Decreased vascular reactivity associated with increased IL-8 in 6-month-old infants of mothers with pre-eclampsia.

BACKGROUND: Offspring born to mothers with pre-eclampsia (Pre-E) suffer higher risks of adult cardiovascular diseases, suggesting that exposure to an antiangiogenic environment in-utero has a lasting impact on the development of endothelial function. The goal of this study is to test the hypothesis that in-utero exposure to Pre-E results in alterations of angiogenic factors/cytokines that negatively impact vascular development during infancy. METHODS: Infants born from mothers with and without Pre-E were recruited and followed up at 6 months. Plasma cytokines, blood pressure, microvessel density, and vascular reactivity were assessed. RESULTS: 6-month-old infants born to mothers with Pre-E had unchanged blood pressure (p = 0.86) and microvessel density (p = 0.57). Vascular reactivity was decreased in infants born to mothers with Pre-E compared to infants born to healthy mothers (p = 0.0345). Interleukin 8 (IL-8) (p = 0.03) and Angiopoeitin-2 (Ang-2) (p = 0.04) were increased in infants born to mothers with Pre-E. We observed that higher IL-8 was associated with lower vascular reactivity (rho = -0.14, p < 0.0001). CONCLUSION: At 6 months of age, infants born to mothers with Pre-E had impaired vascular reactivity and higher IL-8 and Ang-2, but similar blood pressure and microvessel density compared to infants born to non-Pre-E mothers. IMPACT STATEMENT: Changes in cord blood antiangiogenic factors are documented in infants of mothers with pre-eclampsia and may contribute to offspring risks of adult cardiovascular disease. How these factors evolve during early infancy and their correlation with offspring vascular development have not been studied. This study found that 6-month-old infants born to mothers with pre-eclampsia had decreased vascular reactivity, which was correlated with higher IL-8. These findings underscore the lasting impact of maternal pre-eclampsia on offspring vascular development and highlight the need for long-term follow-up in children born to mothers with pre-eclampsia.

Late Diagnosis in the Era of Universal Newborn Screening Negatively Affects Short- and Long-Term Growth and Health Outcomes in Infants with Cystic Fibrosis.

Newborn screening for cystic fibrosis was fully implemented in the US by 2010, but delays in timeliness of evaluation for infants with positive newborn screening tests persist. Through evaluation of national patient registry data, we determined that late initiation of cystic fibrosis care is associated with poorer long-term nutritional outcomes.

Outpatient Respiratory Management of Infants, Children, and Adolescents with Post-Prematurity Respiratory Disease: An Official American Thoracic Society Clinical Practice Guideline.

Background: Premature birth affects millions of neonates each year, placing them at risk for respiratory disease due to prematurity. Bronchopulmonary dysplasia is the most common chronic lung disease of infancy, but recent data suggest that even premature infants who do not meet the strict definition of bronchopulmonary dysplasia can develop adverse pulmonary outcomes later in life. This post-prematurity respiratory disease (PPRD) manifests as chronic respiratory symptoms, including cough, recurrent wheezing, exercise limitation, and reduced pulmonary function. This document provides an evidence-based clinical practice guideline on the outpatient management of infants, children, and adolescents with PPRD. Methods: A multidisciplinary panel of experts posed questions regarding the outpatient management of PPRD. We conducted a systematic review of the relevant literature. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to rate the quality of evidence and the strength of the clinical recommendations. Results: The panel members considered the strength of each recommendation and evaluated the benefits and risks of applying the intervention. In formulating the recommendations, the panel considered patient and caregiver values, the cost of care, and feasibility. Recommendations were developed for or against three common medical therapies and four diagnostic evaluations in the context of the outpatient management of PPRD. Conclusions: The panel developed recommendations for the outpatient management of patients with PPRD on the basis of limited evidence and expert opinion. Important areas for future research were identified.

Pulmonary Outcomes Associated with Long-Term Azithromycin Therapy in Cystic Fibrosis.

