Pediatric Cystic Fibrosis Patients Research Articles

A semiquantitative MRI-Score can predict loss of lung function in patients with cystic fibrosis: Preliminary results.

To evaluate the applicability of a semiquantitative MRI scoring system (MR-CF-S) as a prognostic marker for clinical course of cystic fibrosis (CF) lung disease. This observational study of a single-centre CF cohort included a group of 61 patients (mean age 12.9 ± 4.7years) receiving morphological and functional pulmonary MRI, pulmonary function testing (PFT) and follow-up of 2years. MRI was analysed by three raters using MR-CF-S. The inter-rater agreement, correlation of score categories with forced expiratory volume in 1s (FEV1) at baseline, and the predictive value of clinical parameters, and score categories was assessed for the whole cohort and a subgroup of 40 patients with moderately impaired lung function. The inter-rater agreement of MR-CF-S was sufficient (mean intraclass correlation coefficient 0.92). MR-CF-S (-0.62; p < 0.05) and most of the categories significantly correlated with FEV1. Differences between patients with relevant loss of FEV1 (>3%/year) and normal course were only significant for MR-CF-S (p < 0.05) but not for clinical parameters. Centrilobular opacity (CO) was the most promising score category for prediction of a decline of FEV1 (area under curve: whole cohort 0.69; subgroup 0.86). MR-CF-S is promising to predict a loss of lung function. CO seems to be a particular finding in CF patients with an abnormal course. • Lung imaging is essential in the diagnostic work-up of CF patients • MRI serves as a powerful, radiation-free modality in paediatric CF patients • Observational single-centre study showed significant correlation of MR-CF score and FEV 1 • MR-CF score is promising in predicting a loss of lung function.

Population Pharmacokinetics of Tobramycin Inhalation Solution in Pediatric Patients With Cystic Fibrosis

Tobramycin inhalation solution given as a twice daily inhalation of nebulized aerosols of 300 mg is approved for the treatment of Pseudomonas aeruginosa infection in cystic fibrosis patients over 6 years of age. To investigate tobramycin pharmacokinetics (PK) after inhalation of tobramycin in pediatric cystic fibrosis patients below 7 years, a population PK approach was used to evaluate tobramycin PK data in patients 6 months to 44 years of age from 4 clinical studies. The final model used a 2-compartmental, first-order absorption model with effect of body mass index on the apparent central volume of distribution. Relative bioavailability in patients between 6 months and 7 years increased with age by a linear relationship, and was modeled as a ratio to that of patients over 7 years. Simulation showed that steady-state concentrations of tobramycin are lower in pediatric patients 6 months to 6 years than those in patients over 6 years. However, systemic exposure is not predictive of clinical efficacy due to direct dosing at the infection site. P aeruginosa eradication rate and safety profile in patients less than 7 years of age were similar to patients older than 6 years; therefore, no dose adjustment is warranted in the younger pediatric patients.

Impact of pharmacy services on cystic fibrosis medication adherence.

The purpose of this study is to characterize the impact of pharmacy services on medication adherence and hospitalizations for pediatric cystic fibrosis (CF) patients. A retrospective health insurance claims analysis and patient medical charts review from January 1, 2014 to December 31, 2016 of patients from the Pediatric Intermountain CF Center was performed. Adherence to dornase alfa and hospital admissions for pulmonary exacerbations pre and post the implementation of an integrated pharmacy team were reviewed. Dornase alfa adherence was measured by the medication possession ratio (MPR) both monthly and yearly. Fifty-four patients met inclusion criteria. The mean dornase alfa yearly MPR improved from 0.75 (2014) to 0.92 (2016). Patients were 2.8 times more likely to be adherent to dornase alfa when followed by integrated pharmacy team model (P < 0.001), and 2.4 times more likely to be adherent when followed by a dedicated CF clinic pharmacist only (P = 0.001). The study demonstrated that pharmacy services improved adherence to dornase alfa.

