Clinical care of children with primary ciliary dyskinesia.

Expert Rev Respir Med. 2017 Jul 26;:

Authors: Lucas JS, Alanin MC, Collins S, Harris A, Johansen HK, Nielsen KG, Papon JF, Robinson P, Walker WT

Abstract
INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare heterogeneous disorder, usually inherited as an autosomal recessive condition but X-linked inheritance is also described. Abnormal ciliary function in childhood leads to neonatal respiratory distress in term infants, persistent wet cough, bronchiectasis, chronic rhinosinusitis, and hearing impairment; approximately 50% of patients have situs inversus. There is a paucity of evidence for treating PCD, hence consensus guidelines are predominantly influenced by knowledge from cystic fibrosis (CF). Extrapolation of evidence from other diseases is inappropriate since differences in pathophysiology, morbidity and prognosis risk treatment failure and lack of adherence. Areas covered: Review authors searched PubMed and Cochrane databases for publications relating to management of children with PCD. Because of the paucity of data, we emphasise the need for well-designed clinical trials with PCD patients rather than reliance on evidence from other diseases. Expert commentary: The evidence for treatment of PCD is poor, and management is often extrapolated from studies of patients with CF or chronic rhinosinusitis. However, much work is underway to improve the situation and international consortia and networks are conducting well-designed projects to inform the management of children with PCD.

PMID: 28745925 [PubMed - as supplied by publisher]

Relative resistance index (RRI) - a scoring system for antibiotic resistance in Pseudomonas aeruginosa.

Br J Biomed Sci. 2017 Jul 26;:1-5

Authors: Ewing J, McCaughan J, Moore J, Fairley D, Sutherland B, Reid A, Downey D

Abstract
BACKGROUND: There is a need to measure antibiotic resistance of Pseudomonas aeruginosa (PA) in cystic fibrosis (CF), either qualitatively or quantitatively, to inform patient management. The aim of this study was to develop a simple method by which resistance can be quantified by calculating a relative resistance index (RRI), and to assess correlation of RRIs with clinical variables.
METHODS: In our model, RRIs were calculated based on resistance to aztreonam, ceftazidime, ciprofloxacin, colistin, meropenem, tazocin, temicillin and tobramycin. Eighty-five adults with CF and chronic PA colonisation were identified. For each, all PA cultures were allocated a score of 0 for susceptible, 0.5 for intermediate resistance or 1 for resistance for each antibiotic listed above, and the RRI calculated by dividing the sum of these by the number of antibiotics, giving a maximum score of 1. The mean RRIs for all cultures were correlated with key clinical variables monitored in CF patients (including age, FEV1, IV antibiotic days and BMI).
RESULTS: RRIs for non-mucoid PA exhibited moderate positive correlation with total number of IV days (r = 0.405; p < 0.001) and moderate negative correlation with FEV1 % predicted (r = -0.437; p < 0.001). RRIs were not significantly correlated with duration of colonisation, typing (clonal vs other strain) or BMI. Median RRIs were significantly higher for females (0.26, IQR 0.13-0.54) than males (0.18, IQR 0.07-0.37) for non-mucoid PA only (p = 0.03).
CONCLUSIONS: RRI is an easily calculated measure that correlates with other clinical variables in CF patients and enables quantitative monitoring of resistance.

PMID: 28745144 [PubMed - as supplied by publisher]

Increased prevalence of colonic adenomas in patients with cystic fibrosis.

