Massive hemoptysis during general endotracheal anesthesia in adults with Cystic Fibrosis.

J Clin Anesth. 2017 Aug 06;42:17-18

Authors: Aronsohn J, Dowling O, Kars M, Roseman A

PMID: 28793275 [PubMed - as supplied by publisher]

Ralstonia infection in cystic fibrosis.

Epidemiol Infect. 2017 Aug 09;:1-9

Authors: Green HD, Bright-Thomas R, Kenna DT, Turton JF, Woodford N, Jones AM

Abstract
This study aimed to determine prevalence of Ralstonia spp. in cystic fibrosis patients, look for any evidence of cross infection and to describe clinical outcomes for patients infected by Ralstonia spp. Prevalence of Ralstonia spp. was calculated annually from 2008 to 2016. Pulsed-field gel electrophoresis was performed on ⩾1 sample from patients with an isolation of Ralstonia spp. between 2008 and 2016. A prospective, longitudinal observational study of adult patients was performed with 12 months follow-up from recruitment. Prevalence of Ralstonia spp. rose from 0·6% in 2008 to 2·4% in 2016. In total 12 out of 14 (86%) patients with ⩾1 isolation of Ralstonia spp. developed chronic infection. A pair and a group of three unrelated patients with epidemiological connections shared strains of Ralstonia mannitolilytica. Lung function of Ralstonia spp. infected patients was moderately to severely impaired. Prevalence of Ralstonia spp. is low but increasing. The risk of a patient developing chronic Ralstonia spp. infection following first acquisition is high and cross-infection may be possible. Whether Ralstonia spp. infection causes increased pulmonary exacerbation frequency and lung function decline needs to be evaluated in larger prospective studies.

PMID: 28791938 [PubMed - as supplied by publisher]

Pseudomonas aeruginosa LasB protease impairs innate immunity in mice and humans by targeting a lung epithelial cystic fibrosis transmembrane regulator-IL-6-antimicrobial-repair pathway.

Thorax. 2017 Aug 08;:

Authors: Saint-Criq V, Villeret B, Bastaert F, Kheir S, Hatton A, Cazes A, Xing Z, Sermet-Gaudelus I, Garcia-Verdugo I, Edelman A, Sallenave JM

Abstract
BACKGROUND: Pseudomonas aeruginosa lung infections are a huge problem in ventilator-associated pneumonia, cystic fibrosis (CF) and in chronic obstructive pulmonary disease (COPD) exacerbations. This bacterium secretes virulence factors that may subvert host innate immunity.
OBJECTIVE: We evaluated the effect of P. aeruginosa elastase LasB, an important virulence factor secreted by the type II secretion system, on ion transport, innate immune responses and epithelial repair, both in vitro and in vivo.
METHODS: Wild-type (WT) or cystic fibrosis transmembrane conductance regulator (CFTR)-mutated epithelial cells (cell lines and primary cells from patients) were treated with WT or ΔLasB pseudomonas aeruginosa O1 (PAO1) secretomes. The effect of LasB and PAO1 infection was also assessed in vivo in murine models.
RESULTS: We showed that LasB was the most abundant protein in WT PAO1 secretomes and that it decreased epithelial CFTR expression and activity. In airway epithelial cell lines and primary bronchial epithelial cells, LasB degraded the immune mediators interleukin (IL)-6 and trappin-2, an important epithelial-derived antimicrobial molecule. We further showed that an IL-6/STAT3 signalling pathway was downregulated by LasB, resulting in inhibition of epithelial cell repair. In mice, intranasally instillated LasB induced significant weight loss, inflammation, injury and death. By contrast, we showed that overexpression of IL-6 and trappin-2 protected mice against WT-PAO1-induced death, by upregulating IL-17/IL-22 antimicrobial and repair pathways.
CONCLUSIONS: Our data demonstrate that PAO1 LasB is a major P. aeruginosa secreted factor that modulates ion transport, immune response and tissue repair. Targeting this virulence factor or upregulating protective factors such as IL-6 or antimicrobial molecules such as trappin-2 could be beneficial in P. aeruginosa-infected individuals.

