Efficacy and safety of TOBI Podhaler in infected bronchiectasis patients: iBEST study.

The study aimed to determine the efficacy of a safe and well-tolerated dose and regimen of tobramycin inhalation powder (TIP) on sputum density in patients with bronchiectasis.This is a phase II, double-blind, randomised study in bronchiectasis patients aged ≥18 years with chronic infection. Patients were randomised 1:1:1 to either cohort A: three capsules of TIP once daily (84 mg); cohort B: five capsules once daily (140 mg) or cohort C: four capsules twice daily (224 mg).

Efficacy and safety of tobramycin inhalation powder in bronchiectasis patients with P. aeruginosa infection: Design of a dose-finding study (iBEST-1).

In patients with bronchiectasis (BE), infection with Pseudomonas aeruginosa (Pa) results in disease progression, frequent pulmonary exacerbations and lung function decline. However, at present, no inhaled antibiotics have been approved for the treatment of these patients. Tobramycin inhalation powder (TIP), approved for treatment of Pa infection in cystic fibrosis, could be a promising candidate.

Eradication of early P. aeruginosa infection in children <7 years of age with cystic fibrosis: The early study.

Objective: Antibiotic eradication treatment is the standard-of-care for cystic fibrosis (CF) patients with early Pseudomonas aeruginosa (Pa)-infection; however, evidence from placebo-controlled trials is limited.

Methods: This double-blind, placebo-controlled trial randomised CF patients <7 years (N = 51) with early Pa-infection to tobramycin inhalation solution (TOBI 300 mg) or placebo (twice daily) for 28 days with an optional cross-over on Day 35. Primary endpoint was proportion of patients having throat swabs/sputum free of Pa on Day 29.

Long-term safety of tobramycin inhalation powder in patients with cystic fibrosis: phase IV (ETOILES) study.

Objective: Long-term treatment with inhaled antibiotics is recommended for chronic Pseudomonas aeruginosa (Pa) infection in cystic fibrosis (CF) patients. The ETOILES study (Clinicaltrials.gov identifier: NCT01519661) evaluated the safety of tobramycin inhalation powder (TIP) for 1 year.

One-year safety and efficacy of tobramycin powder for inhalation in patients with cystic fibrosis.

Unlabelled: This is an integrated analysis of data from patients with cystic fibrosis (CF) aged 6-21 years who were treated with up to seven cycles of tobramycin powder for inhalation (TIP(TM) ) over a period of at least 1 year. Safety and key efficacy endpoints were analyzed.

Results: The improvement in lung function and decrease in sputum P.

The road for survival improvement of cystic fibrosis patients in Arab countries.

Cystic fibrosis (CF) is a lethal, monogenic disorder that affects multiple organ systems of the body. The incidence has been described before in the Middle East to be 1 in 2000 to 1 in 5800 live births, and the median survival was estimated to be from 10 to 20 years of age. The present article attempts to revisit various facets of this disease and specifically highlights the most important lacunae that exist in treating CF.

Tobramycin inhalation powder in cystic fibrosis patients: response by age group.

Background: Tobramycin powder for inhalation (TIP) is a drug-device combination designed to reduce treatment time and improve ease of use compared with tobramycin inhalation solution (TIS) in cystic fibrosis (CF) patients. However, the ability of patients to use dry powder inhalers, and the efficacy of the treatments, may vary by age.

Methods: The "Establish a New Gold Standard for Efficacy and Safety With Tobramycin in Cystic Fibrosis" (EAGER) trial was a randomized, 24-week, multicenter, open-label, parallel-group study designed to evaluate the safety of TIP versus TIS in 553 subjects, ages ≥ 6 years, with CF and P.

Tobramycin inhalation powder manufactured by improved process in cystic fibrosis: the randomized EDIT trial.

