Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology

Published by Elsevier
Print ISSN: 1081-1206
To compare the safety and efficacy of ipratropium bromide 0.03% (IB) with beclomethasone dipropionate 0.042% (BDP) in the treatment of perennial rhinitis in children. Thirty-three children with nonallergic perennial rhinitis (NAPR) and 113 with allergic perennial rhinitis (APR) were randomly assigned to either IB or BDP for 6 months in a single-blind, multicenter protocol in which the physician was blinded to treatment. At each visit, patients and physicians rated symptom control of rhinorrhea, nasal congestion, and sneezing. Patients also completed quality of life questionnaires at baseline and after 6 months of therapy. Both treatments showed a significant improvement in control of rhinorrhea, congestion, and sneezing compared with baseline over the 6 months of treatment (P < .05). Only for the control of sneezing was BDP consistently better than IB (P < .05). Among the patients given IB, 61% to 73% assessed the control of rhinorrhea as good or excellent on different study visit days, 43% to 60% similarly rated the control of nasal congestion, and 39% to 43% the control of sneezing. The results for BDP were 68% to 78% for the control of rhinorrhea, 55% to 72% for the control of nasal congestion, and 54% to 68% for the control of sneezing. Quality of life assessment documented that both drugs significantly reduced interference with daily activities and disturbance of mood due to rhinorrhea compared with baseline (P < .05). Both treatments were well tolerated with IB causing less nasal bleeding and irritation than BDP. Ipratropium bromide was safe and effective in controlling rhinorrhea and diminishing the interference by rhinorrhea in school attendance, concentration on school work, and sleep. Ipratropium bromide was as effective as BDP in the control of rhinorrhea and showed a relatively good effect on congestion. Patient and physician assessment favored BDP in the control of sneezing.
Perennial rhinitis is a common condition that affects up to 10% to 20% of the population. Multiple agents are frequently administered since no single agent provides complete relief. Studies assessing the benefit/risk of combined therapy are important especially for newly approved agents such as ipratropium bromide nasal spray 0.03%, a topical anticholinergic agent, approved specifically for the treatment of rhinorrhea in allergic and non-allergic perennial rhinitis. To compare the efficacy and safety of the combined use of ipratropium bromide nasal spray 0.03% (42 microg per nostril tid) and beclomethasone dipropionate nasal spray (84 microg per nostril bid) against that of either active agent alone for the treatment of rhinorrhea. Multicenter, 6-week, double-blind, randomized active- and placebo-controlled, parallel trial. Allergist and general practitioner clinical practices. Five hundred thirty-three patients with perennial rhinitis (279 allergic and 274 non-allergic), 8 to 75 years of age, who had at least a mild degree of severity of rhinorrhea for a minimum of 2 hours per day during the 1 week screening period as well as congestion or sneezing also of at least mild severity. Either (1) ipratropium bromide nasal spray 0.03% (42 microg per nostril tid) plus beclomethasone dipropionate nasal spray (84 microg per nostril bid), (2) ipratropium bromide nasal spray 0.03% (42 microg per nostril tid) alone, (3) beclomethasone dipropionate nasal spray (84 microg per nostril bid) alone, or (4) vehicle [matching placebo nasal spray for the ipratropium bromide (2 sprays per nostril tid)] or beclomethasone dipropionate (2 sprays per nostril bid). Severity and duration of rhinorrhea, and patient and physician global assessment of control of rhinorrhea. Ipratropium bromide nasal spray plus beclomethasone nasal spray was more effective than either active agent alone or vehicle in reducing the average severity and duration of rhinorrhea during 4 weeks of treatment. The advantage of ipratropium bromide plus beclomethasone nasal spray was evident by the first day of combined treatment and continued throughout the 2-week treatment period. Ipratropium bromide nasal spray had a faster onset of action during the first week of treatment and reduced the duration of rhinorrhea more than beclomethasone. Beclomethasone nasal spray was more effective in reducing the severity of congestion and sneezing than ipratropium. In patients who had not responded well to a nasal steroid prior to participation in the study based on a questionnaire administered at screening, ipratropium bromide was as effective in the steroid non-responders as steroid responders, whereas beclomethasone was more effective in steroid responders. Combined active therapy was well tolerated with no increase in adverse events over that seen previously with ipratropium bromide or beclomethasone nasal spray alone. The combined use of ipratropium bromide nasal spray with beclomethasone dipropionate nasal spray is more effective than either active agent for the treatment of rhinorrhea, and does not result in a potentiation of adverse drug reactions. Ipratropium bromide nasal spray 0.03% alone should be considered in patients for whom rhinorrhea is the primary symptom, and its use in combination with a nasal steroid should be considered in patients where rhinorrhea is one of the predominant symptoms, or in patients with rhinorrhea not fully responsive to other therapy.
Rhinorrhea from common colds or allergies in children is similar to that in adults, yet there are few data on the use of ipratropium bromide nasal spray in children younger than 5 years. To evaluate the safety and efficacy of 0.06% ipratropium bromide nasal spray in 2- to 5-year-old children with rhinorrhea from a common cold or allergies. A total of 230 children (43 with common colds and 187 with allergies) participated in an open-label, multicenter study. Patients with a common cold received ipratropium bromide nasal spray (84 microg per nostril) 3 times daily for 4 days; those with allergies received ipratropium bromide nasal spray (42 microg per nostril) 3 times daily for 14 days. In the common cold and allergy groups, 91% and 90% of the parents, respectively, found that ipratropium bromide was either "very useful" or "somewhat useful." Furthermore, 67% and 91% of parents in the common cold and allergy groups, respectively, found that administration of a nasal spray was either "extremely easy" or "very easy." Symptom scores were improved from baseline in both groups. The nasal spray was well tolerated and was not associated with serious or systemic anticholinergic adverse effects. Most adverse events were infrequent and mild to moderate, and study discontinuation due to an adverse event occurred in less than 3% of patients. The 0.06% ipratropium bromide nasal spray, 42 or 84 microg per nostril 3 times daily, is easy to administer, safe, and effective for the control of rhinorrhea in children aged 2 to 5 years with a common cold or allergies.
Allergic rhinoconjunctivitis patients are often treated with nasal or systemic allergy therapy, forgoing therapy for ocular symptoms. This treatment regimen leaves important aspects of the allergic reaction untreated and affects quality of life (QoL). The Rhinoconjunctivitis Quality of Life Questionnaire and the Allergic Conjunctivitis Quality of Life Questionnaire quantify separate aspects of QoL. To determine the benefit gained in QoL, measured by these questionnaires, when antiallergy eyedrops (olopatadine) were added to patients' preexisting regimens of nasal or systemic allergic rhinitis treatment. This was a 4-week prospective, multicenter, open-label, crossover, environmental QoL study. Visit 1 randomized patients to treatment group A or B and included baseline examinations and questionnaires. Group A instilled olopatadine twice daily and concomitantly with previously prescribed nasal or systemic antiallergy medication for 2 weeks. Group B received no ocular therapy and used only previously prescribed antiallergy medication for 2 weeks. Treatment group crossover occurred at visit 2. Patients again completed the questionnaires at visits 2 and 3. Two hundred patients completed the study, 97 in group A and 103 in group B. Groups A and B experienced ocular allergic symptoms for 3.88 and 3.96 days, respectively, during the week before baseline. At visits 2 and 3, questionnaire scores were significantly improved for each group when olopatadine was added compared with the nontreatment periods. By visit 2, olopatadine improved QoL by 49% compared with 5% in the nontreated group (P < .001). In this study, 90.5% of patients with allergic rhinitis treated nasally or systemically also had ocular allergic symptoms. Adding olopatadine to these patients' medication regimens significantly improved ocular allergic symptoms and overall QoL.