J Cyst Fibros. 2017 Jul 22;:

Authors: Hegagi M, Aaron SD, James P, Goel R, Chatterjee A

Abstract
BACKGROUND: Cystic fibrosis (CF) is the most common lethal genetic illness in the Caucasian population. Studies have shown that CF patients are at an elevated risk of developing colon cancer. Colonic adenomas are the precursors of colon cancer. This study aims to determine the prevalence of adenomas in patients with cystic fibrosis.
METHODS: All patients were recruited prospectively at The Ottawa Hospital Cystic Fibrosis Clinic from 2010 through 2015. Baseline demographic and cystic fibrosis disease characteristics were collected from the clinic's CF patient database. Upon presentation at the endoscopy unit, and after a brief history and physical exam, a colonoscopy was performed. Polyps were resected if detected and sent to the pathology department for characterization. Findings were compared with a control group (pairing each CF patient with 5 age and sex-matched controls) of near-average risk patients who underwent a colonoscopy at the same center.
RESULTS: Of the 33 patients that provided informed consent to participate in the study, 30 patients underwent colonoscopy and 13/30 (43.3%) were found to have colonic adenomas compared to 7 (4.7%) of the 150 control patients. The relative risk ratio for adenoma detection in a CF patient as compared to a matched control patient was 9.29 (95% CI 4.04-21.31), p<0.01.
CONCLUSIONS: Colonic adenomas are more prevalent in CF patients compared to the general population. This study suggests the need for additional research to support recently published screening guidelines for CF patients.

PMID: 28743561 [PubMed - as supplied by publisher]

Endocrine aspects in cystic fibrosis.

J Pediatr Endocrinol Metab. 2017 Jul 25;:

Authors: Kiess W, Penke M, Kobelt L, Lipek T, Henn C, Gausche R, Vogel M, Prenzel F

PMID: 28742522 [PubMed - as supplied by publisher]

Sensitivity and specificity of cystic fibrosis-related diabetes screening methods: which test should be the reference method?

J Pediatr Endocrinol Metab. 2017 Jul 25;:

Authors: Boudreau V, Lehoux Dubois C, Desjardins K, Mailhot M, Tremblay F, Rabasa-Lhoret R

PMID: 28742521 [PubMed - as supplied by publisher]

Unilateral Lung Agenesis, Aplasia or Hypoplasia - which one is it?

Congenit Anom (Kyoto). 2017 Jul 25;:

Authors: Nguyen KM, Vala S, Milla S, Guglani L

Abstract
Congenital lung malformations can lead to symptoms in the immediate newborn period or early childhood, but may also be diagnosed incidentally on routine imaging or autopsy, especially if the individual has remained asymptomatic. We report a case where incidental detection of abnormal intrathoracic structures led to a different diagnosis while being evaluated for scoliosis.

PMID: 28742269 [PubMed - as supplied by publisher]

Inhaled Antimicrobials for Ventilator-Associated Pneumonia: Practical Aspects.

Drugs. 2017 Jul 24;:

Authors: Poulakou G, Matthaiou DK, Nicolau DP, Siakallis G, Dimopoulos G

Abstract
Positive experience with inhaled antibiotics in pulmonary infections of patients with cystic fibrosis has paved the way for their utilization in mechanically ventilated, critically ill patients with lower respiratory tract infections. A successful antibiotic delivery depends upon the size of the generated particle and the elimination of drug impaction in the large airways and the ventilator circuit. Generated droplet size is mainly affected by the type of the nebulizer employed. Currently, jet, ultrasonic, and vibrating mesh nebulizers are marketed; the latter can deliver optimal antibiotic particle size. Promising novel drug-device combinations are able to release drug concentrations of 25- to 300-fold the minimum inhibitory concentration of the targeted pathogens into the pulmonary alveoli. The most important practical steps of nebulization include pre-assessment and preparation of the patient (suctioning, sedation, possible bronchodilation, adjustment of necessary ventilator settings); adherence to the procedure (drug preparation, avoidance of unnecessary tubing connections, interruption of heated humidification, removal of heat-moisture exchanger); inspection of the procedure (check for residual in drug chamber, change of expiratory filter, return sedation, and ventilator settings to previous status); and surveillance of the patient for adverse events (close monitoring of the patient and particularly of peak airway pressure and bronchoconstriction). Practical aspects of nebulization are very important to ensure optimal drug delivery and safe procedure for the patient. Therefore, the development of an operational checklist is a priority for every department adopting this modality.

