A comparison of imaging techniques in patients with chronic sinusitis (X-ray, MRI, A-mode ultrasound).

Thirty-five patients age 9 to 67 were evaluated for chronic sinusitis by history, physical and laboratory examination, and imaging techniques (X-ray, magnetic resonance imaging (MRI) and flexible rhinoscopy). MRI was the most predictive. To establish the diagnosis of sinusitis, it was more sensitive than plain X-ray for intrasinus disease. Findings of edema, erythema, and drainage on flexible rhinoscopy were consistent with chronic sinusitis and were confirmed by MRI and sinus X-rays in 41% of the cases. Nasal smears for polymorphonuclear cells and eosinophils were suggestive of a diagnosis of chronic sinusitis, but other laboratory tests (CBC, sedimentation rate, quantitative immunoglobulins, total IgEs) were of very limited value in the diagnosis of chronic sinusitis.

Compliance in clinical trials of two nonbronchodilator, antiasthma medications.

An electronic monitoring device was used to assess patient compliance during clinical trials of two new aerosolized nonbronchodilator, antiasthma drugs. Compliance was poor, but similar, in both trials. Patients took the study drug as instructed on a mean of 37.3% days (range 10% to 77%) in one trial and 37.4% days (range 0% to 63%) in the other. Both underuse and overuse were observed. Underuse was seen on a mean of 38.9% days (range 9% to 81%) and 46.0% (range 15% to 80%) respectively; overuse on a mean of 23.5% days (range 6% to 54%) and 16.6% days (range 0% to 41%). In some patients ten or more activations of the device were recorded at the same time. In six patients such multiple simultaneous activations were recorded on two or more separate days. These patients were among the most noncompliant in the study. Multiple simultaneous activations frequently followed underuse days or preceded followup visits, suggesting the possibility of duplicity. Overall compliance was such that valid conclusions about efficacy of the drugs could only have been drawn in six of 34 patients.

The microbiology of chronic sinus disease in children with respiratory allergy.

Chronic maxillary sinusitis is common in children with respiratory allergy and is associated with increased morbidity. The bacteriology of chronic sinus disease in these children has not been adequately evaluated. Between May 1987 and January 1988, 12 children (aged 3 to 9 years), all with documented respiratory allergy and chronic respiratory symptoms consistent with chronic sinusitis (greater than 30 days), were fully evaluated. History, physical examination, complete blood count, nasal smear, and Waters x-ray were done. All patients had opacification of one or both maxillary sinuses, failed to respond to multiple courses of antibiotics, and subsequently underwent maxillary sinus aspiration and irrigation. Specimens were cultured for aerobic and anaerobic organisms with standard technique, and sensitivities were obtained. Culture results revealed a single organism (Moraxella [Branhamella] catarrhalis) in five patients, one patient yielded M. catarrhalis plus Streptococcus species, three were negative, and three patients grew multiple organisms (two with multiple aerobic streptococcal species and one patient with aerobic streptococci and Peptostreptococcus). All children received appropriate culture-directed antimicrobial therapy. Sequential biweekly follow-up revealed progressive radiographic clearing and significant symptomatic improvement. M. catarrhalis is a common pathogen, whereas anaerobic organisms are unusual as a cause of chronic maxillary sinusitis in allergic children. Some children, despite negative cultures, may benefit from maxillary sinus irrigation.

The natural history and response to therapy of chronic urticaria and angioedema.

