Electrochemical sensors for identifying pyocyanin production in clinical Pseudomonas aeruginosa isolates.

Biosens Bioelectron. 2017 May 24;97:65-69

Authors: Sismaet HJ, Pinto AJ, Goluch ED

Abstract
In clinical practice, delays in obtaining culture results impact patient care and the ability to tailor antibiotic therapy. Despite the advancement of rapid molecular diagnostics, the use of plate cultures inoculated from swab samples continues to be the standard practice in clinical care. Because the inoculation culture process can take between 24 and 48h before a positive identification test can be run, there is an unmet need to develop rapid throughput methods for bacterial identification. Previous work has shown that pyocyanin can be used as a rapid, redox-active biomarker for identifying Pseudomonas aeruginosa in clinical infections. However, further validation is needed to confirm pyocyanin production occurs in all clinical strains of P. aeruginosa. Here, we validate this electrochemical detection strategy using clinical isolates obtained from patients with hospital-acquired infections or with cystic fibrosis. Square-wave voltammetric scans of 94 different clinical P. aeruginosa isolates were taken to measure the concentration of pyocyanin. The results showed that all isolates produced measureable concentrations of pyocyanin with production rates correlated with patient symptoms and comorbidity. Further bioinformatics analysis confirmed that 1649 genetically sequenced strains (99.9%) of P. aeruginosa possess the two genes (PhzM and PhzS) necessary to produce pyocyanin, supporting the specificity of this biomarker. Confirming the production of pyocyanin by all clinically-relevant strains of P. aeruginosa is a significant step towards validating this strategy for rapid, point-of-care diagnostics.

PMID: 28570940 [PubMed - as supplied by publisher]

Preserving Lung Function: The Holy Grail in Managing Cystic Fibrosis.

Ann Am Thorac Soc. 2017 Jun;14(6):833-835

Authors: Sly PD, Wainwright CE

PMID: 28570157 [PubMed - in process]

Ataluren and similar compounds (specific therapies for premature termination codon class I mutations) for cystic fibrosis.

Paediatr Respir Rev. 2017 Apr 27;:

Authors: Aslam A, Jahnke N, Remmington T, Southern KW

PMID: 28566196 [PubMed - as supplied by publisher]

Post-infectious persistent cough: pathogenesis and therapeutic options.

Minerva Pediatr. 2017 May 31;:

Authors: Capristo C, Rossi GA

Abstract
Post-infectious cough is a common symptom associated with common colds and/or upper respiratory tract infection. This cough is expected to last for only for few days and resolve spontaneously, whilst when persists for longer than three weeks is defined "persistent" and is associated tickling or an irritating sensation in the throat which often leads to paroxysms of coughing. Persistent post-infectious cough can cause morbidity since it may interfere with usual living. Despite the recent advances in understanding the mechanisms that regulate cough, in physiological and pathological conditions, current therapeutic options for post-infectious cough are little or only moderately effective.

PMID: 28565899 [PubMed - as supplied by publisher]

Phosphatidylcholine passes through lateral tight junctions for paracellular transport to the apical side of the polarized intestinal tumor cell-line CaCo2.

Biochim Biophys Acta. 2016 09;1861(9 Pt A):1161-9

Authors: Stremmel W, Staffer S, Gan-Schreier H, Wannhoff A, Bach M, Gauss A

Abstract
Phosphatidylcholine (PC) is the most abundant phospholipid in intestinal mucus, indicative of a specific transport system across the mucosal epithelium to the intestinal lumen. To elucidate this transport mechanism, we employed a transwell tissue culture system with polarized CaCo2 cells. It was shown that PC could not substantially be internalized by the cells. However, after basal application of increasing PC concentrations, an apical transport of 47.1±6.3nmolh(-1)mMPC(-1) was observed. Equilibrium distribution studies with PC applied in equal concentrations to the basal and apical compartments showed a 1.5-fold accumulation on the expense of basal PC. Disruption of tight junctions (TJ) by acetaldehyde or PPARγ inhibitors or by treatment with siRNA to TJ proteins suppressed paracellular transport by at least 50%. Transport was specific for the choline containing the phospholipids PC, lysoPC and sphingomyelin. We showed that translocation is driven by an electrochemical gradient generated by apical accumulation of Cl(-) and HCO3(-) through CFTR. Pretreatment with siRNA to mucin 3 which anchors in the apical plasma membrane of mucosal cells inhibited the final step of luminal PC secretion. PC accumulates in intestinal mucus using a paracellular, apically directed transport route across TJs.

