week double-blind matched-pair study involving 66 patients. Patients on active drug received 5.2 mg into each nostril 6 times daily; control patients received a placebo spray. The treated group showed a significant reduction in mouth breathing (p less than 0.001), stuffy nose (p less than 0.002), runny nose (p less than 0.003), and postnasal drip (p less than 0.035). Patients receiving the active drug also reported fewer sneezing episodes (p less than 0.003) and nose blowing episodes (p less than 0.015). One patient using cromolyn solution developed nasal ulceration, tongue swelling, coughing, and wheezing. Other side effects were minimal and occurred with equal frequency in both groups. In the treated group relief of symptoms was most marked in patients with high preseasonal levels of IgE ragweed antibody. Intranasal 4% cromolyn solution appears to be an effective drug for the treatment of ragweed hay fever; measurement of the preseasonal level of IgE ragweed antibody is a useful screening test to identify patients most likely to achieve a maximal beneficial response to treatment.     

Topical ocular administration of cromolyn sodium for treatment in seasonal ragweed conjunctivitis.

We studied topical ocular administration of a 4% solution of cromolyn sodium (CS)for treatment of 112 patients with ragweed conjunctivitis in two 8-wk, double-blind, matched-pair studies. During the 1977 and 1978 ragweed seasons, patients instilled a daily total of 12.8 or 19.2 mg CS into each eye, control patients received placebo drops. Treatment efficacy was assessed by daily symptom score diaries, ophthalmic examinations, and a subjective report by the patient at the end of the trials. In the 1977 trial, CS pair members whose preseasonal immunoglobulin E antibody level was <99 ng/ml showed a significant reduction in eye itching (p < 0.01), eye irritation (p < 0.02), visual blurring (p < 0.025), and nasal congestion (p < 0.025) and required less supplemental medication (p < 0.02) during the peak pollen period. In the 1978 trial all patients had IgE antibody levels >100 ng/ml. CS pair members showed a significant reduction in rhinorrhea (p < 0.004) and nasal congestion (p < 0.007) only; no significant reduction in eye symptoms was noted. Transient eye burning was noted by a total of 38 CS and 39 placebo patients from both studies; ophthalmic examinations were unremarkable; and no other side effects were noted. The 4% CS ophthalmic solution provided significant relief of nasal symptoms in both the 1977 and 1978 trials, but significant relief of ocular symptoms was noted only in the 1977 trial and only in those patients with lower preseasonal IgE ragweed antibody levels.     

Controlled trials with four per cent cromolyn spray in seasonal allergic rhinitis*

Thirty-two patients with seasonal allergic rhinitis due to weed pollen were treated beginning prior to the weed pollen season of 1974 with either 4% cromolyn sodium or placebo nasal spray. The patients were followed on treatment with symptom diary cards and bi-weekly physician examinations for a period of 10 weeks. Radioallergosorbent (RAST) titres for the major weeds in the Denver area (ragweed, Russian thistle, and sage) were determined before the weed pollen season, and one and three months after the weed pollen season. There was no significant difference in symptom scores between the 4% cromolyn sodium- and placebo-treated groups, nor objective evidence on bi-weekly examinations by a physician to suggest differences in the two groups. Significant differences in favor of the 4% cromolyn-treated group were noted in the amount of antihistamines taken for symptomatic relief during the weed pollenating season, suggesting some protective effect of the drug. The clinical significance of this finding is not clear. Selecting patients with high baseline RAST titres for one or more of the major weeds did not alter the results of the study. In a second double-blind study twenty-two patients reporting to the allergy clinic with symptomatic seasonal allergic rhinitis due to weeds were randomly assigned to receive 4% cromolyn sodium or placebo nasal spray and followed through the weed pollen season. There was no difference between the two groups in either symptom scores or use of antihistamines for asymptomatic relief.     

Comparison of intranasal cromolyn sodium, 4%, and oral terfenadine for allergic rhinitis: symptoms, nasal cytology, nasal ciliary clearance, and rhinomanometry.