PMID: 28741229 [PubMed - as supplied by publisher]

Bile salt stimulated lipase: Inhibition by phospholipids and relief by phospholipase A2.

J Cyst Fibros. 2017 Jul 21;:

Authors: Venuti E, Shishmarev D, Kuchel PW, Dutt S, Blumenthal CS, Gaskin KJ

Abstract
INTRODUCTION: Bile salt stimulated lipase (BSSL; Enzyme Commission (EC) number 3.1.1.13) has been a candidate triglyceridase for improving enzyme therapy for pancreatic insufficiency; however, its efficacy is near absent. We hypothesise that similarly to pancreatic lipase, BSSL is inhibited by phospholipids and this inhibition is relieved by Phospholipase A2 (PLA2; EC 3.1.1.4), and the present study was undertaken to explore this possibility.
MATERIALS AND METHODS: Synthetic emulsions of triglyceride and phosphatidylcholine (PC) or lysophosphatidylcholine (LPC)/bile salt mixed micelles were used as a model of intestinal digestion-media. The effect of PLA2 treatment of systems containing PC on BSSL activity was also explored. Automatic titration at constant pH (pH-stat) and nuclear magnetic resonance (NMR) spectroscopy were used to measure the rate and identify products of lipolysis.
RESULTS: PC was inhibitory to BSSL activity, while LPC became inhibitory only above an LPC/bile salt concentration ratio of 0.3. PLA2 treatment relieved the inhibition only below this ratio, despite its complete phospholipid-hydrolysing action. Thus, LPC had an inhibitory effect at higher concentrations.
CONCLUSIONS: These results may implicate a change in the design of enzyme therapy in patients with pancreatic exocrine insufficiency. Supplementation of BSSL with PLA2 could improve patient health with adequate manipulation of phospholipid and lysophospholipid concentrations in the intestinal fluid.

PMID: 28739210 [PubMed - as supplied by publisher]

Analytical and biological variation in repeated sweat chloride concentrations in clinical trials for CFTR modulator therapy.

J Cyst Fibros. 2017 Jul 21;:

Authors: LeGrys VA, Moon TC, Laux J, Rock MJ, Accurso F

Abstract
BACKGROUND: Using sweat chloride as a biomarker for CFTR modifying drugs requires knowledge of analytical and biological variation.
METHODS: 979 sweat chloride concentrations from 128 subjects enrolled in the placebo arm of 2 multicenter, investigational drug trials were analyzed to determine coefficients of variation (CV) as well as reference change value (RCV) and index of individuality (II).
RESULTS: For these populations, calculated values for the two studies were: analytical variation (3.9, 4.1%); within-subject variation (4.4, 6.0%); between-subject variation (8.9, 7.0%); RCV (13.7, 17.0%) and II (0.7, 1.0). Sweat chloride variation was not affected by sex, collection site or sample weight; but was slightly affected by age in one of the two studies.
CONCLUSION: Through determination of analytical as well as between- and within-subject variation, and with a larger sample size, our data allows improved estimates of the RCV and II, and can contribute to future trials of CFTR modulators and inform the design and interpretation of n of 1 trials in both research and clinical settings.

PMID: 28739209 [PubMed - as supplied by publisher]

Gamma tocopherol-enriched supplement reduces sputum eosinophilia and endotoxin-induced sputum neutrophilia in volunteers with asthma.

J Allergy Clin Immunol. 2017 Jul 20;:

Authors: Burbank AJ, Duran CG, Pan Y, Burns P, Jones S, Jiang Q, Yang C, Jenkins S, Wells H, Alexis N, Kesimer M, Bennett WD, Zhou H, Peden DB, Hernandez ML