EPS2.4 Paediatric cystic fibrosis patients' attitudes and beliefs regarding risky health behaviours

EPS2.4 Paediatric cystic fibrosis patients' attitudes and beliefs regarding risky health behaviours

132 Emerging pathogens in cystic fibrosis pediatric patients (CF): cross-sectional reports during the last 30 years

132 Emerging pathogens in cystic fibrosis pediatric patients (CF): cross-sectional reports during the last 30 years

390 Evaluation of a potential impact of specialist cystic fibrosis (CF) pharmacist in the quality of discharge prescriptions in paediatric CF patients

390 Evaluation of a potential impact of specialist cystic fibrosis (CF) pharmacist in the quality of discharge prescriptions in paediatric CF patients

221 Copeptin serum concentrations correlate with symptoms severity in pediatric cystic fibrosis patients

221 Copeptin serum concentrations correlate with symptoms severity in pediatric cystic fibrosis patients

126 Successful treatment of cepacia syndrome with a combination of intravenous antibiotics, oral cyclosporine and corticosteroids in a pediatric cystic fibrosis patient

126 Successful treatment of cepacia syndrome with a combination of intravenous antibiotics, oral cyclosporine and corticosteroids in a pediatric cystic fibrosis patient

231 Factors associated to low pulmonary function in pediatric cystic fibrosis (CF) patients

231 Factors associated to low pulmonary function in pediatric cystic fibrosis (CF) patients

Clinical chronic rhinosinusitis outcomes in pediatric patients with cystic fibrosis.

ObjectivesChronic rhinosinusitis and nasal polyposis are common conditions in cystic fibrosis (CF). Approximately 2–3% of pediatric CF patients per year have sinus disease requiring surgery. It has been well established that there is a significant negative impact on quality of life associated with chronic rhinosinusitis (CRS) in the non‐CF patient population. However, the impact of CRS on the pediatric CF population remains uncertain. The purpose of this article is to review the current state of outcome measures for CRS in pediatric CF patients.Data SourcesPubMed and EMBASE literature reviewMethodsPubMed and EMBASE electronic databases were searched using Boolean searches that incorporated mesh headings and plain language for quality of life, symptom evaluation, pediatric patients, and sinusitis/rhinosinusitis. Studies were included if the study primarily evaluated a pediatric Cystic Fibrosis‐Chronic Rhinosinusitis (CF‐CRS) population and the primary outcome measure was quality of life evaluation.ResultsThe search yielded 34 unique articles. A total of 7 articles met inclusion criteriaConclusionsDespite the high frequency of chronic rhinosinusitis in the pediatric CF patient population, its impact on quality of life is not well understood. Currently there is a lack of a validated disease specific quality of life instruments available to assess the impact of CRS on the pediatric CF patient population.Level of Evidence5.

Safety and Effectiveness of Clofazimine for Primary and Refractory Nontuberculous Mycobacterial Infection

Clofazimine is an antimicrobial agent that has activity invitro against mycobacteria. Increasingly, it has been used for the treatment of nontuberculous mycobacteria (NTM), despite limited data supporting its use in this setting. The objective of this study was to evaluate the safety, tolerability, and clinical outcomes associated with clofazimine in patients with NTM infection. This observational-cohort study assessed clofazimine as used for pediatric and adult cystic fibrosis (CF) and non-CF patients with pulmonary and extrapulmonary NTM infection as part of a multidrug regimen from 2006 to 2014. Treatment regimens and adverse drug reactions (ADRs) were captured. A total of 112 patients were included (median age, 62 years); 24 patients (21%) had CF. Eighty-seven (78%) had refractory disease with failure of previous therapy. Fifty-four patients (48%) had Mycobacterium abscessus complex, 41 (37%) had Mycobacterium avium complex, and 16 (14%) had two NTM species. The median duration of clofazimine use was 383days (range, 3-2,419days). Sixteen patients (14%) stopped clofazimine due to an ADR after a median of 101days (95%CI, 63-119). Forty-one of 82 patients (50%) with pulmonary disease converted to negative NTM cultures within 12months. Clofazimine was a safe, reasonably tolerated, and active oral drug for NTM infection in our heterogeneous population of pediatric and adult CF and non-CF patients. It should be considered as an alternative drug for treatment of NTM disease.

Current Concepts of Transition of Care in Cystic Fibrosis.

