Long-term Respiratory Outcomes Research Articles

Antioxidant Strategies and Respiratory Disease of the Preterm Newborn: An Update

Preterm newborns are challenged by an excessive oxidative burden, as a result of several perinatal stimuli, as intrauterine infections, resuscitation, mechanical ventilation, and postnatal complications, in the presence of immature antioxidant capacities. “Oxygen radical disease of neonatology” comprises a wide range of conditions sharing a common pathway of pathogenesis and includes bronchopulmonary dysplasia (BPD) and other main complications of prematurity. Antioxidant strategies may be beneficial in the prevention and treatment of oxidative stress- (OS-) related lung disease of the preterm newborn. Endotracheal supplementation or lung-targeted overexpression of superoxide dismutase was proved to reduce lung damage in several models; however, the supplementation in preterm newborn failed to reduce the risk of BPD, although long-term respiratory outcomes were improved. Also melatonin administration to small cohorts of preterm newborns suggested beneficial effects on lung OS. The possibility to identify single nucleotide polymorphism affecting the risk of BPD may help to identify specific populations with particularly high risk of OS-related diseases and may pose the basis for individually targeted treatments. Finally, surfactant replacement may lead to local anti-inflammatory and antioxidant effects, thanks to specific enzymatic and nonenzymatic antioxidants naturally present in animal surfactants.

Safety and Long Term Outcomes with High Flow Nasal Cannula Therapy in Neonatology: A Large Retrospective Cohort Study.

High flow nasal cannula therapy (HFT) has been shown to be similar to nasal continuous positive airway pressure (nCPAP) in neonates with respect to avoiding intubation. The objective of the current study is to determine if there are trends for adverse safety and long-term respiratory outcomes in very low birth weight infants (<1500 g) from centers using HFT as their primary mode of non-invasive respiratory support compared to data from the largest neonatal outcomes database (Vermont Oxford Network; VON). A multicenter, retrospective analysis of pulmonary outcomes data was performed for the calendar years 2009, 2010 and 2011. Performance of five HFT centers was compared with population outcomes from the VON database. The five HFT centers routinely use flow rates between 4-8 L/min as described by the mechanistic literature. Weighted average percentages from the five HFT centers were calculated, along with the 95% confidence intervals (CI) to allow for comparison to the VON means. Patient characteristics between the HFT centers and the VON were not different in any meaningful way, despite the HFT having a greater percentage of smaller infants. The average VON center primarily used nCPAP (69% of all infants) whereas the HFT centers primarily used HFT (73%). A lesser percentage of VLBW infants in the HFT cohort experienced mortality and nosocomial infection. Compared to VON data, an appreciably lesser percent of the HFT cohort were receiving oxygen at 36 weeks and less went home on oxygen. Considering there was no trend for adverse events, and there was a trend for better outcomes pertaining to long-term oxygen use, these data support claims of safety for HFT as a routine respiratory management strategy in the NICU.

Lack of Long-term Effects of High-dose Inhaled Beclomethasone for Respiratory Syncytial Virus Bronchiolitis

Previously, we showed that high-dose early initiated inhaled corticosteroids during respiratory syncytial virus bronchiolitis partially and transiently prevents subsequent recurrent wheeze. Here, we study treatment effect on lung function at age 6. This is a 6-year follow-up report of a randomized placebo-controlled trial, in which 185 infants hospitalized for respiratory syncytial virus bronchiolitis were treated with early initiated, high-dose inhaled beclomethasone (n = 86) or placebo (n = 99) for 3 months. The primary outcome was forced expiratory volume in 1 second as percentage predicted. Secondary outcomes were bronchial hyperresponsiveness, physician-diagnosed asthma, hay fever and eczema. Possible toxicity was assessed by linear growth measurements. At age 6, no significant differences were found in mean forced expiratory volume in 1 second percentage predicted between beclomethasone-treated and placebo-treated patients (91.4 vs. 93.4, mean difference 2.05 (95% confidence interval: -1.98 to 6.08). The proportion of bronchial hyperresponsiveness, physician-diagnosed asthma, parent reported hay fever and eczema was comparable between groups. There were no differences in linear growth. Early initiated prolonged treatment with high-dose inhaled beclomethasone during hospitalization for respiratory syncytial virus infection during infancy did not improve the long-term respiratory outcome, but was safe.