Abstract
BACKGROUND: We and others have shown that the gamma tocopherol (γT) isoform of vitamin E has multiple anti-inflammatory and antioxidant actions and that γT supplementation reduces eosinophilic and endotoxin (LPS)-induced neutrophilic airway inflammation in animal models and healthy human volunteers.
OBJECTIVE: To determine if γT supplementation reduces eosinophilic airway inflammation and acute neutrophilic response to inhaled LPS challenge in volunteers with asthma.
METHODS: Participants with mild asthma were enrolled in a double-blinded, placebo controlled crossover study to assess the effect of 1200 mg of γT daily for 14 days on sputum eosinophils, mucins and cytokines. We also assessed the effect on acute inflammatory response to inhaled LPS challenge following γT treatment, focusing on changes in sputum neutrophilia, mucins and cytokines. Mucociliary clearance was measured using gamma scintigraphy.
RESULTS: Fifteen subjects with mild asthma completed both arms of the study. Compared to placebo, γT notably reduced pre-LPS challenge sputum eosinophils and mucins, including MUC5AC, and reduced LPS-induced airway neutrophil recruitment 6 and 24-hours after challenge. Mucociliary clearance was slowed 4-hours post-challenge in the placebo group but not in the γT treatment group. Total sputum mucins (but not MUC5AC) were reduced at 24-hours post-challenge during γT treatment compared to placebo.
CONCLUSION: γT supplementation for 14 days reduced inflammatory features of asthma, including sputum eosinophils and mucins, as well as acute airway response to inhaled LPS challenge when compared to placebo. Larger scale clinical trials are needed to assess the efficacy of γT supplements as a complementary or steroid-sparing treatment for asthma.

PMID: 28736267 [PubMed - as supplied by publisher]

Multidimensional severity assessment in bronchiectasis: an analysis of seven European cohorts.

Thorax. 2016 Dec;71(12):1110-1118

Authors: McDonnell MJ, Aliberti S, Goeminne PC, Dimakou K, Zucchetti SC, Davidson J, Ward C, Laffey JG, Finch S, Pesci A, Dupont LJ, Fardon TC, Skrbic D, Obradovic D, Cowman S, Loebinger MR, Rutherford RM, De Soyza A, Chalmers JD

Abstract
INTRODUCTION: Bronchiectasis is a multidimensional disease associated with substantial morbidity and mortality. Two disease-specific clinical prediction tools have been developed, the Bronchiectasis Severity Index (BSI) and the FACED score, both of which stratify patients into severity risk categories to predict the probability of mortality.
METHODS: We aimed to compare the predictive utility of BSI and FACED in assessing clinically relevant disease outcomes across seven European cohorts independent of their original validation studies.
RESULTS: The combined cohorts totalled 1612. Pooled analysis showed that both scores had a good discriminatory predictive value for mortality (pooled area under the curve (AUC) 0.76, 95% CI 0.74 to 0.78 for both scores) with the BSI demonstrating a higher sensitivity (65% vs 28%) but lower specificity (70% vs 93%) compared with the FACED score. Calibration analysis suggested that the BSI performed consistently well across all cohorts, while FACED consistently overestimated mortality in 'severe' patients (pooled OR 0.33 (0.23 to 0.48), p<0.0001). The BSI accurately predicted hospitalisations (pooled AUC 0.82, 95% CI 0.78 to 0.84), exacerbations, quality of life (QoL) and respiratory symptoms across all risk categories. FACED had poor discrimination for hospital admissions (pooled AUC 0.65, 95% CI 0.63 to 0.67) with low sensitivity at 16% and did not consistently predict future risk of exacerbations, QoL or respiratory symptoms. No association was observed with FACED and 6 min walk distance (6MWD) or lung function decline.
CONCLUSION: The BSI accurately predicts mortality, hospital admissions, exacerbations, QoL, respiratory symptoms, 6MWD and lung function decline in bronchiectasis, providing a clinically relevant evaluation of disease severity.

PMID: 27516225 [PubMed - indexed for MEDLINE]

Thermal unfolding simulations of NBD1 domain variants reveal structural motifs associated with the impaired folding of F508del-CFTR.

