Celiac Disease in Patients with Cystic Fibrosis-Related Bone Disease.

Case Rep Endocrinol. 2017;2017:2652403

Authors: Putman MS, Haagensen A, Neuringer I, Sicilian L

Abstract
Both cystic fibrosis (CF) and celiac disease can cause low bone mineral density (BMD) and fractures. Celiac disease may occur at a higher frequency in patients with CF than the general population, and symptoms of these conditions may overlap. We report on two patients presenting with CF-related bone disease in the past year who were subsequently found to have concurrent celiac disease. Because adherence to a gluten-free diet may improve BMD in patients with celiac disease, this could have important implications for treatment. Clinicians should consider screening for celiac disease in patients with CF who have low BMD, worsening BMD in the absence of other risk factors, and/or difficult to treat vitamin D deficiency.

PMID: 29230333 [PubMed]

Cystic fibrosis research topics featured at the 14th ECFS Basic Science Conference: Chairman's summary.

J Cyst Fibros. 2017 Dec 08;:

Authors: Mall MA, Hwang TC, Brakman I

Abstract
In recent years, tremendous progress has been made in the development of novel drugs targeting the basic defect in patients with cystic fibrosis (CF). This breakthrough is based on a solid foundation of knowledge on CFTR's function in health and how mutations in CFTR cause CF multi-organ disease. This knowledge has been collected and continuously expanded by an active and persistent CF research community and has paved the way for precision medicine for CF. Since 2004, the European Cystic Fibrosis Society (ECFS) has held an annual Basic Science Conference that has evolved as an international forum for interdisciplinary discussion of hot topics and unsolved questions related to CF research. This Special Issue reviews CF research topics featured at the 14th ECFS Basic Science Conference and provides an up-to-date overview of recent progress in our understanding of CFTR structure and function, disease mechanisms implicated in airway mucus plugging, inflammation and abnormal host-pathogen interactions, and advancements with enhanced cell and animal model systems and breakthrough therapies directed at mutant CFTR or alternative targets. In addition, this Special Issue also identifies a number of fundamental questions and hurdles that still have to be overcome to realize the full potential of precision medicine and develop transformative therapies for all patients with CF.

PMID: 29229473 [PubMed - as supplied by publisher]

Pulmonary exacerbations and clinical outcomes in a longitudinal cohort of infants and preschool children with cystic fibrosis.

BMC Pulm Med. 2017 Dec 11;17(1):188

Authors: Hoppe JE, Wagner BD, Sagel SD, Accurso FJ, Zemanick ET

Abstract
BACKGROUND: Pulmonary exacerbations (PEx) in school aged children and adults with cystic fibrosis (CF) lead to increased morbidity and lung function decline. However, the effect of exacerbations in young children with CF is not fully understood. We sought to characterize the frequency and clinical impact of PEx in a pilot study of infants and pre-school aged children with CF.
METHODS: Thirty young children with CF [median (range) 1.5 years (0.2-4.9)] were prospectively followed for 2 years. Exacerbation frequency (hospitalizations and outpatient antibiotic use) was determined. Chest radiographs were performed at enrollment and study completion and assigned a Brasfield score. Lung function at age 7 years was assessed in a subset of children. The association between PEx frequency, chest radiograph score, and lung function was determined using Spearman correlation coefficients and corresponding 95% confidence intervals. Correlations with an absolute magnitude of 0.3 or greater were considered clinically significant.
RESULTS: Over 2 years, participants experienced a median of two PEx (range 0-13). Chest radiograph scores at enrollment and study completion were inversely associated with PEx frequency (R = -0.48 and R = -0.44, respectively). The association between frequency of PEx and lung function [forced expiratory volume in 1 s (FEV1)] at age 7 years was small (R = 0.20). Higher forced vital capacity (FVC) at 7 years was associated with more frequent PEx during the study (R = 0.44).
CONCLUSIONS: Children with worse chest radiograph scores had more frequent PEx over the subsequent 2 years, suggesting a group of patients at higher risk for PEx. Frequent PEx in infants and young children with CF were not associated with lower FEV1 and FVC at 7 years, although spirometry in this age group may not be a sensitive marker of mild lung disease and disease progression.

PMID: 29228933 [PubMed - in process]

Does Breathing Amplify Fibrosis?