There is a limited body of evidence comparing the clinical effects of different inhaled corticosteroids in the treatment of asthma. This study compared the safety and efficacy of inhaled flunisolide and budesonide, both with unique delivery systems that may affect clinical response. This multicenter study was carried out to compare the efficacy and safety of flunisolide, administered via AeroChamber, with budesonide, administered via Turbuhaler, in the treatment of moderate asthma. Patients with moderate asthma, defined as an FEV1 of 40% to 85% of predicted, underwent a 2-week run-in period during which beclomethasone, 750 microg twice daily by MDI, was administered, along with salbutamol prn. Patients (n = 176) were then randomized into two groups. One group received flunisolide administered via AeroChamber, 750 microg (3 puffs), twice daily. The second group received budesonide administered via Turbuhaler, 600 microg (3 puffs), twice daily. All patients took salbutamol prn. At the end of the 6-week treatment period, there were no significant differences (P > .05 for all comparisons) in efficacy between the groups as evaluated by any efficacy parameter. The treatment groups also did not differ significantly in the number of adverse events or in the incidence of oropharyngeal Candida infection. Flunisolide administered by AeroChamber and budesonide administered via Turbuhaler demonstrate similar efficacy and safety in the treatment of moderate asthma.
Human leukocyte antigen (HLA) class II gene products are involved in the antigen presentation of exogenous antigens. The aim of this study was to evaluate whether specific immunoglobulin (Ig)E responses to purified major allergens of Dermatophagoides pteronyssinus (Der p 1 and Der p 2) were associated with genotypes of HLA-DRB1 alleles. Peripheral venous blood samples were collected from two groups of unrelated Korean adolescents: 168 subjects with positive skin response (wheal > or = 3 mm) to crude D. pteronyssinus allergens and 94 age-matched controls with negative skin response and low serum-specific IgE to crude D. pteronyssinus allergens. The former group was found to contain 104 with high serum-specific IgE to crude D. pteronyssinus allergens, 100 with high serum-specific IgE to Der p 1, and 122 with high serum-specific IgE to Der p 2. Genotypes of the HLA-DRB1 alleles were determined using polymerase chain reaction-sequence specific oligonucleotide probes. HLA-DRB1*07 was significantly higher in subjects with a high serum-specific IgE response to crude D. pteronyssinus allergens than the controls (16.3% vs 3.2%, odds ratio [OR] = 5.93, corrected P [Pc] = 0.02). The excess of DRB1*07 was more marked in those with high serum-specific IgE responses to Der p 1 or Der p 2 than the controls (20.0% vs 3.2%, OR = 7.58, Pc = 0.004; 18.9% vs 3.2%, OR = 7.05, Pc = 0.006). Among subjects with high serum IgE to Der p 1, DRB1*13 significantly increased than the controls (32.0% vs 13.8%, OR = 2.93, Pc = 0.03). We clearly observed the association between HLA-DRB1 alleles and specific IgE responsiveness to D. pteronyssinus major allergens. The molecular mechanism of HLA-DRB1*07 and DRB1*13 involvement in D. pteronyssinus-specific IgE responsiveness awaits further investigation.
Recently, a novel percutaneous adhesive tulobuterol preparation, HN-078, has been developed and tests using healthy adult subjects have indicated it to be effective for controlling exacerbations early in the morning if applied at bedtime. In children, percutaneous application is very important to eliminate side effects, including abdominal pain and appetite loss. We report the pharmacokinetics and pharmacodynamics of tulobuterol patch, HN-078, in the treatment of childhood asthma. Single applications of HN-078 were applied transdermally in six children with asthma who had been admitted to a hospital. Subjects weighing less than 30 kg received 1 mg of tulobuterol while subjects weighing 30 kg or above received 2 mg on the chest for 24 hours. Serum tulobuterol levels and peak expiratory flow rate were determined before and after each application. Cmax of tulobuterol was determined to be 1.33 +/- 0.21 ng/mL, Tmax was 14.0 +/- 2.0 hours, and AUCO-t was 27.1 +/- 4.2 These pharmacokinetic parameters per body surface area of children were nearly equivalent to those of adults obtained in other studies. Peak expiratory flow rate values obtained after application of HN-078 significantly increased in comparison to those obtained before application. No significant changes were observed in pulse rate or blood pressure, and no side effects were found with regard to the subjective symptoms and skin conditions. These results suggest that the patch formulation of tulobuterol, HN-078, will be very useful for the treatment of pediatric asthma. It is especially significant that no side effects were observed.
Mometasone furoate (Nasonex), in a new once-daily aqueous nasal spray formulation, has been shown to be as effective and well-tolerated as twice-daily beclomethasone dipropionate aqueous nasal spray in treating symptoms of seasonal allergic rhinitis and perennial rhinitis. To compare the effectiveness and tolerability of mometasone furoate to placebo and to fluticasone propionate aqueous nasal spray, all treatments administered once-daily, in patients with perennial rhinitis. This was a 3-month, randomized, double-blind, double dummy, parallel group study in 550 patients, aged 12 to 77 years, at 25 centers in Canada, Latin America, and Europe. Patients allergic to at least one perennial allergen, with confirmed allergy history, skin test positivity, and moderate to severe symptomatology, were eligible to receive one of the following treatments, once daily in the morning: mometasone furoate 200 micrograms, fluticasone propionate 200 micrograms, or placebo. The primary efficacy variable was the change from baseline in total AM plus PM diary nasal symptom score over the first 15 days of treatment. Four hundred fifty-nine patients were valid for efficacy. For the primary efficacy variable, mometasone furoate was significantly (P < .01) more effective than placebo and was not statistically different from fluticasone propionate (percent reductions from baseline were 37, 39, and 22 for mometasone furoate, fluticasone propionate, and placebo, respectively). Generally, similar trends were seen for physician-evaluated total nasal symptoms, and patient-rated and physician-rated overall condition and response to therapy. Overall, mometasone furoate was at least as effective as fluticasone propionate at equivalent doses. There was no evidence of tachyphylaxis. All treatments were well tolerated. Mometasone furoate and fluticasone propionate adequately controlled symptoms of perennial rhinitis and were well tolerated.
Designing of methods for an accurate diagnosis is a main goal of allergy research. Olive pollen allergy is currently diagnosed using commercially available pollen extracts that do not allow identification of the molecules that elicit the disease. To analyze the suitability of using the N- and C-terminal domains (NtD and CtD, respectively) of the 1,3-beta-glucanase Ole e 9, a major allergen from olive pollen, for in vitro diagnosis. Serum samples from 55 olive-allergic patients were assayed using enzyme-linked immunosorbent assay to study hypersensitive patients with IgE reactivity to Ole e 9. The specific IgEs to NtD and CtD, obtained by recombinant technology, were determined by means of immunoblotting, enzyme-linked immunosorbent assay, and inhibition assays. Thirty-one of 33 serum samples from Ole e 9-allergic patients were IgE reactive to recombinant NtD (rNtD) (n = 26 [79%]), recombinant CtD (rCtD) (n = 22 [67%]), or both (n = 17 [52%]). Nine patients (27%) were exclusively reactive to rNtD and 5 (15%) to rCtD. Inhibition assays of IgE binding to Ole e 9 with a mixture of both domains abolished 90% of the binding, whereas 44% and 45% were abolished when rNtD and rCtD were used, respectively. Because sensitization to NtD or CtD of Ole e 9 could be correlated to vegetable food-latex-pollen cross-reactivity processes or to the exacerbation and persistence of asthma, respectively, these molecules could be used in vitro as markers of disease to classify patients and to design a patient-tailored immunotherapy approach.
