Gary S. Rachelefsky

Sinus disease in children with respiratory allergy.

Sinus disease has been assumed to exist in children with respiratory tract allergy, although a systematic evaluation of the relationship of these two processes has never been reported. We have been impressed that sinus involvement often adds significantly to the morbidity rate of allergic disease; when controlled or eliminated, the allergic respiratory process appears easier to control. This study was ‘undertaken to: (1) better define the prevalence of sinus disease in allergic children, and (2) establish clinical and laboratory diagnostic criteria.

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.

Effect of theophylline on gastroesophageal reflux in normal adults

In a randomized, double-blind manner, 15 normal adults were given a single oral loading dose of anhydrous theophylline (6.5 +/- 0.9 mg/kg) and nine normal adults were given placebo. All subjects were tested for serum theophylline levels, acid reflux (using intraesophageal pH probe), and lower esophageal sphincter pressure (LESP) at 1.5, 4, and 8 hr after treatment. Of subjects with negative baseline acid reflux tests, eight of 13 (61.5%) given theophylline developed positive acid reflux tests compared with none of eight subjects given placebo. One of nine (11%) placebo subjects reported heartburn compared with 11 of 15 (73%) subjects given theophylline. The maximum mean percent change in LESP from baseline was +5.62 +/- 28.8% in the placebo group and -25.01 +/- 23.7% in the theophylline group (p = 0.01) at 4 hr after treatment. While only two of nine (22%) adults given placebo had at least a 14% reduction in LESP following treatment, all of the 15 subjects sustained a minimum of 14% relaxation in LESP. This study confirms that oral theophylline at therapeutic serum levels inhibits LESP and induces gastroesophageal reflux (GER) measured by acid reflux tests in most normal adults.

Introduction and definition of sinusitis

We entered the world of clinical research and clinical practice at the same time but in two different locations. Within a short time we became intrigued by patients who had chronic respiratory symptoms that did not fall into the limited diagnostic pigeonhole diagnoses of the early 1970s. Soon we were reporting our experiences and agreeing that patients who were referred for evaluation of allergies commonly had sinus disease. Over the years our interest in sinusitis has grown as has the number of scientists and practitioners who share our desire to understand and better manage this complex problem. This symposium was an opportunity to assemble many of the most knowledgeable researchers and clinicians devoting time to the study of sinus disease today. We expect their contributions to form a body of knowledge that will appeal to the sophisticated clinician whose expertise surpasses what one finds in a textbook. The topics addressed include anatomy of the paranasal sinuses, physiologic defense mechanisms, diagnostic measures, medical management, surgical management, and the relationship between sinusitis and asthma and sinusitis and cystic fibrosis. We hope that these symposium proceedings will serve multiple purposes: to provide a knowledge base for the interested reader, to allow cross-fertilization of ideas among contributors, and to plant the seeds for further research endeavors.

National guidelines needed to manage rhinitis and prevent complications

OBJECTIVES Rhinitis is an extremely common disease worldwide and nasal allergies are one of the major causes of the condition. Allergic rhinitis not only produces a range of nasal and non-nasal symptoms, but it has been closely associated with other chronic airways diseases, such as asthma and sinusitis. This review was undertaken to evaluate the relationship of allergic rhinitis to these diseases and to provide support for proposing national guidelines for managing rhinitis. DATA SOURCES Relevant studies in English were searched for using MEDLINE, bibliographies from obtained articles, and consultation with experts. STUDY SELECTION All major studies related to the epidemiology and effects of allergic rhinitis and the relationship between allergic rhinitis and asthma, sinusitis, and other airways diseases were reviewed. DATA SYNTHESIS There is substantial scientific and clinical evidence that allergic rhinitis frequently coexists with asthma, and sinusitis and may be a predisposing factor for both. In addition, a number of studies have demonstrated that nasal inflammation and obstruction directly affect pulmonary function and clinical symptoms of asthma. Finally, it has been clearly demonstrated that treating allergic rhinitis with antihistamines, nasal corticosteroids, immunotherapy, and allergen avoidance have a significant, positive effect on lung function and asthma symptomology. CONCLUSIONS The prevalence of allergic rhinitis, asthma, and sinusitis are increasing. Asthma and sinusitis can be debilitating conditions. Asthma alone can be life threatening and costly to treat. The timely and optimal treatment of allergic rhinitis may help prevent these conditions or, at least, prevent them from worsening. Consequently, there is an immediate need to establish national, evidence-based, practice guidelines to assist primary care physicians in diagnosing and managing rhinitis and in evaluating and managing rhinitis and in evaluating and managing allergic rhinitis coexisting with other airways diseases.

