Association of hydrogen peroxide in exhaled breath condensates from infants with respiratory distress syndrome with the development of chronic lung disease.
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Publications and source records attributed to B A Darlow.
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OBJECTIVE: To compare the psychosocial functioning of the parents (mother and father) of infants admitted to a neonatal intensive care unit (NICU) with the parents of infants born at term and not admitted to the NICU. DESIGN: Random sample of NICU parents and term non-NICU parents were assessed across a variety of psychiatric and psychosocial measures shortly after the birth of their infant. SETTING: Christchurch Women's Hospital, New Zealand. Labour ward and level III NICU. PARTICIPANTS: A total of 447 parents (242 mothers; 205 fathers) with an infant admitted to a regional NICU during a 12 month period; 189 parents (100 mothers; 89 fathers) with infants born at term and not requiring NICU admission. MAIN OUTCOME MEASURES: Depression and anxiety symptoms, psychosocial functioning. RESULTS: Overall, levels of anxiety and depression were low in both parent groups. Compared with control parents, a higher percentage of NICU parents had clinically relevant anxiety and were more likely to have had a previous NICU admission and be in a lower family income bracket. Infant prematurity was associated with higher levels of symptomatology in both NICU mothers and fathers. CONCLUSIONS: Specific interventions are not needed for most parents who have an infant admitted to the NICU as they appear to adapt relatively successfully. Infant prematurity impacts negatively on the father as well as the mother. Consequently these parents may benefit from increased clinical attention.
OBJECTIVE: To determine whether regulating vitamin C (ascorbic acid: AA) intake to achieve higher or lower plasma concentrations was associated with improved clinical outcome. DESIGN: A double blind, randomised controlled trial. SETTING: Neonatal intensive care unit at Christchurch Women's Hospital. PATIENTS: Infants with birth weight <1500 g or gestation <32 weeks, admitted to the unit within 48 hours of birth. INTERVENTION: Infants were randomised to one of three protocols with regard to AA supplementation for the first 28 days of life: group LL received low supplementation throughout; group LH received low until day 10 and then high: group HH received high throughout. MAIN OUTCOME MEASURES: Primary outcome measures were oxygen requirement at 28 days and 36 weeks postmenstrual age, total days supplemental oxygen, and retinopathy of prematurity. AA concentrations were measured at study entry (day 2), and days 10, 21, and 28. RESULTS: A total of 119 infants were enrolled over 24 months (mean gestation 28.4 weeks; birth weight 1161 g). Six infants died, and these had significantly higher AA concentrations before randomisation than surviving infants (116 micromol/l (95% confidence interval 90 to 142) v 51 micromol/l (45 to 58), p<0.0001). There were no significant differences in primary outcomes between the groups. However, the proportion of surviving infants with an oxygen requirement at 36 weeks postmenstrual age in group HH (19%) was half that in group LL (41%) (p=0.06). CONCLUSIONS: In a randomised controlled trial, no significant benefits or harmful effects were associated with treatment allocation to higher or lower AA supplementation throughout the first 28 days of life.
AIM: To analyse variations in rates of severe retinopathy of prematurity (ROP) among neonatal intensive care units (NICUs) in the Australian and New Zealand Neonatal Network (ANZNN), adjusting for sampling variability and for case mix. METHODS: 25 NICUs were included in the study of 2105 infants born at less than 29 weeks in 1998 and 1999, who survived to 36 weeks post-menstrual age and were examined for ROP. The observed NICU rates of severe ROP were adjusted for case mix using logistic regression on gestation, weight for gestational age and sex, and for sampling variability using shrinkage estimates. The corrected rate in the best 20% of NICUs was identified and NICU variations in rates were compared with those in 2000-1. RESULTS: The overall (unadjusted) rate of severe ROP in the NICUs was 9.6% (interquartile range 5.4-12.8%). After adjusting for both case mix and sampling variability there remained significant variation among the NICUs. 20% of NICUs had a rate of severe ROP </=5.9%. Variation in rates among NICUs showed a similar pattern in both time periods. If the overall network rate was reduced to 5.9%, the 20th centile of the adjusted rates, there would be 79 fewer cases in a 2 year period, in contrast with 26 fewer if rates in the two units with excess rates improved to the average. CONCLUSIONS: Considerable variation in rates of severe ROP among NICUs remained after adjustment for case mix and sampling variability. These data will facilitate investigation of potentially better practices associated with a reduced risk of severe ROP.