A novel form of food allergy has been described that initially became apparent from IgE reactivity with the drug cetuximab. Ongoing work regarding the etiology, distribution, clinical management, and cellular mechanisms of the IgE response to the oligosaccharide galactose-α-1,3-galactose (α-gal) is reviewed. Brief review of the relevant literature in peer-reviewed journals. Studies on the clinical and immunologic features, pathogenesis, epidemiology, laboratory evaluation, and management of IgE to α-gal are included in this review. Recent work has identified a novel IgE antibody response to the mammalian oligosaccharide epitope, α-gal, that has been associated with 2 distinct forms of anaphylaxis: (1) immediate-onset anaphylaxis during first exposure to intravenous cetuximab and (2) delayed-onset anaphylaxis 3 to 6 hours after ingestion of mammalian food products (eg, beef and pork). Study results have suggested that tick bites are a cause of IgE antibody responses to α-gal in the United States. Patients with IgE antibody to α-gal continue to emerge, and, increasingly, these cases involve children. Nevertheless, this IgE antibody response does not appear to pose a risk for asthma but may impair diagnostic testing in some situations. The practicing physician should understand the symptoms, evaluation, and management when diagnosing delayed allergic reactions to mammalian meat from IgE to α-gal or when initiating treatment with cetuximab in patients who have developed an IgE antibody response to α-gal.
Although it is known that anaphylaxis can follow a biphasic course, reports of its incidence are conflicting. Furthermore, little is known about predictors of biphasic reactivity. To describe the incidence and characteristics of biphasic anaphylaxis occurring in a Canadian tertiary care center. All patients with emergency department visits and inpatients given a diagnosis of "allergic reaction" or "anaphylaxis" during a 3-year period were evaluated. Patients were contacted within 72 hours to establish symptoms and determine the presence of biphasic reactivity. A full medical record review ensued, and uniphasic and biphasic cases were compared using the Mann-Whitney U test for continuous data and the chi2 and Fisher exact tests for ordinal data. A total of 134 patients with anaphylaxis were identified; complete follow-up was obtained for 103 patients. Twenty patients (19.4%) experienced confirmed biphasic reactivity. Average time to onset of the second phase was 10 hours (range, 2-38 hours); 8 patients (40.0%) had their second phase occur more than 10 hours after the initial reaction. The clinical presentations and histories of uniphasic and biphasic reactors were similar. Time to resolution of initial symptoms was significantly longer for biphasic reactors (112 vs 133 minutes; P = .03). Differences in management were noted: biphasic reactors received less epinephrine (P = .048) and tended to receive less corticosteroid (P = .06). Biphasic reactivity occurred with an incidence of 19.4%, consistent with first descriptions. The second-phase onset was 10 hours on average, but it occurred as late as 38 hours. Biphasic anaphylaxis may be related, in part, to undertreatment.
Chronic spontaneous urticaria (CSU) lasting more than 6 weeks is one of the most disabling types of urticaria and often results in severely impaired quality of life. Patients with CSU are often unsatisfied with the standard treatment. Another treatment option recommended for patients with so-called nonresponding CSU according to the newest guidelines is intravenous immunoglobulin (IVIG). To assess the efficacy and safety of high-dose IVIG as a treatment option in patients with therapy-resistant CSU. Six patients with severe CSU unresponsive to other treatment options according to the newest guidelines for several weeks were treated with high-dose IVIG (2 g/kg every 4-6 weeks). The response to treatment was observed on the basis of clinical signs and reduction of co-medications using a special treatment score. Patients were studied during the treatment period and were followed up for an average of 16 months. Adverse events were assessed. Patients showed an improvement in symptoms and a reduction in co-medication use just after the first cycle. Symptoms such as itching, wheals, and edema were reduced after the first or second cycle of IVIG treatment. Four of 6 patients had complete remission after 2 to 4 cycles. One patient needed a longer continuation of treatment to reach a stable state of improvement, and another patient had a slight relapse after the seventh cycle. Adverse effects, such as headache and increased blood pressure, were observed only at the beginning of treatment. High-dose IVIG represents an important therapeutic option in patients with severe CSU.
Interleukin 10 (IL-10) and IL-11 are known to have anti-inflammatory activities, and they have been implicated in the pathogenesis of respiratory syncytial virus (RSV) infection. To determine IL-10, IL-11, and myeloperoxidase levels in nasal secretions of infants with acute RSV bronchiolitis and to investigate whether there are any differences in these levels in patients with vs without atopy. We measured IL-10, IL-11, and myeloperoxidase levels in nasal secretions of 44 infants (20 were atopic) with acute RSV bronchiolitis. The nasal secretion samples were obtained from patients at hospital admission and were stored immediately at -70 degrees C until analysis. Atopy was defined as having at least 1 positive skin prick test reaction to common allergens, a history of atopic dermatitis, or a high serum IgE level compared with age-matched controls. Levels of IL-10, IL-11, and myeloperoxidase increased significantly in samples from infants with acute RSV bronchiolitis. Levels of IL-10 and IL-11 were significantly lower in patients with vs without atopy (P < .05). Myeloperoxidase levels showed no significant difference in patients with vs without atopy (P = .18). Patients with severe symptoms tended to have lower IL-10 levels (P = .09), but no relationship was shown between symptom severity and IL-11 levels. Nasal myeloperoxidase levels were significantly higher in patients with severe symptoms (P < .05). Production of IL-10 and IL-11 was significantly lower in patients with vs without atopy during acute RSV bronchiolitis. The airway inflammation induced by RSV infection may be different in patients with vs without atopy, and this is associated with lower induction of these immunoregulatory cytokines in children with atopy.
Although anaphylaxis is considered a life-threatening event, there is a lack of information on the clinical characteristics at presentation, both in adults and in children. To describe in a nonselected population the clinical characteristics and the treatments of acute anaphylaxis triggered by different agents. This is a retrospective review of the clinical features of 113 episodes of acute anaphylaxis resulting in admission to a university hospital. Initially, the 107 patients visited the emergency room and were then admitted to the hospital. Most anaphylactic events (63%) occurred at home. The most frequent symptoms involved the respiratory system (78%) and the skin (90%). Drugs, especially nonsteroidal anti-inflammatory drugs and antibiotics, were the most frequent cause of anaphylaxis in adults (49%). Patients with drug-induced anaphylaxis were older and more often had cardiovascular symptoms (hypotension and tachycardia) (P = 0.0064). Hymenoptera venom was the second most frequent cause of anaphylaxis (29%). Most of the patients with hymenoptera venom anaphylaxis were male (80%) and more frequently they had no history of atopy (P = 0.012). In food-induced anaphylaxis, the cardiovascular system was less likely to be involved (P < 0.05) (39%). Seafood seems to be frequently involved in food-induced anaphylaxis in our area. Specific immunotherapy-induced anaphylaxis occurred more often in younger patients (P = 0.032). Epinephrine seems to be underused in Italy (only 15% of patients received it), especially for respiratory symptoms. Anaphylaxis triggered by different agents may have different clinical presentations and may occur in different types of patients. In Italy, the inadequate use of epinephrine for anaphylaxis treatment needs to be publicized to both physicians and the general population.
