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Evaluation of continuous constant current and continuous pulsed current in sweat induction for cystic fibrosis diagnosis.
Gomez, CCS, Marson, FAL, Servidoni, MF, Ribeiro, AF, Ribeiro, MÂGO, Gama, VAL, Costa, ET, Ribeiro, JD, Vieira Junior, FU
BMC pulmonary medicine. 2018;(1):153
Abstract
BACKGROUND The sweat test (ST) is the gold standard for the diagnosis of cystic fibrosis (CF). However, little is known about sweat induction using different types of currents and waves. In this context, our objective was to develop a device to induce sweat and compare the use of continuous constant current (CCC) and continuous pulsed current (CPC) in individuals with CF and healthy controls. METHODS A prospective cross-sectional study with experimental intervention. The variables of gender, ethnicity, age, and body mass index (BMI) were considered. The method of Gibson and Cooke was used, and the following markers were evaluated: sweat weight, electrical impedance, sufficient sweat amount, and CF diagnosis. Triangular (TPC) or sinusoidal (SPC) pulsed current was applied to the right arm, and CCC was applied to the left arm. RESULTS The study analyzed 260 individuals, 141/213 (54.2%) were female participants, 135/260 (51.9%) were Caucasians. The distribution of individuals by concentration of chloride at the ST was: (CF) 26/260 (10%); (borderlines) 109/260 (41.9%); (healthy) 97/260 (37.3%); (insufficient weight in sweat) 28/260 (10.8%). No association was observed between the sufficient sweat amount to perform the ST when we compared the currents. However, the SPC showed a higher amount of sweat weight. Using Bland and Altman plot considering the agreement between the sweat chloride values achieved from CPC [SPC and TPC] and CCC, there was no proportional bias and mean values are unrelated and only explain less than 8% of the variation. Moreover, TPC presented higher electrical impedance when compared with SPC and CCC. SPC presented lower electrical impedance and higher sweat weight than CCC. Male participants presented lower electrical impedance and higher sweat weight with CCC and TPC, and higher sweat weight with SPC. CONCLUSIONS The evaluated currents are safe and able to induce and produce sweat in sufficient quantities for the ST. SPC presented lower electrical impedance when compared with other currents. The use of SPC is recommended to induce sweat in patients with sweat problems. Finally, ethnicity, gender, age and BMI did not influence sweat induction at the ST, and no side effect was observed in our study.
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Oral glucose tolerance test and continuous glucose monitoring to assess diabetes development in cystic fibrosis patients.
Clemente León, M, Bilbao Gassó, L, Moreno-Galdó, A, Campos Martorrell, A, Gartner Tizzano, S, Yeste Fernández, D, Carrascosa Lezcano, A
Endocrinologia, diabetes y nutricion. 2018;(1):45-51
Abstract
INTRODUCTION Patients with cystic fibrosis (CF) undergo a slow and progressive process toward diabetes. Oral glucose tolerance test (OGTT) is recommended to diagnose impaired glucose levels in these patients. Continuous glucose monitoring (CGM) measures glucose profiles under real-life conditions. OBJECTIVE To compare OGTT and CGM results in CF patients. METHODS Paired OGTT and 6-day CGM profiles (146.2±9.1h/patient) were performed in 30 CF patients aged 10-18 years. RESULTS According to OGTT, 14 patients had normal glucose tolerance (NGT), 14 abnormal glucose tolerance (AGT), and two cystic fibrosis-related diabetes (CFRD). In 27 patients (13 NGT, 13 AGT, 1 CFRD), CGM showed glucose values ranging from 140 to 200mg/dL during similar monitoring times (2%-14% with NGT, 1%-16.9% with AGT, and 3% with CFRD). Glucose peak levels ≥200mg/dL were seen in seven patients (3 NGT, 3 AGT, 1 CFRD). According to CGM, two patients had all glucose values under 140mg/dL (1 NGT, 1 AGT). Seventeen patients had glucose levels ranging from 140 to 200mg/dL (10 NGT, 6 AGT, 1 CFRD). Ten patients (3 NGT, 7 AGT) had glucose values ≥200mg/dL for ≤1% of the monitoring time and one (CFRD) for >1% of the monitoring time. CONCLUSIONS OGTT results did not agree with those of the CGM. CGM allows for diagnosis of glucose changes not detected by OGTT. Such changes may contribute to optimize pre-diabetes management in CF patients.
