Assessment of endothelial function is reproducible in patients with cystic fibrosis.

J Cyst Fibros. 2019 Apr 04;:

Authors: Derella CC, Lee N, Crandall R, Blackburn M, Looney J, Mangieri A, Rodriguez-Miguelez P, Tucker MA, Harris RA

Abstract
BACKGROUND: New treatments have improved life-expectancy in patients with cystic fibrosis (CF); however, cardiovascular health remains an area of concern in this population. Flow-mediated dilation (FMD), a non-invasive assessment of vascular endothelial function that predicts future cardiovascular disease and events, is attenuated in patients with CF compared to controls. The reproducibility of FMD in CF; however, has yet to be evaluated. Thus, this study sought to examine the within-day, between-day, and between-month reproducibility of FMD in patients with CF.
METHODS: Pulmonary function, baseline diameter (cm), peak diameter (cm), and FMD(%) were assessed 5 times (sessions A-E) over four visits in 13 patients with CF (six males, seven females, age range: 13-43 years old; mean forced expiratory volume in 1 s = 71% predicted). Sessions A and B (within-day), C (between-day), and D and E (between-month) were separated by 3 h, at least 10 days, and ~3 months, respectively. Reproducibility was assessed by: (1) paired t-tests, (2) coefficients of variation (CV), (3) CV prime, (4) Pearson's correlation (r), (5) intra-class correlation coefficient, and (6) Bland-Altman plots. Five acceptable parameters were required to determine reproducibility.
RESULTS: Pulmonary function was stable throughout all visits. FMD(%) and baseline diameter (cm) satisfied all six reproducibility criteria for within-day, while peak diameter (cm) met five of six criteria. All six reproducibility criteria were met for all between-day and between-month assessments.
CONCLUSION: The present study provides evidence that endothelial function assessed by FMD is reproducible in patients with CF not only within-day, but also between-day and between-month.

PMID: 30956017 [PubMed - as supplied by publisher]

Lectin activity of Pseudomonas aeruginosa vaccine candidates PSE17-1, PSE41-5 and PSE54.

Biochem Biophys Res Commun. 2019 Apr 03;:

Authors: Day CJ, Hartley-Tassell LE, Seib KL, Tiralongo J, Bovin N, Savino S, Masignani V, Jennings MP

Abstract
Pseudomonas aeruginosa is an opportunistic pathogen that causes nosocomial infections most commonly in immunocompromised, cystic fibrosis (CF) and burns patients. The pilin and Pseudomonas lectins 1 (PA-IL) and 2 (PA-IIL) are known glycan-binding proteins of P. aeruginosa that are involved in adherence to host cells, particularly CF host airways. Recently, new P. aeruginosa surface proteins were identified by reverse vaccinology and tested in vivo as potential vaccine antigens. Three of these, namely PSE17-1, PSE41-5 and PSE54, were screened for glycan binding using glycan arrays displaying glycan structures representative of those found on human cells. Surface plasmon resonance was used to confirm the lectin activity of these proteins, and determined affinities with several host glycans to be in the nanomolar range. PSE17-1 binds hyaluronic acid and sialyl Lewis A and X. PSE41-5 binds terminal β-linked galactose structures, Lewis and ABO blood group antigens. PSE54 binds to ABO blood group antigens and some terminal β-linked galactose. All three proteins are novel lectins of P. aeruginosa with potential roles in infection of host cells.

PMID: 30954224 [PubMed - as supplied by publisher]

Asymptomatic catheter-related venous thrombosis in a child with cystic fibrosis: When to treat?

J Vasc Nurs. 2019 Mar;37(1):43-45

Authors: Schapkaitz E, Weil R, White D, Klugman S

Abstract
The use of central venous catheters (CVCs) in patients with cystic fibrosis is associated with an increased incidence of right atrial thrombosis. Practically, the management of CVC-related right atrial thrombosis presents a challenge as there are no clinical trials or systematic reviews in pediatric patients with cystic fibrosis. We describe a case of a 5-year-old child who presented with a CVC-related infection due to Candida parapsilosis. Echocardiogram revealed the presence of an incidental thrombus, measuring 1.4 cm × 0.4 cm, at the tip of the catheter, adherent to the right atrial wall and discrete from the tricuspid valve leaflets. Imaging was performed at monthly intervals and showed spontaneous resolution of the thrombus after six months. Follow-up blood cultures were negative, and the course of the patient was uneventful.