Previous reports have suggested that the etiology of chronic urticaria/angioedema (greater than 6 weeks) can be identified 10% to 30% of the time while few reports have addressed the natural history of chronic urticaria/angioedema. An analysis of all patients referred to the authors' practice between 1983-1985 with a diagnosis of urticaria/angioedema was performed. Patients with hereditary angioedema were excluded. Eighty-six of the 214 patients had chronic urticaria/angioedema. In the remaining 128 cases of acute urticaria there were four exercise induced, nine contact, six cold induced, six drug induced, 11 food induced, one viral hepatitis associated, 29 with dermographism, and 62 undetermined. An etiology could not be determined in any of the patients with chronic urticaria/angioedema. Laboratory tests, including CBC, chemistry panel, urinalysis, ANA, rheumatoid factor, complement studies, sedimentation rate, and skin tests were all noninformative. Chronic angioedema without urticaria occurred in only nine cases, 31 cases had chronic urticaria alone, and 46 cases had both chronic urticaria and angioedema. Of the patients followed over the 3-year period, 27 resolved while 48 continued to have urticaria/angioedema. Response to medications was variable and will be discussed. Our study suggests that an etiology is determined in much less than 10% of patients with chronic urticaria; fortunately, 32% of our cases resolved over a 3-year period.

A comparison of inhaled albuterol and cromolyn in the prophylaxis of exercise-induced bronchospasm.

Inhaled albuterol and cromolyn by spinhaler have both been shown to be effective in the treatment of exercise-induced bronchospasm. Eighty subjects with exercise-induced bronchospasm participated in a randomized parallel group study comparing albuterol (180 microgram) and cromolyn (20 mg) administered 15 minutes prior to a standardized treadmill challenge. The cromolyn group was restudied after 2 and 4 weeks of 4 times/day cromolyn therapy. The albuterol group was also studied at 2 and 4 weeks, but they only used their inhaler as needed between study visits. The mean maximum FEV1 drop post-exercise in the albuterol group improved from 33% (screening visit) to 6% (treatment day 1). The cromolyn group showed significantly less (P less than .01) improvement than the albuterol group (31% drop at the screening visit to 14% drop at treatment day 1). When 2 or 4 weeks of continuous cromolyn therapy was given in addition to a dosage 15 minutes prior to exercise, there was no significant difference compared with acute cromolyn administration alone. In summary, acute administration of albuterol was better prophylaxis for exercise-induced bronchospasm than acute or chronic cromolyn treatment.

Immediate hypersensitivity reactions to beta-lactam antibiotics.

Allergic reactions to the beta-lactam antibiotics (penicillins, cephalosporins, carbapenems, and monobactams) are a major factor limiting their use. Immediate hypersensitivity reactions to penicillins depend on the presence of preformed allergic (IgE) antibodies to several penicillin determinants. These materials can be used in in-vivo skin testing to exclude those patients at risk for immediate or accelerated allergic reactions. The cephalosporins have not had their relevant determinants defined as related to allergic reactions. The results of in-vivo challenges of patients with IgE to penicillin suggest the incidence of reactivity of cephalosporins in patients allergic to penicillin is less than generally appreciated. The monocyclic beta-lactam antibiotic, aztreonam (a monobactam), failed to show cross-reactivity with penicillin antibodies, because immune reactivity toward the monobactam was directed against side chain rather than nuclear determinants. On the other hand, the new bicyclic carbapenem beta-lactam drugs, represented by imipenem, showed extensive in-vivo cross-reactivity with penicillins.

Pharmacodynamic evaluation of azelastine in subjects with asthma.

A broad antiallergic compound called azelastine was studied pharmacodynamically in 34 subjects to correlate bronchodilator effect with blood levels of azelastine and desmethyl azelastine, its major metabolic product in man. Despite azelastine and desmethyl azelastine blood levels that were proportionate to the dosage range, the bronchodilator effect as measured by FEV1 and forced expiratory flow rate between 25% and 75% of FVC was proportionately greater with 4 mg of azelastine during the 8-hour study period than the anticipated bronchodilator response with the 8 and 16 mg doses. Azelastine, already proven effective in allergic rhinitis, has a bronchodilator effect at doses that do not produce intolerable side effects.

Behavior abnormalities and poor school performance due to oral theophylline use.

