Positive mental health and wellbeing in adolescents with cystic fibrosis.

J Psychosom Res. 2018 Nov 27;:

Authors: Cronly J, Savage E

PMID: 30579558 [PubMed - as supplied by publisher]

Cluster and CART analyses identify large subgroups of adults with cystic fibrosis at low risk of 10-year death.

Eur Respir J. 2018 Dec 21;:

Authors: Burgel PR, Lemonnier L, Dehillotte C, Sykes J, Stanojevic S, Stephenson AL, Paillasseur JL

Abstract
Our goal was to identify subgroups of cystic fibrosis (CF) adults at low risk of death within 10 years.Factor analysis for mixed data followed by Ward's cluster analysis were conducted using 25 variables from 1572 French CF adults in 2005. Rates of death by subgroups were analysed over 10 years. An algorithm was developed using classification and regression tree (CART) to provide rules for the identification of subgroups of CF adults with low rates of death within 10 years. This algorithm was validated in 1376 Canadian CF adults.Seven subgroups were identified by cluster analysis in French CF adults, including two subgroups with low (∼5%) rates of death at 10 years: one subgroup (22% of patients) was composed of patients with non-classic CF, the other subgroup (17% of patients) was composed of patients with classic CF but low rates of P. aeruginosa infection and diabetes. An algorithm based on CART analysis of data in 2005 allowed to identify most French adults with low rates of death. When tested using data from Canadian CF adults in 2005, the algorithm identified 287/1376 (21%) patients at low risk (10-year death, 7.7%).Large subgroups of CF adults share low risk of 10-year mortality.

PMID: 30578399 [PubMed - as supplied by publisher]

Clinical expression of cystic fibrosis in a large cohort of Italian siblings.

BMC Pulm Med. 2018 Dec 22;18(1):196

Authors: Terlizzi V, Lucarelli M, Salvatore D, Angioni A, Bisogno A, Braggion C, Buzzetti R, Carnovale V, Casciaro R, Castaldo G, Cirilli N, Collura M, Colombo C, Di Lullo AM, Elce A, Lucidi V, Madarena E, Padoan R, Quattrucci S, Raia V, Seia M, Termini L, Zarrilli F

Abstract
BACKGROUND: A clinical heterogeneity was reported in patients with Cystic Fibrosis (CF) with the same CFTR genotype and between siblings with CF.
METHODS: We investigated all clinical aspects in a cohort of 101 pairs of siblings with CF (including 6 triplets) followed since diagnosis.
RESULTS: Severe lung disease had a 22.2% concordance in sib-pairs, occurred early and the FEV1% at 12 years was predictive of the severity of lung disease in the adulthood. Similarly, CF liver disease occurred early (median: 15 years) and showed a concordance of 27.8% in sib-pairs suggesting a scarce contribution of genetic factors; in fact, only 2/15 patients with liver disease in discordant sib-pairs had a deficiency of alpha-1-antitrypsin (a known modifier gene of CF liver phenotype). CF related diabetes was found in 22 pairs (in 6 in both the siblings). It occurred later (median: 32.5 years) and is strongly associated with liver disease. Colonization by P. aeruginosa and nasal polyposis that required surgery had a concordance > 50% in sib-pairs and were poorly correlated to other clinical parameters. The pancreatic status was highly concordant in pairs of siblings (i.e., 95.1%) but a different pancreatic status was observed in patients with the same CFTR mutations. This suggests a close relationship of the pancreatic status with the "whole" CFTR genotype, including mutations in regulatory regions that may modulate the levels of CFTR expression. Finally, a severe course of CF was evident in a number of patients with pancreatic sufficiency.
CONCLUSIONS: Physicians involved in care of patients with CF and in genetic counseling must be aware of the clinical heterogeneity of CF even in sib-pairs that, at the state of the art, is difficult to explain.

PMID: 30577776 [PubMed - in process]

Acute Cellular Rejection and Infection Rates in Alemtuzumab vs Traditional Induction Therapy Agents for Lung and Heart Transplantation: A Systematic Review and Meta-analysis.