BACKGROUND: Selenium is an essential trace element and component of a number of selenoproteins including glutathione peroxidase, which has a role in protecting against oxidative damage. Selenium is also known to play a role in immunocompetence. Blood selenium concentrations in newborns are lower than those of their mothers and lower still in preterm infants. In experimental animals low selenium concentrations appear to increase susceptibility to oxidative lung disease. In very preterm infants low selenium concentrations have been associated with an increased risk of chronic neonatal lung disease and retinopathy of prematurity. OBJECTIVES: To assess the benefits and harms of selenium supplementation in preterm or very low birthweight infants. SEARCH STRATEGY: Searches were made of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2003), MEDLINE (1966-May 2003), and Embase (1980-May 2003). The reference lists of recent trials were also searched and abstracts from the Society for Pediatric Research from 1990 were hand-searched. SELECTION CRITERIA: Randomised controlled trials which compared selenium supplementation either parenterally or enterally with placebo or nothing from soon after birth in preterm or very low birthweight infants and which reported clinical outcomes were considered for the review. DATA COLLECTION AND ANALYSIS: Data on selenium supplementation dose, formulation and route of administration; mortality, oxygen requirement at 28 days and 36 weeks post-menstrual age, retinopathy of prematurity, and one or more episodes of sepsis; blood selenium and glutathione peroxidase concentrations at or close to 28 days, were excerpted by both reviewers independently. Data analysis was conducted according to the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: Three eligible trials were identified. Two trials, including one trial with a much larger sample size than the others combined, were from geographical areas with low population selenium concentrations. Meta-analysis of the pooled data showed a significant reduction in the proportion of infants having one or more episodes of sepsis associated with selenium supplementation [summary RR 0.73 (0.57, 0.93); RD -0.10 (-0.17, -0.02); NNT 10 (5.9, 50)]. Supplementation with selenium was not associated with improved survival, a reduction in neonatal chronic lung disease or retinopathy of prematurity. REVIEWER'S CONCLUSIONS: Supplementing very preterm infants with selenium is associated with benefit in terms of a reduction in one or more episodes of sepsis. Supplementation was not associated with improved survival, a reduction in neonatal chronic lung disease or retinopathy of prematurity. Supplemental doses of selenium for infants on parenteral nutrition higher than those currently recommended may be beneficial. The data are dominated by one large trial from a country with low selenium concentrations and may not be readily translated to other populations.
OBJECTIVE: To determine short term morbidity and mortality outcomes, provision of care, and treatments for a national cohort of high risk infants born in 1998-1999 and admitted to New Zealand neonatal intensive care units (NICUs). SETTING: All level III (six) and level II (13) NICUs in New Zealand. METHODS: Prospective audit by the Australian and New Zealand Neonatal Network (ANZNN) of all infants defined as "high risk" (born at < 32 weeks gestation or < 1500 g birth weight, or received assisted ventilation for four hours or more, or had major surgery). Data were collected from birth until discharge home or death. RESULTS: There were 3368 high risk infants (3.0% of all live births), comprising 1241 (37%) < 32 weeks gestation, 1084 (32%) < 1500 g, 3156 (94%) who received assisted ventilation, and 243 (7%) who received major surgery (categories overlap). Most infants (87%) received some care in tertiary hospitals, and 13% were cared for entirely in non-tertiary hospitals. Survival was 91% for infants < 32 weeks gestation, 97% for infants > or = 32 weeks gestation who received assisted ventilation, and 92% for infants > or = 32 weeks gestation who had major surgery. The proportion of very preterm infants who survived free of early major morbidity was 11%, 28%, 53%, 81%, and 90% for infants born at < 24, 24-25, 26-27, 28-29, and 30-31 weeks gestation respectively. CONCLUSIONS: These unique population based national data provide contemporary information on the care and early morbidity and mortality outcomes for all high risk infants, whether cared for in hospitals with level III or level II NICUs.
