Lung transplant referral for individuals with cystic fibrosis: Cystic Fibrosis Foundation consensus guidelines.

J Cyst Fibros. 2019 Mar 26;:

Authors: Ramos KJ, Smith PJ, McKone EF, Pilewski JM, Lucy A, Hempstead SE, Tallarico E, Faro A, Rosenbluth DB, Gray AL, Dunitz JM, CF Lung Transplant Referral Guidelines Committee, Ramos KJ, Dunitz JM, Rosenbluth DB, Dorgan DJ, Gray AL, Mallory GB, Smith PJ, Markovitz M, Solomon M, Mahoney EL, Lucy A, McArdle JR, Pilewski JM, Faro A, Tallarico E, Hempstead SE

Abstract
OBJECTIVE: Provide recommendations to the cystic fibrosis (CF) community to facilitate timely referral for lung transplantation for individuals with CF.
METHODS: The CF Foundation organized a multidisciplinary committee to develop CF Lung Transplant Referral Consensus Guidelines. Three workgroups were formed: timing for transplant referral; modifiable barriers to transplant; and transition to transplant care. A focus group of lung transplant recipients with CF and spouses of CF recipients informed guideline development.
RESULTS: The committee formulated 21 recommendation statements based on literature review, committee member practices, focus group insights, and in response to public comment. Critical approaches to optimizing access to lung transplant include early discussion of this treatment option, assessment for modifiable barriers to transplant, and open communication between the CF and lung transplant centers.
CONCLUSIONS: These guidelines will help CF providers counsel their patients and may reduce the number of individuals with CF who die without consideration for lung transplant.

PMID: 30926322 [PubMed - as supplied by publisher]

Physical activity and associations with clinical outcome measures in adults with cystic fibrosis; a systematic review.

J Cyst Fibros. 2019 Mar 26;:

Authors: Shelley J, Boddy LM, Knowles ZR, Stewart CE, Dawson EA

Abstract
BACKGROUND: Physical activity (PA) is important in the management of Cystic Fibrosis (CF) and is associated with a number of beneficial effects. PA assessment is not commonplace or consistent in clinical practice, therefore understanding of PA in adults with CF remains limited. The purpose of this review was to evaluate PA levels in this population and compare PA to global recommendations and non-CF peers.
METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were utilised to inform the review process. Original research was identified and screened against inclusion/exclusion criteria. Quality was assessed, data extracted and a narrative synthesis undertaken to describe the findings.
RESULTS: Adults with CF did not achieve recommended PA guidelines and step count targets in 5/8 studies where assessment was possible. No significant differences in PA were found between CF and non-CF peers in 3/5 studies. Associations between PA and improved lung function were inconsistent with 4/9 studies finding a positive association. Evidence for an association between PA and higher exercise capacity was stronger with all 4 studies reviewed reporting a positive association. Quality ratings were low across all studies.
CONCLUSIONS: PA in adults with CF is largely comparable to their non-CF peers, despite being insufficiently active to achieve PA recommendations. Assessment tools used and outcomes reported are variable, many of which do not provide sufficient information to assess relevant components of PA. There is a requirement for high quality studies designed specifically to explore PA in adults with CF, ideally employing standardised PA assessment methods.

PMID: 30926321 [PubMed - as supplied by publisher]

Peripheral localization of the epithelial sodium channel (ENaC) in the apical membrane of bronchial epithelial cells.

Exp Physiol. 2019 Mar 29;:

Authors: Musante I, Scudieri P, Venturini A, Guidone D, Caci E, Castellani S, Conese M, Galietta LJV

Abstract
NEW FINDINGS: What is the central question of this study? The epithelial sodium channel (ENaC) has a key role in absorbing fluid across the human airway epithelium. However, its precise subcellular localization is unknown. What is the main finding and its importance? ENaC protein has an unexpected localization in the peripheral region of the apical membrane of bronchial epithelial cells, very close to tight junctions. This localization may be important in the mechanism of Na+ absorption ABSTRACT: The epithelial sodium channel (ENaC) has a key role in absorbing fluid across the human airway epithelium. Altered activity of ENaC may perturb the process of mucociliary clearance, thus impairing the innate defense mechanisms against microbial agents. The proteins forming ENaC are present on the apical membrane of the epithelium. However, their precise localization is unknown. In the present study, we used two antibodies recognizing the alpha and beta ENaC subunits. Both antibodies revealed a restricted localization of ENaC in the peripheral region of the apical membrane of cultured bronchial epithelial cells, close to but not overlapping with tight junctions. In contrast, CFTR chloride channel was more diffusely expressed on the whole apical membrane. Modulation of ENaC activity by aprotinin or elastase resulted in a decrease or increase in the peripheral localization, respectively. Our results suggest that sodium absorption is mainly occurring close to tight junctions where this cation may be rapidly expelled by the sodium/potassium pump present in lateral membranes. This arrangement of channels and pumps may limit sodium build up in other regions of the cells. This article is protected by copyright. All rights reserved.

