Committee Opinion No. 691: Carrier Screening for Genetic Conditions.

Obstet Gynecol. 2017 03;129(3):e41-e55

Authors: Committee on Genetics

Abstract
Carrier screening is a term used to describe genetic testing that is performed on an individual who does not have any overt phenotype for a genetic disorder but may have one variant allele within a gene(s) associated with a diagnosis. Information about carrier screening should be provided to every pregnant woman. Carrier screening and counseling ideally should be performed before pregnancy because this enables couples to learn about their reproductive risk and consider the most complete range of reproductive options. A patient may decline any or all screening. When an individual is found to be a carrier for a genetic condition, his or her relatives are at risk of carrying the same mutation. The patient should be encouraged to inform his or her relatives of the risk and the availability of carrier screening. If an individual is found to be a carrier for a specific condition, the patient's reproductive partner should be offered testing in order to receive informed genetic counseling about potential reproductive outcomes. If both partners are found to be carriers of a genetic condition, genetic counseling should be offered. What follows is a detailed discussion of some of the more common genetic conditions for which carrier screening is recommended in at least some segments of the population.

PMID: 28225426 [PubMed - indexed for MEDLINE]

Clinical outcome of cystic fibrosis patients colonized by Scedosporium species following lung transplantation: A single-center 15-year experience.

Transpl Infect Dis. 2017 Jun 15;:

Authors: Parize P, Boussaud V, Poinsignon V, Sitterlé E, Botterel F, Lefeuvre S, Guillemain R, Dannaoui E, Billaud EM

Abstract
BACKGROUND: Fungi of the genus Scedosporium are emerging pathogens responsible for severe infections in lung transplant recipients. These infections are associated with poor prognosis and some centers consider now Scedosporium species colonization as a contraindication to lung transplantation (LT) even though no published evidence demonstrates that Scedosporium species colonization is associated with higher morbidity or mortality after LT.
METHODS: Here we aim to describe characteristics and outcome of cystic fibrosis (CF) lung transplant recipients colonized with Scedosporium species in a single center over a 15-year period.
RESULTS: During the study period, 14 patients had scedosporial colonization reported. Only one patient, colonized before transplantation by Lomentospora prolificans, developed scedosporial disease. Among the eight patients colonized before transplantation by Scedosporium apiospermum complex, the median survival was 1.92 year (range 0.21-12.5). All these patients except one became free of fungal colonization after transplantation with antifungal prophylaxis including voriconazole or posaconazole. For the five patients colonized after LT, including two with L. prolificans, the median survival was 1.75 years (range 0.1-13); three of them are still alive.
CONCLUSIONS: It appears to us that scedosporial colonization may not be a contraindication for LT in CF patients, as long as S. apiospermum complex is involved and a life-long azole prophylaxis prescribed. This article is protected by copyright. All rights reserved.

PMID: 28618155 [PubMed - as supplied by publisher]

Patients with Cystic Fibrosis and a G551D or Homozygous F508del Mutation: Similar Lung Function Decline.

Am J Respir Crit Care Med. 2017 Jun 15;195(12):1673-1676

Authors: Sawicki GS, McKone EF, Millar SJ, Pasta DJ, Konstan MW, Lubarsky B, Wagener JS

PMID: 28617084 [PubMed - in process]

Cystic fibrosis prevalence among a group of high-risk children in the main referral children hospital in Iran.

J Educ Health Promot. 2017;6:54

Authors: Modaresi MR, Faghinia J, Reisi M, Keivanfar M, Navaie S, Seyyedi J, Baharzade F

Abstract
BACKGROUND: Knowledge about cystic fibrosis (CF) in Iran is very limited. The objective of this study was to determine the prevalence of CF among a group of high-risk children with suggestive clinical features in the main referral hospital in Iran.
MATERIALS AND METHODS: This study children consisted of 505 patients who had presented with one or more of the following symptoms: chronic or recurrent respiratory symptoms, gastrointestinal symptoms as rectal prolapse, steatorrhea, hepatobiliary disease as prolonged jaundice, failure to thrive, hyperglycemia and glycosuria, hypochloremic metabolic alkalosis, hypoprothrombinemia, anemia or edema, and positive family history of CF. Patients were screened using pilocarpine iontophoresis to collect sweat and chemical analysis of its chloride content with classic Gibson and Cooke technique.
RESULTS: Of 505 patients, 89 (17.6%) had positive sweat chloride screening test. Five (1%) patients had required cystic fibrosis transmembrane conductive regulator protein mutation analysis to confirm CF.
CONCLUSION: Our findings suggest that in Iran, CF is more common than what previously anticipated. Larger studies are warranted to identify the incidence, molecular basis, and clinical pattern of CF in the Iranian population.