OBJECTIVE: To compare the survival and short term morbidity of all New Zealand very low birthweight (VLBW) infants born in two epochs, 1986 and 1998-1999. SETTING: All level III and level II neonatal intensive care units (NICUs) in New Zealand. METHODS: In 1986, data were prospectively collected for a study of retinopathy of prematurity (ROP). In 1998-1999, prospective data were collected by the Australian and New Zealand Neonatal Network (ANZNN). Both cohorts included all VLBW infants born during the calendar year and admitted to a NICU. Data were collected from birth until discharge home or death. RESULTS: More VLBW infants were admitted for care in 1998-1999 (n = 1084, 0.96% of livebirths) than in 1986 (n = 413, 0.78% of livebirths; p < 0.001), including a higher proportion of VLBW infants of < 1000 g birth weight (38% v 32% respectively; p < 0.05). Survival to discharge home increased from 81.8% in 1986 to 90.3% in 1998-1999 (p < 0.001). The 1998-1999 cohort had a higher proportion of infants born in a hospital with a level III NICU (87% v 72% in 1986; p < 0.001) and receiving antenatal corticosteroids (80% v 58% in 1986; p < 0.001). In 1998-1999, the incidence of several morbidities had decreased compared with 1986, including oxygen dependency at 28 days (29% v 39% respectively; p = 0.001) and at 36 weeks postmenstrual age (16% v 23%; p = 0.002), grade 1 intraventricular haemorrhage (IVH) (8% v 24%; p < 0.001), grade 2/3 IVH (5% v 11%; p < 0.001), and stage 3/4 ROP for infants < 1000 g (6% v 13%; p < 0.001). CONCLUSIONS: The outlook for VLBW infants in New Zealand has improved since 1986.
OBJECTIVE: To determine in New Zealand infants the attack rates, risk factors, preventive policies, strain serotype and antibiotic susceptibilities of early-onset neonatal group B streptococcus (GBS) infection. METHOD: A 2-year prospective active surveillance study was conducted in New Zealand's 19 neonatal units. Cases had to present within 48 h of delivery, be unwell, possess abnormal haematological indices and have GBS isolated from sterile sites. RESULTS: Of the 112 402 infants born in New Zealand during 1998-1999, 56 had early-onset GBS infection, an attack rate of 0.5 per 1000 live births (95% confidence interval [CI] 0.38, 0.65). Seven had meningitis and there was one death (case fatality rate of 1.8%; upper 95% CI 9.5%). Univariate analysis identified young maternal age, parity, preterm labour, prolonged membrane rupture, maternal fever and assisted delivery as risk factors. Preventive policies for GBS were reported by 14 (74%) obstetric centres associated with neonatal units. Of the 56 cases, five (9%) were born to mothers receiving intrapartum antibiotics, 32 (57%) had mothers with risk factors but were not treated with antibiotics, and 19 (34%) were born to mothers without identifiable risk factors for GBS prevention. Serotypes Ia and III predominated, while two isolates were resistant to erythromycin and/or clindamycin. CONCLUSIONS: Rates of early-onset GBS infection are similar to other countries following the introduction of prevention policies. Further reductions are possible with full implementation of these guidelines. Meanwhile, emergence of antibiotic resistance complicates the management of women with penicillin allergy. Vaccine development therefore remains a priority.
Traditional gentamicin dosing every 8-24 h depending on age and weight in neonates does not provide the ideal concentration-time profile to both optimize the concentration-dependent killing by aminoglycosides and minimize toxicity. Fifty-three neonates were audited prospectively while receiving gentamicin 2.5 mg/kg every 8-24 h, aiming for peak concentrations (Cmax) of 6-10 mg/L and trough concentrations (Cmin) <2 mg/L. After the first dose, the mean (+/- s.d.) Cmax was 5.5 +/- 0.7 mg/L with sub-therapeutic concentrations (<6 mg/L) in 62% of patients, while the mean Cmin was >2 mg/L in 15% of the neonates. After the third dose the Cmax was 7.5 +/- 1.5 mg/L, with 17% <6 mg/L, whereas the mean Cmin was 2.2 +/- 1.1 mg/L with 49% of values >2 mg/L. An extended interval dosing method (24, 36 and 48 h) for infant weights of 0.75-5 kg was developed by simulation, and audited prospectively in 51 neonates. Prospective analysis of the extended interval dosing method showed a mean Cmax after the first dose of 13.1 +/- 3.6 mg/L, while the mean Cmin was 0.7 +/- 0.6 mg/L. Seventy-eight per cent had Cmax of >10 mg/L after the first dose. The mean area under the concentration versus time curve AUC0-24 was 93 mg*h/L (target = 100 mg*h/L). The extended interval dosing achieved higher Cmax values while ensuring that overall exposure per 24 h was acceptable. Prospective testing of the method demonstrated good predictive ability.