PMID: 30954197 [PubMed - in process]

Dynamic-DeepHit: A Deep Learning Approach for Dynamic Survival Analysis with Competing Risks based on Longitudinal Data.

IEEE Trans Biomed Eng. 2019 Apr 03;:

Authors: Lee C, Yoon J, Van Der Schaar M

Abstract
Currently available risk prediction methods are limited in their ability to deal with complex, heterogeneous, and longitudinal data such as that available in primary care records, or in their ability to deal with multiple competing risks. This paper develops a novel deep learning approach that is able to successfully address current limitations of standard statistical approaches such as landmarking and joint modeling. Our approach, which we call Dynamic-DeepHit, flexibly incorporates the available longitudinal data comprising various repeated measurements (rather than only the last available measurements) in order to issue dynamically updated survival predictions for one or multiple competing risk(s). Dynamic-DeepHit learns the time-to-event distributions without the need to make any assumptions about the underlying stochastic models for the longitudinal and the time-to-event processes. Thus, unlike existing works in statistics, our method is able to learn data-driven associations between the longitudinal data and the various associated risks without underlying model specifications. We demonstrate the power of our approach by applying it to a real-world longitudinal dataset from the UK Cystic Fibrosis Registry which includes a heterogeneous cohort of 5,883 adult patients with annual follow-ups between 2009-2015. The results show that Dynamic-DeepHit provides a drastic improvement in discriminating individual risks of different forms of failures due to cystic fibrosis. Furthermore, our analysis utilizes postprocessing statistics that provide clinical insight by measuring the influence of each covariate on risk predictions and the temporal importance of longitudinal measurements, thereby enabling us to identify covariates that are influential for different competing risks.

PMID: 30951460 [PubMed - as supplied by publisher]

Cystic Fibrosis Inflammation: Hyper-inflammatory, Hypo-inflammatory, or Both?

Am J Respir Cell Mol Biol. 2019 Apr 05;:

Authors: Murphy SV, Ribeiro CMP

PMID: 30951377 [PubMed - as supplied by publisher]

The Economic Burden of Cystic Fibrosis in Germany from a Payer Perspective.

Pharmacoeconomics. 2019 Apr 04;:

Authors: Frey S, Stargardt T, Schneider U, Schreyögg J

Abstract
BACKGROUND: Cystic fibrosis (CF) is a genetic disorder that is most common in white children and young adults. Long-term survival has improved steadily and will likely increase with the recent introduction of neonatal screening and causative treatment. However, these advances have substantial economic consequences for healthcare systems and payers.
OBJECTIVE: This study aims to determine the economic burden of CF and to elucidate the structure of costs and the distribution of resources for different subpopulations, treatment strategies and sites of care for CF in Germany.
METHODS: We conducted an observational cohort study to evaluate the economic burden of CF and the costs of treatment within different CF substrata from a payer perspective. Using claims data from a large German sickness fund, we identify the causal effect of CF on costs, service utilisation, and premature mortality. We compare the outcomes of a CF and a control group using entropy balancing and regression techniques, conduct further analyses for the CF group to gain insight into the economic burden associated with different levels of disease severity, and analyse pharmaceutical expenditures by collecting all CF-related expenses on outpatient drug treatment from the sickness fund database.
RESULTS: Direct medical costs caused by CF in Germany in 2016 average €17,551 per patient-year and appear to be mainly driven by the cost of outpatient drug prescriptions (€12,869). We estimate that the national burden of disease totals €159 million. Costs increase with disease severity and related complications. If all eligible CF patients in the German population were to receive CF mutation-specific drugs, the economic burden of disease would more than triple to €594 million.
CONCLUSION: CF has a constant and wide-ranging economic impact on payers, with considerable differences in the distribution of costs and service utilisation between younger and older patients as well as mild vs. severe patients. Pharmaceutical expenses will increase in the future as causative treatment gains importance. We encourage the use of a control group approach for burden-of-disease studies to be able to identify causal effects and thus to obtain more precise estimates.