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Clinical and laboratory correlations in patients with cystic fibrosis and Pseudomonas aeruginosa infection: The experience of a regional centre.
Smădeanu, R, Moşescu, S, Zăpucioiu, C, Orăşeanu, D
Pneumologia (Bucharest, Romania). 2016;(4):201-6
Abstract
UNLABELLED Pseudomonas aeruginosa (Pa) is the most important pathogen affecting the prognosis of patients with cystic fibrosis (CF). Distinguishing the correlations associated with PA infection may change the way in which investigation and therapeutic plans are approached. This study aims to evaluate the correlations between various factors such as age at diagnosis, nutritional status, homozygous status of delF508 mutation, the number of exacerbations per year, imagistic modifications, the presence of chronic infection with Staphylococcus aureus, serum levels of total immunoglobulins G (IgG) and gammaglobulins and ventilation parameters - forced vital capacity (FVC) and one-second forced expired volume (FEV1) and their association with Pa infection. METHODS The associations between the analyzed parameters have been made by logistic regression; the comparisons between means of continuous variables were performed using Studen t-test; the variables distribution was tested using chi-square-test; and correlations between variables were assessed using Pearson coefficient. RESULTS The mean age at the acquisition of Pa was 5.26 (±5.3 years). Of the 50 patients included in the study, 21 acquired the Pa infection having the median age of primo-infection of 3 years. The study identified a greater number of exacerbations per year in those infected with Pa (2.71 compared to 1.38 exacerbations per year; p=0.002); the increase of radiological score with 1 unit associated with an increased risk of infection with Pa (OR 1.31; 95% CI 1.10-1.56;p=0.002), the mean Brasfield radiologic score is lower for uninfected children (6.9 vs. 11 points, p=0.001); increasing the degree of bronchiectasis associated with Pa infection (OR 3.75;CI 1.77-7.96;p=0.001); gammaglobulin (15.91 vs. 19.42%;p=0.01) or immunoglobulin G values (IgG) (9.8 vs. 11.9 g/L;p=0.05) were higher for those infected. CONCLUSIONS The increased number of exacerbations per year, the severity of imagistic modifications, and IgG and gammaglobulin values are associated with Pa infection. Tracking these parameters guides the therapeutic conduct.
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Comparison of Inhaled Antibiotics for the Treatment of Chronic Pseudomonas aeruginosa Lung Infection in Patients With Cystic Fibrosis: Systematic Literature Review and Network Meta-analysis.
Elborn, JS, Vataire, AL, Fukushima, A, Aballea, S, Khemiri, A, Moore, C, Medic, G, Hemels, ME
Clinical therapeutics. 2016;(10):2204-2226
Abstract
PURPOSE In Europe, 4 inhaled antibiotics (tobramycin, colistimethate sodium, aztreonam, and levofloxacin) are currently approved for the treatment of chronic Pseudomonas aeruginosa lung infection in patients with cystic fibrosis (CF). Levofloxacin inhalation solution (LIS) is the most recently approved inhaled antibiotic for adult patients with CF. A systematic literature review and Bayesian network meta-analysis (NMA) was conducted to compare the relative short-term (4 weeks) and long-term (24 weeks) outcomes of these inhaled antibiotics versus LIS. METHODS A systematic literature search was conducted on February 16, 2016, using EMBASE and Medline via OvidSP. All randomized controlled trials comparing any of the aforementioned inhaled antibiotics with 4 or 24 weeks of follow-up were evaluated. NMA was performed for the following outcomes: relative and absolute percent changes from baseline in forced expiratory volume in 1 second (FEV1%) predicted, change in P aeruginosa sputum density, respiratory symptoms score from the CF questionnaire-revised, hospitalization, additional antibiotics use, and study withdrawal rates. RESULTS Of the 685 articles identified, 7 unique studies were included in the 4 weeks' NMA and 9 unique studies were included in the 24 weeks' NMA. Aztreonam was predicted to result in the greatest numerically increase in FEV1% predicted at 4 weeks, whereas LIS were predicted to be numerically greater than colistimethate sodium, tobramycin inhaled solution (TIS), and tobramycin inhaled powder (TIP). However, all of the 95% credibility intervals (CrIs) of these comparisons included zero. At 24 weeks, none of the treatments was significantly more effective than LIS. The estimates for the mean change from baseline to 24 weeks in relative FEV1% versus LIS was -0.55 (95% CrI, -3.91 to 2.80) for TIS, -2.36 (95% CrI, -7.32 to 2.63) for aztreonam, -2.95 (95% CrI, -10.44 to 4.51) for TIP, and -9.66 (95% CrI, -15.01 to -4.33) for placebo. Compared with LIS, the odds ratio for hospitalization at 24 weeks was 1.92 (95% CrI, 1.01-3.30) for TIS, 2.25 (95% CrI, 1.01-4.34) for TIP, and 3.16 (95% CrI, 1.53-5.78) for placebo, all statistically worse than LIS. P aeruginosa sputum density scores, additional use of antipseudomonal antibiotics, and study withdrawal rates were comparable among all inhaled antibiotics at all times. IMPLICATIONS Based on this NMA, the analyses for many of the outcomes did not provide significant evidence to indicate that the other approved inhaled antibiotics were more effective than LIS for the treatment of chronic P aeruginosa lung infection in patients with CF. Study withdrawal rates seemed to be comparable among these inhaled antibiotics.