Mol Biosyst. 2016 Aug 16;12(9):2834-48

Authors: Estácio SG, Martiniano HF, Faísca PF

Abstract
We employed high-temperature classical molecular dynamics (MD) simulations to investigate the unfolding process of the wild-type (WT) and F508del-NBD1 domains of CFTR protein, with and without second-site mutations. To rationalize the in vitro behavior of F508del-NBD1, namely its lower folding yield and higher aggregation propensity, we focused our analysis of the MD data on the existence of intermediate states with aggregation potential and/or stabilized by a significant number of non-native interactions (i.e. misfolded states). We find that the deletion of phenylalanine 508 is able to forcefully reshape the conformational space of the NBD1 domain to the extent that it uniquely populates intermediate states whose structural traits provide important insights into the molecular events that underlie the impaired folding of F508del-NBD1. In particular, our simulations predict the formation of a misfolded intermediate whose population is highly enhanced by deletion of residue 508. The stabilization of this intermediate is a direct consequence of the enhanced non-native coupling between various key regions of the α-helical subdomain and ATP-binding subdomain; it is singularly characterized by a set of non-native interactions within the ATP-binding subdomain and between that domain and the α-helical subdomain region. The formation of this intermediate is not blocked by second-site suppressor mutations which indicates a limited role of the latter in correcting the rather complex folding process of the CFTR protein missing residue 508.

PMID: 27354240 [PubMed - indexed for MEDLINE]

A Systematic Approach to Multiple Breath Nitrogen Washout Test Quality.

PLoS One. 2016;11(6):e0157523

Authors: Jensen R, Stanojevic S, Klingel M, Pizarro ME, Hall GL, Ramsey K, Foong R, Saunders C, Robinson PD, Webster H, Hardaker K, Kane M, Ratjen F

Abstract
BACKGROUND: Accurate estimates of multiple breath washout (MBW) outcomes require correct operation of the device, appropriate distraction of the subject to ensure they breathe in a manner representative of their relaxed tidal breathing pattern, and appropriate interpretation of the acquired data. Based on available recommendations for an acceptable MBW test, we aimed to develop a protocol to systematically evaluate MBW measurements based on these criteria.
METHODS: 50 MBW test occasions were systematically reviewed for technical elements and whether the breathing pattern was representative of relaxed tidal breathing by an experienced MBW operator. The impact of qualitative and quantitative criteria on inter-observer agreement was assessed across eight MBW operators (n = 20 test occasions, compared using a Kappa statistic).
RESULTS: Using qualitative criteria, 46/168 trials were rejected: 16.6% were technically unacceptable and 10.7% were excluded due to inappropriate breathing pattern. Reviewer agreement was good using qualitative criteria and further improved with quantitative criteria from (κ = 0.53-0.83%) to (κ 0.73-0.97%), but at the cost of exclusion of further test occasions in this retrospective data analysis.
CONCLUSIONS: The application of the systematic review improved inter-observer agreement but did not affect reported MBW outcomes.

PMID: 27304432 [PubMed - indexed for MEDLINE]

The regulator LdhR and the d-lactate dehydrogenase LdhA of Burkholderia multivorans play a role in carbon overflow and in planktonic cellular aggregates formation.

Appl Environ Microbiol. 2017 Jul 21;:

Authors: Silva IN, Ramires MJ, Azevedo LA, Guerreiro AR, Tavares AC, Becker JD, Moreira LM