Topical intranasal cromolyn sodium, 4% solution, and oral terfenadine, 60 mg tablets, both relieve symptoms of allergic rhinitis with few or no adverse effects, but no comparison of their relative efficacy has been reported. In this double-blind, double-dummy study, 79 patients, ages 12-56 years with symptoms of allergic rhinitis, were randomized to receive either active cromolyn sodium, 1 spray in each nostril QID, or active terfenadine BID along with the appropriate placebo spray or tablet for 4 weeks following a 1-week baseline qualification period. Patients' daily symptom scores were reviewed weekly and constituted the primary efficacy measures. Changes in nasal cytology, nasal ciliary clearance, and rhinomanometry were also assessed. The presence of adverse effects and the overall score of medication efficacy at the end of each week was recorded. The cromolyn sodium and terfenadine groups had comparable baseline scores for severity of allergic rhinitis symptoms and both treatments resulted in significant improvement (P less than .0001) with no statistical difference between them for total symptom scores at the end of 4 weeks. Eosinophils in nasal samples were decreased significantly in the cromolyn treated group with no significant change in the terfenadine-treated group. There were no significant differences between treatment groups in ciliary clearance or rhinomanometry. Adverse effects were uncommon and mild. We conclude that cromolyn sodium and terfenadine are comparably effective and well-accepted treatments for allergic rhinitis.     

Efficacy of continuous treatment with astemizole (Hismanal) and terfenadine (Seldane) in ragweed pollen-induced rhinoconjunctivitis

Astemizole (Hismanal; Janssen Pharmaceutica Inc., Mississauga, Ontario, Canada) and terfenadine (Seldane; Merrell Dow Pharmaceuticals [Canada], Inc., Concord, Ontario, Canada) were compared for clinical efficacy in a double-blind randomized trial during the ragweed pollen season. Sixty adults, with a history of ragweed-induced rhinoconjunctivitis, were matched according to sensitivity to ragweed pollen. Half took astemizole, 10 mg/day, and the rest took terfenadine, 60 mg twice daily. Medications were started 1 week before and continued daily until 1 week after the ragweed pollen season (7 weeks). If the trial medication was insufficient to keep symptoms well controlled, a steroid nasal spray and/or eye drops were used in the minimum dose that would ensure symptoms were not troublesome. Subjects completed a diary of nocturnal and daytime nasal and eye symptoms and recorded the amount of concomitant medications used. Astemizole showed greater efficacy than terfenadine in controlling rhinorrhea; in addition, the astemizole group used less nasal spray. Other nasal symptoms, eye symptoms, and use of eye drops were similar in the two groups. Skin test sensitivity to serial dilutions of histamine and ragweed extract was determined 1 and 7 weeks after the start of the trial medication. More tachyphylaxis to histamine was shown by the subjects taking terfenadine, as demonstrated by a larger increase in skin sensitivity over the study period. However, a similar change was not observed for ragweed skin sensitivity. These results suggest that when the medication is started before and continued daily throughout the pollen season, astemizole is more efficacious than terfenadine in controlling nasal symptoms, but there is little difference for eye symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)     

Response of the nonaliergic rhinitis with eosinophilia (HARES) syndrome to 4% cromolyn sodium nasal solution

A double-blind, parallel, multiple-dose drug trial was perforated on 23 adult patients with nonallergic rhinitis with eosinophilia (HARES) syndrome. All patients were characterized clinically as having perennial nasal symptoms of sneezing paroxysms, profuse watery rhinorrhea, and pruritus of the nasopharyngeal and conjunctiva( mucosa, with minimal nasal obstruction to airflow. They had nasal secretion eosinophilia, negative prick or intradermal immediate skin tests, negative serum RAST results to common inhalant allergens, negative methacholine bronchoprovocation challenges, and normal total eosinophil counts and total serum IgE levels. Twelve patients received a 4% cromolyn sodium nasal solution and/I patients received a matching placebo administered six times daily. for 8 wk. Daily symptom scores for itchy nose, runny nose, 'stuffy nose, itchy eyes, itchy throat, mouth breathing, postnasal drainage, sneezing, and nose blowing were recorded by the patients. Eye, ear, nose, and throat (SENT) examinations were performed weekly by one of the investigators, and blood samples for CBC and chemistries were obtained at the start and termination of the study. Chemistries and blood counts showed no adverse effects of the drug. No important differences between the drug and placebo groups were noted in either the .symptom scores or SENT examinations of the two groups. We conclude that 4% cromolyn sodium nasal solution is of no benefit in the treatment of patients with the HARES syndrome.     

