Race-Neutral Equations and Pulmonary Function Test Interpretation in Two Pediatric Cohorts.

OBJECTIVE: To investigate the changes in predicted lung function measurements when using race-neutral equations in children, based upon the new Global Lung Initiative (GLI) reference equations, utilizing a race-neutral approach in interpreting spirometry results compared with the 2012 race-specific GLI equations. STUDY DESIGN: We analyzed data from 2 multicenter prospective cohorts comprised of healthy children and children with history of severe (requiring hospitalization) bronchiolitis. Spirometry testing was done at the 6-year physical exam, and 677 tests were analyzed using new GLI Global and 2012 GLI equations. We used multivariable logistic regression, adjusted for age, height, and sex, to examine the association of race with the development of new impairment or increased severity (forced expiratory volume in the first second (FEV1) z-score ≤ -1.645) as per 2022 American Thoracic Society (ATS) guidelines. RESULTS: Compared with the race-specific GLI, the race-neutral equation yielded increases in the median forced expiratory volume in the first second and forced vital capacity (FVC) percent predicted in White children but decreases in these two measures in Black children. The prevalence of obstruction increased in White children by 21%, and the prevalence of possible restriction increased in Black children by 222%. Compared with White race, Black race was associated with increased prevalence of new impairments (aOR 7.59; 95%CI, 3.00-19.67; P < .001) and increased severity (aOR 35.40; 95%CI, 4.70-266.40; P = .001). Results were similar across both cohorts. CONCLUSIONS: As there are no biological justifications for the inclusion of race in spirometry interpretation, use of race-neutral spirometry reference equations led to an increase in both the prevalence and severity of respiratory impairments among Black children.

Association between household cleaning product exposure in infancy and development of recurrent wheeze and asthma.

OBJECTIVE: Household chemicals may act as irritants in the lungs; however, their association with recurrent wheeze and asthma in children remains controversial. We aimed to investigate if household cleaning product exposure in infancy is associated with recurrent wheezing and asthma development in children. METHODS: We analyzed data from two cohorts: MARC-35 consisting of 815 children with history of severe bronchiolitis in infancy, and MARC-43 consisting of 525 healthy children in infancy. Frequency of use of cleaning product at the child's home during infancy was collected via telephone interview with parents. Outcomes were recurrent wheezing by age 3 years and asthma diagnosis at age 6 years. RESULTS: In MARC-35, there was no association between cleaning product exposure in infancy and recurrent wheeze (adjusted HR = 1.01 [95% CI 0.66-1.54] for 4-7 days/week exposure frequency), nor asthma (adjusted OR = 0.91 [95% CI 0.51-1.63]). In MARC-43, there was also no association between cleaning product exposure in infancy and recurrent wheeze (adjusted HR = 0.69 [95% CI 0.29-1.67] for 4-7 days/week exposure frequency). CONCLUSION: We found no association between household cleaning product exposure in infancy and later development of recurrent wheeze or asthma, even among children who are at high risk for asthma due to history of severe bronchiolitis.

Development of a Pipeline for Removing Allergy Labels in Patients Undergoing Hematopoietic Stem Cell Transplantation.

Penicillin allergy is reported by 10% to 20 % of patients, but when evaluated only 1% to 2% may have a true allergy. Patients undergoing hematopoietic stem cell transplantation (HSCT) have a high likelihood of requiring beta-lactam antibiotics due to increased infection risk, which can be limited by a penicillin allergy label. When a penicillin allergy is recorded, alternatives are needed, including more expensive broader-spectrum antibiotics, with increases in drug-resistant bacteria, longer hospital stays, higher expenditures, and increases in nosocomial infections, such as Clostridium difficile colitis. This group of patients already undergoes extensive pretreatment testing and would especially benefit from allergy delabeling. This study aimed to develop a self-sustaining, low-cost pipeline between an HSCT clinic and an allergy clinic to identify and successfully delabel low-risk patients who endorse an allergy to penicillin, amoxicillin, amoxicillin-clavulanate, piperacillin-tazobactam, or ampicillin before admission to the hospital. We developed a survey to triage allergy risk, identified key stakeholders in building the pipeline, and underwent 4 plan, do, study, act (PDSA) cycles. Changes were made in each of the PDSA cycles to minimize cost and uncompensated provider time, as well as to increase patient retention throughout the pipeline by increasing appointment availability and decreasing reliance on patients to independently progress through the pathway. Of the 410 patients with planned HSCT who were screened over 11 months, 89 (21.7%) were listed as having a penicillin and/or beta lactam allergy. All but 1 (66 of 67; 98.5%) of the participants completed the survey accurately when confirmed by an allergist, and the survey was 100% accurate in predicting delabeling success in low-risk patients. Of eligible patients, 43.8% (n = 39) were successfully delabeled before their transplant date, and 97.4% of these (n = 38) have undergone HSCT to date. This pipeline is maintained by approximately 5 hours of work per week (1 hour of allergy physician time, 4 hours of nurse and/or clinical coordinator time), with no other direct costs. There is an estimated direct savings of at least $1914.93 per patient delabeled. We successfully designed and implemented a pipeline between the HSCT clinic and the allergy clinic as a quality improvement initiative to identify and address high rates of reported beta-lactam allergies. We identified and addressed patient-based factors, logistical, temporal, and financial barriers that impacted patient retention and sustainability. This model is expected to yield significant and sustained cost savings for the healthcare system as well as to improve patient outcomes, and this hypothesis is currently undergoing formal analysis. We anticipate that this model can be used to create a similar pipeline in other healthcare systems for HSCT recipients, as well as patients in other clinical settings, such as oncology and chimeric antigen receptor T cell therapy.