PMID: 27365309 [PubMed - indexed for MEDLINE]

Feasibility of Hypoxic Challenge Testing in Children and Adolescents with Congenital Heart and Lung Disease.

Aerosp Med Hum Perform. 2016 Dec 01;87(12):1004-1009

Authors: Spoorenberg ME, Hulzebos EH, Takken T

Abstract
BACKGROUND: This is a cross-sectional observational study to investigate the safety and feasibility of integrating changing body positions and physical activity in a hypoxic challenge test (HCT). The secondary objective was to compare oxygen saturation (Spo2) in two different locations (forehead and finger).
METHODS: Included were 12 pediatric to young adult patients with congenital heart (N = 7) or lung disease (N = 5). An HCT was performed using breathing room air (21% oxygen) while sitting and breathing a normobaric hypoxic gas mixture (15% oxygen) through a facemask while seated, lying supine, standing, walking 3 km/h, and walking 5 km/h in a nonrandomized order.
RESULTS: All patients, except one, successfully passed the HCT. Three patients reported symptoms, possibly related to hypoxia. Median Spo2 during the HCT decreased in all body positions compared with room air. In 9/12 (finger oximeter) vs. 6/12 (forehead oximeter) patients Spo2 decreased below 90% in one or more body positions at rest. In 11/12 (finger oximeter) vs. 3/12 (forehead oximeter) patients Spo2 decreased below 90% during mild exercise. There was no significant difference in Spo2 between the different body positions. However, patients desaturated significantly more during mild exercise (walking 3km/h and 5 km/h). Spo2% measured at the forehead gave significantly higher values compared to the index finger.
DISCUSSION: HCT is safe and feasible in children and adolescents with congenital heart or lung disease, and gives additional information about oxygenation during physical activity in addition to resting conditions. Simulated hypoxia of 8202 ft (2500 m) induced a small but significant decrease in Spo2%.Spoorenberg ME, Hulzebos EHJ, Takken T. Feasibility of hypoxic challenge testing in children and adolescents with congenital heart and lung disease. Aerosp Med Hum Perform. 2016; 87(12):1004-1009.

PMID: 28323585 [PubMed - indexed for MEDLINE]

An acute chest pain in an adolescent with cystic fibrosis in September: Would you have think about this?

Pediatr Pulmonol. 2017 May 31;:

Authors: Dowaikh H, Morfin-Sherpa F, Reix P

Abstract
Acute chest pain is common in patients with cystic fibrosis (CF). Here we report the case of an adolescent who suffered acute chest pain in September after an history of acute abdominal pain and fever. The reason for this clinical sceneriao was found to be Coxsackievirus B3, known to be responsible of Bornholm disease, a frequent but under recognized viral myositis. The diagnosis is mainly clinical, but evocating this diagnosis may avoid unnecessary exam.

PMID: 28564496 [PubMed - as supplied by publisher]

Sublingual immunotherapy provides long-term relief in allergic rhinitis and reduces the risk of asthma: a retrospective, real-world database analysis.

