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Cystic fibrosis [keywords]
- Mannose-binding lectin 2 gene polymorphism and lung damage in primary ciliary dyskinesia. [JOURNAL ARTICLE]
- Pediatr Pulmonol 2014 Apr 19.
Mannose-binding lectin (MBL) plays an important role in innate immunity and has been reported to be associated with the age-related decline in lung function in cystic fibrosis.MBL polymorphisms are associated with lung function decline in Primary Ciliary Dyskinesia (PCD).We performed sputum microbiology, spirometry pre- and post-administration of salbutamol, ciliary motion analysis, ultrastructural assessment of cilia, ciliogenesis in culture, and chest high resolution computed tomography in children with a clinical history of respiratory tract infections and/or presence of bronchiectasis suggestive of PCD or secondary ciliary dyskinesia (SCD). All subjects were evaluated for single nucleotide polymorphisms in the gene encoding MBL-2.The diagnosis of PCD was established in 45 subjects, while in the remaining 53 the diagnosis was SCD. A significant bronchodilator response was observed only in PCD associated with the MBL2-3 genotype, which is known to be associated with low/undetectable MBL serum levels. Also, bronchiectasis severity was significantly greater in subjects with MBL2-3 in both PCD and SCD. No other association was found between MBL genotypes and clinical findings.MBL plays a relatively minor role as a disease modifier in PCD. A similar finding in SCD supports the likely significance of this result. Pediatr Pulmonol. © 2014 Wiley Periodicals, Inc.
- Inaccurate data in my meta-analysis of Prolonged Macrolides for Patients with Non-cystic fibrosis Bronchiectasis in Adult. [LETTER]
- Pulm Pharmacol Ther 2014 Apr 18.
- [Inhaled treatments in cystic fibrosis: What's new in 2013?] [REVIEW]
- Rev Mal Respir 2014 Apr; 31(4):336-346.
In the past few years some new inhaled drugs and inhalation devices have been proposed for the treatment of cystic fibrosis. Breath-controlled nebulizers allow increased pulmonary deposition, with a lower variability and a shorter delivery time. The new dry powder formulations of tobramycin, colistine and mannitol require a change in the inhalation technique which must be slow and deep. In the field of the inhaled mucolytic drugs, hypertonic saline and mannitol have an indication in some patients. With regard to antibiotics, dry-powder tobramycin and colistine can be substituted for the same drug delivered by nebulization. Nebulized aztreonam needs more studies to determine its place. These new treatments represent a definite advance for cystic fibrosis patients and need to be known by all practitioners. Their position in our therapeutic arsenal remains to be accurately defined.
- [Regeneration of airway epithelium.] [REVIEW]
- Rev Mal Respir 2014 Apr; 31(4):300-311.
Epithelial regeneration is a complex process. It can lead to the remodeling of the airway epithelium as in asthma, COPD or cystic fibrosis.The development of in vivo and in vitro models has allowed the analysis of remodeling mechanisms and showed the role of components of extracellular matrix, proteases, cytokines and growth factors. Airway epithelial progenitors and stems cells have been studied in these models. However, their identification remains difficult.Identification and characterization of airway epithelial progenitor/stem-cells, and a better knowledge of the regeneration process may allow the development of new therapeutic strategies for airway epithelial reconstitution.
- Reply to Professor Taylor. [LETTER]
- J Cyst Fibros 2014 Apr 17.
- Amiloride-sensitive fluid resorption in NCI-H441 lung epithelia depends on an apical Cl(-) conductance. [Journal Article]
- Physiol Rep 2014 Jan 1; 2(1):e00201.
Proper apical airway surface hydration is essential to maintain lung function. This hydration depends on well-balanced water resorption and secretion. The mechanisms involved in resorption are still a matter of debate, especially as the measurement of transepithelial water transport remains challenging. In this study, we combined classical short circuit current (I SC) measurements with a novel D2O dilution method to correlate ion and water transport in order to reveal basic transport mechanisms in lung epithelia. D2O dilution method enabled precise analysis of water resorption with an unprecedented resolution. NCI-H441 cells cultured at an air-liquid interface resorbed water at a rate of 1.5 ± 0.4 μL/(h cm(2)). Water resorption and I SC were reduced by almost 80% in the presence of the bulk Cl(-) channel inhibitor 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) or amiloride, a specific inhibitor of epithelial sodium channel (ENaC). However, water resorption and I SC were only moderately affected by forskolin or cystic fibrosis transmembrane regulator (CFTR) channel inhibitors (CFTRinh-172 and glybenclamide). In line with previous studies, we demonstrate that water resorption depends on ENaC, and CFTR channels have only a minor but probably modulating effect on water resorption. However, the major ENaC-mediated water resorption depends on an apical non-CFTR Cl(-) conductance.
- Quantitative imaging of airway liquid absorption in cystic fibrosis. [JOURNAL ARTICLE]
- Eur Respir J 2014 Apr 17.