PMID: 28790180 [PubMed - as supplied by publisher]

Predictive factors for a one-year improvement in nontuberculous mycobacterial pulmonary disease: An 11-year retrospective and multicenter study.

PLoS Negl Trop Dis. 2017 Aug 07;11(8):e0005841

Authors: Cadelis G, Ducrot R, Bourdin A, Rastogi N

Abstract
BACKGROUND: Nontuberculous mycobacterial pulmonary disease (NTM-PD) has become an emerging infectious disease and is responsible for more deaths than tuberculosis in industrialized countries. NTM-PD mortality remains high in some series reportedly ranging from 25% to 40% at five years and often due to unfavorable evolution of NTM-PD despite established treatment. The purpose of our study was to search for early factors that could predict the favorable or unfavorable evolution of NTM-PD at the first year of treatment.
METHODS: In this retrospective and multicenter study, we selected 119 patients based on clinical, radiological and microbiological data from 2002 to 2012 from three French university hospitals (Guadeloupe, Martinique, Montpellier) with definite (meeting the criteria of the American Thoracic Society and the Infectious Disease Society of America in 2007; ATS/IDSA) or probable (one positive sputum culture) NTM-PD. We compared two patient groups: those who improved at one year (clinical symptoms, radiological lesions and microbiology data) and those who did not improve at one year. The data were analyzed for all patients as well as for subgroups by gender, HIV-positive patients, and Mycobacterium avium complex (MAC) infection.
RESULTS: The average patient age was 50 years ± 19.4; 58% had respiratory comorbidities, 24% were HIV positive and 19% had cystic fibrosis. Coughing concerned 66% of patients and bronchiectasis concerned 45%. The most frequently isolated NTM were MAC (46%). 57% (n = 68) of patients met the ATS criteria and improved status concerned 38.6% (n = 46). The improvement factors at one year of NTM-PD were associated with the duration of ethambutol treatment: (Odds ratio adjusted [ORa]: 2.24, 95% Confidence interval [CI]; 2.11-3.41), HIV-positive status: (ORa: 3.23, 95% CI; 1.27-8.45), and male gender: (ORa: 2.34, 95% CI; 1.26-8.16). For the group with NTM-PD due to MAC, improvement was associated with the duration of macrolide treatment (ORa: 3.27, 95% CI; 1.88-7.30) and an age <50 years (ORa: 1.88, 95% CI; 1.55-8.50).
CONCLUSION: In this retrospective multicenter study, improvement at one year in patients with definite or probable NTM-PD was associated with the duration of ethambutol treatment, HIV-positive status and male gender. For the group of patients infected with MAC, improvement was associated with the duration of macrolide treatment and an age <50 years. Identifying predictors of improvement at one year of NTM-PD is expected to optimize the management of the disease in its early stages.

PMID: 28787454 [PubMed - as supplied by publisher]

Effects of new and emerging therapies on gastrointestinal outcomes in cystic fibrosis.

Curr Opin Pulm Med. 2017 Aug 05;:

Authors: Houwen RHJ, van der Woerd WL, Slae M, Wilschanski M

Abstract
PURPOSE OF REVIEW: Several new therapeutic modalities have recently become available to be used in patients with cystic fibrosis such as potentiators, modulators, and probiotics. Although the effects on pulmonary function have been well documented, gastrointestinal outcomes have been addressed only rarely.
RECENT FINDINGS: Both the potentiator (ivacaftor) and the potentiator/modulator combination (ivacaftor/lumacaftor) that are currently on the market have a positive effect on BMI. Young patients (2-5 years of age) with a gating mutation may show improvement of exocrine pancreatic function on ivacaftor. In this specific patient population this agent also seems to improve intestinal pH and reflux. The effect of these medications on other gastrointestinal outcomes, such as intestinal inflammation and cystic fibrosis liver disease, has not been described so far. Furthermore, the results of several trials suggest that probiotics might reduce intestinal inflammation. Finally, organoids might be used to predict in vitro the clinical effect of potentiators and modulators.
SUMMARY: The effect of new interventions on the gastrointestinal outcomes studied so far is favourable. Future studies should address the effect on other gastrointestinal parameters.