Allergy. 2017 May 31;:

Authors: Zielen S, Devillier P, Heinrich J, Richter H, Wahn U

Abstract
BACKGROUND: Allergy immunotherapy (AIT) is the only treatment for allergic rhinitis (AR) and/or allergic asthma (AA) with long-term efficacy. However, there are few real-life data on the progression of AR and/or AA in patients receiving AIT.
OBJECTIVES: To assess the real-world, long-term efficacy of grass-pollen sublingual immunotherapy (SLIT) tablets in AR and their impact on asthma onset and progression.
METHODS: In a retrospective analysis of a German longitudinal prescription database, AR patients treated with grass pollen SLIT tablets were compared with a control group not having received AIT. Multiple regression was used to compare changes over time in rescue symptomatic AR medication use after treatment cessation, asthma medication use, and the time to asthma onset in the two groups.
RESULTS: After applying all selection criteria, 2851 SLIT and 71275 Control patients were selected for the study.After treatment cessation, AR medication use was 18.8 percentage points lower (after adjustment for covariates, and relative to the pre-treatment period) in SLIT tablet group than in the non AIT group (p<0.001). Asthma onset was less frequent in SLIT tablet group than in non AIT group (odds ratio: 0.696, p=0.002), and time to asthma was significantly longer (hazard ratio: 0.523; p=0.003). After SLIT cessation, asthma medication use fell by an additional 16.7 percentage points (relative to the pre-treatment period) in the SLIT tablet group vs. the non AIT group (p=0.004).
CONCLUSIONS: Real-world treatment of AR patients with grass pollen SLIT tablets was associated with slower AR progression, less frequent asthma onset and slower asthma progression This article is protected by copyright. All rights reserved.

PMID: 28561266 [PubMed - as supplied by publisher]

A contemporary analysis of clinical and demographic factors of chronic rhinosinusitis patients and their association with disease severity.

Ir J Med Sci. 2017 May 30;:

Authors: Hoehle LP, Phillips KM, Caradonna DS, Gray ST, Sedaghat AR

Abstract
BACKGROUND: Chronic rhinosinusitis (CRS) is highly prevalent, significantly decreases quality of life and leads to tremendous health care costs every year. No recent study has characterised the prevalence of potentially CRS-modifying patient characteristics and simultaneously shown their impact on CRS severity.
AIMS: We sought to determine the prevalence of potential clinical and demographic CRS-modifying characteristics and their associations with CRS symptom severity in a large contemporary cohort of CRS patients.
METHODS: Retrospective review of CRS patients who visited our rhinology clinics between February 2016 and February 2017 was conducted. CRS symptom severity was measured using the 22-item Sinonasal Outcomes Test (SNOT-22) questionnaire, which all patients received. Association was sought between SNOT-22 score (as dependent variable) and patients' clinical and demographic characteristics using linear regression.
RESULTS: Of the 572 included patients, the mean age was 51.1 years (SD = 15.8) and the mean SNOT-22 score was 34.3 (SD = 22.6). Prevalence of granulomatous diseases, immunodeficiency and cystic fibrosis were each approximately 5%. Prevalence of aeroallergen hypersensitivity was 42.3% and prevalence of asthma was 27.8%. More severe CRS symptomatology was associated with smoking tobacco (adjusted β = 5.47, p = 0.034) and comorbid asthma (adjusted β = 12.02, p < 0.001), whilst less severe symptomatology was associated with older age (adjusted β = -0.23, p = 0.002) and diagnosis of cystic fibrosis (adjusted β = -11.87, p = 0.009).
CONCLUSIONS: In a contemporary cohort of CRS patients, prevalence of disease-modifying comorbidities ranged from approximately 5 to over 40%. Smoking tobacco and asthma were associated with more severe CRS symptomatology, whilst older age and diagnosis of cystic fibrosis were associated with less severe CRS symptomatology.

PMID: 28560517 [PubMed - as supplied by publisher]

Cystic fibrosis: Thymosin α1 rescues CFTR activity.

Nat Rev Drug Discov. 2017 May 31;16(6):386

Authors: Crunkhorn S

PMID: 28559563 [PubMed - in process]

Molecular typing of Mycobacterium Abscessus isolated from cystic fibrosis patients.

