Unmet needs in asthma: Global Asthma Physician and Patient (GAPP) Survey: global adult findings.

BACKGROUND: The Global Asthma Physician and Patient (GAPP) Survey is the first global quantitative survey designed to uncover asthma attitudes and treatment practices among separate groups of physicians and patients, with the goal of identifying barriers to optimal management. METHOD: A total of 5582 physician and patient interviews were conducted globally online, by telephone and face-to-face. This paper highlights key global findings from the adult arm (3559 interviews) conducted in 16 countries. RESULTS: Physician and patient responses were found to differ when respondents were asked the same set of questions. Perceptions of time spent on asthma education, the quality of physician-patient communications, awareness and experience of side effects and understanding and knowledge of treatment noncompliance were found to differ between these two sets of respondents. CONCLUSIONS: The GAPP Survey not only defines an unmet need in asthma treatment, but also reveals that there is a direct relationship between the quality of physician-patient communication, the level of treatment side effects and the extent of patient compliance. These survey findings highlight a clear need for improved patient-focused care in asthma.

Pharmacokinetics and tolerability of a new intravenous immunoglobulin preparation, IGIV-C, 10% (Gamunex, 10%).

BACKGROUND AND OBJECTIVES: A new intravenous immunoglobulin (IGIV) process has been developed that integrates efficient inactivation of enveloped virus, using caprylate, with immunoglobulin G (IgG) purification and caprylate removal by column chromatography. Two clinical studies were conducted to compare the pharmacokinetics of the new product, IGIV-C, 10% (Gamunex, 10%), formulated with glycine, with the licensed solvent-detergent (SD)-treated intravenous immunoglobulin IGIV-SD, 10% (Gamimune N, 10%), formulated with glycine, and IGIV-C, 5%, formulated with 10% maltose. MATERIALS AND METHODS: Both studies were randomized, multicentre crossover trials of 18 and 20 (respectively) adult patients with primary humoral immune deficiency in which patients received one IGIV product for three consecutive periods (3-4 weeks) before crossing over to the other product. Pharmacokinetic parameters were determined after the third infusion of each product. RESULTS: IGIV-C, 10% was bioequivalent to IGIV-SD, 10%, with half-lives (t1/2) of 35 and 34 days, respectively. IGIV-C, 5%, was bioequivalent to IGIV-C, 10%, with t1/2 of 35 and 36 days, respectively. The products had comparable safety profiles. CONCLUSIONS: The pharmacokinetic profiles observed in these trials indicate that IGIV-C, 10% may replace, and be administered in a manner similar to, IGIV-SD, 10%.

Patient preferences and satisfaction with prescribed nasal steroids for allergic rhinitis.

A telephone survey of 503 patients with seasonal and perennial allergic rhinitis was performed to assess satisfaction with their nasal steroid therapy and their reasons for preferences for particular products. Product attributes such as efficacy and various sensory features (e.g., nasal irritation, odor, and taste) were evaluated. Although patients generally are satisfied with their nasal steroid preparations, they do show clear preferences for the sensory attributes of different products. Patients are willing to switch on their physicians' recommendations and clearly prefer products with no odor and no taste.

Physician prescribing practices: the role of patient preference in the selection of nasal steroids.

A telephone survey of 100 primary care physicians was performed to assess the awareness of the influence patient preference, patient satisfaction, and other factors have on the selection of nasal steroids for the treatment of allergic rhinitis. Results indicated that physicians believe drug efficacy is the primary reason why one product is chosen over another, while sensory attributes are the next most important criteria for distinguishing among products. Physicians agree that patients would prefer a preparation that has no odor or aftertaste and that patients are willing to switch products if their physicians recommend that they do so.

Onset-of-action for antihistamine and decongestant combinations during an outdoor challenge.