Subcutaneous immunoglobulin (SCIG) is an option for replacement therapy in patients with humoral immune deficiencies. To describe a patient with common variable immunodeficiency (CVID) and von Willebrand disease who tolerated immunoglobulin replacement via the subcutaneous route. An 11-year-old boy receiving monthly intravenous immunoglobulin (IVIG) since 5 years of age presented to an academic medical center after moving to the area. The patient also had a history of von Willebrand disease. He had started receiving IVIG because of recurrent infections and an absent IgG subclass 3. Further immunologic assessment revealed a normal B-cell count, decreased IgM level, and an abnormal response to bacteriophage phiX174. Given these findings and the lack of another cause, the patient was diagnosed as having CVID. Because of difficult intravenous access, a port was placed for IVIG administration in 1999. The initial port was removed because of infectious complications, and a second port was found to be distally displaced in the right atrium, requiring removal. Continued difficulties with intravenous access and the potential complications with maintaining a long-term indwelling catheter prompted consideration of alternative methods for immunoglobulin administration. After removal of the port, the patient was prescribed weekly SCIG infusions. He tolerated the infusions well without bleeding complications related to the von Willebrand disease and was able to transition to home infusions. SCIG was well tolerated by a pediatric patient with CVID and von Willebrand disease without any significant bleeding complications.
Hereditary angioedema (HAE) due to C1 inhibitor deficiency is clinically characterized by relapsing skin swellings, abdominal pain attacks, and life-threatening upper airway obstruction. Treatment with androgens prevents attacks for those with this condition. To examine the benefits and risks of long-term treatment with danazol. Data were generated retrospectively from 118 German and Danish patients who had HAE due to C1 inhibitor deficiency and were treated with danazol from 2 months to 30 years. The frequency and severity of acute attacks were registered before and during danazol treatment, and adverse effects to the treatment were noted. Data were collected by using standardized questionnaires. In all, 111 of 118 patients responded to danazol. During treatment, 54 of the 118 patients (45.8%) became symptom free or had 1 attack or less per year. In the other patients, hereditary angioedema ran a mild course. The frequency of acute attacks during danazol treatment was reduced to 16.2%, and the attacks were considerably milder than before treatment. Laryngeal edema was reduced to 4.8%. Adverse effects (weight gain, virilization, menstrual irregularities, headache, depression, and/or liver adenomas) occurred in 93 of the 118 patients and led to discontinuation of danazol therapy in 30 patients. Danazol is highly beneficial in patients with frequent and severe attacks of HAE. Because the risk of adverse effects is high, close monitoring of patients is mandatory. However, many patients accept the adverse effects of prophylactic treatment to avoid the distressing and sometimes life-threatening attacks of this condition.
Although mustard seed allergy has been largely reported during the preceding 20 years, currently only 2 allergens, Sin a 1 and Bra j 1, have been identified. To improve the characterization of the allergenic profile of yellow mustard seeds by reporting the identification and biochemical characterization of an 11S globulin as a new major allergen. Mustard seed proteins were separated using size exclusion and ion-exchange chromatographic columns, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and 2-dimensional polyacrylamide gel electrophoresis. Separation of different polypeptide chains was achieved by reverse-phase high-performance liquid chromatography. Mass spectrometry after tryptic digestion and Edman degradation were used to determine amino acid sequences of peptides. IgE binding assays were performed with 13 serum samples from mustard allergic patients in immunoblotting and enzyme-linked immunosorbent inhibition assays. A protein of 51 kDa was recognized as a major allergen by patients allergic to mustard and called Sin a 2. The allergen was dissociated in 2 chains of 36 and 23 kDa, which also bound IgE. N-terminal end and internal amino acid sequences allowed identification of the new allergen as a seed storage 11S globulin belonging to the Cupin super family. Purified allergen was able to inhibit the IgE binding of sera from allergic patients to mustard seeds extract in up to 55% of the responses. An 11S globulin storage protein has been isolated and identified as a novel major allergen of mustard seeds.
Leptin-related effects on inflammation and bronchial hyperresponsiveness (BHR) in the human airway have not been demonstrated. To investigate the relationship between the levels of serum leptin and BHR and urinary leukotriene E4 (LTE4) and 9α,11β-prostaglandin F2 (9α,11β-PGF(2)) release after exercise challenge in asthmatic children. Eighty-six prepubertal children between 6 and 10 years old were enrolled and divided into 4 groups: 19 obese asthmatic children, 25 normal-weight asthmatic children, 21 obese nonasthmatic children, and 21 healthy controls. We measured serum leptin levels and urinary LTE4 and 9α,11β-PGF2 levels in children before and 30 minutes after the exercise challenge. Serum leptin levels were significantly higher in obese asthmatic children compared with normal-weight asthmatic children. Significant increases in urinary levels of LTE4 and 9α,11β-PGF2 were observed in obese asthmatic children after the exercise challenge. Although smaller than in obese asthmatic children, significant increases in the urinary levels of LTE4 and 9α,11β-PGF2 were also observed in the normal-weight. Asthmatic children Logarithmic serum leptin values were significantly associated with the logarithmic maximum percentage change in forced expiratory volume in 1 second, the logarithmic urinary LTE4 change, and the logarithmic urinary 9α,11β-PGF2 change from baseline to after exercise in both obese and normal-weight asthmatic children. The serum levels of leptin were significantly associated with BHR and urinary LTE4 and 9α,11β-PGF2 release induced by exercise challenge in asthmatic children.
Second-generation antihistamine-decongestant combinations are often used to treat seasonal allergies. However, onset of action and efficacy data for these agents in a controlled setting are limited. Determine onset of action of fexofenadine-pseudoephedrine (Allegra-D, Aventis, Bridgewater, NJ) for treating moderate-to-severe seasonal allergies in an allergen exposure unit. This single-dose, double-blind, placebo-controlled study was conducted during the fall ragweed allergy season. Qualifying subjects attended one to two priming visits; those with sufficient symptom scores returned for treatment and were initially exposed to ragweed pollen for 90 minutes. Symptomatic subjects received fexofenadine-pseudoephedrine or placebo and recorded symptoms for 6 hours postdose. Efficacy variables were major symptom complex (MSC; sneezes, itchy nose, runny nose, watery eyes, itchy eyes, itchy ears/throat, stuffy nose), total symptom complex (nose blows, sniffles, postnasal drip, cough, plus all MSC symptoms), and all individual symptoms as well as headache. Onset of action for each efficacy variable was calculated as the earliest time at which a consistent, significant decrease was seen for fexofenadine-pseudoephedrine versus placebo. Of 571 screened subjects, 298 were randomized. Onset of relief for fexofenadine-pseudoephedrine (n = 148) was 45 minutes postdose (MSC, P = 0.0127; total symptom complex, P = 0.0380). All individual symptoms were reduced to a greater extent with fexofenadine-pseudoephedrine than with placebo (P < 0.05, not adjusted for multiple comparisons). Decrease in headache with fexofenadine-pseudoephedrine versus placebo began 45 minutes postdose (P = 0.0425). Incidence of treatment-related adverse events was 1.4% for fexofenadine-pseudoephedrine and 3.3% for placebo. Fexofenadine-pseudoephedrine was safe and effective in treating a broad range of allergy symptoms, with a rapid onset of action at 45 minutes.
