Predicting hypoxia in cystic fibrosis patients during exposure to high altitudes

Abstract Background For patients with cystic fibrosis (CF)-related partial respiratory insufficiency and reduced arterial oxygen tension at ground level, the mild hypobaric environment on commercial jet aircraft poses the risk of severe hypoxemia. Thus, physicians should be able to estimate the extent of in-flight hypoxia. Objectives To derive tools for estimating the expected drop in arterial oxygen partial pressure (paO 2 ) and oxygen saturation (saO 2 ) in young adult CF patients with mild to moderate airway obstruction during exposure to the hypobaric conditions aboard commercial aircraft and to test the predictive power of a hypobaric chamber simulation. Methods Blood gases of 12 CF pa…

Children Below Five Years Of Age Can Handle Respimat® Soft MistTM Inhaler

The inhalation manager: a new computer-based device to assess inhalation technique and drug delivery to the patient.

The rational choice of an inhalation device is a cornerstone in the effective management of asthma and COPD. In this publication, we describe the development of a new system, the Inhalation Manager, which, for the first time, offers the possibility to assess the entire inhalation maneuver of patients using original devices under everyday conditions. So far the Inhalation Manager allows the measurement of inspiratory maneuvers of patients through placebo inhalation devices of the most common breath-actuated CFC-free inhalers in the market for the three main glucocorticosteroids Budesonide [Turbohaler (TH), dry powder inhaler (DPI)], Beclomethasone dipropionate [Autohaler (AH), breath-actuate…

Multidisciplinary management of Hunter syndrome.

Hunter syndrome is a rare, X-linked disorder caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase. In the absence of sufficient enzyme activity, glycosaminoglycans accumulate in the lysosomes of many tissues and organs and contribute to the multisystem, progressive pathologies seen in Hunter syndrome. The nervous, cardiovascular, respiratory, and musculoskeletal systems can be involved in individuals with Hunter syndrome. Although the management of some clinical problems associated with the disease may seem routine, the management is typically complex and requires the physician to be aware of the special issues surrounding the patient with Hunter syndrome, and a multidiscipl…

Physicochemical compatibility of nebuliser solution admixtures containing colistimethate and hypertonic saline or colistimethate, fluticasone-17-propionate, ipratropium bromide and salbutamol sulfate

Objectives For practical reasons, patients with cystic fibrosis (CF) tend to mix different inhalation solutions for concomitant inhalation instead of inhaling the different medications consecutively. A study was undertaken to examine the compatibility of colistimethate dissolved in 5.85% hypertonic sodium chloride (NaCl) solution and the quadripartite mixtures of colistimethate, fluticasone-17-propionate, ipratropium bromide and salbutamol sulfate. Methods The test solutions were prepared by mixing ordinary doses of the inhalation products and analysed immediately. Microbiological assays of antibiotics and high-performance liquid chromatography assays were used to determine chemical compati…

A novel approach to CFTR mutation testing by pyrosequencing-based assay panels adapted to ethnicities.

Abstract Background: Cystic fibrosis (CF) is a common autosomal recessive genetic disorder caused by a variety of sequence alterations in the CFTR gene [cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7)]. Because the relative prevalence of mutations strongly depends on the ethnic background, first-level testing of CF as defined by recent consensus recommendations ought to be adaptable to the ethnicity of patients. Methods: We therefore developed and implemented a diagnostic approach to first-level testing for CF based on published mutation frequencies and Pyrosequencing (PSQ) technology that we complemented with standard procedures of mutation…

Add-on salmeterol compared to double dose fluticasone in pediatric asthma: A double-blind, randomized trial (VIAPAED)

Rationale In asthmatic children whose symptoms are uncontrolled on standard doses of inhaled corticosteroids (ICS), guidelines recommend to either increase the ICS dose or to add further controller medication, e.g. a long acting s2-agonist (LABA). The aim of this study was to compare the efficacy and safety of doubling the dose of ICS (fluticasone proprionate FP 200 µg twice daily) with adding a long-acting beta-2 agonist to the ICS (SFC, salmeterol 50 µg/ FP 100 µg twice daily) in children with uncontrolled asthma. Methods Children between 4 and 16 years of age were eligible for this multicenter, randomized, double blind, double dummy, parallel-group study. During a 14-day run-in phase, al…

Dysfunction of the non-neuronal cholinergic system in the airways and blood cells of patients with cystic fibrosis.