PMID: 28616421 [PubMed - in process]

Hydrogen sulfide stimulates CFTR in Xenopus oocytes by activation of the cAMP/PKA signalling axis.

Sci Rep. 2017 Jun 14;7(1):3517

Authors: Perniss A, Preiss K, Nier M, Althaus M

Abstract
Hydrogen sulfide (H2S) has been recognized as a signalling molecule which affects the activity of ion channels and transporters in epithelial cells. The cystic fibrosis transmembrane conductance regulator (CFTR) is an epithelial anion channel and a key regulator of electrolyte and fluid homeostasis. In this study, we investigated the regulation of CFTR by H2S. Human CFTR was heterologously expressed in Xenopus oocytes and its activity was electrophysiologically measured by microelectrode recordings. The H2S-forming sulphur salt Na2S as well as the slow-releasing H2S-liberating compound GYY4137 increased transmembrane currents of CFTR-expressing oocytes. Na2S had no effect on native, non-injected oocytes. The effect of Na2S was blocked by the CFTR inhibitor CFTR_inh172, the adenylyl cyclase inhibitor MDL 12330A, and the protein kinase A antagonist cAMPS-Rp. Na2S potentiated CFTR stimulation by forskolin, but not that by IBMX. Na2S enhanced CFTR stimulation by membrane-permeable 8Br-cAMP under inhibition of adenylyl cyclase-mediated cAMP production by MDL 12330A. These data indicate that H2S activates CFTR in Xenopus oocytes by inhibiting phosphodiesterase activity and subsequent stimulation of CFTR by cAMP-dependent protein kinase A. In epithelia, an increased CFTR activity may correspond to a pro-secretory response to H2S which may be endogenously produced by the epithelium or H2S-generating microflora.

PMID: 28615646 [PubMed - in process]

CFTR protects against vascular inflammation and atherogenesis in apolipoprotein E-deficient mice.

Biosci Rep. 2017 Jun 14;:

Authors: Li Z, Shen Z, Xue H, Cheng S, Ji Q, Liu Y, Yang X

Abstract
Atherosclerosis is a chronic inflammatory disease of the vascular wall. Dysfunction of cystic fibrosis transmembrane conductance regulator (CFTR) has been shown to result in inflammatory responses in cystic fibrosis (CF) patients. However, little is known about the role of CFTR in vascular inflammation and atherogenesis. Our results showed that CFTR was dominantly expressed in macrophages of atherosclerotic plaque and reduced in aorta and aortic sinus from atherosclerotic apolipoprotein E-deficient (apoE-/-) mice. In vivo administration of CFTR adenovirus (Ad-CFTR) with apoE-/- mice fed high-fat diet improved plaque stability by decreasing lipid accumulation and necrotic area and increasing smooth muscle cell content and collagen. The Ad-CFTR-treated mice also displayed reduced proinflammatory cytokines levels in aorta and peritoneal macrophages, whereas the anti-inflammatory M2 macrophage markers were increased. Confocal microscopy revealed that the infiltration of T-lymphocytes, neutrophils and macrophages in aortic sinus was markedly attenuated in Ad-CFTR-treated apoE-/- mice. Moreover, in vitro experiments showed that overexpression of CFTR inhibited ox-LDL-induced the migration of peritoneal macrophages. Finally, it was observed that CFTR upregulation suppressed NFκB and MAPKs activity induced by ox-LDL. Inhibition of JNK or ERK abrogated CFTR downregulation-induced NFκB activation, whereas NFκB inhibitor had no effects on JNK or ERK activation. Taken together, these results demonstrate that CFTR prevents inflammation and atherogenesis via inhibiting NFκB and MAPKs activation. Our data suggest that CFTR may present a potential therapeutic target for the treatment of vascular inflammation and development of atherosclerotic disease.