Int J Mycobacteriol. 2017 Apr-Jun;6(2):138-141

Authors: Trovato A, Baldan R, Costa D, Simonetti TM, Cirillo DM, Tortoli E

Abstract
BACKGROUND: The possibility of inter-human transmission of Mycobacterium abscessus in cystic fibrosis centres has been recently hypothesized suggesting the need for the molecular characterization of strains isolated from such patients.
MATERIALS AND METHODS: One hundred and forty one isolates of M. abscessus grown from sputum samples of 29 patients with cystic fibrosis were genotyped resorting to variable number of tandem repeats (VNTR) determination and whole genome sequencing (WGS).
RESULTS: Out of 29 VNTR profiles, 15 were unique to the same number of patients while seven were shared by multiple patients. WGS showed that only two of the patients sharing common VNTR patterns were indeed infected by the same strain. The shared VNTR patterns were mostly present among the isolates of M. abscessus subsp. abscessus.
CONCLUSION: As expected WGS showed a clearly higher discriminatory power in comparison with VNTR and appeared the only molecular epidemiology tool suitable to effectively discriminate the isolates of M. abscessus subsp. abscessus.

PMID: 28559514 [PubMed - in process]

Inhaled Drug Therapy 2016: The Year in Review.

Respir Care. 2017 May 30;:

Authors: Dhand R

Abstract
Some recent salient publications related to inhaled drug therapy are discussed. Unexpectedly, a 2.5-μg once-daily dose of tiotropium (Respimat) had greater efficacy than the 5.0-μg daily dose. Occurrence of a reverse dose response serves to caution us that administering more drug is not always beneficial. Small-airway inflammation contributes to pathogenesis of asthma, especially severe asthma. However, there is no conclusive evidence that the use of small-particle aerosols to target small airways improves clinical outcomes in controlled clinical trials. Clinical outcomes of patients with symptomatic asthma have been better in "real-life" studies when fine-particle aerosols were compared with conventional (large-particle) aerosols. In subjects with COPD, the FLAME study indicates that a long-acting antimuscarinic agent/long-acting β-agonist combination was superior to an inhaled corticosteroid/long-acting β-agonist combination in preventing exacerbations. Another study in children with asthma and adults with asthma or COPD showed that peak inhalation flow must be considered in the context of the dry powder inhaler resistance. Investigators from the United Kingdom have shown modest success in replacing the defective cystic fibrosis transmembrane regulator gene in subjects with cystic fibrosis with a plasmid encoding the normal cystic fibrosis transmembrane regulator gene packaged within a non-viral vector. Also, inhaled antibiotics in patients with non-cystic fibrosis bronchiectasis and inhaled interferon-|gg in patients with idiopathic pulmonary fibrosis have shown encouraging results but are investigational at this time. Compared to combustion cigarettes, use of e-cigarettes reduces exposure to carcinogens and volatile organic compounds. However, high levels of benzaldehyde in the vapor from cherry-flavored cigarettes raise concerns about the safety of some food flavorings in e-cigarettes.

PMID: 28559466 [PubMed - as supplied by publisher]

Efficacy of Rhesus Theta (θ)-Defensin-1 in Experimental Models of Pseudomonas aeruginosa Lung Infection and Inflammation.

Antimicrob Agents Chemother. 2017 May 30;:

Authors: Bensman TJ, Jayne JG, Sun M, Kimura E, Meinert J, Wang JC, Schaal JB, Tran D, Rao AP, Akbari O, Selsted ME, Beringer PM

