Pediatric Cystic Fibrosis Patients Research Articles

Restored Cytokine-Producing Capacities of Mucosal-Associated Invariant T Cells in Pediatric Cystic Fibrosis Patients Treated with Elexacaftor/Tezacaftor/Ivacaftor.

Restored Cytokine-Producing Capacities of Mucosal-Associated Invariant T Cells in Pediatric Cystic Fibrosis Patients Treated with Elexacaftor/Tezacaftor/Ivacaftor.

Elexacaftor/Tezacaftor/Ivacaftor use in Pediatric Cystic Fibrosis Patients with Advanced Liver Disease

BackgroundCystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy extends the life expectancy of people with cystic fibrosis (PwCF). However, CFTR modulators have not been well studied in patients with cystic fibrosis liver disease (CFLD), specifically those with advanced liver disease with portal hypertension. The purpose of this report is to describe the use of elexacaftor/tezacaftor/ivacaftor (ETI) in pediatric CF patients with advanced CFLD. MethodsThis retrospective case series included PwCF < 18 years old with baseline advanced CFLD initiated on ETI. ResultsEleven PwCF and advanced CFLD were treated with ETI; six started a reduced dose regimen. No patient required treatment interruption and four patients received dose changes related to increase in transaminase and/or bilirubin elevations. Mean (SD) change in ppFEV1 from prior to ETI to highest value during therapy was 14.27 % (4.25) (p = 0.007). When evaluating the group as whole, AST decreased from baseline to last reported –15.18 (23.23) units/L (p = 0.054) and ALT slightly increased 0.73 (39.13) units/L (p = 0.96). Bilirubin increased minimally overall for patients with mean change from baseline of 0.83 (1.33) mg/dL [range –0.5–3] (p = 0.17). A model for time on ETI showed a significant decrease in AST over time of 0.955 per month of ETI but no other liver biochemistries were significant. No patient experienced decompensation of CFLD. ConclusionETI therapy in pediatric CF patients with advanced CFLD can be beneficial in improving pulmonary and nutritional outcomes without negative impact on liver biochemistries or hepatic outcomes. Close monitoring is recommended to ensure safety and tolerability.

Ecological patterns and processes of temporal turnover within lung infection microbiota

BackgroundChronic infection and consequent airway inflammation are the leading causes of morbidity and early mortality for people living with cystic fibrosis (CF). However, lower airway infections across a range of chronic respiratory diseases, including in CF, do not follow classical ‘one microbe, one disease’ concepts of infection pathogenesis. Instead, they are comprised of diverse and temporally dynamic lung infection microbiota. Consequently, temporal dynamics need to be considered when attempting to associate lung microbiota with changes in disease status. Set within an island biogeography framework, we aimed to determine the ecological patterns and processes of temporal turnover within the lung microbiota of 30 paediatric and adult CF patients prospectively sampled over a 3-year period. Moreover, we aimed to ascertain the contributions of constituent chronic and intermittent colonizers on turnover within the wider microbiota.ResultsThe lung microbiota within individual patients was partitioned into constituent chronic and intermittent colonizing groups using the Leeds criteria and visualised with persistence-abundance relationships. This revealed bacteria chronically infecting a patient were both persistent and common through time, whereas intermittently infecting taxa were infrequent and rare; respectively representing the resident and transient portions of the wider microbiota. It also indicated that the extent of chronic colonization was far greater than could be appreciated with microbiological culture alone. Using species-time relationships to measure temporal turnover and Vellend’s rationalized ecological processes demonstrated turnover in the resident chronic infecting groups was conserved and underpinned principally by the deterministic process of homogenizing dispersal. Conversely, intermittent colonizing groups, representing newly arrived immigrants and transient species, drove turnover in the wider microbiota and were predominately underpinned by the stochastic process of drift. For adult patients, homogenizing dispersal and drift were found to be significantly associated with lung function. Where a greater frequency of homogenizing dispersal was observed with worsening lung function and conversely drift increased with better lung function.ConclusionsOur work provides a novel ecological framework for understanding the temporal dynamics of polymicrobial infection in CF that has translational potential to guide and improve therapeutic targeting of lung microbiota in CF and across a range of chronic airway diseases.AWnQWdeG2wJZnAAmwW9_w-Video