Am J Respir Crit Care Med. 2016 07 01;194(1):9-11

Authors: Hinz B, Suki B

PMID: 27367884 [PubMed - indexed for MEDLINE]

The association of pancreatic cystosis and IPMN in cystic fibrosis: case report and literature review.

Eur Rev Med Pharmacol Sci. 2017 Nov;21(22):5179-5184

Authors: Pagliari D, Saviano A, Serricchio ML, Dal Lago AA, Brizi MG, Manfredi R, Costamagna G, Attili F

Abstract
Pancreatic cystosis is a rare presentation of cystic fibrosis involving pancreatic gland. To date, only very few cases of pancreatic cystosis have been described in literature. Pancreatic cystosis may begin during the second decade of life and is the rarest presentation of cystic fibrosis. This disease is characterized by the presence of multiloculated cysts without ductal system communication of different sizes in all the pancreatic tissue. Herein, we report a case of a young woman affected by cystic fibrosis that was admitted to our Pancreatic Centre to evaluate a picture of diffuse multiloculated pancreatic cysts. After magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) assessment, we perform the diagnosis of the concomitant presence of the rare condition of pancreatic cystosis with Branch Duct-Intraductal Papillary Mucinous Neoplasm (BD-IPMN). To our knowledge, this is the first reported case of a cystic fibrosis patient with the combination of pancreatic cystosis and IPMN.

PMID: 29228431 [PubMed - in process]

Direct detection of Exophiala and Scedosporium species in sputa of patients with cystic fibrosis.

Med Mycol. 2017 Dec 08;:

Authors: Chen M, Kondori N, Deng S, Gerrits van den Ende AHG, Lackner M, Liao W, de Hoog GS

Abstract
Detection of species of Exophiala and Scedosporium in the respiratory tracts of cystic fibrosis (CF) patients remains controversial because of highly variable results. The results of our study suggested a significantly higher prevalence and more complex colonization than previously estimated. Approximately 17% (27/162) of clinical sputum samples were found to be positive for Exophiala dermatitidis and 30% (49/162) were positive for Scedosporium apiospermum / S. boydii species complex determined by reverse line blot (RLB) hybridization. In contrast, only 14.2% (23/162) and 1.2% (2/162) of clinical sputa were positive for E. dermatitidis and S. apiospermum / S. boydii species complex when tested by culture, respectively. Molecular detection methods, such as loop-mediated isothermal amplification (LAMP) or reverse line blot (RLB) hybridization, have the potential to become powerful alternatives to selective culture, providing a more realistic understanding on the prevalence of E. dermatitidis and S. apiospermum / S. boydii species complex in the respiratory tract of CF patients.

PMID: 29228273 [PubMed - as supplied by publisher]

What matters in chronic Burkholderia cenocepacia infection in cystic fibrosis: Insights from comparative genomics.

PLoS Pathog. 2017 Dec 11;13(12):e1006762

Authors: Nunvar J, Capek V, Fiser K, Fila L, Drevinek P

Abstract
Burkholderia cenocepacia causes severe pulmonary infections in cystic fibrosis (CF) patients. Since the bacterium is virtually untreatable by antibiotics, chronic infections persist for years and might develop into fatal septic pneumonia (cepacia syndrome, CS). To devise new strategies to combat chronic B. cenocepacia infections, it is essential to obtain comprehensive knowledge about their pathogenesis. We conducted a comparative genomic analysis of 32 Czech isolates of epidemic clone B. cenocepacia ST32 isolated from various stages of chronic infection in 8 CF patients. High numbers of large-scale deletions were found to occur during chronic infection, affecting preferentially genomic islands and nonessential replicons. Recombination between insertion sequences (IS) was inferred as the mechanism behind deletion formation; the most numerous IS group was specific for the ST32 clone and has undergone transposition burst since its divergence. Genes functionally related to transition metal metabolism were identified as hotspots for deletions and IS insertions. This functional category was also represented among genes where nonsynonymous point mutations and indels occurred parallelly among patients. Another category exhibiting parallel mutations was oxidative stress protection; mutations in catalase KatG resulted in impaired detoxification of hydrogen peroxide. Deep sequencing revealed substantial polymorphism in genes of both categories within the sputum B. cenocepacia ST32 populations, indicating extensive adaptive evolution. Neither oxidative stress response nor transition metal metabolism genes were previously reported to undergo parallel evolution during chronic CF infection. Mutations in katG and copper metabolism genes were overrepresented in patients where chronic infection developed into CS. Among professional phagocytes, macrophages use both hydrogen peroxide and copper for their bactericidal activity; our results thus tentatively point to macrophages as suspects in pathogenesis towards the fatal CS.