Indian jujube is a fruit abundantly cultivated in Taiwan. Its major allergen in latex-fruit syndrome is Ziz m 1 of the chitinase III family. The Ziz m 1 Pichia (rZiz m 1-P) has chitinase activity but not Ziz m 1 E. coli (rZiz m 1-E). This study examined whether plant chitinase III, using rZiz m 1-P and rZiz m 1-E, can stimulate allergic inflammation similar to that of mammalian chitinases. Five patients allergic to latex-Indian jujube and five nonallergic controls were evaluated. Their peripheral blood mononuclear cells (PBMC) were cultured with rZiz m 1-E or rZiz m 1-P and pulsed with phorbol 12-myristate 13-acetate. Eleven cytokines were measured by FlowCytomix human Th1/Th2 plex kit and interleukin (IL)-13 by sandwich enzyme-linked immunosorbent assay (ELISA). Interleukin-13 significantly increased in rZiz m 1-P stimulated PBMC of allergic subjects but was undetectable when stimulated with rZiz m 1-E. The stimulation index significantly increased in IL-13 (380.6 ± 77.33 vs 13.70 ± 6.92), IL-5 (6.70 ± 0.59 vs 0.70 ± 0.37), IL-1β (32.70 ± 0.83 vs 2.10 ± 1.29), and tumor necrosis factor beta (TNF-β) (17.10 ± 2.66 vs 1.50 ± 0.66) between allergic and nonallergic subjects after rZiz m 1-P stimulation. There was no difference in terms of IL-2, IFN-γ, IL-8, and TNF-α production. The biological function of chitinase activity is required for Ziz m 1 to induce a Th2-specific immune response. This is the first report on PBMC responses of latex-fruit syndrome subjects toward an active exogenous plant class III chitinase that can stimulate multiple cytokines, especially IL-13, from allergic subjects. This implies the role of cross-reactive food allergens in propagating allergic inflammation among allergic subjects.
Diisocyanate asthma (DA) affects 2% to 10% of exposed workers, yet the pathogenetic mechanisms underlying this disorder remain ill defined. To determine if specific single nucleotide polymorphisms (SNPs) of interleukin 4 receptor alpha (IL4RA), IL-13, and CD14 promoter genes are associated with DA. Sixty-two workers with DA confirmed by specific inhalation challenge (SIC) and 75 diisocyanate-exposed, SIC-negative workers were analyzed for SNPs associated with IL4RA, IL-13, and CD14 promoter genes. No associations were found with individual SNPs and DA. When stratified according to specific diisocyanate exposure, a significant association was found between IL4RA (I50V) II and DA among individuals exposed to hexamethylene diisocyanate (HDI) (odds ratio [OR], 3.29; 95% confidence interval [CI], 1.33-8.14; P = .01) only. Similarly, the IL4RA (I50V) II and IL-13 (R110Q) RR combination was significantly associated with DA in HDI-exposed workers (OR, 4.13; 95% CI, 1.35-12.68; P = .01), as was the IL4RA (I50V) II and CD14 (C159T) CT genotype combination (OR, 5.2; 95% CI, 1.82-14.88; P = .002) and the triple genotype combination IL4RA (I50V) II, IL-13 (R110Q) RR, and CD14 (C159T) CT (OR, 6.4; 95% CI, 1.57-26.12; P = .01). Gene-environmental interactions may contribute to the pathogenesis of DA, and gene-gene interactions may modulate this relationship.
Beta2-Adrenergic agonists are the most potent agents clinically used in inhibiting and preventing the immediate response to bronchoconstricting agents and in inhibiting mast cell mediator release. This raises the possibility that an abnormality in beta-adrenergic receptor function or circulating catecholamine levels could contribute to airway hyperresponsiveness. To link interleukin 13 (IL-13) to the pathogenesis of asthma. Almost 4 decades ago, Andor Szentivanyi published a beta-adrenergic theory of atopic abnormality in bronchial asthma. He proposed 9 characteristics to define bronchial asthma. Because he published these 9 tenets of the beta-adrenergic blockade theory of asthma in 1968, it is appropriate and important to evaluate their relevance in light of advances in pharmacology, inflammation, and immunology. We describe the effects of the allergic reaction on beta-adrenergic responses and airway responsiveness. Both IL-1beta and tumor necrosis factor a have been detected in increased amounts in bronchial lavage fluids in allergic airway inflammation. Both IL-13 and the proinflammatory cytokines IL-1beta and tumor necrosis factor a have been demonstrated in airway smooth muscle to cause a decreased relaxation response to beta-adrenergic agonist. However, IL-13 has been shown to be necessary and sufficient to produce the characteristics of asthma. The decreased adrenergic bronchodilator activity and associated hypersensitivity to mediators put forth by Szentivanyi can be elicited with IL-13 and support its role in the pathogenesis of asthma.
To investigate the prevalence and severity of asthma, rhinitis, and atopic eczema in schoolchildren from the northeast of England. We randomly selected 3,000 children from 80 schools. We used the ISAAC (International Study of Asthma and Allergies in Childhood) written questionnaire. The lifetime prevalence rates of symptoms were: rhinitis, 32.8%; wheezing, 31.3%; hay fever, 23.7%; and self-reported asthma, 22.3%. Rhinitis was reported by 53% and 61% of boys and girls with asthma, respectively. Girls 13 to 14 years of age had higher prevalence rates of asthma, rhinitis, and eczema symptoms than boys; a reverse sex ratio has been shown in this age group. Atopic eczema was reported by 32% of boys with asthma and 37% of girls with asthma. The prevalence rates of reported asthma, and symptoms suggestive of asthma, were higher than those previously reported in UK children. The present study would be a suitable baseline for monitoring future trends in the prevalence and severity of asthma and allergic disorders among these children, and provides a framework for further etiologic research into the genetics, lifestyle, environmental, and medical care factors affecting these conditions.
The prevalence of allergic diseases such as asthma, allergic rhinitis, and atopic diseases has increased in recent years. Immunotherapy with allergens is a treatment documented to have an effect on regulating cytokine production and allergen-specific antibody production. The aim of this study was to further investigate immunologic changes during immunotherapy and to explore the possible more efficient approach of immunotherapy. Asthmatic children receiving house dust mite immunotherapy were followed to learn immunologic parameters such as allergen-specific antibody levels, proliferative response of peripheral blood mononuclear cells, and cytokine change during immunotherapy. The data suggested (1) IgG4 anti-mite antibody increased 8 months after immunotherapy while IgE antibody level remained the same; (2) allergen-induced, in vitro production of certain cytokines such as IL-4 and IL-10 decreased after immunotherapy; (3) IL-13 (which can induce IgG4 and IgE antibody production by B cells) increased after immunotherapy. Although this needs more study, IL-13 might play an important role in the generation of IgG4-blocking antibody during immunotherapy.