Association between Early Childhood Vitamin D Status and Age 6-Year Lung Function among Children with a History of Severe Bronchiolitis in Infancy.

Improving lung health in children requires understanding the risk factors for decreased lung function. Our objective was to investigate the association between serum 25-hydroxyvitamin D (25(OH)D) levels and lung function in children. We analyzed data from a prospective cohort of infants hospitalized with bronchiolitis (severe bronchiolitis), a group at high risk for developing childhood asthma. Children were followed longitudinally, and 25(OH)D and spirometry testing were conducted at ages 3 and 6, respectively. We used a multivariable linear regression adjusted for race/ethnicity, annual household income, premature birth, and secondhand smoke exposure to examine the association between serum 25(OH)D level and primary outcomes (percent predicted [pp] of forced expiratory volume in the first second (FEV1) and the forced vital capacity (FVC)) and secondary outcome (FEV1pp/FVCpp). Serum 25(OH)D level and age 6 spirometry were available for 363 children. In adjusted analyses comparing the highest quintile (Q5) of serum 25(OH)D (median 37 ng/mL) to the lowest quintile (Q1; median 18 ng/mL), FEV1pp was 6% lower (p = 0.03) in Q1. Likewise, FVCpp was 7% lower (p = 0.03) in Q1. There was no difference in FEV1pp/FVCpp across the serum 25(OH)D quintiles. Compared to children with higher vitamin D status at age 3, those with lower status had decreased FEV1pp and FVCpp at 6 years.

Association between severe bronchiolitis in infancy and age 6-year lung function.

BACKGROUND AND OBJECTIVES: Understanding early life risk factors for decreased lung function could guide prevention efforts and improve lung health throughout the lifespan. Our objective was to investigate the association between history of severe (hospitalized) bronchiolitis in infancy and age 6-year lung function. METHODS: We analyzed data from two prospective cohort studies: infants hospitalized with bronchiolitis and a parallel cohort of healthy infants. Children were followed longitudinally, and spirometry was performed at age 6 years. To examine the relationship between history of severe bronchiolitis and primary outcomes - FEV1% predicted (pp) and FEV1/FVCpp - we used multivariable linear regression models adjusted for insurance status, perterm birth, secondhand smoke exposure, breastfeeding status, traffic-related air pollution and polygenic risk score. Secondary outcomes included FVCpp and bronchodilator responsiveness (BDR). RESULTS: Age 6-year spirometry was available for 425 children with history of severe bronchiolitis in infancy and 48 controls. Unadjusted analysis revealed that while most children had normal range lung function, children with a history of severe bronchiolitis had lower FEV1pp and FEV1/FVCpp. In adjusted analyses, the same findings were observed: FEV1pp was 8% lower (p = 0.004) and FEV1/FVCpp was 4% lower (p = 0.007) in children with history of severe bronchiolitis versus controls. FVC and BDR did not differ between groups. CONCLUSIONS: Children with severe bronchiolitis in infancy have decreased FEV1 and FEV1/FVC at age 6 years, compared to controls. These children may be at increased risk for chronic respiratory illness later in life.

Epinephrine treatment of food-induced and other cause anaphylaxis in United States and Canadian Emergency Departments: a systematic review and meta-analysis.

INTRODUCTION: Studies from more than 10 years ago showed epinephrine treatment of food-induced anaphylaxis in the emergency department (ED) was unacceptably low. We investigated whether epinephrine treatment of food-induced and other cause anaphylaxis in United States and Canadian EDs has changed over time. METHODS: Guided by a health sciences librarian, we performed a systematic search in Medline, Embase, and Web of Science on 11 January 2023. We included observational studies that reported epinephrine use to treat anaphylaxis in the ED. We stratified by anaphylaxis etiology (food-, venom-, medication-induced, or any cause). Associations between year and epinephrine use were tested using Spearman correlation and proportional meta-analysis. RESULTS: Of 2458 records identified in our initial search, 40 met inclusion criteria. Of these, 14 examined food-induced, 4 venom-induced, 0 medication-induced, and 24 any cause anaphylaxis. For epinephrine treatment of food-induced anaphylaxis in the ED, among studies using similar definition of anaphylaxis, meta-analysis showed a pooled value of 20.7% (95% CI 17.8, 23.8) for studies performed >10 years ago and 45.1% (95% CI 38.4, 52.0) from those in the last 10 years. For anaphylaxis of any cause, there was no change over time, with a pooled value of 45.0% (95% CI 39.8, 50.3) over the last 10 years. DISCUSSION: Epinephrine treatment of food-induced anaphylaxis in the ED has increased over time. There was no clear change for anaphylaxis of any cause. Over the last 10 years, approximately 45% of ED patients with anaphylaxis received epinephrine. A limitation of the evidence is heterogeneity in anaphylaxis definitions.