PMID: 28615349 [PubMed - as supplied by publisher]

Ease of use of tobramycin inhalation powder compared with nebulized tobramycin and colistimethate sodium: a crossover study in cystic fibrosis patients with pulmonary Pseudomonas aeruginosa infection.

Ther Adv Respir Dis. 2017 Jul;11(7):249-260

Authors: Greenwood J, Schwarz C, Sommerwerck U, Nash EF, Tamm M, Cao W, Mastoridis P, Debonnett L, Hamed K

Abstract
BACKGROUND: This study assessed the ease of use of tobramycin inhalation powder (TIP) administered via T-326 inhaler versus tobramycin inhalation solution (TIS) and colistimethate sodium (COLI), both administered via nebulizers, for the treatment of chronic pulmonary Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF).
METHODS: A real-world, open-label, crossover, interventional phase IV study was conducted in CF patients aged ⩾6 years with forced expiratory volume in 1 second (FEV1) ⩾25% to ⩽90% predicted. Patients were assigned to one of the three treatment arms in Cycle 1; all patients received TIP in Cycle 2. Each cycle consisted of 28 days on and 28 days off the treatment.
RESULTS: A total of 60 patients [mean (standard deviation) age, 27.6 (8.4) years] were allocated to three treatment arms [TIS/TIP ( n = 14); COLI/TIP ( n = 28); TIP/TIP ( n = 18)] in Cycle 1. The mean total administration time, which included device setup and cleaning, in Cycle 1 versus Cycle 2 for TIS/TIP, COLI/TIP, and TIP/TIP arms were 37.0 versus 5.0 min, 16.4 versus 3.8 min, and 4.2 versus 3.4 min, respectively. The difference in mean total administration time was significantly shorter in Cycle 2 than in Cycle 1 for TIS/TIP ( p = 0.0112) and COLI/TIP ( p = 0.0016) arms. Overall, 12 patients were found to have contaminated devices across the two treatment cycles. In the TIP/TIP arm, no contamination of the T-326 inhaler was observed in either cycle. Treatment satisfaction, assessed by the Treatment Satisfaction Questionnaire for Medication and ACCEPT® questionnaire, was better overall for TIP compared with TIS and COLI. There were no unexpected adverse events and most were mild or moderate in intensity.
CONCLUSION: The T-326 inhaler used to deliver TIP was easy to use, required shorter total administration time, and was much less frequently contaminated than the nebulizers. The safety findings observed for TIP were generally consistent with its established safety profile.

PMID: 28614995 [PubMed - in process]

Preimplantation genetic screening.

J Med Screen. 2017 Jan 01;:969141317691797

Authors: Harper JC

Abstract
Preimplantation genetic diagnosis was first successfully performed in 1989 as an alternative to prenatal diagnosis for couples at risk of transmitting a genetic or chromosomal abnormality, such as cystic fibrosis, to their child. From embryos generated in vitro, biopsied cells are genetically tested. From the mid-1990s, this technology has been employed as an embryo selection tool for patients undergoing in vitro fertilisation, screening as many chromosomes as possible, in the hope that selecting chromosomally normal embryos will lead to higher implantation and decreased miscarriage rates. This procedure, preimplantation genetic screening, was initially performed using fluorescent in situ hybridisation, but 11 randomised controlled trials of screening using this technique showed no improvement in in vitro fertilisation delivery rates. Progress in genetic testing has led to the introduction of array comparative genomic hybridisation, quantitative polymerase chain reaction, and next generation sequencing for preimplantation genetic screening, and three small randomised controlled trials of preimplantation genetic screening using these new techniques indicate a modest benefit. Other trials are still in progress but, regardless of their results, preimplantation genetic screening is now being offered globally. In the near future, it is likely that sequencing will be used to screen the full genetic code of the embryo.

PMID: 28614992 [PubMed - as supplied by publisher]

Toll-like receptor activation by sino-nasal mucus in chronic rhinosinusitis.

