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Background Given the choice of standard, cluster, and rush build-up for aeroallergen immunotherapy, standard-build immunotherapy has generally been preferred because of a perceived high rate of systemic reactions (SRs) associated with cluster and rush immunotherapy. Objective To characterize the incidence of SRs during standard, cluster, and rush build-up immunotherapy in an allergy practice during a 5-year period. Methods A retrospective review was conducted among patients receiving standard-build, 8- to 10-step cluster, or 2-day rush immunotherapy from January 1, 2010, through December 31, 2014, at Family Allergy & Asthma clinics in Louisville, Kentucky. Investigators excluded reactions that occurred during skin prick testing, venom immunotherapy, and not-true SRs, and identified the build-up method, age, sex, date of reaction, vial concentration, and presence of asthma. Per-shot and per-patient incidence of SRs was computed from these data. Results During our review period, 2,549,643 injections were administered to 11,982 patients. Per-shot incidence of SR was 0.01%, 0.06%, and 0.33% for standard, cluster, and rush immunotherapy, respectively; per-patient incidence of SR was 2.84%, 2.52%, and 11.86% for standard, cluster, and rush immunotherapy, respectively. A total of 42% of SRs were grade 1, 43% were grade 2, 12% were grade 3, and 3% were grade 4. No fatalities were reported. A total of 70% of total SRs, 75% of cluster SR, and 55% of rush SR occurred in females, with an emergent peak in SR from May to October. Conclusion Compared with previously published rates, we observed a decrease in the incidence of SR for standard, cluster, and rush immunotherapy, with peak seasonality from May to October and a female predominance.

This was a 1-week study evaluating the safety and efficacy of two dosage regimens of salmeterol in children with asthma. A total of 243 children, aged 4-11 years, with mild-to-moderate asthma were enrolled in a randomized, double-blind, placebo-controlled, parallel-group, multicenter study evaluating salmeterol xinafoate 21 micrograms and 42 micrograms administered via metered-dose inhaler (MDI) twice daily for 1 week. Patients were allowed to use albuterol MDI as needed for relief of acute symptoms. Inhaled corticosteroids and/or cromolyn at fixed dosages could be continued during the study, but theophylline and oral beta-agonists were not allowed. Twelve-hour serial spirometry (for patients aged 6-11 years) and serial peak expiratory flow rate (PEFR) (all patients) were performed on days 1 and 8 of treatment; morning and evening PEFR were recorded each day prior to inhalation of the study drug. Safety was assessed by monitoring adverse events, clinical laboratory values, vital signs, electrocardiogram (ECG), and 24-hr ECG (Holter) monitoring. Both the 21-micrograms and 42-micrograms doses of salmeterol produced significantly greater bronchodilation, as measured by 12-hr serial forced expiratory volume in 1 sec (FEV1) (p < or = 0.02) and PEFR (p < or = 0.001), than did placebo on days 1 and 8. A small dose-response was observed, with the 42-micrograms dosage producing consistently higher serial FEV1 and PEFR than did the 21-micrograms dosage, although the differences were not statistically significant. Morning and evening PEFR increased significantly (p < or = 0.008) with both dosages of salmeterol compared with placebo. Twelve patients (5%) experienced potentially drug-related adverse events, with headache (4% in each salmeterol group) being the most common. There were no clinically significant changes in heart rate as measured by Holter monitoring, ECGs, vital signs, or clinical laboratory values following treatment with either dose of salmeterol. Salmeterol 21 micrograms or 42 micrograms twice daily was effective in producing bronchodilation in children aged 4-11 years, and both dosages had good safety profiles. Patients treated with salmeterol 42 micrograms twice daily showed a trend toward greater improvement in asthma control compared with those who received salmeterol 21 micrograms.

Although theophylline is recommended by current guidelines for the management of asthma in patients with persistent symptoms, theophylline has a narrow therapeutic index, requiring individual dose titration and regular monitoring of serum theophylline concentrations to avoid adverse effects.To compare the inhaled long-acting bronchodilator, salmeterol, with the oral bronchodilator, theophylline, in the maintenance treatment of asthma.In two multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group studies, patients received salmeterol aerosol 42 micrograms, extended-release theophylline capsules, or placebo twice daily for 12 weeks.Of 638 adult and adolescent patients with moderate asthma who entered the prebaseline theophylline titration period, 154 were withdrawn prior to randomization (71 due to theophylline-related adverse effects); 484 patients comprised the intent-to-treat population. The mean serum theophylline concentration measured approximately seven hours postdose during the titration period in the theophylline group was 12.7 mg/L (70 mumol/L). The same dose during the treatment period resulted in a mean serum theophylline concentration between 7.6 to 7.9 mg/L (42-44 mumol/L) when measured approximately 12 hours postdose. Salmeterol was significantly more effective than theophylline or placebo in improving mean morning PEF over the entire 12 weeks (Por = .02). Mean predose FEV1 improved significantly with salmeterol compared with placebo (P.001); there was no difference between theophylline and placebo. Salmeterol was also significantly more effective than theophylline or placebo (P.02) in improving asthma symptoms, reducing nighttime awakenings, and reducing the daily use of albuterol. After 12 weeks of treatment, patients in the salmeterol group expressed significantly greater overall satisfaction with their asthma medication than did patients who received theophylline (P.01). Patients in the theophylline group experienced more gastrointestinal adverse events than did patients in the salmeterol group (P.05).Salmeterol, 42 mg twice daily, was better tolerated and significantly more effective than extended-release theophylline twice daily in the maintenance treatment of asthma.

The photodimerisation of 2-dimethylamino-4-hydroxy-6-methyl-5-n-butyl-(1), 2-ethylamino-4-hydroxy-6-methyl-5-n-butyl-(2), and 4-hydroxy-5,6-dimethyl-2-dimethylamino-pyrimidine (3) has been investigated in acetonitrile. Quenching experiments have shown that the formation of photodimers involves a triplet state of (1)–(3), the energies of which have been estimated. The quantum yields for intersystem crossing from the singlet to triplet manifolds of (1)–(3) fall in the range 0.09–0.11, and the quantum yields for photodimerisation fall in the range 0.07–0.08. Rate constants for radiationless decay of the triplet state pyrimidines have been determined (2.1–3.0 × 105 s–1), and also the rate constants for reaction of the triplet states of (1)–(3) with the corresponding ground state pyrimidine (1.5–2.0 × 108 l mol–1 s–1). The efficiency of the triplet state dimerisation reactions of (1)–(3) is high compared with that of the analogous triplet state reactions of the biologically important pyrimidines, thymine and uracil.