Abstract
Rationale: Chronic airway infection and inflammation contribute to the progressive loss of lung function and shortened survival of patients with cystic fibrosis (CF). Rhesus theta (θ) defensin-1 (RTD-1) is a macrocyclic host defense peptide with antimicrobial and immunomodulatory activities. Combined with favorable preclinical safety and peptide stability data, RTD-1 warrants investigation to determine its therapeutic potential for treatment of CF lung disease.Objectives: We sought to evaluate the therapeutic potential of RTD-1 for CF airway infection and inflammation using in vitro, ex vivo, and in vivo models.Methods: We evaluated RTD-1's effects on basal and P. aeruginosa induced inflammation in CF sputum leukocytes and CF bronchial epithelial cells. Peptide stability was evaluated by incubation with CF sputum. Airway pharmacokinetics, safety and tolerance studies were performed in naïve mice. Aerosolized RTD-1 treatment effects were assessed by analyzing lung bacterial burden and airway inflammation using an established model of chronic P. aeruginosa endobronchial infection in CF (ΔF508) mice.Measurements and Main Results: RTD-1 directly reduces metalloprotease activity, as well as inflammatory cytokine secretion from CF airway leukocyte and bronchial epithelial cells. Intrapulmonary safety, tolerability and stability data support the aerosol administration route. RTD-1 reduced bacterial lung burden, airway neutrophils, and inflammatory cytokines in CF mice with chronic P. aeruginosa lung infection.Conclusions: Collectively, these studies support further development of RTD-1 for treatment of CF airway disease.

PMID: 28559270 [PubMed - as supplied by publisher]

Aerosolized Polymyxin B for Treatment of Respiratory Tract Infections: Determination of Pharmacokinetic/Pharmacodynamic Indices for Aerosolized Polymyxin B against Pseudomonas aeruginosa in a Mouse Lung Infection Model.

Antimicrob Agents Chemother. 2017 May 30;:

Authors: Lin YW, Zhou QT, Onufrak NJ, Wirth V, Chen K, Wang J, Forrest A, Chan HK, Li J

Abstract
Pulmonary administration of polymyxins is increasingly used for the treatment of respiratory tract infections caused by multidrug-resistant Gram-negative bacteria, such as those in patients with cystic fibrosis. However, there is a lack of pharmacokinetics (PK), pharmacodynamics (PD) and toxicity data of aerosolized polymyxin B to inform rational dosage selection. The PK and PD of polymyxin B following pulmonary and intravenous dosing were conducted in neutropenic infected mice and the data were analyzed by a population PK model. Dose-fractionation study was performed for total daily doses between 2.06 and 24.8 mg base/kg against Pseudomonas aeruginosa ATCC 27853, PAO1, and FADDI-PA022 (MIC = 1 mg/L for all three strains). Histopathological examination of lung was undertaken at 24 h post treatment in both healthy and neutropenic infected mice. A two-compartment PK model was required for both epithelial lining fluid (ELF) and plasma drug exposure. The model consisted of central and peripheral compartments and was described by bidirectional first-order distribution clearance. AUC/MIC was the most predictive PK/PD index to describe the antimicrobial efficacy of aerosolized polymyxin B in treating lung infections in mice (R(2)=0.70-0.88 for ELF and R(2)=0.70-0.87 for plasma). The AUC/MIC targets associated with bacteriostasis against the three P. aeruginosa strains were 1326-1506 in ELF and 3.14-4.03 in plasma. Histopathological results showed that polymyxin B aerosols significantly reduced lung inflammation and preserved lung epithelial integrity. This study highlights the advantageous PK/PD characteristics of pulmonary delivery of polymyxin B over intravenous administration in achieving high drug exposure in ELF.

PMID: 28559256 [PubMed - as supplied by publisher]

Electronic applications for the CFQ-R scoring.

Respir Res. 2017 May 30;18(1):108

Authors: Ronit A, Gelpi M, Argentiero J, Mathiesen I, Nielsen SD, Pressler T, Quittner AL

Abstract
Patient reported outcomes (PROs) have become widely accepted outcome measures in cystic fibrosis (CF) and other respiratory diseases. The Cystic Fibrosis-Questionnaire-Revised (CFQ-R) is the best validated and most widely used PRO for CF. Data collection can be time-intensive, and electronic platforms would greatly facilitate the feasibility, utility and accuracy of administration of the CFQ-R. Given that the CFQ-R is utilized in virtually all clinical trials worldwide and is increasingly integrated into clinical practice, we developed a software application that will help users to administer, score and save CFQ-R data for all versions. All codes are open access, which will enable other PRO users to design similar applications for other respiratory diseases, such as primary ciliary dyskinesia and non-CF bronchiectasis.