Over the past 6 decades, advances in cystic fibrosis (CF) diagnosis and management have extended the life expectancy of patients far beyond childhood; therefore, all pediatric CF patients must prepare for transition to adult care. Readiness assessment, knowledge and skill education, and support structures are all elements of ideal transition. Transition should begin early in life with teaching skills and knowledge for disease care, and in adolescence the readiness to transition should be addressed. Transition is a gradual process of increasing responsibilities in self-care and disease management, an improvement in the understanding of CF, and an iterative process of self-assessment with knowledge acquisition. Communication and collaboration between pediatric and adult providers is necessary to ensure a smooth and successful transition with minimum effect on outcomes. Although there is increased knowledge of successful transition practices, this area presents many opportunities for advancement of care for the patient with CF. [Pediatr Ann. 2017;46(5):e188-e192.].

Microbiology of the Upper and Lower Airways in Pediatric Cystic Fibrosis Patients.

Objective To evaluate the microbiology of the upper and lower airways in pediatric cystic fibrosis (CF) patients who underwent sinus surgery. Study Design Retrospective case series with chart review. Setting Tertiary care children's hospital. Subjects and Methods A total of 201 paired sinus and pulmonary cultures from 105 CF patients were identified between 1996 and 2014. Demographics and culture results were analyzed. Results The mean age of patients was 11.2 ± 5.4 years (range, 1-27 years), and approximately one-half were female. Methicillin-sensitive Staphylococcus aureus was the most common pathogen overall. A significantly higher prevalence of Pseudomonas aeruginosa (32% for pulmonary and 37% for sinus cultures) was observed in older patients versus younger patients ( P < .001). There was low to moderate agreement between sinus and pulmonary cultures (Kappa statistic range, 0.03-0.56). The prevalence of methicillin-resistant S aureus (MRSA) increased significantly for lower respiratory tract culture (from 5% to 16%) and sinus culture (from 5% to 27%) between 1996-2004 and 2010-2014 ( P = .016 and P < .001, respectively). The prevalence of positive sinus cultures increased from 40% to 85% between 1996-2004 and 2010-2014 ( P = .018). Patients with pulmonary MRSA were more likely to be coinfected with pulmonary P aeruginosa (risk ratio, 2.4; 95% CI, 1.2-4.8; P = .015) or Aspergillus fumigatus (risk ratio, 2.2; 95% CI, 1.2-4.8; P = .035). Conclusions There is low to moderate correlation between pulmonary and sinus pathogens in CF patients. This is important to consider when treating infections. The prevalence of MRSA in sinus cultures has increased over time and warrants further investigation.

Piperacillin-tazobactam versus cefepime incidence of acute kidney injury in combination with vancomycin and tobramycin in pediatric cystic fibrosis patients

Cystic fibrosis (CF) patients often receive prolonged courses of broad spectrum antibiotics, such as piperacillin-tazobactam or cefepime in combination with vancomycin and tobramycin. The objective of this study was to determine the difference in AKI for pediatric CF patients receiving piperacillin-tazobactam or cefepime in combination with vancomycin and tobramycin. IRB approval from a single CF center was obtained for this retrospective cohort study. Charts were evaluated from December 1, 2008 to June 30,2015. Patients were included if they had a diagnosis of CF, age 30 days to 18 years, and received intravenous vancomycin, tobramycin, and piperacillin-tazobactam or cefepime. The primary outcome was difference of AKI incidence in patients receiving piperacillin-tazobactam or cefepime, as defined by modified pediatric risk, injury, failure, loss, end stage renal disease (pRIFLE) criteria. Seventy-one patients were included with a median (interquartile range) age 11 years (7-16) and weight 36.2 kg (22.7-50). AKI was identified in 54.5% (18/33) of patients receiving piperacillin-tazobactam and 13.2% (5/38) of patients receiving cefepime (P ≤ 0.0001). One patient receiving piperacillin-tazobactam experienced acute renal failure. There was a slight difference in length of admission (13 vs 10 days, P = 0.042), but no difference in days to maximum SCr (6 vs 3, P = 0.127) nor FEV1 percent predicted on admission (69% vs 65%, P = 1.00). AKI occurred in nearly 55% of patients with piperacillin-tazobactam therapy versus 13% of patients with cefepime therapy, which suggests cefepime may be preferred in combination with vancomycin and tobramycin for pediatric CF patients.