Background: Tobramycin inhalation powder (TIP) was reported to be effective in two Phase III studies in patients with cystic fibrosis (CF) chronically infected with Pseudomonas aeruginosa (Pa). The EDIT study evaluated the efficacy and safety of TIP manufactured by an improved process in CF subjects aged 6-21 years.

Methods: CF patients with a forced expiratory volume in 1 second (FEV₁) ≥25% to ≤80% predicted, positive Pa cultures and inhaled antipseudomonal therapy naïve (or at least for past 4 months) were enrolled into this double-blind, multicenter trial.

A network meta-analysis of the efficacy of inhaled antibiotics for chronic Pseudomonas infections in cystic fibrosis.

Background: Various inhaled antibiotics are currently used for treating chronic Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) patients, however their relative efficacies are unclear. We compared the efficacy of the inhaled antibiotics tobramycin (TIP, TIS-T, TIS-B), colistimethate sodium (colistin) and aztreonam lysine for inhalation (AZLI) based on data from randomised controlled trials.

Methods: In the base case, efficacies of antibiotics were compared using a network meta-analysis of seven trials including change from baseline in forced expiratory volume in 1 second (FEV(1)) % predicted, P.

Safety, efficacy and convenience of tobramycin inhalation powder in cystic fibrosis patients: The EAGER trial.

Background: A light-porous-particle, dry-powder formulation of tobramycin was developed, using PulmoSphere® technology, to improve airway delivery efficiency, substantially reduce delivery time, and improve patient convenience and satisfaction. We evaluated the safety, efficacy and convenience of tobramycin inhalation powder (TIP™) versus tobramycin inhalation solution (TIS, TOBI®) for treating Pseudomonas aeruginosa infection in cystic fibrosis (CF) patients aged ≥6 years.

Methods: In this open-label study, 553 patients were randomized 3:2 to TIP (total 112mg tobramycin) via the Novartis T-326 Inhaler or TIS 300mg/5mL via PARI LC® PLUS nebulizer twice daily for three treatment cycles (28 days on-drug, 28 days off-drug).

Tobramycin inhalation powder for P. aeruginosa infection in cystic fibrosis: the EVOLVE trial.

Tobramycin inhalation solution is used to treat chronic Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) patients. We evaluated the efficacy and safety of a novel, light-porous particle, dry-powder formulation of tobramycin, which was developed to improve delivery efficiency to the airways and substantially reduce the delivery time. In this randomized, double-blind study, patients with CF (age 6-21 years) received tobramycin inhalation powder (112 mg tobramycin) twice daily (n = 46) or placebo (n = 49) via the T-326 Inhaler for one cycle, followed by two open-label cycles (all patients).

Treatment of early Pseudomonas aeruginosa infection in patients with cystic fibrosis: the ELITE trial.

Rationale: Antibiotic therapy for early Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF) is effective, but the optimal therapeutic regimen and duration for early treatment remains unclear. The EarLy Inhaled Tobramycin for Eradication (ELITE) study was designed to assess the efficacy and safety of two regimens (28 and 56 days) of tobramycin inhalation solution (TIS) 300 mg/5 ml twice daily for the treatment of early onset P aeruginosa infection in patients with CF.

Methods: In this open-label randomised multicentre study, patients with CF (aged > or = 6 months) with early P aeruginosa infection were treated for 28 days with TIS twice daily administered by the PARI LC PLUS (PARI GmbH, Starnberg, Germany) jet nebuliser.

Aminoglycoside therapy against Pseudomonas aeruginosa in cystic fibrosis: a review.

In patients with cystic fibrosis (CF), respiratory infections with the opportunistic bacterial pathogen Pseudomonas aeruginosa have a major impact on morbidity and mortality. Aminoglycosides, especially tobramycin, have been used successfully to combat these infections. Aminoglycoside penetration of bronchial secretions is poor when the antibiotic is administered intravenously.

Peptide-binding assays and HLA II transgenic Abeta degrees mice are consistent and complementary tools for identifying HLA II-restricted peptides.