Abstract
LysR-type transcriptional regulators (LTTR) are the most commonly found regulators in Burkholderia cepacia complex, comprising opportunistic pathogens causing chronic respiratory infections in cystic fibrosis (CF) patients. Despite LTTRs being global regulators of pathogenicity in several bacteria, few have been characterized in Burkholderia Here, we showed that gene ldhR of B. multivorans encoding a LTTR is co-transcribed with ldhA encoding a d-lactate dehydrogenase, and evaluate their implication in virulence traits like exopolysaccharide (EPS) synthesis and biofilm formation. Comparison of wild-type (WT) and its isogenic ΔldhR mutant grown in medium with 2% d-glucose revealed a negative impact on EPS biosynthesis and on cells' viability in the presence of LdhR. Loss of viability in WT cells was caused by intracellular acidification as consequence of cumulative organic acids secretion including d-lactate, this last one absent from the ΔldhR mutant supernatant. Furthermore, LdhR is implicated in the formation of planktonic cellular aggregates. WT cell aggregates reached 1000 μm after 24 hours in liquid cultures; in contrast to ΔldhR mutant aggregates that never grew more than 60 μm. Overexpression of d-lactate dehydrogenase LdhA in the ΔldhR mutant partially restored formed aggregates size, suggesting a role for fermentation inside aggregates. Similar results were obtained for surface-attached biofilms, with WT cells producing more biofilm. A systematic evaluation of planktonic aggregates in Burkholderia CF clinical isolates showed aggregates in 40 out of 74. As CF patients' lung environment is microaerophilic and bacteria are found as free aggregates/biofilms, LdhR and LdhA might have central roles in adaptation to this environment.IMPORTANCE Cystic fibrosis patients often suffer from chronic respiratory infections caused by several microorganisms. Among them are the Burkholderia cepacia complex bacteria which cause progressive deterioration of lung function and, in some patients, might develop into fatal necrotizing pneumoniae with bacteremia, known as "cepacia syndrome". Burkholderia pathogenesis is multifactorial since they express several virulence factors, form biofilms, and are highly resistant to antimicrobial compounds, making their eradication from the CF patients' airways very difficult. As Burkholderia is commonly found in the CF lungs in the form of cell aggregates and biofilms, the need to investigate the mechanisms of cellular aggregation is obvious. In this study we demonstrate the importance of a d-lactate dehydrogenase and a regulator, in regulating carbon overflow, cellular aggregates and surface-attached biofilm formation. This not only enhances our understanding of Burkholderia pathogenesis, but can also lead to the development of drugs against these proteins to circumvent biofilm formation.

PMID: 28733286 [PubMed - as supplied by publisher]

Bicarbonate in cystic fibrosis.

J Cyst Fibros. 2017 Jul 18;:

Authors: Kunzelmann K, Schreiber R, Hadorn HB

Abstract
BACKGROUND: Cystic fibrosis (CF, mucoviscidosis) is caused by mutations in the gene encoding CF transmembrane conductance regulator (CFTR), which is a chloride and bicarbonate channel necessary for fluid secretion and extracellular alkalization. For a long time, research concentrated on abnormal Cl(-) and Na(+) transport, but neglected bicarbonate as a crucial factor in CF.
METHODS: The present short review reports early findings as well as recent insights into the role of CFTR for bicarbonate transport and its defects in CF.
RESULTS: The available data indicate impaired bicarbonate transport not only in pancreas, intestine, airways, and reproductive organs, but also in salivary glands, sweat duct and renal tubular epithelial cells. Defective bicarbonate transport is closely related to the impaired mucus properties and mucus blocking in secretory organs of CF patients, causing the life threatening lung disease.
CONCLUSIONS: Apart from the devastating lung disease, abrogated bicarbonate transport also leads to many other organ dysfunctions, which are outlined in the present review.

PMID: 28732801 [PubMed - as supplied by publisher]

Sweat travels: the issue of sweat chloride transportation.

Clin Chem Lab Med. 2017 Jul 21;:

Authors: Collie JTB, Massie J, Jones OAH, Morrison PD, Greaves RF

PMID: 28731852 [PubMed - as supplied by publisher]

Drug delivery to the lungs: challenges and opportunities.

Ther Deliv. 2017 Jul;8(8):647-661

Authors: Newman SP

Abstract
Pulmonary drug delivery is relatively complex because the respiratory tract has evolved defense mechanisms to keep inhaled drug particles out of the lungs and to remove or inactivate them once deposited. In addition to these mechanical, chemical and immunological barriers, pulmonary drug delivery is adversely affected by the behavioral barriers of poor adherence and poor inhaler technique. Strategies to mitigate the effects of these barriers include use of inhaler devices and formulations that deliver drug to the lungs efficiently, appropriate inhaler technique and improved education of patients. Owing to the advantages offered by the pulmonary route, the challenges that the route poses are worth addressing, and if successfully addressed, the pulmonary route offers huge opportunities, often fulfilling unmet clinical needs.

