The role of high frequency oscillatory ventilation in very preterm infants

The role of high frequency oscillatory ventilation (HFOV) for the treatment of respiratory disease in preterm infants remains uncertain. Animal work demonstrates reduced lung injury with HFOV compared to conventional ventilation (CV), and previous human trials suggest that in preterm infants HFOV reduces the incidence of chronic lung disease (CLD). However, the trials themselves have several limitations. In an attempt to conclusively establish the role of HFOV for the prevention of CLD in very preterm infants we conducted a large, UK based, multicentre trial. Preliminary results of this study suggest there are no significant differences between the two modes of ventilation regarding mortality and incidence of CLD.     

Prevention of respiratory syncytial virus infections in high-risk infantsby monoclonal antibody (palivizumab)

Respiratory syncytial virus (RSV) is a major viral pathogen which causes serious respiratory illness in infants and children worldwide. Palivizumab (Synagis) is an anti-RSV monoclonal antibody administered intramuscularly for the prevention of severe RSV respiratory disease in high-risk infants and young children. The IMpact-RSV trial, the pivotal multicenter, randomized, placebo-controlled trial performed in the USA, Canada and the United Kingdom demonstrated an overall 55% reduction in hospitalization rate due to RSV infection in preterm infants (< or = 35 weeks gestation) with and without chronic lung disease (CLD). Subgroup analysis in premature infants without CLD revealed an even greater reduction in RSV hospitalization rates (78%). Adverse events were infrequent and did not differ between placebo and palivizumab groups. Injection site reactions were infrequent and mild; no differences were observed between palivizumab and placebo subjects. Palivizumab does not interfere with administration of other pediatric vaccines. Comprehensive parent education programs regarding prevention of infection, avoidance of risk factors for infection, careful adherence to infection control policies, and recognition of early symptoms of RSV infection remain important components of RSV prevention strategies. In light of the lack of effective vaccines for this serious health risk, palivizumab offers the only option for prophylaxis against RSV disease in high-risk infants.     

Effect of palivizumab prophylaxis in decreasing respiratory syncytial virus hospitalizations in premature infants

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of hospitalization in preterm infants and infants with chronic lung disease (CLD). Palivizumab, a humanized monoclonal antibody, was approved in Europe in 1999 as prophylaxis against severe RSV-related respiratory illness. No multiple season data have been published on palivizumab effectiveness in European populations. Data collected during 4 years in Spain compared RSV hospitalization rates and risk factors in a cohort of palivizumab-prophylaxed and nonprophylaxed preterm infants. METHODS: The first cohort was derived from 2 previous studies and included 1583 infants followed during 2 RSV seasons (1998 to 1999, 1999 to 2000) before palivizumab initiation in Spain. The second cohort included 1919 infants who received palivizumab prophylaxis for 2 subsequent respiratory seasons (2000 to 2001, 2001 to 2002). Both cohorts were preterm (< or =32 weeks gestational age) and < or =6 months old at onset of RSV season. RESULTS: The RSV hospitalization rate in the palivizumab-prophylaxed cohort was 3.95, and it was 13.25% in nonprophylaxed infants This 70% overall difference in RSV hospitalization was observed despite the palivizumab-prophylaxed group's lower gestational ages, more severe neonatal intensive care unit respiratory courses and higher incidence of CLD. Significant risk factors for RSV hospitalization in both cohorts included: lower gestational age; chronologic age <3 months at RSV season onset; school age siblings; and lower parental education. Nonprophylaxed children had a higher risk for RSV-related hospitalization than did prophylaxed patients (odds ratio, 3.86; 95% confidence interval, 2.83 to 5.25). CONCLUSION: Data from this study support the effectiveness of palivizumab in significantly modifying RSV-related hospitalizations in high risk preterm infants, with and without CLD, during two respiratory seasons.     