PMID: 29228063 [PubMed - as supplied by publisher]

ALTERATION IN THE CYTOKINE SECRETION PATTERN IN T CELLS OF PATIENTS WITH CYSTIC FIBROSIS CAUSED BY DNA METHYLTRANSFERASE INHIBITOR 5-AZACITIDINE.

Georgian Med News. 2017 Nov;(272):153-157

Authors: Kvaratskhelia E, Dabrundashvili N, Gagua M, Maisuradze E, Kamkamidze M, Abzianidze E

Abstract
Cystic fibrosis (CF) is the autosomal-recessive disorder caused by mutation in the cystic fibrosis transmembrane conductance regulator gene (CFTR). The Airway inflammation plays a central role in the progression of CF disease. Cystic fibrosis characterized by the overproduction of the pro-inflammatory cytokines and reduced expression of anti-inflammatory cytokines. Although the mechanisms of abnormal cytokine expression is still poorly understood, altered epigenetic regulations in T cells might contribute. In the present study we examined the expression of IFN-γ and IL-10 by CF T cells prior to and following 5-azaC treatment. In addition we investigated DNMTs levels in nuclear extracts of CD4+ T cells derived from CF and non-CF individuals. Seven CF patients (age: 5-12 years) were included in the study and compared to six age-matched healthy subjects (age: 6- 13 years). CD4+ T cells were isolated from PBMC using CD4 MicroBead kit (Miltenyi Biotec GmbH) and were cultured in RPMI 1640 medium at 37°C with 5% CO2, in presence or absence of 5-azacytidine. Concentrations of IL-10 and γ-INF in CD4+ T Cells were measured by ELISA (eBoiscience, san Diego, CA, USA). In our study we showed that 5 Azacytidine alters nuclear levels of DNMT 3a as well as modulates cytokine levels in CD4+ T cells derived from CF patients. After 5-azaC treatment secretion of IFN-γ was significantly decreased in CF T cells, while amount of IL-10 was elevated by ~2.5 times compared to untreated controls (P<0.05). In summary, data presented in this report demonstrates that epigenetic mechanisms such as DNA methylation may be considered as a one of the potential therapeutic target in a treatment of Cystic Fibrosis.

PMID: 29227276 [PubMed - in process]

Association between sequevar and antibiotic treatment outcome in patients with Mycobacterium abscessus complex infections in Japan.

J Med Microbiol. 2017 Dec 11;:

Authors: Yoshida S, Tsuyuguchi K, Kobayashi T, Tomita M, Inoue Y, Hayashi S, Suzuki K

Abstract
PURPOSE: Macrolide susceptibility differs between subspecies in the Mycobacterium abscessus complex, likely due to differences in erm(41) sequevars. Patients with M. abscessus complex infection generally show poor clinical outcomes in response to antibiotic treatment. Here, the association between genotype and treatment outcome was investigated.
METHODOLOGY: We collected 69 isolates from 35 patients with non-cystic fibrosis bronchiectasis: 24 had M. abscessus complex lung disease and non-cystic fibrosis bronchiectasis, and 11 were colonized. Outcome analysis was performed in the 24 infected patients. Molecular analyses, including erm(41) and rrl sequencing, and variable-number tandem-repeat (VNTR) analysis of 69 isolates, from 24 infected and 11 colonized patients, were performed to elucidate the influence of genotype on antibiotic susceptibility.
RESULTS: Among the 24 patients, 18 (14 infected with M. abscessus subsp. abscessus and 4 with M. abscessus subsp. massiliense) showed unfavourable outcomes; six (three infected with M. abscessus subsp. abscessus and three with M. abscessus subsp. massiliense) exhibited favourable outcomes. Patients with unfavourable outcomes showed acquired clarithromycin resistance (33.3 vs 0 %), mixed sequevars (38.9 vs 16.7 %) and differing VNTR patterns between initial and serial isolates (33.3 vs 16.7 %). In contrast, in the 11 colonized patients, M. abscessus subsp. abscessus C28 (sequevar 02) and M. abscessus subsp. massiliense were the most prevalent subspecies.
CONCLUSION: Patients infected with multiple sequevars and genotypes were more likely to exhibit treatment failure and/or recurrence. The precise identification of subspecies and analyses of mycobacterial characteristics may help to predict treatment outcomes in patients with M. abscessus complex lung disease.