Late Preterm Infants: Near Term But Still in a Critical Developmental Time Period

Late preterm (LP) infants are defined as those born at 34-0/7 to 36-6/7 weeks' gestational age. LP infants were previously referred to as near term infants. The change in terminology resulted from the understanding that these infants are not fully mature and that the last 6 weeks of gestation represent a critical period of growth and development of the fetal brain and lungs, and of other systems. There is accumulating evidence of higher risks for health complications in these infants, including serious morbidity and a threefold higher infant mortality rate compared with term infants. This information is of critical importance because of its scientific merits and practical implications. However, it warrants a critical and balanced review, given the apparent overall uncomplicated outcome for the majority of LP infants. Others reviewed the characteristics of LP infants that predispose them to a higher risk of morbidity at the neonatal period. This review focuses on the long-term neurodevelopmental and respiratory outcomes, with the main aim to suggest putative prenatal, neonatal, developmental, and environmental causes for these increased morbidities. It demonstrates parallelism in the trajectories of pulmonary and neurologic development and evolution as a model for fetal and neonatal maturation. These may suggest the critical developmental time period as the common pathway that leads to the outcomes. Disruption in this pathway with potential long-term consequences in both systems may occur if the intrauterine milieu is disturbed. Finally, the review addresses the practical implications on perinatal and neonatal care during infancy and childhood.

A four year follow-up of sleep and respiratory measures in elementary school-aged children with sleep disordered breathing

Little is known of the long-term prognosis of children treated for sleep disordered breathing (SDB) and even less of children with milder forms of SDB who remain untreated. We aimed to investigate the long-term sleep and respiratory outcomes of children with a range of SDB severities. 41 children with SDB and 20 non snoring controls (mean age, 12.9±0.2 y), underwent repeat overnight polysomnography (PSG) 4.0±0.3years after initial diagnosis. SDB severity, presence of snoring, sleep and respiratory parameters, sleep fragmentation index (SFI), the Pediatric Daytime Sleepiness Scale (PDSS), Sleep Disturbance Scale for Children (SDSC), and obstructive sleep apnea 18-item quality of life questionnaire were re assessed. Children with SDB were grouped into resolved (no snoring and obstructive apnea-hypopnea index [OAHI] <1) and unresolved (snoring or an OAHI > or =1). At follow-up OAHI was reduced in both SDB groups (p<0.05); however, 54% (n=22) of children still continued to snore, having either persistent or new OSA (n=4). In this unresolved group, sleep was significantly disrupted; % nonrapid eye movement stage 1 (NREM1) sleep and SFI were increased (p<0.05), and total sleep time (TST) and sleep efficiency were decreased compared to the resolved and control groups (p<0.05). Overall, 29% of children were treated, and of these, 67% had resolved SDB. SDB groups had higher PDSS, SDSC, and OSA-18 scores compared to controls at follow-up (p<0.01). Our study demonstrated that although SDB improved in the long-term, more than 50% of children had residual SDB (mostly primary snoring) and sleep disturbance. As even mild forms of SDB are known to have adverse cardiovascular, learning, and behavioral outcomes, which have implications for the health of these children.

