Prevalence, stability, and clinical significance of an isolated low FEV1 spirometry pattern in children.

OBJECTIVES: In adults, an isolated low FEV1 pattern (an FEV1 below the lower limit of normal with a preserved FVC and FEV1/FVC) has been associated with the risk of developing airway obstruction. Our objective was to examine the prevalence, stability, and clinical significance of an isolated low FEV1 pattern in the pediatric population. METHODS: We conducted a retrospective study of spirometries from children ages 6-21 years and categorized tests into spirometry patterns according to published guidelines and recent literature. In a subgroup of tests with an isolated low FEV1 pattern, we evaluated spirometry technique. We also examined the association of having a test with an isolated low FEV1 pattern with clinical markers of disease severity in a subgroup of children with cystic fibrosis (CF). RESULTS: The isolated low FEV1 pattern was uncommon across the 29,979 tests included (n = 645 [2%]). In the 263 children with an isolated low FEV1 pattern who had a follow-up test performed, the most frequent spirometry pattern at last test was normal (n = 123 [47%]). A primary diagnosis of CF was associated with increased odds of having at least one test with an isolated low FEV1 pattern (OR = 8.37, 95% CI = 4.70-15.96, p < .001). The spirometry quality in a subgroup of tests with an isolated low FEV1 pattern (n = 50) was satisfactory. In the subgroup of children with CF (n = 102), those who had a test with an isolated low FEV1 pattern had higher odds of using oral antibiotics in the last 12 months than those who had a normal pattern (OR = 3.50, 95% CI = 1.15-10.63, p = .03). CONCLUSIONS: The isolated low FEV1 pattern can occur repeatedly over time, usually transitions to a normal pattern, is not due to a poor spirometry technique, and could be clinically relevant in children with chronic lung diseases.

Longitudinal profiling of the intestinal microbiome in children with cystic fibrosis treated with elexacaftor-tezacaftor-ivacaftor.

The intestinal microbiome influences growth and disease progression in children with cystic fibrosis (CF). Elexacaftor-tezacaftor-ivacaftor (ELX/TEZ/IVA), the newest pharmaceutical modulator for CF, restores the function of the pathogenic mutated CF transmembrane conductance regulator (CFTR) channel. We performed a single-center longitudinal analysis of the effect of ELX/TEZ/IVA on the intestinal microbiome, intestinal inflammation, and clinical parameters in children with CF. Following ELX/TEZ/IVA, children with CF had significant improvements in body mass index and percent predicted forced expiratory volume in one second, and required fewer antibiotics for respiratory infections. Intestinal microbiome diversity increased following ELX/TEZ/IVA coupled with a decrease in the intestinal carriage of Staphylococcus aureus, the predominant respiratory pathogen in children with CF. There was a reduced abundance of microbiome-encoded antibiotic resistance genes. Microbial pathways for aerobic respiration were reduced after ELX/TEZ/IVA. The abundance of microbial acid tolerance genes was reduced, indicating microbial adaptation to increased CFTR function. In all, this study represents the first comprehensive analysis of the intestinal microbiome in children with CF receiving ELX/TEZ/IVA.IMPORTANCECystic fibrosis (CF) is an autosomal recessive disease with significant gastrointestinal symptoms in addition to pulmonary complications. Recently approved treatments for CF, CF transmembrane conductance regulator (CFTR) modulators, are anticipated to substantially improve the care of people with CF and extend their lifespans. Prior work has shown that the intestinal microbiome correlates with health outcomes in CF, particularly in children. Here, we study the intestinal microbiome of children with CF before and after the CFTR modulator, ELX/TEZ/IVA. We identify promising improvements in microbiome diversity, reduced measures of intestinal inflammation, and reduced antibiotic resistance genes. We present specific bacterial taxa and protein groups which change following ELX/TEZ/IVA. These results will inform future mechanistic studies to understand the microbial improvements associated with CFTR modulator treatment. This study demonstrates how the microbiome can change in response to a targeted medication that corrects a genetic disease.

Gilbert's syndrome leads to elevated bilirubin after initiation of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis.