PMID: 29227218 [PubMed - as supplied by publisher]

Clinical Strains of Chryseobacterium and Elizabethkingia spp. Isolated from Pediatric Patients in a University Hospital: Performance of MALDI-TOF MS-Based Identification, Antimicrobial Susceptibilities, and Baseline Patient Characteristics.

Microb Drug Resist. 2017 Dec 11;:

Authors: Mirza HC, Tuncer Ö, Ölmez S, Şener B, Tuğcu GD, Özçelik U, Gürsoy NC, Otlu B, Büyükçam A, Kara A, Sancak B

Abstract
Our objective was to evaluate the performance of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) for identification of the Chryseobacterium and Elizabethkingia spp. isolated from pediatric patients at Hacettepe University Hospital using 16S rRNA gene sequencing as the gold standard and to determine the antimicrobial susceptibility patterns of the isolates and baseline characteristics of patients. All stored Chryseobacterium and Elizabethkingia spp. isolated from various clinical specimens (sputum, blood, and urine) of pediatric patients at Hacettepe University Hospital between 2012 and 2016 were included in this study. Minimum inhibitory concentrations of 10 antimicrobial agents were determined by Etest for all isolates. To determine the baseline characteristics of patients, medical records of all patients were retrospectively reviewed. In total, 18 isolates of Chryseobacterium spp. (16 C. indologenes, 2 C. gleum) and 5 isolates of Elizabethkingia spp. (3 E. meningoseptica, 2 E. anophelis) were identified by 16S rRNA sequencing. MALDI-TOF MS correctly identified 19 (82.6%) isolates to the species level. The quinolones (ciprofloxacin and levofloxacin), trimethoprim/sulfamethoxazole and piperacillin/tazobactam showed the highest spectrum of activity against the overall collection of isolates. Cystic fibrosis (CF) was the underlying disease in 81.8% of patients. To our knowledge, this study includes the largest number of Chryseobacterium spp. isolated from clinical specimens of pediatric patients in Turkey. In this study, we also report the first clinical isolate of E. anophelis in Turkey. Since, the majority of strains were isolated from patients with CF; larger, prospective clinical studies are needed to establish whether chryseobacteria could be considered as an emerging opportunistic pathogen in patients with CF.

PMID: 29227188 [PubMed - as supplied by publisher]

Prevalence of Pelvic Incontinence in Patients With Cystic Fibrosis.

Glob Pediatr Health. 2017;4:2333794X17743424

Authors: Neemuchwala F, Ahmed F, Nasr SZ

Abstract
Cystic fibrosis (CF) patients are at risk for developing pelvic (urinary and/or fecal) incontinence due to progressive weakness of pelvic floor muscles secondary to recurrent episodes of coughing and respiratory infections. Many patients do not bring these symptoms to the attention of their health care providers because of social embarrassment and lack of knowledge of available effective treatment. Several studies have identified the prevalence of incontinence in CF adults and adolescents. However, few studies identified the problem in children with CF. Our study aims are to identify the prevalence of pelvic incontinence in CF patients aged 6 to 21 years, to identify the correlation between incontinence and severity of lung disease, and to help develop treatment strategy in collaboration with physical therapy to address these issues.

PMID: 29226186 [PubMed]

Severe piperacillin-tazobactam-induced hemolysis in a cystic fibrosis patient.

Clin Case Rep. 2017 Dec;5(12):2059-2061

Authors: Kerkhoff AD, Patrick L, Cornett P, Kleinhenz ME, Brondfield S

Abstract
Piperacillin-tazobactam is one of the most common causes of drug-induced immune hemolytic anemia (DIIHA) and is frequently utilized, especially in patients with cystic fibrosis (CF). Here, we report a case of life-threatening piperacillin-tazobactam-associated DIIHA in a 30-year-old woman with CF and propose management recommendations for piperacillin-tazobactam-associated DIIHA in CF patients.