Rationale: Chronic azithromycin is commonly used in cystic fibrosis based on short controlled clinical trials showing reductions in pulmonary exacerbations and improved FEV1. Long-term effects are unknown.Objectives: Examine pulmonary outcomes among chronic azithromycin users compared with matched controls over years of use and consider combined azithromycin use in cohorts using chronic inhaled tobramycin or aztreonam.Methods: This retrospective cohort study used the U.S. cystic fibrosis Foundation Patient Registry. Incident chronic azithromycin users were compared with matched controls by FEV1% predicted rate of decline and rates of intravenous antibiotic use to treat pulmonary exacerbations. Propensity score methods were utilized to address confounding by indication. Predefined sensitivity analyses based on lung function, Pseudomonas aeruginosa (PA) status, and follow-up time intervals were conducted.Measurements and Main Results: Across 3 years, FEV1% predicted per-year decline was nearly 40% less in those with PA using azithromycin compared with matched controls (slopes, -1.53 versus -2.41% predicted per yr; difference: 0.88; 95% confidence interval [CI], 0.30-1.47). This rate of decline did not differ based on azithromycin use in those without PA. Among all cohorts, use of intravenous antibiotics was no different between azithromycin users and controls. Users of inhaled tobramycin and azithromycin had FEV1% predicted per-year decline of -0.16 versus nonusers (95% CI, -0.44 to 0.13), whereas users of inhaled aztreonam lysine and azithromycin experienced a mean 0.49% predicted per year slower decline than matched controls (95% CI, -0.11 to 1.10).Conclusions: Results from this study provide additional rationale for chronic azithromycin use in PA-positive patients to reduce lung function decline.

Early Neonatal Oxygen Exposure Predicts Pulmonary Morbidity and Functional Deficits at 1 Year.

OBJECTIVE: To evaluate the predictive value of cumulative oxygen exposure thresholds over the first 2 postnatal weeks, linking them to bronchopulmonary dysplasia (BPD) and 1-year pulmonary morbidity and lung function in extremely low gestational age newborns. STUDY DESIGN: Infants (N = 704) enrolled in the Prematurity and Respiratory Outcomes Program, a multicenter prospective cohort study, that survived to discharge were followed through their neonatal intensive care unit hospitalization to 1-year corrected age. Cumulative oxygen exposure (OxygenAUC14) thresholds were derived from univariate models of BPD, stratifying infants into high-, intermediate-, and low-oxygen exposure groups. These groups were then used in multivariate logistic regressions to prospectively predict post-prematurity respiratory disease (PRD), respiratory morbidity score (RMS) in the entire cohort, and pulmonary function z scores (N = 108 subset of infants) at 1-year corrected age. RESULTS: Over the first 14 postnatal days, infants exposed to high oxygen averaged ≥33.1% oxygen, infants exposed to intermediate oxygen averaged 29.1%-33.1%, and infants exposed to low oxygen were below both cutoffs. In multivariate models, infants exposed to high oxygen showed increased PRD and RMS, whereas infants exposed to intermediate oxygen demonstrated increased moderate/severe RMS. Infants in the high/intermediate groups had decreased forced expiratory volume at 0.5 seconds/forced vital capacity ratio. CONCLUSIONS: OxygenAUC14 establishes 3 thresholds of oxygen exposure that risk stratify infants early in their neonatal course, thereby predicting short-term (BPD) and 1-year (PRD, RMS) respiratory morbidity. Infants with greater OxygenAUC14 have altered pulmonary function tests at 1 year of age, indicating early evidence of obstructive lung disease and flow limitation, which may predispose extremely low gestational age newborns to increased long-term pulmonary morbidity. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01435187.

A Retrospective Cohort Study of Growth in the First 2 Years of Life in Preterm Infants With Cystic Fibrosis.

BACKGROUND: Late preterm infants (born 34-36 weeks gestation) without cystic fibrosis (CF) are at risk for growth failure during the first 2 years of life. Infants with CF are at risk of being born premature, and thus at risk for growth failure. The aim for this study was to assess weight-for-length (WFL) at 2 years of age for late preterm infants compared with term infants with CF. METHODS: Data were collected from the US CF Foundation Patient Registry. We compared growth parameters between late preterm and term infants with CF born from 2010 to 2013. Our primary outcome was WFL <10 and <50 percentile at 2 years of age. A multivariate logistical regression analysis evaluated late preterm gestation and WFL<10 or <50 percentile. RESULTS: A total of 2955 infants were born from 2010 to 2013 with CF. Eight percentage late preterm. Forty-five percentage late preterm versus 43% term were below the 50th percentile for WFL at age 2 years (P = 0.75). Twelve percentage late preterm versus 6% term for WFL <10 percentile at age 2 years (P = 0.010). The multivariate regression model identified 2-fold increased odds of being <10th percentile for WFL at age 2 years (P = 0.025) for preterm over term. Late preterm infants used higher calorie dense feeds and more feeding tubes (P = 0.035 and P = 0.006). CONCLUSIONS: Late preterm infants with CF are at higher risk of being below the 10th percentile for WFL at 2 years of age compared with their term peers. This indicates a population that is at risk for growth failure.

