Search PubMed⌕ Search

Biomedical subjects

P S Creticos

Publications and source records attributed to P S Creticos.

At least 19 recordsLinked to original sources
PubMed2001

The consideration of immunotherapy in the treatment of allergic asthma.

BACKGROUND: Immunotherapy (IT) has undergone rigorous trials to evaluate its therapeutic benefit in the treatment of allergic respiratory disease. The tools of molecular biology have provided a framework with which to begin to understand the mechanistic effects of IT on the underlying inflammatory component of allergic respiratory disease. RESULTS: The clinical relevance of these observations belies our understanding of allergic inflammation as the subsoil for the development of abnormal airway physiology, heightened bronchial reactivity, and the development of chronic asthmatic symptomatology. CONCLUSIONS: IT provides the potential to downregulate this inflammatory cascade, reduce IgE antibody production, and attenuate symptoms. Conceptually, early intervention of allergic disease holds the most promise as a therapeutic intervention capable of arresting the progression of the disease, altering the severity of the disease, and/or preventing the development of the respiratory disease process.

Animals↗
PubMed2001

Immunostimulatory sequence DNA linked to the Amb a 1 allergen promotes T(H)1 cytokine expression while downregulating T(H)2 cytokine expression in PBMCs from human patients with ragweed allergy.

BACKGROUND: Recent studies have demonstrated that bacterially derived immunostimulatory sequences (ISSs) of DNA can activate the mammalian innate immune system and promote the development of T(H)1 cells. Promotion of T(H)1 immunity by means of immunotherapy in allergic patients has led to the alleviation of symptoms that result from allergen-specific T(H)2 responses. OBJECTIVE: Our purpose was to investigate whether the T(H)1-enhancing properties of ISSs could be used to alter the T(H)2-dominated immune response of allergic PBMCs in vitro. METHODS: Ragweed protein-linked ISS (PLI) was generated from a specific, highly active 22-base ISS and Amb a 1, the immunodominant allergen in ragweed pollen, to combine the T(H)1-enhancing properties of ISSs with allergen selectivity, and its activity was investigated in PBMC cultures from subjects with ragweed allergy. RESULTS: PLI was markedly successful at reversing the dominant allergen-induced T(H)2 profile while greatly enhancing IFN-gamma production. Delivering ISSs in a linked form proved to be much more effective at modulating the resulting cytokine profile than delivering free ISSs in a mixture with unlinked Amb a 1. PLI also demonstrated cytokine-modulating properties, even when used to stimulate cells that had already been primed for 6 days with Amb a 1. The antigen specificity of the action of PLI was confirmed by the observations that PLI enhances Amb a 1--specific T-cell proliferation. CONCLUSION: These data indicate that delivery of ISSs within an antigen-specific context exhibits potent cytokine-modulating activity and, combined with its reduced allergenicity, makes this molecule a strong candidate for use in improved immunotherapy applications.

Adjuvants, Immunologic↗
PubMed2000

The consideration of immunotherapy in the treatment of allergic asthma.

Immunotherapy has undergone rigorous trials to assess its therapeutic benefit in the treatment of allergic respiratory disease. The tools of molecular biology have provided a framework with which to begin to understand the mechanistic effects of immunotherapy on the underlying inflammatory component of allergic respiratory disease. The clinical relevance of these observations belies our understanding of allergic inflammation as the subsoil for the development of abnormal airway physiology, heightened bronchial reactivity, and the development of chronic asthmatic symptoms. Immunotherapy provides the potential to downregulate this inflammatory cascade, reduce IgE antibody production, and attenuate symptoms. Conceptually, early intervention of allergic disease holds the most promise as a therapeutic intervention capable of arresting the progression of the disease, altering the severity of the disease, and/or preventing the development of the respiratory disease process.

Allergens↗
PubMed2000

Conjugation of immunostimulatory DNA to the short ragweed allergen amb a 1 enhances its immunogenicity and reduces its allergenicity.