PMID: 28730933 [PubMed - in process]

Ataluren in cystic fibrosis: development, clinical studies and where are we now?

Expert Opin Pharmacother. 2017 Jul 21;:

Authors: Zainal Abidin N, Haq IJ, Gardner AI, Brodlie M

Abstract
INTRODUCTION: Cystic fibrosis (CF) is one of the most common genetically-acquired life-limiting conditions worldwide. The underlying defect is dysfunction of the cystic fibrosis transmembrane-conductance regulator (CFTR) which leads to progressive lung disease and other multi-system effects. Around 10% of people with CF have a class I nonsense mutation that leads to production of shortened CFTR due to a premature termination codon (PTC). Areas covered: We discuss the discovery of the small-molecule drug ataluren, which in vitro has been shown to allow read-through of PTCs and facilitate synthesis of full-length protein. We review clinical studies that have been performed involving ataluren in CF. Early-phase short-term cross-over studies showed improvement in nasal potential difference. A follow-up phase III randomised controlled trial did not show a significant difference for the primary outcome of lung function, however a post-hoc analysis suggested possible benefit in patients not receiving tobramycin. A further randomised controlled trial in patients not receiving tobramycin has been reported as showing no benefit but has not yet been published in full peer-reviewed form. Expert opinion: A small-molecule approach to facilitate read-through of PTCs in nonsense mutations makes intuitive sense. However, at present there is no high-quality evidence of clinical efficacy for ataluren in people with CF.

PMID: 28730885 [PubMed - as supplied by publisher]

Blood eosinophil count and exacerbation risk in patients with COPD.

Eur Respir J. 2017 Jul;50(1):

Authors: Kerkhof M, Sonnappa S, Postma DS, Brusselle G, Agustí A, Anzueto A, Jones R, Papi A, Pavord I, Pizzichini E, Popov T, Roche N, Ryan D, Thomas M, Vogelmeier C, Chisholm A, Freeman D, Bafadhel M, Hillyer EV, Price DB

PMID: 28729477 [PubMed - in process]

Detection and monitoring of lung inflammation in cystic fibrosis during respiratory tract exacerbation using diffusion-weighted magnetic resonance imaging.

Eur Respir J. 2017 Jul;50(1):

Authors: Ciet P, Bertolo S, Ros M, Andrinopoulou ER, Tavano V, Lucca F, Feiweier T, Krestin GP, Tiddens HAWM, Morana G

Abstract
The aim was to investigate whether diffusion-weighted magnetic resonance imaging (DWI) detects and monitors inflammatory and lung function changes during respiratory tract exacerbations (RTE) treatment in patients with cystic fibrosis (CF).29 patients with RTE underwent DWI pre- and post-antibiotic treatment. A control group of 27 stable patients, matched for age and sex, underwent DWI with the same time gap as those undergoing RTE treatment. Clinical status and lung function were assessed at each DWI time point. The CF-MRI scoring system was used to assess structural lung changes in both CF groups.Significant reduction in the DWI score over the course of antibiotic treatment (p<0.0001) was observed in patients with RTE, but not in the control group. DWI score had a strong inverse correlation with clinical status (r=-0.504, p<0.0001) and lung function (r=-0.635, p<0.0001) in patients with RTE. Interestingly, there were persistent significant differences in the CF-MRI score between the RTE and control group at both baseline and follow-up (p<0.001), while the differences in DWI score were only observed at baseline (p<0.001).DWI is a promising imaging method for noninvasive detection of pulmonary inflammation during RTE, and may be used to monitor treatment efficacy of anti-inflammatory treatment.

PMID: 28729470 [PubMed - in process]