Surgical and medical management of chronic rhinosinusitis in pediatric cystic fibrosis patients: Impact on olfactory symptoms

Background and purposeOlfactory dysfunction (OD) commonly occurs in patients with sinonasal dysfunction, but the prevalence and severity of olfactory issues in adolescents with cystic fibrosis (AwCF) is unclear. OD may contribute to dietary deficiencies and exacerbate nutritional challenges. We sought to review literature on the effectiveness of medical and surgical management of sinonasal symptoms in AwCF and the associated impact on olfactory function. MethodsWe performed a systematic literature search of PubMed, Embase, Web of Science, and Ebsco CINAHL from 1980 to 2022 per PRISMA-ScR protocols to conduct a scoping review in an effort to compile data on study design, patient demographics, clinical characteristics and outcomes, along with risk of bias. ResultsOf 368 abstracts, 3 articles exclusively evaluated AwCF for a total of 34 patients. Two studies evaluated endoscopic sinus surgery (ESS) and dornase alfa. An additional 6 articles were included for mixed pediatric and adult CF populations totaling 313 patients. Interventions included ESS, elexacaftor-tezacaftor-ivacaftor (ETI), ivacaftor, saline, dornase alfa, hyaluronic acid, and hyaluronic acid-tobramycin combination. Outcome measures included subjective assessment of OD using non-validated (4/9) and validated (4/9) surveys, and psychophysical (1/9) smell testing. Studies evaluating ESS, FESS, dornase alfa, ivacaftor, and both hypertonic and isotonic saline reported statistically significant improvement in OD, whereas ETI failed to improve OD despite improvement in other quality of life measures. ConclusionsThere is limited data regarding the impact of medical and surgical interventions on olfaction for AwCF. Assessment of olfaction was often limited to subjective and qualitative self-report. We suggest that tracking of olfactory outcomes with psychophysical testing is critical in this population with dietary challenges and weight management issues.

A skin-interfaced, miniaturized platform for triggered induction, capture and colorimetric multicomponent analysis of microliter volumes of sweat

Eccrine sweat can serve as a source of biomarkers for assessing physiological health and nutritional balance, for tracking loss of essential species from the body and for evaluating exposure to hazardous substances. The growing interest in this relatively underexplored class of biofluid arises in part from its non-invasive ability for capture and analysis. The simplest devices, and the only ones that are commercially available, exploit soft microfluidic constructs and colorimetric assays with purely passive modes of operation. The most sophisticated platforms exploit batteries, electronic components and radio hardware for inducing sweat, for electrochemical evaluation of its content and for wireless transmission of this information. The work reported here introduces a technology that combines the advantages of these two different approaches, in the form of a cost-effective, easy-to-use device that supports on-demand evaluation of multiple biomarkers in sweat. This flexible, skin-interfaced, miniaturized system incorporates a hydrogel that contains an approved drug to activate eccrine sweat glands, electrodes and a simple circuit and battery to delivery this drug by iontophoresis through the surface of the skin, microfluidic channels and microreservoirs to capture the induced sweat, and multiple colorimetric assays to evaluate the concentrations of chloride, zinc, and iron. As demonstrated in healthy human participants monitored before and after a meal, such devices yield results that match those of traditional laboratory analysis techniques. Clinical studies that involve cystic fibrosis pediatric patients illustrate the use of this technology as a simple, painless, and reliable alternative to traditional hospital systems for measurements of sweat chloride.