Transplant Proc. 2018 Dec;50(10):3739-3747

Authors: Li KHC, Ho JCS, Recaldin B, Gong M, Ho J, Li G, Liu T, Wu WKK, Wong MCS, Xia Y, Dong M, Tse G, International Health Informatics Study (IHIS) Network

Abstract
BACKGROUND AND OBJECTIVES: Heart and lung transplantation is a high-risk procedure, requiring intensive immunosuppressive therapy for preventing organ rejection. Alemtuzumab, a CD52-specific monoclonal antibody, is increasingly used for induction therapy compared with conventional agents. However, there has been no systematic review comparing its efficacy with traditional therapeutic drugs.
METHODS: PubMed and EMBASE were searched to October 1, 2017, for articles on alemtuzumab in cardiothoracic transplant surgery. Of the 433 studies retrieved, 8 were included in the final meta-analysis.
RESULTS: In lung transplantation, alemtuzumab use was associated with lower odds of acute cellular rejection compared with antithymocyte globulin (odds ratio [OR], 0.21; 95% CI, 0.11-0.40; P < .001), lower acute rejection rates (OR, 0.12; 95% CI, 0.03-0.55; P < .01), and lower infection rates (OR, 0.69; 95% CI, 0.35-1.36; P = .33) when compared with basiliximab. Multivariate meta-regression analysis found that mean age, male sex, single lung transplant, double lung transplant, cytomegalovirus or Epstein-Barr virus status, idiopathic pulmonary fibrosis, cystic fibrosis, and mean ischemic time did not significantly influence acute rejection outcomes. For heart transplantation, alemtuzumab use was associated with lower acute rejection rates when compared with tacrolimus (OR, 0.44; 95% CI, 0.30-0.66; P < .001).
CONCLUSIONS: Alemtuzumab use was associated with lower rejection rates when compared with conventional induction therapy agents (antithymocyte globulin, basiliximab, and tacrolimus) in heart and lung transplantation. However, this was based on observational studies. Randomized controlled trials are needed to verify its clinical use.

PMID: 30577265 [PubMed - in process]

Survival After Lung Transplant for Cystic Fibrosis in Italy: A Single Center Experience With 20 Years of Follow-up.

Transplant Proc. 2018 Dec;50(10):3732-3738

Authors: Savi D, Mordenti M, Bonci E, Troiani P, Giordani B, D'Alù V, Bertasi S, Cimino G, Rossi P, Poggi C, Palange P, Quattrucci S

Abstract
OBJECTIVES: Lung transplantation is currently the only treatment for end-stage respiratory failure in patients with cystic fibrosis (CF). In this study we retrospectively analyzed our experience since the start of the transplantation program in 1996 with focus on survival analysis.
METHODS: All patients with CF who underwent lung transplant at our center were included (1996-2016). Survival analysis after lung transplant was performed using the Kaplan-Meier estimate, comparing by sex and by 4 eras (1996-2000, 2001-2005, 2006-2010, and 2011-2016).
RESULTS: In a 20-year period, 243 patients with CF were listed for lung transplant; 123 patients (61 male, 62 female) underwent transplant, and 85 died while waiting for donor organs. The mean (SD) and median age at transplant was 27.7 (8.7) years and 26.9 years (range, 9.1 - 52.1 years), respectively. Mean (SD) forced expiratory volume in the first second was 27.6 (9.7)% predicted; 115 patients (92.0%) were pancreatic insufficient, and 43 patients (34.0%) had CF-related diabetes. Removing patients with CF who died within the first 3 postoperative months, the mean (SD) and median survival after transplant were 8.2 (5.7) years and 7.5 years (range, 3 months-20 years), respectively. Overall post-lung transplant 1-year survival was 93.6%, 5-year survival was 71.4%, 10-year survival was 53.6%, 15-year survival was 36.7%, and 20-year survival was 31.6%. We found no difference in survival between sex (P = .22) and among the 4 eras (P = .56).
CONCLUSIONS: Survival after lung transplant in our single center is similar to international data.

PMID: 30577264 [PubMed - in process]

Acute Cellular Rejection and Infection Rates in Alemtuzumab vs Traditional Induction Therapy Agents for Lung and Heart Transplantation: A Systematic Review and Meta-analysis.

Transplant Proc. 2018 Dec;50(10):3723-3731

Authors: Li KHC, Ho JCS, Recaldin B, Gong M, Ho J, Li G, Liu T, Wu WKK, Wong MCS, Xia Y, Dong M, Tse G, International Health Informatics Study Network