PMID: 28558706 [PubMed - in process]

A randomised control trial of atorvastatin in bronchiectasis patients infected with Pseudomonas aeruginosa- a proof of concept study.

Chest. 2017 May 26;:

Authors: Bedi P, Chalmers JD, Graham C, Clarke A, Donaldson S, Doherty C, Govan JR, Davidson DJ, Rossi AG, Hill AT

Abstract
INTRODUCTION: There are no randomised control trials of statin therapy in patients with severe bronchiectasis, chronically infected with Pseudomonas aeruginosa.
METHODS: 32 patients chronically infected with P. aeruginosa were recruited in this double blind cross over RCT. 16 patients were recruited in each arm, given atorvastatin 80mg or placebo for 3months, followed by a washout period for 6weeks, crossed over and administered the alternative therapy for 3months.
RESULTS: 27 patients completed the study. Atorvastatin did not significantly improve the primary endpoint of cough as measured by Leicester Cough Questionnaire [mean difference=1.92, 95% CI for difference (-0.57, 4.41), p=0.12]. However, atorvastatin treatment resulted in improved St Georges Respiratory Questionnaire (-5.62points, p=0.016), reduced serum CXCL8 (p=0.04), TNF (p=0.01) and ICAM1 (p=0.04). There was a trend towards improvement in serum CRP and serum neutrophil counts (p=0.07 and p=0.06 respectively). In vitro, we demonstrated that atorvastatin 10μM reduced fMLF induced upregulation of CD11b expression and changes in calcium flux reflecting an ability to decrease neutrophil activation.
CONCLUSION: We demonstrated that atorvastatin reduced systemic inflammation and improved quality of life in bronchiectasis patients infected with P. aeruginosa. These effects may be due to an ability of atorvastatin to modulate neutrophil activation.

PMID: 28554732 [PubMed - as supplied by publisher]

β-Sitosterol Reduces the Expression of Chemotactic Cytokine Genes in Cystic Fibrosis Bronchial Epithelial Cells.

Front Pharmacol. 2017;8:236

Authors: Lampronti I, Dechecchi MC, Rimessi A, Bezzerri V, Nicolis E, Guerrini A, Tacchini M, Tamanini A, Munari S, D'Aversa E, Santangelo A, Lippi G, Sacchetti G, Pinton P, Gambari R, Agostini M, Cabrini G

Abstract
Extracts from Nigella arvensis L. seeds, which are widely used as anti-inflammatory remedies in traditional medicine of Northern Africa, were able to inhibit the expression of the pro-inflammatory neutrophil chemokine Interleukin (IL)-8 in Cystic Fibrosis (CF) bronchial epithelial IB3-1 cells exposed to the Gram-negative bacterium Pseudomonas aeruginosa. The chemical composition of the extracts led to the identification of three major components, β-sitosterol, stigmasterol, and campesterol, which are the most abundant phytosterols, cholesterol-like molecules, usually found in plants. β-sitosterol (BSS) was the only compound that significantly reproduced the inhibition of the P. aeruginosa-dependent expression of IL-8 at nanomolar concentrations. BSS was tested in CF airway epithelial CuFi-1 cells infected with P. aeruginosa. BSS (100 nM), showed a significant and consistent inhibitory activity on expression of the P. aeruginosa-stimulated expression chemokines IL-8, GRO-α GRO-β, which play a pivotal role in the recruitment of neutrophils in CF inflamed lungs. Preliminary mechanistic analysis showed that BSS partially inhibits the P. aeruginosa-dependent activation of Protein Kinase C isoform alpha, which is known to be involved in the transmembrane signaling activating IL-8 gene expression in bronchial epithelial cells. These data indicate BSS as a promising molecule to control excessive lung inflammation in CF patients.

PMID: 28553226 [PubMed - in process]

β1-Integrin Accumulates in Cystic Fibrosis Luminal Airway Epithelial Membranes and Decreases Sphingosine, Promoting Bacterial Infections.

