Childhood exposure to cannabidiol and lung function: A pilot study
Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado, USA
Section of Pediatric Pulmonary and Sleep Medicine, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado, USA
Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
Article notes
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Revised 2024 Jul 11; Received 2024 Jun 14; Accepted 2024 Jul 13; Issue date 2024 Dec.
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Keywords: asthma, cannabidiol, cannabis, children, lung function
To the editor,
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Cannabidiol (CBD) use has increased substantially in recent years, particularly since the legalization of hemp‐derived CBD through the United States 2018 Agriculture Improvement Act. In the same year, the World Health Organization indicated that CBD is generally well‐tolerated with a good safety profile. Consequently, by 2020, one in three American adults reported using a CBD product.
CBD exposure among children may also be increasing, but no published studies have quantified the prevalence of this exposure. A 2022 poll reported that 7% of parents had given or considered giving their child a CBD product. However, this may underestimate children's actual exposure to CBD.
Concurrent with this trend, pediatric respiratory health is a global health priority. Asthma alone affects one in 12 children and is the leading cause of medical‐related school absenteeism. Respiratory health is thought to be driven by genetic and environmental factors, such as CBD exposure. Research surrounding the impact of CBD on respiratory function is limited to mouse models, which show that intraperitoneal injection or intranasal instillation of CBD reduces pulmonary inflammation, 1 , 2 , 3 , 4 whereas CBD administered by vape induces pulmonary inflammation. 5
To address these gaps in the literature, we conducted a pilot study by leveraging data from Healthy Start, an ethnically and racially diverse pre‐birth cohort based in Colorado. Our aims were to objectively quantify childhood exposure to CBD at age 5 years and examine the relationship between biomarker‐confirmed exposure and lung function at age 5 and 10 years.
1.METHODS
Between 2010 and 2014, Healthy Start recruited pregnant patients from the University of Colorado Hospital outpatient obstetrics clinics. Exclusions were multiple births and chronic disease. Visits occurred in pregnancy and childhood. Written consent was obtained before participation. The Colorado Multiple Institution Review Board approved the study protocol.
Healthy Start began in 2010 as a study to better understand how overnutrition in pregnancy impacts obesity and cardiometabolic health of the offspring (NCT02273297). Beginning in October 2018, Healthy Start began to collect measures on lung function among eligible children as a pilot study.
We measured CBD and delta 9‐tetrahydrocannabinol (Δ9‐THC, the most abundant cannabinoid) in urine collected at 5 years. Samples were analyzed by iC42 Clinical Research and Development (Aurora, CO) using a validated, specific, and highly sensitive liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) assay. The LC‐MS/MS system consisted of a 1200 high‐performance liquid chromatography system (Agilent Technologies) and an API5000 tandem mass spectrometer (Sciex) connected via an atmospheric pressure chemical ionization source run in the positive mode. CBD exposure was dichotomized as exposed (>limit of quantification [LOQ]; generally, 0.78 ng/mL) or not exposed (<LOQ).
Healthy Start did not collect any self‐reported data on CBD use by parents, adults in the home, or their children. Thus, we do not have information about the potential route, dose, or frequency of CBD exposure in childhood.
Lung function was measured using the tremoflo® C‐100 Airwave Oscillometry SystemTM (Thorasys) with the composite 5−37 Hz sinusoidal waveform. In this analysis, we evaluated resistance (R5) and reactance (X5) at 5 Hz, frequency dependence of resistance (R5‐19), area of reactance (AX), and resonant frequency (Fres). At least three measurements were taken and averaged for a R5 coefficient of variation <15%. Device impedance was verified with a 2 cmH2O/L/s test load before each session. Z‐scores were generated from race‐neutral reference equations. In the few cases where reactance did not cross zero before 37 Hz (n = 14), Fres was imputed between 37 and 43 Hz.
Separate generalized linear models estimated the associations between CBD exposure at 5 years with R5, R5‐19, X5, AX, and Fres at 5 and 10 years. Models were adjusted for household income, education, prepregnancy BMI, birthweight, gestational age at birth, postnatal exposure to tobacco (measured via urinary cotinine), child sex, and child age. An ⍺ of .05 determined statistical significance. Analyses were performed using Stata, version 14.2 (StataCorp LP).
2.RESULTS
This pilot study was conducted among a convenience subsample of Healthy Start participants. Of the 1410 initially enrolled, 744 children provided urine samples at the 5‐year visit, which were analyzed for CBD. Oscillometry was added to the protocol in October 2018, resulting in 66 children with lung function measured at 5 years and 276 children with lung function measured at 10 years.
Compared to the full cohort, there were some differences in household income (in the larger sample, 32% had household incomes >$70,000 vs. 27% in the 5‐year analytic sample and 47% in the 10‐year analytic sample), college education (67%, 80%, and 83%, respectively), the child's race and ethnicity (Hispanic was indicated in 29%, 39%, and 27% of participants, respectively), and childhood exposure to tobacco (cotinine detected in 31%, 23%, and 22% of participants, respectively) (Supporting Information S1: Table 1).
In our 5‐year‐old analytic sample (n = 66), 12% (n = 8) were exposed to CBD, and none of the children had detectable levels of Δ9‐THC. In our 10‐year‐old analytic sample (n = 276), 19% (n = 53) were exposed to CBD, and none of the children had detectable levels of Δ9‐THC (Supporting Information S1: Table 2).