PMID: 30949989 [PubMed - as supplied by publisher]

Bacteriophage PEV20 and Ciprofloxacin Combination Treatment Enhances Removal of Pseudomonas aeruginosa Biofilm Isolated from Cystic Fibrosis and Wound Patients.

AAPS J. 2019 Apr 04;21(3):49

Authors: Chang RYK, Das T, Manos J, Kutter E, Morales S, Chan HK

Abstract
Antibiotic resistance in Pseudomonas aeruginosa biofilms necessitates the need for novel antimicrobial therapy with anti-biofilm properties. Bacteriophages (phages) are recognized as an ideal biopharmaceutical for combating antibiotic-resistant bacteria especially when used in combination with antibiotics. However, previous studies primarily focused on using phages against of P. aeruginosa biofilms of laboratory strains. In the present study, biofilms of six P. aeruginosa isolated from cystic fibrosis and wound patients, and one laboratory strain was treated singly and with combinations of anti-Pseudomonas phage PEV20 and ciprofloxacin. Of these strains, three were highly susceptible to the phage, while one was partially resistant and one was completely resistant. Combination treatment with PEV20 and ciprofloxacin enhanced biofilm eradication compared with single treatment. Phage and ciprofloxacin synergy was found to depend on phage-resistance profile of the target bacteria. Furthermore, phage and ciprofloxacin combination formulation protected the lung epithelial and fibroblast cells from P. aeruginosa and promoted cell growth. The results demonstrated that thorough screening of phage-resistance is crucial for designing phage-antibiotic formulation. The addition of highly effective phage could reduce the ciprofloxacin concentration required to combat P. aeruginosa infections associated with biofilm in cystic fibrosis and wound patients.

PMID: 30949776 [PubMed - in process]

Cystic Fibrosis: From Qualification to Lung Transplantation, a Single Center Experience.

Ann Transplant. 2019 Apr 05;24:185-190

Authors: Ochman M, Latos M, Urlik M, Stącel T, Nęcki M, Tatoj Z, Zawadzki F, Wajda-Pokrontka M, Przybyłowski P, Zembala M

Abstract
BACKGROUND Cystic fibrosis (CF) is congenital multisystem disorder, that leads to gradual deterioration of pulmonary function. Advancements in therapy of CF-related lung disease have delayed its progression. However, lung transplantation remains the only therapeutic option for majority of such patients. Aim of the study was to assess qualification process and outcome of lung transplantation as a treatment of CF patients qualified in a single center between 2011 and 2018. MATERIAL AND METHODS This retrospective study assessed 41 patients who were qualified to be treated by means of lung transplantation due to CF in Lung Transplant Program of Silesian Center for Heart Diseases between 2011 and 2018. Analysis of patients during qualification process and after lung transplantation was performed. Lung recipients were observed during 1-year follow-up by means of pulmonary function tests. RESULTS 1-year survival was noted among 80% of the patients; 3-year survival and 5-year survival were noted among 70% of the recipients. Mean forced expiratory volume in 1 second (FEV1) increased after lung transplantation: 21.19% at qualification; and 76.67% at 12 months after lung transplantation. Mean forced vital capacity (FVC) results also improved: 34.18% at qualification and 78.34% at 12 months after lung transplantation. The 6-minute walk test (6MWT) before and after treatment noted an increase of 175.55 m. CONCLUSIONS Lung transplantation improves respiratory capacity of CF patients and prolongs their life.

PMID: 30948702 [PubMed - in process]

Hepatic Manifestations of Cystic Fibrosis.

Clin Liver Dis. 2019 May;23(2):263-277

Authors: Sakiani S, Kleiner DE, Heller T, Koh C

Abstract
Cystic fibrosis liver disease (CFLD) remains the third leading cause of death in patients with cystic fibrosis. Although most patients with CFLD present in childhood, recent studies suggest a second wave of liver disease in adulthood. There are no clear guidelines for diagnosing CFLD. Treatment options for CFLD remain limited, and while UDCA is widely used, its long-term benefit is unclear. Those who develop hepatic decompensation or uncontrolled variceal bleeding may benefit from liver transplant, either alone, or in combination with lung transplant.