Abstract The non-neuronal cholinergic system is widely expressed in human airways, skin and immune cells. Choline acetyltransferase (ChAT), acetylcholine and nicotine/muscarine receptors are demonstrated in epithelial surface cells, submucosal glands, airway smooth muscle fibres and immune cells. Moreover, acetylcholine is involved in the regulation of cell functions like proliferation, differentiation, migration, organization of the cytoskeleton, cell–cell contact, secretion and transport of ions and water. Cystic fibrosis (CF), the most frequent genetic disorder, is known to be caused by a mutation of the CF-gene coding for the cystic fibrosis transmembrane regulator protein (CFTR). CFTR …

Mass Output and Particle Size Distribution of Glucocorticosteroids Emitted from Different Inhalation Devices Depending on Various Inspiratory Parameters

Efficient inhalation therapy depends on successful delivery of the drug to the lung. The efficacy of drug delivery is not only influenced by the characteristics of the inhalation device, but also by the patient's handling of the device and by the inspiratory maneuver achieved through the device. We analyzed the output characteristics of three different chlorofluorocarbon (CFC)-free breath-actuated inhalers for inhaled glucocorticosteroids (BUD Turbohaler, FP Diskus/Accuhaler and HFA-BDP Autohaler, respectively). Mass output and particle size distribution of drug aerosol delivered by the inhalers were determined depending on different inhalation parameters in vitro using an Andersen cascade …

Clinical characteristics of adults with slowly progressing mucopolysaccharidosis VI: a case series.

To assess clinical features and general health status of adult patients with mucopolysaccharidosis (MPS) VI. This report includes the clinical history of patients older than 18 years with slowly progressing MPS VI and the retrospective analysis of the outcomes of available data collected between September 2003 and October 2008 at the Center of Pediatric and Adolescent Medicine, University Medical Center, Johannes Gutenberg-University of Mainz, Germany. Variables included were urinary glycosaminoglycan (uGAG) level, mutation analysis, body height, forced vital capacity (FVC), 6-minute walk test, echocardiographic findings, the need for craniocervical decompression surgery, orthopaedic findin…

Physicochemical compatibility of mixtures of dornase alfa and tobramycin containing nebulizer solutions

Patients suffering from cystic fibrosis (CF) often need to inhale multiple doses of different nebulizable drugs per day. Patients attempt to shorten the time consuming administration procedure by mixing drug solutions/suspensions for simultaneous inhalation. The objective of this experimental study was to determine whether mixtures of the nebulizer solution dornase alfa (Pulmozyme) with tobramycin nebulizer solutions (TOBI and GERNEBCIN 80 mg) are physico-chemically compatible. Drug combinations were prepared by mixing the content of one respule Pulmozyme with either one respule TOBI or one ampoule GERNEBCIN 80 mg. Test solutions were stored at room temperature and exposed to light. Dornase…

Transient suppression of atopy in early childhood is associated with high vaccination coverage.

Objective. To analyze prevalences of allergic sensitization and atopic disease in relation to vaccination coverage. Methods. A German atopy risk-enhanced birth cohort of 1314 neonates who were born in 1990 in 5 German cities was studied. A total of 943 children participated in the follow-up visit at 5 years of age. Atopic symptoms and diagnoses (derived from structured interviews), total serum immunoglobulin E, and specific immunoglobulin E against 9 common allergens (CAP Radio-Allergo-Sorbent Test Fluoro-Enzyme Immunoassay) were evaluated. Children were grouped into dose percentiles according to cumulative doses of any vaccine given up to 5 years of age (<10%, 0–11 doses; 10%–50%, 1…

