Association of clinical severity of cystic fibrosis with variants in the SLC gene family (SLC6A14, SLC26A9, SLC11A1 and SLC9A3).

Gene. 2017 Jul 26;:

Authors: Pereira SV, Ribeiro JD, Bertuzzo CS, Marson FAL

Abstract
INTRODUCTION: Cystic fibrosis (CF) manifests with clinical and histopathological variability depending on environmental and genetic factors. Moreover, the genes encoding ion channels[rs3788766(SLC6A14), rs7512462(SLC26A9), rs17235416(SLC11A1) and rs17563161(SLC9A3)] have been insufficiently studied as modifier genes. Then, our objective was associate the variants in the genes of SLC family with 43 CF severity markers.
METHODS: The variants were identified by real-time-PCR in 188 CF patients considering the CFTR genotype. Statistical analyses were performed by parametric and nonparametric tests. The correction by multiple testing was performed by the False Rate Discovery test, alpha=0.05.
RESULTS: Depending on the CFTR mutations, we found association of: (i) rs3788766*CC with mucoid Pseudomonas aeruginosa (OR=0.171; 95%CI=0.029-0.696), non-mucoid P. aeruginosa (OR=0.283; 95%CI=0.094-0.853) and Staphyloccocus aureus (OR=4.443; 95%CI=1.019-40.64), largest FEFmax(p=0.041) and best response to bronchodilator for FEF50%(p=0.033) and FEV1/FVC(p=0.044); (ii) rs3788766*CT with early start of pulmonary symptom (OR=3.524; 95%CI=1.229-10.1) and osteoporosis (OR=0.203; 95%CI=0.022-0.883); (iii) rs3788766*TT with lowest body mass index (OR=4.242; 95%CI=1.505-11.95), presence of mucoid P. aeruginosa (OR=3.176; 95%CI=1.29-7.819) and S. aureus (OR=0.116; 95%CI=0.004-0.881), highest Bhalla score (p=0.047) and lowest FEFmax(p=0.028) and FEF25%(p=0.031) values; (iv) rs7512462*CC with highest Shwachman-Kulczycki score (p=0.019), FVC(p=0.043), FEV1(p=0.047), FEV1/FVC(p=0.022), FEF50%(p=0.038) and FEF25-75%(p=0.016); (v) rs7512462*CT with lowest values of FVC(p=0.034), FEV1(p=0.047), FEV1/FVC(p=0.022), FEF25%(p=0.012), FEF50%(p=0.038), FEF75%(p=0.008), FEF25-75%(p=0.016) and ERV(p=0.023); (vi) rs7512462*TT with best response to the inhaled bronchodilator for FEV1(p=0.011), FEF50%(p=0.019), FEF75%(p=0.036) and FEF25-75%(p=0.008); (vii) rs17234516*Normal allele with lowest value of SaO2 (p=0.010) and S. aureus (OR=3.333; 95%CI=1.085-10.24); (viii) rs17563161*GG with lowest age for onset of digestive symptoms (OR=2.564; 95%CI=1.234-5.33).
CONCLUSIONS: The clinical and laboratory variability of CF were associated with the variants in the genes of SLC family in our sample.

PMID: 28756021 [PubMed - as supplied by publisher]

The CFTR trafficking mutation F508del inhibits the constitutive activity of SLC26A9.

Am J Physiol Lung Cell Mol Physiol. 2017 Jun 01;312(6):L912-L925

Authors: Bertrand CA, Mitra S, Mishra SK, Wang X, Zhao Y, Pilewski JM, Madden DR, Frizzell RA