Nine people with cystic fibrosis (pwCF) were found to have isolated elevations in serum total bilirubin after starting elexacaftor/tezacaftor/ivacaftor (ETI) that were associated with Gilbert's Syndrome. In longitudinal examination, total bilirubin levels increased substantially after initiation of ETI without elevations in liver transaminases in those with this syndrome. Because elevated bilirubin levels in Gilbert's Syndrome are benign, ETI was able to be continued in these individuals. Genetic testing for this relatively common syndrome should be strongly considered for pwCF experiencing isolated hyperbilirubinemia after starting ETI, since appropriate diagnosis may help pwCF avoid unnecessary interruption in this therapy with significant health benefits in CF.

Fetal Sexual Dimorphism and Preeclampsia Among Twin Pregnancies.

BACKGROUND: In singleton pregnancies, fetal sexual dimorphism has been observed in hypertensive disorders of pregnancy, particularly preeclampsia, a morbid syndrome that increases the risk of adult-onset cardiovascular disease for mothers and their offspring. However, few studies have explored the effect of fetal sex on hypertensive disorders of pregnancy among twin pregnancies. METHODS: We conducted a retrospective cohort study of 1032 twin pregnancies between 2011 and 2022 using data from a perinatal database that recruits participants from 3 hospitals in Houston, TX. We categorized pregnancies based on fetal sex pairings into female/female, male/male, and female/male. Pregnancies with female/female pairs were used as our reference group. Our primary outcomes included gestational hypertension, preeclampsia, superimposed preeclampsia, and preeclampsia subtyped by gestational age of delivery. A modified Poisson regression model with robust error variance was used to calculate the relative risk and 95% CI for the association between fetal sex pairs and hypertensive disorders of pregnancy. RESULTS: Adjusted models of female/male pairs were associated with preterm preeclampsia (relative risk, 2.01 [95% CI, 1.15-3.53]) relative to those with female/female pairs. No associations with other hypertensive disorders of pregnancy were observed among pregnancies with male/male pairs compared with those with female/female fetal sex pairs. CONCLUSIONS: We found some evidence of sexual dimorphism for preterm preeclampsia among female/male twin pairs. Additional research is needed to understand what biological mechanisms could explain these findings.

The relationship between the intestinal microbiome and body mass index in children with cystic fibrosis.

BACKGROUND: The nutritional status of children with cystic fibrosis (CF), as assessed by their body mass index percentile (BMIp), is a critical determinant of long-term health outcomes. While the intestinal microbiome plays an important role in nutrition, little is known regarding the relationship of the microbiome and BMIp in children with CF. METHODS: Pediatric patients (< 18 years old) with CF and healthy comparison patients (HCs) were enrolled in the study and stool samples obtained. BMIp was categorized as Green Zone (BMIp > 50th), Yellow Zone (BMIp 25th-49th) and Red Zone (BMIp < 25th). Intestinal microbiome assessment was performed via 16S rRNA gene sequencing; microbial richness, diversity, and differential species abundance were assessed. RESULTS: Stool samples were collected from 107 children with CF and 50 age-matched HCs. Compared to HCs, children with CF were found to have lower bacterial richness, alpha-diversity, and a different microbial composition. When evaluating them by their BMIp color zone, richness and alpha-diversity were lowest in those in the Red Zone. In addition, an unclassified amplicon sequence variant (ASV) of Blautia, a known butyrate-producing anaerobe, was of lowest abundance in children in the Red Zone. CONCLUSION: Children with CF have a dysbiotic intestinal microbiome with specific changes that accompany changes in BMIp. Longitudinal assessments of the microbiome and its metabolic activities over time are needed to better understand how improvements in the microbiome may improve nutrition and enhance long-term survival in children with CF.

Fetal sexual dimorphism and preeclampsia among twin pregnancies.

Background: In singleton pregnancies, fetal sexual dimorphism has been observed in hypertensive disorders of pregnancy (HDP), particularly preeclampsia, a morbid syndrome that increases risk of adult onset cardiovascular disease for mothers and their offspring. However, few studies have explored the effect of fetal sex on HDP among twin pregnancies. Methods: We conducted a retrospective cohort study of 1,032 twin pregnancies between 2011 - 2022 using data from a perinatal database that recruits participants from three hospitals in Houston, TX. We categorized pregnancies based on fetal sex pairings into female/female, male/male, and female/male. Pregnancies with a female/female fetal sex were used as our reference group. Our primary outcomes included gestational hypertension, preeclampsia, superimposed preeclampsia, and preeclampsia subtyped by gestational age of delivery. A modified Poisson regression model with robust error variance was used to calculate the relative risk (RR) and 95% confidence interval (CI) for the association between fetal sex pairs and HDP. Results: Adjusted models of female/male fetal sex pairs were associated with preterm preeclampsia (RR 2.01, 95% CI 1.15-3.53) relative to those with female/female fetuses. No associations with other HDP were observed among pregnancies with male/male fetal sex compared to those with female/female fetal sex pairs. Conclusions: We found some evidence of sexual dimorphism for preterm preeclampsia among female/male twin pairs. Additional research is needed to understand what biological mechanisms could explain these findings.