Rhinology. 2017 Mar 01;55(1):59-69

Authors: Biswas K, Chang A, Hoggard M, Radcliff FJ, Jiang Y, Taylor MW, Darveau R, Douglas RG

Abstract
BACKGROUND: The sino-nasal disease chronic rhinosinusitis (CRS) is primarily an inflammatory condition that manifests in several ways. However, the aetiology of this complex disease is poorly understood. The aim of this study was to explore the association between toll-like receptor (TLR) activation, host immune response and sino-nasal mucus in healthy and diseased patients.
METHODS: The activation of TLR2/1 and TLR4 by sino-nasal mucus from 26 CRS patients and 10 healthy controls was measured. In addition, 7 inflammatory cytokines, bacterial community composition and bacterial abundance within the sino-nasal mucus were measured using molecular and diagnostic tools.
RESULTS: TLR activity was observed in 9/36 samples, including 2 healthy controls. There was a strong, positive correlation between members of the Gammaproteobacteria (Haemophilus, Enterobacter, Pseudomonas) and TLR2/1 and TLR4 activity. Bacterial abundance and cytokine (tumour necrosis factor) abundance were also positively correlated with TLR activity.
CONCLUSIONS: These findings suggest that a small proportion (20-30%) of individuals in each sub-group are more predisposed to TLR activity, which may be related to bacterial composition, diversity and abundance in the sinuses.

PMID: 28025987 [PubMed - indexed for MEDLINE]

Diagnosis of Primary Ciliary Dyskinesia by a Targeted Next-Generation Sequencing Panel: Molecular and Clinical Findings in Italian Patients.

J Mol Diagn. 2016 Nov;18(6):912-922

Authors: Boaretto F, Snijders D, Salvoro C, Spalletta A, Mostacciuolo ML, Collura M, Cazzato S, Girosi D, Silvestri M, Rossi GA, Barbato A, Vazza G

Abstract
Primary ciliary dyskinesia (PCD) is a rare genetic disorder that alters mucociliary clearance, with consequent chronic disease of upper and lower airways. Diagnosis of PCD is challenging, and genetic testing is hampered by the high heterogeneity of the disease, because autosomal recessive causative mutations were found in 34 different genes. In this study, we clinically and molecularly characterized a cohort of 51 Italian patients with clinical signs of PCD. A custom next-generation sequencing panel that enables the affordable and simultaneous screening of 24 PCD genes was developed for genetic analysis. After variant filtering and prioritization, the molecular diagnosis of PCD was achieved in 43% of the patients. Overall, 5 homozygous and 27 compound heterozygous mutations, 21 of which were never reported before, were identified in 11 PCD genes. The DNAH5 and DNAH11 genes were the most common cause of PCD in Italy, but some population specificities were identified. In addition, the number of unsolved cases and the identification of only a single mutation in six patients suggest further genetic heterogeneity and invoke the need of novel strategies to detect unconventional pathogenic DNA variants. Finally, despite the availability of mutation databases and in silico prediction tools helping the interpretation of variants in next-generation sequencing screenings, a comprehensive segregation analysis is required to establish the in trans inheritance and support the pathogenic role of mutations.

PMID: 27637300 [PubMed - indexed for MEDLINE]

Bronchiectasis in Children: Current Concepts in Immunology and Microbiology.

Front Pediatr. 2017;5:123

Authors: Pizzutto SJ, Hare KM, Upham JW

Abstract
Bronchiectasis is a complex chronic respiratory condition traditionally characterized by chronic infection, airway inflammation, and progressive decline in lung function. Early diagnosis and intensive treatment protocols can stabilize or even improve the clinical prognosis of children with bronchiectasis. However, understanding the host immunologic mechanisms that contribute to recurrent infection and prolonged inflammation has been identified as an important area of research that would contribute substantially to effective prevention strategies for children at risk of bronchiectasis. This review will focus on the current understanding of the role of the host immune response and important pathogens in the pathogenesis of bronchiectasis (not associated with cystic fibrosis) in children.

PMID: 28611970 [PubMed - in process]

Uncovering Differences in Virulence Markers Associated with Achromobacter Species of CF and Non-CF Origin.