Abstract
Several members of the SLC26A family of anion transporters associate with CFTR, forming complexes in which CFTR and SLC26A functions are reciprocally regulated. These associations are thought to be facilitated by PDZ scaffolding interactions. CFTR has been shown to be positively regulated by NHERF-1, and negatively regulated by CAL in airway epithelia. However, it is unclear which PDZ-domain protein(s) interact with SLC26A9, a SLC26A family member found in airway epithelia. We have previously shown that primary, human bronchial epithelia (HBE) from non-CF donors exhibit constitutive anion secretion attributable to SLC26A9. However, constitutive anion secretion is absent in HBE from CF donors. We examined whether changes in SLC26A9 constitutive activity could be attributed to a loss of CFTR trafficking, and what role PDZ interactions played. HEK293 coexpressing SLC26A9 with the trafficking mutant F508del CFTR exhibited a significant reduction in constitutive current compared with cells coexpressing SLC26A9 and wt CFTR. We found that SLC26A9 exhibits complex glycosylation when coexpressed with F508del CFTR, but its expression at the plasma membrane is decreased. SLC26A9 interacted with both NHERF-1 and CAL, and its interaction with both significantly increased with coexpression of wt CFTR. However, coexpression with F508del CFTR only increased SLC26A9's interaction with CAL. Mutation of SLC26A9's PDZ motif decreased this association with CAL, and restored its constitutive activity. Correcting aberrant F508del CFTR trafficking in CF HBE with corrector VX-809 also restored SLC26A9 activity. We conclude that when SLC26A9 is coexpressed with F508del CFTR, its trafficking defect leads to a PDZ motif-sensitive intracellular retention of SLC26A9.

PMID: 28360110 [PubMed - indexed for MEDLINE]

How Do Dual Long-Acting Bronchodilators Prevent Exacerbations of Chronic Obstructive Pulmonary Disease?

Am J Respir Crit Care Med. 2017 Jul 15;196(2):139-149

Authors: Beeh KM, Burgel PR, Franssen FME, Lopez-Campos JL, Loukides S, Hurst JR, Fležar M, Ulrik CS, Di Marco F, Stolz D, Valipour A, Casserly B, Ställberg B, Kostikas K, Wedzicha JA

Abstract
Decreasing the frequency and severity of exacerbations is one of the main goals of treatment for patients with chronic obstructive pulmonary disease. Several studies have documented that long-acting bronchodilators can reduce exacerbation rate and/or severity, and others have shown that combinations of long-acting β2-adrenergic agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) provide greater reductions in exacerbation frequency than either their monocomponents or LABA/inhaled corticosteroid combinations in patients at low and high risk for these events. In this review, small groups of experts critically evaluated mechanisms potentially responsible for the increased benefit of LABA/LAMA combinations over single long-acting bronchodilators or LABA/inhaled corticosteroids in decreasing exacerbation. These included effects on lung hyperinflation and mechanical stress, inflammation, excessive mucus production with impaired mucociliary clearance, and symptom severity. The data assembled and analyzed by each group were reviewed by all authors and combined into this manuscript. Available clinical results support the possibility that effects of LABA/LAMA combinations on hyperinflation, mucociliary clearance, and symptom severity may all contribute to decreasing exacerbations. Although preclinical studies suggest LABAs and LAMAs have antiinflammatory effects, such effects have not been demonstrated yet in patients with chronic obstructive pulmonary disease.

PMID: 27922741 [PubMed - indexed for MEDLINE]

Mycobacterium abscessus displays fitness for fomite transmission.

Appl Environ Microbiol. 2017 Jul 28;:

Authors: Malcolm KC, Caceres SM, Honda JR, Davidson RM, Epperson LE, Strong M, Chan ED, Nick JA

Abstract
Mycobacterium abscessus (Mab) is a rapidly growing nontuberculous mycobacterium (NTM) increasingly reported in soft tissue infections and chronic lung diseases, including cystic fibrosis. The environmental source of Mab has not been definitively identified, but NTM have been detected in soil and water. To determine the potential of soil-derived Mab as an infectious source we explored the association, growth, and survival of Mab with defined mineral particulates, including kaolin, halloysite, and silicone dioxide, and house dust as possible Mab fomites. Mab physically associated with particulates and growth of Mab was enhanced in the presence of both kaolin and house dust. Mab survived desiccation for two weeks but was not viable after three weeks. The rate of decline of Mab viability during desiccation was reduced in the presence of house dust. Evidence for enhanced growth and survival of Mab during alternating growth and drying periods suggest that dissemination could occur when in wet or dry environments. These studies are important to understand environmental survival and acquisition of NTM.Importance The environmental source of pulmonary Mycobacterium abscessus (Mab) infections is not known. Fomites are non-living carriers of infectious agents and may contribute to acquisition of Mab This study provides evidence that Mab growth is enhanced in the presence of particulates, using kaolin, an abundant natural clay mineral, and house dust, as experimental fomites. Moreover, Mab survived desiccation for up to two weeks in the presence of house dust, kaolin and several chemically defined mineral particulates; mycobacterial viability during extended periods in a dry condition was enhanced by the presence of house dust. The growth characteristics of Mab with particulates suggest a fomite mechanism of transmission may contribute the Mab acquisition, and suggest strategies to better control infections by Mab and related organisms.