BACKGROUND: Allergen immunotherapy is inconvenient and associated with the risk of anaphylaxis. Efforts to improve the safety of immunotherapy by means of chemical modification of allergens have not been successful because it greatly reduced their antigenicity. Recently, immunostimulatory DNA sequences (ISS or CpG motifs) have been shown to act as strong T(H)1 response-inducing adjuvants. OBJECTIVE: We sought to determine whether conjugation of ISS to the major short ragweed allergen Amb a 1 results in enhanced immunotherapeutic potential in mice and decreased allergenicity in human subjects. METHODS: A 22-mer ISS oligodeoxynucleotide (ISS-ODN) was coupled to Amb a 1 and used for immunization of mice, rabbits, and monkeys. RESULTS: In mice the Amb a 1-ISS conjugate induced a T(H)1 response (IFN-gamma secretion), whereas Amb a 1 induced a T(H)2 response (IL-5 secretion). The T(H)1 response was not observed with an Amb a 1-non-ISS conjugate. Coinjection of Amb a 1 with ISS-ODN was much less effective in inducing a T(H)1 response. In mice primed for a T(H)2 response, injection with Amb a 1-ISS conjugate induced a de novo T(H)1 response and suppressed IgE antibody formation after challenge with Amb a 1. Amb a 1-ISS conjugate induced high-titer anti-Amb a 1 IgG antibodies in rabbits and cynomolgus monkeys, whereas Amb a 1 alone or Amb a 1 coinjected with ISS-ODN did not induce a detectable response. Amb a 1-ISS conjugate was less allergenic than Amb a 1 alone, as shown by a 30-fold lower histamine release from human basophils of patients with ragweed allergy, whereas mixing ISS-ODN with Amb a 1 did not reduce histamine release. CONCLUSION: Amb a 1-ISS conjugate has an enhanced T(H)1-biased immunogenicity and reduced allergenicity. It may offer a more effective and safer approach for allergen immunotherapy than currently available methods.

Allergens↗
PubMed2000

Managing asthma in adults.

Asthma is a chronic inflammatory disorder of the airways with a spectrum of presentations--from intermittent but mild symptoms to persistent symptoms with chronicity. The key to successful management of the disease process is not only to treat the acute symptoms of wheezing, breathlessness, chest tightness, and cough but also to suppress the underlying inflammatory component. Management requires an integrated approach that incorporates patient education, control of environmental triggers, the judicious use of an appropriate agent to suppress underlying inflammation, addition of adjunctive therapy to optimize primary control, and the supplemental use of a bronchodilator to control breakthrough symptoms. Inhaled corticosteroids are the most effective agents for primary control of patients with persistent asthma. The nonsteroidal antiinflammatory agents cromolyn and nedocromil are alternative choices for primary control. Adjunctive or secondary controllers include maintenance bronchodilators such as salmeterol and long-acting theophylline as well as leukotriene modifiers. Concurrent therapy with an inhaled corticosteroid and a long-acting beta agonist has been shown to provide better asthma control than therapy with either an inhaled corticosteroid plus a leukotriene modifier, an inhaled corticosteroid plus theophylline, or higher doses of an inhaled corticosteroid alone.

Adult↗
PubMed1998

The efficacy of slow versus faster inhalation of cromolyn sodium in protecting against allergen challenge in patients with asthma.

BACKGROUND: Approximately one third of patients with allergy-induced asthma who are treated with aerosolized cromolyn sodium (CS) fail to achieve a full therapeutic effect. This lack of effectiveness could involve nonhomogeneous distribution of drug in the lung as a result of high inspiratory flow rates. OBJECTIVE: We sought to determine the efficacy of slow versus faster inhalation of CS in protecting against allergen challenge in patients with asthma. METHODS: Eight patients with asthma underwent two allergen challenges 30 minutes after pretreatment with CS that was inhaled from a large holding chamber at approximately 30 L/min or approximately 70 L/min. Percent decreases in FEV1 at a common dose of allergen on the two challenge days were compared. Values of skew (an indicator of aerosol distribution homogeneity) obtained from gamma camera lung images after slow and faster inhalation of radiolabeled CS were also compared. RESULTS: Mean (+/- SD) allergen-induced decrease in FEV1 was 5.4% +/- 4.2% after slow inspiration of CS, which was significantly less than the allergen-induced decrease in FEV1 after faster inhalation of CS with 12.6% +/- 11% (p < 0.05). Mean skew values were also significantly decreased after slow inspiration of CS, and differences in decreases in allergen FEV1 and skew values for the two breathing maneuvers were significantly correlated. CONCLUSION: These data indicate that protection against allergen-induced asthma can be optimized by slowly inspiring CS from a large holding chamber compared with faster inhalation of the drug. These results appear to be related to enhanced distribution homogeneity of CS within the lungs.