Multicenter placebo-controlled study of nedocromil sodium 1% nasal solution in ragweed seasonal allergic rhinitis

An 8-week double-blind study was carried out in 177 ragweed patients with seasonal allergic rhinitis to compare nedocromil sodium 1% nasal solution (Tilarin, QID, Fisons plc) and placebo. Symptoms of rhinitis were significantly reduced by nedocromil sodium during the peak 3-week pollen season (P = .001 for diary summary score) and the active treatment was rated effective by 74% of patients.     

Deposition of ragweed pollen and extract on nasal mucosa of patients with allergic rhinitis: Effect on nasal airflow resistance and nasal mucus velocity

This study was undertaken to ascertain whether nasal mucus velocity (NMV) could be altered by short-term exposure to antigen. Asymptomatic patients with a history of allergic rhinitis who had a positive cutaneous reaction to ragweed extract were investigated. The plan was to achieve approximately a fourfold elevation of nasal airflow resistance (NAR) with antigen challenge and then obtain serial measurements of NAR and NMV. NMV was not significantly altered when the antigen was introduced by nasal inhalation of (1) ragweed pollen grains, (2) nebulized ragweed extract for 10 breaths, and (3) nebulized ragweed extract for 30 min on each of 3 successive days. When ragweed extract was introduced by direct instillation of the solution into the nose, NMV fell below baseline values at either 0.5 or 1.5 hr, or at both times after administration. Persistence of impairment of mucociliary transport at a time when nasal airway constrictor response had dissipated suggested that a chemical mediator might have been responsible for the alteration of clearance. The failure to demonstrate depression of mucus transport with the inhalation studies might have been due to insensitivity of the radiopaque Teflon disk method or to a qualitatively different allergic reaction to direct instillation of antigen solution.     

Canadian trial of sublingual swallow immunotherapy for ragweed rhinoconjunctivitis.

BACKGROUND: Sublingual swallow immunotherapy has been increasingly recognized as a safe and efficacious alternative to parenteral specific immunotherapy. OBJECTIVE: To determine the safety and efficacy of sublingual swallow immunotherapy ragweed allergen extract for rhinoconjunctivitis treatment starting just before and continuing through the ragweed pollen season. METHODS: This randomized, double-blind, placebo-controlled study was performed in children and adults with a documented history of allergic rhinoconjunctivitis during ragweed season at 9 Canadian allergy centers. Active treatment was standardized extract of ragweed allergen administered as sublingual swallow drops at increasing doses starting shortly before the pollen season and maintenance doses continued daily during the season. Primary efficacy variables were symptom and medication scores, and secondary variables included global evaluation of efficacy and immunologic measurements. RESULTS: Eighty-three patients were included in the safety analysis; 76 patients were included in the intent-to-treat analysis. Nine placebo recipients and 1 treatment recipient withdrew for lack of efficacy (P = .004). Nine patients in the treatment group withdrew because of adverse events, none serious (P = .003). Investigator evaluation of efficacy showed that significantly more patients improved and fewer deteriorated in the treatment group vs the placebo group (P = .047). Ragweed IgE and IgG4 levels increased significantly in treatment recipients vs placebo users (P < .001). Sneezing and nasal pruritus approached significant improvement in the treatment group vs the placebo group (P = .09 and .06, respectively). Quebec City experienced low pollen counts. Excluding Quebec City, significant improvement was seen for these 2 symptoms (P = .04). CONCLUSION: Sublingual swallow immunotherapy seems to be safe and efficacious for ragweed rhinoconjunctivitis even when started immediately before the ragweed pollen season.     