Indoor air pollution and respiratory health in the elderly

Data on respiratory effects of indoor air pollution in elderly are scanty. The purpose of this review is to summarize current knowledge on adverse respiratory effects of indoor air pollution in individuals aged over 65 years, by presenting existing epidemiological evidence. Using MEDLINE database through PubMed, we identified relevant publications published between 1991 and 2011 in English on respiratory health effects of indoor air pollution in elderly (>65 years). A total of 61 studies were found and after application of the inclusion criteria: (i) epidemiologic studies published in English in peer-reviewed journals between January 1991 and December 2011, (ii) study population with age over or equal 65 years, and (iii) outcome of respiratory symptoms and disease with the exclusion of lung cancer, 33 relevant publications were selected. Most of them showed significant relationships between exposure to major indoor air pollutants and various short-term and long-term respiratory health outcomes such as wheezing, breathlessness, cough, phlegm, asthma, COPD, lung cancer and more rarely lung function decline. The most consistent relationship is found between chronic obstructive pulmonary disease (COPD) and environmental tobacco smoke (ETS). Further studies in the elderly population are needed in order to define causal relationships between exposures to indoor air pollution and underlying mechanisms in this sub-population.

Neonatal Lung Disease and Respiratory Failure

Neonatal Lung Disease and Respiratory Failure

Long-Gap Esophageal Atresia: a Meta-Analysis of Jejunal Interposition, Colon Interposition, and Gastric Pull-Up

There is still no consensus about the optimal surgical approach for esophageal replacement in the case of long-gap esophageal atresia (LGEA) or extensive corrosive strictures. The aim of this article was to perform a meta-analysis comparing the most widely used techniques for esophageal replacement in children: jejunal interposition (JI), colon interposition (CI), and gastric pull-up (GPU). Review of the English-language literature published in the past 5 years about esophageal replacement in children was done. The focus was on postoperative survival rate, morbidity (gastrointestinal complications such as anastomotic stenosis/leakage and respiratory complications such as pneumothorax, pneumonia, and atelectasis), and long-term follow-up when available. Among long-term gastrointestinal outcomes were dysphagia, reflux, and dumping; among long-term respiratory outcomes were recurrent pneumonia and recurrent aspiration leading to chronic lung disease. Data were computed by Comprehensive Meta-Analysis software (Version 2.2.064). A total of 15 studies (4 comparative retrospective, 8 retrospective, and 3 prospective) including 470 patients (264 LGEA) were identified; 344 (73%) patients underwent CI, 99 (21%) GPU, and 27 (6%) JI. Among these 15 studies, 9 provided data about long-term follow-up. Proper prospective comparative studies are lacking. GPU and CI appear comparable regarding postoperative mortality, anastomotic complications, and graft loss. On the long-term, GPU seems to be associated with a higher respiratory morbidity but fewer gastrointestinal complications than CI. Based on this article only two series provide data about JI, and they show highly divergent results. JI appears to be a valid replacement technique when performed by experienced centers; however larger numbers are needed to assess the outcomes of this procedure.

Late administration of surfactant replacement therapy increases surfactant protein-B content: a randomized pilot study

Background:Surfactant dysfunction may contribute to the development of bronchopulmonary dysplasia (BPD) in persistently ventilated preterm infants. We conducted a multicenter randomized, blinded, pilot study to assess the safety and efficacy of late administration of doses of a surfactant protein-B (SP-B)-containing surfactant (calfactant) in combination with prolonged inhaled nitric oxide (iNO) in infants ≤1,000 g birth weight (BW).Methods:We randomized 85 preterm infants ventilated at 7–14 d after birth to receive either late administration of surfactant (up to 5 doses) plus prolonged iNO or iNO alone. Large aggregate surfactant was isolated from daily tracheal aspirates (TAs) for measurement of SP-B content, total protein, and phospholipid (PL).Results:Late administration of surfactant had minimal acute adverse effects. Clinical status as well as surfactant recovery and SP-B content in tracheal aspirate were transiently improved as compared to the controls; these effects waned after 1 d. The change in SP-B content with surfactant dosing was positively correlated with SP-B levels during treatment (r = 0.50, P = 0.02).Conclusion:Low SP-B values increased with calfactant administration, but the relationship of this response to SP-B levels suggests that degradation is a contributing mechanism for SP-B deficiency and surfactant dysfunction. We conclude that late therapy with surfactant in combination with iNO is safe and transiently increases surfactant SP-B content, possibly leading to improved short- and long-term respiratory outcomes.