Administration, Inhalation↗
PubMed1998

Metered dose inhaler: past, present, and future.

BACKGROUND: The metered dose inhaler (MDI) to treat respiratory diseases was introduced many years ago. Due to the recently proposed ban on chlorofluorocarbon (Freon) production, the survival of the conventional MDI is uncertain. It is therefore incumbent on asthma caretakers to familiarize themselves with newer versions of the inhaler. OBJECTIVE: To review the different modalities of aerosolized treatment employed in the management of asthma. This article is specifically focused on issues related to MDIs, the propellants, and the modifications since its introduction. DATA SOURCE: The MEDLINE database was used to review MDI related literature in the English language. CONCLUSION: Dry powder inhalers (especially the multi-dose type) and Freon-free pressurized MDIs appear promising and probably will replace conventional freon-propelled pressurized MDIs when Freon is no longer available.

Aerosols↗
PubMed1997

A double-blind study of the discontinuation of ragweed immunotherapy.

BACKGROUND: Immunotherapy effectively treats the symptoms of allergic rhinitis and improves its pathophysiology. We studied whether the effects of immunotherapy on the early response to nasal challenge with antigen and seasonal symptoms persist after discontinuation. METHODS: Twenty subjects with ragweed allergy who were receiving immunotherapy and who had nasal challenges performed before initiation of treatment were selected. The patients had been receiving maintenance therapy with aqueous ragweed extract at a dose of 12 microg of Amb a 1 equivalent for a minimum of 3 years, at which point they were randomized to receive either placebo injections or to continue with the maintenance dose. Nasal challenges were performed before and 1 year after randomization. Nasal challenges were monitored by counting the number of sneezes and measuring histamine, N-alpha-tosyl-L-arginine methyl ester-esterase activity, and kinins in recovered nasal lavages. In the same year symptom diaries were collected during the ragweed season. RESULTS: The initial immunotherapy significantly reduced responses to nasal challenge in both groups. The group continuing to receive active treatment showed no significant changes from the response before randomization. In contrast, the group randomized to placebo treatment showed a partial return of histamine, kinins, and N-alpha-tosyl-L-arginine methyl ester-esterase in nasal secretions and the numbers of sneezes. IgG antibodies to ragweed declined only in the group switched to placebo treatment. Seasonal rises of IgE antibodies to ragweed did not return during the first season after treatment was stopped. Symptoms reported during the ragweed season were not different between the groups. CONCLUSIONS: One year after discontinuation of ragweed immunotherapy, nasal challenges showed partial recrudescence of mediator responses even though reports during the season appeared to indicate continued suppression of symptoms.

Adolescent↗
PubMed1996

Ragweed immunotherapy in adult asthma.

BACKGROUND: Although allergen immunotherapy is effective for allergic rhinitis, its role in treating asthma is unclear. METHODS: We examined the efficacy of immunotherapy for asthma exacerbated by seasonal ragweed exposure. During an observation phase, adults with asthma who were sensitive to ragweed kept daily diaries and recorded peak expiratory flow rates between July and October. Those who reported seasonal asthma symptoms and medication use as well as decreased peak expiratory flow were randomly assigned to receive placebo or ragweed-extract immunotherapy in doses that increased weekly for an additional two years. RESULTS: During the observation phase, the mean (+/- SE) peak expiratory flow rate measured in the morning during the three weeks representing the height of the pollination season was 454 +/- 20 liters per minute in the immunotherapy group and 444 +/- 16 liters per minute in the placebo group. Of the 77 patients who began the treatment phase, 64 completed one year of the study treatment and 53 completed two years. During the two treatment years, the mean peak expiratory flow rate was higher in the immunotherapy group (489 +/- 16 liters per minute, vs. 453 +/- 17 in the placebo group [P = 0.06] during the first year, and 480 +/- 12 liters per minute, vs. 461 +/- 13 in the placebo group [P = 0.03] during the second). Medication use was higher in the immunotherapy group than in the placebo group during observation and lower during the first treatment year (P = 0.01) but did not differ in the two groups during the second year (P = 0.7). Asthma-symptom scores were similar in the two groups (P = 0.08 in year 1 and P = 0.3 in year 2). The immunotherapy group had reduced hay-fever symptoms, skin-test sensitivity to ragweed, and sensitivity to bronchial challenges and increased IgG antibodies to ragweed as compared with the placebo group; there was no longer a seasonal increase in IgE antibodies to ragweed allergen in the immunotherapy group after two years of treatment. Reduced medication costs were counterbalanced by the costs of immunotherapy. CONCLUSIONS: Although immunotherapy for adults with asthma exacerbated by seasonal ragweed exposure had positive effects on objective measures of asthma and allergy, the clinical effects were limited and many were not sustained for two years.