Front Cell Infect Microbiol. 2017;7:224

Authors: Filipic B, Malesevic M, Vasiljevic Z, Lukic J, Novovic K, Kojic M, Jovcic B

Abstract
Achromobacter spp. are recognized as emerging pathogens in hospitalized as well as in cystic fibrosis (CF) patients. From 2012 to 2015, we collected 69 clinical isolates (41 patient) of Achromobacter spp. from 13 patients with CF (CF isolates, n = 32) and 28 patients receiving care for other health conditions (non-CF isolates, n = 37). Molecular epidemiology and virulence potential of isolates were examined. Antimicrobial susceptibility, motility, ability to form biofilms and binding affinity to mucin, collagen, and fibronectin were tested to assess their virulence traits. The nrdA gene sequencing showed that A. xylosoxidans was the most prevalent species in both CF and non-CF patients. CF patients were also colonized with A. dolens/A. ruhlandii, A. insuavis, and A. spiritinus strains while non-CF group was somewhat less heterogenous, although A. insuavis, A. insolitus, and A. piechaudii strains were detected beside A. xylosoxidans. Three strains displayed clonal distribution, one among patients from the CF group and two among non-CF patients. No significant differences in susceptibility to antimicrobials were observed between CF and non-CF patients. About one third of the isolates were classified as strong biofilm producers, and the proportion of CF and non-CF isolates with the ability to form biofilm was almost identical. CF isolates were less motile compared to the non-CF group and no correlation was found between swimming phenotype and biofilm formation. On the other hand, CF isolates exhibited higher affinity to bind mucin, collagen, and fibronectin. In generall, CF isolates from our study exhibited in vitro properties that could be of importance for the colonization of CF patients.

PMID: 28611955 [PubMed - in process]

Bronchial Epithelial Cells from Cystic Fibrosis Patients Express a Specific Long Non-coding RNA Signature upon Pseudomonas aeruginosa Infection.

Front Cell Infect Microbiol. 2017;7:218

Authors: Balloy V, Koshy R, Perra L, Corvol H, Chignard M, Guillot L, Scaria V

Abstract
Pseudomonas aeruginosa (Pa) is the leading cause of chronic lung infection in Cystic Fibrosis (CF) patients. It is well recognized that CF epithelial cells fail to develop an appropriate response to infection, allowing bacterial colonization and a chronic inflammatory response. Since long non-coding RNAs (lncRNAs), are known to play a key role in regulating mammalian innate immune response, we hypothesized that CF cells exposed to Pa could express a specific lncRNA signature responsible of the maladaptative CF response. We analyzed transcriptomic datasets to compare the expression profiles of lncRNAs in primary CF and non-CF epithelial cells infected with Pa at 0, 2, 4, and 6 h of infection. Our analysis identified temporal expression signatures of 25, 73, 15, and 26 lncRNA transcripts differentially expressed at 0, 2, 4, and 6 h post-infection respectively, between CF and non-CF cells. In addition, we identified profiles specific to CF and non-CF cells. The differential expression of two candidate lncRNAs were independently validated using real-time PCR. We identified a specific CF signature of lncRNA expression in a context of Pa infection that could potentially play a role in the maladaptive immune response of CF patients.

PMID: 28611953 [PubMed - in process]

Improvement in exercise duration, lung function and well-being in G551D-Cystic Fibrosis patients: a double-blind, placebo-controlled, randomised, cross-over study with ivacaftor.

Clin Sci (Lond). 2017 Jun 13;:

Authors: Keating DT, Edgeworth D, Ellis M, Button B, Williams E, Clark D, Tierney A, Heritier S, Kotsimbos A, Wilson J