PMID: 28787381 [PubMed - as supplied by publisher]

The SEeMORE strategy: single-tube electrophoresis analysis-based genotyping to detect monogenic diseases rapidly and effectively from conception until birth.

Clin Chem Lab Med. 2017 Aug 08;:

Authors: Cariati F, Savarese M, D'Argenio V, Salvatore F, Tomaiuolo R

Abstract
BACKGROUND: The development of technologies that detect monogenic diseases in embryonic and fetal samples are opening novel diagnostic possibilities for preimplantation genetic diagnosis (PGD) and prenatal diagnosis (PND) thereby changing laboratory practice. Molecular diagnostic laboratories use different workflows for PND depending on the disease, type of biological sample, the presence of one or more known mutations, and the availability of the proband. Paternity verification and contamination analysis are also performed. The aim of this study was to test the efficacy of a single workflow designed to optimize the molecular diagnosis of monogenic disease in families at-risk of transmitting a genetic alteration.
METHODS: We used this strategy, which we designated "SEeMORE strategy" (Single-tube Electrophoresis analysis-based genotyping to detect MOnogenic diseases Rapidly and Effectively from conception to birth). It consists of a multiplex PCR that simultaneously carries out linkage analysis, direct analysis, maternal contamination and parenthood testing. We analyzed samples from previously diagnosed families for PND (cystic fibrosis or Duchenne muscular dystrophy) without, however, knowing the results.
RESULTS: The results obtained with the SEeMORE strategy concurred with those obtained with traditional PND. In addition, this strategy has several advantages: (i) use of one or a few cells; (ii) reduction of the procedure to 1 day; and (iii) a reduction of at least 2-3-fold of the analytic cost.
CONCLUSIONS: The SEeMORE strategy is effective for the molecular diagnosis of monogenic diseases, irrespective of the amount of starting material and of the disease mutation, and can be used for PND and PGD.

PMID: 28787268 [PubMed - as supplied by publisher]

How can the cystic fibrosis respiratory microbiome influence our clinical decision-making?

Curr Opin Pulm Med. 2017 Aug 03;:

Authors: Rogers GB, Bruce KD, Hoffman LR

Abstract
PURPOSE OF REVIEW: Almost 15 years have now passed since bacterial community profiling techniques were first used to analyse respiratory samples from people with cystic fibrosis. Since then, many different analytical approaches have been used to try to better understand the contribution of the cystic fibrosis lung microbiota to disease, with varying degrees of success. We examine the extent to which cystic fibrosis respiratory microbiome research has been successful in informing clinical decision-making, and highlight areas that we believe have the potential to yield important insight.
RECENT FINDINGS: Recent research on the cystic fibrosis lung microbiome can be broadly divided into efforts to better characterize microbiota composition, particularly relative to key clinical events, and attempts to understand the cystic fibrosis lung microbiology as an interactive microbial system. The latter, in particular, has led to the development of a number of models in which microbiome-mediated processes precipitate clinical events.
SUMMARY: Growing technological sophistication is enabling increasingly detailed microbiological data to be generated from cystic fibrosis respiratory samples. However, translating these data into clinically useful measures that accurately predict outcomes and guide treatments remains a formidable challenge. The development of systems biology approaches that enable the integration of complex microbiome and host-derived data provide an exciting opportunity to address this goal.

PMID: 28786882 [PubMed - as supplied by publisher]

Pediatric lung transplantation and end of life care in cystic fibrosis: Barriers and successful strategies.

Pediatr Pulmonol. 2017 Aug 08;:

Authors: Dellon E, Goldfarb SB, Hayes D, Sawicki GS, Wolfe J, Boyer D

Abstract
Pediatric lung transplantation has advanced over the years, providing a potential life-prolonging therapy to patients with cystic fibrosis. Despite this, many challenges in lung transplantation remain and result in worse outcomes than other solid organ transplants. As CF lung disease progresses, children and their caregivers are often simultaneously preparing for lung transplantation and end of life. In this article, we will discuss the current barriers to success in pediatric CF lung transplantation as well as approaches to end of life care in this population.

PMID: 28786560 [PubMed - as supplied by publisher]

Small Colony Variants of Pseudomonas aeruginosa Display Heterogeneity in Inhibiting Aspergillus fumigatus Biofilm.