PMID: 28754702 [PubMed - as supplied by publisher]

Pathophysiologic implications of innate immunity and autoinflammation in the biliary epithelium.

Biochim Biophys Acta. 2017 Jul 25;:

Authors: Strazzabosco M, Fiorotto R, Cadamuro M, Spirli C, Mariotti V, Kaffe E, Scirpo R, Fabris L

Abstract
The most studied physiological function of biliary epithelial cells (cholangiocytes) is to regulate bile flow and composition, in particular the hydration and alkalinity of the primary bile secreted by hepatocytes. After almost three decades of studies it is now become clear that cholangiocytes are also involved in epithelial innate immunity, in inflammation, and in the reparative processes in response to liver damage. An increasing number of evidence highlights the ability of cholangiocyte to undergo changes in phenotype and function in response to liver damage. By participating actively to the immune and inflammatory responses, cholangiocytes represent a first defense line against liver injury from different causes. Indeed, cholangiocytes express a number of receptors able to recognize pathogen- or damage-associated molecular patterns (PAMPs/DAMPs), such as Toll-like receptors (TLR), which modulate their pro-inflammatory behavior. Cholangiocytes can be both the targets and the initiators of the inflammatory process. Derangements of the signals controlling these mechanisms are at the basis of the pathogenesis of different cholangiopathies, both hereditary and acquired, such as cystic fibrosis-related liver disease and sclerosing cholangitis. This article is part of a Special Issue entitled: Cholangiocytes in Health and Diseaseedited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.

PMID: 28754453 [PubMed - as supplied by publisher]

Relevance of multidrug-resistant Pseudomonas aeruginosa infections in cystic fibrosis.

Int J Med Microbiol. 2017 Jul 19;:

Authors: Stefani S, Campana S, Cariani L, Carnovale V, Colombo C, Lleo MM, Iula VD, Minicucci L, Morelli P, Pizzamiglio G, Taccetti G

Abstract
Multidrug-resistant (MDR) Pseudomonas aeruginosa is an important issue for physicians who take care of patients with cystic fibrosis (CF). Here, we review the latest research on how P. aeruginosa infection causes lung function to decline and how several factors contribute to the emergence of antibiotic resistance in P. aeruginosa strains and influence the course of the infection course. However, many aspects of the practical management of patients with CF infected with MDR P. aeruginosa are still to be established. Less is known about the exact role of susceptibility testing in clinical strategies for dealing with resistant infections, and there is an urgent need to find a tool to assist in choosing the best therapeutic strategy for MDR P. aeruginosa infection. One current perception is that the selection of antibiotic therapy according to antibiogram results is an important component of the decision-making process, but other patient factors, such as previous infection history and antibiotic courses, also need to be evaluated. On the basis of the known issues and the best current data on respiratory infections caused by MDR P. aeruginosa, this review provides practical suggestions to optimize the diagnostic and therapeutic management of patients with CF who are infected with these pathogens.

PMID: 28754426 [PubMed - as supplied by publisher]

Age-related levels of fecal M2-pyruvate kinase in children with cystic fibrosis and healthy children 0 to 10years old.

J Cyst Fibros. 2017 Jul 25;:

Authors: Garg M, Leach ST, Pang T, Needham B, Coffey MJ, Katz T, Strachan R, Widger J, Field P, Belessis Y, Chuang S, Day AS, Jaffe A, Ooi CY

Abstract
BACKGROUND: The pathogenesis of gut inflammation, bacterial dysbiosis and increased rates of malignancy in CF is unclear. Fecal M2-pyruvate kinase (M2-PK) is a biomarker indicative of cellular proliferation that may be raised in intestinal malignancy and inflammation. Biomarkers, including M2-PK, may be useful in assessing effects of novel therapies on the gastrointestinal tract.
METHODS: M2-PK was measured in stools collected from patients with CF and HC (0-10years). Linear mixed model analysis was used.
RESULTS: M2-PK levels did not significantly change in children with CF (36 patients, 77 samples) (P=0.998) or HC (45 patients, 45 samples) (P=0.21), over the age range 0-10years. Patients with CF had elevated M2-PK compared to HC (median [IQR; range]: 10.7 [5.7-28.6; 1.0-239.1] (n=77) vs. 1.0 [1.0-1.0; 1.0-50.0] (n=45) U/mL, respectively; P=0.001).
CONCLUSIONS: Fecal M2-PK was elevated in children with CF compared with HC during infancy and throughout childhood suggesting abnormalities in the CF gut exist in early life.

