Trimethoprim-sulfamethoxazole-graded challenge in HIV-infected patients: long-term follow-up regarding efficacy and safety.
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Drug Hypersensitivity↗
Biomedical subjects
P Demoly
Publications and source records attributed to P Demoly.
Epidemiologic evidence for asthma and rhinitis comorbidity.
Asthma and rhinitis are often comorbid conditions, and the overall characteristics of the diseases and the treatment options for the disorders are similar. Several recent epidemiologic studies in the general population have provided evidence to strongly associate the development of asthma with a previous history of either allergic or perennial rhinitis. Additional links between asthma and rhinitis include a description of increased aspirin intolerance in both disorders and the observation that most subjects with occupational asthma experience rhinitis. Further, the likelihood of the development of asthma is much higher in individuals with both perennial and seasonal rhinitis than for individuals with either condition alone. Asthma and rhinitis were found to be comorbidities regardless of atopic state, and perennial rhinitis has been associated with an increase in nonspecific bronchial hyperresponsiveness. Several studies have identified rhinitis as a risk factor for asthma, with the prevalence of allergic rhinitis in asthmatic patients being 80% to 90%. These studies and others demonstrate that the coexistence of asthma and allergic rhinitis is frequent, that allergic rhinitis usually precedes asthma, and that allergic rhinitis is a risk factor for asthma. Finally, studies that have examined the age of onset of atopy as a confounding factor for the development of asthma and allergic rhinitis have suggested that early age atopy may be an important predictive factor for respiratory symptoms that continue into late childhood. In conclusion, rhinitis and asthma are strongly associated, and rhinitis has been identified as a risk factor for asthma.
Asthma↗
Transcriptional potencies of inhaled glucocorticoids.
Glucocorticoids (GC) are the most effective anti-inflammatory drugs used in asthma. By a process called trans-activation, they increase the transcription of genes involved in either beneficial processes or certain side effects. Through trans-repression, they inhibit the transcription factors nuclear factor kappa B (NF-kappaB) and activator protein-1 (AP-1), thereby decreasing the expression of many genes encoding inflammatory mediators such as the cytokine RANTES. We have measured the trans-activation and trans-repression potencies of the five currently available inhaled GC using reporter gene assays. The rank order of trans-activation potencies in HeLa cells stably transfected with a GC-inducible luciferase gene was fluticasone propionate > budesonide and triamcinolone acetonide > beclomethasone dipropionate and flunisolide. For all GC except beclomethasone dipropionate, there was a highly significant correlation between their potency to trans-activate in HeLa cells and their capacity to induce the gluconeogenic enzyme tyrosine aminotransferase in hepatoma tissue culture (HTC) cells. The rank order of trans-repression potencies in A549 lung cells transiently transfected with an AP-1- or NF-kappaB-dependent luciferase gene was fluticasone propionate > budesonide > beclomethasone dipropionate, triamcinolone acetonide, and flunisolide. The same rank order was found for inhibition of RANTES release. Thus, determination of trans-repression and trans-activation potencies of GC may help to predict their capacity to produce anti-inflammatory and side effects, respectively.
Administration, Inhalation↗
Glucocorticoid receptor alpha and beta in glucocorticoid dependent asthma.