Clinical characteristics of chronic lung disease without preceding respiratory distress syndrome in preterm infants

BACKGROUND: Recently, the incidence of atypical presentation of chronic lung disease (CLD) that develops in infants without a history of preceding respiratory distress syndrome (RDS) is increasing. Therefore, the clinical characteristics of CLD without RDS in comparison with CLD with RDS were assessed. METHODS: Prospective cohort analysis was done from 117 very low-birthweight infants who were born in Seoul National University Hospital and survived more than 36 weeks postmenstrual age (PMA). RESULTS: Of the 117 infants analyzed, CLD developed in 44 infants (38%). Among these 44 infants, CLD with RDS developed in 27 infants (23%) and CLD without RDS developed in 17 infants (15%). Each type of CLD was subgrouped according to the presence of chorioamnionitis (CA): RDS(+)CA(+) CLD (n = 8) and RDS(+)CA(-) CLD (n = 19); and RDS(-)CA(+) CLD (n = 12) and RDS(-)CA(-) CLD (n = 5). There were no significant differences in the demographic characteristics between CLD with RDS and CLD without RDS. Chorioamnionitis was significantly more common in CLD without RDS, while patent ductus arteriosus was more common in CLD with RDS. Although the severity of initial respiratory failure was not greater than that of CLD with RDS, CLD without RDS showed a gradually increasing chronic oxygen requirement pattern. Chronic oxygen requirement pattern showed that infants with RDS(+)CA(+)CLD required the highest concentrations of oxygen not only initially but also thereafter until the 28th day of life and 36 weeks PMA. CONCLUSIONS: Although CLD without RDS was still less common than CLD with RDS, it comprised over a third of all cases of CLD in our study. Clinical characteristics and chronic oxygen requirement pattern of CLD without RDS seems to be less severe than those of CLD with RDS. Our data suggest that CLD without RDS may be developed by causes other than initial acute lung injury. Chorioamnionitis may be one of antecedents of CLD without RDS.     

Ureaplasma urealyticum and its association with chronic lung disease in Asian neonates

OBJECTIVE: The aim of the present prospective cohort study was to evaluate the relationship between lower respiratory tract colonization with Ureaplasma urealyticum and development of chronic lung disease (CLD) in a high-risk neonatal population. METHODS: Prospective cohort study of preterm infants with a birthweight < 1,500 g needing mechanical ventilation within 24 h of birth in a tertiary care neonatal unit. Endotracheal aspirates from these infants were cultured within 24 h for U. urealyticum and the rate of colonization was determined. The primary outcome measure was the incidence of CLD at 28 days of life. RESULTS: Of the 41 infants studied, 10 (24%) infants were colonized with U. urealyticum. The colonization rate was higher in babies < 1,000 g compared with babies weighing 1,000-1,500 g (P = 0.04). There was no significant difference between the colonized and non-colonized groups with regard to the antenatal use of steroids, maternal prolonged rupture of membranes, gestational age, birthweight, sex, respiratory distress syndrome, use of surfactant, patent ductus arteriosus and gastrooesophageal reflux. Of the 37 survivors, 20 (54%) developed CLD; eight infants (88.5%) in the colonized group developed CLD compared with 12 infants (42.8%) in the non-colonized group (P = 0.01). CONCLUSIONS: Neonates colonized with U. urealyticum were twice as likely to have CLD than non-colonized babies (relative risk 2.01; 95% confidence interval 1.27-3.37). These data suggest a significant association between colonization with U. urealyticum and CLD in infants weighing < 1,500 g.     

Prophylactic high-frequency oscillatory ventilation in preterm infants

The role of high-frequency oscillatory ventilation (HFOV) for the treatment of respiratory disease in preterm infants remains uncertain. Several randomized trials, comparing HFOV and conventional ventilation (CV) have been performed and their results suggest that HFOV may reduce the incidence of chronic lung disease (CLD) in preterm infants. However, the trials have several limitations and it remains unclear whether HFOV might increase intracranial pathology in very prematurely born infants. UKOS, a large, UK-based, multicentre trial was conducted to establish conclusively the role of prophylactic HFOV for the prevention of CLD in infants born prior to 29 wk of gestational age.
Conclusion : There is still a need to fully evaluate prophylactic HFOV with particular emphasis on both short and long term respiratory and neurological outcomes.     