125 Copd in the Next 50 Years-Should we Blame the Neonatologists?

In this talk, the current knowledge of respiratory sequelae following preterm birth in adulthood will be summarized. Specifically it will review respiratory symptoms, pulmonary function, exercise capacity and structural lung...

Long‐term evaluation of respiratory status after esophageal atresia repair

Esophageal atresia (EA) is a congenital malformation. Nowadays, its initial prognosis is excellent thanks to improvements in neonatal and surgical management. However, the assessment of long-term respiratory outcome has become necessary in affected children and was thus performed in this study. The benefits of cardiopulmonary function testing were also examined. The medical records of 77 children operated on for EA between 1990 and 2004 were reviewed. The results of respiratory function testing and cardiopulmonary response to effort were collected, together with neonatal and anthropometric data. Acceptable measurements were obtained in 31 children with EA. These children were comparable to the ones lost during follow-up. The results of pulmonary function tests (PFTs) were abnormal in 21 cases (68%). A poor ventilatory response was detected in 14 children (45%) by cardiopulmonary function testing. Ten children who had abnormal results on PFTs were not under any anti-asthmatic treatment. Impaired lung function was noted in children with repaired EA. Indeed, cardiopulmonary function tests results correlated with standard spirometric parameters and revealed minimal clinical symptoms. Moreover, many children with EA had a limited ventilatory reserve (VR). These results indicate that respiratory symptoms are often neglected in children with repaired EA and reinforce the need to provide adequate treatment.

Long-term respiratory outcome of babies born prematurely

Chronic respiratory morbidity is a common adverse outcome of premature birth, particularly in infants who develop bronchopulmonary dysplasia (BPD). Prematurely born infants who had BPD may require supplementary oxygen at home for many months, but few remain oxygen dependent beyond 2 years of age. Readmission to hospital is common, particularly for those who had BPD, but only in the first 2 years after birth. The readmissions are usually for respiratory problems, particularly respiratory syncytial virus lower respiratory infections. Recurrent respiratory symptoms requiring treatment are common, particularly in those who had BPD, even at school age and in adolescence. Affected children have evidence of airways obstruction. Pulmonary function does improve with age, but children with BPD may have ongoing airflow limitation. Computed tomography of the chest gives helpful information at follow up of patients with ongoing respiratory problems who had BPD.

High-Dose Docosahexaenoic Acid Supplementation of Preterm Infants: Respiratory and Allergy Outcomes

Docosahexaenoic acid (DHA) has been associated with downregulation of inflammatory responses. To report the effect of DHA supplementation on long-term atopic and respiratory outcomes in preterm infants. This study is a multicenter, randomized controlled trial comparing the outcomes for preterm infants <33 weeks' gestation who consumed expressed breast milk from mothers taking either tuna oil (high-DHA diet) or soy oil (standard-DHA) capsules. Data collected included incidence of bronchopulmonary dysplasia (BPD) and parental reporting of atopic conditions over the first 18 months of life. Six hundred fifty-seven infants were enrolled (322 to high-DHA diet, 335 to standard), and 93.5% completed the 18-month follow-up. There was a reduction in BPD in boys (relative risk [RR]: 0.67 [95% confidence interval (CI): 0.47-0.96]; P=.03) and in all infants with a birth weight of <1250 g (RR: 0.75 [95% CI: 0.57-0.98]; P=.04). There was no effect on duration of respiratory support, admission length, or home oxygen requirement. There was a reduction in reported hay fever in all infants in the high-DHA group at either 12 or 18 months (RR: 0.41 [95% CI: 0.18-0.91]; P=.03) and at either 12 or 18 months in boys (RR: 0.15 [0.03-0.64]; P=.01). There was no effect on asthma, eczema, or food allergy. DHA supplementation for infants of <33 weeks' gestation reduced the incidence of BPD in boys and in all infants with a birth weight of <1250 g and reduced the incidence of reported hay fever in boys at either 12 or 18 months.

