Daily Symptom Scores Research Articles

A double-blind histamine placebo—controlled trial of polymerized whole grass for immunotherapy of grass allergy

Twenty-six patients were recruited for a study of the safety and efficacy of immunotherapy with IPG. They were randomly assigned to two groups based on skin test titrations to grass allergens. One group was treated in a double-blind fashion before the 1982 grass season with 12 weekly injections totaling approximately 48,000 PNU, and the other group was treated with 12 weekly injections of caramelized glucose histamine placebo. Daily symptom and medication score sheets were completed by all patients each day of the grass season. Blocking antibody rose ninefold in the IPG group ( p < 0.007) but was unchanged in the placebo group. There was no significant change in IgE against rye grass group I in either the IPG or the placebo group. Symptom-score mean in the IPG group was 217 ± 71 (S.E.M.), statistically lower ( p < 0.02) than the mean in the placebo group 496 ± 117 (S.E.M.). There were no systemic reactions and only minor local reactions. There was no change in routine laboratory tests in either group. Although two prior studies with grass allergen immunotherapy reported efficacy, these studies did not use symptom-score analysis. This is the first double-blind, histamine placebo-controlled study of grass immunotherapy that demonstrates efficacy by symptom-score index evaluation. IPG is a safe, clinically effective, and potentially cost-effective therapy for grass pollinosis.

The structuring of an allergy index based on IgE-mediated skin sensitivity to common environmental allergens

We computed skin-test sensitivity levels in 485 adults puncture-tested with eight standardized, high-quality inhalant allergens tested at single concentrations. In order to quantitate the “average” IgE-mediated skin sensitivity of each subject, we used both nonparametric and parametric statistical methods to generate two “allergy indices” (Allergy Index I and Allergy Index II) based on sensitivity end-point data from the subpopulations of individuals positive to six of the eight allergens. For the 192 skin test-positive subjects, Allergy Index I and Allergy Index II were significantly correlated with each other (r s = 0.98, p < 0.001) and with the number of positive skin-test reactions (r s ∼- 0.9, p < 0.001) as well as with log[total serum IgE] (r ∼- 0.4, p < 0.01). In 102 ragweed-positive subjects, log[specific IgE to ragweed] was significantly correlated with ragweed-specific “ragweed indices I and II” (r ∼- 0.6, p < 0.01). Furthermore, the average daily symptom scores reported by 14 ragweed-positive subjects during the ragweed pollination season were significantly correlated with ragweed indices I and II (p < 0.05). We propose the use of Allergy Index II in epidemiologic and genetic studies of allergic phenotypes as well as in clinical decisions for diagnosis and immunotherapeutic intervention.

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.

A double-blind, placebo-controlled trial of polymerized whole ragweed for immunotherapy of ragweed allergy

Immunotherapy with polymerized ragweed (PRW) has been demonstrated to be safe and effective when compared with monomeric ragweed or untreated controls. To further establish the efficacy of PRW, a trial was conducted comparing PRW, placebo, and no treatment in ragweed-sensitive individuals. In a double-blind manner, 21 patients were treated before the 1981 ragweed season with 15 weekly injections of PRW totaling about 50,000 PNU and 1200 μg antigen E, while 19 patients were treated with 15 weekly injections of a caramelized glucose and histamine placebo. An additional control group received no injections. Blood was drawn for IgE against ragweed antigen E (IgE-a-AgE) and for blocking antibody against AgE before treatment, after treatment (before season), and after season. In the untreated patients, blood was drawn before season and after season. Daily symptom score sheets were completed by patients each day of the ragweed season. Blocking antibody rose more than 40-fold with treatment (p = 0.0001) in the PRW group but was unchanged in the placebo group with treatment. IgE-a-AgE rose with PRW therapy. Clinical efficacy of PRW was again confirmed in this study. Symptom score mean in the PRW group was statistically lower than the mean in the placebo group (p = 0.022) and in the untreated group (p = 0.018). There were no systemic reactions and only minor local reactions during treatment. In summary, PRW is an improved form of immunotherapy.

Beclomethasone dipropionate nasal spray in children

SummaryTwenty children with extrinsic perennial allergic rhinitis were treated with inhaled beclomethasone dipropionate, 50 μg into each nostril 4-times daily, for a period of 6 weeks. No change in rhinorrhoea, itching and sneezing was observed after provocation testing but there was a reduction in the swelling and size of turbinates (p<0.005). The daily subjective symptom scores (p<0.01), total eosinophil counts (p<0.03) and serum IgE levels (p<0.04) had significantly decreased after treatment. It is suggested that inhaled beclomethasone dipropionate has a useful role in the management of children with perennial allergic rhinitis.