Treatment of ragweed allergic conjunctivitis with 2% cromolyn solution in unit doses

Previous studies have shown the effectiveness of topical cromolyn solution in the treatment of allergic conjunctivitis. However, the preservative, phenylethanol, produces an immediate burning or stinging sensation when the drops are first instilled in the eye. A double-blind, crossover, placebo controlled study using 2% cromolyn solution was conducted, without the preservative and supplied in unit doses. Twenty six patients took part in the trial. They had ragweed pollen-induced conjunctivitis. The results of the trial indicate that the active drug was effective in controlling the signs and symptoms of allergic conjunctivitis in 22 of the 26 patients, i.e., 84.6% (p less than 0.001). Two patients preferred the placebo. There were no complaints of stinging or burning sensation after the instillation of the drops in the eyes. There were no cases of infection of the eye. Without the preservative, the cromolyn solution does not damage the soft contact lens.     

Cromolyn sodium in seasonal allergic conjunctivitis

A formulation of 2% cromolyn sodium (CS) ophthalmic solution without the preservative, 2-phenylethanol, was compared with placebo in 58 patients with seasonal allergic conjunctivitis. Selection was based on history and positive skin tests. Neither immunotherapy nor use of antihistamines was allowed. This study was double-blinded and stratified by RAST scores to assure comparable groups. Either CS or placebo was used six times daily. Patients were observed weekly for 5 weeks during the peak of the fall weed-pollen exposure. Nasal symptoms were treated as required with beclomethasone nasal spray, and uncontrolled ocular symptoms were treated with boric acid and ephedrine solution. Nasal and ocular symptoms were recorded. There was a significant suppression of eye symptoms in the group receiving CS ophthalmic solution (p less than 0.02) during weeks 2, 4, and 5. There was a trend for nasal symptoms and the requirement for nasal beclomethasone to be less in patients receiving CS.     

A controlled study of the effectiveness of the Rinkel method of immunotherapy for ragweed pollen hay fever

In a double-blind study, we compared the effects of the Rinkel method of immunotherapy with ragweed pollen extract and placebo on symptoms of ragweed hay fever and immunologic parameters in 24 ragweed-sensitive patients. Each had a skin-test end point by Rinkel serial dilution titration to ragweed pollen extract at 1:312,500 w/v or greater dilution, a 2+ skin test to ragweed AgE at 0.1 μg/ml or greater dilution, and in vitro leukocyte histamine release by ragweed pollen extract. None had had immunotherapy for at least 7 yr. Patients matched on the basis of leukocyte histamine release by ragweed were assigned to two treatment groups (12 patients in each group). One group received ragweed pollen extract, and the other, placebo, both administered by the Rinkel method between June and October, 1978. Treatment doses were derived from skin-test end points. The median maintenance (“optimal dose”) for patients receiving ragweed pollen extract was 0.53 ml of 1:312,500 w/v and the mean cumulative dose of ragweed pollen extract given during the study contained 0.094 μg of ragweed AgE. Symptom-medication scores of all patients rose and fell with ragweed pollen counts. No significant differences were observed in mean daily symptom-medication scores, antiragweed IgG or IgE levels, leukocyte histamine release by ragweed, total IgE levels, or skin-test end-point dilutions with ragweed pollen extract between the group receiving ragweed pollen extract and the group receiving placebo. Despite the absence of specific effect on symptom-medication scores and measured immunologic variates, 10 of the 12 ragweed-treated patients and 10 of the 12 placebo-treated patients were of the opinion that their hay fever symptoms during the ragweed pollen season were less severe in 1978 than in 1977 and that they had been helped by Rinkel method immunotherapy. Under the conditions of the study, Rinkel method immunotherapy with ragweed pollen extract was no more effective than placebo given in an imitation of the Rinkel method.     

Clinical evaluation of intranasal topical flunisolide therapy in allergic rhinitis.