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Pulsed direct and constant direct currents in the pilocarpine iontophoresis sweat chloride test.
Gomez, CC, Servidoni, Mde F, Marson, FA, Canavezi, PJ, Vinagre, AM, Costa, ET, Ribeiro, AF, Ribeiro, MA, Toro, AA, Pavan, CR, et al
BMC pulmonary medicine. 2014;:198
Abstract
BACKGROUND The classic sweat test (CST) is the golden standard for cystic fibrosis (CF) diagnosis. Then, our aim was compare the production and volume of sweat, and side effects caused by pulsed direct current (PDC) and constant direct current (CDC). To determine the optimal stimulation time (ST) for the sweat collection. To verify the PDC as CF diagnosis option. METHODS Prospective study with cross-sectional experimental intervention. Experiment 1 (right arm): PDC and CDC. ST at 10 min and sweat collected at 30 min. Currents of 0.5; 0.75; 1.0 and 1.5 mA and frequencies of 0, 200, 1,000 and 5,000 Hz applied. Experiment 2 (left arm): current of 1.0 mA, ST at 5 and 10 min and sweat collected at 15 and 30 min with frequencies of 0; 200; 1,000 and 5,000 Hz applied Experiments 1 and 2 were performed with current density (CD) from 0.07 to 0.21 mA/cm2. Experiment 3: PDC was used in typical CF patients with two CFTR mutations screened and or with CF diagnosis by rectal biopsy and patients with atypical CF. RESULTS 48 subjects (79.16% female) with average of 29.54 ± 8.87 years old were enrolled. There was no statistical difference between the interaction of frequency and current in the sweat weight (p = 0.7488). Individually, positive association was achieved between weight sweat and stimulation frequency (p = 0.0088); and current (p = 0.0025). The sweat production was higher for 10 min of stimulation (p = 0.0023). The sweat collection was better for 30 min (p = 0.0019). The skin impedance was not influenced by ST and sweat collection (p > 0.05). The current frequency was inversely associated with the skin impedance (p < 0.0001). The skin temperature measured before stimulation was higher than after (p < 0.0001). In Experiment 3 (29 subjects) the PDC showed better kappa index compared to CDC (0.9218 versus 0.5205, respectively). CONCLUSIONS The performance of the CST with CDC and PDC with CD of 0.14 to 0.21 mA/cm2 showed efficacy in steps of stimulation and collection of sweat, without side effects. The optimal stimulation time and sweat collection were, respectively, 10 and 30 min.
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Induced sputum compared to bronchoalveolar lavage in young, non-expectorating cystic fibrosis children.