PMID: 30947876 [PubMed - in process]

The emerging burden of liver disease in cystic fibrosis patients: A UK nationwide study.

PLoS One. 2019;14(4):e0212779

Authors: Toledano MB, Mukherjee SK, Howell J, Westaby D, Khan SA, Bilton D, Simmonds NJ

Abstract
OBJECTIVE: Cystic fibrosis associated liver disease (CFLD) is the third largest cause of mortality in CF. Our aim was to define the burden of CFLD in the UK using national registry data and identify risk factors for progressive disease.
METHODS: A longitudinal population-based cohort study was conducted. Cases were defined as all patients with CFLD identified from the UK CF Registry, 2008-2013 (n = 3417). Denominator data were derived from the entire UK CF Registry. The burden of CFLD was characterised. Regression analysis was undertaken to identify risk factors for cirrhosis and progression.
RESULTS: Prevalence of CFLD increased from 203.4 to 228.3 per 1000 patients during 2008-2013. Mortality in CF patients with CFLD was more than double those without; cirrhotic patients had higher all-cause mortality (HR 1.54, 95% CI 1.09 to 2.18, p = 0.015). Median recorded age of cirrhosis diagnosis was 19 (range 5-53) years. Male sex, Pseudomonas airway infection and CF related diabetes were independent risk factors for cirrhosis. Ursodeoxycholic acid use was associated with prolonged survival in patients without cirrhosis.
CONCLUSIONS: This study highlights an important changing disease burden of CFLD. The prevalence is slowly increasing and, importantly, the disease is not just being diagnosed in childhood. Although the role of ursodeoxycholic acid remains controversial, this study identified a positive association with survival.

PMID: 30947265 [PubMed - in process]

Appetitive characteristics in children with cystic fibrosis: Questionnaire validation and associations with nutritional status.

Appetite. 2019 Apr 01;:

Authors: Papantoni A, Reinblatt SP, Findling RL, Moran TH, Mogayzel PJ, Carnell S

Abstract
BACKGROUND: Appetitive characteristics are an important factor in the nutritional status of children with cystic fibrosis (CF). We administered a brief parent-report eating behavior questionnaire, validated in healthy children, to determine the relationship between appetitive characteristics and body weight in children with CF.
METHODS: Parents of children attending the Johns Hopkins Pediatric CF Clinic completed the Child Eating Behavior Questionnaire (CEBQ) at a routine clinic visit. Responses were correlated with anthropometric and other clinical data.
RESULTS: Parents of 64 children with CF aged 7.74 ± 3.17 years (mean ± SD) completed the CEBQ. The CEBQ subscales demonstrated good internal consistency (Cronbach's α = 0.76-0.94). Higher scores on food avoidance subscales (Slowness in Eating) were associated with lower body mass index (BMI) z-scores, and higher scores on food approach subscales (Food Responsiveness, Enjoyment of Food, Emotional Overeating) with higher BMI z-scores. Children with feeding aids (i.e. gastric tube or appetite-stimulating medications) demonstrated greater food avoidance (Slowness in Eating, p < 0.001) and lesser food approach (Enjoyment of Food subscale, p = 0.009) when compared to those without feeding aids. Children with pancreatic insufficiency also demonstrated greater food avoidance (Slowness in Eating, p = 0.011).
CONCLUSIONS: The CEBQ can be used in a clinical setting to identify children with CF with appetitive characteristics associated with difficulty gaining weight. These children could potentially benefit from earlier interventions to aid in weight gain. Characterization of appetite using the CEBQ could aid investigation of the biological etiology of low appetite, and optimization of clinical and parental approaches to achieving a healthy nutritional status.

PMID: 30946864 [PubMed - as supplied by publisher]

Deep Convolutional Neural Networks With Multiplane Consensus Labeling for Lung Function Quantification Using UTE Proton MRI.