Patients with glucocorticoid (GC)-dependent asthma present an ongoing inflammation of the airways despite chronic long-term treatment with oral GC. Interleukin (IL)-8 and granulocyte/macrophage colony-stimulating factor (GM-CSF) have been implicated in airway inflammation in severe asthma and their synthesis is normally repressed by GC. To further characterize the inflammatory process in GC-dependent asthma, we measured the release of IL-8 and GM-CSF by peripheral blood mononuclear cells (PBMC) of eight normal subjects, six untreated controlled asthmatics, six untreated uncontrolled asthmatics, and nine GC-dependent asthmatics. We show that PBMC from GC-dependent asthmatics released high amounts of these cytokines despite chronic in vivo exposure to GC (p < 0.001 versus normal subjects). In contrast, when untreated uncontrolled asthmatics were given a short course of oral GC, IL-8 and GM-CSF production was inhibited (p = 0.0078). Release of IL-8 and GM-CSF by PBMC of GC-dependent asthmatics was reduced after in vitro GC treatment (p < 0.002). We investigated whether the incapacity of GC to inhibit production of these cytokines in vivo was the result of a dysregulation of the glucocorticoid receptor (GR) in GC-dependent asthma. GRalpha and GRbeta are, respectively, the functional receptor and a putative dominant negative form of the receptor. Western blot and polymerase chain reaction (PCR) analyses indicated that GRalpha was expressed at similar level in all groups and was largely predominant over GRbeta. Thus, persistent release of IL-8 and GM-CSF in GC-dependent asthma is not associated with low expression of GRalpha or overexpression of GRbeta.
Adult↗
[Allergic post-transfusion reactions].
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Blood↗
[Drug allergies: a public health problem].
Adverse drug reactions occur in 10 to 20% of hospitalized patients and up to one third are due to allergic and pseudoallergic reactions. Allergic reactions are unpredictable reactions related to immunologic mechanisms. Pseudo-allergic reactions mimic allergic reactions but no drug specific antibody or T cell proliferation can be demonstrated. A true diagnosis is rarely set up and the tools for it are lacking. In this review, we will focus on some epidemiological data concerning these reactions, including data on incidence, mortality and cost.
Drug Hypersensitivity↗
[Update on drug allergies induced by antibiotics and anti-retroviral agents].
Allergic reactions to antibiotics have raised considerable concerns, and are still underevaluated. It is a daily problem for general practitioners and allergologists. Their clinical manifestations are numerous, ranging from mild maculo-papular eruptions to sometimes deadly anaphylactic shocks or epidermal necrolisis. Atopy is not a risk factor, but concomitant viral infections, including Epstein-Barr virus and HIV infections are. HIV-infected patients indeed suffer more frequently from drug-induced hypersensitivity reactions than immunocompetent subjects or even non-HIV immunodeficient patients. We are lacking clinical and biological tools and the available ones still need to be validated. However, a precise diagnosis is required in order to set up prevention measures. In some cases, graded challenges (desensitization when an IgE mechanism is involved) is possible and efficacious (quinolones for cystic fibrosis, sulfonamides for HIV-infected patients).
Anti-Bacterial Agents↗
[Genetics of asthma and atopy].
The genetics of asthma and atopy has made tremendous progresses over the last couple of years. It has been known for ages that allergies and asthma are concentrating within families. Modern genetics has pinpointed some gene areas such as 5q31.1, 6p21.3, 11q13, 12q15, 14q11.1 and 16p12. Much of the information available today has been fragmentary and not always confirmed. Alleles at multiple loci are likely to be involved and the ultimate picture is most likely determined by many genetic and environmental factors.
Alleles↗
[From allergic rhinitis to sinus diseases (sinusitis/nasal polyps): epidemiologic and experimental links].
The relationships between rhinitis and chronic sinusitis are close and complex, those between allergic rhinitis and nasal polyposis are controversial. These relationships can be demonstrated not only in terms of anatomy, physiology and epidemiology (by comparing the prevalence of one disease in patients suffering from the other disease), but also experimentally (by studying the sinus involvement following nasal allergen provocations), and pathophysiologically (by phenotyping and comparing the inflammation present in both diseases). Results of such studies are convincing and have confirmed the fundamental role of nasal inflammation in general and allergic inflammation in particular in the genesis of sinusitis (it is now therefore recommended to utilize the term 'rhinosinusitis'). The importance of allergy in the etiologic development of nasal polyps remains controversal and doubtful. Because the diagnosis of allergic rhinitis provides useful therapeutic options, an appropriate evaluation for underlying allergies in indicated in any patient with chronic upper respiratory tract symptoms.
Diagnosis, Differential↗
[Vaccination with allergens in children].