PMID: 30924990 [PubMed - as supplied by publisher]

Management and clinical outcomes after lung transplantation in patients with pre-transplant Mycobacterium abscessus infection: a single center experience.

Transpl Infect Dis. 2019 Mar 29;:e13084

Authors: Perez AA, Singer JP, Schwartz BS, Chin-Hong P, Shah RJ, Kleinhenz ME, Gao Y, Venado A, Leard LE, Golden JA, Kukreja J, Greenland JR, Hays SR

Abstract
BACKGROUND: Preoperative Mycobacterium abscessus infection is often considered a contraindication to lung transplantation because of its association with poor outcomes after transplant. Detailed strategies for bridging to transplant, post-operative management, and data regarding outcomes are lacking.
METHODS: We reviewed outcomes in subjects with M abscessus infection who underwent lung transplantation between 2010 and 2018 at the University of California San Francisco. M abscessus infection was defined by ATS criteria. Data collected included age, FEV1 , BMI, LAS, antibiotic regimens, and other management decisions. Time to CLAD and survival were also assessed.
RESULTS: Of 387 lung transplant recipients, 7 were infected with M abscessus at the time of listing. All received multiple antibiotics before transplant. While all subjects converted to smear negative for acid-fast bacilli before listing, 5 of 7 remained culture-positive at the time of transplant. After transplant, subjects received a median of 6 months of a multi-antibiotic regimen. One subject developed a post-operative M abscessus soft tissue infection that was treated medically. Six of 7 subjects survived the observation period; one died unrelated to M abscessus. Time to CLAD and survival were similar to a contemporary comparator group of CF transplant recipients.
CONCLUSION: Lung transplant recipients with M abscessus infection have a low incidence of recurrent infection, excellent survival, and freedom from CLAD when an aggressive management and surveillance strategy is utilized. Given these findings, M abscessus infection may not be considered a contraindication to lung transplantation. This article is protected by copyright. All rights reserved.

PMID: 30924986 [PubMed - as supplied by publisher]

[Experience with nebulised colistin in patients with non-cystic fibrosis bronchiectasis colonised with Pseudomonas aeruginosa].

Rev Esp Quimioter. 2019 Mar 28;:

Authors: López-Gil Otero MM, Romero-Ventosa EY, Feijoo-Meléndez D, Casanova-Martínez C, Otero-Millán L, Piñeiro-Corrales G

Abstract
OBJECTIVE: Chronic colonisation/infection by Pseudomonas aeruginosa of the bronchiectasis is related to a faster deterioration of lung function, an increase in the number of exacerbations and a higher morbidity and mortality. Nebulised colistin decreases bacteria load. Therefore, a reduction in the number and in the severity of exacerbations and a delay of pulmonary decline is expected. The main objective is to evaluate if the treatment with nebulised colistin, for at least 6 months reduces the number of admissions and visits to the emergency department.
METHODS: Observational, retrospective and non-interventionist study carried out in an organizational structure with an integrated management. Patients with non-cystic fibrosis bronchiectasis colonised / infected by P. aeruginosa, older than 18 years, were selected. Patients must have received nebulized colistin during at least 6 months. Clinical, microbiological and therapeutic data from the patients were collected from the SERGAS computerized clinical history (IANUS® v.4.20.0503) and the electronic prescription, which were divided into two time periods: 1) 6 months pre-treatment and during the treatment and 2) 12 months pre-treatment and during the treatment, in those who completed 1 year of treatment.
RESULTS: Forty-four patients were included and of these, 29 (65.9%) had a follow-up of 12 months. The use of nebulized colistin decreased significantly the number of visits to the emergency (at 6 months), the frequency and duration of hospitalizations admissions (at 6 and 12 months), the antibiotic consumption (at 6 and 12 months) and the positive cultures. The treatment was well tolerated in almost all patients.
CONCLUSIONS: The treatment with nebulised colistin during 6 and 12 months of non-cystic fibrosis bronchiectasis, colonised/infected by P. aeruginosa, seems beneficial for the patient, from the clinical and quality of life point of view, and could reduce the economic cost of the process.