Abstract
BACKGROUND AND OBJECTIVES: Heart and lung transplantation is a high-risk procedure requiring intensive immunosuppressive therapy for preventing organ rejection. Alemtuzumab, a CD52-specific monoclonal antibody, is increasingly used for induction therapy compared with conventional agents. However, there has been no systematic review comparing its efficacy with traditional therapeutic drugs.
METHODS: PubMed and EMBASE were searched to October 1, 2017, for articles on alemtuzumab in cardiothoracic transplant surgery. Of the 433 studies retrieved, 8 were included in the final meta-analysis.
RESULTS: In lung transplantation, alemtuzumab use was associated with lower odds of acute cellular rejection compared with antithymocyte globulin (odds ratio [OR], 0.21; 95% CI, 0.11-0.40; P < .001), lower acute rejection rates (OR, 0.12; 95% CI, 0.03-0.55; P < .01), and infection rates (OR, 0.69; 95% CI, 0.35-1.36; P = .33) when compared with basiliximab. Multivariate meta-regression analysis found that mean age, male sex, single lung transplant, double lung transplant, cytomegalovirus or Epstein-Barr virus status, idiopathic pulmonary fibrosis, cystic fibrosis, and mean ischemic time did not significantly influence acute rejection outcomes. For heart transplantation, alemtuzumab use was associated with lower acute rejection rates when compared with tacrolimus (OR, 0.44; 95% CI, 0.30-0.66; P < .001).
CONCLUSIONS: Alemtuzumab use was associated with lower rejection rates when compared with conventional induction therapy agents (antithymocyte globulin, basiliximab, and tacrolimus) in heart and lung transplantation. However, this was based on observational studies. Randomized controlled trials are needed to verify its clinical use.

PMID: 30577263 [PubMed - in process]

Vaporized E-Cigarette Liquids Induce Ion Transport Dysfunction in Airway Epithelia.

Am J Respir Cell Mol Biol. 2018 Dec 21;:

Authors: Lin VY, Fain MD, Jackson PL, Berryhill TF, Wilson LS, Mazur M, Barnes SJ, Blalock JE, Raju SV, Rowe SM

Abstract
Cigarette smoking is associated with chronic obstructive pulmonary disease and chronic bronchitis. Acquired ion transport abnormalities, including CFTR dysfunction, caused by cigarette smoking have been proposed as potential mechanisms for mucus obstruction in chronic bronchitis. Although popular and perceived to be safe, it remains unclear if e-cigarette use harms the airways via mechanisms altering ion transport. Here, we sought to determine if e-cigarette vapor, like cigarette smoke, had the potential to induce acquired CFTR dysfunction, and to what degree. Electrophysiologic methods demonstrated reduced chloride transport caused by vaporized e-cigarette liquid or vegetable glycerin at various exposures (30 min: 57.2% and 14.4% respectively, vs. control, p<0.0001), but not by unvaporized liquid (60 min: 17.6% vs. untreated), indicating that thermal degradation of these products is required to induce the observed defects. We also observed reduced ATP-dependent responses (-10.8±3.0 vs. -18.8±5.1 µA/cm2 control) and ENaC activity (95.8% reduction) in primary HBE cells after 5 min, suggesting exposures dramatically inhibit epithelial ion transport beyond CFTR, even without diminished transepithelial resistance or cytotoxicity. Vaporizing e-cigarette liquid produced reactive aldehydes including acrolein (shown to induce acquired CFTR dysfunction), as quantified by mass spectrometry, demonstrating that respiratory toxicants in cigarette smoke can also be found in e-cigarette vapor (30 min: air 224.5±15.99, unvaporized liquid 284.8±35.03, vapor 54,468±3908 ng/mL, p<0.0001). E-cigarettes can induce ion channel dysfunction in airway epithelial cells, partly through acrolein production. These findings indicate a heretofore unknown toxicity of e-cigarette use known to be associated with chronic bronchitis onset and progression, and COPD severity.

PMID: 30576219 [PubMed - as supplied by publisher]

Six-minute walk, lung clearance index, and QOL in bronchiolitis obliterans and cystic fibrosis.

Pediatr Pulmonol. 2018 Dec 21;:

Authors: Gur M, Masarweh K, Toukan Y, Nir V, Bar-Yoseph R, Hanna M, Manor E, Hakim F, Bentur L

Abstract
INTRODUCTION: The 6-min walk test (6MWT) predicts outcome in pulmonary hypertension. Recently, its use was reported in both cystic fibrosis (CF) and bronchiolitis obliterans (BO). While the 6MWT is a simple, non-invasive and inexpensive tool, lung clearance index (LCI) measurement requires expensive equipment and expertise. We aimed to evaluate 6MWT in BO and CF, and to compare to MBW (multiple breath washout), pulmonary function tests and quality of life (QOL).
METHODS: A prospective single center study assessing 6MWT, MBW, spirometry, whole-body plethysmography and QOL (SF-36 questionnaire) in BO and CF patients and correlations between them.
RESULTS: Thirty-three BO patients and 37 CF patients. LCI was significantly higher in BO (12.4 ± 4.2 vs 10.5 ± 3.4, P = 0.044) while FEF 25-75% was significantly lower in BO (43.9 ± 24.4 vs 60.8 ± 30.8, P = 0.014). 6MWD was 474.8 ± 76.3 in BO and 506.6 ± 70 in CF (P > 0.05). There was no correlation between 6MWD and LCI in these small study groups There were few correlation between spirometry prameters and 6MWD. In CF, SF-36 scores correlated with pulmonary functions.
CONCLUSIONS: The 6MWT is an easy-to-perform test that may be helpful in chronic lung diseases in regions with limited resources. However,with the current limited data, 6MWT cannot replace LCI or spirometry as a marker of disease progression. Is is suggested that, together with QOL, the 6MWT may provide a global estimation of the physiological and general well-being of these patients. Further larger multi-center studies are warranted to evaluate the correlations of 6MWT with pulmonary physiology parameters in various chronic diseases.