Lung clearance index short-term variability in cystic fibrosis: a pre-post pulmonary exacerbation study

BackgroundMultiple Breath washout (MBW) represents an important tool to detect early a possible pulmonary exacerbation especially in Cystic Fibrosis (CF) disease. Lung clearance index (LCI) is the most commonly reported multiple breath washout (MBW) index and in the last years was used as management measure for evaluation. Our aim was to analyze clinical utility of LCI index variability in pulmonary exacerbation in CF after intravenous (IV) antibiotic therapy.MethodsA single-center study was conducted at CF Unit of Bambino Gesù Children’s Hospital among hospitalized > 3 years patients for pulmonary exacerbations and treated with antibiotic IV treatment for 14 days. MBW and spirometry were evaluated within 72 h of admission to hospital and at the end of hospitalization. Descriptive analysis was conducted and correlations between quantitative variables were investigated.ResultsFifty-seven patients (M22/F35) with an average age 18.56 (± 8.54) years were enrolled. LCI2.5 was significantly reduced at the end of antibiotic treatment in both pediatric and adult populations with an average reduction of -6,99%; 37/57 patients denoted an improvement, 20/57 are stable or worsened in LCI2.5 values and 4/57 (7.02%) had a significant deterioration (> 15%) at end of treatment. On the contrary a significative elevation of FEV1 and FVC were found, respectively of + 7,30% and of + 5,46%. A positive good correlection among LCI 2.5 and Scond (rho = + 0,615, p = 0.000) and LCI 2.5 and Sacin (rho = + 0,649, p = 0.000) and a negative strong correlation between FEV1 and LCI 2.5 were found in post treatment period. A similar modification of LCI 2.5 and FEV1 was noticed in both adult and pediatric population.ConclusionsLCI may have a role in the routine clinical care of both adult and pediatric CF patients as a good tool to assess response to IV antibiotic end-therapy in the same way as FEV1.

NorA efflux pump mediates Staphylococcus aureus response to Pseudomonas aeruginosa pyocyanin toxicity.

Endogenous transporters protect Staphylococcus aureus against antibiotics and also contribute to bacterial defense from environmental toxins. We evaluated the effect of overexpression of four efflux pumps, NorA, NorB, NorC, and Tet38, on S. aureus survival following exposure to pyocyanin (PYO) of Pseudomonas aeruginosa, using a well diffusion assay. We measured the PYO-created inhibition zone and found that only an overexpression of NorA reduced S. aureus susceptibility to pyocyanin killing. The MICPYO of the NorA overexpressor increased threefold compared to that of wild-type RN6390 and was reduced 2.5-fold with reserpine, suggesting that increased NorA efflux caused PYO resistance. The PYO-created inhibition zone of a ΔnorA mutant was consistently larger than that of a plasmid-borne NorA overexpressor. PYO also produced a modest increase in norA expression (1.8-fold at 0.25 µg/mL PYO) that gradually decreased with increasing PYO concentrations. Well diffusion assays carried out using P. aeruginosa showed that ΔnorA mutant was less susceptible to killing by PYO-deficient mutants PA14phzM and PA14phzS than to killing by PA14. NorA overexpression led to reduced killing by all tested P. aeruginosa. We evaluated the NorA-PYO interaction using a collection of 22 clinical isolates from adult and pediatric cystic fibrosis (CF) patients, which included both S. aureus (CF-SA) and P. aeruginosa (CF-PA). We found that when isolated alone, CF-PA and CF-SA expressed varying levels of PYO and norA transcripts, but all four CF-PA/CF-SA pairs isolated concurrently from CF patients produced a low level of PYO and low norA transcript levels, respectively, suggesting a partial adaptation of the two bacteria in circumstances of persistent co-colonization.

Effects of Social Determinants of Health on Clinical Outcomes in Pediatric Cystic Fibrosis Patients