PMID: 30924621 [PubMed - as supplied by publisher]

Perspectives on anemia and iron deficiency from the cystic fibrosis care community.

Pediatr Pulmonol. 2019 Mar 28;:

Authors: Garlow GM, Gettle LS, Felicetti NJ, Polineni D, Gifford AH

PMID: 30924325 [PubMed - as supplied by publisher]

Evaluation of Gastric Emptying in Cystic Fibrosis Using Bedside Ultrasonography.

J Ultrasound Med. 2019 Mar 28;:

Authors: Nazareth D, Mohan K, Fewins H, Walshaw M

Abstract
OBJECTIVES: Although gastric emptying rate (GER) influences incretin response and nutrient absorption, both defective in people with cystic fibrosis (CF), there are few studies in this group, and the circadian rhythm is unknown. We employed an ultrasonographic technique to assess GER in people with CF following liquid and mixed meals and also evaluated the circadian rhythm, compared to normal controls.
METHODS: Thirteen pancreatic-insufficient adults with CF and 10 healthy controls underwent a fasting oral glucose tolerance test (OGTT; liquid meal) and on a second visit underwent a fasting mixed meal test (MMT) thrice on the same day. GER was measured during the OGTT and each MMT using a 3.5-MHz abdominal transducer probe at baseline and 30, 60, 90, and 120 minutes.
RESULTS: Controls had normal GER for both OGTT and MMT. Compared to controls, people with CF had delayed GER60 for OGTT (mean 46%), which increased with time (P = .001), and also delayed GER90 for MMT in the morning (mean 56%), afternoon (58%), and evening (59%). The GER in the control group was better at all time points throughout the day compared to patients with CF.
CONCLUSIONS: This is the first study to use ultrasonography, an inexpensive bedside technique, to assess GER in adults with CF. For the first time, we have shown that adults with CF have delayed GER for both liquid and mixed meals, and this delay continues throughout the day.

PMID: 30924192 [PubMed - as supplied by publisher]

Bone mineral density in cystic fibrosis patients using low-dose chest CT: a pilot study.

Eur Respir J. 2019 Mar 28;:

Authors: Feijó Andrade RG, Forte GC, Hochhegger B, Pinto LA

PMID: 30923186 [PubMed - as supplied by publisher]

A two-center analysis of hyperpolarized 129Xe lung MRI in stable pediatric cystic fibrosis: Potential as a biomarker for multi-site trials.

J Cyst Fibros. 2019 Mar 25;:

Authors: Couch MJ, Thomen R, Kanhere N, Hu R, Ratjen F, Woods J, Santyr G

Abstract
BACKGROUND: The ventilation defect percent (VDP), measured from hyperpolarized (HP) 129Xe magnetic resonance imaging (MRI), is sensitive to functional changes in cystic fibrosis (CF) lung disease. The purpose of this study was to measure and compare VDP from HP 129Xe MRI acquired at two institutions in stable pediatric CF subjects with preserved lung function.
METHODS: This retrospective analysis included 26 participants from two institutions (18 CF, 8 healthy, age range 10-17). Pulmonary function tests, N2 multiple breath washout (to measure lung clearance index, LCI), and HP 129Xe MRI were performed. VDP measurements were compared between two trained analysts using mean-anchored linear binning. Correlations were investigated for VDP compared to the forced expiratory volume in one second (FEV1) and LCI.
RESULTS: VDP measurements agreed for the two analysts with an intraclass correlation coefficient of 0.99. In the combined dataset, VDP measured by Analyst 1 was 5.96 ± 1.82% and 15.96 ± 6.76% for the healthy and CF groups, respectively (p = .0004). Analyst 2 showed similar differences between healthy and CF (p = .0003). VDP measured by either analyst was shown to correlate with FEV1 (R2 = 0.33, p = .003; and R2 = 0.26, p = .009 for Analysts 1 and 2, respectively) and LCI (R2 = 0.76, p < .0001; and R2 = 0.77, p < .0001 for Analysts 1 and 2, respectively).
CONCLUSION: HP 129Xe MRI provides a robust measurement of ventilation heterogeneity in stable pediatric CF subjects at two sites. Since measurements performed at two sites yielded similar VDP values with near-identical values between different analysts, implementation of the technique in multi-center trials in CF appears feasible.