A double-blind, vehicle control, parallel clinical trial evaluated the effectiveness and safety of the local application of flunisolide, a potent new topical steroid, in the treatment of ragweed hay fever. Fifty patients with well-defined, poorly controlled ragweed allergy were studied during the 1974 ragweed season. Analysis of the data showed that the active drug group had a significant decrease in individual symptoms of sneezing, nasal stuffiness, and nasal secretions, compared with the placebo group. Antihistamine usage was statistically decreased in the active drug over placebo group. There was no evidence of adrenal suppression. This study indicates that intranasal administration of flunisolide in adult patients is both efficacious and safe in the treatment of seasonal allergic rhinitis.     

Bronchoprovocation: effect on priming and desensitization phenomenon in the lung.

Priming, or increased sensitivity to antigen, has not been demonstrated in the lung and could play a role in asthmatic symptomatology during seasonal pollen exposure. It is also an important consideration in the design of any experimental protocol requiring serial bronchoprovocations with antigen. Thirteen patients with a history of asthma symptoms during the pollen season and a positive skin test to ragweed extract were selected. Patients were given bronchial challenge out of season on 4 successive days with stepwise inhalations of antigen, and airways conductance was monitored in the body plethysmograph. Antigen dose-response curves were drawn, and the cumulative dose required for a 35% reduction in specific airway conductance was calculated and designated Provocation Dose (PD35). No regular trend toward either priming or desensitization was noted. The daily changes in antigen sensitivity did not correlate with daily variation of baseline pulmonary function. To determine if there was any priming due to natural exposure to pollen, 9 patients were brought back and rechallenged during the pollen season with no significant increase in bronchial sensitivity to ragweed extract. The PD35 method provides figures useful for comparing dose-response curves and shows a one-log variation from day to day. Any evaluation by bronchial challenge of antigen sensitivity or drug efficacy must take into account such variation.     

Cromolyn sodium in the management of systemic mastocytosis

A multicenter, double-blind, placebo-controlled trial of the efficacy of oral cromolyn sodium (200 mg orally four times per day) was conducted in 11 patients with systemic mastocytosis who had been maintained with the drug on an individualized compassionate-need basis. Efficacy was measured by physician assessment of overall disease severity based on history and physical examination at specified intervals and by the average daily patient symptom diary scores for each of three mastocytosis-related symptoms that had previously appeared to be alleviated by the use of this drug. Efficacy variables were compared for a 4-week baseline period, during which patients received open-labeled cromolyn sodium, and at 4-week intervals during a 16-week period of random assignment to cromolyn sodium or placebo. Overall disease severity and symptoms recorded in patient diaries were graded on a scale of 0 (absent) to 5 (incapacitating). The average physician assessment of disease severity and symptom scores of the patients in the placebo-treated group increased significantly during the randomization phase relative to patients in the cromolyn sodium-treated group, reflecting an exacerbation of symptoms with drug withdrawal (p less than 0.05 and less than 0.028, respectively). When the symptom scores were analyzed separately for gastrointestinal manifestations of disease (diarrhea, abdominal pain, nausea, and vomiting), cromolyn sodium treatment was significantly beneficial relative to placebo (p less than 0.02), whereas the benefit for nongastrointestinal manifestations did not reach statistical significance.     

Treatment of ragweed hay fever with intranasally administered disodium cromoglycate*

In a double-blind study the therapeutic effect of a 4% disodium cromoglycate (DSCG) nasal solution was evaluated in thirty-nine patients with acute symptoms of ragweed hay fever. Patients were randomly assigned to the DSCG or placebo group as they presented with allergic rhinitis. Overall, the DSCG was not more effective than placebo in controlling the symptoms of rhinitis or in decreasing the need for concomitant antihistamines or corticosteroids. Among patients with the highest pretreatment serum ragweed-specific IgE (RW IgE) levels, drug-treated patients had some reduction in symptoms as compared to their placebo controls during the peak of the ragweed pollen season. DSCG treatment did not influence the usual seasonal rise in RW IgE. Side effects from both the active and placebo aerosols were frequent but mild. We conclude that DSCG nasal solution used for the treatment of seasonal ragweed allergic rhinitis is relatively ineffective.     

