Daniel J. Weiner

Rationale: It is unclear if recent updates to pulmonary function testing (PFT) guidelines impact calculation of the Lung Function Score (LFS), which is based on FEV1 and DLCO and is associated with post-stem cell transplant (SCT) survival. Objective: To recalculate the LFS according to the updated PFT guidelines and test if an abnormal LFS using updated PFT guidelines is associated with post-SCT mortality. Methods: This was a secondary analysis of a dataset of children aged 6-21 years who underwent SCT. The LFS was calculated using 6 different definitions (defined using one of three reference equations and z-score or % predicted (%pred) thresholds). We examined the association of an abnormal LFS (>2) with post-SCT survival using Kaplan-Meier curves and Cox proportional hazard regression models adjusted for site and race. Results: Of the 278 children included, 67-81% had an abnormal LFS, depending on LFS definition. Children with an abnormal LFS defined using NHANES reference equations and %pred had 120% increased hazard of death compared to those with a normal LFS (adjusted hazard ratio [aHR]=2.20, 95% confidence interval [CI]=1.30 to 3.74, P = .003). Using GLI race-neutral reference equations and %pred, an abnormal LFS was associated with a 60% increased hazard of death (aHR = 1.60, 95% CI = 1.05 to 2.46, P = .03), while an abnormal LFS calculated using GLI race-neutral reference equations and z-scores was not associated with mortality (aHR = 1.17, 95% CI = 0.80 to 1.72, P = .4). Conclusion: Choice of reference equations and thresholds impacted the LFS calculation. While the original LFS using NHANES reference data and %pred was associated with mortality, having an abnormal LFS calculated using the current PFT guidelines was not associated with an increased risk of death.

Background: The use of home spirometry (HSPIR) has increased in pediatric cystic fibrosis (CF) care, but how it has been used clinically and its impact on clinical care have not been described. The purpose of this study was to address this knowledge gap through a secondary analysis of data from a HSPIR quality improvement project to characterize clinical use of HSPIR in children with CF (CwCF). Methods: HSPIR devices were distributed to 161 CwCF (age ≥ 5 years) across three CF centers. Remote encounters were reviewed to identify HSPIR use from July 2023 to February 2025. Data collected included the clinical indication for testing and its impact on clinical decision making. Differences between HSPIR users and non‐users were analyzed using Wilcoxon rank‐sum, Pearson's chi‐squared, and Fisher's exact tests as appropriate, and descriptive statistics were used to characterize clinical HSPIR use. Results: Among 161 CwCF who were provided HSPIR devices, 50 (31%) used their HSPIR a total of 107 times and submitted tracking forms to their care teams over 20 months. There were no significant differences in demographics or clinical characteristics between HSPIR users and non‐users. The most common reasons for HSPIR use were clinic follow‐ups (44%) and sick calls (33%), with clinicians reporting that HSPIR data informed clinical decisions in 72% of encounters. In 41% of remote clinical encounters, we identified a missed opportunity for using HSPIR. Conclusion: In patients and families motivated to use HSPIR, its use avoided the need to return to the clinic for follow‐up spirometry and influenced clinical decision making, suggesting that HSPIR can be a useful clinical tool. The overall low uptake of HSPIR highlights the need for further research to address patient and clinician barriers to its use. The impact of HSPIR on long‐term CF outcomes also requires further study.

Introduction: Prior studies of pediatric asthma control and lung function after COVID‐19 have been limited by short follow‐up intervals. We aimed to evaluate symptom control and lung function in children with asthma up to 34 months post‐COVID‐19. Methods: We conducted a prospective observational chart review study. We reviewed electronic health records of children with asthma in the Western Pennsylvania COVID‐19 Registry, abstracting pre‐ and all post‐infection spirometry results and Childhood Asthma Control Test (C‐ACT) or Asthma Control Test (ACT) scores (to measure symptom control) through August 2023. We conducted adjusted mixed models with linear spline to compare C‐ACT/ACT or FEV ₁ before and after COVID‐19. For individuals with worse outcomes at initial follow‐up, we evaluated characteristics associated with lack of eventual recovery. Results: We found no significant differences between baseline and post‐infection symptom control ( n = 267) or lung function ( n = 196). Of the 28% of children who had worse lung function at initial follow‐up, 34% fully recovered at final follow‐up. Of the 19% with worse C‐ACT/ACT score at initial follow‐up, 38% fully recovered at final follow‐up. Final follow‐up median C‐ACT/ACT scores and mean FEV ₁ were in the normal range even for the group without eventual recovery. Obesity ( p = 0.04) was associated with hindered symptom control recovery. Conclusion: There were no significant differences between baseline and follow‐up symptom control or lung function in children with asthma up to 34 months post‐COVID‐19. Only a small proportion of children worsened and did not recover, and decrements were generally small. Obesity was associated with impaired symptom control recovery.