Background and Objective: &#x0D; Advances in the treatment of cystic fibrosis (CF) with cystic fibrosis transmembrane regulator modulators have improved morbidity and mortality, however, clinical outcomes vary among genetically similar patients due to contributions of social determinants of health (SDOH). Pancreatic insufficiency, CF-related diabetes (CFRD), Pseudomonas infections, and lower BMI increase risk of severe lung disease, measured by forced expiratory volume in 1 second (FEV1). This project aims to identify socially vulnerable patients and evaluate the impact of SDOH on clinical outcomes. &#x0D; Methods: &#x0D; From January to July 2023, SDOH screeners were distributed to families of children with CF at Riley Hospital for Children, documenting transportation, housing, food insecurity, insurance, and medication costs. Clinical outcomes for each patient including FEV1% predicted, BMI/WFL percentile, CFRD, hospitalizations, respiratory infections with Pseudomonas aeruginosa, and pancreatic insufficiency within the past 12 months were recorded. Patients were categorized by SDOH vulnerability, and associations with poor clinical outcomes were analyzed using the Chi-squared test of independence. &#x0D; Results: &#x0D; A total of 193 screeners were analyzed: males represented 52.6% of the cohort, 2.60% identified as non-white race, and 3.65% reported Hispanic ethnicity. Overall, 51.8% screened positive for at least one SDOH (SDOH+) and 48.1% screened negative (SDOH-). The average FEV1% predicted decline among SDOH+ patients was 5.79% and 3.51% among SDOH- patients. SDOH+ patients were more likely to have at least a 5% decline in FEV1% predicted (p=0.037) and to be hospitalized due to exacerbations of CF lung disease at least once in the past 12 months (p=0.030). Although low BMI percentile, Pseudomonas infection, and CFRD were not significantly associated with SDOH, socially vulnerable patients demonstrated higher rates of these clinical outcomes. &#x0D; Conclusion and Clinical Implications: &#x0D; SDOH impact CF clinical outcomes. Screeners are effective in identifying socially vulnerable patients and serve as the first step in addressing unmet social needs.

Extracellular vesicles from BALF of pediatric cystic fibrosis and asthma patients increase epithelial sodium channel activity in small airway epithelial cells

Extracellular Vesicles (EVs) are nanosized vesicles derived from all cell types. EV cargo allows for intercellular communication, intracellular signaling, and regulation of proteins in recipient cells. We tested the hypothesis that EVs isolated from the bronchoalveolar-lavage fluid (BALF) of pediatric cystic fibrosis (CF) or pediatric asthma patients increase epithelial sodium channel (ENaC) activity in normal human small airway epithelial cells (SAECs) and the mechanism involves specific EV lipids. We characterized EVs from BALF of pediatric CF and pediatric asthma patients by nanoparticle tracking analysis, transmission electron microscopy, and Western blotting. The CF and asthma pediatric groups were similar in BALF electrolytes concentration and cell count, except for neutrophils, which were higher in the CF group. Lipidomic analyses for each group of EVs were performed using targeted mass spectrometry. Phosphatidylethanolamine, sphingomyelins, and triacylglycerol were enriched in both groups, but phosphatidylcholine and phosphatidylinositol concentrations were greater in the CF group compared to the asthma group, and the opposite trend was found for phosphatidylserine. Endogenous ENaC activity, measured by the single-channel patch-clamp technique, increased in normal human SAECs after challenging SAEC with EVs from either the CF or asthma groups compared to control EVs. In conclusion, EVs isolated from BALF of pediatric patients with CF or asthma have unique lipid profiles. Despite the differences, both types of EVs increase ENaC activity in normal human SAECs compared to control EVs isolated from the conditioned media of these cells.

P321 Impact of short-term CFTR modulators treatment on changes in nutritional and glucose status in cystic fibrosis paediatric patients with different glucose tolerance

Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies are drugs that could change the course of the disease in cystic fibrosis (CF) patients and also nutrition status and glucose metabolism. Our study aimed to assess the impact of CFTR modulators treatment on nutritional and glucose status in CF pediatric patients with different glucose tolerance.

P342 Serum sodium, chloride and potassium levels after start CFTR modulators treatment in CF pediatric patients

Cystic fibrosis can lead to electrolyte imbalance. Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies target the underlying cause of cystic fibrosis (CF) and also could change the ions’ status. However, there is a lack of evidence on whether the electrolyte level in the blood differs after CFTR modulator treatment.

