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Chronic lung disease is the most common adverse outcome in survivors of prematurity. These infants experience frequent hospitalisation because of respiratory-related illness in their first year, as well as persistent cough, wheeze and oxygen dependence. Although the severity of respiratory illness decreases and supplemental oxygen is needed less as their lungs mature, childhood is still complicated by persistent wheeze, cough and reduced exercise tolerance in comparison with their peers. Although there is little longitudinal follow-up data beyond adolescence, imaging studies suggest that these infants are highly likely to suffer with respiratory problems akin to chronic obstructive pulmonary disease in later adulthood. The nature of their long-term respiratory problems, the impact of cigarette smoking and the effect on life expectancy are all unanswered questions that need addressing as these infants grow up.

In a double blind randomised controlled trial, 30 infants with chronic lung disease received fluticasone propionate or placebo for one year. There were no significant differences between treatment groups in the incidence of any day or night time symptoms or any other outcome measures.

Background: Intramuscular supplementation with vitamin A in large doses may reduce the incidence of chronic lung disease., Aim: To investigate whether oral supplementation with vitamin A would reduce the incidence of chronic lung disease in a group of extremely low birthweight infants., Methods: Infants with birth weight < 1000 g were randomised at birth to receive oral vitamin A supplementation (5000 IU/day) or placebo for 28 days. The primary outcome was oxygen dependency at 28 days of age or death., Results: A total of 154 infants were randomised; 77 received vitamin A (median birth weight (interquartile range) 806 (710-890) g), and 77 received placebo (median birth weight (interquartile range) 782 (662-880) g). Plasma vitamin A concentrations in the supplemented group were significantly higher at 24 hours of age but did not differ significantly at birth, 12 hours of age, 7 days, or 28 days of life. There were no significant differences in the proportion of infants who survived, required oxygen at 28 days, required oxygen at 36 weeks postmenstrual age, survived without chronic lung disease at 36 weeks, survived without significant retinopathy, or who survived without significant intraventricular haemorrhage., Conclusions: Oral supplementation with 5000 IU vitamin A in extremely low birthweight infants does not significantly alter the incidence of chronic lung disease. However, this dose may have been inadequate to achieve optimal serum retinol concentrations.

Unlabelled: Persistent acquired lobar overinflation (PALO) may complicate bronchopulmonary dysplasia (BPD). From infants admitted to the regional neonatal intensive care unit or who had been followed up at the chronic lung disease clinic in Liverpool over a 6.5-year period, 11 children with BPD and PALO were identified and details of their neonatal and subsequent outcome obtained. Their median gestational age was 29 weeks (range 24-33) and median birth weight was 1317 g (range 676-1968 g). All had received ventilatory support for severe neonatal respiratory distress syndrome for a median of 26 days (range 5-86). The median age the acquired lobar overinflation was detected was 82 days (range 45424 days). Nine patients required continued neonatal or paediatric intensive care re-admission for deteriorating respiratory function. Six children have subsequently died at a median age of 9.5 months (range 6.5-20). Five patients underwent bronchoscopy, four suggesting the presence of bronchomalacia. Three patients had ventilation-perfusion scans all showing that the overinflated lobe had no mismatch defect unlike other areas of the lung., Conclusion: The place of specific therapies for persistent acquired lobar overinflation is unclear. Surgery to remove the overinflated lobe in such cases may be inappropriate and the outcome of this complication of bronchopulmonary dysplasia appears to be poor.

To determine the outcome of congenital lung abnormalities, data were collected retrospectively between January 1991 and December 1996 on any foetus found to have a lung lesion on antenatal ultrasound. A total of 23 foetuses had lung lesions on antenatal ultrasound. In two foetuses the antenatal ultrasound showed bilateral enlarged "bright" echogenic lungs with evidence of hydrops. Both pregnancies were terminated and tracheal atresia was confirmed. In 15 foetuses the antenatal ultrasound appearance was of a unilateral "bright" echogenic lung. There was one case of bronchial atresia and two cases of congenital lobar emphysema, which all had surgery. In nine cases there was a reduction in the size of the lesion on serial antenatal ultrasounds and no lesion was detected after birth. In three cases a small lesion was present after birth on chest radiography. In six foetuses the antenatal ultrasound appearance was of unilateral cystic or mixed cystic and echogenic lung lesions. Two pregnancies were terminated; both had congenital cystic adenomatoid malformation. Four pregnancies were continued and three infants had surgery soon after birth and were confirmed to have had congenital cystic adenomatoid malformation. One infant has been managed conservatively. In conclusion, a definitive diagnosis cannot usually be made antenatally. A large lesion on initial scan does not necessarily predict a poor outcome. The natural history of small asymptomatic postnatal lesions is unknown and a long-term prospective study is needed to determine the outcome of these lesions.

Four cases of infants with chronic lung disease of prematurity in whom a tracheostomy was performed for acquired subglottic stenosis are reported. The feasibility of administration of inhaled drugs and supplemental oxygen are discussed.