Elexacaftor/tezacaftor/ivacaftor (ETI) has had a substantial positive impact for people living with cystic fibrosis (pwCF). However, there can be substantial variability in efficacy, and we lack adequate biomarkers to predict individual response. We thus aimed to identify transcriptomic profiles in nasal respiratory epithelium that predict clinical response to ETI treatment. We obtained nasal epithelial samples from pwCF before ETI initiation and performed a transcriptome-wide analysis of baseline gene expression to predict changes in forced expiratory volume in 1 second (ΔFEV1), year’s best FEV1 (ΔybFEV1), and body mass index (ΔBMI). Using the top differentially expressed genes, we generated transcriptomic risk scores (TRSs) and evaluated their predictive performance. The study included 40 pwCF ≥6 years of age (mean, 27.7 [SD, 15.1] years; 40% female). After ETI initiation, FEV1 improved by ≥5% in 22 (61.1%) participants, and ybFEV1 improved by ≥5% in 19 (50%). TRSs were constructed using top overexpressed and underexpressed genes for each outcome. Adding the ΔFEV1 TRS to a model with age, sex, and baseline FEV1 increased the area under the receiver operating characteristic curve (AUC) from 0.41 to 0.88, the ΔybFEV1 TRS increased the AUC from 0.51 to 0.88, and the ΔBMI TRS increased the AUC from 0.46 to 0.92. Average accuracy was thus ∼85% in predicting the response to the three outcomes. Results were similar in models further adjusted for F508del zygosity and previous CFTR modulator use. In conclusion, we identified nasal epithelial transcriptomic profiles that help accurately predict changes in FEV1 and BMI with ETI treatment. These novel TRSs could serve as predictive biomarkers for clinical response to modulator treatment in pwCF.

Background: Multiple breath washout is a lung function test based on tidal breathing that assesses lung volume and ventilation distribution. The aim of this analysis was to use the Global Lung Function Initiative methodology to develop all-age reference equations for the multiple breath washout indices lung clearance index (LCI) and functional residual capacity (FRC). Methods: Multiple breath washout data from healthy individuals were collated from sites. Data were re-analysed using the latest software versions. Reference equations were derived using the lambda-mu-sigma method using the generalised additive models of location shape and scale programme in R. The impact of equipment type, inert tracer gas and equipment dead space volume on the derived reference ranges were investigated. Results: Data from 23 sites (n=3647 test occasions) were submitted. Reference equations were derived from 1579 unique observations from participants between the ages of 2 and 81 years. Equipment type, inert tracer gas and equipment dead space volume did not significantly affect the prediction equations for either LCI or FRC. Reference equations for LCI include age as the only predictor, whereas sex-specific reference equations for FRC included height and age. Conclusions: Global Lung Function Initiative reference equations for multiple breath washout variables provide a standard for reporting and interpretation of LCI and FRC.

Importance: The implications of adopting race-neutral reference equations on spirometry interpretation in children remain unknown.Objective: To examine how spirometry results and patterns change when transitioning from Global Lung Function Initiative (GLI) race-specific reference equations (GLIR, 2012) to GLI race-neutral reference equations (GLIN, 2023).Design, Setting, and Participants: Cross-sectional study of spirometry tests conducted in children aged 6 to 21 years between 2012 and 2022 at 2 large academic pediatric institutions in the US. Data were analyzed from September 2023 to March 2024.Exposures: Data on participant characteristics and raw test measurements were collected. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC z scores and percent predicted were calculated using both GLIR and GLIN. In addition, test results were categorized into normal, obstructive, suspected restrictive, mixed, suspected dysanapsis, and uncategorized patterns based on z scores calculated using GLIR or GLIN.Main Outcomes: For each spirometry result, the difference between z scores and percent predicted when transitioning from GLIR to GLIN was calculated. The proportion of tests with a normal pattern and individual spirometry patterns changed by GLI reference equation applied were also examined.Results: Data from 24 630 children were analyzed (mean [SD] age, 12.1 [3.8] years). There were 3848 Black children (15.6%), 19 503 White children (79.2%), and 1279 children of other races (5.2%). Following implementation of GLIN, FEV1 and FVC z scores decreased in Black children (mean difference, −0.814; 95% CI, −0.823 to −0.806; P < .001; and −0.911; 95% CI, −0.921 to −0.902; P < .001, respectively), while FEV1 and FVC z scores slightly increased (0.073; 95% CI, 0.069 to 0.076; P < .001). Similar changes were found when using percent predicted. In Black children, the number of tests with a normal pattern decreased from 2642 (68.7%) to 2383 (61.9%) (χ²₁ = 204.81; P < .001), mostly due to tests with a normal pattern transitioning to a suspected restrictive or uncategorized pattern. Opposite, albeit smaller, changes in spirometry results and patterns were seen in White children. In adjusted models, Black children had approximately 3-fold higher odds than White children of changing spirometry pattern following the implementation of GLIN (adjusted odds ratio, 3.15; 95% CI, 2.86 to 3.48; P < .001).Conclusions: Pronounced differences in spirometry results and patterns were found when switching between GLI reference equations, which markedly differed by race. These findings suggest that the implementation of GLIN is likely to change the treatment of children with chronic lung diseases that are more prevalent in underrepresented minorities, such as asthma.