PMID: 28754328 [PubMed - as supplied by publisher]

Cystic Fibrosis Related Liver Disease: Research Challenges and Future Perspectives.

J Pediatr Gastroenterol Nutr. 2017 Jul 27;:

Authors: Debray D, Narkewicz MR, Bodewes FAJA, Colombo C, Housset C, de Jonge HR, Jonker JW, Kelly DA, Ling SC, Poynard T, Sogni P, Trauner M, Witters P, Baumann U, Wilschanski M, Verkade HJ

Abstract
OBJECTIVES: Hepatobiliary complications are a leading cause of morbidity and mortality in cystic fibrosis (CF) patients. However, knowledge of the underlying pathological aspects and optimal clinical management is sorely lacking.
METHODS: We provide a summary of the lectures given by international speakers at the ESPGHAN monothematic conference on CF-related liver disease (CFLD) held in Paris in January 2016, to discuss the status of our current knowledge of liver disease in CF patients, to define the critical areas that need to be addressed and to resolve actions to elucidate relevant mechanisms of disease to optimise future therapeutic options.
CONCLUSIONS: The need for a universal consensus on the definition of CFLD to clarify disease stage and to identify relevant biomarkers to assess disease severity was highlighted. A deeper understanding of the pathophysiology and prognostic factors for the long-term evolution of CFLD is fundamental to move forward, and has a strong bearing on identifying potential treatments. Novel experimental models and new treatment options under investigation are discussed and offer hope for the near future of CFLD.

PMID: 28753176 [PubMed - as supplied by publisher]

A pilot study demonstrating the altered gut microbiota functionality in stable adults with Cystic Fibrosis.

Sci Rep. 2017 Jul 27;7(1):6685

Authors: Fouhy F, Ronan NJ, O'Sullivan O, McCarthy Y, Walsh AM, Murphy DM, Daly M, Flanagan ET, Fleming C, McCarthy M, Shortt C, Eustace JA, Shanahan F, Rea MC, Ross RP, Stanton C, Plant BJ

Abstract
Cystic Fibrosis (CF) and its treatment result in an altered gut microbiota composition compared to non-CF controls. However, the impact of this on gut microbiota functionality has not been extensively characterised. Our aim was to conduct a proof-of-principle study to investigate if measurable changes in gut microbiota functionality occur in adult CF patients compared to controls. Metagenomic DNA was extracted from faecal samples from six CF patients and six non-CF controls and shotgun metagenomic sequencing was performed on the MiSeq platform. Metabolomic analysis using gas chromatography-mass spectrometry was conducted on faecal water. The gut microbiota of the CF group was significantly different compared to the non-CF controls, with significantly increased Firmicutes and decreased Bacteroidetes. Functionality was altered, with higher pathway abundances and gene families involved in lipid (e.g. PWY 6284 unsaturated fatty acid biosynthesis (p = 0.016)) and xenobiotic metabolism (e.g. PWY-5430 meta-cleavage pathway of aromatic compounds (p = 0.004)) in CF patients compared to the controls. Significant differences in metabolites occurred between the two groups. This proof-of-principle study demonstrates that measurable changes in gut microbiota functionality occur in CF patients compared to controls. Larger studies are thus needed to interrogate this further.

PMID: 28751714 [PubMed - in process]

Pseudo-Bartter syndrome as the sole manifestation of cystic fibrosis in a child with 711+G>T/IVS8-5T mutation: a new face of an old disease.

