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Original Research: Pediatrics |

Encouraging Pulmonary Outcome for Surviving, Neurologically Intact, Extremely Premature Infants in the Postsurfactant EraGood Pulmonary Outcome of Extreme Prematurity

Eytan Kaplan, MD; Ephraim Bar-Yishay, PhD; Dario Prais, MD; Gil Klinger, MD; Meir Mei-Zahav, MD; Huda Mussaffi, MD; Guy Steuer, MD; Shai Hananya, MD; Yelena Matyashuk; Nassrin Gabarra; Lea Sirota, MD; Hannah Blau, MBBS
Author and Funding Information

Funding/Support: This study was supported by a grant from the Israel Association for Clinical Pediatrics.

Funding/Support: This study was supported by a grant from the Israel Association for Clinical Pediatrics.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2012;142(3):725-733. doi:10.1378/chest.11-1562
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Objective:  The aim of this study was to determine the long-term pulmonary outcome of extreme prematurity at a single tertiary-care center from 1997 to 2001 in the postsurfactant era.

Methods:  We assessed symptoms, exhaled nitric oxide, spirometry, methacholine challenge (provocative concentration of methacholine required to decrease FEV1 by 20% [PC20]), lung volumes, diffusion, and cardiopulmonary exercise tolerance.

Results:  Of 279 infants born, 192 survived to discharge, and 79 of these developed bronchopulmonary dysplasia (BPD) (65 mild, 12 moderate, two severe). We studied a subgroup of 53 neurologically intact preterm subjects aged 10 ± 1.5 years (28 with BPD [born, 26.2 ± 1.4 weeks; birth weight, 821 ± 164 g] and 25 without BPD [born, 27.2 ± 1 weeks; birth weight, 1,050 ± 181 g]) and compared them with 23 term control subjects. Of the BPD cases, 21 were mild, seven were moderate, and none was severe; 77.4% of subjects received antenatal steroids, and 83% received postnatal surfactant. Sixty percent of the preterm subjects wheezed at age < 2 years compared with 13% of the control subjects (P < .001), but only 13% wheezed in the past year compared with 0% of control subjects (not significant). For preterm and control subjects, respectively (mean ± SD), FEV1 % predicted was 85% ± 10% and 94% ± 10% (P < .001), with limited reversibility; residual volume/total lung capacity was 29.3% ± 5.5% and 25% ± 8% (P < .05); diffusing capacity/alveolar volume was 89.6% ± 9.2% and 97% ± 10% (P < .005); and PC20 was 6.5 ± 5.8 mg/mL and 11.7 ± 5.5 mg/mL (P < .001). PC20 was < 4 mg/mL in 49% of preterm subjects despite normal exhaled nitric oxide. Most measurements were similar in premature subjects with and without BPD. Peak oxygen consumption and breathing reserve were normal, but % predicted maximal load (measured in Watts) was 69% ± 15% for subjects with BPD compared with 88% ± 23% for subjects without and 86% ± 20% for control subjects (P < .01).

Conclusions:  Pulmonary outcome was encouraging at mid-childhood for neurologically intact survivors in the postsurfactant era. Despite mechanical ventilation and oxygen therapy, most had no or mild BPD. Changes found probably reflect the hypoplastic lungs of prematurity.

From the Pulmonary Institute (Drs Kaplan, Bar-Yishay, Prais, Mei-Zahav, Mussaffi, Steuer, Hananya, Blau and Mss Matyashuk and Gabarra) and Department of Neonatal Intensive Care (Drs Klinger and Sirota), Schneider Children’s Medical Center of Israel, Petah Tikva; and Sackler Faculty of Medicine (Drs Prais, Klinger, Mei-Zahav, Mussaffi, Sirota, and Blau), Tel Aviv University, Tel Aviv, Israel.

Correspondence to: Hannah Blau, MBBS, Pulmonary Institute, Schneider Children’s Medical Center of Israel, 14 Kaplan St, Petah Tikva, 49202, Israel; e-mail: hblau@post.tau.ac.il

Author contributions: Dr Blau 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.

Dr Kaplan: contributed to the study conception and design, patient recruitment, performance of lung function tests, analysis and interpretation of data, and writing of the manuscript.

Dr Bar-Yishay: contributed to the performance of lung function tests, analysis and interpretation of data, and revision of the manuscript.

Dr Prais: contributed to the performance of lung function tests, analysis and interpretation of data, and revision of the manuscript.

Dr Klinger: contributed to the patient recruitment, data collection, and revision of the manuscript.

Dr Mei-Zahav: contributed to the interpretation of data and revision of the manuscript.

Dr Mussaffi: contributed to the interpretation of data and revision of the manuscript.

Dr Steuer: contributed to the interpretation of data and revision of the manuscript.

Dr Hananya: contributed to the interpretation of data and revision of the manuscript.

Ms Matyashuk: contributed to the performance of the pulmonary function tests, to collate data within the study database, and the writing of the manuscript.

Ms Gabarra: contributed to the performance of the pulmonary function tests, to collate data within the study database, and the writing of the manuscript.

Dr Sirota: contributed to the patient recruitment, data collection, and revision of the manuscript.

Dr Blau: contributed to the study conception and design, patient recruitment, analysis and interpretation of data, and writing of the manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Prais has received pharmaceutical grant money from Abbott Laboratories and has done academic lectures to medical staff, receiving honoraria from Merck Sharp & Dohme Corp. Drs Kaplan, Bar-Yishay, Klinger, Mei-Zahav, Mussaffi, Steuer, Hananya, Sirota, and Blau and Mss Matyashuk and Gabarra have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of sponsors: The Israel Association of Clinical Pediatrics provided unconditional financial support. The sponsor had no role in the design of the study, the collection and analysis of the data, or in the preparation of the manuscript.

Other contributions: This study was performed at the Schneider Children’s Medical Center of Israel. We are grateful to Pearl Lilos, BSc, for her patience and dedication in statistical analysis of this study. We thank all the subjects for participating in a long day of lung function testing.

Funding/Support: This study was supported by a grant from the Israel Association for Clinical Pediatrics.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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