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.

Number of children in the household influences respiratory morbidities in children with bronchopulmonary dysplasia in the outpatient setting.

BACKGROUND: Bronchopulmonary dysplasia (BPD), a common complication of prematurity, is associated with outpatient morbidities, including respiratory exacerbations. Daycare attendance is associated with increased rates of acute and chronic morbidities in children with BPD. We sought to determine if additional children in the household conferred similar risks for children with BPD. METHODS: The number of children in the household and clinical outcomes were obtained via validated instruments for 933 subjects recruited from 13 BPD specialty clinics in the United States. Clustered logistic regression models were used to test for associations. RESULTS: The mean gestational age of the study population was 26.5 ± 2.2 weeks and most subjects (69.1%) had severe BPD. The mean number of children in households (including the subject) was 2.1 ± 1.3 children. Each additional child in the household was associated with a 13% increased risk for hospital admission, 13% increased risk for antibiotic use for respiratory illnesses, 10% increased risk for coughing/wheezing/shortness of breath, 14% increased risk for nighttime symptoms, and 18% increased risk for rescue medication use. Additional analyses found that the increased risks were most prominent when there were three or more other children in the household. CONCLUSIONS: We observed that additional children in the household were a risk factor for adverse respiratory outcomes. We speculate that secondary person-to-person transmission of respiratory viral infections drives this finding. While this risk factor is not easily modified, measures do exist to mitigate this disease burden. Further studies are needed to define best practices for mitigating this risk associated with household viral transmission.

Cardiovascular Measures of All-Cause Mortality in Duchenne Muscular Dystrophy.

BACKGROUND: Cardiopulmonary failure is the leading cause of death in Duchenne muscular dystrophy (DMD). Research into DMD-specific cardiovascular therapies is ongoing, but there are no Food and Drug Administration-approved cardiac end points. To adequately power a therapeutic trial, appropriate end points must be chosen and the rate of change for these end points reported. The objective of this study was to evaluate rate of change for cardiac magnetic resonance and blood biomarkers and to determine which measures associate with all-cause mortality in DMD. METHODS: Seventy-eight DMD subjects underwent 211 cardiac magnetic resonance studies analyzed for left ventricular (LV) ejection fraction, indexed LV end diastolic and systolic volumes, circumferential strain, late gadolinium enhancement presence and severity (global severity score, and full width half maximum), native T1 mapping, T2 mapping, and extracellular volume. Blood samples were analyzed for BNP (brain natriuretic peptide), NT-proBNP (N-terminal pro-B-type natriuretic peptide), and troponin I. Cox proportional hazard regression modeling was performed with all-cause mortality as the outcome. RESULTS: Fifteen subjects (19%) died. LV ejection fraction, indexed end systolic volumes, global severity score, and full width half maximum worsened at 1 and 2 years while circumferential strain and indexed LV end diastolic volumes worsened at 2 years. LV ejection fraction, indexed LV end diastolic and systolic volumes, late gadolinium enhancement full width half maximum, and circumferential strain associated with all-cause mortality (P<0.05). NT-proBNP was the only blood biomarker that associated with all-cause mortality (P<0.05). CONCLUSIONS: LV ejection fraction, indexed LV volumes, circumferential strain, late gadolinium enhancement full width half maximum, and NT-proBNP are associated with all-cause mortality in DMD and may be the best end points for use in cardiovascular therapeutic trials. We also report change over time of cardiac magnetic resonance and blood biomarkers.

Respiratory Outcomes for Ventilator-Dependent Children With Bronchopulmonary Dysplasia.

OBJECTIVES: To describe outpatient respiratory outcomes and center-level variability among children with severe bronchopulmonary dysplasia (BPD) who require tracheostomy and long-term mechanical ventilation. METHODS: Retrospective cohort of subjects with severe BPD, born between 2016 and 2021, who received tracheostomy and were discharged on home ventilator support from 12 tertiary care centers participating in the BPD Collaborative Outpatient Registry. Timing of key respiratory events including time to tracheostomy placement, initial hospital discharge, first outpatient clinic visit, liberation from the ventilator, and decannulation were assessed using Kaplan-Meier analysis. Differences between centers for the timing of events were assessed via log-rank tests. RESULTS: There were 155 patients who met inclusion criteria. Median age at the time of the study was 32 months. The median age of tracheostomy placement was 5 months (48 weeks' postmenstrual age). The median ages of hospital discharge and first respiratory clinic visit were 10 months and 11 months of age, respectively. During the study period, 64% of the subjects were liberated from the ventilator at a median age of 27 months and 32% were decannulated at a median age of 49 months. The median ages for all key events differed significantly by center (P ≤ .001 for all events). CONCLUSIONS: There is wide variability in the outpatient respiratory outcomes of ventilator-dependent infants and children with severe BPD. Further studies are needed to identify the factors that contribute to variability in practice among the different BPD outpatient centers, which may include inpatient practices.

Validation of an outpatient questionnaire for bronchopulmonary dysplasia control.

INTRODUCTION: Despite bronchopulmonary dysplasia (BPD) being a common morbidity of preterm birth, there is no validated objective tool to assess outpatient respiratory symptom control for clinical and research purposes. METHODS: Data were obtained from 1049 preterm infants and children seen in outpatient BPD clinics of 13 US tertiary care centers from 2018 to 2022. A new standardized instrument was modified from an asthma control test questionnaire and administered at the time of clinic visits. External measures of acute care use were also collected. The questionnaire for BPD control was validated in the entire population and selected subgroups using standard methodology for internal reliability, construct validity, and discriminative properties. RESULTS: Based on the scores from BPD control questionnaire, the majority of caregivers (86.2%) felt their child's symptoms were under control, which did not differ by BPD severity (p = 0.30) or a history of pulmonary hypertension (p = 0.42). Across the entire population and selected subgroups, the BPD control questionnaire was internally reliable, suggestive of construct validity (albeit correlation coefficients were -0.2 to -0.4.), and discriminated control well. Control categories (controlled, partially controlled, and uncontrolled) were also predictive of sick visits, emergency department visits, and hospital readmissions. CONCLUSION: Our study provides a tool for assessing respiratory control in children with BPD for clinical care and research studies. Further work is needed to identify modifiable predictors of disease control and link scores from the BPD control questionnaire to other measures of respiratory health such as lung function testing.