Studies evaluating adverse effects of oral theophylline on learning and behavior have been performed on children with asthma receiving long-term theophylline therapy. To further differentiate the effects of asthma itself from the drugs used, we evaluated 20 asthmatic children (6 to 12 years of age) who had not received oral bronchodilators for at least 6 months. A double blind, placebo-controlled, parallel format was used with a 4-week theophylline or placebo period preceded by a 2-week baseline. Theophylline serum levels were maintained between 10 to 20 micrograms/mL. During baseline and treatment periods, the child's home and school behavior/performance were monitored independently by their parents and teachers using standardized report forms. A battery of psychologic tests was administered at the end of baseline and treatment periods. Seven children receiving theophylline were noted to have a change in school behavior and/or performance during their 4 weeks on drug compared to baseline, whereas none of the children receiving placebo were noted to be different (P = .004). Thus, the short-term administration of theophylline to asymptomatic asthmatic children not receiving oral bronchodilators can adversely affect school performance and behavior. Because this population represents the majority of asthmatic children, one needs to use theophylline cautiously in this age group, monitor school performance closely, or seek other treatment modalities.

Use of a tube spacer to improve the efficacy of a metered-dose inhaler in asthmatic children.

Many children with asthma do not use the standard metered-dose inhaler (MDI) skillfully. To improve drug delivery, correct problems of hand-lung incoordination, and reduce local side effects, a number of spacer devices have been developed. We evaluated one such device, a tube spacer (Aerochamber), in 16 asthmatic children (5 to 12 years). On four separate days and in a randomized, double-blind, placebo-controlled manner, they received either metaproterenol sulfate by MDI aerosol (130 micrograms) or placebo with and without the tube spacer. To maximize techniques, at each visit the children had proper instructions, including viewing a videotape. Spirometry was performed at baseline and 5, 15, and 30 minutes, and hourly for six hours, and the patient was monitored. Analysis of the entire group (forced expiratory volume at 1 s and midmaximal expiratory volume) revealed no difference between metaproterenol administered with or without the tube spacer, and both were significantly different than placebo through two hours. Six children had longer and three had better bronchodilatation with the MDI plus tube spacer than with the MDI alone. Side effects and vital signs did not differ between treatments. Under the circumstances of our study, the tube spacer device might enhance the use of the MDI in children who are not properly taught and/or who forget or cannot perform proper technique.

Efficacy of doxepin in the treatment of chronic idiopathic urticaria.

Doxepin hydrochloride, a tricyclic antidepressant, was evaluated in a double-blind, placebo-controlled crossover trial for the treatment of chronic idiopathic urticaria in 16 adults. Efficacy was evaluated by symptom scores, concomitant antihistamine use, and suppression of histamine- and codeine-induced wheal response. Doxepin-treated subjects experienced fewer lesions (p less than 0.001), less waking hours with lesions (p less than 0.01), lesser degree of itch and/or discomfort (p less than 0.001), and less swelling or angioedema (p less than 0.001) as compared to placebo-treated subjects. Doxepin-treated subjects required less daily concomitant antihistamine use (mean 0.13 tablets versus 1.48 tablets, p less than 0.05). Doxepin also significantly suppressed histamine- and codeine-induced cutaneous wheal response as compared to placebo. Lethargy was commonly observed but diminished with continued use. Dry mouth and constipation were also commonly observed. We conclude that doxepin is an effective agent for the treatment of chronic idiopathic urticaria.

Correlation between A-mode ultrasound and radiography in the diagnosis of maxillary sinusitis.

A-mode ultrasound examination of the maxillary sinuses with the Echosine and Sinusvu 2500 units was compared with roentgenographic examination in the diagnosis of maxillary and frontal sinusitis. A-mode ultrasound was primarily useful in the detection of secretions within the sinus and not mucosal thickening. Both ultrasound devices had high specificities (92% for Echosine and 94% for Sinusvu 2500) in the diagnosis of maxillary sinusitis, but the Echosine had a greater overall sensitivity (61%) than the Sinusvu 2500 (29%). More significantly, as the opacification of the roentgenogram increased (a higher probability of secretion), the Echosine demonstrated better agreement with the x-ray film. Ultrasound appeared to be less helpful in diagnosing frontal sinusitis, but there were too few cases of frontal sinusitis for statistical analysis. The Echosine is a useful screening device because of the high specificity of a positive result. Although A-mode ultrasound provides limited value in diagnosing mucosal thickening, it is particularly useful in following the course of therapy once a positive diagnosis of sinusitis has been established without subjecting the patient to additional x-ray exposure.