Cognitive development at 5.5 years of children with chronic lung disease of prematurity

BACKGROUND: Preterm infants with chronic lung disease (CLD) had impaired cognitive development and poorer eye-hand coordination at 10 months of age. AIMS: To study whether this effect of CLD persisted until school age and whether the severity of CLD affected outcome. METHOD: Cognition and visual-motor skills were examined (Wechsler preschool and primary scale of intelligence, and tests from the Nepsy scale) in 60 very preterm children, without intraventricular haemorrhage or periventricular leucomalacia, at 5.5 years of age. Thirty two children suffered from CLD and 28 were controls. RESULTS: The groups did not differ significantly in cognitive outcome. Children with CLD and controls attained a full scale intelligence quotient (IQ) of 94.4 and 99.1, a verbal IQ of 99.6 and 101.5, and a performance IQ of 90.9 and 96.7 respectively. Similarly, no difference was found in tests of eye-hand control. However, the children with the most severe form of CLD had significantly lower performance (84.8) and full scale(87.6) IQs and worse visual-motor performance than the controls. CLD grade III, together with the need for glasses or lenses, had a significant impact on the explained variance. CONCLUSIONS: At school age, children born very preterm and who experienced severe CLD had deficits in cognition, visual-motor perception, and performance. The findings suggest a need to consider intervention programmes for such infants.     

Vitamin A status in preterm neonates with and without chronic lung disease

It has been proposed that there is an association between vitamin A (VA) deficiency and the development of chronic lung disease (CLD) in preterm infants. This study was designed to measure the VA status in preterm infants and to compare the results in the group of babies who developed CLD with the group who did not. Vitamin A status was assessed by measuring plasma VA, retinol binding protein (RBP) and the plasma VA:RBP molar ratio in 25 infants of less than 31 weeks gestation during the first 28 days of life. Eleven babies developed CLD and 14 did not. There was no significant difference in plasma VA levels between the CLD and non CLD groups during the first 28 days. The majority of infants had adequate VA status, with a subgroup being deficient.     

The role of inflammation in the development of chronic lung disease in neonates

 Chronic lung disease (CLD) has been associated with chorioamnionitis and upper respiratory tract colonisation with Ureaplasma urealyticum. The aim of this review is to describe the increasing evidence that inflammation plays a critical role in the early stages of CLD of the neonate. Ongoing lung damage in the premature infant may be caused by failure to downregulate and control this inflammatory response. Tumour necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and IL-8 are important pro-inflammatory cytokines of which IL-8 is an important chemotactic factor in the lung. Data suggest that preterm newborns with lung inflammation may be unable to activate the anti-inflammatory cytokine IL-10. Therefore, early post-natal anti-inflammatory therapy could help in preventing development of CLD. Prophylactic dexamethasone therapy cannot yet be recommended. There are a number of potential interactions between surfactant and cytokine effects on the preterm lung which have not been evaluated. Surfactant protein A may be an important modulator of the immune response to lung injury. The role of high-frequency ventilation in the prevention of CLD still remains unclear. Conclusion Many aspects of the pathogenesis of the inflammatory response in the development of chronic lung disease remain to be elucidated. Further research to identify preterm infants at highest risk for the development of this multifactorial and complex disease is needed. Received: 17 January 2001 / Accepted: 11 April 2001     

Development of chronic lung disease in preterm infants treated with surfactant

BACKGROUND: Chronic lung disease (CLD) is generally known to develop among preterm infants who have severe respiratory distress syndrome (RDS) at birth. Many clinical trials have established the efficacy of surfactant replacement therapy to treat RDS at birth with differing doses. In this study, the preterm infants diagnosed to have RDS at birth and treated with one or two doses of surfactant, depending on the severity of the RDS, were studied to evaluate the effect of surfactant on the later development of CLD. METHODS: A retrospective examination of case records of preterm infants who were born at < or = 28 weeks gestation period were studied. The subjects received a natural surfactant product (survanta) between September 1994 and April 1996 at the Monash Medical Center, Australia. RESULTS: Despite less severe initial lung disease, the subsequent respiratory outcome of infants who received one dose of surfactant, showed a trend towards being poorer compared to those who were diagnosed as having severe RDS at birth and received two doses of surfactant. At the corrected gestational age of 36 weeks, 54% of those infants began with mild RDS required oxygen, while only 44% of those who started with a severe RDS required supplemental O2. CONCLUSION: This study reports the infants with severe RDS at birth had responded slightly better or equally, compared to those with mild RDS, in terms of later development of CLD under surfactant treatment proportional to the severity.     