Fluticasone affects airway bronchial hyperresponsiveness (BHR) and enhances bronchodilation and bronchoprotection induced by beta-adrenergic agonists. Interleukin 13 (IL-13), however, induces BHR. To test the hypotheses that fluticasone inhibits BHR after either allergen sensitization or IL-13 administration and that fluticasone restores the bronchodilation and bronchoprotective effects of beta-agonists. The BHR to methacholine induced by IL-13 or ovalbumin was determined in BALB/c mice, and the provocation concentration of methacholine that caused an increase in enhanced pause in expiration of 200% (PC200) was calculated. We compared this response to methacholine in control mice with the response after treatment with IL-13 receptor alpha 2-IgGFc fusion protein (IL-13R alpha 2) (an IL-13 blocker), fluticasone, albuterol, salmeterol, fluticasone-albuterol, and fluticasone-salmeterol. IL-13R alpha 2 (PC200, 17.59) completely blocks the BHR-induced effects of IL-13 (PC200, 7.28; P < .005). After IL-13 therapy (PC200, 5.90; P < .005), 1 mg/mL of albuterol (PC200, 3.38; P = .33), fluticasone (PC200, 4.59; P = .40), or fluticasone plus 50 microg/mL of salmeterol (PC200, 5.59; P = .11) showed no significant bronchoprotection. In nonsensitized mice, fluticasone plus 0.25 microg/mL of salmeterol (PC200, 25.90; P < .005) showed significantly greater bronchoprotection than did salmeterol alone (PC200, 11.08; P = .26). Fluticasone plus 0.3 mg/mL of albuterol and fluticasone plus 1 mg/mL of albuterol were significantly more protective than was fluticasone or albuterol alone in ovalbumin-sensitized mice. The protective effects of fluticasone, beta-agonists, and fluticasone plus beta-agonists are significantly less in IL-13-treated mice than in nonsensitized or ovalbumin-sensitized mice.
A new variant of hereditary angioedema has been reported during the last decade. Three main characteristics distinguish it from classic hereditary angioedema: normal C1 inhibitor activity, predominance in women, and different genetic alterations. To assess the symptoms, laboratory findings, and treatment of a population with type III hereditary angioedema from Northwest Spain. We studied 29 patients (26 female and 3 male) from 13 different families. The 26 female patients showed a similar clinical pattern to the classic forms of hereditary angioedema, and 22 of these patients had the estrogen-dependent phenotype. Three patients had a negative family history, and 1 of the parents was confirmed as an asymptomatic carrier in 2 of them. All had functional C1 inhibitor activity within the normal range in periods without high estrogen levels, but during attacks (in female patients) and pregnancy, activity decreased to below 50%. One male patient had normal C1 inhibitor activity during attacks, and he was initially diagnosed as having idiopathic angioedema. The C4 and antigenic C1 inhibitor levels were always normal. All studied patients had the c.1032C>A, Thr309Lys mutation in the factor XII gene. The mutation was also found in asymptomatic relatives: 5 of 6 men studied and 1 of 8 women studied. Positive family history is a diagnosis criterion, but it could be lacking because there may be asymptomatic relatives, primarily males.
To review the results of the first anti-IgE agent to undergo clinical evaluation in the treatment of allergic asthma and allergic rhinitis. Treatment protocols conducted in Europe and the United States in moderate to severe allergic asthmatic patients who continued to show symptoms despite treatment with inhaled corticosteroids with the addition of monoclonal humanized anti-IgE treatment. Double-blind, placebo-controlled studies, published and in press, are reviewed. Treatment with anti-IgE allowed a decrease in inhaled corticosteroid and rescue medication use and significantly reduced the incidence and frequency of asthma exacerbations among these patients over a 28-week time period and a 6-month extension period. Anti-IgE shows great promise as an adjunctive therapy in moderate to severe asthmatic patients.
The prevalence of asthma and allergic diseases in children has increased worldwide. To perform the phase 3 survey of the International Study of Asthma and Allergies in Children (ISAAC) to report the time trend of the prevalence and severity of asthma and allergic diseases in children in Taipei. Two junior high schools in each of the 12 school districts in Taipei were randomly chosen to enter the study. All students aged 13 to 14 years in the chosen schools were invited to participate in written and video questionnaires in Chinese (identical to those of the ISAAC phase 1 survey). The study was performed between December 1, 2001, and January 31, 2002. All data analysis followed the protocol of the ISAAC and then was submitted to the ISAAC International Data Center. Of 6653 eligible children from 23 high schools (1 school refused participation), 6381 (95.9%) participated. The prevalence of symptoms of asthma, allergic rhinitis, and atopic eczema in the past 12 months in 13- to 14-year-old children increased by 37%, 51%, and 193%, respectively, on written questionnaires during a 7-year period. The severity of asthma symptoms, including more than 4 wheezing attacks in the past 12 months, wheezing that disturbs sleep more than once per week, and wheezing that limited speech in the past 12 months, did not show any significant changes on written questionnaires during the 7 years. The increasing prevalence of symptoms of asthma, allergic rhinitis, and atopic eczema in 13- to 14-year-old children in Taipei in a 7-year period is a significant burden on public health systems in Taiwan.
The role of interleukin (IL) 13 and IL-17A in aspirin-exacerbated respiratory disease (AERD) remains unknown. To analyze the IL-13 and IL-17A gene polymorphisms in Japanese patients with AERD. The single-nucleotide polymorphisms in each gene were examined in patients with AERD, patients with aspirin-tolerant asthma (ATA), and healthy controls. Frequencies of the TT/CT genotype of the IL-13 -1111C>T gene were higher than frequencies of the CC genotype in AERD patients compared with ATA patients (P < .001). In female patients with AERD, frequencies of the TT/CT genotype were higher than those of the CC genotype compared with female patients with ATA (P < .001). However, genotype frequencies of IL-13 Arg110Gln did not differ between AERD and ATA patients. Frequencies of the CC genotype of the IL-17A -737C>T gene were higher than those of the TT/CT genotype in AERD patients compared with ATA patients (P = .02). In female patients with AERD, frequencies of the CC genotype were higher than those of the TT/CT genotype compared with female patients with ATA (P = .03). Forced expiratory volume in 1 second (percentage predicted) in AERD patients with the CC genotype of the IL-13 -1111C>T gene was lower than that in the patients with the TT/CT genotype. AERD patients with the TT/CT genotype of the IL-17A -737C>T gene had a higher peripheral total eosinophil count compared with the patients with the CC genotype. The comparison of the clinical characteristics according to the IL-13 Arg110Gln gene polymorphism showed no difference. These findings suggest that the IL-13 -1111C>T and IL-17A -737C>T gene sequence variations might have a role in the development of AERD.