Black Race Is Associated with a Lower Risk of Bronchopulmonary Dysplasia.

OBJECTIVE: To use a large current prospective cohort of infants <29 weeks to compare bronchopulmonary dysplasia (BPD) rates in black and white infants. STUDY DESIGN: The Prematurity and Respiratory Outcome Program (PROP) enrolled 835 infants born in 2011-2013 at <29 weeks of gestation; 728 black or white infants survived to 36 weeks postmenstrual age (PMA). Logistic regression was used to compare BPD outcomes (defined as supplemental oxygen requirement at 36 weeks PMA) between the races, adjusted for gestational age (GA), antenatal steroid use, intubation at birth, and surfactant use at birth. RESULTS: Of 707 black or white infants with available BPD outcomes, BPD was lower in black infants (38% vs 45%), even though they were of significantly lower GA. At every GA, BPD was more common in white infants. The aOR for BPD was 0.60 (95% CI, 0.42-0.85; P = .004) for black infants compared with white infants after adjusting for GA. Despite the lower rate of BPD, black infants had a higher rate of first-year post-prematurity respiratory disease (black, 79%; white, 63%). CONCLUSIONS: In this large cohort of recently born preterm infants at <29 weeks GA, compared with white infants, black infants had a lower risk of BPD but an increased risk of persistent respiratory morbidity.

Applying Cystic Fibrosis Transmembrane Conductance Regulator Genetics and CFTR2 Data to Facilitate Diagnoses.

OBJECTIVE: As a Mendelian disease, genetics plays an integral role in the diagnosis of cystic fibrosis (CF). The identification of 2 disease-causing mutations in the CF transmembrane conductance regulator (CFTR) in an individual with a phenotype provides evidence that the disease is CF. However, not all variations in CFTR always result in CF. Therefore, for CFTR genotype to provide the same level of evidence of CFTR dysfunction as shown by direct tests such as sweat chloride or nasal potential difference, the mutations identified must be known to always result in CF. The use of CFTR genetics in CF diagnosis, therefore, relies heavily on mutation interpretation. STUDY DESIGN: Progress that has been made on mutation interpretation and annotation was reviewed at the recent CF Foundation Diagnosis Consensus Conference. A modified Delphi method was used to identify consensus statements on the use of genetic analysis in CF diagnosis. RESULTS: The largest recent advance in CF genetics has come through the Clinical and Functional Translation of CFTR (CFTR2) project. This undertaking seeks to characterize CFTR mutations from patients with CF around the world. The project also established guidelines for the clinical, functional, and population/penetrance criteria that can be used to interpret mutations not yet included in CFTR2's review. CONCLUSIONS: The use of CFTR genetics to aid in diagnosis of CF requires that the mutations identified have a known disease liability. The demonstration of 2 in trans mutations known to always result in CF is satisfactory evidence of CFTR dysfunction. However, if the identified mutations are known to be associated with variable outcomes, or have unknown consequence, that genotype may not result in a CF phenotype. In these cases, other tests of CFTR function may help.

Cystic Fibrosis Transmembrane Conductance Regulator-Related Metabolic Syndrome and Cystic Fibrosis Screen Positive, Inconclusive Diagnosis.