Pharmacologic prophylaxis of allergic rhinitis: Relative efficacy of hydroxyzine and chlorpheniramine

The efficacy of hydroxyzine and chlorpheniramine in preventing exacerbations of ragweed allergic rhinitis was compared in a double-blind, randomized manner. Ninety-five subjects with positive skin tests, a history of two previous symptomatic seasons, and discontinuation of immunotherapy for at least 1 yr received either hydroxyzine 150 mg/day, chlorpheniramine 24 mg/day, or placebo during the 1978 ragweed season. Subjects in the placebo group experienced annoying or disabling sneezing 50% of days during the period of highest pollen counts whereas those in the chlorpheniramine and hydroxyzine groups experienced this symptom with equal severity only 22% and 12% of days, respectively. Suppression of rhinorrhea and itchy nose was similar although less dramatic. Both antihistamines were more effective than placebo in altering conjunctivitis, but neither decreased the frequency or severity of nasal stuffiness. Skin tests to ragweed decreased in diameter during the season by 38%, 13%, and 3% among patients receiving hydroxyzine, chlorpheniramine, and placebo, respectively. Frequent drowsiness occurred initially in subjects taking both antihistamines but did not persist. Thus, prophylactic antihistamine therapy effectively prevents most symptoms of seasonal allergic rhinitis without persistent drowsiness. These data further suggest a therapeutic advantage for hydroxyzine over chlorpheniramine in the doses used.     

Effect of corticosteroids on seasonal increases in IgE antibody

We analyzed seasonal changes in IgE antibodies to ragweed antigens in 28 patients with ragweed hay fever during the 1972 pollination season. Thirteen patients were treated with an injection of 60 mg. of triamcinolone acetonide suspension and 16 mg. of methylprednisolone orally on 3 successive days shortly after the onset of their symptoms in late August. Fifteen patients were untreated and served as controls. Serum samples were obtained in July (control group) or just prior to steroid treatment in August, and from both groups in mid-September and finally in mid-October. Initially, IgE antibody levels did not differ between the groups. IgE antibody increased after pollen exposure in both groups, but there was no significant difference in the increases. In contrast, symptom scores were significantly less in patients treated with steroids (P < 0.01). The results indicate that corticosteroid treatment does not prevent the seasonal increase in IgE antibody after pollen exposure but does significantly reduce the severity of hay fever symptoms.     

Comparison of five new antihistamines (H1-receptor antagonists) in patients with allergic rhinitis using nasal provocation studies and skin tests

BACKGROUND: It was the aim of the authors to compare all of the latest second-generation antihistamines and to see if there were significant differences in their efficacy. It is important for ENT specialists to know if these differences exist, as it is for general practitioners trying to choose between these drugs. METHODS: In 12 confirmed grass pollen allergic patients the authors performed nasal smears to asses eosinophilia, histamine/grass pollen skin tests, and grass pollen nasal provocation tests. All tests were performed before and after administration of one of five different antihistamines (cetirizine, loratadine, ebastine, fexofenadine, mizolastine) or placebo. The order of administration of antihistamines and placebo was randomised, and patients were not aware of which drug they were given. A decrease in nasal eosinophilia (nasal smear), or nasal or skin reactivity (provocation tests) was looked for. RESULTS: A significant decrease in nasal eosinophilia was observed for all antihistamines but not for placebo. For the grass pollen nasal provocation tests, the decrease was significant for nasal blockage and sneezing; for rhinorrhea there was an insignificant decrease that was true for all antihistamines. A significant reduction in histamine/grass pollen skin test reactivity was also observed for all antihistamines, during an 8 h observation period. A significant difference in efficacy between the different antihistamines could not be found with any of the tests performed. CONCLUSIONS: For the newer nonsedating H1-antagonists there appears to be no clinically relevant differences in activities--at least not in our study. Preference of the patient may be the most important factor in making a choice between these drugs.