Blau, H, Linnane, B, Carzino, R, Tannenbaum, EL, Skoric, B, Robinson, PJ, Robertson, C, Ranganathan, SC
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society. 2014;(1):106-10
Abstract
BACKGROUND Induced sputum (IS) is feasible and safe in young CF children and is a readily accessible, non-invasive technique. However, it has not been compared to bronchoalveolar lavage (BAL), the gold standard for diagnosing lower airway infection. METHODS We compared bacterial yield from IS and BAL in 11 non-expectorating CF children, aged 3 to 7.4 years. IS samples were obtained in 10/11 cases. RESULTS Eight out of ten had the same predominant bacteria cultured from IS and BAL: Pseudomonas aeruginosa and Stenotrophomonas maltophilia[1], Staphylococcus aureus[3], and upper respiratory tract flora [4]. In one, Serratia marcescens and Haemophilus parainfluenzae were cultured from IS alone, whereas in one, non-group B Haemophilus influenzae was cultured from BAL alone. CONCLUSIONS As proof of principle, IS samples showed good bacteriologic correlation with BAL. Larger studies are recommended to confirm IS as a clinically valuable tool and measure for early intervention studies in young CF children.
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Dietary essential amino acids are highly anabolic in pediatric patients with cystic fibrosis.
Engelen, MP, Com, G, Wolfe, RR, Deutz, NE
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society. 2013;(5):445-53
Abstract
BACKGROUND Current nutritional approaches have been partially successful in Cystic Fibrosis (CF). Essential amino acids mixtures with high Leucine levels (EAA) have anabolic properties in catabolic conditions, however data in CF are lacking. METHODS On two days according a randomized crossover design, 15 pediatric CF patients ingested 6.7 g EAA versus mixture of total amino acids as present in whey. Whole body protein and Arginine metabolism (as EAA lack Arginine) were assessed by stable isotope methodology. RESULTS Protein synthesis (P<0.05) but not protein breakdown was higher after EAA and 70% higher values for net anabolism (P<0.001)were found both in patients with and without nutritional failure. Arginine turnover was lower (P<0.001) and de novo Arginine synthesis tended lower (P=0.09) after EAA. Nitric oxide synthesis was not different. CONCLUSIONS CF patients are highly responsive to EAA intake independent of their nutritional status. Addition of Arginine to the EAA mixture may be warranted in CF.
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An international randomized multicenter comparison of nasal potential difference techniques.
Solomon, GM, Konstan, MW, Wilschanski, M, Billings, J, Sermet-Gaudelus, I, Accurso, F, Vermeulen, F, Levin, E, Hathorne, H, Reeves, G, et al
Chest. 2010;(4):919-28
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Abstract
BACKGROUND The transepithelial nasal potential difference (NPD) is used to assess cystic fibrosis transmembrane conductance regulator (CFTR) activity. Unreliability, excessive artifacts, and lack of standardization of current testing systems can compromise its use as a diagnostic test and outcome measure for clinical trials. METHODS To determine whether a nonperfusing (agar gel) nasal catheter for NPD measurement is more reliable and less susceptible to artifacts than a continuously perfusing nasal catheter, we performed a multicenter, randomized, crossover trial comparing a standardized NPD protocol using an agar nasal catheter with the same protocol using a continuously perfusing catheter. The data capture technique was identical in both protocols. A total of 26 normal adult subjects underwent NPD testing at six different centers. RESULTS Artifact frequency was reduced by 75% (P < .001), and duration was less pronounced using the agar catheter. The measurement of sodium conductance was similar between the two catheter methods, but the agar catheter demonstrated significantly greater CFTR-dependent hyperpolarization, because Δ zero Cl- + isoproterenol measurements were significantly more hyperpolarized with the agar catheter (224.2 ± 12.9 mV with agar vs 18.2 ± 9.1 mV with perfusion, P < .05). CONCLUSIONS The agar nasal catheter approach demonstrates superior reliability compared with the perfusion nasal catheter method for measurement of NPD. This nonperfusion catheter method should be considered for adoption as a standardized protocol to monitor CFTR activity in clinical trials.
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Safety and tolerability of a new formulation of pancrelipase delayed-release capsules (CREON) in children under seven years of age with exocrine pancreatic insufficiency due to cystic fibrosis: an open-label, multicentre, single-treatment-arm study.