Longitudinal Profiling of the Intestinal Microbiome in Children with Cystic Fibrosis Treated with Elexacaftor-Tezacaftor-Ivacaftor.

The intestinal microbiome influences growth and disease progression in children with cystic fibrosis (CF). Elexacaftor-tezacaftor-ivacaftor (ELX/TEZ/IVA), the newest pharmaceutical modulator for CF, restores function of the pathogenic mutated CFTR channel. We performed a single-center longitudinal analysis of the effect of ELX/TEZ/IVA on the intestinal microbiome, intestinal inflammation, and clinical parameters in children with CF. Following ELX/TEZ/IVA, children with CF had significant improvements in BMI, ppFEV1 and required fewer antibiotics for respiratory infections. Intestinal microbiome diversity increased following ELX/TEZ/IVA coupled with a decrease in the intestinal carriage of Staphylococcus aureus, the predominant respiratory pathogen in children with CF. There was a reduced abundance of microbiome-encoded antibiotic-resistance genes. Microbial pathways for aerobic respiration were reduced after ELX/TEZ/IVA. The abundance of microbial acid tolerance genes was reduced, indicating microbial adaptation to increased CFTR function. In all, this study represents the first comprehensive analysis of the intestinal microbiome in children with CF receiving ELX/TEZ/IVA.

Prevalence, Risk Factors, and Sequelae of Asymptomatic Clostridioides difficile Colonization in Children with Cystic Fibrosis.

Patients with CF (pwCF) have high antibiotic use and an altered intestinal microbiome, known risk factors for infection with Clostridioides difficile. However, in adults with CF, C. difficile infection (CDI) is uncommon and asymptomatic colonization with C. difficile occurs frequently, for reasons that remain unclear. We investigated the rate, risk factors, and sequelae of asymptomatic C. difficile colonization in children with CF (cwCF). We identified that 32% of cwCF were colonized with C. difficile without acute gastrointestinal symptoms. Higher BMI and exposure to specific antibiotic classes (cephalosporins, fluoroquinolones, and vancomycin) were significantly associated with C. difficile colonization. No children developed symptomatic CDI in 90-days following enrollment.

Wrist-Worn devices to encourage affected upper limb movement in unilateral cerebral palsy: Participatory design workshops.

Background: Unilateral (Hemiplegic) cerebral palsy (UCP) causes weakness and stiffness affecting one sided of the body, often impacting activities of daily living. Upper limb therapy at effective intensity is not accessible to most. Aim: To determine stakeholder views on design of an approach using wrist-worn devices and a smartphone application to encourage use of the affected upper limb for children with hemiplegia. Method: Four participatory design workshops and one young people's advisory group workshop incorporating views of five young people with hemiplegia, 13 typically developing peers aged 8-18 years, four parents, three occupational therapists, one teacher and two paediatricians. Two special educational needs co-ordinators were consulted separately. Peers were included to explore a study design whereby each child with hemiplegia would have a participating "buddy". Topics included views on an acceptable wrist-worn device and smartphone application, participant age range, involvement of a buddy, and barriers to using the technology in a school setting. Ethical/welfare considerations included data security, and potential risks around providing smartphones to young children. Results: Children wanted a comfortable, conventional-appearing wristband incorporating a watch face and a secure, well-fitting strap. They were prepared to wear a band on each wrist. They wanted support with explaining the study to schoolteachers. Most schools restricted smartphone use during the school day: the study design accommodated this. Children agreed with a game as reward but had different views on an acceptable game; direct access to feedback data was preferred by some. Parents commented on the lack of access to upper limb therapy for children with UCP; therapists concurred. The proposed participant age range was widened based on feedback. Typically developing children were prepared to be buddies to help a friend with CP. Stakeholders were reassured by data security explanations and plans to provide internet safety information to participants. Conclusion: The participatory design process informed plans for the proof-of-concept stage of the study, hopefully leading to an approach that will be fun, easy to integrate into everyday life, and have the capacity to increase use of the affected arm and hand.

