Internal Medicine

Osteoporosis affects 40% of white women older than 45 years of age and 15% of white men older than 50 years of age, resulting in approximately 1.5 million annual fractures in the United States. Systemic corticosteroid therapy increases the probability of osteoporosis, even with alternate-day dosing and with dosages sufficiently low so as not to affect the hypothalamic-pituitary-adrenal axis. Inhaled corticosteroid therapy may affect bone density if high-dose therapy is given to select individuals. The potential of increasing osteoporosis with inhaled corticosteroid asthma therapy is a concern because of the availability of more potent inhaled corticosteroid agents and recommendations that inhaled corticosteroid therapy be initiated earlier in the course of asthma. This article provides suggestions, on the basis of the medical literature and consensus of the authors when specific information was not available, for assessing and treating osteoporosis in subjects with asthma. Suggested risk categories are "low risk" (inhaled corticosteroid dosage of ≤800 µg of beclomethasone dipropionate [BDP]/day in adults or ≤400 µg BDP or equivalent in children), "moderate risk" (inhaled BDP >800 µg/day in adults or >400 µg/day in children), and "high risk" (systemic corticosteroid therapy 4 times a year or daily or alternate-day systemic corticosteroid therapy). Dosage of nasal corticosteroid probably should be added to the orally inhaled corticosteroid for total burden of inhaled corticosteroid. Potential treatment strategies based on risk factors and bone density if indicated are offered to assist physicians treating patients with asthma. (J Allergy Clin Immunol 1998;102:353-62.)

Asthma in the elderly (AIE) is under diagnosed and under treated and there is a paucity of knowledge. The National Institute on Aging convened this workshop to identify what is known, what gaps in knowledge remain and suggest research directions needed to improve the understanding and care of AIE. Asthma presenting at an advanced age often has similar clinical and physiologic consequences as seen with younger individuals but co-morbid illnesses and the psychosocial effects of aging may affect the diagnosis, clinical presentation and care of asthma in this population. At least two phenotypes exist among elderly asthma; those with long-standing asthma have more severe airflow limitation and less complete reversibility than those with lateonset asthma. Many challenges exist in the recognition and treatment of asthma in the elderly. Furthermore, the pathophysiological mechanisms of AIE are likely to be different from those seen in young asthmatics and these differences may influence the clinical course and outcomes of asthma in this population.

Five lipoxygenase (5-LO) is the first committed enzyme in the metabolic pathway leading to the synthesis of the leukotrienes. We examined genomic DNA isolated from 25 normal subjects and 31 patients with asthma (6 of whom had aspirin-sensitive asthma) for mutations in the known transcription factor binding regions and the protein encoding region of the 5-LO gene. A family of mutations in the G ϩ C-rich transcription factor binding region was identified consisting of the deletion of one, deletion of two, or addition of one zinc finger (Sp1/Egr-1) binding sites in the region 176 to 147 bp upstream from the ATG translation start site where there are normally 5 Sp1 binding motifs in tandem. Reporter gene activity directed by any of the mutant forms of the transcription factor binding region was significantly ( P Ͻ 0.05) less effective than the activity driven by the wild type transcription factor binding region. Electrophoretic mobility shift assays (EMSAs) demonstrated the capacity of wild type and mutant transcription factor binding regions to bind nuclear extracts from human umbilical vein endothelial cells (HUVECs). These data are consistent with a family of mutations in the 5-LO gene that can modify reporter gene transcription possibly through differences in Sp1 and Egr-1 transactivation. ( J. Clin. Invest. 1997Invest. . 99: 1130Invest. -1137

RATIONALE: Although there are rare reports of cutaneous reactions from inhalation of specific beta-agonists or soy-derived excipients in metered dose inhalers, to our knowledge cutaneous reactions to multiple beta-agonist agents have not been previously reported. METHODS: Case report. RESULTS: A 3-year-old girl with a history of asthma and recurrent idiopathic urticaria presented with a history of acute episodes of urticaria triggered by inhalation of multiple inhaled short-and long-acting betaagonists, including albuterol, levalbuterol, pirbuterol, terbutaline, metaproterenol, and salmeterol. After the patient had been free of urticaria for at least two weeks, 2 inhaled albuterol challenges were performed under medical observation, and generalized urticaria developed within 20 minutes of each challenge. Percutaneous skin testing with albuterol and terbutaline was negative. Intradermal skin testing with 10-2 M dilutions of albuterol and terbutaline resulted in respectively 16mm erythema/2 mm wheal and 17mm erythema/ 2mm wheal responses, a response not observed in a control subject. Laboratory studies were notable for a positive thyroid peroxidase autoantibody (29 IU/ml, normal <2 IU/ml). CONCLUSIONS: This is the first known report of urticaria developing acutely from inhalation of multiple beta-agonists. We cannot entirely exclude the possibility that urticaria would have developed irrespective of beta-agonist exposure in this patient with idiopathic urticaria. However, an IgE mediated mechanism is possible, with potential immunologic cross reactivity to common structural elements of beta-agonists. Alternatively, a non-IgE mediated pharmacologic class effect is conceivable but it is difficult to propose a mechanism given the known mast cell stabilizing effects of beta-agonists.

Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re-evaluate and fine-tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype-specific treatment choices; however, this goal has not yet been achieved.

This study evaluated the prevalence of upper respiratory symptoms (URS) among patients with symptomatic gastroesophageal reflux disease (GERD). Seventy-four subjects with heartburn completed a URS questionnaire before dual-probe, 24-h esophageal pH monitoring. The URS questionnaire was also completed by 74 normal volunteers without previous or current symptoms of GERD. Esophageal pH monitoring results were classified as normal, distal, or proximal and distal gastroesophageal reflux using standardized criteria. Mean URS scores (Ϯ SD) were 8.31 Ϯ 3.98 in the 52 subjects with GERD and 4.57 Ϯ 3.57 in the 22 subjects with negative pH probe studies, p ϭ 0.02. Subjects with negative pH probe studies and normal volunteers scored similarly on the URS questionnaire. Reflux episodes/24 h correlated with URS scores, r ϭ 0.47, p ϭ 0.0001. Seventy-five percent of subjects with upper reflux, 68% of subjects with lower reflux, 36% of subjects with normal esophageal pH studies, and 9% of normal volunteers reported laryngeal symptoms for at least 5 d/mo. Sixty-nine percent of subjects with upper reflux, 50% of subjects with lower reflux, 31% of subjects with normal pH studies, and 14% of normal volunteers reported nasal symptoms for at least 5 d/mo. URS are frequent among subjects with GERD.