Mycopathologia. 2017 Aug 07;:

Authors: Anand R, Moss RB, Sass G, Banaei N, Clemons KV, Martinez M, Stevens DA

Abstract
Pseudomonas aeruginosa and Aspergillus fumigatus are major microbes in cystic fibrosis (CF). We reported non-mucoid P. aeruginosa isolates more inhibitory to A. fumigatus than mucoid ones. Another CF P. aeruginosa phenotype, small colony variants (SCVs), is an unknown factor in intermicrobial competition with A. fumigatus. Clinical SCV isolates and reference CF non-mucoid isolate (Pa10, producing normal-sized colonies) were compared. Live cells of P. aeruginosa or filtrates from P. aeruginosa planktonic or biofilm cultures were co-incubated with A. fumigatus growing under conditions allowing biofilm formation or with preformed biofilm. Metabolic activity of A. fumigatus biofilm was then measured. When necessary, assays were done after adjustment for growth differences by adding fresh medium to the planktonic culture filtrate. Pyoverdine determinations were performed spectrophotometrically on the planktonic culture filtrates. In all experimental conditions (live cells and planktonic or biofilm culture filtrates of P. aeruginosa versus A. fumigatus biofilm formation or preformed biofilm), three SCV isolates were less inhibitory than Pa10, two equal or more inhibitory. Adjusting planktonic culture filtrates for growth differences showed SCV inhibition differences variably related to growth or deficient inhibitor production. Studies suggested the principal P. aeruginosa inhibitor to be pyoverdine. SCV isolates appear heterogeneous in their capacity to inhibit A. fumigatus biofilm. SCV isolates can be important in the CF microbiome, because they are capable of intermicrobial inhibition.

PMID: 28785939 [PubMed - as supplied by publisher]

E-Liquid Autofluorescence can be used as a Marker of Vaping Deposition and Third-Hand Vape Exposure.

Sci Rep. 2017 Aug 07;7(1):7459

Authors: Davis ES, Sassano MF, Goodell H, Tarran R

Abstract
In the past 5 years, e-cigarette use has been increasing rapidly, particularly in youth and young adults. Due to the novelty of e-cigarettes (e-cigs) and e-cigarette liquids (e-liquids), research on their chemo-physical properties is still in its infancy. Here, we describe a previously unknown and potentially useful property of e-liquids, namely their autofluorescence. We performed an emission scan at 9 excitation wavelengths common to fluorescent microscopy and found (i) that autofluorescence differs widely between e-liquids, (ii) that e-liquids are most fluorescent in the UV range (between 350 and 405 nm) and (iii) fluorescence intensity wanes as the emission wavelength increases. Furthermore, we used the autofluorescence of e-liquids as a marker for tracking e-cig aerosol deposition in the laboratory. Using linear regression analysis, we were able to quantify the deposition of a "vaped" e-liquid onto hard surfaces. Using this technique, we found that every 70 mL puff of an e-cigarette deposited 0.019% e-liquid (v/v) in a controlled environment. Finally, we vaped a surface in the laboratory and used our method to detect e-cig aerosol third-hand exposure. In conclusion, our data suggest that e-cigarette autofluorescence can be used as a marker of e-cigarette deposition.

PMID: 28785072 [PubMed - in process]

Correction of CFTR function in nasal epithelial cells from cystic fibrosis patients predicts improvement of respiratory function by CFTR modulators.

Sci Rep. 2017 Aug 07;7(1):7375

Authors: Pranke IM, Hatton A, Simonin J, Jais JP, Le Pimpec-Barthes F, Carsin A, Bonnette P, Fayon M, Stremler-Le Bel N, Grenet D, Thumerel M, Mazenq J, Urbach V, Mesbahi M, Girodon-Boulandet E, Hinzpeter A, Edelman A, Sermet-Gaudelus I