Aim: To compare mortality and respiratory morbidity in preterm infants born at 4 United Kingdom centers during 1994 and 1995., Method: Collection of CRIB scores, respiratory parameters and mortality rates from unit databases., Results: Mortality in center A was 27% (actual number of deaths 36/135), in center B was 30% (39/130), in center C was 28% (51/182), in center D was 39% (60/156). The rate of chronic lung disease (36 week definition) in center A was 16%, in center B was 12%, in center C was 13%, in center D was 15%. The predicted number of deaths by CRIB scores in center A was 54 (95% confidence intervals 45-63), in center B was 33 (25-41), in center C was 53 (43-63), in center D was 46 (37-56)., Conclusion: Center A had a lower than predicted mortality. Center D had a higher than predicted mortality. There is an urgent need for a national neonatal database to allow comparison between center and to identify reasons for variation in outcomes.

Aim: To determine if pulmonary artery pressure (PAP) in ventilated preterm infants is independently associated with the development of chronic lung disease (CLD) and whether early assessment has any prognostic value., Methods: Two cohorts (development n = 55; and validation n = 28) of preterm infants were studied at 24 hours of age. PAP was assessed non-invasively using its inverse correlation with the corrected acceleration time to right ventricular ejection time ratio (AT:RVET(c)), calculated from the pulmonary artery Doppler waveform. Clinical and respiratory variables were also collected. Using logistic regression analysis to identify factors independently associated with CLD, a prognostic score was developed to predict CLD. The ability of the score to predict CLD was described using receiver operating characteristic (ROC) curves., Results: Birthweight, inspired oxygen concentration, and AT:RVET(c) were independently predictive of CLD. The area under the ROC curve was 0.96 for the development and 0.89 for the validation cohort. Exclusion of AT:RVET(c) resulted in a reduction to 0.88 and 0.73, respectively., Conclusion: PAP is independently associated with CLD. An early assessment of PAP using AT:RVET(c) may permit the early prediction of CLD as part of a multifactorial scoring system.

Aim: To determine whether treatment with inhaled nitric oxide (NO) and/or dexamethasone reduces the incidence of chronic lung disease (CLD) and/or death in high risk preterm infants., Methods: Infants below 32 weeks of gestation were recruited at 96 hours of age if they were deemed to be at high risk of developing CLD. Infants were randomly assigned to one of four treatment groups using a factorial design: (1) 5-20 parts per million inhaled NO for 72 hours; (2) 0.5-1 mg/kg/day intravenous dexamethasone for 6 days; (3) both drugs together; (4) continued conventional management., Results: Forty two infants were randomised: 10 infants received inhaled NO alone; 11 dexamethasone alone; 10 both treatments; and 11 neither treatment. There was no difference in the combined incidence of CLD and/or death before discharge from hospital between either infants treated with inhaled NO and controls (RR 1.05, 95% CI 0.84-1.25), or those treated with dexamethasone and controls (RR 0.95, 95% CI 0.79-1.18)., Conclusions: At 96 hours of age, neither treatment with inhaled NO nor dexamethasone prevented CLD or death.

Aim: To investigate changes in various cardiorespiratory variables with inhaled nitric oxide (NO), as part of a randomised controlled trial., Methods: Infants were treated with inhaled NO for 72 hours. Changes in oxygenation were assessed using the oxygenation index (OI). Serial changes in pulmonary artery pressure (PAP) were assessed using the Doppler derived acceleration time to right ventricular ejection time ratio (AT:RVET). Doppler measurements of right ventricular output, pulmonary blood flow, and systolic PAP was performed in a subset of infants., Results: Twenty infants received inhaled NO and 22 acted as controls. Infants were treated at a median dose of 5 (range 5 to 20) ppm. There was a fall in median OI by 17% in treated infants within 30 minutes of treatment. The fall in OI in treated infants was significantly different from the response in controls until 96 hours. Infants treated with inhaled NO showed a rapid response with a median rise in AT:RVET of 0.04 (range -0.06 to 0.12) within 30 minutes. The change in AT:RVET was significantly different from controls until 4 hours. Median systolic PAP also fell in treated infants by 6.1 (range -14.4 to -4.4) mm Hg within 1 hour. Changes in OI were significantly associated with changes in PBF (r = 0.44), but not with changes in AT:RVET., Conclusion: Treatment with inhaled NO rapidly improves oxygenation and lowers PAP in preterm infants. However, these effects are transient and treatment does not influence long term outcome.

Chronic lung disease of prematurity (CLD) can be classified using the chest radiograph taken on day 28 into type 1 (homogeneous opacification) or type 2 (the presence of cystic change) and it has been suggested that the presence of pulmonary interstitial emphysema (PIE) leads to the development of type 2 CLD. To further study this relationship we examined the chest radiographs taken on days 1-7, 14, 21 and 28, of 202 infants treated at Liverpool Maternity Hospital between January 1980 and December 1989 who developed CLD. 39% (54/137) of infants who developed type 1 CLD had suffered from PIE compared with 78% (51/65) with type 2 CLD (p < 0.001). There was no difference in the incidence of PIE in infants who developed CLD and subsequently died compared with those who survived. In the infants who survived there was no significant difference in length of oxygen dependency between those who suffered from PIE (median 99 days oxygen dependent) and those who had no PIE (median 105 days). We conclude that the presence of PIE is associated with subsequent development of type 2 CLD but is not a prerequisite for this radiographic type of chronic lung disease. Of those infants who survive to develop CLD, the presence of PIE does not alter prognosis in terms of duration of oxygen dependency or mortality.