J Magn Reson Imaging. 2019 Apr 04;:

Authors: Zha W, Fain SB, Schiebler ML, Evans MD, Nagle SK, Liu F

Abstract
BACKGROUND: Ultrashort echo time (UTE) proton MRI has gained popularity for assessing lung structure and function in pulmonary imaging; however, the development of rapid biomarker extraction and regional quantification has lagged behind due to labor-intensive lung segmentation.
PURPOSE: To evaluate a deep learning (DL) approach for automated lung segmentation to extract image-based biomarkers from functional lung imaging using 3D radial UTE oxygen-enhanced (OE) MRI.
STUDY TYPE: Retrospective study aimed to evaluate a technical development.
POPULATION: Forty-five human subjects, including 16 healthy volunteers, 5 asthma, and 24 patients with cystic fibrosis.
FIELD STRENGTH/SEQUENCE: 1.5T MRI, 3D radial UTE (TE = 0.08 msec) sequence.
ASSESSMENT: Two 3D radial UTE volumes were acquired sequentially under normoxic (21% O2 ) and hyperoxic (100% O2 ) conditions. Automated segmentation of the lungs using 2D convolutional encoder-decoder based DL method, and the subsequent functional quantification via adaptive K-means were compared with the results obtained from the reference method, supervised region growing.
STATISTICAL TESTS: Relative to the reference method, the performance of DL on volumetric quantification was assessed using Dice coefficient with 95% confidence interval (CI) for accuracy, two-sided Wilcoxon signed-rank test for computation time, and Bland-Altman analysis on the functional measure derived from the OE images.
RESULTS: The DL method produced strong agreement with supervised region growing for the right (Dice: 0.97; 95% CI = [0.96, 0.97]; P < 0.001) and left lungs (Dice: 0.96; 95% CI = [0.96, 0.97]; P < 0.001). The DL method averaged 46 seconds to generate the automatic segmentations in contrast to 1.93 hours using the reference method (P < 0.001). Bland-Altman analysis showed nonsignificant intermethod differences of volumetric (P ≥ 0.12) and functional measurements (P ≥ 0.34) in the left and right lungs.
DATA CONCLUSION: DL provides rapid, automated, and robust lung segmentation for quantification of regional lung function using UTE proton MRI.
LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019.

PMID: 30945385 [PubMed - as supplied by publisher]

Author Correction: Squaramide-based synthetic chloride transporters activate TFEB but block autophagic flux.

Cell Death Dis. 2019 Apr 03;10(4):301

Authors: Zhang S, Wang Y, Xie W, Howe ENW, Busschaert N, Sauvat A, Leduc M, Gomes-da-Silva LC, Chen G, Martins I, Deng X, Maiuri L, Kepp O, Soussi T, Gale PA, Zamzami N, Kroemer G

Abstract
In the version of this article originally submitted, it was stated that the first three authors (Shaoyi_ Than, Yan Wang, Wei Xie) had contributed equally. However, in the published version this information was missing.

PMID: 30944306 [PubMed - in process]

Thymosin α-1 does not correct F508del-CFTR in cystic fibrosis airway epithelia.

JCI Insight. 2019 Apr 04;4(7):

Authors: Tomati V, Caci E, Ferrera L, Pesce E, Sondo E, Cholon DM, Quinney NL, Boyles SE, Armirotti A, Ravazzolo R, Galietta LJ, Gentzsch M, Pedemonte N

PMID: 30944255 [PubMed - in process]

Oscillating Positive Expiratory Pressure Therapy May Be Performed Poorly by Children With Cystic Fibrosis.