PMID: 30575341 [PubMed - as supplied by publisher]

Ventilation inhomogeneity is associated with OGTT-derived insulin secretory defects in cystic fibrosis.

Pediatr Pulmonol. 2018 Dec 21;:

Authors: Colombo C, Alicandro G, Gambazza S, Mileto P, Mari A, Grespan E, Nazzari E, Russo MC, Battezzati A

Abstract
Progressive deterioration of β-cell function is the main mechanism underlying diabetes in cystic fibrosis (CF). Diabetes negatively impacts the clinical status of CF patients years before its onset. We aimed to evaluate if OGTT-derived indices of β-cell function are associated with early markers of lung disease. We carried out a cross-sectional study on 80 CF patients who performed OGTT, spirometry, and nitrogen-multiple breath washout test. β-cell glucose sensitivity and the insulinogenic indices were used as markers of β-cell function and first-phase insulin response to glucose stimulus. We used sex- and age-adjusted multiple linear regression models to estimate the association between OGTT-derived indices and lung function measures. An increment of β-cell glucose sensitivity equal to its interquartile range was associated with an increase in ppFEV1 of 7.6 points (95%CI: 0.8; 14.4) as well as with a decrease in LCI of -1.96 units (95%CI: -3.40; -0.51) and in Scond of -0.016 L-1 (95%CI: -0.026; -0.007). The corresponding figures for insulinogenic index were: 8.6 (95%CI: 3.4; 13.9) for ppFEV1 , -2.03 (95%CI: -3.13; -0.94) for LCI, and -0.014 L-1 (95%CI: -0.021; -0.071) for Scond . When adjusting also for 2-h plasma glucose, both β-cell glucose sensitivity and insulinogenic index remained inversely associated with Scond . Deterioration of β-cell function is related to early lung disease in young patients with mild to normal pulmonary function. This relationship is independent from hyperglycemia and mainly involves conductive airways.

PMID: 30575293 [PubMed - as supplied by publisher]

"If We Would Have Known": A Couple's Regret Over a Missed Opportunity to Have a Biological Child After Lung Transplantation.

J Patient Exp. 2018 Dec;5(4):320-322

Authors: Ladores S, Bray LA, Brown J

Abstract
Cystic fibrosis (CF) is a genetic, chronic disease that results in thickened secretions in the respiratory, gastrointestinal, and reproductive tracts. Over 95% of males with CF have congenital bilateral absence of the vas deferens causing infertility. This is a case study of a 29-year-old male who underwent a lung transplant after 8 months of oxygen dependency secondary to poor lung function. Approximately 1 year posttransplant, he and his wife decided that they wanted to start a family and consulted a fertility specialist who advised them to utilize donor sperm due to the teratogenic effects of posttransplant medications. Taken by surprise with this news, they expressed regret about the missed opportunity for pretransplant sperm aspiration and cryopreservation to conceive a biological child. He reported, "If we would have known, we would have made sure I [banked] my own [sperm]." This case study highlights a critical gap in CF comprehensive clinical care.

PMID: 30574555 [PubMed]

Cell Volume-Activated and Volume-Correlated Anion Channels in Mammalian Cells: Their Biophysical, Molecular, and Pharmacological Properties.

Pharmacol Rev. 2019 Jan;71(1):49-88

Authors: Okada Y, Okada T, Sato-Numata K, Islam MR, Ando-Akatsuka Y, Numata T, Kubo M, Shimizu T, Kurbannazarova RS, Marunaka Y, Sabirov RZ