Abstract
Clinical studies with modulators of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) protein have demonstrated that functional restoration of the mutated CFTR can lead to substantial clinical benefit. However, studies have shown highly variable patient responses. The objective of this study was to determine a biomarker predictive of the clinical response. CFTR function was assessed in vivo via nasal potential difference (NPD) and in human nasal epithelial (HNE) cultures by the response to Forskolin/IBMX and the CFTR potentiator VX-770 in short-circuit-current (∆IscF/I+V) experiments. CFTR expression was evaluated by apical membrane fluorescence semi-quantification. Isc measurements discriminated CFTR function between controls, healthy heterozygotes, patients homozygous for the severe F508del mutation and patients with genotypes leading to absent or residual function. ∆IscF/I+V correlated with CFTR cellular apical expression and NPD measurements. The CFTR correctors lumacaftor and tezacaftor significantly increased the ∆IscF/I+V response to about 25% (SEM = 4.4) of the WT-CFTR level and the CFTR apical expression to about 22% (SEM = 4.6) of the WT-CFTR level in F508del/F508del HNE cells. The level of CFTR correction in HNE cultures significantly correlated with the FEV1 change at 6 months in 8 patients treated with CFTR modulators. We provide the first evidence that correction of CFTR function in HNE cell cultures can predict respiratory improvement by CFTR modulators.

PMID: 28785019 [PubMed - in process]

CFTR reduces microtubule-dependent Campylobacter jejuni invasion.

Infect Immun. 2017 Aug 07;:

Authors: Kido J, Shimohata T, Amano S, Hatayama S, Nguyen AQ, Sato Y, Kanda Y, Tentaku A, Fukushima S, Nakahashi M, Uebanso T, Mawatari K, Takahashi A

Abstract
Campylobacter jejuni (C. jejuni) is gastroenteritis inducible food-born pathogen. Invasion and adhesion process are essential for leading gastroenteritis in C. jejuni infection process. As against bacterial strategy for efficacy invasion and adhesion, mucosal layer play a key role in defense systems, which modulated by several ion channels and transporters mediated water flux on the intestine. Cystic fibrosis transmembrane conductance regulator (CFTR) play the main role in waterfulux in intestine, and it closely related with bacterial clearance. We previously reported that C. jejuni infection suppresses CFTR channel activity in intestinal epithelial cells, however the mechanism and importance of this suppression is unclear. This study seeks to elucidate the role of CFTR in C. jejuni-infection. Using HEK293 cells that stably express wild type and mutated CFTR, we found that CFTR attenuated C. jejuni invasion, it was not involved bacterial adhesion or intracellular survival but associated with microtubule-dependent cellular transport. Moreover we revealed that CFTR attenuated function of microtubule motor protein but not microtubule stability, which causes inhibition of C. jejuni-invasion. Meanwhile, the CFTR mutant G551D-CFTR, which has defects in channel activity, suppressed C. jejuni-invasion, whereasΔF508-CFTR, which has defects in maturation, did not suppress, suggesting that CFTR suppression of C. jejuni-invasion is related to CFTR maturation but not channel activity.Taken together, mature CFTR inhibited C. jejuni invasion by regulating microtubule-mediated pathways. We suggest that CFTR plays a critical role in cellular defenses against C. jejuni-invasion, and CFTR suppression may be an initial step in promoting cellular invasion during C. jejuni-infection.

PMID: 28784926 [PubMed - as supplied by publisher]

17β-estradiol dysregulates innate immune responses to Pseudomonas aeruginosa respiratory infection and is modulated by estrogen receptor antagonism.

Infect Immun. 2017 Aug 07;:

Authors: Abid S, Xie S, Bose M, Shaul PW, Terada LS, Brody SL, Thomas PJ, Katzenellenbogen JA, Kim SH, Greenberg DE, Jain R

