A novel breath actuated device (Autohaler) consistently actuates during the early phase of inspiration.

OBJECTIVE: To establish and quantify the point during inspiration that the Autohaler (AH) inhalation system releases a metered dose of aerosol (placebo). The second objective was to determine if the Autohaler system actuates consistently, regardless of the canister life. DESIGN: Double-blind, randomized, two-period crossover, one-day trial. SETTING: Community based allergy and asthma clinic. PARTICIPANTS: Twelve patients with mild to moderate asthma. RESULTS: Mean verbal training time for the AH which included the patient demonstrating their ability to correctly use the AH was approximately 6 minutes. The mean time for actuation for the AH early in its canister life ("new canister") was 195 msec compared to 205 msec for the AH late in its canister life ("old canister") (p = 0.589). This represented the early part of inspiration as patients had a mean inspiratory duration of 2231 msec for the "new" AH and 2343 msec for the "old" AH. The mean percentage of inspiration time required to actuate the "new" AH was 8.92% compared to 8.82% for the "old" AH. Patients rated the system as easier to much easier to use compared with their current standard press and breathe inhaler. CONCLUSIONS: The AH consistently actuates early during inspiration, which is considered the optimal time for drug delivery, regardless of the canister life.

Double-blind assessment of azelastine in the treatment of perennial allergic rhinitis.

Azelastine is a chemically novel multifunctional antiallergy investigational drug capable of inhibiting mast-cell activation and the synthesis and/or release of chemical mediators of the upper and lower airway inflammatory response. In previous controlled clinical trials, azelastine was shown to be effective in treating the symptoms of both seasonal allergic rhinitis and perennial allergic rhinitis. The objective of this 8-week double-blind trial was to evaluate further azelastine's efficacy and safety in improving the symptoms of perennial allergic rhinitis over a prolonged period of treatment. One hundred ninety-nine patients with symptomatic perennial allergic rhinitis were randomized to receive in a double-blind fashion azelastine, 2 mg bid, clemastine fumarate, 1.34 mg bid, or placebo bid for 8 weeks. Patients treated with azelastine had superior mean percent improvements in the total symptom complex score (nose blows, sneezes, stuffy nose, runny nose, itchy nose, and itchy eyes/ears/throat) versus placebo at each evaluation point and overall across all 8 weeks (P < .01) of the trial. Improvements in the individual symptoms of rhinitis were statistically significant (P < or = .04) for nose blows, sneezes, runny nose, itchy nose, and itchy eyes, ears, and throat. Treatment with azelastine also resulted in a clinically meaningful improvement in nasal congestion. Improvement in congestion was accompanied by a decreased requirement for backup decongestant medication. The adverse experiences were generally mild and well tolerated. Azelastine provided effective prolonged relief of the symptoms of perennial allergic rhinitis with no adverse effects that would limit its long-term use.

Effectiveness of azelastine nasal solution in seasonal allergic rhinitis.

Azelastine is a novel antiallergy medication currently under investigation for the treatment of allergic rhinitis and asthma. Pharmacologic studies in laboratory animals and in vitro model systems indicate that azelastine exerts multiple actions including modulation of airways smooth muscle response, interference with inflammatory processes, and inhibition of allergic reactions. In a previous controlled clinical trial, azelastine nasal solution (ASTELIN N.S.) demonstrated effectiveness in controlling symptoms of seasonal allergic rhinitis (SAR). The objective of this 2-week double-blind, parallel-group study was to further assess the effectiveness of azelastine nasal solution in improving allergic rhinitis symptoms. Two hundred forty-seven patients (> or = 12 years) with symptomatic SAR who satisfied a minimum symptoms score during a 1-week, single-blind, baseline evaluation period were randomized to receive azelastine 2 sprays per nostril bid, azelastine 2 sprays per nostril qd, chlorpheniramine 12 mg bid, or placebo using a double-dummy technique to insure blinding. The primary efficacy variables were changes in Major Symptom Complex (nose blows, sneezes, runny nose/sniffles, itch nose, and watery eyes) and Total Symptom Complex (Major plus itchy eyes/ears/throat/palate, cough, and postnasal drip) severity scores. Patients treated with azelastine nasal solution qd and bid had mean percent improvements in the Total and Major Symptom Complex severity scores that were clinically significant (> or = 50% improvement over placebo) after both weeks, at endpoint, and overall. The improvements for the azelastine bid group were statistically significant (P < or = .05) at all evaluation points. Adverse experiences occurred infrequently, and none was considered serious or potentially limiting to the clinical utility of the nasal solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration errors with a conventional metered dose inhaler versus a novel breath actuated device.