Neonatal lower respiratory tract colonisation with mycoplasma organisms was examined for an association with chronic lung disease. Ureaplasma urealyticum colonised 9/70 (13%) infants less than 1500 g. Seven (78%) colonised and 33 (54%) non-colonised infants developed chronic lung disease. Logistic regression analyses revealed early gestation, but not mycoplasma colonisation, was independently associated with chronic lung disease.

The outcome of infants who were admitted to the neonatal intensive care unit at Liverpool Maternity Hospital between January 1980 and December 1989 and who developed chronic lung disease (n = 242) was determined. Forty-three (18%) died in hospital and 18 (9% of survivors) were discharged with home oxygen therapy. The number of days spent receiving supplementary oxygen significantly correlated with the number of days of ventilatory support received and the inspired oxygen concentration on day 28. Logistic regression analysis revealed that death in the hospital was independently associated with being male, and correlated with the number of days of ventilatory support received and the inspired oxygen concentration on day 28. An equation that predicted the probability of death in infants with chronic lung disease was derived and was validated for infants with chronic lung disease at another center (Nottingham). This equation may be useful clinically and for research.

Objective:Prematurely born infants often have recurrent wheeze and long-term respiratory morbidity at follow-up. Assessment of airways obstruction in preschool children is feasible using the interrupter resistance (Rint) but has rarely been examined in preterm children with and without chronic lung disease (CLD). The objective of this study was to determine lung function measured by the interrupter technique, its feasibility in the ambulatory setting and respiratory health in prematurely born preschool children with and without CLD.Study Design:Preterm children of 2 to 4 years with severe CLD (>30% oxygen at 36 weeks and discharged home receiving supplemental oxygen) (n=43, median gestational age 27 weeks and median birth weight 995 g) and without CLD (n=33, median gestational age 29 weeks and median birth weight 1366 g) attempting lung function test for the first time were enrolled. Respiratory symptoms score was calculated using a questionnaire. A single set of 10 consecutive Rint measurements was obtained using a portable device (MicroRint). Median of at least five occlusions with consistent shape of mouth pressure–time curves was taken to be a Rint measurement. To assess feasibility the children were categorized as ‘satisfactory’, ‘failure’ and ‘rejected’ depending on the outcome of the test. Outcome variables were respiratory symptoms score and Rint.Result:Satisfactory Rint measurement was obtained in 46 (61%) children, 9 (36%) 2-year olds, 17 (65%) 3-year olds and 20 (80%) 4-year olds. As compared with the preterm control children (n=18), CLD children (n=28) had significantly higher respiratory symptoms score (18.5 vs 6, P<0.01) and Rint expressed as absolute values (kPa l−1) and z-scores (1.33 vs 1.16 and 1.42 vs 1.0, P<0.01), respectively.Conclusion:Rint measurement is feasible in prematurely born children of preschool age in the ambulatory setup. Preschool children with severe CLD may be identified from preterm children without CLD by increased Rint that may be used as a screening tool and as an outcome measure for interventions.Journal of Perinatology (2008) 28, 199–204; doi:10.1038/sj.jp.7211911; published online 10 January 2008 [ABSTRACT FROM AUTHOR]

Background: In prematurely born infants with chronic lung disease (CLD), RSV hospitalisation is associated with increased health service utilisation and costs in the first two years after birth. Aims: To determine whether RSV hospitalisation in the first two years was associated with chronic respiratory morbidity during the preschool years in prematurely born children who had had CD. Methods: Retrospective review of readmissions, outpatient attendances, and community care in years 2-4 and, at age 5 years, assessment of the children's respiratory status and their health related quality of life. Comparison was made of the results of children who had had at least one hospitalisation in the first two years after birth for RSV infection (RSV group) to those of the rest of the cohort. Participants were 190 of an original cohort of 235 infants with CLD and a median gestational age 27 (range 22-33) weeks. Results: The 33 children in the RSV group, compared to the rest of the cohort, had a greater duration of hospital stay and more outpatient appointments. The RSV group had required more prescriptions for all treatments and respiratory medications, and more had used an inhaler. The cost of care of the RSV group was higher (median £2630 [€4000, US$4800], range £1 24-18 091 versus £1360 [€2500, US$3000], range £5-18 929) and their health related quality of life was lower. Conclusion: In prematurely born children who had developed CLD, RSV hospitalisation in the first two years was associated with chronic respiratory morbidity and increased cost of care. [ABSTRACT FROM AUTHOR]