BACKGROUND: Medications containing a combination antihistamine-decongestant are commonly used for allergic rhinitis yet onset-of-action comparisons for symptom relief after a single dose have not been performed. OBJECTIVE: To determine the onset of symptom relief and efficacy of antihistamine-decongestant medications (acrivastine-pseudoephedrine and loratadine-pseudoephedrine) compared with placebo in an outdoor park. METHODS: This study was conducted during the spring of 1997 using a double-blind, placebo-controlled design. Patients completed baseline rhinitis symptom diaries from 7:30 to 9:30 AM. Subjects with qualifying symptom scores received one dose of either acrivastine-pseudoephedrine, loratadine-pseudoephedrine, or placebo at 10:00 AM. Symptom diaries were recorded for the next 4 hours. RESULTS: Of 593 patients randomized to treatment, 592 were included in efficacy analysis. Acrivastine-pseudoephedrine and loratadine-pseudoephedrine demonstrated a mean onset-of-action by 45 and 30 minutes respectively for total symptom and rhinitis symptom scores for the five sites. Onset-of-action for nasal congestion scores was 45 minutes for both medications. Sites having higher pollen exposure (>100 pollen grains over 6 hours) demonstrated a difference between the antihistamine combinations: acrivastine-pseudoephedrine had an onset of action at 45 minutes for total symptom and rhinitis symptom scores, and 15 minutes for nasal congestion scores whereas loratadine-pseudoephedrine had onset-of-action for nasal congestion score of 105 minutes but failed to reach significance at any timepoint for total symptom and rhinitis symptom scores. CONCLUSIONS: Both antihistamine-decongestant combinations demonstrate an onset-of-action within 60 minutes of administration but under conditions of higher pollen exposure, the acrivastine combination was more effective for total symptoms, rhinitis symptoms, and nasal congestion with an onset-of-action within 45 minutes for rhinitis symptoms and 15 minutes for congestion.

Differential metabolism of arachidonic acid in nasal polyp epithelial cells cultured from aspirin-sensitive and aspirin-tolerant patients.

The mechanism of aspirin (acetylsalicylic acid [ASA]) sensitivity associated with severe asthma and chronic rhinosinusitis with nasal polyps ("aspirin triad") has been attributed to arachidonic metabolism alternations, although the putative biochemical defects have not been elucidated. The aim of this study was assessment of the hypothesis that local production of eicosanoids in the respiratory epithelium in patients with ASA-sensitive asthma/rhinosinusitis (ASARS) differs from that of ASA-tolerant patients with rhinosinusitis (ATRS). Nasal polyps were obtained from 10 patients with ASARS and 15 with ATRS during routine polypectomies, and epithelial cells (ECs) were cultured on bovine collagen type I matrix (Vitrogen 100), in medium supplemented with growth factors. The generation of eicosanoids in supernatants of confluent ECs (6 to 8 d of culture; purity > 98%) was quantified by immunoassays. Unstimulated ECs from ASARS patients generated significantly less prostaglandin E(2)(PGE(2)) compared with ATRS (0.8 +/- 0.3 versus 2. 4 +/- 0.5 ng/microg double-stranded deoxyribonucleic acid [dsDNA], respectively), although a similar relative increase in response to calcium ionophore and inhibition with ASA was observed in both groups. Basal levels of 15-hydroxyeicosatetraenoic acid (15-HETE) were not different between groups, and calcium ionophore enhanced its production to a similar extent. However, cells incubation with 200 microM ASA for 60 min resulted in a significant increase (mean +359%) in 15-HETE generation only in ASARS patients, whereas no effect of ASA on 15-HETE generation in ATRS patients was observed. PGF(2alpha) generation was similar in both groups, and no significant generation of PGD(2) or leukotriene C(4) (LTC(4)) was observed in epithelial cell cultures from either group. Our results indicate that nasal polyps ECs from ASA-sensitive patients have significant abnormality in basal and ASA-induced generation of eicosanoids which may be causally related to the mechanism of ASA sensitivity.

Direct expenditures for the treatment of allergic rhinoconjunctivitis in 1996, including the contributions of related airway illnesses.