Comparison of the bronchodilatory effects of cetirizine, albuterol, and both together versus placebo in patients with mild-to-moderate asthma

BACKGROUND Many potential users of the H1 antihistamine cetirizine are asthmatic and may be using inhaled albuterol. This study was conducted to assess the possible bronchodilatory effect of cetirizine in patients with mild-to-moderate asthma and to determine whether cetirizine interacts with albuterol. METHODS In a randomized, double-blind, placebo-controlled, crossover study, the effects on pulmonary function of 5, 10, and 20 mg oral doses of cetirizine with and without inhaled albuterol (180 micrograms) were determined in 12 patients at 11 time points over 8 hours. The primary measure of efficacy was forced expiratory volume in 1 second (FEV1). RESULTS Cetirizine with or without albuterol significantly increased FEV1, peak expiratory flow rate, and forced expiratory flow rate between 25% and 75% of vital capacity relative to baseline and placebo but did not have a significant effect on forced vital capacity. The effect of 20 mg of cetirizine on FEV1 was generally greater than that of 10 or 5 mg, but the difference was statistically significant only at the 30-minute time point (p < 0.05). All three cetirizine doses produced significantly greater increases than placebo in FEV1 and forced expiratory flow rate between 25% and 75% of vital capacity for 8 hours and in peak expiratory flow rate for 7 hours (p < 0.02). Albuterol alone had a significant effect on the four pulmonary function variables from 1 to 5 hours after baseline (p < 0.05), which is consistent with albuterols recommended dosing frequency of every 4 to 6 hours. Albuterol alone increased FEV1 significantly more than 5 mg of cetirizine alone but not 10 mg or 20 mg of cetirizine alone at 60, 90, and 120 minutes after baseline, but all three doses of cetirizine increased FEV1 significantly more than albuterol 7 and 8 hours after baseline (p < 0.05), indicating that the bronchodilatory action of cetirizine lasts longer than that of albuterol. Cetirizine neither potentiated nor inhibited the bronchodilatory action of albuterol, but the two drugs appeared to have an additive bronchodilatory effect. None of the cetirizine treatments caused a worsening of pulmonary function, and all were well tolerated. CONCLUSIONS Cetirizine has a significant bronchodilatory effect in patients with mild-to-moderate asthma and can be used to treat concomitant conditions (e.g., allergic rhinitis) without concern that it will interfere with the bronchodilatory effect of albuterol or cause worsening of asthma by itself.

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.

Improvement of bronchial hyperresponsiveness in asthmatic children treated for concomitant sinusitis.

BACKGROUND There appears to be an association between sinusitis and asthma. The effect on bronchial hyperresponsiveness of clinical therapy for sinusitis in children may help to decipher whether sinusitis and asthma are independent manifestations of the same disease. OBJECTIVE To evaluate the effect of clinical treatment for sinusitis in patients with rhinitis and/or asthma on symptoms and on bronchial hyperresponsiveness to methacholine. METHODS Open label, randomized, non-treatment control in a teaching hospital in São Paulo, Brazil. Forty-six atopic and 20 normal children were studied. The atopic children consisted of 18 with allergic rhinitis (12 without sinusitis and 6 with sinusitis), and 28 children with rhinitis with asthma (13 with normal sinus radiographs and 15 with complete opacification of the maxillary sinuses). Methacholine PC20 was determined before and 30 days after treatment with nasal saline, sulfamethoxazole-trimethoprim, antihistamine/decongestant, and five days of prednisone. Sinus radiographs were also repeated. RESULTS The only patients with increase in methacholine PC20 were patients with rhinitis and asthma with opacified maxillary sinuses at entry and who at 30 days had normal sinus radiographs (P < .05). CONCLUSION In this study, children with allergic rhinitis and sinusitis with asthma improved their bronchial hyperresponsiveness to methacholine and decreased their symptoms with appropriate response of their sinuses to clinical therapy.

Gastroesophageal fundoplication for the management of chronic pulmonary disease in children

Gastroesophageal reflux is a common cause of chronic pulmonary disease in children. Forty-two children with recurrent pneumonia or severe asthma were evaluated and shown to have signicant reflux. Esophagography and esophageal pH testing proved the best diagnostic tests for determining reflux. Although the pulmonary symptoms were often due to repeated aspiration, they appeared in several cases to be related to bronchospasm caused by acid in the upper esophagus. All of the children underwent Nissen fundoplication and gastrostomy an average of 30 months after the onset of pulmonary symptoms. Of the children who had preoperative pneumonia, 87 percent had no recurrence after operation. In 13 of the 14 asthmatic children who underwent operation, symptoms improved and less bronchodilator medication was required. Morbidity and mortality were closely related to the duration and severity of pulmonary disease.

Chronic sinusitis in children with respiratory allergy: the role of antimicrobials☆

We evaluated the role of antimicrobials in the treatment of chronic maxillary sinusitis in children with respiratory allergy. Night and day cough, nasal obstruction, rhinorrhea, postnasal seen. Eighty-four children were treated in a double-blind manner with either amoxicillin, erythromycin, trimethoprim-sulfamethoxazole, or an antihistamine decongestant (carbinoxamine maleate-pseudoephedrine HCl). Radiographic and clinical responses were best with amoxicillin, but trimethoprim-sulfamethoxazole was an adequate alternative. This study demonstrates that allergic children with chronic sinusitis with associated chronic respiratory symptoms are likely to respond clinically and radiologically with antimicrobial treatment.