Ann Biol Clin (Paris). 2017 Aug 01;75(4):466-473

Authors: Tinsa F, Hadj Fredj S, Bel Hadj I, Khalsi F, Abdelhak S, Boussetta K, Messaoud T

Abstract
Pseudo-Bartter syndrome (PBS) describes an uncommon complication of cystic fibrosis leading to hypochloraemic, hypokalaemic metabolic alkalosis. PBS as the sole manifestation of cystic fibrosis in children is extremely rare and has never been described in patients carrying 5T variant. We report a clinical, biochemical and genetic study of a four year-old boy presenting a pseudo-Bartter syndrome as the sole manifestation of cystic fibrosis. All 27 exons and the flanking intron regions of the CFTR gene were analysed by PCR and direct sequencing. Direct sequencing was also used to analyse TGmTn and M470V polymorphisms in the patient and his parents. Two sweat tests were abnormal with elevated chloride levels at 78 and 88 mmol/L. DNA sequencing revealed a heterozygous mutation 711+1 G>T and an IVS8-T5 allele. The mutation 711+1 G>T is in trans with the IVS8-T5-TG11 allele and the child carried M470/V470 genotype. To the best of our knowledge, the genotype 711+1 G>T /IVS8-5T found in our patient is described for the first time. The role of TG11-5T-V470 allele in cases of cystic fibrosis with PB syndrome remains to be determined.

PMID: 28751295 [PubMed - in process]

Comment on data sparsity - Diagnostic and prognostic significance of systemic alkyl quinolones for P. aeruginosa in cystic fibrosis: A longitudinal study.

J Cyst Fibros. 2017 Jul 24;:

Authors: Ayubi E, Hallajzadeh J, Safiri S

PMID: 28751115 [PubMed - as supplied by publisher]

Acute pancreatitis caused by Campylobacter jejuni in a child with cystic fibrosis.

Med Clin (Barc). 2017 Jul 24;:

Authors: Villamañán Montero A, Martín de Vicente C, García Romero R

PMID: 28751082 [PubMed - as supplied by publisher]

Low-Dose Nitric Oxide as Targeted Anti-biofilm Adjunctive Therapy to Treat Chronic Pseudomonas aeruginosa Infection in Cystic Fibrosis.

Mol Ther. 2017 Jul 24;:

Authors: Howlin RP, Cathie K, Hall-Stoodley L, Cornelius V, Duignan C, Allan RN, Fernandez BO, Barraud N, Bruce KD, Jefferies J, Kelso M, Kjelleberg S, Rice SA, Rogers GB, Pink S, Smith C, Sukhtankar PS, Salib R, Legg J, Carroll M, Daniels T, Feelisch M, Stoodley P, Clarke SC, Connett G, Faust SN, Webb JS

Abstract
Despite aggressive antibiotic therapy, bronchopulmonary colonization by Pseudomonas aeruginosa causes persistent morbidity and mortality in cystic fibrosis (CF). Chronic P. aeruginosa infection in the CF lung is associated with structured, antibiotic-tolerant bacterial aggregates known as biofilms. We have demonstrated the effects of non-bactericidal, low-dose nitric oxide (NO), a signaling molecule that induces biofilm dispersal, as a novel adjunctive therapy for P. aeruginosa biofilm infection in CF in an ex vivo model and a proof-of-concept double-blind clinical trial. Submicromolar NO concentrations alone caused disruption of biofilms within ex vivo CF sputum and a statistically significant decrease in ex vivo biofilm tolerance to tobramycin and tobramycin combined with ceftazidime. In the 12-patient randomized clinical trial, 10 ppm NO inhalation caused significant reduction in P. aeruginosa biofilm aggregates compared with placebo across 7 days of treatment. Our results suggest a benefit of using low-dose NO as adjunctive therapy to enhance the efficacy of antibiotics used to treat acute P. aeruginosa exacerbations in CF. Strategies to induce the disruption of biofilms have the potential to overcome biofilm-associated antibiotic tolerance in CF and other biofilm-related diseases.

PMID: 28750737 [PubMed - as supplied by publisher]

Air pollution exposure is associated with MRSA acquisition in young U.S. children with cystic fibrosis.