UNLABELLED: Parenteral lipids are susceptible to light-induced peroxidation, particularly under phototherapy. Ascorbic acid is protective. The aim of this study was to investigate whether dark delivery tubing and/or coadministration of multivitamin preparations could prevent peroxidation of Intralipid without undue vitamin loss. In experiments carried out on the benchtop, lipid peroxidation occurred in ambient light and was more extensive under phototherapy. Dark tubing decreased peroxide formation, but only by about 65%. In simulated clinical conditions in which solutions were pumped through standard clear or dark minibore plastic tubing. Intralipid accumulated lipid peroxides as measured by the FOX assay (280 microM) or as triglyceride hydroperoxides (52 microM). Multivitamin preparations (MVIP or Soluvit/Vitlipid) inhibited peroxide formation almost completely, and were fully protective when used with dark tubing. There was loss of riboflavin (65% from Soluvit and 35% from MVIP) in clear tubing but this was decreased to 18% and 11%, respectively, in dark tubing. Ascorbate loss was 20% (MVIP) and 50% (Soluvit) and only slightly less in dark tubing. Ascorbate loss was also seen in the absence of Intralipid and is due to riboflavin-induced photo-oxidation. CONCLUSION: Multivitamin preparations protect Intralipid against light-induced formation of lipid hydroperoxides, and administering multivitamins with Intralipid via dark delivery tubing provides a practical way of preventing peroxidation of the lipid while limiting vitamin loss. This procedure should be considered for routine use as well as with phototherapy.
OBJECTIVE: To examine the association between duration of breast milk feeding and cognitive ability at 7-8 years in a birth cohort of very low birthweight infants. DESIGN: 280 survivors from a national birth cohort of 413 New Zealand very low birthweight infants born in 1986 were assessed at age 7-8 years on measures of verbal and performance intelligence quotient (IQ) using the WISC-R. At the same time mothers were questioned as to whether they had elected to provide expressed breast milk at birth and the total duration of breast milk feeding. RESULTS: Some 73% of mothers provided expressed breast milk and 37% breast fed for four months or longer. Increasing duration of breast milk feeding was associated with increases in both verbal IQ (p < 0.001) and performance IQ (p < 0.05): children breast fed for eight months or longer had mean (SD) verbal IQ scores that were 10.2 (0.56) points higher and performance IQ scores that were 6.2 (0.35) points higher than children who did not receive breast milk. These differences were substantially reduced after control for selection factors associated with receipt of breast milk. Nevertheless, even after control for confounding, there remained a significant (p < 0.05) association between duration of breast milk feeding and verbal IQ: children breast fed for eight months or longer had adjusted mean (SD) verbal IQ scores that were 6 (0.36) points higher than the scores of those who did not receive breast milk. CONCLUSIONS: These findings add to a growing body of evidence to suggest that breast milk feeding may have small long term benefits for child cognitive development.
UNLABELLED: In order to establish how cold storage of human milk affects levels of bioavailable vitamin C, 11 samples were stored for 24 h in the refrigerator or up to 2 mo in the freezer. Total vitamin C levels decreased on average by one-third in the refrigerator or after I mo of freezing, with wide variations between individuals (6 to 76% and 3 to 100%, respectively). After 2 mo of freezing, the average decrease was two-thirds (7-100%). CONCLUSION: We recommend a change in human milk storage practices, to under 24 h in a refrigerator or under 1 mo in a freezer. Alternatively, vitamin C supplementation may be considered.