The identification of MHC class II-restricted peptides has become a priority for the development of peptide-based prophylactic and therapeutic vaccines. The aim of this study was to assess the correlations between peptide-binding assays on purified HLA II molecules and immunization of human HLA II transgenic mice deficient in murine class II molecules (Abeta degrees ). We used as models two MHC class II-restricted peptides, one derived from the HIV Nef regulatory protein (Nef (56-68)) and the other from the Schistosoma mansoni 28-kDa glutathione-S-transferase (Sm28GST (190-211)).

Effect of glycoamphiphiles on the solubilization and dendritic cell uptake of a lipopeptide: a preliminary study.

The selective delivery of antigens to professional antigen-presenting cells represents a promising approach to improve vaccine efficacy. Addition of a glycoamphiphile to a lipopeptide, whose interest for vaccination is now well-established, greatly favors its solubilization in aqueous solutions through the formation of mixed vesicles. Flow cytometry experiments indicate that this formulation does not diminish the uptake of the lipopeptide by the dendritic cells (DCs).

Comparison of HLA-DR1-restricted T cell response induced in HLA-DR1 transgenic mice deficient for murine MHC class II and HLA-DR1 transgenic mice expressing endogenous murine MHC class II molecules.

Transgenic mice expressing human HLA class II molecules provide a useful model for identifying HLA-restricted CD4+ epitopes. However, the influence of endogenous murine H-2-restricted T cell responses on HLA-restricted responses is not known. In the present study, we show that HLA-DR1 transgenic mice deficient for H-2 class II expression (HLA-DR1+/+/IAbeta0/0) exhibit an equivalent expression level of the transgene HLA-DR1 and a similar diversity in the TCR repertoire, but a slightly different number of CD4+ peripheral T cells, when compared to HLA-DR1 transgenic mice in which H-2 class II molecules were retained (HLA-DR1+/+/IAbeta+/+).

Grafting of synthetic mannose receptor-ligands onto onion vectors for human dendritic cells targeting.

A practical preparation of onion vesicles targeted to dendritic cells involves the grafting of mannose-mimetic clusters, bearing a hydrazino group, onto the surface of onion vesicles containing an aldehyde functionalized lipid.

Involvement of the mannose receptor in the uptake of Der p 1, a major mite allergen, by human dendritic cells.

Background: Immature dendritic cells (DCs) take up antigens in peripheral tissues and, after antigen processing, mature to efficiently stimulate T cells in secondary lymph nodes. In allergic airway diseases DCs have been shown to be involved in the induction and maintenance of a T(H)2-type profile.

Objective: The present study was undertaken to determine pathways of Der p 1 (a house dust mite allergen) uptake by human DCs and to compare Der p 1 uptake between DCs from patients with house dust mite allergy and DCs from healthy donors.

Synthesis and mannose receptor-mediated uptake of clustered glycomimetics by human dendritic cells: effect of charge.

Effect of charge and shape of multivalent lysine-based cluster glycomimetics on their mannose receptor-mediated uptake by human dendritic cells has been evaluated: The capture is strongly affected by the shape of the ligands. The effect of charge is less pronounced although positive charges on the ligands seem to favor non-specific endocytosis capture.

Evidences of conformational changes in class II Major Histocompatibility Complex molecules that affect the immunogenicity.

The N-terminal part of class II-associated invariant chain peptide (CLIP) is assumed to interact with an accessory peptide-binding site on the class II Major Histocompatibility Complex (MHC) molecule, and promote a conformational modification. We have linked this immunoregulatory segment (residues 81-88) to the N-terminus of the influenza hemagglutinin (HA) 307-319 epitope in order to evaluate relationships between the MHC conformational changes and their implication in immune responses. Our chimeric peptide, named CLIP-HA, bind with the same affinity to class II HLA-DR1 molecules as the HA peptide, and is normally recognized by HA-specific T cells.