BACKGROUND: Previous estimates of the national economic burden of allergic rhinoconjunctivitis (AR/AC) have relied on data analyses in which AR/AC was the primary International Classification of Diseases-ninth revision-Clinical Modification (ICD-9-CM)-coded diagnosis. These studies ignore the costs when AR/AC was a secondary diagnosis to other disorders such as asthma and sinusitis. OBJECTIVE: We sought to determine the national direct cost of illness for AR/AC. METHODS: An expert panel used the Delphi technique to estimate the proportion of visits coded by other primary ICD-9-CM diagnoses in which AR/AC was a significant secondary comorbid condition. The costs of this proportion were deemed to be "attributable" to AR/AC and were added to the costs when allergic rhinitis and allergic conjunctivitis were the primary diagnoses. RESULTS: The cost when AR/AC was the primary diagnosis was $1.9 billion (in 1996 dollars). The cost when AR/AC was a secondary diagnosis was estimated at $4.0 billion, giving an estimate of $5.9 billion for the overall direct medical expenditures attributable to AR/AC. Outpatient services (63%, $3.7 billion), medications (25%, $1.5 billion), and inpatient services (12%, $0.7 billion) accounted for the expenditures. Children 12 years and younger accounted for $2.3 billion (38.0%). CONCLUSION: Upper airway allergy is an expensive disease process because of its readily apparent manifestations as AR/AC and its contribution to other airway disorders.

Healthcare expenditures for sinusitis in 1996: contributions of asthma, rhinitis, and other airway disorders.

BACKGROUND: There have been no recent assessments of the economic burden of sinusitis in the peer-reviewed literature. OBJECTIVE: We sought to estimate the 1996 total direct health care expenditures for the treatment of sinusitis. METHODS: This study determined (1) direct expenditures of medical and surgical encounters in which sinusitis was the primary diagnosis and (2) attributable expenditures when related airway diseases were the primary diagnosis and sinusitis was a comorbid condition. An expert panel used the Delphi consensus-building technique to determine the proportions for the latter. RESULTS: Overall health care expenditures attributable to sinusitis in 1996 were estimated at $5.8 billion, of which $1.8 billion (30.6%) was for children 12 years or younger. A primary diagnosis of acute or chronic sinusitis accounted for 58.7% of all expenditures ($3.5 billion). About 12% each of the costs for asthma and chronic otitis media and eustachian tube disorders were attributed to diagnosis and treatment of comorbid sinusitis. Nearly 90% of all expenditures ($5.1 billion) were associated with ambulatory or emergency department services. CONCLUSION: The economic burden of sinusitis in the United States is significant. However, the limitations of this type of evaluation suggest the $5.8 billion amount may be an underestimate of the true direct costs.

Aminopeptidase activity in human nasal mucosa.

BACKGROUND: Aminopeptidases activate bradykinin and degrade many inflammatory peptides. OBJECTIVE: The objective of this study was to identify the types of aminopeptidase activities in human nasal mucosa. METHODS: Human nasal mucosa was homogenized (n = 12), and cytoplasmic (S2) and membrane-rich (P2) fractions were obtained. Several aminopeptidase (Ap) activities were defined by (1) substrate specificity with leucine-enkephalin (leu-Ap) and alanine-nitroanilide (ala-Ap), (2) inhibitor studies with puromycin and bestatin, (3) enzyme activity histochemistry (zymography), (4) immunohistochemistry, and (5) gel electrophoresis. Human volunteers had methacholine, histamine, and allergen nasal provocations to determine the mechanisms controlling nasal aminopeptidase secretion in vivo. RESULTS: P2 was the largest reservoir of puromycin-resistant aminopeptidase activity (630 pmol leu-enk/min/mg protein). S2 contained 32 pmol leu-enk/min/mg activity, with 80% representing puromycin-resistant activity and 20% puromycin-sensitive aminopeptidase (PS-Ap). Ala-Ap was detected in both P2 and S2 fractions and was localized by zymography to epithelial and gland cells. Anti-rat brain-soluble PS-Ap IgG detected immunoreactive material in epithelium, glands, and endothelium. In nasal provocation studies, leu-AP correlated with glandular exocytosis but not vascular leak. CONCLUSIONS: The predominant aminopeptidase in human nasal epithelial and submucosal gland cells was membrane-bound puromycin-resistant aminopeptidase. A novel soluble puromycin-resistant aminopeptidase and lower amounts of soluble PS-Ap were also detected.

Treatment of sinusitis in the next millennium.

Sinusitis is an increasingly more important disease due to its increasing prevalence, costs, and recognition. Most acute sinusitis episodes follow colds or acute allergic rhinitis. Chronic sinusitis is most commonly due to allergic and nonallergic rhinitis or anatomical defects in the nose. Several common immunologic abnormalities usually present as sinusitis and may be recognized first by the allergist-immunologist. Treatment involves a carefully selected antibiotic prescribed for an adequate period of time, nasal hygiene using nasal saline washes, topical nasal corticosteroids, and decongestants. Medical management of sinusitis tends to be effective, even in patients with long-standing sinus disease.