Abstract
Rationale: Females have a more severe clinical course than males in several inflammatory lung conditions. Notably, females with cystic fibrosis (CF) suffer worse outcomes, particularly in the setting of Pseudomonas aeruginosa infection. Sex hormones are implicated in experimental and clinical studies, however immune mechanisms responsible for this sex-based disparity are unknown and the specific sex hormone target for therapeutic manipulation has not been identified.Objectives: Assess mechanisms behind the impact of female sex hormones on host immune responses to P.aeruginosa.Methods: Wild type and CF mice, hormone manipulated and inoculated with P. aeruginosa, were examined for outcomes and inflammatory responses. Neutrophils isolated from mice and human subjects were tested for responses to P. aeruginosaResults: Female mice inoculated with P. aeruginosa died earlier and showed slower bacterial clearance than males (p < 0.0001). Ovariectomized females supplemented with 17β-estradiol succumbed to P. aeruginosa challenge earlier than progesterone- or vehicle-supplemented mice (p = 0.0003). 17β-estradiol-treated ovariectomized female mice demonstrated increased lung levels of inflammatory cytokines, and when rendered neutropenic, the mortality difference was abrogated. Neutrophils treated with 17β-estradiol demonstrated an enhanced oxidative burst, but decreased P. aeruginosa killing and earlier cell necrosis. The estrogen receptor (ER) antagonist, ICI 182,780, improved survival in female mice infected with P. aeruginosa and restored neutrophil function.Conclusions: ER antagonism rescues estrogen-mediated neutrophil dysfunction and improves survival in response to P. aeruginosa. ER-mediated processes may explain the sex-based mortality gap in CF and other inflammatory lung illnesses, and ER blockade represents a rationale therapeutic strategy.

PMID: 28784925 [PubMed - as supplied by publisher]

Pharmacokinetic-Pharmacodynamic Target Attainment Analyses to Determine Optimal Dosing of Ceftazidime-Avibactam for the Treatment of Acute Pulmonary Exacerbations in Cystic Fibrosis.

Antimicrob Agents Chemother. 2017 Aug 07;:

Authors: Bensman TJ, Wang J, Jayne J, Fukushima L, Rao AP, D'Argenio DZ, Beringer PM

Abstract
Background: Acute pulmonary exacerbations (APE) involving Pseudomonas aeruginosa are associated with increased morbidity and mortality in CF. Drug resistance is a significant challenge to treatment. Ceftazidime-avibactam (CZA) demonstrates excellent in vitro activity against isolates recovered from CF; including drug-resistant strains. Altered pharmacokinetics (PK) of several beta-lactam antibiotics have been reported in CF. Therefore, this study sought to characterize the PK of CZA and perform target-attainment analyses to determine the optimal treatment regimen.Methods: The PK of CZA was determined from 12 adult CF patients administered 3 intravenous doses of 2.5g q8h infused over 2h. Population modeling utilized the maximum-likelihood expectation method. Monte Carlo simulations determined the probability of target attainment (PTA). Exposure targets of free-ceftazidime (CAZ) above MIC (fT>MIC), and free-avibactam (AVI) above a 1 mg/L threshold concentration (fT>Ct) were evaluated. Published CAZ and CZA MIC distributions were incorporated to evaluate cumulative response probabilities.Results: CAZ and AVI were best described by 1-compartment models. Total body clearances (CAZ CLt: 7.53 ± 1.28 L/h, AVI CLt: 12.30 ± 1.96 L/h) and volumes of distribution (CAZ Vd: 18.80 ± 6.54 L, AVI Vd: 25.30 ± 4.43 L) were broadly similar to published healthy adults. CAZ achieved a PTA (50% fT>MIC) > 0.9 for MICs ≤ 16 mg/L and AVI PTA (50% fT>Ct of 1.0) >0.99. The overall likelihood of treatment response was 0.82 with CZA vs. 0.42 for CAZ.Conclusions: These data demonstrate improved pharmacodynamics of CZA in comparison with CAZ and provide guidance on optimal dosing of (CZA) for future studies.

PMID: 28784670 [PubMed - as supplied by publisher]

In cellulo analyses of the p.Val322Ala mutation on the CFTR protein conformation and activity.

C R Biol. 2017 Aug 04;:

Authors: Farhat R, El-Seedy A, Sari AIP, Norez C, Pasquet MC, Becq F, Kitzis A, Ladevèze V

Abstract
Cystic fibrosis is caused by mutations on the Cystic Fibrosis Transmembrane conductance Regulator gene (CFTR). Exonic mutations may have variable effect on the CFTR protein and may alter the normal localization of CFTR on the apical membrane of epithelial cells or/and its function as a chloride channel. Identifying the effect of a missense mutation can be a first step in helping the medical counseling and the therapeutic strategies. In this study, the effect of the c.965T>C exon 8 mutation that induces a valine-to-alanine substitution (p.Val322Ala) into the fifth helix of the first membrane spanning domain was determined by in silico and in cellulo analyses. The confocal microscopy analyses and functionality test showed, in the tested cell line, that this mutation should have no impact on the function of the p.Val322Ala-CFTR protein. However, regarding the importance of this Val322 amino acid in the CFTR protein, precautions and individual follow-up are still required when c.965T>C if associated with other mutation(s).