Abstract
There are a number of mammalian anion channel types associated with cell volume changes. These channel types are classified into two groups: volume-activated anion channels (VAACs) and volume-correlated anion channels (VCACs). VAACs can be directly activated by cell swelling and include the volume-sensitive outwardly rectifying anion channel (VSOR), which is also called the volume-regulated anion channel; the maxi-anion channel (MAC or Maxi-Cl); and the voltage-gated anion channel, chloride channel (ClC)-2. VCACs can be facultatively implicated in, although not directly activated by, cell volume changes and include the cAMP-activated cystic fibrosis transmembrane conductance regulator (CFTR) anion channel, the Ca2+-activated Cl- channel (CaCC), and the acid-sensitive (or acid-stimulated) outwardly rectifying anion channel. This article describes the phenotypical properties and activation mechanisms of both groups of anion channels, including accumulating pieces of information on the basis of recent molecular understanding. To that end, this review also highlights the molecular identities of both anion channel groups; in addition to the molecular identities of ClC-2 and CFTR, those of CaCC, VSOR, and Maxi-Cl were recently identified by applying genome-wide approaches. In the last section of this review, the most up-to-date information on the pharmacological properties of both anion channel groups, especially their half-maximal inhibitory concentrations (IC50 values) and voltage-dependent blocking, is summarized particularly from the standpoint of pharmacological distinctions among them. Future physiologic and pharmacological studies are definitely warranted for therapeutic targeting of dysfunction of VAACs and VCACs.

PMID: 30573636 [PubMed - in process]

CFTR activation suppresses glioblastoma cell proliferation, migration and invasion.

Biochem Biophys Res Commun. 2018 Dec 17;:

Authors: Zhong X, Chen HQ, Yang XL, Wang Q, Chen W, Li C

Abstract
The aim of this study was to investigate the function of Cystic fibrosis transmembrane conductance regulator (CFTR) in human glioblastoma (GBM) cells. Data dining results of the Human Protein Atlas showed that low CFTR expression was associated with poor prognosis for GBM patients. We found that CFTR protein expression was lower in U87 and U251 GBM cells than that in normal humane astrocyte cells. CFTR activation significantly reduced GBM cell proliferation. In addition, CFTR activation significantly abrogated migration and invasion of GBM cells. Besides, CFTR activator Forskolin treatment markedly reduced MMP-2 protein expression. These effects of CFTR activation were significantly inhibited by CFTR inhibitor CFTRinh-172 pretreatment. Our findings suggested that JAK2/STAT3 signaling was involved in the anti-glioblastoma effects of CFTR activation. Moreover, CFTR overexpression in combination with Forskolin induced a synergistic anti-proliferative response in U87 cells. Overall, our findings demonstrated that CFTR activation suppressed GBM cell proliferation, migration and invasion likely through the inhibition of JAK2/STAT3 signaling.

PMID: 30573361 [PubMed - as supplied by publisher]

Biodegradable microparticles designed to efficiently reach and act on cystic fibrosis mucus barrier.

Mater Sci Eng C Mater Biol Appl. 2019 Feb 01;95:19-28

Authors: Cristallini C, Barbani N, Ventrelli L, Summa C, Filippi S, Capelôa T, Vitale E, Albera C, Messore B, Giachino C

Abstract
Cystic fibrosis (CF) is a progressive genetic disease caused by mutations in the gene that produces the CF transmembrane conductance regulator (CFTR) protein. The malfunction of the CFTR protein causes a thick buildup of mucus in the lungs that clogs the airways and traps bacteria, thus leading to infections, extensive lung damage and respiratory failure. Micro-delivery systems are currently being investigated as an efficient way to cross the viscous and complex architecture of the CF mucus. In this study, we produced synthetic and natural microparticles (MPs) based on poly(dl‑lactide‑co‑glycolide) (PLGA) or gellan gum through tailored water/oil emulsion procedures. Morphological and physico-chemical characterizations were carried out on both classes of MPs showing particles having diameters within suitable ranges to reach the CF airways. In vitro biocompatibility tests were also performed on both MPs using a human lung cancer cell line (A549) demonstrating that treatment with MPs induces no cytotoxic effects. Both classes of MPs were loaded with a mucolytic agent (N‑acetyl cysteine, NAC) and their release kinetics evaluated using high performance liquid chromatography (HPLC). The analysis pointed out that the amount of NAC released from MPs resulted in a dose-dependent increment, with a rapid release kinetic to satisfy the requirement for inducing an early mucus degradation. Finally, mucolytic action of NAC-loaded MPs was evaluated in an artificial sputum model through its rheological analysis obtaining the lowest viscosity profile after the addition of drug-loaded MPs. Taken together, gained results allowed us to select suitable MPs as potential drug targeting platforms having a mucolytic action for CF treatment.

PMID: 30573241 [PubMed - in process]

German National Guideline for Treating Chronic Respiratory Failure with Invasive and Non-Invasive Ventilation - Revised Edition 2017: Part 2.