(729) - Determination of Modifiable Risk Factors for Infection in the Early Post Lung Transplant Period for Pediatric Cystic Fibrosis Patients

(729) - Determination of Modifiable Risk Factors for Infection in the Early Post Lung Transplant Period for Pediatric Cystic Fibrosis Patients

Evaluation of Functional Characteristics of 4 Oscillatory Positive Pressure Devices in a Simulated Cystic Fibrosis Model

Oscillatory positive expiratory pressure (OPEP) is an airway clearance therapy that delivers positive pressure and air-flow oscillations during exhalation. This study described functional characteristic differences of 4 OPEP devices during an active exhalation in a simulated model. We hypothesized peak pressure (Ppeak), positive expiratory pressure (PEP), oscillatory frequency (f), and pressure amplitude will differ, depending upon the device used, device resistance setting, and time (repeated consecutive active exhalations through the device). The ASL 5000 was scripted to simulate pulmonary mechanics of a pediatric cystic fibrosis patient with moderate to severe lung disease. Airway resistance was standardized at 17.1 cm H2O/L/s, pulmonary compliance at 42.1 mL/cm H2O, active exhalation at 22 breaths/min, and tidal volume at 409 mL. Resistance settings for the Acapella, RC-Cornet, Flutter, and Aerobika were adjusted to low, medium, and high. Values for f, Ppeak, PEP, and pressure amplitude were recorded for 1 min and graphically displayed. Significant effects for time, device, and resistance (P < .01) were noted for Ppeak, PEP, and pressure amplitude at each resistance level, demonstrating that the devices functioned differently as more than one repetition of a series of consecutive active exhalations are performed. Significant interaction effects for device, resistance level, and time indicate inconsistent output for Ppeak (P < .01), PEP (P < .01), and pressure amplitude (P < .01). Oscillatory f values fell within the respective manufacturers' operational parameters. The Aerobika provided the most consistent pressure amplitude across resistance settings and produced the highest mean pressure amplitude at medium and high resistance settings. Statistically significant and clinically relevant variations in Ppeak, PEP, and pressure amplitude occurred between devices and within a device, as the resistance setting changed. The combination of device, time, and resistance settings affects OPEP device output for pressure, amplitude, and oscillatory frequency. Functional variations may impact therapeutic effectiveness, warranting additional study to determine clinical impact.

Steady-State Therapy with Azithromycin or Low-Dose Prednisolone in Paediatric Cystic Fibrosis Patients: Inflammatory Markers and Disease Progression

Background: Anti-inflammatory therapy is a logical approach to slowing the inevitable lung function deterioration in cystic fibrosis (CF) patients. This study's aim was to evaluate inflammatory markers and disease progression in paediatric CF patients chronically treated with azithromycin or low-dose prednisolone. Methods: The study included 204 patients with CF and 100 healthy controls; 102 CF patients were treated with basic therapy only (without anti-inflammatory treatment; WAT), and 102 individuals received basic therapy along with azithromycin (n = 59) or low-dose prednisolone (n = 43). The median duration of therapy was 24 months (range 12-82) with azithromycin and 31 months (range 12-180) with prednisolone. A cross-sectional analysis of plasma and sputum biomarkers was performed. Results: Compared with the healthy controls, the WAT group showed elevated IFN-γ, IL-10 (total), and TGFβ₁ concentrations, and decreased TNFα (total) and adrenocorticotropic hormone (ACTH) levels (all p < 0.05). Plasma TNFα (total) concentrations in azithromycin/prednisolone patients were significantly higher than those in WAT patients and similar to those of healthy children. In contrast, IL-10 (total) levels were significantly decreased in azithromycin/prednisolone-treated patients compared with WAT patients. Children from the azithromycin group demonstrated ACTH levels similar to those of healthy controls. Azithromycin-treated patients showed a significantly reduced rate of CF-related liver disease and a significantly increased incidence of glucose metabolism disturbances. Conclusions: Steady-state anti-inflammatory treatments may have a sustained immunomodulatory action at systemic and local levels in CF patients. Further investigations are needed to assess the effects of supportive azithromycin therapy on the hypothalamic-pituitary-adrenal axis and the incidence of non-pulmonary CF complications.