Hospital admissions in the first year of life in very preterm infants

OBJECTIVE: To analyse hospital readmissions to 1 year in infants < 33 weeks' gestation. STUDY DESIGN: Cohort of very preterm infants born in Western Australia. METHODS: Parental social class, history of asthma, race, gestational age, birthweight, sex, severity of respiratory disease and oxygen requirement at 28 days chronic lung disease (CLD), 36 weeks and term, maternal smoking, cohabitation with siblings, breast-feeding duration and hospital readmissions were recorded prospectively. RESULTS: Data were available for 538 of 560 (96%) infants discharged. Eight died in the first year. Two hundred and twenty-five infants (42%) had 443 readmissions, of which 370 were medical and 73 surgical. Risk factors for medical readmission were Aboriginal race, male sex and CLD. Breast-feeding was protective. Risk factors for surgical admission were male sex, lower gestation, severe hyaline membrane disease, severe CLD and birthweight < 10th centile. CONCLUSIONS: Readmission is common after very preterm birth. Risk factors for medical and surgical admission differ with CLD being the only perinatal factor associated with both medical and surgical admission.     

Rehospitalization in the first 2 years of life in children born preterm

Aim: Aim of the study is to investigate the frequency of and predictors for rehospitalization within the first 2 years of life among preterm infants. Methods: All children born before 32 weeks of gestation in Northern Tyrol between January 2003 and July 2008 were prospectively enrolled. Data on rehospitalizations were obtained from hospital admission records. The association between candidate risk factors and readmission was analysed by means of logistic regression analysis. Results: In the first and second years of life, 151 and 93 of 377 children (40.1% and 24.7%), respectively, were readmitted to one of the hospitals in Northern Tyrol. The most common causes of rehospitalization were respiratory disorders, accounting for 42.1% and 47.4% of total readmissions in the first and second years of life. Chronic lung disease (CLD), male sex and smoking in pregnancy were risk conditions relevant to readmission in the first year of life, but only CLD in the second year. Conclusion: Infants born before 32 weeks of gestation have a high risk of rehospitalization with respiratory illness significantly contributing to postdischarge morbidity. Neonatal intensive care should aim to further improve respiratory health in preterm infants, and adequate follow‐up services must be offered.     

Comparison of neonatal outcome for inborn and outborn very low-birthweight preterm infants

Background:  The aim of the present study was to compare the neonatal outcome of very low-birthweight (VLBW) preterm infants with regard to inborn and outborn status in a medical center of Southern Taiwan, where short-distance neonatal transport is the rule and maternal transport was not well established.
Methods:  This retrospective study included outborn VLBW preterm infants admitted to the neonatal intensive care unit of Chang Gung Memorial Hospital at Kaohsiung after neonatal transport during the period from 1999 through 2003. An equal number of inborn preterm infants matched for gender and birthweight were included as controls. Infants with lethal congenital anomalies or who died in the delivery room were excluded. Data were collected from reviewing medical charts.
Results:  A total of 34 inborn VLBW infants and 34 outborn VLBW infants with neonatal transport were included. Chronic lung disease (CLD) was significantly more frequent in the outborn group according to McNemar test ( P  = 0.0124) and logistic regression. Logistic regression also showed that outborn status ( P  = 0.0173) and birthweight ( P  = 0.0024) were the two most important risk factors for development of CLD.
Conclusion:  Well-trained short distance neonatal transport is useful and valuable for VLBW infants with gestation age of 27–34 weeks in Southern Taiwan. The respiratory outcome, however, was poor in the outborn group in terms of incidence of CLD. To improve the respiratory outcome, further modification of respiratory care during transportation or antenatal maternal transport is crucial.     

Identification and quantification of ureaplasmas colonizing the respiratory tract and assessment of their role in the development of chronic lung disease in preterm infants.