A multi-institutional trial of polymerized whole ragweed for immunotherapy of ragweed allergy

Eighty ragweed-sensitive patients in four cities were recruited to study the safety and efficacy of partially purified, polymerized whole ragweed (PRW) as an improved form of immunotherapy. Groups of 20 patients in Chicago, Boston, Memphis, and St. Louis had blood drawn for immunologic studies before and after the 1978 and 1979 ragweed seasons and completed detailed daily symptom score sheets each day of the 1978 and 1979 ragweed pollen seasons. Beginning in March, 1979, all patients except one received 15 weekly injections of PRW totaling 50,000 protein nitrogen units (PNU) and containing about 500 μg ragweed AgE. One patient received 25,000 PNU. Symptom score indices of the posttreatment 1979 season were compared with those from the pretreatment 1978 season and also with the scores of similar groups of ragweed-sensitive patients in each city treated only with medication for symptomatic relief during the 1979 season. Local reactions to polymerized ragweed immunotherapy were minimal. No abnormalities in complete blood count, erythrocyte sedimentation rate, chest x-ray film, urinalysis, or rheumatoid factor occurred in the immunotherapy-treated groups. Total serum antibody binding of ragweed AgE increased 12-fold following immunotherapy. When compared either with their 1978 untreated group scores or when compared with scores from the untreated group in each city in 1979 (control group), the symptom score indices of the immunotherapy-treated groups in 1979 were significantly improved. PRW is efficacious in the treatment of ragweed hay fever and can be administered more safely and in higher doses with fewer injections than conventional extracts. It represents an improved form of immunotherapy.

Short-term efficacy and side effects of cloprednol in children with asthma.

Efficacy and safety of alternate-day prednisolone compared to single daily cloprednol were evaluated over a six-week period in 11 children with severe asthma requiring in-residence medical supervision and long-term corticosteroid therapy. Clinical indices of efficacy, including daily pulmonary symptom scores, number of asthma attacks, asthma severity scores, and bronchodilator usage, all favored cloprednol. Afternoon pulmonary function tests (FEV1, FVC, and PEFR) were all significantly improved during the cloprednol period. Although plasma cortisol values remained within the broad range of normal during the cloprednol period, mean values were consistent with partial pituitary-adrenal suppression similar in degree to that observed 24 hours after administration of an alternate-day program of prednisolone therapy. The results of this trial showed cloprednol in single daily doses to be more effective than prednisolone in alternate doses for the treatment of children with severe asthma.

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.

Treatment of Chronic Childhood Asthma With Beclomethasone Dipropionate Aerosols: II. Effect on Pituitary-Adrenal Function After Substitution for Oral Corticosteroids

The effects of beclomethasone, dipropionate aerosol (DBA) (400 microgram/day) on clinical course, pulmonary function, and pituitary-adrenal function was studied in 34 steroid-dependent asthmatic children. Asthma severity was assessed by daily symptom and medication scores, peak flow measured three times a day, and weekly spirometry. Pituitary-adrenal function was evaluated by diurnal cortisol levels, cortisol responses to intravenous (IV) corticotropin (ACTH), and steroid responses to IV metyrapone. After 12 weeks of BDA therapy, 30 of 34 patients no longer required prednisone. Mean weekly symptom and medication scores and the number of attacks decreased significantly (P less than .01)). A significant improvement was demonstrated in the patients' peak flow (P less than .01), forced expiratory volume in one second, and maximum midexpiratory flow rates (P less than .01). Thirty of the 34 patients initially had abnormal metyrapone responses, 28 had abnormal diurnal cortisol levels, whereas only 14 had abnormal IV ACTH response tests. Although significant improvement was noted in the mean metyrapone and diurnal cortisol tests, only partial recovery of pituitary-adrenal function was observed in 20 patients, complete recovery in 5, and no change in 9. BDA was found to be therapeutically superior to oral steroids in the group of steroid-dependent asthmatic children and produced no serious adverse effects.

Nebulized sodium cromoglycate in young asthmatic children. Double-blind trial.

Seventeen asthmatic children under 5 years of age took part in a double-blind controlled trial of nebulized sodium cromoglycate solution. Daily symptom scores kept by the parents showed improvement in 11 children during active treatment, and a significant improvement in scores for cough by day and night was obtained for the group as a whole.

Treatment of Chronic Childhood Asthma With Beclomethasone Dipropionate Aerosol: I. A Double-Blind Crossover Trial in Nonsteroid-Dependent Patients