Abstract
G551D , a mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, results in impaired chloride channel function in cystic fibrosis (CF) with multiple end-organ manifestations. The effect of ivacaftor, a CFTR-potentiator, on exercise capacity in cystic fibrosis (CF) is unknown. Twenty G551D-CF patients were recruited to a single-centre, double-blind, placebo-controlled, 28-day crossover study of ivacaftor. Variables measured included percentage change from baseline (%Δ) of VO2max (maximal oxygen consumption, primary outcome) during cardiopulmonary exercise testing (CPET), relevant other CPET physiological variables, lung function, BMI, sweat chloride, and disease specific health related quality of life (QOL) measures (CFQ-R and Alfred Wellness (AWEscore)). %ΔVO2max was unchanged compared to placebo as was %Δminute ventilation. However, %Δexercise time (mean 7.3, CI 0.5-14,1, p=0.0222) significantly increased as did %ΔFEV1 (11·7%, range 5.3-18.1, p<0·005) and %ΔBMI (1·2%, range 0.1-2.3, p=0·0393) whereas sweat chloride decreased (mean -43·4; range -55.5-18.1 mmol·L(-1), p<0·005). Total and activity based domains in both CFQ-R and AWEscore also increased. A positive treatment effect on spirometry, BMI (increased), SCT (decreased) and total and activity based CF-specific QOL measures was expected. However, the lack of discernible improvement in VO2max and VE despite other positive changes including spirometric lung function and exercise time with a 28 day ivacaftor intervention suggests that ventilatory parameters are not the sole driver of change in exercise capacity in this study cohort. Investigation over a more prolonged period may delineate the potential interdependencies of the observed discordances over time.
TRIAL REGISTRATION NUMBER: ClinicalTrials.gov-NCT01937325.

PMID: 28611235 [PubMed - as supplied by publisher]

Altering Metabolic Profiles of Drugs by Precision Deuteration 2: Discovery of a Deuterated Analog of Ivacaftor With Differentiated Pharmacokinetics for Clinical Development.

J Pharmacol Exp Ther. 2017 Jun 13;:

Authors: Harbeson SL, Morgan AJ, Liu JF, Aslanian AM, Nguyen S, Bridson GW, Brummel CL, Wu L, Tung RD, Pilja L, Braman V, Uttamsingh V

Abstract
Ivacaftor is currently used for the treatment of cystic fibrosis as both monotherapy (Kalydeco®) and combination therapy with lumacaftor (Orkambi®). Each therapy targets specific patient populations: Kalydeco treats patients carrying one of nine gating mutations in the cystic fibrosis transmembrane conductance regulator protein (CFTR), while Orkambi treats patients homozygous for the F508del CFTR mutation. In this study, we explored the pharmacological and metabolic effects of precision deuteration chemistry on ivacaftor by synthesizing two novel deuterated ivacaftor analogs, CTP-656 (d9-ivacaftor) and d18-ivacaftor. Ivacaftor is administered twice daily and is extensively converted in humans to major metabolites M1 and M6; therefore, the corresponding deuterated metabolites were also prepared. Both CTP-656 and d18-ivacaftor showed similar in vitro pharmacologic potency to ivacaftor, and the deuterated M1 and M6 metabolites showed equivalent pharmacology to the corresponding metabolites of ivacaftor, consistent with previous studies of deuterated compounds. However, CTP-656 exhibited markedly enhanced stability when tested in vitro. The deuterium isotope effects for CTP-656 metabolism (DV = 3.8, DV/K = 2.2) were notably large for a CYP-mediated oxidation. The pharmacokinetic (PK) profile of CTP-656 and d18-ivacaftor were assessed in six healthy volunteers in a single-dose crossover study, which provided the basis for advancing CTP-656 in development. The overall PK profile, including the 15.9 hour t1/2 for CTP-656 suggests that CTP-656 may be dosed once daily thereby enhancing patient adherence. Together, these data continue to validate deuterium substitution as a viable approach for creating novel therapeutic agents with potentially differentiated properties to existing drugs.

PMID: 28611092 [PubMed - as supplied by publisher]

Impaired innate immune cells in cystic fibrosis: Is it really a surprise?

J Cyst Fibros. 2017 Jun 10;:

Authors: Bonfield T, Chmiel JF

PMID: 28610881 [PubMed - as supplied by publisher]

StatPearls

Book. 2017 06

Authors:

Abstract
Intussusception is a condition in which part of the intestine folds into the section next to it. Intussusception usually involves the small bowel and rarely the large bowel. Symptoms include abdominal pain which may wax and wane, vomiting, bloating, and bloody stool. It may result in a small bowel obstruction. Other complications may include peritonitis or bowel perforation. The cause is typically unknown in children while in adults a lead point due to cancer is often present. Risk factors in children include infections, cystic fibrosis, and intestinal polyps. Risk factors in adults include endometriosis, bowel adhesions, and intestinal tumors. Medical imaging often supports a diagnosis. In children, ultrasound is a preferred the method to diagnose while in adults a CT scan is preferred. Intussusception requires rapid treatment. Treatment in children is typically by an enema with surgery if not successful. In adults removal of part of the bowel is more often required. Intussusception occurs more commonly in children than adults. In Intussusception occurs more commonly in children than adults, in children it is more common in males than females. The usual age of occurrence is six to 18 months old.