Spirometry correlates with physical activity in patients with Duchenne muscular dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) is associated with progressive muscle weakness and respiratory decline. To date, studies have focused on respiratory decline and loss of ambulation as a metric of loss of skeletal muscle strength. However, new functional measures can assess skeletal muscle disease regardless of ambulatory status. The relationship between these tests and concurrent lung function is currently unexplored. OBJECTIVE: To assess the correlation between spirometry measurements and functional muscle assessments such as accelerometry and quantitative muscle testing (QMT). METHODS: Enrolled patients with DMD underwent accelerometry and QMT at study clinic visits. Any pulmonary function testing within 6 months of visit was obtained from the electronic medical record. The Spearman correlation coefficient was used to assess the relationship between spirometry and functional muscle testing. RESULTS: Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1 ) demonstrated the strongest correlation with accelerometry. Both FVC and FEV1 showed a similar relationship to accelerometry when activity was divided into intensity categories, with low intensity and moderate-to-vigorous activity categories showing the strongest correlation. Maximal expiratory pressure (MEP) and FVC showed the most robust correlations with total QMT (p < 0.001 and p < 0.01, respectively). CONCLUSION: Lung function, specifically FVC percent predicted and FEV1 %p, shows a good correlation with upper and lower extremity skeletal muscle functional testing such as accelerometry and QMT.

Leveraging cardiac magnetic resonance imaging to assess skeletal muscle progression in Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is characterized by muscle deterioration and progressive weakness. As a result, patients with DMD have significant cardiopulmonary morbidity and mortality that worsens with age and loss of ambulation. Since most validated muscle assessments require ambulation, new functional measures of DMD progression are needed. Despite several evaluation methods available for monitoring disease progression, the relationship between these measures is unknown. We sought to assess the correlation between imaging metrics obtained from cardiac magnetic resonance imaging (CMR) and functional assessments including quantitative muscle testing (QMT), spirometry, and accelerometry. Forty-nine patients with DMD were enrolled and underwent CMR, accelerometry and QMT at baseline, 1-year and 2-year clinic visits with temporally associated pulmonary function testing obtained from the medical record. Imaging of the upper extremity musculature (triceps and biceps) demonstrated the most robust correlations with accelerometry (p<0.03), QMT (p<0.02) and spirometry (p<0.01). T1-mapping of serratus anterior muscle showed a similar, but slightly weaker relationship with accelerometry and QMT. T2-mapping of serratus anterior demonstrated weak indirect correlation with aspects of accelerometry. These images are either routinely obtained in standard CMR or can be added to a protocol and may allow for a more comprehensive assessment of a patient's disease progression.

Improving Access and Guideline Adherence in Pulmonary Care in Patients With Duchenne Muscular Dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a devastating, progressive neuromuscular disease that results in cardiopulmonary failure and death. In 2018, the DMD Care Considerations guidelines were updated to improve the multidisciplinary approach to care and promote early respiratory management. We sought to evaluate the impact of a multidisciplinary clinic on access to pulmonary care and adherence to respiratory care guidelines. METHODS: Utilizing retrospective data, we assessed for pulmonary care between 2016-2019 and congruence with guidelines from March 2018-February 2019. Using a standardized visit protocol, subjects were monitored for adherence to pulmonary function testing (PFT) and polysomnography (PSG) recommendations. RESULTS: Of the 84 subjects with DMD, only 51.2% had prior pulmonary involvement, and approximately one-third were seen in the year prior to clinic onset. Only 23% of subjects with a pulmonary referral completed this visit. After clinic initiation, the average age of a subject's first pulmonary contact decreased from 11.8 y to 7.9 y (P < .001), and 45% of the 77 unique clinic subjects had no previous pulmonary encounter. Adherence to PFT guidelines increased in both ambulatory (8.7% to 86.1%) and non-ambulatory subjects (25.9% to 90.1%). Approximately 79% of subjects seen in clinic either completed or had an order for PSG in the last 12 months. CONCLUSIONS: Development of a multispecialty clinic expanded access to pulmonary care and evaluation in subjects with DMD. Continued care in this clinic will allow a better understanding of barriers to access and the opportunity to monitor long-term pulmonary health.

E-cigarette and vaping product use-associated lung injury in the pediatric population: A critical review of the current literature.

Use of electronic nicotine delivery systems (ENDS), also known as e-cigarettes, in the adolescent population has significantly increased over the past several years. This rise led to an outbreak of e-cigarette or vaping product use-associated lung injury (EVALI) in the summer of 2019. Since that time, numerous case reports and case series on vaping and EVALI have been published but the majority of literature highlights the adult population with few articles focusing on pediatric patients. Given the addictive nature of these products and the lack of full understanding of the human health effects, there is concern that use of ENDS may have lasting impacts on users, especially adolescents and young adults. The goal of this review is to critically assess published data on ENDS use in children, report our institutional experience, discuss the reasons why the use of ENDS have increased among young individuals, outline the current understanding of EVALI as it pertains to the pediatric population, and discuss future opportunities for health policy implementation.