Early childhood lung function is a stronger predictor of adolescent lung function in cystic fibrosis than early Pseudomonas aeruginosa infection

Jessica E. Pittman, Hannah Noah, Hollin E. Calloway, Stephanie Davis, Margaret W. Leigh, Mitchell Drumm, Scott D. Sagel, Frank J. Accurso, Michael R. Knowles, Marci K. Sontag

Research output: Contribution to journalArticle

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Abstract

Objective: Pseudomonas aeruginosa has been suggested as a major determinant of poor pulmonary outcomes in cystic fibrosis (CF), although other factors play a role. Our objective was to investigate the association of early childhood Pseudomonas infection on differences in lung function in adolescence with CF. Methods: Two populations of subjects with CF were studied: from the Gene Modifier Study (GMS), 346 F508del homozygotes with severe vs. mild adolescent lung disease, and from the Colorado Newborn Screen Study (NBS) 172 subjects diagnosed with CF by newborn screening. Associations of Pseudomonas infection and lung function in early childhood with lung function in adolescence were investigated using multivariate linear regression analyses. Results: Among GMS subjects, those with severe adolescent lung disease had worse lung function in childhood (FEV1 25 percentage points lower) compared to subjects with mild adolescent lung disease, regardless of early childhood Pseudomonas status. Among NBS subjects, those with lowest adolescent lung function had significantly lower early childhood lung function and faster rate of decline in FEV1 than subjects with highest adolescent lung function; early Pseudomonas infection was not associated with rate of FEV1 decline. The strongest predictor of adolescent lung function was early childhood lung function. Subjects with a higher percentage of cultures positive for Pseudomonas before age 6 or a lower BMI at 2-4 years old also had lower adolescent lung function, though these associations were not as strong as with early childhood lung function. Conclusions: In separate analyses of two distinct populations of subjects with CF, we found a strong correlation between lower lung function in early childhood and adolescence, regardless of early childhood Pseudomonas status. Factors in addition to early Pseudomonas infection have a strong impact on lung function in early childhood in CF. Further exploration may identify novel underlying genetic or environmental factors that predispose children with CF to early loss of lung function.

Original languageEnglish (US)
Article number0177215
JournalPLoS One
Volume12
Issue number5
DOIs
StatePublished - May 1 2017

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Pseudomonas Infections
cystic fibrosis
lung function
Pseudomonas aeruginosa
childhood
Cystic Fibrosis
Lung
infection
Pseudomonas
adolescence
Pulmonary diseases
respiratory tract diseases
Modifier Genes
Lung Diseases
neonates
modifiers (genes)
Newborn Infant
homozygosity
Homozygote
Linear regression

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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Early childhood lung function is a stronger predictor of adolescent lung function in cystic fibrosis than early Pseudomonas aeruginosa infection. / Pittman, Jessica E.; Noah, Hannah; Calloway, Hollin E.; Davis, Stephanie; Leigh, Margaret W.; Drumm, Mitchell; Sagel, Scott D.; Accurso, Frank J.; Knowles, Michael R.; Sontag, Marci K.

In: PLoS One, Vol. 12, No. 5, 0177215, 01.05.2017.

Research output: Contribution to journalArticle

Pittman, JE, Noah, H, Calloway, HE, Davis, S, Leigh, MW, Drumm, M, Sagel, SD, Accurso, FJ, Knowles, MR & Sontag, MK 2017, 'Early childhood lung function is a stronger predictor of adolescent lung function in cystic fibrosis than early Pseudomonas aeruginosa infection', PLoS One, vol. 12, no. 5, 0177215. https://doi.org/10.1371/journal.pone.0177215
Pittman, Jessica E. ; Noah, Hannah ; Calloway, Hollin E. ; Davis, Stephanie ; Leigh, Margaret W. ; Drumm, Mitchell ; Sagel, Scott D. ; Accurso, Frank J. ; Knowles, Michael R. ; Sontag, Marci K. / Early childhood lung function is a stronger predictor of adolescent lung function in cystic fibrosis than early Pseudomonas aeruginosa infection. In: PLoS One. 2017 ; Vol. 12, No. 5.
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abstract = "Objective: Pseudomonas aeruginosa has been suggested as a major determinant of poor pulmonary outcomes in cystic fibrosis (CF), although other factors play a role. Our objective was to investigate the association of early childhood Pseudomonas infection on differences in lung function in adolescence with CF. Methods: Two populations of subjects with CF were studied: from the Gene Modifier Study (GMS), 346 F508del homozygotes with severe vs. mild adolescent lung disease, and from the Colorado Newborn Screen Study (NBS) 172 subjects diagnosed with CF by newborn screening. Associations of Pseudomonas infection and lung function in early childhood with lung function in adolescence were investigated using multivariate linear regression analyses. Results: Among GMS subjects, those with severe adolescent lung disease had worse lung function in childhood (FEV1 25 percentage points lower) compared to subjects with mild adolescent lung disease, regardless of early childhood Pseudomonas status. Among NBS subjects, those with lowest adolescent lung function had significantly lower early childhood lung function and faster rate of decline in FEV1 than subjects with highest adolescent lung function; early Pseudomonas infection was not associated with rate of FEV1 decline. The strongest predictor of adolescent lung function was early childhood lung function. Subjects with a higher percentage of cultures positive for Pseudomonas before age 6 or a lower BMI at 2-4 years old also had lower adolescent lung function, though these associations were not as strong as with early childhood lung function. Conclusions: In separate analyses of two distinct populations of subjects with CF, we found a strong correlation between lower lung function in early childhood and adolescence, regardless of early childhood Pseudomonas status. Factors in addition to early Pseudomonas infection have a strong impact on lung function in early childhood in CF. Further exploration may identify novel underlying genetic or environmental factors that predispose children with CF to early loss of lung function.",
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AU - Noah, Hannah