PMID: 28784578 [PubMed - as supplied by publisher]

Intra-session and inter-session variability of nitric oxide pulmonary diffusing capacity in adults with cystic fibrosis.

Respir Physiol Neurobiol. 2017 Aug 03;:

Authors: Radtke T, Benden C, Maggi-Beba M, Kriemler S, van der Lee I, Dressel H

Abstract
We evaluated the intra-session and inter-session variability of the diffusing capacity of nitric oxide (DLNO), carbon monoxide (DLCO), membrane diffusing capacity for carbon monoxide (DMCO) and pulmonary capillary blood volume (Vc) in patients with cystic fibrosis (CF). Patients performed single-breath diffusing capacity measurements during all of 3 consecutive study visits. Precision of gas diffusing parameters was quantified by within- subject standard deviation (SDws) and coefficient of variation (CV). Intra-session and inter-session reproducibility was determined by SDws*2.77. 15 clinically stable patients were included. The intra-session precision of gas diffusing parameters improved over the study visits. The inter-session SDws for DLNO, DLCO, DMCO, and Vc was 4.8, 1.3, 2.4, and 4.3, respectively. Reproducibility was 13.3, 3.8, 6.7 and 12.0mL.min(-1).mmHg(-1); CV was 4.4, 4.7, 4.4 and 5.8%, respectively. The intra-session variability of DLNO, DLCO, DMCO and Vc improves with breath-hold maneuver training in test-naïve patients with CF, indicating a learning effect. Inter-session reproducibility data are lower than those previously reported in healthy subjects.

PMID: 28782664 [PubMed - as supplied by publisher]

What's unique about acute pancreatitis in children: risk factors, diagnosis and management.

Nat Rev Gastroenterol Hepatol. 2017 Jun;14(6):366-372

Authors: Husain SZ, Srinath AI

Abstract
Pancreatitis in children is an appreciable problem that has become increasingly prevalent. This Review covers the principles related to the definitions, epidemiology, risk factors, diagnosis and management of acute pancreatitis in children and identifies features that are unique among children. Additionally, knowledge gaps related to management principles are identified.

PMID: 28293024 [PubMed - indexed for MEDLINE]

Biomarkers Predictive of Exacerbations in the SPIROMICS and COPDGene Cohorts.

Am J Respir Crit Care Med. 2017 Feb 15;195(4):473-481

Authors: Keene JD, Jacobson S, Kechris K, Kinney GL, Foreman MG, Doerschuk CM, Make BJ, Curtis JL, Rennard SI, Barr RG, Bleecker ER, Kanner RE, Kleerup EC, Hansel NN, Woodruff PG, Han MK, Paine R, Martinez FJ, Bowler RP, O'Neal WK, COPDGene and SPIROMICS Investigators ‡

