Year‐in‐review 2010: Asthma, COPD, cystic fibrosis and airway biology

Reddel, Helen K.; Lim, Tow Keang; Mishima, Michiaki; Wainwright, Claire; Knight, Darryl A.

doi:10.1111/j.1440-1843.2011.01949.x

Cited by 5 publications

(7 citation statements)

References 133 publications

(138 reference statements)

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“…( 23 ) Much remains to be learned about the mechanism that involves the expression of the CFTR protein associated with the F508del mutation, ( 24 ) because F508del acts in multiple steps in the biogenesis of CFTR. ( 25 ) …”

Section: Discussionmentioning

confidence: 99%

Screening for F508del as a first step in the molecular diagnosis of cystic fibrosis

et al. 2013

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OBJECTIVE: To determine the relevance of screening for the F508del mutation of the cystic fibrosis transmembrane conductance regulator gene as a first step in the genetic diagnosis of cystic fibrosis (CF) by associating the genotype with various clinical variables. METHODS: We evaluated 180 CF patients regarding the F508del mutation. The clinical data were obtained from the medical records of the patients and from interviews with their parents or legal guardians. RESULTS: Of the 180 patients studied, 65 (36.1%) did not carry the F508del mutation (group 0 [G0]), 67 (37.2%) were F508del heterozygous (G1), and 48 (26.7%) were F508del homozygous (G2). All three groups showed associations with the clinical variables. Homozygosis was associated with younger patients, younger age at CF diagnosis, and younger age at the first isolation of Pseudomonas aeruginosa (PA), as well as with higher prevalence of pancreatic insufficiency (PI) and non-mucoid PA (NMPA) colonization. In comparison with G1+G2 patients, G0 patients were older; first experienced clinical symptoms, digestive disease, and pulmonary disease at an older age; were older at CF diagnosis and at first PA isolation; and had a lower prevalence of PI and meconium ileus, as well as of colonization by NMPA, mucoid PA, and Burkholderia cepacia. In G1 patients, values were intermediate for age at CF diagnosis; age at first PA isolation, first pulmonary symptoms, and first clinical manifestations; MPA colonization; and OR for PI. CONCLUSIONS: The identification of F508del in 63.9% of the patients studied showed that this can be a useful tool as a first step in the genetic diagnosis of CF. The F508del genotype was associated with clinical severity of the disease, especially with the variables related to CF onset.

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Section: Discussionmentioning

confidence: 99%

Screening for F508del as a first step in the molecular diagnosis of cystic fibrosis

et al. 2013

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“…For setup B, the polycarbonate membrane was removed from the donor compartment and mild heat was used to form notches in the base in order to support the glass microfiber filter/filter paper that would be placed on it. 1 As these conditions are not crucial for the here proposed work, details of the set-up are not provided. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 5 For both set-up A and B, the filter paper carrying the drug was placed face up into the donor compartment of the Transwell ® system.…”

Section: Introductionmentioning

confidence: 98%

“…Humidity (100% at 37 o C was maintained using an external humidifier device. 1 In some experiments, a seven stage Next Generation Impactor was employed along with a flow control and measurement unit and a pump (Copley Scientific, Nottingham, UK).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Transwell System for Characterization of Dissolution Behavior of Inhalation Drugs: Effects of Membrane and Surfactant

et al. 2015

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Assessing the dissolution behavior of orally inhaled drug products (OIDs) has been proposed as an additional in vitro test for the characterization of innovator and generic drug development. A number of suggested dissolution methods (e.g., commercially available Transwell or Franz cell systems) have in common a membrane which provides the separation between the donor compartment, containing nondissolved drug particles, and an acceptor (sampling) compartment into which dissolved drug will diffuse. The goal of this study was to identify and overcome potential pitfalls associated with such dissolution systems using the inhaled corticosteroids (ICS), viz., budesonide, ciclesonide, and fluticasone propionate, as model compounds. A respirable fraction (generally stage 4 of a humidity, flow, and temperature controlled Andersen Cascade Impactor (ACI) or a Next Generation Impactor (NGI)) was collected for the tested MDIs. The dissolution behavior of these fractions was assessed employing the original and an adapted Transwell system using dissolution media which did or did not contain surfactant (0.5% sodium dodecyl sulfate). The rate with which the ICS transferred from the donor to the acceptor compartment was assessed by HPLC. Only a modified system that incorporated faster equilibrating membranes instead of the original 0.4 μm Transwell membrane resulted in dissolution and not diffusion being the rate-limiting step for the transfer of drug from the donor to the acceptor compartment. Experiments evaluating the nature of the dissolution media suggested that the presence of a surfactant (e.g., 0.5% SDS) is essential to obtain rank order of dissolution rates (e.g., for budesonide, fluticasone propionate, and ciclesonide) that is in agreement with absorption rates of these ICS obtained in studies of human pharmacokinetics. Using the optimized procedure, the in vitro dissolution behavior of budesonide, ciclesonide, and fluticasone propionate agreed approximately with descriptors of in vivo absorption. The optimized procedure, using membranes with increased permeability and surfactant containing dissolution medium, represents a good starting point to further evaluate in vitro/in vivo correlations.

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“…These two common diseases are a major burden for public health and affect over 500 million people worldwide (World Health Organization: WHO/NMH/CHP/CPM/05.4.). Other chronic inflammatory lung diseases are hypersensitivity pneumonitis which is caused by antigen exposure and lung fibrosis, the cause of which is unknown and therefore the pathology is widely uncertain [1–7]. To an unknown reason the prevalence of all chronic inflammatory lung diseases is on the rise especially in Asia [8, 9].…”

Section: Chronic Inflammatory Lung Diseasesmentioning

confidence: 99%

Is There a Regulatory Role of Immunoglobulins on Tissue Forming Cells Relevant in Chronic Inflammatory Lung Diseases?

Roth

2011

Journal of Allergy

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Epithelial cells, fibroblasts and smooth muscle cells together form and give structure to the airway wall. These three tissue forming cell types are structure giving elements and participate in the immune response to inhaled particles including allergens and dust. All three cell types actively contribute to the pathogenesis of chronic inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease (COPD). Tissue forming cells respond directly to allergens through activated immunoglobulins which then bind to their corresponding cell surface receptors. It was only recently reported that allergens and particles traffic through epithelial cells without modification and bind to the immunoglobulin receptors on the surface of sub-epithelial mesenchymal cells. In consequence, these cells secrete pro-inflammatory cytokines, thereby extending the local inflammation. Furthermore, activation of the immunoglobulin receptors can induce proliferation and tissue remodeling of the tissue forming cells. New studies using anti-IgE antibody therapy indicate that the inhibition of immunoglobulins reduces the response of tissue forming cells. The unmeasured questions are: (i) why do tissue forming cells express immunoglobulin receptors and (ii) do tissue forming cells process immunoglobulin receptor bound particles? The focus of this review is to provide an overview of the expression and function of various immunoglobulin receptors.

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Year‐in‐review 2010: Asthma, COPD, cystic fibrosis and airway biology

Cited by 5 publications

References 133 publications

Screening for F508del as a first step in the molecular diagnosis of cystic fibrosis

Screening for F508del as a first step in the molecular diagnosis of cystic fibrosis

Evaluation of the Transwell System for Characterization of Dissolution Behavior of Inhalation Drugs: Effects of Membrane and Surfactant

Is There a Regulatory Role of Immunoglobulins on Tissue Forming Cells Relevant in Chronic Inflammatory Lung Diseases?

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