AU - Calloway, Hollin E.

AU - Davis, Stephanie

AU - Leigh, Margaret W.

AU - Drumm, Mitchell

AU - Sagel, Scott D.

AU - Accurso, Frank J.

AU - Knowles, Michael R.

AU - Sontag, Marci K.

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N2 - Objective: Pseudomonas aeruginosa has been suggested as a major determinant of poor pulmonary outcomes in cystic fibrosis (CF), although other factors play a role. Our objective was to investigate the association of early childhood Pseudomonas infection on differences in lung function in adolescence with CF. Methods: Two populations of subjects with CF were studied: from the Gene Modifier Study (GMS), 346 F508del homozygotes with severe vs. mild adolescent lung disease, and from the Colorado Newborn Screen Study (NBS) 172 subjects diagnosed with CF by newborn screening. Associations of Pseudomonas infection and lung function in early childhood with lung function in adolescence were investigated using multivariate linear regression analyses. Results: Among GMS subjects, those with severe adolescent lung disease had worse lung function in childhood (FEV1 25 percentage points lower) compared to subjects with mild adolescent lung disease, regardless of early childhood Pseudomonas status. Among NBS subjects, those with lowest adolescent lung function had significantly lower early childhood lung function and faster rate of decline in FEV1 than subjects with highest adolescent lung function; early Pseudomonas infection was not associated with rate of FEV1 decline. The strongest predictor of adolescent lung function was early childhood lung function. Subjects with a higher percentage of cultures positive for Pseudomonas before age 6 or a lower BMI at 2-4 years old also had lower adolescent lung function, though these associations were not as strong as with early childhood lung function. Conclusions: In separate analyses of two distinct populations of subjects with CF, we found a strong correlation between lower lung function in early childhood and adolescence, regardless of early childhood Pseudomonas status. Factors in addition to early Pseudomonas infection have a strong impact on lung function in early childhood in CF. Further exploration may identify novel underlying genetic or environmental factors that predispose children with CF to early loss of lung function.

AB - Objective: Pseudomonas aeruginosa has been suggested as a major determinant of poor pulmonary outcomes in cystic fibrosis (CF), although other factors play a role. Our objective was to investigate the association of early childhood Pseudomonas infection on differences in lung function in adolescence with CF. Methods: Two populations of subjects with CF were studied: from the Gene Modifier Study (GMS), 346 F508del homozygotes with severe vs. mild adolescent lung disease, and from the Colorado Newborn Screen Study (NBS) 172 subjects diagnosed with CF by newborn screening. Associations of Pseudomonas infection and lung function in early childhood with lung function in adolescence were investigated using multivariate linear regression analyses. Results: Among GMS subjects, those with severe adolescent lung disease had worse lung function in childhood (FEV1 25 percentage points lower) compared to subjects with mild adolescent lung disease, regardless of early childhood Pseudomonas status. Among NBS subjects, those with lowest adolescent lung function had significantly lower early childhood lung function and faster rate of decline in FEV1 than subjects with highest adolescent lung function; early Pseudomonas infection was not associated with rate of FEV1 decline. The strongest predictor of adolescent lung function was early childhood lung function. Subjects with a higher percentage of cultures positive for Pseudomonas before age 6 or a lower BMI at 2-4 years old also had lower adolescent lung function, though these associations were not as strong as with early childhood lung function. Conclusions: In separate analyses of two distinct populations of subjects with CF, we found a strong correlation between lower lung function in early childhood and adolescence, regardless of early childhood Pseudomonas status. Factors in addition to early Pseudomonas infection have a strong impact on lung function in early childhood in CF. Further exploration may identify novel underlying genetic or environmental factors that predispose children with CF to early loss of lung function.

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