BACKGROUND: The role of Ureaplasma urealyticum in the development of chronic lung disease (CLD) in preterm infants continues to be disputed. Recently U. urealyticum has been found to consist of two species, U. urealyticum and Ureaplasma parvum, a finding that has not been considered in previous studies of CLD. This study examined the possible relationships between development of CLD and respiratory colonization by these newly redefined species, their concentrations in lower respiratory secretions and the effect of pulmonary surfactant treatment on these relationships in preterm infants with birth weights < 1500 g. METHODS: Endotracheal aspirates (ETA) were collected from intubated infants when airway suctioning was medically required. ETA were stored at -80 degrees C until quantitative cultures for ureaplasmas and Mycoplasma hominis were performed. Culture results were correlated with development of CLD. RESULTS: Of 475 infants (birth weights < 1500 g) admitted during the 2-year study period, 272 were excluded because they were not intubated or were extubated before ETA could be obtained. An additional 28 infants died, were discharged or were transferred before they could be assessed for CLD. From the remaining 175 infants ureaplasmas were isolated from 66 (38%). No statistically significant associations were identified between development of CLD and the Ureaplasma species isolated, or concentration of ureaplasmas in lower respiratory secretions. These findings were not altered by treatment with pulmonary surfactant (Survanta). CONCLUSION: Lower respiratory colonization by ureaplasmas does not appear to be a contributory cause of CLD in preterm infants.     

Effect of chronic lung disease on blood pressure levels at follow up

Thirteen preterm infants (median gestational age 28 weeks) who had developed neonatal chronic lung disease (CLD) and 13 gender- and gestational agematched controls (without CLD) were prospectively followed. The infants were seen at monthly intervals for 6 months. At each attendance the infants were examined and their blood pressure (BP) measured using a noninvasive Doppler technique. No infant developed symptoms related to hypertension and there were no significant differences in their BP levels at follow up. Our results suggests significant BP elevation is uncommon following neonatal CLD.     

Interleukin 8 and granulocyte elastase in the tracheobronchial aspirate of infants without respiratory distress syndrome or intrauterine infection and development of chronic lung disease

To elucidate the mechanism of the development of chronic lung disease (CLD) in infants without respiratory distress syndrome or intra-uterine infection, we serially measured the concentrations of interleukin 8 (IL-8) and granulocyte elastase α₁ proteinase inhibitor complex (E-α₁ PI) and elastase activity in the tracheobronchial aspirate of very low birth weight infants without respiratory distress syndrome or intra-uterine infection until day 28. IL-8 concentration and elastase activity between day 21 and 28 in infants who developed CLD later were significantly higher compared with those in infants who did not develop CLD. E-α₁ PI concentration between day 25 and 28 in infants who developed CLD later was significantly higher compared with those in infants who did not develop CLD. The area under the curve of the IL-8 and E-α₁ PI concentrations and elastase activity between day 1 and day 28 in infants with CLD was significantly higher than those in infants without CLD. These data suggest that the lung tissue injury caused by the enzymes from neutrophils accumulated and activated by IL-8 also play an important role in the development of this type of CLD.     

Ascorbate acid concentration in airways lining fluid from infants who develop chronic lung disease of prematurity

Chronic lung disease of prematurity (CLD) remains a common cause of morbidity and mortality in preterm infants. Oxygen toxicity remains a major risk factor for the development of CLD and as a consequence the antioxidant status of CLD babies is a major focus of interest. In the present study, we determined whether ascorbate, urate, and total glutathione concentrations were decreased in infants who developed CLD when compared to those who did not. From 34 preterm infants, 141 serial bronchoalveolar lavage fluid (BALF) and plasma samples were collected: 12 developed CLD (median gestation 26 weeks, range 23–28 weeks, median birth weight 780 g, range 630–1070 g), 16 developed and recovered from respiratory distress syndrome (RDS) (median gestation 31 weeks, range 26–39 weeks, median birth weight 1820 g, range 840–4160 g), and six were ventilated for non-respiratory reasons, (median gestation 35 weeks, range 32–38 weeks, median birth weight 2180 g, range 1100–2860 g). Following birth, the concentration of BALF ascorbate, urate and glutathione decreased over the 1st week in all three groups. Thereafter, BALF ascorbate increased in RDS and control infants during the 2nd week but this increase was delayed by 2 weeks in the CLD infants. No differences were noted between the RDS and CLD groups for urate and total glutathione in BALF or urate in plasma. BALF protein concentration was similar in all three groups except for a rise at day 7 in the CLD group but this did not reach statistical significance. Conclusion A delayed increase in bronchoalveolar lavage fluid ascorbate concentration might be associated with an increased risk of developing chronic lung disease of prematurity. Received: 3 May 2000 / Accepted: 17 October 2000     

Downregulatory cytokines in tracheobronchial aspirate fluid from infants with chronic lung disease of prematurity