To determine the prevalence of asthma and allergic diseases in 13 to 14 years old children in Kuwait. Supervised self-administered written and video questionnaires of the international study of asthma and allergies in childhood (ISAAC). Students at third and fourth years from 40 intermediate level schools chosen randomly from across Kuwait. 3,110 students were surveyed. The prevalence rates (95% CI) in the written questionnaire for wheeze ever, current wheeze (within the last 12 months), and physician diagnosis of asthma are 25.9% (24.5 to 27.4), 16.1% (15.8 to 17.4), and 16.8% (15.5 to 18.1) respectively. The prevalence rates (95% CI) for symptoms of allergic rhinitis (AR) ever, current symptoms of allergic rhinitis (AR), and diagnosis of AR are 43.9% (42.2 to 45.6), 30.7% (29.1 to 32.4) and 17.1% (14.8 to 18.4) respectively. The prevalence rates (95% CI) for itchy rash ever, current itchy rash, and diagnosis of eczema are 17.5% (16.2 to 18.8), 12.6% (11.4 to 13.8), and 11.3% (10.2 to 12.4) respectively. The prevalence of wheeze ever, wheeze during the last year, and physician diagnosis of asthma are higher in males compared with females, P < .01. In multiple logistic regression: male gender (OR 1.6, 95% CI, 1.3 to 2.0) and diagnosis of AR (OR 1.7, 95% CI, 1.4 to 2.2) were associated with the physician diagnosis of asthma even after controlling for symptoms of asthma. This is the first study on the prevalence of allergic diseases in Kuwait and it shows that children in Kuwait have a moderate prevalence of asthma, AR, and eczema compared with other countries where the ISAAC study is done. The prevalence of asthma is higher in boys compared with girls.
Small airways inflammation is a recognized pathologic component of asthma, and it is postulated that the observed airway-wall remodeling in small airways could be due to uncontrolled inflammation in airways that are not penetrated by conventional inhaled corticosteroids. Thus, extrafine particle formulations of inhaled corticosteroids are of clinical interest. To compare 2 extrafine solution hydrofluoroalkane-134a formulations of beclomethasone dipropionate (Beclate and Qvar). Fifteen asthmatic patients (mean +/- SEM forced expiratory volume in 1 second [FEV1], 2.62 +/- 0.21 L; provocative concentration of methacholine causing a 20% decrease in FEV1 [PC20], 1.06 +/- 0.58) were randomized to completion in a placebo-controlled, double-blind, crossover manner to receive Beclate or Qvar at doses of 100 or 400 microg/d for 2 weeks, with a 1-week washout period before each randomized treatment. Methacholine hyperresponsiveness was the primary outcome measure. The 2 formulations were equivalent in terms of predefined equivalence limits of +/- 1 doubling dilution for PC20 at both doses: -0.25 (95% confidence interval [CI], -0.77 to 0.27) doubling dilution difference between the 100-microg doses and a 0.26 (95% CI, -0.29 to 0.82) doubling dilution difference between the 400-microg doses for the difference between Beclate and Qvar, respectively. Both formulations, at either dose, produced a statistically significant (P < .05) reduction in mean exhaled nitric oxide levels: 400 microg/d of Beclate, 14.1 ppb (95% CI, 5.6 to 22.6 ppb); and 400 microg/d of Qvar, 14.2 ppb (95% CI, 6.0 to 22.4 ppb). The higher doses produced a statistically significant (P < .05) reduction in early morning urinary cortisol-creatinine ratio (geometric mean fold suppression: Beclate, 1.48 [95% CI, 1.16 to 1.89]; and Qvar, 1.42 [95% CI, 1.12 to 1.79]). Both formulations significantly improved peak expiratory flow, FEV1, and forced expiratory flow between 25% and 75% of forced vital capacity at the higher doses (P < .05). Beclate and Qvar were equivalent for all primary and secondary outcome measures.
Triamcinolone acetonide (TAA) inhalation aerosol (Azmacort Inhalation Aerosol), a well-established corticosteroid treatment for bronchial asthma, utilizes the chlorofluorocarbon (CFC) propellant P-12, which will be phased out because of environmental concerns. Two TAA aerosol formulations have been developed using a non-chlorofluorocarbon propellant, HFA-134a (Azmacort HFA Inhalation Aerosol delivering TAA 75 microg/puff or 225 microg/puff). This study compared the efficacy and safety of the new 225 microg/puff formulation (TAA-HFA 225) to the marketed TAA inhalation aerosol (TAA-CFC) and to placebo in adult patients with moderate-to-severe persistent asthma. After a 5-day to 21-day baseline period during which all patients received TAA-CFC 150 microg/day, 538 patients were randomized to one of the following treatment schedules: TAA-HFA 450, 900, or 1800 microg/day; TAA-CFC 450 or 900 microg/day; or placebo for 12 weeks. All active treatment groups showed statistically significant improvement compared with placebo in pulmonary function (FEV1, FEF25-75%, morning and evening PEF), use of rescue albuterol, and asthma symptom scores. Improvements in all variables occurred within 1 week of treatment. The TAA-HFA 225 exhibited similar safety and efficacy profiles to the two equivalent doses of TAA-CFC studied. Our findings indicate that TAA-HFA is a safe and effective replacement for the currently marketed CFC-containing product. The higher strength 225 microg/puff formulation provides effective control of asthma with fewer inhalations.
Fixed combination fluticasone-salmeterol is the most used anti-inflammatory asthma treatment in North America, yet no studies report the actual respiratory tract dose or the distribution of drug within the lungs. Inflammation due to asthma affects all airways of the lungs, both large and small. Inhaled steroid delivery to airways results from a range of drug particle sizes, with emphasis on smaller drug particles capable of reaching the peripheral airways. Previous studies suggested that smaller drug particles increase pulmonary deposition and decrease oropharyngeal deposition. To characterize the dose of fluticasone-salmeterol hydrofluoroalkane-134a (HFA) (particle size, 2.7 μm) delivered to asthmatic patients and examine the drug distribution within the lungs. The results were compared with the inhalation delivery of HFA beclomethasone (particle size, 0.7 μm). A crossover study was conducted in asthmatic patients with commercial formulations of fluticasone-salmeterol and HFA beclomethasone radiolabeled with technetium Tc 99m. Deposition was measured using single-photon emission computed tomography/computed tomography gamma scintigraphy. Two-dimensional planar image analysis indicated that 58% of the HFA beclomethasone and 16% of the fluticasone-salmeterol HFA were deposited in the patient's lungs. The oropharyngeal cavity and gut analyses indicated that 77% of the fluticasone-salmeterol HFA was deposited in the oropharynx compared with 35% of the HFA beclomethasone. The decreased peripheral airway deposition and increased oropharyngeal deposition of fluticasone-salmeterol HFA was a result of its larger particle size. The smaller particle size of HFA beclomethasone allowed a greater proportion of lung deposition with a concomitant decrease in oropharyngeal deposition.
After the signing of the Montreal Protocol in 1987, new propellants for use in pressurized metered-dose inhalers that are non-ozone-depleting have been developed. This study was designed to compare the efficacy and tolerability of single doses of albuterol/HFA 134a with albuterol/CFC and to demonstrate a dose-response among the different doses of both formulations. A single-center, randomized, double-blind, placebo-controlled, cross-over study. Sixty-three adolescent and adult asthmatic patients were randomized to receive at separate treatment visits single doses via a pressurized metered-dose inhaler of either placebo/hydrofluoroalkane (HFA) 134a; 100 microg, 200 microg, or 400 microg albuterol/HFA 134a; 100 microg or 200 microg albuterol/chlorofluorocarbon (CFC). Triplicate measurements of forced expiratory volume in 1 second (FEV1) were made immediately before dosing and 15 minutes, 30 minutes, 1, 2, 3, 4, 5, and 6 hours postdose. The primary efficacy variables were area under the entire 6-hour FEV1 curve, relative to baseline subtracted from the area above baseline (AUC(0-6)) and peak effect (derived from serial FEV1 measurements). Analysis of AUC(0-6) and peak effect showed that all doses of albuterol had a significantly greater effect than placebo (HFA 134a propellant). Comparisons of the two formulations at 100 microg and 200 microg showed no difference in AUC(0-6) (100 microg, -0.23 Lhr, P = 0.114 and 200 microg -0.08 Lhr, P = 0.590) or in peak effect, percentage of baseline (100 microg, -1.3%, P = 0.354 and 200 microg, 0.17%, P = 0.902). There were no differences seen among formulations in the incidence of adverse events or with any of the other safety parameters, including electrocardiograms, vital signs, clinical laboratory assessments, and asthma exacerbations. The study demonstrated comparability in terms of efficacy and safety between albuterol/HFA 134a and albuterol/CFC.