Respir Care. 2019 Apr;64(4):398-405

Authors: O'Sullivan KJ, Collins L, McGrath D, Linnane B, O'Sullivan L, Dunne CP

Abstract
BACKGROUND: Oscillating positive expiratory pressure devices aid removal of excess secretions and reduce gas trapping in patients with hypersecretory pulmonary diseases, for example, cystic fibrosis. Oscillating positive expiratory pressure works when the patient exhales actively against a fixed resistor, which generates mean intrapulmonary pressures of 10-20 cm H2O with rapid fluctuations of at least 1 cm H2O from the mean. In this study, we evaluated the performance of oscillating positive expiratory pressure therapy by pediatric subjects with cystic fibrosis to determine adherence to target therapeutic pressures.
METHODS: Twenty-one pediatric subjects were recruited. Each had a history of using an oscillating positive expiratory pressure device twice daily and had received standardized training and instructions from the same specialist physiotherapist. Performance was evaluated by using a flow and pressure sensor placed in-line between the participant's mouth and the device. The participants performed expirations as per their normal routine.
RESULTS: None of the participants achieved target therapeutic pressure ranges during expiration. The mean ± SD pressure generated was 16.2 ± 6.8 cm H2O, whereas mean ± SD flow was 31.3 ± 8.9 L/min. The mean ± SD expiration length was 2.5 ± 1.4 s.
CONCLUSIONS: Despite standardized instruction, the results demonstrated considerable variation among the participants and overall poor technique during use. Outcomes of this study indicated that airway clearance effects of oscillating positive expiratory pressure were compromised due to poor technique.

PMID: 30944227 [PubMed - in process]

The Pseudomonas aeruginosa population among Cystic Fibrosis patients in Quebec, Canada: a disease hotspot without known epidemic isolates.

J Clin Microbiol. 2019 Apr 03;:

Authors: Jeukens J, Freschi L, Kukavica-Ibrulj I, Emond-Rheault JG, Allard C, Barbeau J, Cantin A, Charette SJ, Déziel E, Malouin F, Milot J, Nguyen D, Popa C, Boyle B, Levesque RC

Abstract
The Canadian province of Quebec has among the highest prevalence rates of Cystic Fibrosis (CF) in the world, with an average of 1 in 2,500 newborns (cysticfibrosis.ca, 1), and up to 1 in 902 in the region of Saguenay-Lac-Saint-Jean (2-4).….

PMID: 30944192 [PubMed - as supplied by publisher]

Mucus accumulation in the lungs precedes structural changes and infection in children with cystic fibrosis.

Sci Transl Med. 2019 Apr 03;11(486):

Authors: Esther CR, Muhlebach MS, Ehre C, Hill DB, Wolfgang MC, Kesimer M, Ramsey KA, Markovetz MR, Garbarine IC, Forest MG, Seim I, Zorn B, Morrison CB, Delion MF, Thelin WR, Villalon D, Sabater JR, Turkovic L, Ranganathan S, Stick SM, Boucher RC

Abstract
Although destructive airway disease is evident in young children with cystic fibrosis (CF), little is known about the nature of the early CF lung environment triggering the disease. To elucidate early CF pulmonary pathophysiology, we performed mucus, inflammation, metabolomic, and microbiome analyses on bronchoalveolar lavage fluid (BALF) from 46 preschool children with CF enrolled in the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) program and 16 non-CF disease controls. Total airway mucins were elevated in CF compared to non-CF BALF irrespective of infection, and higher densities of mucus flakes containing mucin 5B and mucin 5AC were observed in samples from CF patients. Total mucins and mucus flakes correlated with inflammation, hypoxia, and oxidative stress. Many CF BALFs appeared sterile by culture and molecular analyses, whereas other samples exhibiting bacterial taxa associated with the oral cavity. Children without computed tomography-defined structural lung disease exhibited elevated BALF mucus flakes and neutrophils, but little/no bacterial infection. Although CF mucus flakes appeared "permanent" because they did not dissolve in dilute BALF matrix, they could be solubilized by a previously unidentified reducing agent (P2062), but not N-acetylcysteine or deoxyribonuclease. These findings indicate that early CF lung disease is characterized by an increased mucus burden and inflammatory markers without infection or structural lung disease and suggest that mucolytic and anti-inflammatory agents should be explored as preventive therapy.

PMID: 30944166 [PubMed - in process]

Recruitment manoeuvres dislodge mucus towards the distal airways in an experimental model of severe pneumonia.