Cell Host Microbe. 2017 May 25;:

Authors: Grassmé H, Henry B, Ziobro R, Becker KA, Riethmüller J, Gardner A, Seitz AP, Steinmann J, Lang S, Ward C, Schuchman EH, Caldwell CC, Kamler M, Edwards MJ, Brodlie M, Gulbins E

Abstract
Chronic pulmonary colonization with bacterial pathogens, particularly Pseudomonas aeruginosa, is the primary cause of morbidity and mortality in patients with cystic fibrosis (CF). We observed that β1-integrins accumulate on the luminal membrane of upper-airway epithelial cells from mice and humans with CF. β1-integrin accumulation is due to increased ceramide and the formation of ceramide platforms that trap β1-integrins on the luminal pole of bronchial epithelial cells. β1-integrins downregulate acid ceramidase expression, resulting in further accumulation of ceramide and consequent reduction of surface sphingosine, a lipid that kills bacteria. Interrupting this vicious cycle by triggering surface β1-integrin internalization via anti-β1-integrin antibodies or the RGD peptide ligand-or by genetic or pharmacological correction of ceramide levels-normalizes β1-integrin distribution and sphingosine levels in CF epithelial cells and prevents P. aeruginosa infection in CF mice. These findings suggest a therapeutic avenue to ameliorate CF-associated bacterial infections.

PMID: 28552668 [PubMed - as supplied by publisher]

Spirometry-Assisted High Resolution Chest Computed Tomography in Children: Is it Worth the Effort?

Curr Probl Diagn Radiol. 2017 Apr 07;:

Authors: Otjen JP, Swanson JO, Oron A, DiBlasi RM, Swortzel T, van Well JAM, Gommers EAE, Rosenfeld M

Abstract
BACKGROUND: Image quality of high resolution chest computed tomographies (HRCTs) depends on adequate breath holds at end inspiration and end expiration. We hypothesized that implementation of spirometry-assisted breath holds in children undergoing HRCTs would improve image quality over that obtained with voluntary breath holds by decreasing motion artifact and atelectasis.
METHODS: This is a retrospective case-control study of HRCTs obtained at a tertiary care children's hospital before and after implementation of a spirometry-assisted CT protocol, in which children ≥8 years of age are first trained in supine slow vital capacity maneuvers and then repeat the maneuvers in the CT scanner, coached by a respiratory therapist. Spirometry-assisted CT scans (cases) were matched by age, gender and diagnosis (cystic fibrosis vs other) to CT scans obtained with voluntary breath holds in the 6 years before implementation of the spirometry assistance protocol (controls), and evaluated by 2 blinded pediatric radiologists.
RESULTS: Among both cases and controls (N = 50 each), 10 carried the diagnosis of cystic fibrosis and 40 had other diagnoses. Mean age was 12.9 years (range: 7.5-20.1) among cases and 13.0 (7.1-19.7) among controls. Mean (SD) inspiratory image density among cases was -852 (37) Hounsfield units (HU) and -828 (43) among controls (p = 0.006). Mean (SD) expiratory image density was -629 (95) HU among cases and -688 (83) HU among controls (p = 0.002). Mean (SD) change in image density between inspiratory and expiratory images was +222 (85) HU among cases and +140 (76) HU among controls (p < 0.001). Motion artifact was present on inspiratory images in 5 cases and 9 controls (p = 0.39 by Fisher's exact test), and on expiratory images in 20 cases and 18 controls (p > 0.80). Atelectasis was present on inspiratory images in 8 cases and 9 controls and on expiratory images in 9 cases and 10 controls (p > 0.80).
CONCLUSIONS: Spirometry-assisted CTs had a significantly greater difference in lung density between inspiratory and expiratory scans than those performed with voluntary breath holds, likely improving the ability to detect air trapping. No appreciable difference in image quality was detected for the presence of motion artifact or atelectasis.

PMID: 28552547 [PubMed - as supplied by publisher]

Bacteriology and treatment of infections in the upper and lower airways in patients with primary ciliary dyskinesia: adressing the paranasal sinuses.