Adult↗
PubMed1996

Comparison of triamcinolone acetonide nasal inhaler with astemizole in the treatment of ragweed-induced allergic rhinitis.

BACKGROUND: Few clinical trials have directly compared the efficacy of antihistamines with topical nasal corticosteroids. OBJECTIVE: The study was performed to compare the efficacy and safety of triamcinolone acetonide nasal spray at a dose of 110 micro g in each nostril once daily with 10 mg of oral astemizole once daily for the treatment of seasonal allergic rhinitis. METHODS: A multicenter, double-blind, parallel-group study was conducted in 239 patients who were randomized to receive either triamcinolone acetonide or astemizole. A 5-day, drug-free, lead-in period was followed by 4 weeks of double-blind treatment. One hundred four patients treated with triamcinolone acetonide and 105 patients treated with astemizole could be evaluated. RESULTS: Overall, triamcinolone acetonide was more effective than astemizole in reducing total nasal symptoms, nasal stuffiness, nasal itching, and sneezing (p </= 0.01). Triamcinolone acetonide was superior to astemizole at weeks 1, 2, and 3 in reduction of the total nasal symptom score (p </= 0.0401) and in reduction of nasal stuffiness (p </= 0.05). Improvements in individual nasal symptoms (itching, postnasal drip, runny nose, and sneezing) were greater for triamcinolone acetonide at week 2 (p </= 0.01). Ocular symptoms improved from baseline in both groups. When pollen counts were correlated to mean nasal rhinitis scores, the triamcinolone acetonide group showed continued improvement from week 1 to week 2 in nasal symptoms when pollen counts were at their highest. During the same period, patients treated with astemizole failed to show improvement from week 1 to week 2. This study demonstrated that once daily administration of triamcinolone acetonide was more effective than astemizole for controlling nasal symptoms of seasonal allergic rhinitis, especially during the peak pollination period.

Administration, Intranasal↗
PubMed1996

Treatment of cat allergy with T-cell reactive peptides.

We induced in allergic humans the counterpart of murine experimental T-cell tolerance. T-cell lines from cat-allergic humans were used to map T-cell epitopes for the principal allergen of cat dander, Fel d 1. Two peptides of 27 amino acids each were synthesized to contain the dominant epitopes (ALLERVAX CAT). After a safety trial, we carried out a blinded study of the dose required for efficacy. We randomly divided 95 cat-sensitive patients into placebo, 7.5 micrograms, 75 micrograms, and 750 micrograms groups. Patients received a subcutaneous injection weekly for 4 wk. Before and after treatment, patients were exposed in a room inhabited by live cats and scored by nose and lung symptoms. Baseline nasal and lung scores (+/-SEM) were 6.2 +/- 0.56 and 5.4 +/- 0.73 in the 750 micrograms group; 7.8 +/- 0.53 and 4.7 +/- 0.68 in the placebo group. Six weeks after treatment, scores adjusted for baseline differences were reduced in the 750 micrograms group: -2.3 +/- 4.9 and -2.3 +/- 0.59 compared with -0.84 +/- 0.50 and -0.85 +/- 0.62 in the placebo group. The 75 micrograms group showed intermediate effects and the 7.5 micrograms group no effect. Linear trend analysis indicated a significant dose response effect: p = 0.05 for nose and 0.03 for lung symptoms. Allergic side effects occurred an hour or more after the first 750 micrograms dose in 16 of 24 patients but required little or no treatment with one exception. T-cell reactive treatment peptides safely improved allergic responses to cats.

Allergens↗
PubMed1996

Effects of nedocromil sodium on inflammation and symptoms in therapeutic studies.