As a result of the pending ban on chlorofluorocarbon production, the non-chlorofluorocarbon propellant 1,1,1,2-tetrafluoroethane (HFA-134a) is being evaluated as a replacement for CFCs in metered-dose inhalers. This cumulative dose response study compared the safety and bronchodilator efficacy of 16 cumulative inhalations of albuterol sulfate in an HFA-134a, CFC-free propellant system (108 microg of albuterol sulfate, equivalent to 90 microg of albuterol base) with that of equivalent doses of albuterol in a conventional CFC propellant system. Twenty-two patients with at least a 12-month history of stable asthma, who were currently taken an inhaled beta-adrenergic bronchodilator, and who had a FEV1 between 40% and 80% of predicted, were enrolled in this randomized, modified-blind, two-period crossover study. One, 1, 2, 4, and 8 inhalations of study drug were self-administered at 30-minute intervals, resulting in 16 cumulative inhalations. Pulmonary function and safety measures were assessed after each dosing interval. A significant dose response was found for HFA-134a albuterol sulfate and CFC albuterol with regard to changes in FEV1, serum potassium, heart rate, and blood pressure after 16 cumulative inhalations. No significant differences were demonstrated between HFA-134a albuterol sulfate and CFC albuterol for any FEV1 or safety parameter at any cumulative dose level. No clinically meaningful laboratory or physical examination abnormalities were found with administration of either HFA-134a albuterol sulfate or CFC albuterol. HFA-134a albuterol sulfate provides bronchodilation comparable to CFC albuterol and has a similar safety profile.
Cysteinyl leukotrienes have been found to exert potent inflammatory effects in the upper airways and play a fundamental role in the pathogenesis of allergic rhinitis. Previous studies have reported increased levels of exhaled nitric oxide (eNO) in patients with allergic rhinitis without asthma symptoms. To investigate the role of treatment with montelukast on symptoms, eNO levels, and peripheral eosinophil counts of children with seasonal allergic rhinitis during pollen season. A randomized, double-blind, parallel-group study performed between April and June 2005 in 57 children aged 7 to 14 years with seasonal allergic rhinitis was performed. The study comprised a 1-week screening period, a 1-week run-in period, and a 2-week treatment period with once daily montelukast, 5 mg, or matching placebo. No significant difference at baseline was found in symptom scores, eNO levels, and blood eosinophil counts between the treatment and placebo groups. After 2 weeks of montelukast treatment, improvements from the baseline in the daytime nasal, composite, and daytime eye symptoms scores were significantly greater in the montelukast group compared with the placebo group (P < .001, P < .001, and P < .01, respectively). A significant decrease was also found in eosinophil counts (P < .001) in the montelukast group compared with the placebo group after treatment. Montelukast treatment did not produce a significant effect on eNO levels compared with placebo (P = .96). Montelukast treatment provided significant improvement in symptoms and peripheral eosinophil counts of school-age children with seasonal allergic rhinitis; however, it did not show a significant effect on eNO levels.
Tracheal hamartomas are rare in all age groups and have not been previously described in adolescence. To report the first case of a tracheal chondroid hamartoma presenting as exercise intolerance and wheezing and previously misdiagnosed and treated as asthma. Symptoms, pulmonary function tests, chest x-ray examination, chest computed tomography, and histologic examination of the specimen were performed. The pulmonary function tests obtained throughout several years revealed progressive decreases (approximately 30% of predicted) in peak expiratory flow and forced expiratory volume in 1 second (approximately 50% of predicted). The inspiratory and expiratory flow-volume curve suggested a fixed central airway obstruction. Both the chest x-ray examination and computed tomography revealed an intraluminal tracheal tumor that was surgically excised. Histologic examination revealed a chondroid hamartoma. Rare benign primary tracheal tumors, including chondroid hamartoma, can present in adolescence with asthma-like symptoms for years and should be considered in the differential diagnosis, especially in the setting of appropriately abnormal spirometry or when asthma is very difficult to control.
Inhaled corticosteroids have become the mainstay of asthma therapy. Few studies however, have compared inhaled steroids in children. We compared the efficacy of inhaled fluticasone propionate (FP), 880 microg/day (2 puffs of 220 microg/puff, BID) with inhaled flunisolide (FLU), 1500 microg/day (3 puffs of 250 microg/puff, BID). Thirty children with moderate to severe asthma, mean age 12.7 years (range 10 to 17 years), mean duration of asthma 8.4 years, initially received flunisolide 1500 microg/day for 1 year, and then were switched to fluticasone propionate 880 microg/day and followed for an additional year. Pulmonary function tests (PFTs) were monitored and analyzed before and after the switch for the duration of study. Mean percent predicted for age values for FVC, FEV1, FEF25-75%, and FEFR were compared at 1 month, 2 to 6-month intervals, and 7 to 12-month intervals and during the same season of the year. Pulmonary function tests within 3 weeks of an exacerbation were not included in the study. The number of asthma exacerbations, emergency room visits, hospital admissions, and number of school days lost were also compared. There was significant improvement in mean asthma exacerbations/patient/year (1.7 +/- 1.66 SD) versus (4 +/- 2.6) (P < .0002); mean emergency room visits/patient/year (0.23 +/- 0.62) versus (1.2 +/- 1.74) (P = .004); mean hospital admissions for asthma/patient/year (0.2 +/- 0.61) versus (1.13 +/- 1.45) (P < .0002); and number of school days lost/patient/year (1.4 +/- 2.38) versus (7.93 +/- 6.7) (P < .0002) while patients were receiving fluticasone propionate as compared with flunisolide. Also, the mean percent values predicted for age in all time-periods (at 1 month, 2 to 6 months, and 7 to 12 months) revealed significant improvement in FEV1 and FEF25-75% (P < .05 for both parameters). As PFT can be affected by seasonal changes, PFT parameters were compared during the same season of the year and significant improvement in FVC and FEV1 was observed in all seasons while patients were receiving fluticasone propionate (FP) compared with flunisolide (FLU) (P < .05 for all parameters). Significant improvement in PEFR and FEF25-75% was observed only in spring and summer season. Fluticasone propionate 880 microg/day improved lung function and quality of life in adolescents with moderate-to-severe asthma when compared with flunisolide 1500 microg/day.
Top-cited authors
Sheldon Spector
  • Asthma Allergy & Immunology Institute
James T C Li
  • Mayo Foundation for Medical Education and Research
Jay Portnoy
  • University of Missouri - Kansas City
David Khan
  • University of Texas Southwestern Medical Center
Canonica Walter
  • Università degli Studi di Genova