Twenty-two children with chronic asthma requiring daily administration of bronchodilators but not steroids were administered 400 µg of beclomethasone dipropionate aerosol (BDA) or a placebo (vehicle) in a double-blind crossover study. The experimental design consisted of four study periods (four weeks each): (1) baseline, (2) BDA or placebo treatment, (3) washout, (4) BDA or placebo treatment. Evaluation of effectiveness was assessed by daily symptom and medication scores, Wright Peak Flow (WPF) measurements three times each day, and weekly spirometry. Pituitary-adrenal function was evaluated by diurnal measurement of cortisol level, intravenous (IV) metyrapone tests, and IV adrenocorticotropic hormone responses. Quantitative throat cultures for Candida were taken monthly. Twenty-one of 22 patients correctly identified BDA. The mean weekly symptom score was 76.5 ± 10.8 (mean ± SE) during placebo compared to 21.3 ± 5.3 during BDA therapy (P &amp;lt; .005). The number of attacks per week was 7.1 ± 1.4 in those receiving placebo and 1.6 ± 0.6 in those receiving BDA (P &amp;lt; .005). Mean medication score was 39.6 ± 3.6 during placebo and 21.6 ± 1.3 during BDA therapy (P &amp;lt; .005). Mean weekly average WPF measurements increased 33% with BDA therapy compared to placebo. Eighty percent of patients showed an increase in forced expiratory volume in one second and in maximum midexpiratory flow rate during BDA therapy. All throat cultures were negative. No pituitary-adrenal function suppression was noted in any of the parameters studied. BDA was shown to be highly effective in controlling asthma and produced no adverse effects.

Beclomethasone dipropionate aerosol in perennial rhinitis

Beclomethasone dipropionate aerosol (BDA), 50 μg four times daily sprayed into each nostril, was compared with placebo in a double-blind crossover trial in 26 patients with perennial rhinitis. Patients received BDA for 3 weeks and placebo for 3 weeks; the order of administration was randomized. Response was assessed with daily symptom score cards and twice weekly measurements of nasal airway inspiratory resistance at a standard flow rate of 0.4 L/sec. Symptom score and nasal resistance during BDA treatment were significantly lower than those during placebo treatment (p < 0.02 and p < 0.05, respectively) in the third week. Eighteen of the patients expressed a preference for BDA, 6 for placebo, and 2 for neither (p < 0.05). Acceptable symptomatic improvement (moderate or marked) was achieved by 54%. Mild side effects were noted by 5 patients; these included nasal irritation and bleeding in 2, aerosol-induced sneezing in 2, and headache in 1. These side effects occurred in 3 patients who used BDA, 1 who used placebo, and 1 who used both. After a 6-mo follow-up period, in which the dose of BDA was adjusted and concurrent initial oral prednisone was administered to patients who were treatment failures, 73% of the patients obtained moderate or marked symptomatic improvement. No further side effects were noted during this time. Results in those in whom a possible allergic component could be identified were not different from those of the whole group. We conclude that BDA is a useful addition to the therapy of perennial rhinitis.

Betahistine hydrochloride in Méniére's disease

A double-blind, placebo-controlled, cross-over clinical trial was performed to assess the effect of betahistine hydrochloride (Serc) in Ménière's disease. The diagnosis was based on paroxysmal attacks of rotational vertigo, with tinnitus, and a fluctuating sensori-neural deafness, together with the results of auditory and vestigular tests. Twenty-eight patients were admitted to the trial over 3 years. Twenty-two patients completed the trial. In total, they received betahistine 32 mg daily, for a period of 16 weeks, and placebo also for the same length of time, preceded in every case by a 4-week pre-treatment period. Daily symptom score cards were kept. There was a statistically significant improvement in favour of the drug with regard to vertigo, tinnitus and deafness. Vertigo was the most responsive symptom. No adverse reactions were observed.

TREATMENT OF VASOMOTOR RHINITIS WITH INTRANASAL BECLOMETHASONE DIPROPIONATE (BECOTIDE®)

The effect of beclomethasone dipropionate (Becotide) intranasally in vasomotor rhinitis has been studied on 39 adult volunteers in a double-blind cross-over study during 9 weeks in February-April 1975. The dose of beclomethasone dipropionate was 300 mug/day. Twenty-five patients preferred the beclomethasone dipropionate period, 5 patients the placebo period, and 9 patients had no preference. About three-quarters (74 per cent) of the patients considered themselves free of symptoms or greatly improved after the treatment with beclomethasone dipropionate. Statistical calculation of the daily nasal symptoms score confirms the improvement. The speediest effect was registered for sneezing, followed by nasal catarrh, nasal itching, and blocking. No changes in the levels of cortisol occurred during the treatment. The bacteriological and mycological findings (analysed with regard to Candida albicans) were fairly constant.

A Clinical Index of Disability Due to Chronic Asthma Tested During a Trial of Cromolyn Sodium Treatment

An ordinal ranking system for clinically grading disability due to chronic asthma is described, by which to quantitate the changing course of individual patients during time-sequence observations. Experience over two years with 47 asthmatic patients undergoing various trials of disodium cromoglycate therapy indicates this index is very sensitive, reasonably reproducible in the hands of clinicians trained in its use, and specific for asthma rather than for coexisting chronic obstructive lung disease in this patient population. Duplicate scoring by trained observers is recommended. Correlations between disability and daily asthma symptom scores were generally statistically significant, but coefficients were low. Correlations of disability with pulmonary function parameters (measured fortnightly) were not significant. Statistically significant improvement was evident in most asthma indices after a month of disodium cromoglycate treatment. Disability scores improved a great deal, which implies that the observed “statistically significant” improvement in the asthma patient after disodium cromoglycate treatment represents a real clinical advantage.