Br J Anaesth. 2019 Feb;122(2):269-276

Authors: Li Bassi G, Comaru T, Martí D, Xiol EA, Chiurazzi C, Travierso C, Carbonara M, Ranzani OT, Amaro R, Frigola G, Fuster C, Saco MA, Zanella A, De Rosa F, Rigol M, Fernandez L, Luque N, Ramirez J, Blasi F, Suen J, Fraser J, Torres A

Abstract
BACKGROUND: Recruitment manoeuvres generate a transient increase in trans-pulmonary pressure that could open collapsed alveoli. Recruitment manoeuvres might generate very high inspiratory airflows. We evaluated whether recruitment manoeuvres could displace respiratory secretions towards the distal airways and impair gas exchange in a porcine model of bacterial pneumonia.
METHODS: We conducted a prospective randomised study in 10 mechanically ventilated pigs. Pneumonia was produced by direct intra-bronchial introduction of Pseudomonas aeruginosa. Four recruitment manoeuvres were applied randomly: extended sigh (ES), maximal recruitment strategy (MRS), sudden increase in driving pressure and PEEP (SI-PEEP), and sustained inflation (SI). Mucus transport was assessed by fluoroscopic tracking of radiopaque disks before and during each recruitment manoeuvre. The effects of each RM on gas exchange were assessed 15 min after the intervention.
RESULTS: Before recruitment manoeuvres, mucus always cleared towards the glottis. Conversely, mucus was displaced towards the distal airways in 28.6% ES applications and 50% of all other recruitment manoeuvres (P=0.053). Median mucus velocity was 1.26 mm min-1 [0.48-3.89] before each recruitment manoeuvre, but was reversed (P=0.007) during ES [0.10 mm min-1 [-0.04-1.00]], MRS [0.10 mm min-1 [-0.4-0.48]], SI-PEEP [0.02 mm min-1 [-0.14-0.34]], and SI [0.10 mm min-1 [-0.63-0.75]]. When PaO2 failed to improve after recruitment manoeuvre, mucus was displaced towards the distal airways in 68.7% of the cases, compared with 31.2% recruitment manoeuvres associated with improved PaO2 (odds ratio: 4.76 (95% confidence interval: 1.13-19.97).
CONCLUSIONS: Recruitment manoeuvres dislodge mucus distally, irrespective of airflow generated by different recruitment manoeuvres. Further investigation in humans is warranted to corroborate these pre clinical findings, as there may be limited benefits associated with lung recruitment in pneumonia.

PMID: 30686313 [PubMed - indexed for MEDLINE]

A young woman with upper lobe predominant bronchiectasis.

BMJ. 2019 Jan 10;364:k5244

Authors: Riley LE, Nadkarni AP

PMID: 30630819 [PubMed - indexed for MEDLINE]

Novel mutations and deletions in cystic fibrosis in a tertiary cystic fibrosis center in Istanbul.

Pediatr Pulmonol. 2019 Apr 02;:

Authors: Atag E, Bas Ikizoglu N, Ergenekon AP, Gokdemir Y, Eralp EE, Ata P, Ersu R, Karakoc F, Karadag B

Abstract
BACKGROUND: Cystic fibrosis (CF) genotyping has garnered increased attention since the discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989 led to the identification of over 1700 mutations on chromosome 7. Yet, little is known about the genetic profile of CF patients in Turkey. This study sought to determine the mutation distribution among CF patients seeking care at Marmara University.
METHODS: Two hundred fifty previously diagnosed CF patients were included in the study. CFTR gene exons 1 to 27 were amplified by a polymerase chain reaction and whole DNA sequencing was performed. Duplications and deletions were investigated by the multiplex ligation-dependent probe amplification (MLPA) technique in patients with one or two unidentified mutations in sequence analysis.
RESULTS: CFTR mutation analysis revealed 80 mutations and five large deletions were present in our study population. The five most common mutations were (delta) F508 (c.1521-1523delCTT) (28.4%), 1677delTA (c.1545-1546delTA) (6.4%), 2789 + 5G- > A (c.2657 + 5G > A) (5.8%), N1303K (c.3909C > G) (2.4%), and c.2183AA- > G (c.2051-2052delAAinsG) (4.0%). Large deletions were found in 16 patients. Four novel mutations and two novel deletions were detected in this study.
CONCLUSIONS: We have identified four novel mutations and two novel deletions using next-generation DNA sequencing and the MLPA technique and obtained an overall mutation detection rate of 91.4%. Detection of novel variants in CF patients will assist in genetic counseling and in determining appropriate patients for new therapies.

PMID: 30938940 [PubMed - as supplied by publisher]