BMC Pulm Med. 2017 Jul 27;17(1):106

Authors: Psoter KJ, De Roos AJ, Wakefield J, Mayer JD, Rosenfeld M

Abstract
BACKGROUND: The role of air pollution in increasing susceptibility to respiratory tract infections in the cystic fibrosis (CF) population has not been well described. We recently demonstrated that chronic PM2.5 exposure is associated with an increased risk of initial Pseudomonas aeruginosa acquisition in young children with CF. The purpose of this study was to determine whether PM2.5 exposure is a risk factor for acquisition of other respiratory pathogens in young children with CF.
METHODS: We conducted a retrospective study of initial acquisition of methicillin susceptible and methicillin resistant Staphylococcus aureus (MSSA and MRSA), Stenotrophomonas maltophilia and Achromobacter xylosoxidans in U.S. children <6 years of age with CF using the CF Foundation Patient Registry, 2003-2009. Multivariable Weibull regression with interval-censored outcomes was used to evaluate the association of PM2.5 concentration in the year prior to birth and risk of acquisition of each organism.
RESULTS: During follow-up 63%, 17%, 24%, and 5% of children acquired MSSA, MRSA, S. maltophilia, and A. xylosoxidans, respectively. A 10 μg/m(3) increase in PM2.5 exposure was associated with a 68% increased risk of MRSA acquisition (Hazard Ratio: 1.68; 95% Confidence Interval: 1.24, 2.27). PM2.5 was not associated with acquisition of other respiratory pathogens.
CONCLUSIONS: Fine particulate matter is an independent risk factor for initial MRSA acquisition in young children with CF. These results support the increasing evidence that air pollution contributes to pulmonary morbidities in the CF community.

PMID: 28750627 [PubMed - in process]

Autophagy and inflammation.

Clin Transl Med. 2017 Dec;6(1):24

Authors: Qian M, Fang X, Wang X

Abstract
Autophagy is a homeostatic mechanism involved in the disposal of damaged organelles, denatured proteins as well as invaded pathogens through a lysosomal degradation pathway. Recently, increasing evidences have demonstrated its role in both innate and adaptive immunity, and thereby influence the pathogenesis of inflammatory diseases. The detection of autophagy machinery facilitated the measurement of autophagy during physiological and pathophysiological processes. Autophagy plays critical roles in inflammation through influencing the development, homeostasis and survival of inflammatory cells, including macrophages, neutrophils and lymphocytes; effecting the transcription, processing and secretion of a number of cytokines, as well as being regulated by cytokines. Recently, autophagy-dependent mechanisms have been studied in the pathogenesis of several inflammatory diseases, including infectious diseases, Crohn's disease, cystic fibrosis, pulmonary hypertension, chronic obstructive pulmonary diseases and so on. These studies suggested that modulation of autophagy might lead to therapeutic interventions for diseases associated with inflammation. Here we highlight recent advances in investigating the roles of autophagy in inflammation as well as inflammatory diseases.

PMID: 28748360 [PubMed]

Toward the Standardization of Mycological Examination of Sputum Samples in Cystic Fibrosis: Results from a French Multicenter Prospective Study.

Mycopathologia. 2017 Jul 26;:

Authors: Coron N, Pihet M, Fréalle E, Lemeille Y, Pinel C, Pelloux H, Gargala G, Favennec L, Accoceberry I, Durand-Joly I, Dalle F, Huet F, Fanton A, Boldron A, Loeuille GA, Domblides P, Coltey B, Pin I, Llerena C, Troussier F, Person C, Marguet C, Wizla N, Thumerelle C, Turck D, Bui S, Fayon M, Duhamel A, Prévotat A, Wallaert B, Leroy S, Bouchara JP, Delhaes L

Abstract
Fungal respiratory colonization of cystic fibrosis (CF) patients emerges as a new concern; however, the heterogeneity of mycological protocols limits investigations. We first aimed at setting up an efficient standardized protocol for mycological analysis of CF sputa that was assessed during a prospective, multicenter study: "MucoFong" program (PHRC-06/1902). Sputa from 243 CF patients from seven centers in France were collected over a 15-month period and submitted to a standardized protocol based on 6 semi-selective media. After mucolytic pretreatment, sputa were plated in parallel on cycloheximide-enriched (ACT37), erythritol-enriched (ERY37), benomyl dichloran-rose bengal (BENO37) and chromogenic (CAN37) media incubated at 37 °C and on Sabouraud-chloramphenicol (SAB27) and erythritol-enriched (ERY27) media incubated at 20-27 °C. Each plate was checked twice a week during 3 weeks. Fungi were conventionally identified; time for detection of fungal growth was noted for each species. Fungal prevalences and media performances were assessed; an optimal combination of media was determined using the Chi-squared automatic interaction detector method. At least one fungal species was isolated from 81% of sputa. Candida albicans was the most prevalent species (58.8%), followed by Aspergillus fumigatus (35.4%). Cultivation on CAN37, SAB27, ACT37 and ERY27 during 16 days provided an optimal combination, detecting C. albicans, A. fumigatus, Scedosporium apiospermum complex and Exophiala spp. with sensitivities of 96.5, 98.8, 100 and 100%. Combination of these four culture media is recommended to ensure the growth of key fungal pathogens in CF respiratory specimens. The use of such consensual protocol is of major interest for merging results from future epidemiological studies.