There were some univariate differences in participants by CBD exposure status, though none of the differences were statistically significant (Supporting Information S1: Table 2). In the 5‐year analytic sample (n = 66), CBD‐exposed children were more likely to be Hispanic (37% in the nonexposed group vs. 50% in the CBD‐exposed group), to be born to mothers with lower gestational weight gain (13 ± 7 vs. 11 ± 8kg), and to have concurrent exposure to tobacco (21% vs. 38%). In the 10‐year analytic sample (n = 276), CBD‐exposed children were more likely to be Hispanic (25% in the nonexposed group vs. 37% in the CBD‐exposed group), to be born to mothers with higher prepregnancy BMI (28 vs. 26 kg/m2), and to have household incomes greater than $70,000 (25% vs. 30%). There were no cases of maternal or child asthma among those with CBD exposure in the 5‐ or 10‐year analytic samples. There were no statistically significant differences in maternal age, child sex, birthweight, or gestational age at birth.
Figure 1 illustrates the oscillometry tracings for each child at the 5‐year visit. The shaded gray lines reflect individual curves over nine frequencies (5−37 Hz) for unexposed (n = 58) and exposed (n = 8) children. The average respiratory system resistance is indicated by the blue line and average respiratory system reactance is indicated by the red line. This unadjusted data suggests that CBD‐exposed children have lower R5 and R19 values, a smaller AX, and higher (less negative) X5 and X19 values.
CBD exposure was associated with a lower area of reactance (mean Z‐score difference: −0.7; 95% CI: −1.3 to −0.1: p = .03) and resonant frequency (−0.9; 95% CI: −1.5 to −0.4: p < .01) at 5 years (Table 1). There were no differences in lung function at 10 years.
| Oscillometry measure | Description | Z‐score at 5 years | Z‐score at 10 years |
|---|---|---|---|
| Resistance 5 Hz (R5) | ↓values indicate less pulmonary obstruction | −0.6 (−1.2 to 0.04); p = .07 | −0.2 (−0.5 to 0.1); p = .20 |
| Resistance 5−19 Hz (R5‐19) | 0 indicates no airway obstruction | 0.0 (−0.7 to 0.6); p = .84 | −0.1 (−0.4 to 0.2); p = .61 |
| Reactance 5 Hz (X5) | Values closer to 0 indicate healthier lungs | 0.1 (−0.4 to 0.7); p = .61 | 0.1 (−0.2 to 0.4); p = .54 |
| Resonance frequency (Fres) | ↓values demonstrate healthy lung elastance | −0.9 (−1.5 to −0.4); p < .01 | 0.0 (−0.3 to 0.3); p = .89 |
| Area under the curve (AX) | ↓values reflect efficient respiratory emptying | −0.7 (−1.3 to −0.1); p = .03 | 0.0 (−0.3 to 0.3); p = .92 |
3.DISCUSSION
Our pilot study is the first to examine the association between childhood exposure to CBD (without Δ9‐THC) and its impacts on respiratory function. Compared to nonexposed children, CBD‐exposed children had lower AX and Fres measures at 5 years, corresponding to increased respiratory system compliance.
CBD is known to have anti‐inflammatory, immunomodulatory, and bronchodilatory properties, 6 all of which could improve child lung function. However, these effects may be short‐lived. In this study, we observed that CBD exposure at 5 years was associated with improved lung function at 5 years, but not 10 years. This is consistent with animal models, which show that anti‐inflammatory effects in the lungs peak 7 days after CBD administration, with no further changes after 7 days. 4
Our pilot study is not without limitations. First, we lacked information on how children were exposed to CBD. Murine models report different effects depending on how CBD was administered, 1 , 2 , 3 , 4 , 5 which warrants further study in longitudinal cohorts.
Second, CBD exposure was measured once at age 5 years, which prohibited our ability to examine windows of heightened susceptibility. CBD has been shown to cross the placental barrier and could interfere with fetal lung development. However, none of the participants in this substudy had prenatal exposure to CBD (as measured in urine collected at 27 weeks gestation; data not presented). Furthermore, CBD exposure in the first 3 years of life may disrupt postnatal lung development (e.g., maturation of alveoli, thinning of blood−air barrier). Future human studies and animal models are needed to better understand how the timing of exposure to CBD may impact lung function.
Lastly, only 5% of the children initially enrolled in the study had complete data on CBD exposure and lung function at 5 years. However, our results may still be generalizable to ethnically diverse populations since included and excluded children were similar with respect to household income, race, ethnicity, and other environmental factors.
A notable strength of our approach is the use of oscillometry, an effort‐independent measure of pulmonary function that has clinical utility for diagnosing respiratory disease in young patients. Additionally, CBD was measured objectively through biomarkers, which minimizes reporting bias due to the perceived stigma of CBD exposure in childhood. Finally, our approach is in line with the American Thoracic Society's recommendation to use race‐neutral lung function assessments so as not to mask or exaggerate health disparities.
In summary, our pilot study results suggest that exposure to CBD at 5 years is associated with some improvements in lung function at 5 years. However, our pilot study is limited by the small sample size, objective measurement of CBD at a one‐time point, and a lack of information on how the child was exposed to CBD. Given the lack of data on this important and timely topic, more longitudinal data is needed to understand how CBD may impact child respiratory health.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflict of interest.
Supporting information
ACKNOWLEDGMENTS
This work was supported by the National Institutes of Health (R01DK076648, UH3OD023248, R00ES028711).
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Younoszai N, Hollander C, Kinney GL, et al. Childhood exposure to cannabidiol and lung function: a pilot study. Pediatr Pulmonol. 2024;59:3766‐3769. 10.1002/ppul.27187
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
REFERENCES
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Associated Data
Supplementary Materials
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.