P213 Post-acute sequelae of COVID-19 in children with cystic fibrosis: a case-control study

This study was aimed to evaluate the prevalence and characteristics of post-acute sequelae of COVID-19 (PASC) in cystic fibrosis (CF) pediatric patients, including clinical data, persistent symptoms, change in pulmonary exacerbations and self-rated health.

P045 Physical fitness of paediatric cystic fibrosis patients in the era of CFTR modulators

P045 Physical fitness of paediatric cystic fibrosis patients in the era of CFTR modulators

Impact of omega-3 supplementation on children and adolescents patients with cystic fibrosis: A systematic review and meta-analysis of randomized-controlled trials.

Clinical trial research have provided evidence that omega-3 may have larger potential benefits for treating cystic fibrosis (CF). This study's objective was to assess the impact of three supplementation on pediatric CF patients. Scopus, PubMed/Medline, Web of Science, Cochrane, and Embase databases were searched from commencement until July 20, 2022 using standard keywords to identify all randomized controlled studies (RCTs) examining the effects of omega-3 supplementation on young patients with CF. The eligible studies were subjected to a random-effects model meta-analysis. A meta-analysis of 12 the eligible studies was performed. Findings of the study showed that omega-3 supplementation significantly increased the levels of docosahexaenoic acid (weighted mean [WMD]: 2.06%, 95% confidence interval [CI]: 1.29, 2.82, p < 0.001) and eicosapentaenoic acid (WMD: 0.32%, 95% CI: 0.15, 0.48, p < 0.001) as well as decreased arachidonic acid (WMD: -0.78%, 95% CI: -1.50, -0.05, p = 0.035) and C-receptive protein (CRP) (WMD: -3.76 mg/L, 95% CI: -7.42, -0.10, p = 0.044) especially when used in higher doses and for a longer period of time compared to the control group. However, no significant effect was observed on other factors including forced expiratory volume 1, forced vital capacity as well as anthropometric parameters. In addition, high heterogeneity was reported for all fatty acids, but heterogeneity was low and nonsignificant for other variables. The finding showed that in pediatric patients with CF, omega-3 supplementation showed benefits only in plasma fatty acid profile and serum CRP.

16S rRNA-Based Microbiota Profiling Assists Conventional Culture Analysis of Airway Samples from Pediatric Cystic Fibrosis Patients.

16S-based sequencing provides broader information on the respiratory microbial community than conventional culturing. However, it (often) lacks species- and strain-level information. To overcome this issue, we used 16S rRNA-based sequencing results from 246 nasopharyngeal samples obtained from 20 infants with cystic fibrosis (CF) and 43 healthy infants, which were all 0 to 6 months old, and compared them to both standard (blind) diagnostic culturing and a 16S-sequencing-informed "targeted" reculturing approach. Using routine culturing, we almost uniquely detected Moraxella catarrhalis, Staphylococcus aureus, and Haemophilus influenzae (42%, 38%, and 33% of samples, respectively). Using the targeted reculturing approach, we were able to reculture 47% of the top-5 operational taxonomical units (OTUs) in the sequencing profiles. In total, we identified 60 species from 30 genera with a median of 3 species per sample (range, 1 to 8). We also identified up to 10 species per identified genus. The success of reculturing the top-5 genera present from the sequencing profile depended on the genus. In the case of Corynebacterium being in the top 5, we recultured them in 79% of samples, whereas for Staphylococcus, this value was only 25%. The success of reculturing was also correlated with the relative abundance of those genera in the corresponding sequencing profile. In conclusion, revisiting samples using 16S-based sequencing profiles to guide a targeted culturing approach led to the detection of more potential pathogens per sample than conventional culturing and may therefore be useful in the identification and, consequently, treatment of bacteria considered relevant for the deterioration or exacerbation of disease in patients like those with CF. IMPORTANCE Early and effective treatment of pulmonary infections in cystic fibrosis is vital to prevent chronic lung damage. Although microbial diagnostics and treatment decisions are still based on conventional culture methods, research is gradually focusing more on microbiome and metagenomic-based approaches. This study compared the results of both methods and proposed a way to combine the best of both worlds. Many species can relatively easily be recultured based on the 16S-based sequencing profile, and it provides more in-depth information about the microbial composition of a sample than that obtained through routine (blind) diagnostic culturing. Still, well-known pathogens can be missed by both routine diagnostic culture methods as well as by targeted reculture methods, sometimes even when they are highly abundant, which may be a consequence of either sample storage conditions or antibiotic treatment at the time of sampling.