Abstract
RATIONALE: Chronic obstructive pulmonary disease exacerbations are associated with disease progression, higher healthcare cost, and increased mortality. Published predictors of future exacerbations include previous exacerbation, airflow obstruction, poor overall health, home oxygen use, and gastroesophageal reflux.
OBJECTIVES: To determine the value of adding blood biomarkers to clinical variables to predict exacerbations.
METHODS: Subjects from the SPIROMICS (Subpopulations and Intermediate Outcomes Measures in COPD Study) (n = 1,544) and COPDGene (Genetic Epidemiology of COPD) (n = 602) cohorts had 90 plasma or serum candidate proteins measured on study entry using Myriad-RBM multiplex panels. We defined total exacerbations as subject-reported worsening in respiratory health requiring therapy with corticosteroids and/or antibiotics, and severe exacerbations as those leading to hospitalizations or emergency room visits. We assessed retrospective exacerbations during the 12 months before enrollment and then documented prospective exacerbations in each cohort. Exacerbations were modeled for biomarker associations with negative binomial regression including clinical covariates (age, sex, percent predicted FEV1, self-reported gastroesophageal reflux, St. George's Respiratory Questionnaire score, smoking status). We used the Stouffer-Liptak test to combine P values for metaanalysis.
MEASUREMENTS AND MAIN RESULTS: Between the two cohorts, 3,471 total exacerbations (1,044 severe) were reported. We identified biomarkers within each cohort that were significantly associated with a history of exacerbation and with a future exacerbation, but there was minimal replication between the cohorts. Although established clinical features were predictive of exacerbations, of the blood biomarkers only decorin and α2-macroglobulin increased predictive value for future severe exacerbations.
CONCLUSIONS: Blood biomarkers were significantly associated with the occurrence of exacerbations but were not robust between cohorts and added little to the predictive value of clinical covariates for exacerbations.

PMID: 27579823 [PubMed - indexed for MEDLINE]

Validation of a Cystic Fibrosis Medication Knowledge Questionnaire.

Glob Pediatr Health. 2017;4:2333794X17719803

Authors: FitzPatrick B, Hawboldt J, Jane Smith M, Lee T

Abstract
Low adherence to cystic fibrosis (CF) treatment is associated with poor health outcomes, while knowledge of the disease and medication regimen can positively influence adherence. This study's purpose was to develop and validate a questionnaire to help determine CF medication knowledge of pediatric patients and caregivers. Our questionnaire had 37 items: 22 selected-response and 15 open-response questions. We used validation processes from the Standards for Educational and Psychological Testing. CF experts analyzed validity evidence based on content. Then, the questionnaire was field tested with 17 pediatric patients and 18 caregivers. The correlation between age and medication knowledge was medium (r = .33), but was not significant (P = .189). Cronbach's α for the overall test was .84. Participants thought the questionnaire was important and suitable, with a few minor suggestions to improve wording. Strong validity evidence indicates the questionnaire could be used to assess medication knowledge and allow more personalized education to improve adherence.

PMID: 28781991 [PubMed]

Serotypes and antibiotic susceptibility of Streptococcus pneumoniae isolated from hospitalized patients with community-acquired pneumonia in Italy.

SAGE Open Med. 2017;5:2050312117720058

Authors: Di Pasquale M, Aliberti S, Azzari C, Moriondo M, Nieddu F, Blasi F, Mantero M

Abstract
BACKGROUND: Pneumonia remain an important public health problem. The primary objective was to determine the proportion of community-acquired pneumonia that is attributable to Streptococcus pneumoniae infection; secondary objectives were the description of community-acquired pneumonia attributable to Streptococcus pneumoniae according to socio-demographic and clinical variables, the clinical evolution of community-acquired pneumonia and the description of the serotype distribution of vaccine-preventable disease and antibiotic resistance rate of pneumococcal infections.
METHODS: An observational, prospective study was conducted on consecutive patients coming from the community, who were hospitalized with pneumonia. Data on admission, at discharge and 30 days after discharge were collected. Logistic regression models were used to evaluate the risk factors independently associated with pneumococcal pneumonia.
RESULTS: Among the 193 patients enrolled in the study, the etiology of community-acquired pneumonia was identified in 60 patients (33%) and 35 (18%) of evaluable patients had community-acquired pneumonia due to Streptococcus pneumoniae. Of all clinical characteristics, if no previous antibiotic treatment was performed, there was a 13-fold higher risk of presenting community-acquired pneumonia due to Streptococcus pneumoniae (odds ratio, 12.9; 95% confidence interval, 1.42-117.9). Moreover, the most frequent isolated serotypes were 35F, 3 and 24 (29%, 23% and 16%, respectively).
CONCLUSION: The most frequent serotypes in pneumococcal community-acquired pneumonia are 35F, 3, 24, 6 and 7A, and thus almost 50% of Streptococcus pneumoniae strains could be covered by pneumococcal conjugate vaccine 13 in adult patients with risk factors for pneumococcal infections.

PMID: 28781877 [PubMed]