Respiration. 2018;96(2):171-203

Authors: Windisch W, Geiseler J, Simon K, Walterspacher S, Dreher M, on behalf of the Guideline Commission

Abstract
Today, invasive and non-invasive home mechanical ventilation have become a well-established treatment option. Consequently, in 2010, the German Respiratory Society (DGP) has leadingly published the guidelines on "Non-Invasive and Invasive Mechanical Ventilation for Treatment of Chronic Respiratory Failure." However, continuing technical evolutions, new scientific insights, and health care developments require an extensive revision of the guidelines. For this reason, the updated guidelines are now published. Thereby, the existing chapters, namely technical issues, organizational structures in Germany, qualification criteria, disease-specific recommendations including special features in pediatrics as well as ethical aspects and palliative care, have been updated according to the current literature and the health care developments in Germany. New chapters added to the guidelines include the topics of home mechanical ventilation in paraplegic patients and in those with failure of prolonged weaning. In the current guidelines, different societies as well as professional and expert associations have been involved when compared to the 2010 guidelines. Importantly, disease-specific aspects are now covered by the German Interdisciplinary Society of Home Mechanical Ventilation (DIGAB). In addition, societies and associations directly involved in the care of patients receiving home mechanical ventilation have been included in the current process. Importantly, associations responsible for decisions on costs in the health care system and patient organizations have now been involved.

PMID: 29945156 [PubMed - indexed for MEDLINE]

[Characterization of the physical capacity in children of the Chilean National Program of Cystic Fibrosis].

Rev Chil Pediatr. 2018 Oct;89(5):638-643

Authors: Puppo H, Von Oetinger A, Benz E, Torres-Castro R, Zagolín M, Boza ML, Astorga L, Bozzo R, Jorquera P, Kogan R, Perillán J

Abstract
INTRODUCTION: Cystic fibrosis (CF) is an inherited, progressive, multisystem disease. Better physical capacity may slow disease progression, thus improving prognosis and survival. The objective of this research was to evaluate the physical capacity of children admitted to the National CF Pro gram of the Metropolitan Region, Chile.
PATIENTS AND METHOD: A multicenter, cross-sectional stu dy design was used. The inclusion criteria were children aged 6 to 12 years enrolled in the National CF Program; Tanner sexual maturity stage I, no respiratory exacerbations in the last 30 days, and no musculoskeletal pathologies. The maximum aerobic capacity was assessed through the peak oxygen uptake (VO2peak) and determined with an incremental protocol in a magnetic cycle ergometer connected to an ergo-spirometer with which, at the same time, respiratory gases, oxygen consumption and carbon dioxide production values every 30 seconds, anaerobic threshold, and maximum workload were analyzed. The values of forced vital capacity (FVC), forced expiratory volume in 1 second (FEVJ, FEVj/FVC ratio, and forced expiratory flows between 25% and 75% of vital capacity were assessed through ergo-spirometry. At the beginning of the ergo-spirometry, arterial oxygen saturation, respiratory rate, heart rate, blood pressure, tidal volume and the per ception of lower extremity fatigue and dyspnea were recorded using the modified Borg scale. The test lasted approximately 10 minutes.
RESULTS: The clinical records of 43 children collected from six health centers were reviewed. Out of these, 29 children met inclusion criteria, and 23 were re cruited. Two children were unable to participate, reducing the final subject group to 21 (13 males, 8 females). The mean age was 8.8 ± 2 years; weight 30.5 ± 10.9 kg; height 1.32 ± 0.11 m; and body mass index 17.1 ± 3.5 (z-score 0.01 ± 1.34). More than half of the children (61%) had normal weight. The obtained VO2peak was 43.7 ± 6.5 ml/min/kg (106.7 ± 19.8% of the predictive values). Only 10% of the children had values lower than those predicted by sex and age. No correlations were found between VO2peak and anthropometric and pulmonary function variables. Conclu sion: Most of the evaluated children (90%) had physical capacity similar to healthy subjects by sex and age.

PMID: 30571807 [PubMed - in process]

The role of neonatal screening in nutritional evolution in the first 12 months after diagnosis of cystic fibrosis.