Safety of anti-IgE treatment with omalizumab in children with seasonal allergic rhinitis undergoing specific immunotherapy simultaneously

Kamin W, Kopp MV, Erdnuess F, Schauer U, Zielen S, Wahn U. Safety of anti-IgE treatment with omalizumab in children with seasonal allergic rhinitis undergoing specific immunotherapy simultaneously. Pediatr Allergy Immunol 2010: 21: e160–e165. © 2009 John Wiley & Sons A/S Introduction  Seasonal allergic rhinitis (SAR) affects at least 10–25% of the Caucasian race and about 40% of patients are children. Standard treatment of SAR is specific immunotherapy (SIT), but anti-allergic drugs can significantly enhance efficacy of SIT. One candidate is the humanized monoclonal anti-IgE antibody omalizumab. Material and Methods  Randomized, double-blind, placebo-controlled, multi-centre trial in German…

Aerosolcharakteristika ausgewählter Druckluftvernebler für Erwachsene in Simulationsmodellen und Verneblung von Salbutamol

Zusammenfassung Ziel Der Erfolg einer Inhalationstherapie wird durch Menge und Qualität des inhalierten Aerosols bestimmt. Die Auswahl eines Verneblers bedarf der Kenntnis der entsprechenden Aerosolcharakteristika. Methoden Die Aerosolperformance von 9 marktüblichen Druckluftverneblern wurde in vitro in 2 Simulationsmodellen geprüft. Salbutamol (Sultanol forte® Fertiginhalat 2,5 mg/2,5 ml; GSK) wurde über 4 Minuten vernebelt. Die Outputparameter wurden mit dem Atemzugsimulator PARI Compas II (Erwachsenenmanöver nach Ph.Eur.9.0; n = 5/6 Verneblungen) und die aerodynamische Partikelgrößenverteilung mit dem Next Generation Impaktor (Ph.Eur.9.0, Copley Scientific; n = 3 Verneblungen) per HPLC b…

Inhalation solutions — Which ones may be mixed? Physico-chemical compatibility of drug solutions in nebulizers — Update 2013

AbstractMany patients suffering from chronic respiratory diseases rely on inhalation therapy with nebulizers. About 25% of patients who need to inhale several different drugs per day save time by mixing them for simultaneous inhalation. This review presents a comprehensive overview of the available data concerning physico-chemical compatibility of commonly mixed nebulizer solutions and suspensions. Information is based on our in vitro studies and a thorough literature search.Results indicate that many nebulizer solutions/suspensions are mixable without provoking incompatibilities. However, certain excipients contained in some of the tested drug products could be identified as a reason for i…

Inhalation solutions: which one are allowed to be mixed? Physico-chemical compatibility of drug solutions in nebulizers.

AbstractTherapy of chronic respiratory diseases often involves inhalation therapy with nebulizers. Patients often attempt to shorten the time consuming administration procedure by mixing drug solutions/suspensions for simultaneous inhalation. This article considers the issue of physico-chemical compatibility of admixtures of drug solutions/suspensions in nebulizers.A search of databases, prescribing information and primary literature was conducted to locate literature concerning the physico-chemical compatibility of inhalation solutions/suspensions. This was supplemented by telephone interviews.Admixtures of albuterol with ipratropium and/or cromolyn, of albuterol and budesonide, or tobramy…

Physicochemical compatibility and stability of nebulizable drug admixtures containing Dornase alfa and tobramycin.

The objective of this in-vitro study was to determine whether admixtures of the inhalation solutions Pulmozyme(®) (Dornase alfa) and either Bramitob(®) or Tobi(®) (both containing Tobramycin) are physicochemically compatible and to analyze the aerodynamic parameters of these admixtures. After mixing, test solutions were stored at room temperature and under ambient light conditions over a period of 24 h. Tobramycin concentrations were determined by using a fluorescence immunoassay. Stability of dornase alfa was determined by size-exclusion high performance liquid chromatography, ultraviolet spectroscopy, sodium dodecyl sulfate polyacrylamide gel electrophoresis and tentacle strong cation-exc…