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Research Letters |

Childhood Course of Lung Function in Survivors of Bronchopulmonary Dysplasia FREE

Marco Filippone, MD; Gea Bonetto, MD; Emanuele Cherubin, MD; Silvia Carraro, MD; Eugenio Baraldi, MD
JAMA. 2009;302(13):1418-1420. doi:10.1001/jama.2009.1419.
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To the Editor: Bronchopulmonary dysplasia (BPD) is the primary respiratory complication of premature birth, associated with a reduced maximal lung function that may carry a risk of a chronic obstructive pulmonary disease (COPD)–like phenotype developing later in life.1 There is little prospective evidence about the evolution of lung function in long-term survivors of BPD.

This prospective study was performed between October 1992 and April 2008 with 17 survivors of BPD. Maximum flow at functional residual capacity (VmaxFRC) was measured at age 2 years2 and lung function at ages 93 and 15 years. Bronchopulmonary dysplasia was defined as oxygen dependence persisting at 28 days in infants born with a weight less than 1250 g.3

Two control groups matched for sex and age (within 6 months) comprised 34 healthy children born at term and 17 children born preterm without BPD who had spirometry performed at age 9 years and again at age 14 to 15 years. Lung function measurements were compared using z scores.4,5 The study was approved by the University Hospital of Padua ethics committee, and parents provided written consent.

The study had a power of at least 84%, with a 2-sided significance level of .05, to detect a between-groups effect size of 1.0 or more. Repeated measures analysis of variance, t test, and linear regression were used for data analysis with SAS version 9.1.3 for Windows (SAS Institute Inc, Cary, North Carolina).

The BPD group showed consistent lung function tracking, indicated by no significant change in mean z score between ages 2 years (VmaxFRCz score, −1.48; 95% confidence interval [CI], −2.19 to −0.77), 9 years (z score for forced expiratory volume in 1 second [FEV1], −1.74, 95% CI, −2.27 to −1.21), and 15 years (FEV1z score, −1.71; 95% CI, −2.60 to −0.82; P = .62) (Table). There was no change in mean z score for spirometry variables between ages 9 and 15 years in the control groups. Values for FEV1 were significantly lower in the BPD group than in premature non-BPD and term-born children at both 9 and 15 years old. Prematurely born non-BPD participants also had significantly lower FEV1 values than the term-born controls.

Table Graphic Jump LocationTable. Participant Characteristics and Lung Function Resultsa

The prematurely born children showed no correlation between birth weight or gestational age and spirometry results. Among BPD participants, the z scores for VmaxFRC at 2 years old (zVmaxFRC) were correlated with the z scores for FEV1 (zFEV1) at age 15 years (r = 0.74, P < .001) and with the individual differences in zFEV1 between 9 and 15 years (Figure). zFEV1 declined significantly (P = .01) between 9 and 15 years in the 9 BPD survivors with VmaxFRC less than the 5th percentile at age 2 years (corresponding to a zVmaxFRC <−1.645) but increased (P = .01) in the 8 individuals with VmaxFRC greater than the 5th percentile (Figure); the former did not differ from the latter in perinatal-neonatal characteristics and somatic growth. Those below the 5th percentile had a lower annual rate of FEV1 growth compared with those above the 5th percentile (160 mL/y; 95% CI, 109 to 211 mL/y, vs 245 mL/y; 95% CI, 202 to 288 mL/y; P = .01) and a significantly lower zFEV1 at 15 years (−2.77; 95% CI, −3.90 to −1.64; vs −0.52; 95% CI, −1.44 to 0.40; P = .003).

Place holder to copy figure label and caption
Figure. Relationship Between Airway Function at Age 2 Years and Lung Function Change Between Ages 9 and 15 Among 17 Survivors of Bronchopulmonary Dysplasia
Graphic Jump Location

Between ages 9 and 15 years, zFEV1 increased in all patients with a VmaxFRC greater than the 5th percentile (open circles) while it decreased in all but 1 patient with VmaxFRC less than the 5th percentile (filled circles). Dashed lines indicate 95% confidence interval for the regression line; zVmaxFRC, the z score of the maximum flow at functional residual capacity; zFEV1, the z score of the forced expiratory volume in 1 second.

Early lung injuries may influence lifetime respiratory health. In the general population, low VmaxFRC values shortly after birth are a primary risk factor for airflow obstruction in adulthood.6 While our findings should be considered preliminary because of the small sample size, severe early airflow obstruction at 2 years identified survivors of BPD at greater risk of disrupted lung growth during their childhood, suggesting a guarded long-term respiratory prognosis. Patients with better airflow at 2 years showed an improvement in lung function in later childhood, suggesting some degree of functional recovery. In addition, our findings suggest that preterm delivery without BPD may also affect long-term lung function, although to a lesser extent than in patients with BPD.