PMID: 30922812 [PubMed - as supplied by publisher]

Vitamin D inhibits pro-inflammatory cytokines in the airways of cystic fibrosis patients infected by Pseudomonas aeruginosa- pilot study.

Ital J Pediatr. 2019 Mar 29;45(1):41

Authors: Olszowiec-Chlebna M, Koniarek-Maniecka A, Brzozowska A, Błauż A, Rychlik B, Stelmach I

Abstract
BACKGROUND: Vitamin D plays an important role in inflammatory responses after antigen exposure. Interleukin-23 (Il-23) promotes Il-17-dependent inflammation during Pseudomonas aeruginosa (P. aeruginosa) pulmonary infection. We aimed to compare the ability of calcitriol and cholecalciferol to modulate the inflammatory response of the CF airways infected with P. aeruginosa.
METHODS: This was a randomized, placebo-controlled, double-blind, cross-over trial. Twenty-three patients with CF (aged 6-19), chronically infected by P. aeruginosa were randomly assigned to: calcitriol group receiving 1,25(OH)2D 0,5 mcg daily or cholecalciferol group receiving cholecalciferol 1000 IU daily for three months. The levels of Il-23 and Il-17A in the exhaled breath concentrate (EBC) were measured. Calcium-phosphorus balance was also evaluated (serum concentration of calcium, phosphorus, 25OHD, parathormone (PTH) and calcium/creatinine ratio in urine). Data were analyzed using means of Stata/Special Edition, release 14.2. A level of P < 0.05 was considered statistically significant.
RESULTS: The level of Il-17A in EBC significantly decreased in calcitriol group from 0,475 pg/mL (± SD 0,515 pg/mL) to 0,384 pg/mL (± SD 0,429 pg/mL) (p = 0,008); there was no change in cholecalciferol group (p = 0,074). The level of Il-23 in EBC did not significantly change in calcitriol group (p = 0,086); there was significant decrease in cholecalciferol group from 8,90 pg/mL (± SD 4,07 pg/mL) to 7,33 pg/mL (± SD 3,88 pg/mL) (p = 0,001). In calcitriol group serum phosphorus and PTH significantly decreased (p = 0,021 and p = 0,019 respectively), the concentration of calcium significantly increased (p = 0,001); there were no changes in cholecalciferol group.
CONCLUSIONS: Both analogs of vitamin D revealed their anti-inflammatory effect and reduced the level of Il-17A and Il-23 in the airway of CF patients with chronic P. aeruginosa infection. We observed improvement in calcium-phosphorus metabolism after supplementation with calcitriol, without adverse effects. It is recommended to use vitamin D in CF patients.

PMID: 30922377 [PubMed - in process]

Congenital emphysematous lung disease associated with a novel Filamin A mutation. Case report and literature review.

BMC Pediatr. 2019 Mar 29;19(1):86

Authors: Pelizzo G, Collura M, Puglisi A, Pappalardo MP, Agolini E, Novelli A, Piccione M, Cacace C, Bussani R, Corsello G, Calcaterra V

Abstract
BACKGROUND: Progressive lung involvement in Filamin A (FLNA)-related cerebral periventricular nodular heterotopia (PVNH) has been reported in a limited number of cases.
CASE PRESENTATION: We report a new pathogenic FLNA gene variant (c.7391_7403del; p.Val2464Alafs*5) in a male infant who developed progressive lung disease with emphysematous lesions and interstitial involvement. Following lobar resection, chronic respiratory failure ensued necessitating continuous mechanical ventilation and tracheostomy. Cerebral periventricular nodular heterotopia was also present.
CONCLUSIONS: We report a novel variant of the FLNA gene, associated with a severe lung disorder and PNVH. The lung disorder led to respiratory failure during infancy and these pulmonary complications may be the first sign of this disorder. Early recognition with thoracic imaging is important to guide genetic testing, neuroimaging and to define optimal timing of potential therapies, such as lung transplant in progressive lung disease.

PMID: 30922288 [PubMed - in process]

Synthesis of phenylpyrimidinones as guanylyl cyclase C inhibitors.