Rev Assoc Med Bras (1992). 2018 Nov;64(11):1032-1037

Authors: Martins JP, Forte GC, Simon MISDS, Epifanio M, Pinto LA, Marostica PJC

Abstract
OBJECTIVE: to assess the progression of pediatric cystic fibrosis (CF) patients' nutritional status during the first 12 months after diagnosis and to establish its association with neonatal screening and clinical variables. Patients were recruited from two reference centers in Southern Brazil.
METHODS: Retrospective cohort study was carried out with all the patients diagnosed between 2009 and 2014. Anthropometric, clinic and neonatal screening were collected from medical files. Analysis of anthropometric markers over time was performed by generalized estimating equations. A multivariate regression analysis model to predict the Δ percentile body mass index (BMI) (BMI percentile difference between one year after the treatment and BMI percentile at diagnosis) was done.
RESULTS: Forty-seven patients were included in the study. Analysis of nutritional data over the period between six months and one year after diagnosis showed significant improvement of BMI, weight/age and weight/height percentiles and Z scores. The neonatal screening was associated with a significant increase of 31.2 points in ΔBMI percentile at the one-year evaluation (p<0.05). On the other hand, a one-point increase of initial BMI percentile was associated with a reduction of 0.6 points in ΔBMI percentile.
CONCLUSION: This study demonstrated the role of neonatal screening in the nutritional status of patients diagnosed with CF in the first year after diagnosis. Early diagnosis can significantly contribute to the achievement of appropriate anthropometric indicators and important nutritional recovery of CF patients.

PMID: 30570057 [PubMed - in process]

Expression of miR‑542‑3p in osteosarcoma with miRNA microarray data, and its potential signaling pathways.

Mol Med Rep. 2018 Dec 13;:

Authors: Li Z, Yao JN, Huang WT, He RQ, Ma J, Chen G, Wei QJ

Abstract
Osteosarcoma (OS) is the most common pediatric primary bone tumor, with high malignancy rates and a poor prognosis following metastasis. At present, the role of microRNA (miR)‑542‑3p in OS remains to be elucidated. The purpose of the present study was to investigate the expression level of miR‑542‑3p in OS, and its potential molecular mechanisms, via a bioinformatics analysis. First, the expression of miR‑542‑3p in OS based on the continuous variables of the Gene Expression Omnibus database and PubMed was studied. Subsequently, the potential target genes of miR‑542‑3p were predicted using gene expression profiles and bioinformatics software. On the basis of the Database for Annotation, Visualization and Integrated Discovery, version 6.8, a study of gene ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway knowledge base was conducted to explore the biological value of miR‑542‑3p in OS. Finally, the protein‑protein interaction (PPI) network was completed using the STRING database. The expression of miR‑542‑3p in OS was revealed to be significantly higher compared with that in normal tissue. In total, 1,036 target genes of miR‑542‑3p were obtained. The results of the GO enrichment analysis revealed that the significant terms were 'bone development', 'cell cycle arrest' and 'intracellular signal transduction'. The results of the KEGG analysis revealed the highlighted pathways that were targeted to miR‑542‑3p, including the sphingolipid signaling pathway (P=3.91x10‑5), the phosphoinositide 3‑kinase (PI3K)‑AKT serine/threonine kinase (AKT) signaling pathway (P=3.17x10‑5) and the insulin signaling pathway (P=1.04x10‑5). The PPI network revealed eight hub genes: Ubiquitin‑60S ribosomal protein L40, Ras‑related C3 botulinum toxin substrate, mitogen‑activated protein kinase 1, epidermal growth factor receptor, cystic fibrosis transmembrane conductance regulator, PI3K regulatory subunit 1, AKT1, and actin‑related protein 2/3 complex subunit 1A, which may be the key target genes of miR‑542‑3p in OS. Taken together, these results have demonstrated that miR‑542‑3p was overexpressed in OS. The potential target genes and biological functions of miR‑542‑3p may provide novel insights into the differentially expressed genes that are involved in OS.

PMID: 30569116 [PubMed - as supplied by publisher]

Children and Adults Tai Chi Study (CF-CATS2): a randomised controlled feasibility study comparing internet-delivered with face-to-face Tai Chi lessons in cystic fibrosis.

ERJ Open Res. 2018 Oct;4(4):

Authors: Carr SB, Ronan P, Lorenc A, Mian A, Madge SL, Robinson N

Abstract
Virtual healthcare is fast entering medical practice. Research into the feasibility of using it to teach treatment regimens such as exercise has not been explored. Maintaining an exercise regime can be difficult in cystic fibrosis: group classes risk potential infection, yet motivation is hard to maintain when alone. Tai Chi is a low-impact exercise and involves gentle, demanding movements. This study aimed to assess the feasibility, safety and acceptability of learning Tai Chi via an internet-based approach and compared patient-reported outcomes. Children and adults with cystic fibrosis were recruited to a randomised, comparative effectiveness trial. Participants learnt eight Tai Chi movements; teaching was delivered in eight lessons over 3 months: delivered either via the internet or face-to-face. Assessments were at 3-monthly intervals over 9 months. Outcomes included health status, quality of life, sleep, mindfulness and instructor-led questions. 40 adults and children completed the eight sets of Tai Chi lessons. The median age was 22.8 years (range 6.1-51.5 years); 27 patients were female. The cohort comprised 26 adults (aged >16 years), six teenagers and eight children (aged <12 years). The groups were well matched. Feasibility and safety were demonstrated. Participants showed significant improvements in self-reported sleep, cough (both daytime and night-time), stomach ache and breathing. No differences in lung function, health status, quality of life, sleep or mindfulness was shown before or after completing the lessons. Tai Chi was safe and well tolerated; it was feasible to deliver individual lessons via the internet, reducing concerns regarding cross-infection, and appeared to improve self-reported symptoms.