PMID: 28748285 [PubMed - as supplied by publisher]

Attention and memory impairments in pediatric patients with cystic fibrosis and inflammatory bowel disease in comparison to healthy controls.

J Investig Med. 2017 Jul 26;:

Authors: Piasecki B, Stanisławska-Kubiak M, Strzelecki W, Mojs E

Abstract
The main aim of the study was to analyze and compare attention and memory performance in pediatric patients with cystic fibrosis (CF), inflammatory bowel disease (IBD) and in healthy controls. 28 patients with CF, 30 patients with IBD and 30 healthy subjects took part in the study (all in age range of 7-17). All subjects were in intellectual norm. To analyze the functioning of attention, the d2 Test of Attention by Brickenkamp (d2 test) was applied. Memory performance was assessed using the Benton Visual Retention Test (BVRT) and the Trial of 10 words. The CF and IBD groups committed significantly more errors in the d2 test than the healthy controls. The CF group also had significantly higher fluctuation rates and received significantly lower scores in overall concentration performance than the control group. Patients with CF made more mistakes and had fewer correct memory projections in BVRT than the healthy controls. Patients with IBD committed significantly more errors in BVRT than the control group. Patients with CF and IBD also got significantly lower scores in the Trial of 10 words than the control group. Pediatric patients with CF and IBD performed more poorly than the healthy controls on attention and memory tests. More distinct cognitive impairments were observed in the CF group. Further research is needed to find the underlying mechanisms and clinical and/or functional significance of observed cognitive deficits.

PMID: 28747318 [PubMed - as supplied by publisher]

Persistence of Candida dubliniensis and lung function in patients with cystic fibrosis.

BMC Res Notes. 2017 Jul 26;10(1):326

Authors: AbdulWahab A, Salah H, Chandra P, Taj-Aldeen SJ

Abstract
OBJECTIVES: Candida dubliniensis is an emerging yeast and demonstrated a high adherence property to cystic fibrosis respiratory tract. Therefore, it is important to determine the persistence of C. dubliniensis and to assess the possible relationship to the body mass index (BMI) and forced expiratory volume in 1st second (FEV1).
RESULTS: Candida isolates were identified by MALDI-TOF MS to species level from 40/52 (76.9%) cystic fibrosis patients. C. dubliniensis was the most common organism isolated from 50/77 (65%) lower respiratory specimens of 29 patients. Patients with persistent C. dubliniensis isolates have higher mean BMI in comparison to intermittent C. dubliniensis group. However, this difference did not reach statistical significance (P = 0.539). In contrast, patients with persistent C. dubliniensis isolates have significantly lower FEV1% mean in comparison to intermittent C. dubliniensis group particularly at initial two visits (P < 0.05); however, at subsequent visit the difference observed was not statistically significant (P = 0.456). The persistence of C. dubliniensis is more frequent in adults having more advanced disease, co-infections with chronic P. aeruginosa, cystic fibrosis related diabetes, long-term nebulized tobramycin and oral Zithromax therapy than patients with intermittent C. dubliniensis. Patients with persistent C. dubliniensis have lower FEV1 percentage and higher BMI than the intermittent C. dubliniensis.

PMID: 28747217 [PubMed - in process]

Pancreatic enzyme replacement therapy in cystic fibrosis: dose, variability and coefficient of fat absorption.

Rev Esp Enferm Dig. 2017 Jul 27;109:

Authors: Calvo-Lerma J, Martínez-Barona S, Masip E, Fornés V, Ribes-Koninckx C

Abstract
OBJECTIVES: Pancreatic enzyme replacement therapy (PERT) remains a backbone in the nutritional treatment of cystic fibrosis. Currently, there is a lack of an evidence-based tool that allows dose adjustment. To date, no studies have found an association between PERT dose and fat absorption. Therefore, the aim of the study was to assess the influence of both the PERT dose and the variability in this dose on the coefficient of fat absorption (CFA).
METHODS: This is a retrospective longitudinal study of 16 pediatric patients (192 food records) with three consecutive visits to the hospital over a twelve-month period. Dietary fat intake and PERT were assessed via a four-day food record and fat content in stools was determined by means of a three-day stool sample collection. A beta regression model was built to explain the association between the CFA and the interaction between the PERT dose (lipase units [LU]/g dietary fat) and the variability in the PERT dose (standard deviation [SD]).
RESULTS: The coefficient of fat absorption increased with the PERT dose when the variability in the dose was low. In contrast, even at the highest PERT dose values, the CFA decreased when the variability was high. The confidence interval suggested an association, although the analysis was not statistically significant.
CONCLUSION: The variability in the PERT dose adjustment should be taken into consideration when performing studies on PERT efficiency. A clinical goal should be the maintenance of a constant PERT dose rather than trying to obtain an optimal value.

PMID: 28747058 [PubMed - as supplied by publisher]

Brazilian guidelines for the diagnosis and treatment of cystic fibrosis.

J Bras Pneumol. 2017 May-Jun;43(3):219-245

Authors: Athanazio RA, Silva LVRFD, Vergara AA, Ribeiro AF, Riedi CA, Procianoy EDFA, Adde FV, Reis FJC, Ribeiro JD, Torres LA, Fuccio MB, Epifanio M, Firmida MC, Damaceno N, Ludwig-Neto N, Maróstica PJC, Rached SZ, Melo SFO, Grupo de Trabalho das Diretrizes Brasileiras de Diagnóstico e Tratamento da Fibrose Cística.

Abstract
Cystic fibrosis (CF) is an autosomal recessive genetic disorder characterized by dysfunction of the CFTR gene. It is a multisystem disease that most often affects White individuals. In recent decades, various advances in the diagnosis and treatment of CF have drastically changed the scenario, resulting in a significant increase in survival and quality of life. In Brazil, the current neonatal screening program for CF has broad coverage, and most of the Brazilian states have referral centers for the follow-up of individuals with the disease. Previously, CF was limited to the pediatric age group. However, an increase in the number of adult CF patients has been observed, because of the greater number of individuals being diagnosed with atypical forms (with milder phenotypic expression) and because of the increase in life expectancy provided by the new treatments. However, there is still great heterogeneity among the different regions of Brazil in terms of the access of CF patients to diagnostic and therapeutic methods. The objective of these guidelines was to aggregate the main scientific evidence to guide the management of these patients. A group of 18 CF specialists devised 82 relevant clinical questions, divided into five categories: characteristics of a referral center; diagnosis; treatment of respiratory disease; gastrointestinal and nutritional treatment; and other aspects. Various professionals working in the area of CF in Brazil were invited to answer the questions devised by the coordinators. We used the PubMed database to search the available literature based on keywords, in order to find the best answers to these questions. RESUMO A fibrose cística (FC) é uma doença genética autossômica recessiva caracterizada pela disfunção do gene CFTR. Trata-se de uma doença multissistêmica que ocorre mais frequentemente em populações descendentes de caucasianos. Nas últimas décadas, diversos avanços no diagnóstico e tratamento da FC mudaram drasticamente o cenário dessa doença, com aumento expressivo da sobrevida e qualidade de vida. Atualmente, o Brasil dispõe de um programa de ampla cobertura para a triagem neonatal de FC e centros de referência distribuídos na maior parte desses estados para seguimento dos indivíduos. Antigamente confinada à faixa etária pediátrica, tem-se observado um aumento de pacientes adultos com FC tanto pelo maior número de diagnósticos de formas atípicas, de expressão fenotípica mais leve, assim como pelo aumento da expectativa de vida com os novos tratamentos. Entretanto, ainda se observa uma grande heterogeneidade no acesso aos métodos diagnósticos e terapêuticos para FC entre as diferentes regiões brasileiras. O objetivo dessas diretrizes foi reunir as principais evidências científicas que norteiam o manejo desses pacientes. Um grupo de 18 especialistas em FC elaborou 82 perguntas clínicas relevantes que foram divididas em cinco categorias: características de um centro de referência; diagnóstico; tratamento da doença respiratória; tratamento gastrointestinal e nutricional; e outros aspectos. Diversos profissionais brasileiros atuantes na área da FC foram convidados a responder as perguntas formuladas pelos coordenadores. A literatura disponível foi pesquisada na base de dados PubMed com palavras-chave, buscando-se as melhores respostas às perguntas dos autores.

PMID: 28746534 [PubMed - in process]