Pharmazie. 2019 01 01;74(1):15-17

Authors: Magli E, Fiorino F, Severino B, Corvino A, Perissutti E, Frecentese F, Giordano F, Saccone I, Luciano P, Zaminelli T, Santagada V, Caliendo G, de Nucci G

Abstract
Diarrhea is one of the most important causes of mortality in the developing world, being responsible for 2.5 million deaths each year. Many of these deaths are caused by enterotoxigenic strains of bacteria, like Escherichia coli, that produce enterotoxins that cause acute watery diarrhea, commonly defined as secretory diarrhea. Studies on symptomatic patients indicate a high prevalence of enterotoxigenic E. coli strains producing the heat-stable toxin, STa. STa is a small, cysteine-rich peptide that binds to the extracellular receptor domain of guanylyl cyclase C (GCC), located at the luminal membrane of intestinal epithelial cells. GCC and its endogenous peptide ligands, guanylin and uroguanylin, play a key role in balancing water absorption and hydration of the intestinal lumen, as exemplified by the finding that loss of GCC function causes severe dehydration of the intestinal lumen, culminating in intestinal obstruction. From a mechanistic viewpoint, reduction of GCC activity offers an efficient approach to limit enterotoxigenic E. coli- provoked secretory diarrhea. Inhibition of GCC-mediated cGMP production would not only reduce anion secretion, but would also restore NHE3 activity, resulting in a comprehensive antidiarrheal action. In the present study, two novel phenylpyrimidinone derivatives were simultaneously synthesized and tested for their ability to block STa-induced CFTR activity in T84 cells.

PMID: 30782244 [PubMed - indexed for MEDLINE]

Trafficking Ion Transporters to the Apical Membrane of Polarized Intestinal Enterocytes.

Cold Spring Harb Perspect Biol. 2018 01 02;10(1):

Authors: Engevik AC, Goldenring JR

Abstract
Epithelial cells lining the gastrointestinal tract require distinct apical and basolateral domains to function properly. Trafficking and insertion of enzymes and transporters into the apical brush border of intestinal epithelial cells is essential for effective digestion and absorption of nutrients. Specific critical ion transporters are delivered to the apical brush border to facilitate fluid and electrolyte uptake. Maintenance of these apical transporters requires both targeted delivery and regulated membrane recycling. Examination of altered apical trafficking in patients with Microvillus Inclusion disease caused by inactivating mutations in MYO5B has led to insights into the regulation of apical trafficking by elements of the apical recycling system. Modeling of MYO5B loss in cell culture and animal models has led to recognition of Rab11a and Rab8a as critical regulators of apical brush border function. All of these studies show the importance of apical membrane trafficking dynamics in maintenance of polarized epithelial cell function.

PMID: 28264818 [PubMed - indexed for MEDLINE]

Personalised anti-inflammatory therapy for bronchiectasis and cystic fibrosis: selecting patients for controlled trials of neutrophil elastase inhibition.

ERJ Open Res. 2019 Feb;5(1):

Authors: Keir HR, Fong CJ, Crichton ML, Barth P, Chevalier E, Brady G, Kennedy G, Zimmermann J, Bruijnzeel PLB, Dicker AJ, Chalmers JD

Abstract
Background: Neutrophil elastase (NE) has been linked to lung neutrophil dysfunction in bronchiectasis and cystic fibrosis (CF), making NE inhibition a potential therapeutic target. NE inhibitor trials have given mixed result perhaps because not all patients have elevated airway NE activity.
Methods: We tested whether a single baseline sputum NE measurement or a combination of clinical parameters could enrich patient populations with elevated NE activity for "personalised medicine". Intra- and interindividual variations of total and active NE levels in induced sputum from patients with CF or bronchiectasis were monitored over 14 days. Patients with established CF and bronchiectasis (n=5 per group) were recruited. NE was measured using three different methods: one total and two active NE assays. Subsequently, we analysed the association between clinical parameters and NE from a large bronchiectasis cohort study (n=381).
Results: All three assays showed a high degree of day-to-day variability (0-233% over 14 days). There were strong correlations found between all assays (p<0.0001). Despite high day-to-day variability, patients could be stratified into "high" or "low" groups based on moderate cut-off levels. In the bronchiectasis cohort study, factors most associated with high sputum NE levels were: Pseudomonas aeruginosa infection (β-estimate 11.5, 95% CI -6.0-29.0), sputum colour (β-estimate 10.4, 95% CI 4.3-16.6), Medical Research Council dyspnoea score (β-estimate 6.4, 95% CI 1.4-11.4) and exacerbation history (β-estimate 3.4, 95% CI 1.4-5.3). Collectively, P. aeruginosa infection, sputum colour and exacerbation frequency provided the greatest specificity for "high" NE (98.7%, 95% CI 7.0-99.6%).
Conclusion: These results show that patients with bronchiectasis and CF can be effectively divided into "high" or "low" groups, based on sputum NE assays or clinical inclusion criteria.