Medical management of sinusitis.

Sinusitis is both prevalent and costly, affecting more than 14% of the population and costing more than $3.5 billion. The signs and symptoms of sinusitis can be subtle: a night cough, chronic nasal congestion, postnasal drip, or recurring headaches. Diagnosis requires a comprehensive understanding of nasal physiology, anatomy, and allergic and immunologic abnormalities, and sinonasal microbiology. The most common events leading to sinusitis are colds, allergic and nonallergic rhinitis, and anatomic defects which interfere with the sinus outflow tracks. Treatment involves drainage of the congested sinuses and elimination of the pathogenic bacteria. Drainage can be accomplished medically by opening the sinus ostia through the use of decongestants and topical corticosteroids; bacteria are effectively eliminated by washing the sinuses with saline and through use of appropriate antibiotics. In patients with recurrent disease, it may be appropriate to continue nasal washing and topical corticosteroids for extended periods of time, or even permanently. With proper medical treatments, most patients do extremely well and do not require surgery. Surgery is aimed at facilitating sinus drainage by widening the outflow tracks and removing anatomic obstructions to adequate drainage. Although we now understand some of the dynamics of sinusitis, more research is needed to clarify our unanswered questions.

Enhancement of histamine--induced vascular permeability in guinea pigs infected with Bordetella bronchiseptica.

In the nasal mucosa, histamine induces vascular permeability, stimulates nociceptive nerves, and recruits parasympathetic reflexes that regulate glandular exocytosis. Unilateral histamine nasal provocations were performed in a group of guinea pigs in the prodromal stage of undiagnosed Bordetella bronchiseptica infection. Vascular permeability in the histamine challenged nostrils was increased approximately 2- to 4-fold compared to healthy animals (p < 0.001). The duration of significant vascular leak was prolonged from 10 to 30 minutes. In the contralateral, nonchallenged nostrils, secretion of total protein and albumin, but not exudation of intravenously infected 125I-bovine serum albumin, was increased, suggesting an augmentation of parasympathetic reflexes without changes in contralateral vascular leak. These observations suggest that Bordetella bronchiseptica infection leads to hyperresponsiveness to histamine in the nasal mucosa with increased vascular permeability and recruitment of nociceptive nerve-parasympathetic reflexes.

Sinusitis: bench to bedside. Current findings, future directions.

Sinusitis, an inflammatory disease of the sinus, is one of the most commonly reported diseases in the United States, affecting an estimated 14% of the population. The prevalence of sinusitis is rising. Between 1990 and 1992, persons with sinusitis reported approximately 73 million restricted activity days-an increase from the 50 million restricted activity days reported between 1986 and 1988. Because critical questions remain unanswered about its cause, pathophysiology, and optimal treatment, sinusitis continues to generate significant health care costs and affects the quality of life of a large segment of the U.S. population. To identify critical directions for research on sinus disease, the American Academy of Allergy, Asthma and Immunology and the American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc., convened a meeting in January 1996 in collaboration with the National Institutes of Allergy and Infectious Disease. This document summarizes the proceedings of that meeting and presents what is intended to be the background for future investigation of the many unanswered questions related to sinusitis.

Sinusitis: bench to bedside. Current findings, future directions.

Sinusitis, an inflammatory disease of the sinus, is one of the most commonly reported diseases in the United States, affecting an estimated 14% of the population. The prevalence of sinusitis is rising. Between 1990 and 1992, persons with sinusitis reported approximately 73 million restricted activity days--an increase from the 50 million restricted activity days reported between 1986 and 1988. Because critical questions remain unanswered about its cause, pathophysiology, and optimal treatment, sinusitis continues to generate significant health care costs and affects the quality of life of a large segment of the U.S. population. To identify critical directions for research on sinus disease, the American Academy of Allergy, Asthma and Immunology and the American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc., convened a meeting in January 1996 in collaboration with the National Institutes of Allergy and Infectious Disease. This document summarizes the proceedings of that meeting and presents what is intended to be the background for future investigation of the many unanswered questions related to sinusitis.