Several studies have suggested that very low birthweight (VLBW < 1500 g) is associated with increased rates of respiratory problems in childhood and that the presence of chronic lung disease further increases the risk. We aimed to assess rates of asthma at 7-8 years of age in a national cohort of VLBW infants born in 1986 and for whom perinatal data were available. Two hundred ninety-nine former VLBW children (96% of surviving children living in New Zealand) were assessed at a home visit. Parents were asked a comprehensive questionnaire, including three questions aimed at assessing morbidity from asthma: 1) was the child diagnosed as having asthma before age 7 years; 2) was the child still experiencing asthma at the age of 7 years; and 3) was the child prescribed daily medication for asthma at the age of 7 years. Overall, 50% of the cohort had been diagnosed with asthma before age 7, compared with 27% of a sample of New Zealand children assessed contemporaneously in an international study; 32% had asthma at age 7, and 11% were taking daily medication. All three categories of asthma were associated with a family history of asthma, but there was no association with any perinatal factors. A diagnosis of asthma before age 7 was more likely when the mother smoked in pregnancy (P < 0.005) and currently smoked (P < 0.01), and trended so when parents lacked high school qualifications and in Maori or Pacific Island families (P < 0.10). In contrast, daily medication was more frequent when parents had educational qualifications and in non-Maori or Pacific Island families (P < 0.05). On multiple logistic regression, a family history of asthma was a significant predictor for any and current asthma (P < 0.001) and daily medication (P < 0.05); maternal smoking in pregnancy was a significant predictor for any asthma (P < 0.05); and non-Maori or Pacific Island ethnicity was a significant predictor for asthma treatment (P < 0.05). We conclude that rates of childhood asthma are high in this VLBW cohort, but the high prevalence appears to be unrelated to perinatal factors, including respiratory morbidity. There are suggestions that social factors contribute to both asthma risk and treatment.
BACKGROUND: Vitamin A is necessary for normal lung growth and the ongoing integrity of respiratory tract epithelial cells. Preterm infants have low vitamin A status at birth and this has been associated with increased risk of developing chronic lung disease. Several studies have been undertaken to assess whether vitamin A supplementation beyond that routinely given in multivitamin preparations can reduce the incidence of this outcome. OBJECTIVES: To assess the benefit of supplementation with vitamin A in very low birthweight infants. SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal Trials, MEDLINE, Cochrane Controlled Trials Register, and Science Citation Index. The reference lists of relevant trials, recent issues of paediatric and nutrition journals, abstracts and proceedings from relevant conferences in the English language were hand searched. SELECTION CRITERIA: Randomised controlled trials which compared the effects of supplemental vitamin A with standard vitamin A regimes in infants with birthweight </=1500g, and which reported clinical outcomes (death, chronic lung disease or bronchopulmonary dysplasia) and/or vitamin A concentrations were considered for the review. DATA COLLECTION AND ANALYSIS: Data on mortality, requirement for supplemental oxygen at one month of age and at 36 weeks post-menstrual age, retinopathy of prematurity and nosocomial sepsis were excerpted by both reviewers independently. Data analysis was conducted according to the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: Six eligible trials were identified, one having a much larger sample size than the others combined. The meta-analysis suggests supplementation with vitamin A results in benefit in terms of reducing oxygen requirement at 36 weeks post-menstrual age [summary RR 0.85 (0.73, 0.98), RD -8.5% (-15.9, -1.1), NNT 11.8 (6.3, 90.9)] and trends towards reduction in death or oxygen requirement at 36 weeks post-menstrual age [summary RR 0.89 (0.79, 1.00)], oxygen use in survivors at one month of age [summary RR 0.93 (0.86, 1.01)], and death or oxygen requirement at one month of age [summary RR 0.93 (0. 86, 1.00)]. Meta-analysis of the two studies which reported on retinopathy of prematurity suggests a trend towards reduced incidence in vitamin A supplemented infants. REVIEWER'S CONCLUSIONS: Supplementing very low birthweight infants with vitamin A is associated with a reduction in oxygen requirement amongst survivors at 36 weeks post-menstrual age. Whether clinicians decide to utilise repeat intramuscular doses of vitamin A to prevent chronic lung disease may depend upon the local incidence of this outcome and the value attached to achieving a modest reduction in this outcome, balanced against the lack of other proven benefits and the acceptability of treatment. The benefits, in terms of vitamin A status, safety and acceptability of delivering vitamin A in an intravenous emulsion compared with repeat intramuscular injections should be assessed in a further trial.