Chronic lung disease of prematurity: long-term respiratory outcome

Chronic respiratory morbidity is a common adverse outcome of preterm birth, especially in infants who develop bronchopulmonary dysplasia (BPD), which is still a major cause of long-term lung dysfunction with a heavy burden on health care services and medical resources throughout childhood. The most severely affected patients remain symptomatic even in adulthood, and this may be influenced also by environmental variables (e.g. smoking), which can contribute to persistent obstruction of airflow. Of all obstructive lung diseases in humans, BPD has the earliest onset and probably lasts the longest. Since the prevention of BPD is an elusive goal, minimizing neonatal lung injury and closely monitoring survivors remain the best courses of action. This review describes the clinical and functional changes characteristic of the long-term pulmonary sequelae of preterm birth, focusing particularly on BPD. © 2014 S. Karger AG, Basel

Syndromic craniosynostosis: complicated airway obstruction calls for progressive strategies in surgical management

Evaluation of: Bannink N, Nout E, Wolvius EB, Hoeve HL, Joosten KF, Mathijssen IM. Obstructive sleep apnea in children with syndromic craniosynostosis: long-term respiratory outcome of midface advancement. Int. J. Oral Maxillofac. Surg. 39(2), 115–121 (2010).Children with syndromic craniosynostosis are at high risk for upper airway obstruction due to midface hypoplasia. Le Fort III osteotomy with midface advancement can expand the naso- and palatopharynx and potentially relieve obstruction. Short-term success has been demonstrated with these surgical techniques; however, little is known regarding the long-term effect of midface advancement on maintaining airway patency. The purpose of this study was to evaluate the long-term effect of midface advancement for treatment of severe obstructive sleep apnea in patients with syndromic craniosynostosis. Results showed that midface advancement had short-term (4 months) success in six of 11 patients with resolution of the need for positive airway pressure, tracheostomy or oxygen (54%); however, long-term success was maintained in only four of these six patients. All failures had concomitant hypopharyngeal obstruction, which cannot be corrected by midface advancement. Endoscopy and 3D CT scan may be useful for predicting which patients will require additional surgical procedures, such as mandibular or genio-hyoid advancement.

Obstructive sleep apnea in children with syndromic craniosynostosis: long-term respiratory outcome of midface advancement

Almost 50% of patients with Apert, Crouzon or Pfeiffer syndrome develop obstructive sleep apnea (OSA), mainly due to midface hypoplasia. Midface advancement is often the treatment of choice, but the few papers on long-term outcome report mixed results. This paper aimed to assess the long-term respiratory outcome of midface advancement in syndromic craniosynostosis with OSA and to determine factors contributing to its efficacy. A retrospective study was performed on 11 patients with moderate or severe OSA, requiring oxygen, continuous positive airway pressure (CPAP), or tracheostomy. Clinical symptoms, results of polysomnography, endoscopy and digital volume measurement of the upper airways on CT scan before and after midface advancement were reviewed. Midface advancement had a good respiratory outcome in the short term in 6 patients and was ineffective in 5. In all patients without respiratory effect or with relapse, endoscopy showed obstruction of the rhino- or hypopharynx. The volume measurements supported the clinical and endoscopic outcome. Despite midface advancement, long-term dependence on, or indication for, CPAP or tracheostomy was maintained in 5 of 11 patients. Pharyngeal collapse appeared to play a role in OSA. Endoscopy before midface advancement is recommended to identify airway obstruction that may interfere with respiratory improvement after midface advancement.