OBJECTIVE: An unintended consequence of cystic fibrosis (CF) newborn screening (NBS) is the identification of infants with a positive NBS test but inconclusive diagnostic testing. These infants are classified as CF transmembrane conductance regulator-related metabolic syndrome (CRMS) in the US and CF screen positive, inconclusive diagnosis (CFSPID) in other countries. Diagnostic and management decisions of these infants are challenges for CF healthcare professionals and stressful situations for families. As CF NBS has become more widespread across the world, increased information about the epidemiology and outcomes of these infants is becoming available. These data were reviewed at the 2015 CF Foundation Diagnosis Consensus Conference, and a harmonized definition of CRMS and CFSPID was developed. STUDY DESIGN: At the consensus conference, participants reviewed published and unpublished studies of CRMS/CFSPID and used a modified Delphi methodology to develop a harmonized approach to the definition of CRMS/CFSPID. RESULTS: Several studies of CRMS/CFSPID from populations around the world have been published in the past year. Although the studies vary in the number of infants studied, study design, and outcome measures, there have been some consistent findings. CRMS/CFSPID occurs relatively frequently, with CF:CRMS that ranges from 3 to 5 cases of CF for every 1 case of CRMS/CFSPID in regions where gene sequencing is not used. The incidence varies by NBS protocol used, and in some regions more cases of CRMS/CFSPID are detected than cases of CF. The majority of individuals with CRMS/CFSPID do not develop CF disease or progress to a diagnosis of CF. However, between 10% and 20% of asymptomatic infants can develop clinical features concerning for CF, such as a respiratory culture positive for Pseudomonas aeruginosa. Most studies have only reported short-term outcomes in the first 1-3 years of life; the long-term outcomes of CRMS/CFSPID remain unknown. The European CF Society definition of CFSPID and the CF Foundation definition of CRMS differ only slightly, and the consensus conference was able to create a unified definition of CRMS/CFSPID. CONCLUSIONS: CRMS/CFSPID is a relatively common outcome of CF NBS, and clinicians need to be prepared to counsel families whose NBS test falls into this classification. The vast majority of infants with CRMS/CFSPID will remain free from disease manifestations early in life. However, a small proportion may develop clinical features concerning for CF or demonstrate progression to a clinical phenotype compatible with a CF diagnosis, and their long-term outcomes are not known. A consistent international definition of CRMS/CFSPID will allow for better data collection for study of outcomes and result in improved patient care.

Diagnosis of Cystic Fibrosis in Nonscreened Populations.

OBJECTIVE: Although the majority of cases of cystic fibrosis (CF) are now diagnosed through newborn screening, there is still a need to standardize the diagnostic criteria for those diagnosed outside of the neonatal period. This is because newborn screening started relatively recently, it is not performed everywhere, and even for individuals who were screened, there is the possibility of a false negative. To limit irreversible organ pathology, a timely diagnosis of CF and institution of CF therapies can greatly benefit these patients. STUDY DESIGN: Experts on CF diagnosis were convened at the 2015 CF Foundation Diagnosis Consensus Conference. The participants reviewed and discussed published works and instructive cases of CF diagnosis in individuals presenting with signs, symptoms, or a family history of CF. Through a modified Delphi methodology, several consensus statements were agreed upon. These consensus statements were updates of prior CF diagnosis conferences and recommendations. RESULTS: CF diagnosis in individuals outside of newborn screening relies on the clinical evidence and on evidence of CF transmembrane conductance regulator (CFTR) dysfunction. Clinical evidence can include typical organ pathologies seen in CF such as bronchiectasis or pancreatic insufficiency but often represent a broad range of severity including mild cases. CFTR dysfunction can be demonstrated using sweat chloride testing, CFTR molecular genetic analysis, or CFTR physiologic tests. On the basis of the large number of patients with bona fide CF currently followed in registries with sweat chloride levels between 30 and 40 mmol/L, the threshold considered "intermediate" was lowered from 40 mmol/L in the prior diagnostic guidelines to 30 mmol/L. The CF diagnosis was also discussed in the context of CFTR-related disorders in which CFTR dysfunction may be present, but the individual does not meet criteria for CF. CONCLUSIONS: CF diagnosis remains a rare but important condition that can be diagnosed when characteristic clinical features are seen in an individual with demonstrated CFTR dysfunction.

Diagnosis of Cystic Fibrosis: Consensus Guidelines from the Cystic Fibrosis Foundation.

