Socioeconomic Status, Smoke Exposure, and Health Outcomes in Young Children With Cystic Fibrosis

Ong, Thida; Schechter, Michael S.; Yang, Jing; Peng, Limin; Emerson, Julia; Gibson, Ronald L.; Morgan, Wayne J.; Rosenfeld, Margaret

doi:10.1542/peds.2016-2730

Cited by 60 publications

(63 citation statements)

References 44 publications

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“…Our data support recent work that demonstrated early postnatal SHSe in a murine muco-obstructive airway model alters immune function and disrupts bacterial clearance of P. aeruginosa 46. Smoke exposure has been previously shown to augment expression of MRSA virulence factors in non-CF murine models,47 48 and impact phagocytosis of P. aeruginosa in CF49 and non-CF cells in a CFTR-dependent manner 50. Early P. aeruginosa acquisition predicts long-term outcomes in children with CF,51 52 thereby predicting that detection and prevention of SHSe in young children with CF can aid in delaying establishment of certain chronic bacterial infections and subsequently worsened outcomes.…”

Section: Discussionsupporting

confidence: 88%

“…Additionally, we used hair nicotine to detect SHSe, which allows for a more accurate reflection of long-term exposure. Our data are more closely aligned with recent data from the Early Pseudomonas Infection Control (EPIC) observational study, which reported subjective SHSe in 52% of children over the 3 months prior to study inclusion 50. Regardless of reporting measure, our data suggest that young infants and children with CF are frequently exposed to tobacco products and greatly impacted by such exposures.…”

Section: Discussionsupporting

confidence: 86%

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Secondhand smoke alters arachidonic acid metabolism and inflammation in infants and children with cystic fibrosis

Kopp

Thompson

Kim

et al. 2019

Thorax

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BackgroundMechanisms that facilitate early infection and inflammation in cystic fibrosis (CF) are unclear. We previously demonstrated that children with CF and parental-reported secondhand smoke exposure (SHSe) have increased susceptibility to bacterial infections. SHSe hinders arachidonic acid (AA) metabolites that mediate immune function in patients without CF, and may influence CF immune dysfunction. We aimed to define SHSe’s impact on inflammation mediators and infection in children with CF.MethodsSeventy-seven children with CF <10 years of age (35 infants <1 year; 42 children 1–10 years) were enrolled and hair nicotine concentrations measured as an objective surrogate of SHSe. AA signalling by serum and macrophage lipidomics, inflammation using blood transcriptional profiles and in vitro macrophage responses to bacterial infection after SHSe were assessed.ResultsHair nicotine concentrations were elevated in 63% of patients. Of the AA metabolites measured by plasma lipidomics, prostaglandin D2 (PGD2) concentrations were decreased in children with CF exposed to SHSe, and associated with more frequent hospitalisations (p=0.007) and worsened weight z scores (p=0.008). Children with CF exposed to SHSe demonstrated decreased expression of the prostaglandin genes PTGES3 and PTGR2 and overexpression of inflammatory pathways. These findings were confirmed using an in vitro model, where SHSe was associated with a dose-dependent decrease in PGD2 and increased methicillin-resistant Staphylococcus aureus survival in human CF macrophages.ConclusionsInfants and young children with CF and SHSe have altered AA metabolism and dysregulated inflammatory gene expression resulting in impaired bacterial clearance. Our findings identified potential therapeutic targets to halt early disease progression associated with SHSe in the young population with CF.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 86%

Secondhand smoke alters arachidonic acid metabolism and inflammation in infants and children with cystic fibrosis

Kopp

Thompson

Kim

et al. 2019

Thorax

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“…Further limitations of this study need to be mentioned. The impact of socioeconomic status and of the environment, for example, exposure to environmental tobacco smoke, on disease severity in CF have been described . The communal life of Hutterite families, their stable economic situation, and their strong condemnation of smoking tobacco let us assume that these risk factors are unlikely contributors to the observed disease severity in our study.…”