PMID: 30918898 [PubMed]

ATP-Dependent Signaling in Simulations of a Revised Model of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR).

J Phys Chem B. 2019 Mar 28;:

Authors: Strickland KM, Stock G, Cui G, Hwang H, Infield DT, Schmidt-Krey I, McCarty NA, Gumbart JC

Abstract
Cystic fibrosis transmembrane conductance regulator (CFTR) is a member of the ATP-binding cassette (ABC) transporter superfamily that has uniquely evolved to function as a chloride channel. It binds and hydrolyzes ATP at its nucleotide binding domains to form a pore providing a diffusive pathway within its transmembrane domains. CFTR is the only known protein from the ABC superfamily with channel activity, and its dysfunction causes the disease cystic fibrosis. While much is known about the functional aspects of CFTR, significant gaps remain, such as the structure-function relationship underlying signaling of ATP binding. In the present work, we refined an existing homology model using an intermediate-resolution (9 Å) published cryo-electron microscopy map. The newly derived models have been simulated in equilibrium molecular dynamics simulations for a total of 2.5 μs in multiple ATP-occupancy states. Putative conformational movements connecting ATP binding with pore formation are elucidated and quantified. Additionally, new inter-domain interactions between E543, K968, and K1292 have been identified and confirmed experimentally; these interactions may be relevant for signaling ATP binding and hydrolysis to the transmembrane domains and induction of pore opening.

PMID: 30921517 [PubMed - as supplied by publisher]

Pancreatoscopy-Directed Electrohydraulic Lithotripsy in a Pediatric Patient with Pancreas Divisum and Cystic Fibrosis.

J Pediatr Gastroenterol Nutr. 2019 Mar 26;:

Authors: Queliza K, Raijman I, Fishman DS

PMID: 30921253 [PubMed - as supplied by publisher]

Genomic and transcriptomic characterization of Pseudomonas aeruginosa small colony variants derived from a chronic infection model.

Microb Genom. 2019 Mar 28;:

Authors: Irvine S, Bunk B, Bayes HK, Spröer C, Connolly JPR, Six A, Evans TJ, Roe AJ, Overmann J, Walker D

Abstract
Phenotypic change is a hallmark of bacterial adaptation during chronic infection. In the case of chronic Pseudomonas aeruginosa lung infection in patients with cystic fibrosis, well-characterized phenotypic variants include mucoid and small colony variants (SCVs). It has previously been shown that SCVs can be reproducibly isolated from the murine lung following the establishment of chronic infection with mucoid P. aeruginosa strain NH57388A. Using a combination of single-molecule real-time (PacBio) and Illumina sequencing we identify a large genomic inversion in the SCV through recombination between homologous regions of two rRNA operons and an associated truncation of one of the 16S rRNA genes and suggest this may be the genetic switch for conversion to the SCV phenotype. This phenotypic conversion is associated with large-scale transcriptional changes distributed throughout the genome. This global rewiring of the cellular transcriptomic output results in changes to normally differentially regulated genes that modulate resistance to oxidative stress, central metabolism and virulence. These changes are of clinical relevance because the appearance of SCVs during chronic infection is associated with declining lung function.

PMID: 30920365 [PubMed - as supplied by publisher]

Impaired glucose tolerance, body mass index and respiratory function in patients with cystic fibrosis: A systematic review.

Clin Respir J. 2019 Mar 28;:

Authors: Iwanicki C, Logomarsino JV

Abstract
OBJECTIVES: This systematic review aims to evaluate body mass index (BMI) and forced expiratory volume in one second (FEV1 ) in patients with cystic fibrosis (CF) diagnosed with impaired glucose tolerance (IGT) compared to those with normal glucose tolerance (NGT). The significance of this topic stems from concern that individuals with CF and IGT may have an overall worse clinical status as indicated by BMI and FEV1 .
DATA SOURCE: An exhaustive literature search was completed between July 2017 and September 2017 using PubMed, CINAHL, Web of Science, Dissertations & Theses, PsycINFO, and Open Grey. Studies were limited to human subjects with CF. There were no restrictions on publication date, study design, or language.
STUDY SELECTION: Included studies examined BMI and FEV1 as outcome measures in individuals with CF and IGT compared to those with NGT. After screening for inclusion criteria, 12 observational studies met the specified conditions.
RESULTS: Two studies showed a significantly worse BMI and FEV1 in subjects with CF and IGT compared to those with NGT. The remaining 10 studies found no significant associations with BMI and FEV1 in subjects with CF and IGT compared to NGT.
CONCLUSION: Although this review does not prove cause and effect, BMI and FEV1 are important outcome measures in patients with CF. Considering the inconclusive findings, practitioners should individualize care for this patient population. Additional research should focus on clinical status and interventions/treatment for individuals with CF and IGT. This article is protected by copyright. All rights reserved.

PMID: 30919537 [PubMed - as supplied by publisher]

Transmission of bacteria in bronchiectasis and chronic obstructive pulmonary disease: Low burden of cough aerosols.

Respirology. 2019 Mar 27;:

Authors: Stockwell RE, Chin M, Johnson GR, Wood ME, Sherrard LJ, Ballard E, O'Rourke P, Ramsay KA, Kidd TJ, Jabbour N, Thomson RM, Knibbs LD, Morawska L, Bell SC

Abstract
BACKGROUND AND OBJECTIVE: Aerosol transmission of Pseudomonas aeruginosa has been suggested as a possible mode of respiratory infection spread in patients with cystic fibrosis (CF); however, whether this occurs in other suppurative lung diseases is unknown. Therefore, we aimed to determine if (i) patients with bronchiectasis (unrelated to CF) or chronic obstructive pulmonary disease (COPD) can aerosolize P. aeruginosa during coughing and (ii) if genetically indistinguishable (shared) P. aeruginosa strains are present in these disease cohorts.
METHODS: People with bronchiectasis or COPD and P. aeruginosa respiratory infection were recruited for two studies. Aerosol study: Participants (n = 20) underwent cough testing using validated cough rigs to determine the survival of P. aeruginosa aerosols in the air over distance and duration. Genotyping study: P. aeruginosa sputum isolates (n = 95) were genotyped using the iPLEX20SNP platform, with a subset subjected to the enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) assay to ascertain their genetic relatedness.
RESULTS: Aerosol study: Overall, 7 of 20 (35%) participants released P. aeruginosa cough aerosols during at least one of the cough aerosol tests. These cough aerosols remained viable for 4 m from the source and for 15 min after coughing. The mean total aerosol count of P. aeruginosa at 2 m was two colony-forming units. Typing study: No shared P. aeruginosa strains were identified.
CONCLUSION: Low viable count of P. aeruginosa cough aerosols and a lack of shared P. aeruginosa strains observed suggest that aerosol transmission of P. aeruginosa is an unlikely mode of respiratory infection spread in patients with bronchiectasis and COPD.

PMID: 30919511 [PubMed - as supplied by publisher]

Antibiotic susceptibility and production of endotoxin by Ochrobactrum anthropi isolated from environment and from patients with cystic fibrosis.

Folia Microbiol (Praha). 2019 Mar 27;:

Authors: Chmelař D, Holý O, Kasáková I, Hájek M, Lazarová A, Gonzalez-Rey C, Lasák J, Raclavský V, Čižnár I

Abstract
The aim of this work was to compare production of endotoxin and to determine susceptibility to antibiotics in two groups of specimens-wild-type strains Ochrobactrum anthropi isolated from the environment and the strains isolated from patients with cystic fibrosis. The determination of the endotoxin produced by the test strains was carried on by using a limulus amebocyte lysate test (LAL test). Determination of ATB sensitivity was accomplished by means of a broth dilution method in a microtiter plate (MIC). No significant difference was found between the group of ochrobacters isolated from the environment and the group of ochrobacters isolated from cystic fibrosis patients. Antibiotic sensitivity testing has indicated that the resistance to tigecycline, trimethoprim/sulfamethoxazole, and gentamicin was slightly higher in strains isolated from cystic fibrosis patients in comparison with strains isolated from the environment. In general, most of the test strains were sensitive to most of the antibiotics tested. Significant resistance has been demonstrated for cefotaxime. Resistance was also found for gentamicin in strains number 4 and 7. The MIC was equal to the breakpoint for this antibiotic (8000 mg/L).

PMID: 30919306 [PubMed - as supplied by publisher]