PMID: 28613732

Home Monitoring in CF to Identify and Treat Acute Pulmonary Exacerbations: eICE Study Results.

Am J Respir Crit Care Med. 2017 Jun 13;:

Authors: Lechtzin N, Mayer-Hamblett N, West NE, Allgood S, Wilhelm E, Khan U, Aitken ML, Ramsey BW, Boyle MP, Mogayzel PJ, Gibson RL, Orenstein D, Milla C, Clancy JP, Antony V, Goss CH, eICE Study Team

Abstract
RATIONALE: Individuals with cystic fibrosis (CF) suffer frequent acute pulmonary exacerbations, which lead to decreased lung function and reduced quality of life.
OBJECTIVES: The goal of this study was to determine if an intervention directed toward early detection of pulmonary exacerbations using home spirometry and symptom monitoring would result in slower decline in lung function compared to controls.
METHODS: A multicenter randomized trial at 14 CF centers in subjects ≥14 years. The Early Intervention arm measured home spirometry and symptoms electronically twice/week. Sites were notified if a participant met criteria for an exacerbation and contacted participants to determine if treatment for acute exacerbation was required. Participants in the Usual Care arm were seen every three months and asked to contact the site if they were concerned about worsening pulmonary symptoms.
MEASUREMENTS: The primary outcome was the 52 week change in FEV1. Secondary outcomes included time to first exacerbation and subsequent exacerbation, quality of life, and change in weight.
MAIN RESULTS: 267 patients were randomized and the study arms were well matched at baseline. There was no significant difference between study arms in 52 week mean change in FEV1 slope (mean slope difference=0.00L, 95%C.I.=-0.07-0.07, p=0.99). The Early Intervention arm detected exacerbations more frequently than Usual Care (time to first exacerbation, HR=1.45, 95%C.I.=1.09-1.93, p=0.01). Adverse events were not significantly different between treatment arms.
CONCLUSIONS: An intervention of home monitoring in CF was able to detect more exacerbations than usual care but this did not result in slower decline in lung function. Clinical trial registration available at www.clinicaltrials.gov, ID NCT01104402.

PMID: 28608719 [PubMed - as supplied by publisher]

Impact of pharmacy services on cystic fibrosis medication adherence.

Pediatr Pulmonol. 2017 Jun 13;:

Authors: Zobell JT, Schwab E, Collingridge DS, Ball C, Nohavec R, Asfour F

Abstract
OBJECTIVES: The purpose of this study is to characterize the impact of pharmacy services on medication adherence and hospitalizations for pediatric cystic fibrosis (CF) patients.
METHODS: A retrospective health insurance claims analysis and patient medical charts review from January 1, 2014 to December 31, 2016 of patients from the Pediatric Intermountain CF Center was performed. Adherence to dornase alfa and hospital admissions for pulmonary exacerbations pre and post the implementation of an integrated pharmacy team were reviewed. Dornase alfa adherence was measured by the medication possession ratio (MPR) both monthly and yearly.
RESULTS: Fifty-four patients met inclusion criteria. The mean dornase alfa yearly MPR improved from 0.75 (2014) to 0.92 (2016). Patients were 2.8 times more likely to be adherent to dornase alfa when followed by integrated pharmacy team model (P < 0.001), and 2.4 times more likely to be adherent when followed by a dedicated CF clinic pharmacist only (P = 0.001).
CONCLUSION: The study demonstrated that pharmacy services improved adherence to dornase alfa.

PMID: 28608652 [PubMed - as supplied by publisher]

Cystic fibrosis year in review 2016.

Pediatr Pulmonol. 2017 Jun 13;:

Authors: Savant AP, McColley SA

Abstract
In this article, we highlight cystic fibrosis (CF) research and case reports published in Pediatric Pulmonology during 2016. We also include articles from a variety of journals that are thematically related to these articles, or are of special interest to clinicians.

PMID: 28608632 [PubMed - as supplied by publisher]