Evaluation of serum VIP and aCGRP during pulmonary exacerbation in cystic fibrosis: A longitudinal pilot study of patients undergoing antibiotic therapy.

Objective monitoring of improvement during treatment of pulmonary exacerbation can be difficulty in children when pulmonary function testing cannot be obtained. Thus, the identification of predictive biomarkers to determine the efficacy of drug treatments is of high priority. The major aim of the current study was to investigate the serum levels of vasoactive intestinal peptide (VIP) and alpha calcitonin gene related peptide (aCGRP) of cystic fibrosis pediatric patients during pulmonary exacerbation and post-antibiotic therapy, and possible associations of their levels with different clinicopathological parameters. 21 patients with cystic fibrosis were recruited at onset of pulmonary exacerbation. Serum was collected at time of admission, three days post-antibiotic therapy, and two weeks post-antibiotic therapy (end of antibiotic therapy). Serum VIP and aCGRP levels were measured using ELISA. Overall least square means of serum aCGRP level but not VIP changed from time of exacerbation to completion of antibiotic therapy (p = 0.005). Serum VIP was significantly associated with the presence of diabetes mellitus (p = 0.026) and other comorbidities (p = 0.013), and with type of antibiotic therapy (p = 0.019). Serum aCGRP level was significantly associated with type of antibiotic therapy (p = 0.012) and positive Staphylococcus aureus microbiology test (p = 0.046). This study could only show significant changes in serum aCGRP levels following treatment of pulmonary exacerbations. Future studies with larger sample size are required to investigate the clinical importance of VIP and aCGRP in cystic fibrosis patients.

Exhaled breath profiles to detect lung infection with Staphylococcus aureus in children with cystic fibrosis

BackgroundAn electronic nose (eNose) can be used to detect volatile organic compounds (VOCs). Exhaled breath contains numerous VOCs and individuals’ VOCs mixtures create distinct breath profiles. Previous reports have shown that eNose can detect lung infections. Whether eNose can detect Staphylococcus aureus airway infections in breath of children with cystic fibrosis (CF) is currently unclear. MethodsIn this cross-sectional observational study, a cloud-connected eNose was used for breath profile analysis of clinically stable paediatric CF patients with airway microbiology cultures positive or negative for CF pathogens. Data-analysis involved advanced signal processing, ambient correction and statistics based on linear discriminant and receiver operating characteristics (ROC) analyses. ResultsBreath profiles from 100 children with CF (median predicted FEV1 91%) were obtained and analysed. CF patients with positive airway cultures for any CF pathogen were distinguishable from no CF pathogens (no growth or usual respiratory flora) with accuracy of 79.0% (AUC-ROC 0.791; 95% CI: 0.669–0.913) and between patients positive for Staphylococcus aureus (SA) only and no CF pathogen with accuracy of 74.0% (AUC-ROC 0.797; 95% CI: 0.698–0.896). Similar differences were seen for Pseudomonas aeruginosa (PA) infection vs no CF pathogens (78.0% accuracy, AUC-ROC 0.876, 95% CI: 0.794–0.958). SA- and PA-specific signatures were driven by different sensors in the SpiroNose suggesting pathogen-specific breath signatures. ConclusionsBreath profiles of CF patients with SA in airway cultures are distinct from those with no infection or PA infection, suggesting the utility of eNose technology in the detection of this early CF pathogen in children with CF.