BACKGROUND: Low selenium (SE) status has been documented in preterm infants and has been suggested to be a risk factor for chronic lung disease. METHODS: A total of 534 infants with birth weight <1500 g were enrolled in 8 New Zealand centers in a double-blind placebo-controlled randomized trial of SE supplementation from week 1 of life until 36 weeks' postmenstrual age or discharge home. Supplemented infants received 7 microg/kg/d of SE when fed parenterally and 5 microg/kg/d when fed orally. Plasma SE and glutathione peroxidase concentrations were measured in mothers after delivery and in infants before randomization and at 28 days and 36 weeks' postmenstrual age. Primary outcome measures were oxygen dependency at 28 days and total days oxygen dependency. RESULTS: No significant differences were seen between the groups with respect to primary or secondary outcome measures, with the exception that fewer supplemented infants had an episode of sepsis after the first week of life (P <.038). Mean plasma SE concentrations were 0.33 micromol/L before randomization in both groups and at 28 days had risen in the supplemented group (0.56 micromol/L) but fallen in the control group (0.29 micromol/L) (P <.0001). There was no association between outcome measures and SE concentrations at 28 days or 36 weeks' postmenstrual age. However, lower maternal and infant prerandomization SE concentrations were associated with increased respiratory morbidity. CONCLUSIONS: Postnatal SE supplementation in very low birth weight infants did not improve neonatal outcome. Further investigation of SE supplementation of mothers from the second half of pregnancy is warranted.
OBJECTIVE: To determine whether regional differences in early neonatal morbidity in a national cohort of very low-birthweight (VLBW) infants persisted at 7-8 years of age. METHODS: Perinatal data collected prospectively from birth on all VLBW infants born in New Zealand in 1986 and admitted to a neonatal unit included the hospital principally caring for the infant: hospitals A-D being level III hospitals and 'Other' including the smallest level III and all level II hospitals. At 7-8 years of age, 298 surviving children (96% survivors living in New Zealand) were assessed at a home visit. Parents were given a comprehensive questionnaire to complete, the children underwent a visual examination and were tested with the Revised Wechsler Intelligence Scale for Children and the child's teacher was sent a questionnaire to complete. RESULTS: Neonatal survival was significantly greater in the two largest hospitals (A and B) and this difference in survival remained at 7-8 years of age after adjustment for perinatal factors (P < 0.05). There were no differences between hospitals in risks of long-term sensorineural disability and behavioural or educational outcomes. There were interhospital differences in rates of visual problems and, after adjustment for confounding factors, there remained a marginally significant (P = 0.06) increased risk of myopia in hospital D. CONCLUSIONS: Despite differences in early morbidity favouring larger hospitals, there were no substantive differences in long-term (7-8 years) outcomes across a range of measures in this national cohort of VLBW infants.
The purpose of this study is to determine whether the oxidative injury markers, protein carbonyls and malondialdehyde (MDA), are elevated in tracheal aspirates from very low birth weight (< 1500 g) infants; to determine whether levels correlate with myeloperoxidase as a marker of neutrophil inflammation; and to assess whether high levels are associated with poor respiratory outcome. Tracheal aspirates (144 samples) were collected from 86 infants < 1500 g at times of routine suctioning. Aspirates (82 samples) from 54 infants > or = 1500 g who required intubation for a variety of diagnoses were analyzed for comparison. Analyses were performed for protein carbonyls by ELISA, total malondialdehyde by HPLC, and myeloperoxidase activity. Respiratory outcome was assessed as oxygen requirement at 28-d or 36-wk postmenstrual age, and as the number of days of oxygen requirement. Protein carbonyls were significantly higher in infants < 1500 g than larger infants, and were highest close to birth. MDA concentrations were also higher in the earlier samples. There was a strong positive correlation between protein carbonyls and myeloperoxidase, suggesting a link between protein oxidation and neutrophil activation. A similar but weaker correlation was seen for MDA. Carbonyls in samples taken after steroid administration were less than for controls with a similar age distribution. We did not see significant associations between oxidant marker levels and development of chronic lung disease. Our findings of higher amounts of protein and lipid oxidation products in tracheal aspirates with high myeloperoxidase activity, taken together with other studies showing a link between neutrophil accumulation and chronic lung disease, suggest a possible contribution by neutrophil-derived reactive oxygen species to the injury.