PMID: 29225856 [PubMed]

Outbreak of Hospital Infection from Biofilm-embedded Pan Drug-resistant Pseudomonas aeroginosa, Due to a Contaminated Bronchoscope.

. 2017;2(2):

Authors: Alipour N, Karagoz A, Taner A, Gaeini N, Alipour N, Zeytin H, Yildiz F, Durmaz R

Abstract
Background: Colistin-resistant Pseudomonas aeruginosa (P. aeruginosa) has been defined as pandrug-resistant (PDR) strain. Outbreaks of PDR P. aeruginosa especially in pulmonary tract infections due to contaminated bronchoscopes have rarely been reported. The emergence of pandrug-resistant strains in both CF (Cystic Fibrosis) and non-CF clinical isolates over recent years remains of a great concern. Hospital wards contaminated with PDR P. aeruginosa infection, must be shot down until their eradication. Health Authorities must be informed immediately and infection control strategies must be implemented.
Aim: To report such an outbreak and modify the infection control strategy in an academic hospital in Ankara Turkey.
Methods: From October to December 2013, PDR-Pseudomonas aerogionsa were identified from bronchial cultures of 15 patients who had undergone bronchoscopy prior to the infection. Three batches of surveillance cultures were obtained from the environmental objects and healthcare workers related to the procedures. Pulsed-field gel electrophoresis (PFGE) was used for bacterial typing. Antimicrobial susceptibility was assessed by disc diffusion and E-test methods.
Findings: A total of 70 specimens were obtained during the first surveillance operation. One Colistin-resistant P. aeroginosa was isolated from a bronchoscope. Although the disinfection protocols for bronchoscope were revised and implemented, seven additional bronchial cases were identified thereafter. The pathogen was identified from two subsequent surveillance cultures and was not eliminated until Ethylene oxide sterilization was added to the disinfection protocol. PFGE revealed that all 15 isolates from the patients and the three isolates from the bronchoscope shared a common pattern with minor variance. XbaI restriction enzyme turned out better than SpeI in interpreting bacterial pulse types with BioNumerics 6.0. The most suitable cut off value for SpeI was above 80% Dice similarity while for XbaI above 95%Dice similarity with BioNumerics 6.0.
Conclusion: The outbreak of "Colistin" pan drug-resistant Pseudomonas aeroginosa was caused by a contaminated bronchoscope and was terminated by the implementation of a revised disinfection protocol for bronchoscope.

PMID: 29225413 [PubMed]

Microbial diversity within the airway microbiome in chronic pediatric lung diseases.

Infect Genet Evol. 2017 Dec 07;:

Authors: Hahn A, Warnken S, Pérez-Losada M, Freishtat RJ, Crandall KA

Abstract
The study of the airway microbiome in children is an area of emerging research, especially in relation to the role microbial diversity may play in acute and chronic inflammation. Three such pediatric airway diseases include cystic fibrosis, asthma, and chronic lung disease of prematurity. In cystic fibrosis, the presence of Pseudomonas spp. is associated with decreased microbial diversity. Decreasing microbial diversity is also associated with poor lung function. In asthma, early viral infections appear to drive changes in bacterial diversity which may be associated with asthma risk. Premature infants with Ureaplasma spp. are at higher risk for chronic lung disease due to inflammation. Microbiome changes due to prematurity also appear to affect the inflammatory response to viral infections post-natally. Importantly, microbial diversity can be measured using metataxonomic (e.g., 16S rRNA sequencing) and metagenomic (e.g., shotgun sequencing) approaches. A metagenomics approach may be preferable as it can provide further granularity of the sample composition, identifying the bacterial species or strain, information on additional microbial components, including fungal and viral components, information about functional genomics of the microbiome, and information about antimicrobial resistance mutations. Future studies of pediatric airway diseases incorporating these techniques may provide evidence for new treatment approaches for these vulnerable patient populations.

PMID: 29225146 [PubMed - as supplied by publisher]

Long-term intestinal obstruction sequelae and growth in children with cystic fibrosis operated for meconium ileus: expectancies and surprises.