Dan Med J. 2017 May;64(5):

Authors: Alanin MC

Abstract
The respiratory tract is lined with motile cilia that transport respiratory mucus. Primary ciliary dyskinesia (PCD) is a chronic genetic disease caused by mutations in genes responsible for ciliary structure and function. Non-functional airway cilia impair the mucociliary clearance (MCC), causing mucostasis, lung infections and destruction, chronic rhinosinusitis (CRS) and hearing impairment. It is of paramount importance to postpone chronic lung infection mainly with Gram-negative bacteria (GNB) in patients with an impaired MCC. When successful, lung function can be stabilized and quality of life (QoL) improved. In this thesis, we evaluated whether PCD patients can benefit from the experience we have gained from our operative approach towards the paranasal sinuses in cystic fibrosis (CF) patients. In CF, it has been established that bacterial sinusitis can be a focus for initial lung colonization and chronic lung infection. Combined endoscopic sinus surgery (ESS) and adjuvant therapy can eradicate sinus bacteria, reduce pulmonary infections and improve quality of life (QoL).      Currently, approximately 120 patients are diagnosed with PCD in Denmark and all are affiliated with the Danish PCD Centre. Patients included in this thesis were recruited from this cohort. In papers (I, IV), we found that the most frequent sinus pathogen was P. aeruginosa, which was isolated in 12 out of 31 (39%) patients who underwent ESS. In searching for a non-pulmonary infectious focus, we observed simultaneous sinus and lung infec-tions with identical pathogens in two out of three patients. This supports our hypothesis of a bacterial reservoir in the sinuses. Next (II), we examined the bacterial flora associated with acute and chronic pulmonary infections in PCD. A high prevalence of chronic infections encouraged a search for new treatment regimens, including ESS with adjuvant therapy, to impact the course of infection. We revealed that P. aeruginosa frequently colonizes the airways in PCD and during the 11-year study period a total of 42 out of 107 (39%) patients fulfilled the definition of chronic lung infection at some point. Importantly, 10 out of 12 patients (83%) with chronic lung infection had the same clone type of P. aeruginosa for years, as determined by pulsed field gel-electrophoresis (PFGE), thus substantiating factual chronic airway infection. Further, we found an increase in the prevalence of P. aeruginosa with age and observed a negative association between early PCD diagnosis and prevalence of P. aeruginosa. This indicates a positive effect of early diagnosis and initiation of therapy. In paper (III), we performed whole genome sequencing (WGS) of P. aeruginosa isolated from the same 12 patients who were included in the PFGE analysis in paper II. By sequencing and phenotypically characterizing multiple isolates from the same patients we were able to study the with-in host bacterial evolution for the first time in PCD. The analyses provided detailed insight into how P. aeruginosa evolves in PCD when they are stressed by the host immune system and antibiotics. We verified the persistence of clonal lineages and confirmed that different clone types of P. aeruginosa can establish persistent infections in PCD patients. Further, we showed that P. aeruginosa acclimatizes grad-ually to the PCD airway by accumulating pathoadaptive mutations and phenotypic characteristics similar to those of CF. Such information may provide valuable clinical information, and as an example we identified mutations in genes responsible for the development of antibiotic resistance. Based on our research we conclude that P. aeruginosa is a major pathogen in PCD and that future research should focus on pre-venting or eradicating these bacteria. Implementing ESS with adjuvant therapy to PCD patients (I, IV) significantly ameliorated CRS symptoms. Further, postoperatively patients tended to have fewer positive lower airway cultures and better lung function; approximately one out of four operated patients, in search of an infectious focus, remained free of lung colonization with P. aeruginosa during follow-up for at least six months. Based on these results, it is tempting to speculate that ESS with adjuvant therapy can eradicate sinus bacteria and thereby reduce lung re-colonization from the sinuses. However, further evidence is needed to support this hypothesis, preferably from a multicentre randomized controlled trial.

PMID: 28552099 [PubMed - in process]