Specific immunotherapy or allergen vaccination has been in routine use since 1911 for the treatment of respiratory allergic diseases. It is more effective in children and young adults than later in life. Its efficacy has been demonstrated in double-blind placebo controlled studies in both allergic rhinoconjunctivitis and allergic asthma. The improvement of allergenic extracts (in particular by standardization), the better understanding of the mechanisms of action of immunotherapy, the use of local administration routes and the publication of guidelines have legitimate its definite role to play in the therapeutic management of allergic respiratory diseases in childhood.
Administration, Oral↗
[Corticosteroid-resistant asthma: basic aspects].
A CONTROVERSIAL DEFINITION: The current definition of corticosteroid-resistant asthma is a spirometry definition. There is however, no consensus on dose, treatment duration, steroid administration route and the degree of FEV1 non-reversibility allowing the diagnosis of corticosteroid-resistant asthma. Finally, the beneficial effect of steroids in clinical terms (symptom frequency, number of hospitalizations, quality of life) is not taken into consideration, thus nearly one-half al all patients included in studies on corticosteroid resistance are taking long-term oral steroids. This subgroup of patients must be considered individually when examining these studies. COMPLEX PATHOGENESIS: There are a wide range of anomalies described in the literature involving: glucocorticoid pharmacokinetics, cytokine regulation, cell function (monocytes, lymphocytes, eosionophils), and transcription factors (glucocorticoid and AP-1 receptors). DIFFICULT THERAPEUTIC MANAGEMENT: There are several prerequisites before proposing exceptional regimens using cyclosporine, gold salts, methotrexate, or immunoglobulins: i) certain diagnosis of asthma (with CT scan and ultrasonographic explorations if needed, ii) proper control of environmental factors and good compliance, iii) proof of the absence of clinical benefit with long-term corticosteroids. These exceptional therapeutic schemes have their disadvantages and are only warranted by clinically patent corticosteroid resistance (whatever the "biological" cause).
Adrenal Cortex Hormones↗
Unmet needs in the pharmacological treatment of asthma.
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Administration, Inhalation↗
Medication errors at the administration stage in an intensive care unit.
OBJECTIVE: To assess the type, frequency and potential clinical significance of medication-administration errors. DESIGN: Prospective study using the observation technique as described by the American Society of HealthSystem Pharmacists but eliminating the disguised aspect. SETTING: Medical intensive care unit (ICU) in a university hospital. PATIENTS AND PARTICIPANTS: 2009 medication administration interventions by nurses. INTERVENTIONS: Pharmacist-performed observation of preparation and administration of medication by nurses, comparison with the original medical order and comparison with the data available in the literature. MEASUREMENTS AND RESULTS: 132 (6.6% of 2009 observed events) errors were detected. Their distribution is as follows: 41 dose errors, 29 wrong rate, 24 wrong preparation technique, 19 physicochemical incompatibility, 10 wrong administration technique and 9 wrong time errors. No fatal errors were observed, but 26 of 132 errors were potentially life-threatening and 55 potentially significant. CONCLUSION: According to this first observation-based study of medication administration errors in a European ICU, these errors were due to deficiencies in the overall organisation of the hospital medication track, in patient follow-up and in staff training.
France↗
Comparison between nasal provocation tests and skin tests in patients treated with loratadine and cetirizine.
BACKGROUND: The effect of H1-blockers may differ depending on the target organ. OBJECTIVE: A double-blind, placebo-controlled study was carried out to compare the effect of a 7-day treatment with loratadine (10 mg daily) or cetirizine (10 mg daily) on nasal challenge with grass pollen grains and skin tests with allergen or histamine. METHODS: Twenty-four patients were enrolled, but the analysis was carried out on 23. Nasal challenge was carried out by using 5-fold increasing numbers of pollen grains. Skin prick tests were done with serial concentrations of allergens and 1 concentration of histamine. Patients were tested in a cross-over design, with each treatment being administered for the previous 7 days and with a 2-week washout period. RESULTS: By comparison with placebo, loratadine and cetirizine increased significantly the threshold number of pollen grains required to induce a positive nasal challenge (P <.001). There was no difference between loratadine and cetirizine. Skin test responses to allergen were significantly reduced by loratadine and cetirizine by comparison with placebo. Skin test responses to histamine were significantly decreased by the 2 H1-blockers, but they were more profoundly decreased by cetirizine than by loratadine. CONCLUSIONS: Both H1-blockers reduced similarly allergen-induced skin test and nasal challenge responses. Cetirizine was more effective on histamine skin test responses.