J Pediatr Surg. 2017 Nov 15;:

Authors: Mentessidou A, Loukou I, Kampouroglou G, Livani A, Georgopoulos I, Mirilas P

Abstract
BACKGROUND/PURPOSE: In the few studies on intestinal complications and growth of cystic fibrosis (CF) patients with a history of meconium ileus (MI), operated MI has not been investigated separately. We aimed to investigate the incidence of long-term intestinal obstruction sequelae [constipation, distal intestinal obstruction syndrome (DIOS)] and growth in CF patients operated for MI.
METHODS: Retrospective study (1989-2016) including operative diagnoses and procedures, constipation and DIOS events, yearly Body Mass Index (BMI) measurements. Outcomes were examined in subgroups operated for MI only and for MI with atresia and/or volvulus.
RESULTS: Of 49 patients followed-up for 15 (mean) years, 5 (10.2%) developed constipation and 14 (28.6%) DIOS. BMI was within normal percentiles in 53 patients over a 10-year follow-up. MI only and MI with atresia and/or volvulus did not differ in constipation and/or DIOS incidence (11/34 vs. 7/15, p=0.39) or in BMI (p=0.47). Cases with ileocecal valve resection (ICV-R) showed lower constipation and/or DIOS incidence than those without ICV-R (0/6 vs. 11/28, p=0.02) and no different BMI (p>0.05).
CONCLUSIONS: CF patients operated for MI were in long-term risk for constipation/DIOS; their growth was normal. Interestingly, underlying atresia/volvulus neither increased constipation/DIOS risk nor affected growth. Strikingly, ICV-R showed no constipation/DIOS risk and no impact on growth.
TYPE OF STUDY: Retrospective comparative study.
LEVEL OF EVIDENCE: III.

PMID: 29224788 [PubMed - as supplied by publisher]

Bronchial Artery Embolization for the Treatment of Acute Hemoptysis.

Tech Vasc Interv Radiol. 2017 Dec;20(4):263-265

Authors: Cody O'Dell M, Gill AE, Hawkins CM

Abstract
Massive hemoptysis is a life-threatening condition often defined as coughing up 300-600mL of blood in 24 hours in an adult, or >8mL/kg in 24 hours in a child. Although the definition is controversial, one should view massive hemoptysis as any volume of expectorated blood that can cause respiratory failure. This is because mortality in the setting of hemoptysis is usually associated with asphyxiation, rather than exsanguination. Massive hemoptysis accounts for only about 5% of cases of hemoptysis, but when treated conservatively, has a reported mortality rate between 50% and 85%. Etiologies vary widely based on demographics. In children, infectious causes predominate in developing countries, and cystic fibrosis predominates among children of European descent. In adults, malignancy, bronchiectasis, and chronic infection are the most common causes. Treatment begins with resuscitation and airway protection, followed by minimally invasive bronchoscopic and endovascular techniques. Surgical interventions are considered last line therapy due to mortality rates of 37%-43% in the setting of massive hemoptysis. Bronchial artery embolization is now considered the treatment of choice for massive hemoptysis.

PMID: 29224659 [PubMed - in process]

Structural abnormalities in islets from very young children with cystic fibrosis may contribute to cystic fibrosis-related diabetes.

Sci Rep. 2017 Dec 08;7(1):17231

Authors: Bogdani M, Blackman SM, Ridaura C, Bellocq JP, Powers AC, Aguilar-Bryan L

Abstract
Cystic fibrosis (CF)-related diabetes (CFRD) is thought to result from beta-cell injury due in part to pancreas exocrine damage and lipofibrosis. CFRD pancreata exhibit reduced islet density and altered cellular composition. To investigate a possible etiology, we tested the hypothesis that such changes are present in CF pancreata before the development of lipofibrosis. We evaluated pancreas and islet morphology in tissues from very young CF children (<4 years of age), and adult patients with CF and CFRD. The relative number of beta-cells in young CF tissues was reduced by 50% or more when compared to age-matched controls. Furthermore, young CF tissues displayed significantly smaller insulin-positive areas, lower proportion of beta-cells positive for the proliferation marker Ki67 or the ductal marker CK19 vs. control subjects, and islet inflammatory cell infiltrates, independently of the severity of the exocrine lesion and in the absence of amyloid deposits. CFRD pancreata exhibited greater islet injury with further reduction in islet density, decreased relative beta-cell number, and presence of amyloid deposits. Together, these results strongly suggest that an early deficiency in beta-cell number in infants with CF may contribute to the development of glucose intolerance in the CF pediatric population, and to CFRD, later in life.