Effectiveness of a stepwise Pseudomonas aeruginosa eradication protocol in children with cystic fibrosis

IntroductionAntibiotic eradication therapy (AET) for initial Pseudomonas aeruginosa (Pa) infection is standard of care in children with cystic fibrosis (CF), but information is limited on treatment for patients who fail initial AET. The aim of this study was to evaluate the effectiveness of a multi-step protocol for AET for new-onset Pa infections in children with CF. MethodsA three-step AET protocol which includes: (step 1) 28days of tobramycin inhalation solution (TIS) for new-onset Pa infection; (step 2) a second course of TIS for patients with positive respiratory tract culture after step 1; (step 3) 14days of intravenous antibiotics followed by 28days of TIS for patients with a subsequent positive culture. We conducted a retrospective review of all pediatric CF patients who underwent the eradication protocol between January 2010 and December 2015. The success rate of each step and of the overall protocol was recorded. ResultsDuring the study period, 128 patients had a total of 213 new-onset Pa infections. Of 195 asymptomatic episodes, 150 (76.9%, 95% CI 70.4; 82.6) cleared after step 1 and 12 cleared after step 2 (33.3% (95% CI 18.6; 50.9) stepwise success rate and 87.1% (95% CI 77.1; 88.1) cumulative success rate). Intravenous antibiotics followed by 28days of TIS were administered in 24 episodes; this was successful in 10 episodes (41.7%; 95% CI 22.1; 63.4). The regimen in asymptomatic patients failed in fourteen episodes (7.5%; 95% CI 4.2; 12.3) then considered chronically infected with Pa. Overall, the cumulative success rate of the asymptomatic arm was 88.2% (95% CI 82.8; 92.4). ConclusionThe first step of the AET protocol led to the greatest eradication success. Subsequent eradication attempts have a success rate below 50%. Prospective studies of eradication protocols for this population are needed to determine the most effective treatment strategy.

High attainment of optimal nutritional and growth status observed among Greek pediatric cystic fibrosis patients: results from the GreeCF study.

Pediatric cystic fibrosis (CF) patients suffer high rates of undernutrition, subject to several parameters. We aimed to assess growth and nutritional status of Greek children and adolescents with CF. Eighty-four patients (35 boys) formed the sample. Anthropometrics and FEV1 were measured, growth and weight status were assessed. Body mass index (BMI), arm circumference (MUAC), fat (MUAFA) and muscle (MUAMA) were calculated. In the total sample, 6.0% of the patients were underweight, 4.8% stunted, 8.3% wasted and 17.9% in nutritional failure, whereas 59.5% attained the ideal BMI for CF. FEV1 positively associated with BMI (B=0.03, p≤0.003), weight (B=0.03, p≤0.003) and MUAMA z-scores (B=0.04, p≤0.005). Meconium ileus negatively associated with FEV1 (B=-14.17, p≤0.003) and stature (B=-0.65, p≤0.043). Pancreatic insufficiency negatively influenced MUAC and MUAFA z-scores (p≤0.05 for both). The examined CF patients appear to be thriving. Unlike published research, the participants' sex, gene mutation and acquisition of pathogens did not affect growth.

Red blood cell distribution width is not a reliable biomarker for low iron stores in children with cystic fibrosis

ABSTRACTLow iron stores in children, absolute iron deficiency (AID), can lead to impaired neurodevelopment and requires iron therapy. In the presence of infection/inflammation, like in cystic fibrosis (CF), serum ferritin (SF) is not a reliable biomarker for AID. Red blood cell distribution width (RDW) is a promising alternative reported not to be influenced by infection in healthy children. Currently, there are no data on the diagnostic capacity of RDW to detect AID in pediatric CF patients. This was a prospective observational study that investigated iron status biomarkers in 53 Dutch pediatric CF patients. AID was defined using World Health Organization criteria for SF in stable patients (no recent pulmonary exacerbation) and C-reactive protein (CRP) ≤10 mg/l. Patients with AID had higher RDW levels than patients without AID (p = 0.019). An RDW ≥13.2% showed the following test statistics: sensitivity 100%; specificity 39.4%; positive predictive value 20%; and negative predictive value 100%. Furthermore, we found a correlation between RDW and CRP in the total group that originated from the stable patients (r = 0.308; p = 0.042). In conclusion, the diagnostic capacity of RDW for detecting AID in pediatric CF patients seems limited because RDW levels might also be influenced by chronic infection/inflammation in these patients.