Importance of Vitamin D Status and Nerve Conduction in Pediatric Cystic Fibrosis Patients

AbstractCystic fibrosis is one of the most common inherited diseases. It presents with recurrent respiratory infections, pancreatic insufficiency, and growth retardation. Neurological involvement becomes more common as life expectancy increases. Chronic hypoxia, impaired glucose intolerance, autoimmune mechanisms, vasculitis changes, and micronutrient deficiencies seem to cause neuropathy in cystic fibrosis. This study was aimed to investigate peripheral neuropathy in pediatric cystic fibrosis patients. Twenty-one cystic fibrosis patients and 19 healthy control subjects between the ages of 7 and 17 years were included. Their nerve conduction study results and laboratory investigations were analyzed. Participants were classified into four groups; 1. Cystic fibrosis with vitamin D deficiency, 2. Cystic fibrosis with normal vitamin D levels, 3. Healthy subjects with vitamin D deficiency, 4. Healthy subjects with normal vitamin D levels. We found statistically significantly lower sensory median nerve sensorial nerve action potential, sensorial sural nerve conduction velocity, and motor peroneal nerve compound motor action potential in cystic fibrosis patients with vitamin D deficiency than in other cases. We also found that the main difference between cystic fibrosis and control groups was especially in patients with low vitamin D levels. Nerve damage starts at an early age, especially in cystic fibrosis patients especially those with vitamin D deficiency. Electrophysiological evaluation to assess neuropathy is important even in asymptomatic patients. Prevention of hypovitaminosis D is important to prevent neuropathy in cystic fibrosis patients.

Airway clearance therapy in the school environment: Retrospective analysis of a cohort of pediatric patients with cystic fibrosis

BackgroundAdherence to airway clearance therapy (ACT) in pediatric cystic fibrosis (CF) patients is reported to be below 50% and inability to sustain daily care is linked to poor health outcomes7,8,9. Through a collaboration between a CF care center and several schools, we hypothesized that ACT completed at school by pediatric CF patients will improve lung function while decreasing pulmonary exacerbations (PEx), days of antibiotics (abx) and hospitalizations. MethodsThis was a retrospective case-control study at a single CF care center consisting of 50 CF patients age < 18 at time when data was recorded (2012–2020). The case group used high-frequency chest wall oscillation or positive expiratory pressure devices at school for at least 1 year after self-reported or physician identified inadequate use at home. Lung function and measures of healthcare utilization were collected. ResultsIn the case group (n = 14), paired t-tests showed that after initiation of ACT at school, there were significant reductions in PEx requiring IV or PO abx (P = 0.010), total days of abx (P = 0.032), and visits to the CF care center (P = 0.037). There was no change in these outcomes in the matched control group (n = 36). ConclusionsThis is the first known study to highlight an initiative between a CF care center and schools which utilized airway clearance devices at school to ensure pediatric CF patients completed ACT. Through increased adherence, this relationship was associated with improved health outcomes. Use of alternative strategies may help patients with CF sustain adequate airway clearance.

Efficacy of the Simeox® Airway Clearance Technology in the Homecare Treatment of Children with Clinically Stable Cystic Fibrosis: A Randomized Controlled Trial.

Cystic fibrosis (CF) patients require regular airway clearance therapy (ACT). The aim of this study was to evaluate homecare therapeutic effects of a new ACT (Simeox®) added to the optimal standard of care, including home chest physiotherapy, in the treatment of clinically stable children. Forty pediatric CF patients (8-17 years old) with stable disease were randomized 1:1 in a single-center, prospective, open-label, cross-over trial into two groups: with or without Simeox®. Lung function (impulse oscillometry, spirometry, body plethysmography, multi-breath nitrogen washout) results, health-related quality of life, and safety were assessed during the study after 1 month of therapy at home. A significant decrease in proximal airway obstruction (as supported by improvement in airway resistance at 20 Hz (R20Hz) and maximum expiratory flow at 75% of FVC (MEF75)) compared to the control group was observed after 1 month of therapy with the device. Lung-clearance index was stable in the study group, while it worsened in the control group. In addition, the device group demonstrated a significant increase in the Cystic Fibrosis Questionnaire-Revised (CFQ-R) physical score. No side effects were identified during the study. Simeox® may improve drainage of the airways in children with clinically stable CF and could be an option in chronic treatment of the disease.