Metered dose inhalers are difficult for patients to use. A device that eliminates coordination and timing of actuation may simplify the use of metered dose inhalers. This trial compared (1) number of errors made and (2) specific errors made between the conventional press and breathe metered dose inhaler (MDI) and the novel breath actuated Autohaler inhalation device in 24 subjects. We studied the use of each device in 12 patients trained and experienced in using an MDI and in 12 volunteers who had never been exposed to any inhalation device. We observed that even experienced patients continue to have difficulty with the coordination and timing of metered dose inhalers. The volunteer group had equal difficulty with both devices but it appeared that it was easier for them to learn how to use the breath actuated device than the MDI.

Sensitivity of FEV1 response following one and two inhalations of albuterol: a pilot study.

Eleven patients entered a pilot study designed to evaluate the proportion of eligible responders following a single inhalation of albuterol aerosol, the degree of response, and the sensitivity to distinguish between one and two inhalations based on FEV1 response. Each patient received a single inhalation at 0 and 60 minutes. FEV1 was measured 30 and 60 minutes after each inhalation. Most patients (82%) responded to a single inhalation and the majority (73%) were capable of further response after two inhalations. This study design was able to distinguish FEV1 responses to one and two inhalations of albuterol and provide upward and downward sensitivity sufficient to detect major differences in products.

Synovial fluid inorganic pyrophosphate concentration and nucleotide pyrophosphohydrolase activity in basic calcium phosphate deposition arthropathy and Milwaukee shoulder syndrome.

Synovial fluid (SF) inorganic pyrophosphate (PPi) concentration is elevated in calcium pyrophosphate dihydrate (CPPD) crystal deposition arthropathy. Since CPPD and basic calcium phosphate (BCP) crystals often are present in the same joints, we determined [PPi] and activity of the PPi-generating enzyme, nucleotide pyrophosphohydrolase (NPPH), in SF from the joints of patients with various arthropathies, including those with BCP crystals. We found elevated SF [PPi] in joints with BCP crystals, as well as in joints with CPPD crystals. The presence of BCP crystals in synovial fluids was also predictive of elevated NPPH activity.

Serious adverse reactions to protamine sulfate: are alternatives needed?

Protamine sulfate is a strongly cationic polypeptide that is used commonly in clinical medicine. It is administered regularly after cardiac catheterization, cardiothoracic and vascular surgical procedures, and less frequently after dialysis and leukapheresis because of its capacity to reverse the anticoagulant activity of heparin. In addition, because it delays the absorption of insulin, protamine is combined with insulin in protamine zinc insulin and neutral protamine Hagedorn insulin. Recently, there have been reports of adverse reactions to protamine (Table I). Although most of these reactions were relatively mild, three were fatal; one was clearly the result of type I anaphylaxis. Reactions occur predominantly in patients who were previously exposed to protamine through protamine-containing insulins or during heparin neutralization. Almost 50% of these patients were diabetic; most of whom received neutral protamine Hagedorn insulin, thereby enhancing their chance for presensitization. In 1983 we encountered three patients who suffered adverse reactions to protamine sulfate. Two of these patients will be presented here; the third patient, who died of IgE-mediated anaphylaxis, has already been reported and therefore is mentioned only briefly. We shall discuss adverse reactions to protamine sulfate and alternatives to the routine use of this drug.