Efficacy of parenteral albuterol in the treatment of asthma. Comparison of its metabolic side effects with subcutaneous epinephrine.

Three parenteral routes of albuterol sulfate were compared with placebo in their effects on serum potassium and glucose levels, heart rate, and pulmonary function in adult asthmatic subjects. In addition, the metabolic effects of subcutaneous epinephrine were compared directly with subcutaneous albuterol. Intravenous (IV) albuterol (250 micrograms) caused similar decreases in serum potassium (mean 0.6 +/- 0.3 mEq/L) as 500 micrograms albuterol by intramuscular (IM) or subcutaneous routes. With the combined data from all three albuterol routes, glucose increases (mean 25 +/- 15 mg/dl) and heart rate increases (mean 11 +/- 6 beats/min) were clinically less important than potassium decreases. Subcutaneous epinephrine (0.3 ml, 1:1,000) gave changes in serum potassium, serum glucose, and heart rate statistically similar to those of subcutaneous albuterol (500 micrograms). Peak FEV1 improvement (mean 61 percent) was similar with IV albuterol (250 micrograms), IM albuterol (500 micrograms) or subcutaneous albuterol (500 micrograms). Although the efficacy of albuterol in the doses studied was similar, the decrement in serum K+ produced was also similar and comparable to that produced by a standard dose of epinephrine. The potassium decrease may have important clinical implications.

Compliance of patients with asthma with an experimental aerosolized medication: implications for controlled clinical trials.

A Nebulizer Chronolog, a portable device that houses a standard nebulizer canister, was used in a unique method to measure compliance with aerosolized medication. Each actuation is tabulated to within 4 minutes of the actual time of usage and can subsequently be displayed in a day-hour-minute format. Of the 19 patients studied for 12 weeks with a cromolyn-like agent, appropriate usage four times a day ranged from 4.3% to 94.8%. Underusage exceeded overusage and ranged from 5.2% to 95% of the study days. Younger subjects and male subjects were less likely to use the aerosol appropriately. Patients failed to write the truth in their diaries with overreporting of appropriate usage more than 50% of the times. Lack of compliance with aerosolized medication represents an important medical issue for the physicians caring for patients with asthma. The Nebulizer Chronolog elicits new insight into the disparity between reported and observed compliance.

Twice-daily beclomethasone dipropionate in the treatment of childhood asthma.

Chronic nonsteroid-dependent childhood asthma was treated by adding beclomethasone dipropionate (BDP) or placebo (P) to the daily regimen of theophylline (T). Subjects (6-12 years) were selected based on daily control of asthma by T at necessary T levels in sera of 10-20 micrograms. Active BDP (200 micrograms b.i.d.) and P groups were randomly assigned. Each subject's baseline values were evaluated on a 4-week open phase followed by a 10-12 week double-blind phase. Daily diaries were kept for signs, symptoms, Wright peak flow recordings, and medication requirements. Visits were monitored for urine and serum cortisols, pulmonary function tests (PFT), objective changes, and medication compliance. Demographics between both groups were nonsignificant (NS). Baseline PFTs in P group were significantly better than the BDP group. Serum and urine cortisols and ACTH responses were NS (p less than 0.05). Drug efficacy for asthma characteristics was significantly improved in the BDP group (p less than 0.05) only. The BDP group maximized their response by 8 weeks, with improvement of their FEV1 and FEF25-75 PFT. Thus, b.i.d. BDP provided good asthma control and the twice-daily program should insure improved compliance.