Chronic lung disease of prematurity (CLD) is associated with an inflammatory response in the preterm lung and increased levels of proinflammatory cytokines in tracheobronchial aspirate fluid (TAF). We investigated TAF levels of transforming growth factor-beta1 (TGF-beta1), interleukin-10 (IL-10), interleukin-4 (IL-4) and interleukin-12 (IL-12) cytokines possibly important in downregulating the proinflammatory response and/or inducing lung fibrosis in infants with developing and established CLD. Infants with CLD (n = 24) were compared with preterm infants with RDS that resolved (n = 22) and postoperative infants without lung disease (n = 23). TAF levels of TGF-beta1, IL-10, IL-4 and IL-12 were studied by quantitative enzyme immunoassay. Levels of TGF-beta1 were significantly higher during the first week of life in infants who developed CLD, remained high at 2 wk and past 4 wk of age. TAF levels of TGF-beta1 did not decrease significantly in six infants with CLD after treatment with steroids. TAF IL-10 was detected in 12/46 (26%) preterm infants. Infants with CLD or RDS were more likely to have measurable TAF levels of IL-10, compared with the postoperative infants without lung disease (p < 0.02 and 0.04, respectively). TAF levels of IL-4 or IL-12 were below the detection limits in all samples. Conclusions: We have demonstrated a sustained increase of TGF-beta1 levels in TAF from preterm infants who develop CLD, suggesting an important role for TGF-beta1 in the fibrotic response in the CLD lung. The elevated TGF-beta1 levels, combined with an absent or irregular secretion of IL-4, IL-10 and IL-12, can have importance for the increased tendency for the development of CLD in preterm infants.     

Optimal level of physical activity in children with chronic lung diseases

Aim: To determine the optimal level of physical activity and its relationship with disease severity in children with chronic lung diseases (CLD). Methods: Pulmonary function and exercise tests were compared between 18 CLD children (aged 13.5 ± 2.4 years, 33% male) and 18 healthy controls without any history of lung diseases (age and sex matched). Results: CLD children had lower forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV)₁, forced expiratory flow rate between 25% and 75% of vital capacity (FEF)_25–75% and total lung capacity (TLC) and higher residual volume (RV)/TLC ratio than controls (77.3 ± 22.6 vs. 97.9 ± 12.5%pred; p = 0.002, 74.3 ± 17.6 vs. 104.0 ± 12.6%pred; p < 0.001, 49.9 ± 23.1 vs. 75.6 ± 18.6%pred; p < 0.001, 82.8 ± 18.6 vs. 95.6 ± 9.8%pred; p = 0.04, 30.8 ± 10.2 vs. 24.4 ± 5.9%; p = 0.04, respectively). Oxygen consumption at anaerobic threshold (AT) and optimal level of physical activity (metabolic equivalents [METs] at AT) were not different between the two groups and between mild and moderate to severe CLD. However, when the exercise was continued beyond the AT, CLD children demonstrated poorer exercise performance than normal controls. Conclusion: Children with CLD demonstrated the same level of optimal physical activity as normal children despite their lower lung function. The optimal level of physical activity was not related to disease severity. The exercise test and exercise should not be performed beyond the AT by the CLD children. Proper exercise test should be done to determine their optimal exercise activity.     

Chronic respiratory failure after acquired cytomegalovirus infection in a very low birthweight infant

The case of a female infant who developed chronic respiratory failure after an acquired cytomegalovirus (CMV) infection is presented here. She was a very low birthweight (VLBW) infant and was free from oxygen supplement until 2 months after birth. Interstitial pneumonia occurred at 2 months of age, and her respiratory condition gradually deteriorated. A chest roentgenogram at 4 months revealed hyperinflation and reticular shadow, similar to that of severe chronic lung disease (CLD) in preterm infants. She was mechanically ventilated because of progressive respiratory deterioration, and oxygen dependency continued for 5 months after extubation. There are several previous reports of CMV pneumonia in term neonates or infants. However, there appears to be no published report on the pulmonary sequelae of CMV pneumonia in VLBW infants. The present case seems to indicate that acquired CMV pneumonia in VLBW infants causes chronic respiratory failure even when mechanical ventilation is not administered, and this respiratory failure is very similar to CLD in clinical symptoms and chest roentgenogram.