PMID: 29222447 [PubMed - in process]

The relationship between sweat chloride levels and mortality in cystic fibrosis varies by individual genotype.

J Cyst Fibros. 2017 Dec 05;:

Authors: Espel JC, Palac HL, Bharat A, Cullina J, Prickett M, Sala M, McColley SA, Jain M

Abstract
RATIONALE: The association between CFTR genotype, sweat chloride and mortality has been inconsistent, but no previous analyses have examined the association stratified by individual genotypes.
OBJECTIVES: To evaluate the genotype-specific association between sweat chloride and mortality.
METHODS: The CFF Patient Registry was assessed and included all patients in the registry between 1996 and 2012 with at least one F508del allele. We excluded patients without a documented genotype or plausible sweat chloride level. The primary outcome was time to mortality during the observation period. We examined 15 genotypes using the three most prevalent alleles in each of 5 classes. We compared subgroups of sweat chloride using Kaplan-Meier curves, log-rank tests, and multivariable Cox PH models. The overall predictive value of sweat chloride on mortality was assessed using area under the receiver operating characteristic curves.
MEASUREMENTS AND MAIN RESULTS: 18,893 subjects met inclusion criteria. Sweat chloride distribution was similar across genotypes in patients with class 1 mutations, but was significantly different across genotypes in mutation classes 2-5. The R117H/F508del genotype patients demonstrated an association between sweat chloride and mortality (HR: 1.32 for every 10mmol/L increase in sweat chloride [95% CI 1.12-1.54]. There were also significant associations in patients with F508del/F508del, I507del/F508del, G551D/F508del and 2789+5G→A/F508del genotypes, though the clinical relevance for these genotypes is unclear.
CONCLUSIONS: There is significant variability in sweat chloride distribution across CFTR class 2-5 genotypes. The relationship between sweat chloride and mortality varies by genotype with a relatively strong relationship in R117H/F508del patients.

PMID: 29221674 [PubMed - as supplied by publisher]

Editorial overview: Respiratory: Transformational therapies for cystic fibrosis.

Curr Opin Pharmacol. 2017 Jun;34:viii-xi

Authors: Sheppard DN, Bear CE, de Jonge HR

PMID: 29221574 [PubMed - in process]

Distance-saturation product of the 6-minute walk test predicts mortality of patients with non-cystic fibrosis bronchiectasis.

J Thorac Dis. 2017 Sep;9(9):3168-3176

Authors: Hsieh MH, Fang YF, Chung FT, Lee CS, Chang YC, Liu YZ, Wu CH, Lin HC

Abstract
Background: Previous surveillance methods to monitor the prognoses of patients with bronchiectasis are too complex for use in daily practice. The 6-minute walk test (6MWT) is a simple exercise test to predict the prognosis of chronic obstructive airway disease and numerous chronic lung diseases, including idiopathic pulmonary fibrosis. No studies have investigated exercise-induced oxygen desaturation (EID) and distance-saturation product (DSP) of 6MWT to predict the prognoses of patients with bronchiectasis.
Methods: This was a prospective study to identify correlations between variables of 6MWT and mortality in patients with bronchiectasis over a 6-year period. The study cohort included 69 patients with stable non-cystic fibrosis (non-CF) bronchiectasis who were regularly evaluated for functional status via 6-minute walk distance (6MWD), spirometry, BODE index, EID, and DSP.
Results: Of the 69 patients, 9 (13%) died and 60 (87%) survived during the 6-year follow-up period. The percentage of EID was higher [7 of 9 patients (78%) vs. 22 of 60 patients (27%), P=0.003] in the non-survivors group. The 6MWD (467.9±77.1 vs. 363.7±126.7 m, P=0.001) was higher in the survivors group. DSP was significantly lower in the non-survivors group (411.0±78.4 vs. 283.9±90.0 m%, P<0.001). Multivariate analysis showed that DSP (OR =0.983; 95% CI: 0.974-0.993, P=0.001) was the best parameter of 6MWT to predict mortality. Patients with a lower DSP of <280 m% were at a 66.5-fold greater risk (OR =66.5; 95% CI: 9.4-469.2) of 6-year mortality compared with those with DSP >280 m% (P<0.001).
Conclusions: DSP is a simple parameter to predict 6-year mortality in patients with non-CF bronchiectasis.

PMID: 29221293 [PubMed]