Graff, GR, McNamara, J, Royall, J, Caras, S, Forssmann, K
Clinical drug investigation. 2010;(6):351-64
Abstract
Exocrine pancreatic insufficiency (EPI) is a deficiency of digestive enzymes caused by diseases such as cystic fibrosis (CF). Patients with EPI due to CF require pancreatic enzyme replacement therapy (PERT) in order to maintain adequate nutrition. A new formulation of pancrelipase delayed-release capsules (CREON) recently received US FDA approval and has demonstrated efficacy and safety in patients with CF aged > or =7 years. The objectives of this study were to observe the safety and tolerability of new formulation pancrelipase delayed-release capsules (study drug) versus the standard of care PERT (standard therapy) in children aged <7 years with CF and EPI. Secondary objectives were to assess the ease of accurate dosing of study drug, monitor clinical symptoms and compare the efficacy of both treatments. This was an open-label, multicentre, single-treatment-arm study in children aged <7 years with a confirmed diagnosis of CF and EPI. After the screening period (approximately 14 days), all patients entered a 3-day assessment period on their usual PERT (standard therapy), followed by the study drug treatment phase (10-14 days; target dose 8000 lipase units/kg bodyweight/day), which included a second 3-day assessment period. The safety and tolerability of both treatments were documented by recording adverse events (AEs). Clinical symptoms (mean daily stool frequency, abdominal pain, stool consistency and flatulence) were monitored and ease of accurate dosing, as judged by caregivers, was reported. Efficacy was determined by comparison of percent stool fat in spot stool samples collected during both 3-day assessment periods. Of the 19 patients who had informed consent from their parent/legally acceptable representative, one was withdrawn as a screen failure and was excluded from the safety and efficacy analyses; thus, 18 patients completed the study. The median age (range) was 23 (4-71) months and 13 (72%) were male. During study drug treatment, patients received a mean +/- SD dose in lipase units/kg bodyweight/day of 7542 +/- 1335 versus 6966 +/- 3392 on standard therapy. Overall, nine (50%) patients had at least one treatment-emergent AE (TEAE) whilst receiving either treatment. All TEAEs in this study were reported as mild and none resulted in patient discontinuation. The caregivers had a slight preference for study drug over standard therapy in terms of ease of accurate dosing: six (33.3%) caregivers thought the study drug was easier to dose while only one (5.6%) thought the study drug was harder to dose than standard therapy. Clinical symptom assessment results were similar between treatments. There was no clinically meaningful difference (significance not tested) between study drug and standard therapy in the mean +/- SD percent of stool fat: 28.1 +/- 9.9 and 27.9 +/- 8.9, respectively. In this study in children aged <7 years with EPI due to CF, the new formulation pancrelipase delayed-release capsules (CREON) were clinically comparable with standard therapy in terms of safety, tolerability and efficacy.
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Chest physiotherapy in cystic fibrosis: short-term effects of autogenic drainage preceded by wet inhalation of saline versus autogenic drainage preceded by intrapulmonary percussive ventilation with saline.
Van Ginderdeuren, F, Verbanck, S, Van Cauwelaert, K, Vanlaethem, S, Schuermans, D, Vincken, W, Malfroot, A
Respiration; international review of thoracic diseases. 2008;(2):175-80
Abstract
BACKGROUND Chest physiotherapy has been used for many years to assist in the removal of abnormal viscid bronchial secretions in cystic fibrosis (CF) patients. OBJECTIVES This study compared the short-term effects of two physiotherapy regimens in patients with CF: autogenic drainage (AD) preceded by either saline inhalation ('saline(NEB) + AD') or by intrapulmonary percussive ventilation (IPV) with saline ('saline(IPV) + AD'). METHODS In a randomized crossover design, 20 clinically stable CF patients with similar pulmonary function at baseline received either 'saline(NEB) + AD' or 'saline(IPV) + AD' on 2 consecutive days. Transcutaneous oxygen saturation, heart rate, Borg dyspnea score and mucus wet weight were evaluated after 15 min of either saline(NEB) or saline(IPV), and after a subsequent 30 min of AD. RESULTS There were no significant changes in oxygen saturation, heart rate or Borg score at any point of either physiotherapy intervention. There was no significant difference in sputum wet weight recovered with either saline(NEB) (2.2 +/- 1.8 g, mean +/- SD) or saline(IPV) (1.7 +/- 1.9 g) alone. Subsequent AD did produce significantly greater amounts of sputum wet weight (p < 0.0001 for both) than in the initial saline delivery period, yet the amount of wet weight was similar irrespective of whether AD was preceded by saline(NEB) (9.7 +/- 6.5 g) or saline(IPV) (11.6 +/- 7.3 g). CONCLUSIONS Recovered sputum weight is similar whether AD is preceded by saline(NEB) or saline(IPV). The much greater amount of mucus obtained during the AD period than during the saline delivery period warrants further investigation.