Adult↗
IgE reactivity to Api g 1, a major celery allergen, in a Central European population is based on primary sensitization by Bet v 1.
BACKGROUND: Up to 70% of patients with tree pollen allergy display allergic symptoms when eating certain fruits and vegetables. Homologous proteins with allergenic features are present in a wide range of plant species and can cause allergic reactions. OBJECTIVE: The aim of this study was to evaluate recombinant Api g 1, a major celery allergen, for in vivo and in vitro diagnosis of celery allergy in populations from Davos, Switzerland, and Montpellier, France. METHODS: A group of patients with celery and birch pollen allergy from Davos was tested, and the results from those tests were compared with results from a group of patients allergic to celery from Montpellier. Skin prick tests were performed with a commercial celery extract, crude celery, and purified recombinant Api g 1. Quantitative and qualitative serology was done with natural and recombinant allergens by means of RASTs and immunoblotting. RESULTS: Recombinant Api g 1 allowed accurate in vivo diagnosis of celery allergy in all patients from the Swiss group. RAST results with celery extract were negative in 8 of 24 patients; results of immunoblotting with celery extract were negative in 4 of 24 patients, and results of immunoblotting with recombinant (r)Api g 1 were negative in 8 of 24 patients. In the French group 11 of 12 patients had a positive skin reaction with crude celery extract, but only 2 patients reacted with rApi g 1. RAST results for celery were positive in 8 of 12 patients. In immunoblotting experiments 8 patient sera displayed IgE directed against various celery allergens, whereas no patients sera had rApi g 1-specific IgE. CONCLUSION: Our results document that rApi g 1 allows accurate in vivo diagnosis only in areas where birch trees are common. In areas where no birch trees grow, primary sensitization takes place through different pollen allergens (eg, mugwort pollen). Moreover, it became evident that birch pollen and celery allergy are highly related in Central Europe, whereas in Southern Europe the mugwort-celery type is predominant.
Adult↗
Nevirapine-induced cutaneous hypersensitivity reactions and successful tolerance induction.
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Adult↗
Predictive capacity of histamine release for the diagnosis of drug allergy.
BACKGROUND: The diagnosis of immediate allergic reactions to drugs is difficult, requiring in vitro test development. Basophils are likely to be involved in these reactions, and to evaluate the sensitivity, the specificity, and the predictive values of the histamine-release test, we performed a prospective study in 68 patients tested for suspected drug allergy. METHODS: Positive diagnosis was established by history, skin tests, and, if needed, oral provocation tests. Histamine release in the presence of the drug was assessed on heparinized whole blood by enzyme immunoassay (Immunotech, France), and the cutoff value was set at 5% of total histamine content. Spontaneous and anti-IgE-induced histamine release was also studied in all subjects. RESULTS: All patients presented to our clinic with reactions ranging from maculopapular exanthema to anaphylactic shock. Thirty-five patients had proven drug allergy; 33 were not allergic to drugs and served as a control group together with 40 other subjects with no history of drug allergy. Net histamine release was positive in 18/35 allergics and 27/73 nonallergics, giving poor sensitivity (51.4%), specificity (63.0%), and positive predictive value (29.3%), but valuable negative predictive value (81.1%). CONCLUSIONS: The usefulness of the in vitro histamine-release test for the diagnosis of drug allergy appears to be insufficient.
Acetaminophen↗