Author Contributions: Dr Baraldi had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Filippone, Baraldi.

Acquisition of data: Bonetto, Cherubin.

Analysis and interpretation of data: Filippone, Bonetto, Cherubin, Carraro, Baraldi.

Drafting of the manuscript: Filippone, Carraro, Baraldi.

Critical revision of the manuscript for important intellectual content: Filippone, Bonetto, Cherubin, Carraro, Baraldi.

Statistical analysis: Filippone, Cherubin, Carraro.

Administrative, technical, or material support: Baraldi.

Study supervision: Filippone, Baraldi.

Financial Disclosures: None reported.

Additional Contributions: Maurizio Schiavon, MD (Department of Social Health, Padua, Italy), contributed to recruitment of study participants and to their lung function assessment. Anna Chiara Frigo, MSc (University of Padua), contributed to statistical analysis. Neither received compensation for their role in this study.

Baraldi E, Filippone M. Chronic lung disease after premature birth.  N Engl J Med. 2007;357(19):1946-1955
PubMed   |  Link to Article
Baraldi E, Filippone M, Trevisanuto D, Zanardo V, Zacchello F. Pulmonary function until 2 years of life in infants with bronchopulmonary dysplasia.  Am J Respir Crit Care Med. 1997;155(1):149-155
PubMed   |  Link to Article
Filippone M, Sartor M, Zacchello F, Baraldi E. Flow limitation in infants with bronchopulmonary dysplasia and respiratory function at school age.  Lancet. 2003;361(9359):753-754
PubMed   |  Link to Article
Hoo AF, Dezateux C, Hanrahan JP, Cole TJ, Tepper RS, Stocks J. Sex-specific prediction equations for Vmax(FRC) in infancy: a multicenter collaborative study.  Am J Respir Crit Care Med. 2002;165(8):1084-1092
PubMed   |  Link to Article
Stanojevic S, Wade A, Stocks J,  et al.  Reference ranges for spirometry across all ages: a new approach.  Am J Respir Crit Care Med. 2008;177(3):253-260
PubMed   |  Link to Article
Stern DA, Morgan WJ, Wright AL, Guerra S, Martinez FD. Poor airway function in early infancy and lung function by age 22 years: a non-selective longitudinal cohort study.  Lancet. 2007;370(9589):758-764
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Figure. Relationship Between Airway Function at Age 2 Years and Lung Function Change Between Ages 9 and 15 Among 17 Survivors of Bronchopulmonary Dysplasia
Graphic Jump Location

Between ages 9 and 15 years, zFEV1 increased in all patients with a VmaxFRC greater than the 5th percentile (open circles) while it decreased in all but 1 patient with VmaxFRC less than the 5th percentile (filled circles). Dashed lines indicate 95% confidence interval for the regression line; zVmaxFRC, the z score of the maximum flow at functional residual capacity; zFEV1, the z score of the forced expiratory volume in 1 second.

Tables

Table Graphic Jump LocationTable. Participant Characteristics and Lung Function Resultsa

References

Baraldi E, Filippone M. Chronic lung disease after premature birth.  N Engl J Med. 2007;357(19):1946-1955
PubMed   |  Link to Article
Baraldi E, Filippone M, Trevisanuto D, Zanardo V, Zacchello F. Pulmonary function until 2 years of life in infants with bronchopulmonary dysplasia.  Am J Respir Crit Care Med. 1997;155(1):149-155
PubMed   |  Link to Article
Filippone M, Sartor M, Zacchello F, Baraldi E. Flow limitation in infants with bronchopulmonary dysplasia and respiratory function at school age.  Lancet. 2003;361(9359):753-754
PubMed   |  Link to Article
Hoo AF, Dezateux C, Hanrahan JP, Cole TJ, Tepper RS, Stocks J. Sex-specific prediction equations for Vmax(FRC) in infancy: a multicenter collaborative study.  Am J Respir Crit Care Med. 2002;165(8):1084-1092
PubMed   |  Link to Article
Stanojevic S, Wade A, Stocks J,  et al.  Reference ranges for spirometry across all ages: a new approach.  Am J Respir Crit Care Med. 2008;177(3):253-260
PubMed   |  Link to Article
Stern DA, Morgan WJ, Wright AL, Guerra S, Martinez FD. Poor airway function in early infancy and lung function by age 22 years: a non-selective longitudinal cohort study.  Lancet. 2007;370(9589):758-764
PubMed   |  Link to Article
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