Section: Discussionmentioning

confidence: 93%

Cystic fibrosis in Canadian Hutterites

Pasterkamp

Menzies

Bayomi

2019

Pediatric Pulmonology

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Background The Hutterite Brethren are a communal group of Anabaptists who live in the Western regions of North America, predominantly in the Western Canadian provinces. Due to a founder effect, Hutterites have a high rate of cystic fibrosis (CF) with genotypes limited to only two CFTR mutations. One‐third of Hutterite patients with CF are pancreatic sufficient. Previously we found an unexplained younger age at death in Hutterites compared with nonHutterites homozygous for the common F508del mutation. The present study expanded the data collection and analysis for confirmation and further exploration. Methods Anonymized information, based on Hutterite surnames, was extracted from the Canadian CF Registry. Summary data on nonHutterite patients with CF homozygous for F508del served as control. Statistical analyses explored the effects of genotype within Hutterites and compared nutritional status, lung function, and microbiologic findings between the groups. Results The younger average age at death in Hutterites compared with controls was confirmed, but there was no suggestion of a generally shortened life expectancy. While the nutritional status in Hutterite children was better than that of controls, their lung function was slightly but significantly lower. Staphylococcus aureus was more frequent in Hutterites while there was no difference between the groups regarding Pseudomonas aeruginosa. Conclusions Despite less pancreatic insufficiency, better nutrition, communal life in socioeconomic stability, and without exposure to environmental tobacco smoke, the clinical course of CF appears to be more severe in a significant number of Hutterites. Investigations of gene‐environment interactions and of CF disease gene modifiers may help to explain this conundrum.

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“…For example, in the Unite States, tobacco smoke exposure occurs most often in families with low socioeconomic status, and has independent effects on pulmonary outcomes. A recent report indicated that children exposed to tobacco smoke were more likely to have crackles and wheezes on exam . While disparities in CF lung disease related to socioeconomic status have not been explained by differential treatment of pulmonary exacerbations, the presence of these respiratory findings are associated with increased frequency of antibiotic courses .…”

Section: Discussionmentioning

confidence: 99%

“…A recent report indicated that children exposed to tobacco smoke were more likely to have crackles and wheezes on exam. 30 While disparities in CF lung disease related to socioeconomic status have not been explained by differential treatment of pulmonary exacerbations, 27 the presence of these respiratory findings are associated with increased frequency of antibiotic courses. 31 Tobacco smoke exposure is likely underreported in the CFFPR, and so we did not evaluate it in our models.…”

Section: Discussionmentioning

confidence: 99%

Poor recovery from cystic fibrosis pulmonary exacerbations is associated with poor long‐term outcomes

Sanders

Zhao

et al. 2017

Pediatric Pulmonology

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Rationale People with CF treated with IV antibiotics for a pulmonary exacerbation (PEx) frequently fail to recover to baseline FEV1. The long-term impact of these events has not been studied. Objectives To determine if a patient’s spirometric recovery after a PEx is associated with time to next PEx within 1 year, the spirometric recovery after the next PEx, and/or the number of PEx episodes in the next 3 years. Methods We used data from the CF Foundation Patient Registry from 2004–2011. We randomly selected one PEx per patient that met inclusion/exclusion criteria. Patients were defined as Non-Responders if their best FEV1 (in liters) recorded in the 3 months after the PEx was <90% of the best FEV1 (in liters) in the 6 months before the PEx. We compared Responders and Non-Responders using multivariable regression models. Results We randomly chose 13,954 PEx episodes that met inclusion/exclusion criteria. 2,762 (19.8%) patients were classified as Non-Responders. Non-Responders had a shorter median time to the next PEx, 235 (95% CI 218, 252) days, versus >365 days for Responders. Thirty-four percent of Non-Responders at the initial PEx were also Non-Reponders at the next PEx, versus 20% of Responders at the initial PEx. Non-Responders had more PEx episodes over the next 3 years, 4.99 (95% CI 4.84, 5.13), than Responders, 3.46 (95% CI 3.41, 3.51). Conclusions Poor recovery after a PEx is associated with a shorter time to the next PEx, increased risk of poor recovery at a second PEx, and more frequent subsequent PEx treatments.

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Socioeconomic Status, Smoke Exposure, and Health Outcomes in Young Children With Cystic Fibrosis

Cited by 60 publications

References 44 publications

Secondhand smoke alters arachidonic acid metabolism and inflammation in infants and children with cystic fibrosis

Secondhand smoke alters arachidonic acid metabolism and inflammation in infants and children with cystic fibrosis

Cystic fibrosis in Canadian Hutterites

Poor recovery from cystic fibrosis pulmonary exacerbations is associated with poor long‐term outcomes

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