OBJECTIVE: Cystic fibrosis (CF), caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, continues to present diagnostic challenges. Newborn screening and an evolving understanding of CF genetics have prompted a reconsideration of the diagnosis criteria. STUDY DESIGN: To improve diagnosis and achieve standardized definitions worldwide, the CF Foundation convened a committee of 32 experts in CF diagnosis from 9 countries to develop clear and actionable consensus guidelines on the diagnosis of CF and to clarify diagnostic criteria and terminology for other disorders associated with CFTR mutations. An a priori threshold of ≥80% affirmative votes was required for acceptance of each recommendation statement. RESULTS: After reviewing relevant literature, the committee convened to review evidence and cases. Following the conference, consensus statements were developed by an executive subcommittee. The entire consensus committee voted and approved 27 of 28 statements, 7 of which needed revisions and a second round of voting. CONCLUSIONS: It is recommended that diagnoses associated with CFTR mutations in all individuals, from newborn to adult, be established by evaluation of CFTR function with a sweat chloride test. The latest mutation classifications annotated in the Clinical and Functional Translation of CFTR project (http://www.cftr2.org/index.php) should be used to aid in diagnosis. Newborns with a high immunoreactive trypsinogen level and inconclusive CFTR functional and genetic testing may be designated CFTR-related metabolic syndrome or CF screen positive, inconclusive diagnosis; these terms are now merged and equivalent, and CFTR-related metabolic syndrome/CF screen positive, inconclusive diagnosis may be used. International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes for use in diagnoses associated with CFTR mutations are included.

Official American Thoracic Society Clinical Practice Guidelines: Diagnostic Evaluation of Infants with Recurrent or Persistent Wheezing.

BACKGROUND: Infantile wheezing is a common problem, but there are no guidelines for the evaluation of infants with recurrent or persistent wheezing that is not relieved or prevented by standard therapies. METHODS: An American Thoracic Society-sanctioned guideline development committee selected clinical questions related to uncertainties or controversies in the diagnostic evaluation of wheezing infants. Members of the committee conducted pragmatic evidence syntheses, which followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The evidence syntheses were used to inform the formulation and grading of recommendations. RESULTS: The pragmatic evidence syntheses identified few studies that addressed the clinical questions. The studies that were identified constituted very low-quality evidence, consisting almost exclusively of case series with risk of selection bias, indirect patient populations, and imprecise estimates. The committee made conditional recommendations to perform bronchoscopic airway survey, bronchoalveolar lavage, esophageal pH monitoring, and a swallowing study. It also made conditional recommendations against empiric food avoidance, upper gastrointestinal radiography, and gastrointestinal scintigraphy. Finally, the committee recommended additional research about the roles of infant pulmonary function testing and food avoidance or dietary changes, based on allergy testing. CONCLUSIONS: Although infantile wheezing is common, there is a paucity of evidence to guide clinicians in selecting diagnostic tests for recurrent or persistent wheezing. Our committee made several conditional recommendations to guide clinicians; however, additional research that measures clinical outcomes is needed to improve our confidence in the effects of various diagnostic interventions and to allow advice to be provided with greater confidence.

Pediatric pulmonology year in review 2023: Physiology.

Application of the principles of pulmonary physiology and lung development to the care and management of respiratory disease in children is a distinguishing feature of pediatric pulmonology. In 2023, this was evident in numerous publications in Pediatric Pulmonology and other journals. This review will highlight some of the papers in this area.

Clinical features associated with pulmonary exacerbation diagnosis in infants and young children with cystic fibrosis.

RATIONALE: Diagnosing cystic fibrosis (CF) pulmonary exacerbations (PEx) in very young people with CF <3 years (VY-PwCF) is challenging because of the frequency of respiratory viral infections in this age group, and there are limited data on the clinical features associated with the diagnosis of PEx in this age group. The goal of this study was to identify clinical features associated with the diagnosis of PEx in VY-PwCF. METHODS: We reviewed the medical records of VY-PwCF followed at the Children's Hospital of Philadelphia born between 2013 and 2019. We collected data from all encounters with respiratory symptoms. PEx was defined by treatment with oral or intravenous antibiotics. Clinical features of PEx and non-PEx encounters were compared using descriptive statistics, and odds ratios of PEx diagnosis were calculated. RESULTS: A total of 78 patients were included in the analysis. The mean (SD) number of PEx per patient was 6.17 (5.88). The presence of a wet or nighttime cough and symptoms >3 days in duration were significantly associated with PEx diagnosis (p < .001). In contrast, symptoms such as sore throat or rhinorrhea were not associated with a higher likelihood of PEx. CONCLUSIONS: The presence of a wet or night-time cough and longer symptom duration are common features of PEx in VY-PwCF, whereas symptoms suggestive of upper respiratory viral infection are not. Our results will be helpful in counseling families of VY-PwCF in the signs and symptoms of PEx and in planning future research in PEx in this age group.