New measures are needed to rapidly assess emerging treatments for cystic fibrosis (CF) lung disease. Using an imaging approach, we evaluated the absorptive clearance of the radiolabeled small molecule probe diethylene triamine penta-acetic acid (DTPA) as an in vivo indicator of changes in airway liquid absorption.DTPA absorption and mucociliary clearance rates were measured in 21 patients with CF (12 adults and nine children) and nine adult controls using nuclear imaging. The effect of hypertonic saline on DTPA absorption was also studied. In addition, in vitro studies were conducted to identify the determinants of transepithelial DTPA absorption.CF patients had significantly increased rates of DTPA absorption compared with control subjects but had similar mucociliary clearance rates. Treatment with hypertonic saline resulted in a decrease in DTPA absorption and an increase in mucociliary clearance in 11 out of 11 adult CF patients compared with treatment with isotonic saline. In vitro studies revealed that ∼50% of DTPA absorption can be attributed to transepithelial fluid transport. Apically applied mucus impedes liquid and DTPA absorption. However, mucus effects become negligible in the presence of an osmotic stimulus.Functional imaging of DTPA absorption provides a quantifiable marker of immediate response to treatments that promote airway surface liquid hydration.
- SFTA3, a novel protein of the lung: three-dimensional structure, characterisation and immune activation. [JOURNAL ARTICLE]
- Eur Respir J 2014 Apr 17.
The lung constantly interacts with numerous pathogens. Thus, complex local immune defence mechanisms are essential to recognise and dispose of these intruders. This work describes the detection, characterisation and three-dimensional structure of a novel protein of the lung (surfactant-associated protein 3 (SFTA3/SP-H)) with putative immunological features.Bioinformatics, biochemical and immunological methods were combined to elucidate the structure and function of SFTA3. The tissue-specific detection and characterisation was performed by using electron microscopy as well as fluorescence imaging.Three-dimensional structure generation and analysis led to the development of specific antibodies and, as a consequence, to the localisation of a novel protein in human lung under consideration of cystic fibrosis, asthma and sepsis. In vitro experiments revealed that lipopolysaccharide induces expression of SFTA3 in the human lung alveolar type II cell line A549. By contrast, the inflammatory cytokines interleukin (IL)-1β and IL-23 inhibit expression of SFTA3 in A549. Sequence- and structure-based prediction analysis indicated that the novel protein is likely to belong to the family of lung surfactant proteins.The results suggest that SFTA3 is an immunoregulatory protein of the lung with relevant protective functions during inflammation at the mucosal sites.
- Viability of Pseudomonas aeruginosa in cough aerosols generated by persons with cystic fibrosis. [JOURNAL ARTICLE]
- Thorax 2014 Apr 17.
Person-to-person transmission of respiratory pathogens, including Pseudomonas aeruginosa, is a challenge facing many cystic fibrosis (CF) centres. Viable P aeruginosa are contained in aerosols produced during coughing, raising the possibility of airborne transmission.Using purpose-built equipment, we measured viable P aeruginosa in cough aerosols at 1, 2 and 4 m from the subject (distance) and after allowing aerosols to age for 5, 15 and 45 min in a slowly rotating drum to minimise gravitational settling and inertial impaction (duration). Aerosol particles were captured and sized employing an Anderson Impactor and cultured using conventional microbiology. Sputum was also cultured and lung function and respiratory muscle strength measured.Nineteen patients with CF, mean age 25.8 (SD 9.2) years, chronically infected with P aeruginosa, and 10 healthy controls, 26.5 (8.7) years, participated. Viable P aeruginosa were detected in cough aerosols from all patients with CF, but not from controls; travelling 4 m in 17/18 (94%) and persisting for 45 min in 14/18 (78%) of the CF group. Marked inter-subject heterogeneity of P aeruginosa aerosol colony counts was seen and correlated strongly (r=0.73-0.90) with sputum bacterial loads. Modelling decay of viable P aeruginosa in a clinic room suggested that at the recommended ventilation rate of two air changes per hour almost 50 min were required for 90% to be removed after an infected patient left the room.Viable P aeruginosa in cough aerosols travel further and last longer than recognised previously, providing additional evidence of airborne transmission between patients with CF.
- Relationship Between Fat-Soluble Vitamin Supplementation and Blood Concentrations in Adolescent and Adult Patients With Cystic Fibrosis. [JOURNAL ARTICLE]
- Nutr Clin Pract 2014 Apr 17.
Background: Pancreatic insufficiency is common in patients with cystic fibrosis (CF) and leads to malabsorption of fat-soluble vitamins. Multivitamins, including vitamins A, D, E, and K, are routinely prescribed to patients with CF to prevent vitamin deficiencies. Our objective was to examine the relationship between fat-soluble vitamin supplements and their impact on blood concentrations. Methods: This was a retrospective chart review of patients with CF who were treated at Emory Clinic and Emory University Hospital during 2008-2012. The amount of fat-soluble vitamin supplementation, serum markers of fat-soluble vitamin concentrations, CF transmembrane conductance regulator genotype, and other demographic information were recorded from electronic medical records. Mixed-effects models were used to investigate the trends over time of fat-soluble vitamin supplements and serum vitamin concentrations. Results: In total, 177 charts were eligible. Mean (SD) age was 26.1 (10.2) years. Ninety-two percent of patients had pancreatic insufficiency and 52% had the homozygous ΔF508 mutation. Recorded fat-soluble vitamin supplementation increased in the past 5 years (P < .001 for all). Serum 25-hydroxyvitamin D increased slightly (3% increase; P < .01); however, there were no changes in the blood concentrations of vitamins A, E, and K (P = .26-.96). Conclusions: Despite a near doubling of recorded fat-soluble vitamin supplementation over the past 5 years, there was no parallel increase in blood concentrations of these vitamins. Potential reasons include suboptimal dosages, low adherence, or ongoing issues with malabsorption.