This review cites clinical evidence demonstrating that nedocromil sodium can reverse the clinical features of airway inflammation in asthma, as shown by decreased bronchial responsiveness, decreased diurnal variation in peak expiratory flow, improved baseline lung function, and a decrease in the frequency and severity of chronic symptoms. Clinical trials have also shown that nedocromil sodium has a statistically significant and clinically relevant effect on daytime and nighttime asthma symptoms within 3 days of starting treatment. On an analysis of relevant trials, the effect on asthmatic cough was significant within 24 hours. This rapid effect on symptoms, together with a reversal of the underlying airways inflammation, is a beneficial combination in the management of asthma.

Asthma↗
PubMed1993

Intranasal steroids inhibit seasonal increases in ragweed-specific immunoglobulin E antibodies.

We performed two seasonal studies to evaluate the effect of continuous treatment with intranasal steroids, beginning approximately 1 week before the appearance of ragweed pollen, on the level of ragweed-specific IgE antibodies in serum. In both studies the control groups showed the anticipated rise in ragweed-specific IgE antibodies after the ragweed season. In the first study, employing aqueous beclomethasone dipropionate (168 micrograms twice daily), no rise occurred in serum ragweed IgE after seasonal exposure and the level actually decreased in eight of 12 treated subjects. In the second study, with triamcinolone acetonide (220 micrograms twice daily), the expected rise in ragweed IgE antibody was also reduced, although less dramatically, probably as a result of the lower potency of the dose delivered. Our studies not only support the benefits of intranasal steroids in the treatment of seasonal allergic rhinitis but also suggest that specific IgE production may be down-regulated by their continuous use, which may alter the subsequent clinical course of the disease.

Administration, Intranasal↗
PubMed1992

The nasal response to histamine challenge: effect of the pollen season and immunotherapy.

To evaluate changes in the nasal response to histamine, we challenged 19 subjects with allergic rhinitis caused by ragweed (RW) before, during, and after the RW season with increasing doses of histamine diphosphate. We compared their response, as measured by symptoms and the levels of TAME-esterase activity and albumin recovered in the nasal lavage fluid, with response of two groups with allergic rhinitis undergoing immunotherapy with moderate-dose (N = 16) and high-dose (N = 11) RW (2 and 24 micrograms of antigen E [Amb a I] as maintenance dose, respectively). Four challenges with histamine were performed in each group: before, at the peak of, near the end of, and 2 weeks after the RW season. The three groups of subjects had similar skin sensitivity to antigen and levels of TAME-esterase activity and albumin recovered from nasal lavages after histamine challenge performed before seasonal exposure. Symptom diaries obtained throughout the season revealed a significant reduction only in the high-dose immunotherapy-treated group. At the peak of the season, the untreated group had more symptoms in response to the challenge compared with the challenges before and after the season (p = 0.04 for both groups). The saline challenge occurring before challenging with histamine also demonstrated a significant increase at the peak of the season compared with increases before the season (p = 0.02). This observation was also true for the levels of albumin and TAME-esterase activity. If the response after saline challenge was subtracted from each response after histamine challenge, no difference was found in the results between any of the visits.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Budesonide in grass pollen rhinitis.

To determine the relative efficacy, to compare the incidence of adverse experiences, and to assess the systemic glucocorticoid effect of nasal preparations of budesonide, 200 micrograms bid, and placebo, 50 adult patients with seasonal allergic rhinitis due to grass pollen were studied in a stratified, double-blind parallel group design. After a 2-week baseline period, budesonide nasal spray, 100 microgram per nostril twice a day, was compared with placebo nasal spray over a 4-week treatment period. Supplementary treatment with chlorpheniramine, 4-mg tablets, was permitted when necessary to control symptoms. Daily symptom and medication diaries were kept by the patients. Investigator assessments of symptoms and side effects were made at clinic visits at 2-week intervals. At baseline and again towards the end of the study, blood samples were drawn for the determination of plasma cortisol levels and 24-hour urine samples collected for the measurement of 17-hydroxycorticosteroid output. Of the 24 men and 26 women entering, 49 completed the study. Symptom scores for sneezing, stuffy nose, and nasal secretion all decreased dramatically from baseline when budesonide treatment was started. The decrease in symptoms was greater for budesonide than for placebo (P < .001). There was no difference between budesonide and placebo with regard to eye itch and rescue medication used. Morning nasal washes were taken during the grass season before treatment was started and 16 to 17 days after. They showed a significant decrease in TAME esterase levels in secretions in the budesonide treated patients (P = .03) but not in the placebo-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