Treatment of small as well as large declines in lung function enhances recovery to baseline in people with CF.

BACKGROUND: The benefit of antibiotic treatment of acute drops in FEV1 percent predicted (FEV1pp) has been clearly established, but data from the early 2000s showed inconsistent treatment. Further, there is no empirical evidence for what magnitude of drop is clinically significant. METHODS: We used data from the CF Foundation Patient Registry (CFFPR) from 2016 to 2019 to determine the association between treatment (any IV antibiotics, only oral or newly prescribed inhaled antibiotics, or no antibiotic therapy) following a decline of ≥5% from baseline FEV1pp and return to 100% baseline FEV1pp days using multivariable logistic regression including an interaction between the magnitude of decline and treatment category. RESULTS: Overall, 16,495 PWCF had a decline: 16.5% were treated with IV antibiotics, 25.0% non-IV antibiotics, and 58.5% received no antibiotics. Antibiotic treatment was more likely for those with lower lung function, history of a positive PA culture, older age and larger FEV1 decline (p < 0.001). Treatment with IV antibiotics or oral/inhaled antibiotics was associated with a higher odds of recovery to baseline compared to no treatment across all levels of decline, including declines of 5%-10%. CONCLUSIONS: A large proportion of acute drops in FEV1pp continue to be untreated, especially in younger patients and those with higher baseline lung function. Acute drops as small as 5% predicted are less likely to be recovered if antibiotic treatment is not prescribed. These findings suggest the need for more aggressive antimicrobial treatment of acute drops in FEV1, including those of a magnitude previously believed to be associated with self-recovery.

Clinical outcomes at 9-10 years of age in children born with cystic fibrosis transmembrane conductance regulator related metabolic syndrome.

BACKGROUND AND OBJECTIVES: There are limited data on cystic fibrosis (CF) transmembrane conductance regulator-related metabolic syndrome (CRMS) outcomes beyond infancy. The goal of this study was to analyze outcomes of infants with CRMS up to the age of 9-10 years using the CF Foundation Patient Registry (CFFPR). METHODS: We analyzed data from the CFFPR for individuals with CF and CRMS born between 2010 and 2020. We classified all patients based on the clinical diagnosis reported by the CF care center and the diagnosis using CFF guideline definitions for CF and CRMS, classifying children into groups based on agreement between clinical report and guideline criteria. Descriptive statistics for the cohort were calculated for demographics, nutritional outcomes, and microbiology for the first year of life and lung function and growth outcomes were summarized for ages 6-10 years. RESULTS: From 2010 to 2020, there were 8765 children with diagnosis of CF or CRMS entered into the CFFPR with sufficient diagnostic data for classification, of which 7591 children had a clinical diagnosis of CF and 1174 had a clinical diagnosis of CRMS. CRMS patients exhibited normal nutritional indices and pulmonary function up to age 9-10 years. The presence of respiratory bacteria associated with CF, such as Pseudomonas aeruginosa from CRMS patients ranged from 2.1% to 9.1% after the first year of life. CONCLUSIONS: Children with CRMS demonstrate normal pulmonary and nutritional outcomes into school age. However, a small percentage of children continue to culture CF-associated respiratory pathogens after infancy.

Lung T1 MRI assessments in children with mild cystic fibrosis lung disease.