A planetary health model for reducing exposure to faecal contamination in urban informal settlements: Baseline findings from Makassar, Indonesia.

BACKGROUND: The intense interactions between people, animals and environmental systems in urban informal settlements compromise human and environmental health. Inadequate water and sanitation services, compounded by exposure to flooding and climate change risks, expose inhabitants to environmental contamination causing poor health and wellbeing and degrading ecosystems. However, the exact nature and full scope of risks and exposure pathways between human health and the environment in informal settlements are uncertain. Existing models are limited to microbiological linkages related to faecal-oral exposures at the individual level, and do not account for a broader range of human-environmental variables and interactions that affect population health and wellbeing. METHODS: We undertook a 12-month health and environmental assessment in 12 flood-prone informal settlements in Makassar, Indonesia. We obtained caregiver-reported health data, anthropometric measurements, stool and blood samples from children < 5 years, and health and wellbeing data for children 5-14 years and adult respondents. We collected environmental data including temperature, mosquito and rat species abundance, and water and sediment samples. Demographic, built environment and household asset data were also collected. We combined our data with existing literature to generate a novel planetary health model of health and environment in informal settlements. RESULTS: Across the 12 settlements, 593 households and 2764 participants were enrolled. Two-thirds (64·1%) of all houses (26·3-82·7% per settlement) had formal land tenure documentation. Cough, fever and diarrhoea in the week prior to the survey were reported among an average of 34.3%, 26.9% and 9.7% of children aged < 5 years, respectively; although proportions varied over time, prevalence among these youngest children was consistently higher than among children 5-14 years or adult respondents. Among children < 5 years, 44·3% experienced stunting, 41·1% underweight, 12.4% wasting, and 26.5% were anaemic. There was self- or carer-reported poor mental health among 16.6% of children aged 5-14 years and 13.9% of adult respondents. Rates of potential risky exposures from swimming in waterways, eating uncooked produce, and eating soil or dirt were high, as were exposures to flooding and livestock. Just over one third of households (35.3%) had access to municipal water, and contamination of well water with E. coli and nitrogen species was common. Most (79·5%) houses had an in-house toilet, but no houses were connected to a piped sewer network or safe, properly constructed septic tank. Median monthly settlement outdoor temperatures ranged from 26·2 °C to 29.3 °C, and were on average, 1·1 °C warmer inside houses than outside. Mosquito density varied over time, with Culex quinquefasciatus accounting for 94·7% of species. Framed by a planetary health lens, our model includes four thematic domains: (1) the physical/built environment; (2) the ecological environment; (3) human health; and (4) socio-economic wellbeing, and is structured at individual, household, settlement, and city/beyond spatial scales. CONCLUSIONS: Our planetary health model includes key risk factors and faecal-oral exposure pathways but extends beyond conventional microbiological faecal-oral enteropathogen exposure pathways to comprehensively account for a wider range of variables affecting health in urban informal settlements. It includes broader ecological interconnections and planetary health-related variables at the household, settlement and city levels. It proposes a composite framework of markers to assess water and sanitation challenges and flood risks in urban informal settlements for optimal design and monitoring of interventions.

Monitoring of diverse enteric pathogens across environmental and host reservoirs with TaqMan array cards and standard qPCR: a methodological comparison study.