PMID: 30568967 [PubMed]

A Closer Look at the Genomic Variation of Geographically Diverse Mycobacterium abscessus Clones That Cause Human Infection and Disease.

Front Microbiol. 2018;9:2988

Authors: Davidson RM

Abstract
Mycobacterium abscessus is a multidrug resistant bacterium that causes pulmonary and extrapulmonary disease. The reported prevalence of pulmonary M. abscessus infections appears to be increasing in the United States (US) and around the world. In the last five years, multiple studies have utilized whole genome sequencing to investigate the genetic epidemiology of two clinically relevant subspecies, M. abscessus subsp. abscessus (MAB) and M. abscessus subsp. massiliense (MMAS). Phylogenomic comparisons of clinical isolates revealed that substantial proportions of patients have MAB and MMAS isolates that belong to genetically similar clusters also known as 'dominant clones'. Unlike the genetic lineages of Mycobacterium tuberculosis that tend to be geographically clustered, the MAB and MMAS clones have been found in clinical populations from the US, Europe, Australia and South America. Moreover, the clones have been associated with worse clinical outcomes and show increased pathogenicity in macrophage and mouse models. While some have suggested that they may have spread locally and then globally through 'indirect transmission' within cystic fibrosis (CF) clinics, isolates of these clones have also been associated with sporadic pulmonary infections in non-CF patients and unrelated hospital-acquired soft tissue infections. M. abscessus has long been thought to be acquired from the environment, but the prevalence, exposure risk and environmental reservoirs of the dominant clones are currently not known. This review summarizes the genomic studies of M. abscessus and synthesizes the current knowledge surrounding the geographically diverse dominant clones identified from patient samples. Furthermore, it discusses the limitations of core genome comparisons for studying these genetically similar isolates and explores the breadth of accessory genome variation that has been observed to date. The combination of both core and accessory genome variation among these isolates may be the key to elucidating the origin, spread and evolution of these frequent genotypes.

PMID: 30568642 [PubMed]

Spotlight on inhaled ciprofloxacin and its potential in the treatment of non-cystic fibrosis bronchiectasis.

Drug Des Devel Ther. 2018;12:4059-4066

Authors: Chorepsima S, Kechagias KS, Kalimeris G, Triarides NA, Falagas ME

Abstract
Non-cystic fibrosis bronchiectasis (NCFB) is a severe chronic illness characterized by irreversible dilation of airways and thickening of bronchial walls, chronic inflammation, repeated infections, and progressive obstruction of the airways. In contrast to cystic fibrosis bronchiectasis (CFB), which is a well-defined genetic disorder, NCFB is a heterogeneous disease caused by many different medical entities. Inhaled antibiotics are effective for patients with CFB, but their efficacy in NCFB has not been proven. The main pathogens involved in the colonization of patients with bronchiectasis are Haemophilus influenza, Moraxella catarrhalis, Staphylococcus aureus, and Pseudomonas aeruginosa. The latter is associated with increased morbidity and mortality. In addition, in NCFB, P. aeruginosa strains are frequently more resistant than those in CFB. At present, there are no approved inhaled antibiotic therapies for NCFB patients. Inhaled ciprofloxacin has been under investigation in the last few years. In two phase II randomized, double-blind, placebo-controlled trials, the use of inhaled ciprofloxacin was significantly associated with reduction in sputum bacterial density and greater eradication rates. In four phase III randomized, double-blind, placebo-controlled trials, the results regarding the time of the first exacerbation and the rate of exacerbations were inconsistent. Specifically, ORBIT-4 and RESPIRE-1 trials showed clinical benefit (prolongation of the time of the first exacerbation and reduced rate of exacerbations in the treatment group compared to the placebo group), whereas the ORBIT-3 and RESPIRE-2 failed to achieve their primary endpoints. The RESPIRE-1 was the first trial that examined the 14-days on/off course separate from the standard 28-days on/off regimen, which is based on CFB protocol treatments. The current data on the efficacy of inhaled ciprofloxacin are encouraging, but further evaluation is needed to determine the appropriate target group and the ideal duration of treatment.

PMID: 30568427 [PubMed - in process]