RATIONALE: Lung T1 MRI is a potential method to assess cystic fibrosis (CF) lung disease that is safe, quick, and widely available, but there are no data in children with mild CF lung disease. OBJECTIVE: Assess the ability of lung T1 MRI to detect abnormalities in children with mild CF lung disease. METHODS: We performed T1 MRI, multiple breath washout (MBW), chest computed tomography (CT), and spirometry in a cohort of 45 children with mild CF lung disease (6-11 years of age). MAIN RESULTS: Despite mean normal ppFEV1 values, the majority of children with CF in this study exhibited mild lung disease evident in lung clearance index (LCI) measured by MBW, chest CT Brody scores, and percent normal lung perfusion (%NLP) measured by T1 MRI. The %NLP correlated with chest CT Brody scores, as did LCI, but %NLP and LCI did not correlate with each other. Analysis of the Brody subscores showed that %NLP and LCI largely correlated with different Brody subscores. CONCLUSIONS: T1 MRI can detect mild CF lung disease in children and correlates with chest CT findings. The %NLP from T1 MRI and LCI correlate with different chest CT Brody subscores, suggesting they provide complementary information about CF lung disease.

Factors associated with prescription of elexacaftor/tezacaftor/ivacaftor among people with cystic fibrosis aged 12 years or older with at least one F508del allele.

BACKGROUND: This study aims to characterize the uptake of elexacaftor/tezacaftor/ivacaftor (ETI) following Food and Drug Administration (FDA) approval in October 2019. METHODS: People with cystic fibrosis (PwCF) ≥12 years enrolled in the CF Foundation Patient Registry (CFFPR) from 2019-2022 with at least one copy of F508del were included. We calculated summary statistics according to ETI prescription status. We used a Kaplan-Meier estimator to determine median days to ETI prescription to identify differences in prescription uptake by lung function, race, and ethnicity and a Cox proportional hazards model to identify risk factors associated with timing of first ETI prescription. RESULTS: A total of 17,183 people (91 %) were prescribed ETI. The median time to prescription was 121 days (95 % CI: 119, 122), with 75 % prescribed within 311 days (95 % CI: 301, 325). PwCF prescribed ETI were younger, had lower lung function, more pulmonary exacerbations in the prior year, earlier age of diagnosis, and were more likely to have been prescribed another CFTR modulator (if eligible). Public health insurance, ppFEV1 >90, Black race and Hispanic ethnicity were associated with lower hazards (e.g., later) of ETI prescription whereas prior modulator prescription, pancreatic insufficiency, increased exacerbation frequency and prior infections were associated with a higher hazard (earlier) of prescription. CONCLUSIONS: While over 90 % of eligible individuals were prescribed ETI within three years, time of first prescription was associated with demographic factors and disease severity. Further research should investigate the reasons for this delay and approaches to reduce time to initiation for ETI and future therapies.

Cystic Fibrosis Foundation Evidence-Based Guideline for the Management of CRMS/CFSPID.

A multidisciplinary committee developed evidence-based guidelines for the management of cystic fibrosis transmembrane conductance regulator-related metabolic syndrome/cystic fibrosis screen-positive, inconclusive diagnosis (CRMS/CFSPID). A total of 24 patient, intervention, comparison, and outcome questions were generated based on surveys sent to people with CRMS/CFSPID and clinicians caring for these individuals, previous recommendations, and expert committee input. Four a priori working groups (genetic testing, monitoring, treatment, and psychosocial/communication issues) were used to provide structure to the committee. A systematic review of the evidence was conducted, and found numerous case series and cohort studies, but no randomized clinical trials. A total of 30 recommendations were graded using the US Preventive Services Task Force methodology. Recommendations that received ≥80% consensus among the entire committee were approved. The resulting recommendations were of moderate to low certainty for the majority of the statements because of the low quality of the evidence. Highlights of the recommendations include thorough evaluation with genetic sequencing, deletion/duplication analysis if <2 disease-causing variants were noted in newborn screening; repeat sweat testing until at least age 8 but limiting further laboratory testing, including microbiology, radiology, and pulmonary function testing; minimal use of medications, which when suggested, should lead to shared decision-making with families; and providing communication with emphasis on social determinants of health and shared decision-making to minimize barriers which may affect processing and understanding of this complex designation. Future research will be needed regarding medication use, antibiotic therapy, and the use of chest imaging for monitoring the development of lung disease.

Pediatric pulmonology year in review 2021 and 2022: Physiology.

Pulmonary physiology is a core element of pediatric pulmonology care and research. This article reviews some of the notable publications in physiology that were published in Pediatric Pulmonology in 2021 and 2022.