Complications respiratoires des noyades accidentelles chez l’enfant

Accidental drownings are severe and sometimes mortal events in children. Our study aims to better clarify the epidemiology and the respiratory complications of these accidents in our hospital. We led a retrospective study over 10 years concerning the children hospitalized for accidental drowning in our hospital centre. Age at the moment of the accident, sex, history of accident, hospitable care, thoracic imaging and neurological outcome of the children were studied. In total, 83 children were hospitalized (5 years on average, 70% being boys). The drowning especially took place in fresh water (71%), particularly in swimming pools (51.8%). Stages III and IV of drowning concerned 40.9% of the population. The coverage was the following one: admittance in ICU 57.8%, mechanical ventilation 34.9%, oxygen therapy 16.9%, antibiotics 87.9%. A normal chest x-ray was present in 45.7% of the cases. Drowning in fresh water, especially in contaminated fresh water (canal, WC, etc.), induced atelectasis (10.8%), whereas drowning in sea water induced diffuse infiltrates (8.4%). Aspiration pneumonia (33.7%) was present in both cases and a pulmonary oedema (6%) was only noticed during stage IV drowning. The secondary infections were rare (1 case was suspected and another probable). A child presented a secondary acute respiratory distress syndrome (1.2 %). Finally, 7 deaths (8.4%) and 1 case with severe neurological sequelae (1.2%) were noted. Accidental drowning causes important consequences in children. The long-term respiratory outcomes have not been properly studied. Prevention of such accidents is based on parental vigilance during their child's bathe.

Bronchopulmonary dysplasia: Definitions and long-term respiratory outcome

Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease that develops as a consequence of perinatal/neonatal lung injury, and it is one of the most important sequelae of premature birth. In this article we discuss recent changes in the definition of BPD, the main differences between the old and the new form and we summarize recent data on long-term respiratory outcome. The diagnosis of BPD is currently based on the need for supplemental oxygen for at least 28 days after birth, and its severity is graded according to the respiratory support required at 36 postmenstrual weeks. The “new BPD” is mainly a developmental disorder in which the immature lung fails to reach its full structural complexity. Longitudinal studies on children with BPD identified, at all ages, a greater need to use inhaled asthma medication and a significant airflow obstruction. Whether survivors of BPD and prematurity have a risk of developing a COPD-like phenotype with aging is a question that only lung function studies extended to middle-age and beyond will answer.

Long-term functional results after surgical treatment of parapneumonic thoracic empyema

Retrospective evaluation of long-term functional results of surgical treatment of chronic pleural empyema. Two different surgical procedures (debridement vs. decortication) and approaches (VATS vs. thoracotomy) were analyzed. Three end-points were considered: short-term surgical results, short- and long-term radiological results, clinico-functional long-term results. Fifty-one debridement (52% VATS, 48% thoracotomy) and 68 decortication were performed. Postoperative mortality and morbidity were 1.5% and 24%, respectively. Older age (>70 years old) had worse postoperative morbidity (P=0.048). Video-assisted thoracic surgery (VATS) debridement had lower postoperative hospital stay (P=0.006) and shorter duration of chest drainage (P=0.006). The infectious process was resolved in all patients. All patients presented a postoperative radiological improvement, 63 patients (60%) with a complete pulmonary re-expansion. Sixty patients (58%) referred a complete respiratory recovery. VATS debridement had a greater improvement in subjective dyspnea degree (P=0.041). The long-term spirometric evaluation was normal in 58 patients (56%). Age >70 years old resulted the only variable associated to poor long-term results (FEV(1)% < 60% and/or MRC grade > or = 2) at multivariate analysis. Surgical treatment of pleural empyema achieves excellent long-term respiratory outcomes. VATS is associated to less postoperative mortality and shorter postoperative hospital stay. In elderly patients, postoperative morbidity could be higher and long-term functional improvement less warranted.

Automated respiratory support in newborn infants

A considerable proportion of premature infants requires mechanical ventilatory support and supplemental oxygen. Due to their immaturity, exposure to these forms of respiratory support contributes to the development of lung injury, oxidative stress and abnormal retinal development. These conditions are associated with poor long-term respiratory and neurological outcome. Mechanically ventilated preterm infants present with frequent fluctuations in ventilation and gas exchange. Currently available ventilatory modes and manual adjustment to the ventilator or supplemental oxygen cannot effectively adapt to these recurrent fluctuations. Moreover, the respiratory support often exceeds the infant's real needs. Techniques that adapt the mechanical ventilatory support and supplemental oxygen to the changing needs of preterm infants are being developed in order to improve stability of gas exchange, to minimise respiratory support and to reduce personnel workload. This article describes the preliminary evidence on the application of these new techniques in preterm infants and animal models.