BACKGROUND: Multiple bacteria, viruses, protists, and helminths cause enteric infections that greatly impact human health and wellbeing. These enteropathogens are transmited via several pathways through human, animal, and environmental reservoirs. Individual qPCR assays have been extensively used to detect enteropathogens within these types of samples, whereas the TaqMan array card (TAC), which allows simultaneous detection of multiple enteropathogens, has only previously been validated in human clinical samples. METHODS: In this methodological comparison study, we compared the performance of a custom 48-singleplex TAC relative to standard qPCR. We established the sensitivity and specificity of each method for the detection of eight enteric targets, by using spiked samples with varying levels of PCR inhibition. We then tested the prevalence and abundance of pathogens in wastewater from Melbourne (Australia), and human, animal, and environmental samples from informal settlements in Suva, Fiji using both TAC and qPCR. FINDINGS: Both methods exhibited similarly h specificity (TAC 100%, qPCR 94%), sensitivity (TAC 92%, qPCR 100%), and quantitation accuracy (TAC 91%, qPCR 99%) in non-inhibited sample matrices with spiked gene fragments. PCR inhibitors substantially affected detection via TAC, though this issue was alleviated by ten-fold sample dilution. Among samples from informal settlements, the two techniques performed similarly for detection (89% agreement) and quantitation (R2 0·82) for the eight enteropathogen targets. The TAC additionally included 38 other enteric targets, enabling detection of diverse faecal pathogens and extensive environmental contamination that would be prohibitively labour intensive to assay by standard qPCR. INTERPRETATION: The two techniques produced similar results across diverse sample types, with qPCR prioritising greater sensitivity and quantitation accuracy, and TAC trading small reductions in these for a cost-effective larger enteropathogen panel enabling a greater number of enteric pathogens to be analysed concurrently, which is beneficial given the abundance and variety of enteric pathogens in environments such as urban informal settlements. The ability to monitor multiple enteric pathogens across diverse reservoirs could allow better resolution of pathogen exposure pathways, and the design and monitoring of interventions to reduce pathogen load. FUNDING: Wellcome Trust Our Planet, Our Health programme.

Study design, rationale and methods of the Revitalising Informal Settlements and their Environments (RISE) study: a cluster randomised controlled trial to evaluate environmental and human health impacts of a water-sensitive intervention in informal settlements in Indonesia and Fiji.

INTRODUCTION: Increasing urban populations have led to the growth of informal settlements, with contaminated environments linked to poor human health through a range of interlinked pathways. Here, we describe the design and methods for the Revitalising Informal Settlements and their Environments (RISE) study, a transdisciplinary randomised trial evaluating impacts of an intervention to upgrade urban informal settlements in two Asia-Pacific countries. METHODS AND ANALYSIS: RISE is a cluster randomised controlled trial among 12 settlements in Makassar, Indonesia, and 12 in Suva, Fiji. Six settlements in each country have been randomised to receive the intervention at the outset; the remainder will serve as controls and be offered intervention delivery after trial completion. The intervention involves a water-sensitive approach, delivering site-specific, modular, decentralised infrastructure primarily aimed at improving health by decreasing exposure to environmental faecal contamination. Consenting households within each informal settlement site have been enrolled, with longitudinal assessment to involve health and well-being surveys, and human and environmental sampling. Primary outcomes will be evaluated in children under 5 years of age and include prevalence and diversity of gastrointestinal pathogens, abundance and diversity of antimicrobial resistance (AMR) genes in gastrointestinal microorganisms and markers of gastrointestinal inflammation. Diverse secondary outcomes include changes in microbial contamination; abundance and diversity of pathogens and AMR genes in environmental samples; impacts on ecological biodiversity and microclimates; mosquito vector abundance; anthropometric assessments, nutrition markers and systemic inflammation in children; caregiver-reported and self-reported health symptoms and healthcare utilisation; and measures of individual and community psychological, emotional and economic well-being. The study aims to provide proof-of-concept evidence to inform policies on upgrading of informal settlements to improve environments and human health and well-being. ETHICS: Study protocols have been approved by ethics boards at Monash University, Fiji National University and Hasanuddin University. TRIAL REGISTRATION NUMBER: ACTRN12618000633280; Pre-results.

Sleep screening for cystic fibrosis patients: A survey of cystic fibrosis programs.

OBJECTIVE: The prevalence of sleep disorders in patients with cystic fibrosis (CF) is unknown, and no standardized screening or treatment guidelines exist to address sleep disorders in CF. The objective of this study is to characterize current sleep screening practices in adult, pediatric, combined, and affiliate CF programs. METHODS: A survey was developed in Research Electronic Data Capture and distributed to program directors of accredited CF programs in the United States. RESULTS: Eighty-eight program directors responded (36% adult, 43% pediatric, 16% combined, 3% affiliate, and 1% unidentified). Of the respondents, 68% were part of an academic institution, 24% were associated with an academic institution, and 8% were part of a community or private program. Program sizes ranged from less than 50 to more than 500 patients. Routine or informal sleep screening was not performed in 44% of adults, 29% of pediatricians, and 35% of combined and affiliate programs. Most programs (>80%) have access to otolaryngology and sleep medicine although not all of these programs refer patients for evaluation of sleep disorders. Most program directors (77%) perceive sleep disorders as a problem in CF and would recommend routine sleep screening. Possible barriers to sleep screening included clinic flow, screening fatigue, and lack of recommendations for sleep screening. CONCLUSIONS: Formal sleep screening is inconsistent among CF care centers although most survey respondents would recommend the inclusion of screening in routine CF care. Future work is needed to further evaluate the impact of sleep disorders in CF and determine best practices for standardization of sleep screening and treatment.

Broad approaches to cholera control in Asia: Water, sanitation and handwashing.

Cholera has been eliminated as a public health problem in high-income countries that have implemented sanitation system separating the community's fecal waste from their drinking water and food supply. These expensive, highly-engineered systems, first developed in London over 150 years ago, have not reached low-income high-risk communities across Asia. Barriers to their implementation in communities at highest risk for cholera include the high capital and operating costs for this technological approach, limited capacity and perverse incentives of local governments, and a decreasing availability of water. Interim solutions including household level water treatment, constructing latrines and handwashing promotion have only marginally reduced the risk of cholera and other fecally transmitted diseases. Increased research to develop and policy flexibility to implement a new generation of solutions that are designed specifically to address the physical, financial and political constraints of low-income communities offers the best prospect for reducing the burden of cholera across Asia.

Chronic rhino-sinusitis treatment in children with cystic fibrosis: A cross-sectional survey of pediatric pulmonologists and otolaryngologists.

OBJECTIVES: Children with cystic fibrosis (CF) have a high incidence of chronic rhinosinusitis (CRS); however, no clinical care guidelines currently exist for the management of CRS in these patients. As a result, there is variation in the treatment of CRS in children, especially when it comes to the frequency of surgery for nasal polyposis. METHODS: A 28-question survey was sent to pediatric otolaryngologists (POs) and pulmonologists (PPs) who care for pediatric CF patients. Questions assessed the level of agreement that practitioners had with various approaches to CRS care in pediatric CF patients. RESULTS: Responses from 114 POs and 50 PPs were included in our final analysis. Each group demonstrated significantly different approaches to the medical and surgical management of CRS in pediatric CF patients. POs prefer multi-modal approach while PPs prefer single-modal approaches. With respect to medical management, PPs incline towards IV antibiotics while POs tend toward oral steroids. CONCLUSION: POs and PPs strongly agree that CRS has an impact on overall disease state and quality of life of pediatric CF patients. However, POs and PPs significantly differ in their approach to treating CRS, demonstrating a potential need for clinical care guidelines for the management these common sequelae of CF.

Evaluating the sinus and Nasal Quality of Life Survey in the pediatric cystic fibrosis patient population.

INTRODUCTION: The Sinus and Nasal Quality of Life Survey (SN-5) is a validated quality of life (QOL) questionnaire for chronic rhinosinusitis in patients age 2-12. Its utility in the cystic fibrosis (CF) has been studied, but not yet validated. The purpose of this study is to determine the effectiveness of the SN-5 for evaluation of sinonasal symptoms in the pediatric CF population. METHODS: This retrospective study analyzed SN-5 surveys completed between 2012 and 2015 by pediatric CF patients and caregivers. Baseline and follow-up overall QOL scores and specific symptom scores were obtained from surveys completed in the three-year span. Non-parametric statistics were conducted to identify differences in survey data. RESULTS: A total of 165 patients completed baseline and follow-up surveys. The overall QOL of the patient cohort did not change over the duration of the study (p = 0.660). Thirty-seven patients indicated higher overall QOL, with all five symptom scores showing significant improvement. Analysis by age group showed that QOL was significantly correlated with all five symptoms for children ages 0-4. In patients 5-12 years, overall QOL was only correlated with sinus infection (r = -0.3090, p = 0.01). QOL was significantly correlated with sinus infection (r = -0.2903, p = 0.04) and allergy symptoms (r = -0.5644, p < 0.01) in patients >12 years of age. CONCLUSION: There remains a need for a validated CRS QOL tool for children with CF. Though the SN-5 has previously been described as a potential instrument, our data suggest that it may be more valuable in children ages 0-4.