Airway dimensions in bronchopulmonary dysplasia: implications for airflow obstruction

The cause of lung function abnormalities in bronchopulmonary dysplasia (BPD) is incompletely understood, even in the "new era" of this disease. Altered airway wall dimensions are important in the pathogenesis of airflow obstruction in diseases such as asthma and chronic obstructive pulmonary disease. Whether airway wall dimensions contribute to lung function abnormalities in BPD is unknown. The purpose of this study was to investigate airway wall dimensions in relation to airway size in BPD. Lung tissue of patients with BPD was obtained at autopsy, and lung tissue from children who died from sudden infant death syndrome (SIDS) served as control. Airway wall dimensions and epithelial loss were measured in 75 airways from 5 BPD patients and 176 airways from 11 SIDS patients. Repeated measures analysis of variance was used to assess the relationships between airway wall dimensions and airway size for BPD and SIDS patients. Little epithelial loss was present in the BPD patients while extensive loss was observed in some of the SIDS patients. The inner wall area, outer wall area, epithelium area and smooth muscle area were all substantially larger (all P < 0.001) in BPD than in SIDS patients. It is likely that the increased thickness of the airway wall components contributes to airflow obstruction in BPD patients.     

Diffusing capacity of the lung in school-aged children born very preterm,with and without bronchopulmonary dysplasia

The aim of this study was to determine the extent to which bronchopulmonary dysplasia (BPD) affects the diffusing properties of lung tissue in childhood. Pulmonary function in 31 prematurely born children (BW. < 1250 g) was examined at ages 7–11 years. Twenty out of 31 prematurely born children met the criteria for BPD. The remaining 11 children had milder forms of neonatal lung disease. Twenty healthy children of the same age and born at term served as a control group. The diffusing capacity of the lung for carbon monoxide (D_LCO) was measured by the single breath method. Lung volumes were determined in a body plethysmograph and expiratory flow rates with a flow/volume spirometer. D_LCO values of children with histories of BPD did not differ significantly from those of the prematurely born children without BPD. However, D_LCO values in both prematurely born study groups were significantly lower than those in controls born at term. Thoracic gas volumes measured with a body plethysmograph were similar in all groups. Spirometry demonstrated reduced flow rates in both BPD and non-BPD prematurely born children. The results suggest that some structural changes in lung tissues and airways persist for years in children who are born very preterm regardless of whether they develop BPD or not. Pediatr Pulmonol. 1996; 21:353–360. © 1996 Wiley-Liss, Inc.     

Frontiers in pulmonary hypertension in infants and children with bronchopulmonary dysplasia

Pulmonary hypertension (PH) is an increasingly recognized complication of premature birth and bronchopulmonary dysplasia (BPD), and is associated with increased morbidity and mortality. Extreme phenotypic variability exists among preterm infants of similar gestational ages, making it difficult to predict which infants are at increased risk for developing PH. Intrauterine growth retardation or drug exposures, postnatal therapy with prolonged positive pressure ventilation, cardiovascular shunts, poor postnatal lung and somatic growth, and genetic or epigenetic factors may all contribute to the development of PH in preterm infants with BPD. In addition to the variability of severity of PH, there is also qualitative variability seen in PH, such as the variable responses to vasoactive medications. To reduce the morbidity and mortality associated with PH, a multi‐pronged approach is needed. First, improved screening for and increased recognition of PH may allow for earlier treatment and better clinical outcomes. Second, identification of both prenatal and postnatal risk factors for the development of PH may allow targeting of therapy and resources for those at highest risk. Third, understanding the pathophysiology of the preterm pulmonary vascular bed may help improve outcomes through recognizing pathways that are dysregulated in PH, identifying novel biomarkers, and testing novel treatments. Finally, the recognition of conditions and exposures that may exacerbate or lead to recurrent PH is needed to help with developing treatment guidelines and preventative strategies that can be used to reduce the burden of disease. Pediatr Pulmonol. 2012. 47:1042–1053. © 2012 Wiley Periodicals, Inc.     

Bronchodilators and diuretics in children with bronchopulmonary dysplasia

Pulmonary function tests (PFT) were obtained during the course of a self-controlled study of six children aged 5 to 43 months who had moderate to severe bronchopulmonary dysplasia (BPD). Changes after the administration of intravenous (IV) furosemide (2 mg/kg), inhaled isoproterenol (0.2 cc, 1:200), inhaled atropine sulfate (0.05 mg/kg), and a placebo were assessed. The study indicated the furosemide and atropine significantly (P less than 0.05) increased dynamic compliance (CL) for the group. A decrease in total pulmonary resistance (RL) and work of breathing (W) was observed after isoproterenol, although the responses were not significant (P = 0.08 and P = 0.09, respectively). It was speculated that pulmonary edema and increased vagal tone may contribute to small airway dysfunction in children who have BPD.     

Cystic fibrosis in three children with bronchopulmonary dysplasia

Cystic fibrosis (CF) and bronchopulmonary dysplasia (BPD) are two common causes of chronic lung disease in children. Patients with BPD or CF often have recurrent respiratory symptoms, failure to thrive, and/or metabolic alkalosis during infancy and childhood. Thus, recognizing the diagnosis of CF in an infant with BPD can be difficult. We present three infants with both BPD and CF. The infants shared a history of respiratory distress and prolonged oxygen requirements. All three also had difficulty gaining weight, even after pancreatic enzyme supplementation was instituted. Metabolic alkalosis was observed in two infants. Previous studies in children with CF suggest that early diagnosis may impact both lung health and nutritional status. A high index of suspicion is necessary for clinicians to identify these children early and intervene with appropriate therapy.     

Bronchial responsiveness to methacholine and adenosine 5'-monophosphate in preschool children with bronchopulmonary dysplasia

Bronchial hyperresponsiveness (BHR) is a characteristic feature of asthma, but it is also frequently present in children and adults with chronic obstructive lung diseases. Bronchopulmonary dysplasia (BPD) is a chronic lung disease, most commonly developing after mechanical ventilation and oxygen therapy in premature infants. BHR is usually measured by bronchial challenges, using direct or indirect stimuli. The aim of this study was to evaluate BHR to direct and indirect stimuli in young children with BPD. Methacholine and adenosine 5'-monophosphate (AMP) bronchial challenges were performed on preschool children with BPD (n = 19), using a modified auscultation method. The endpoint was defined as the appearance of wheezing and/or oxygen desaturation. The results obtained were then compared with those of asthmatic (n = 25) and control (n = 23) preschool children. A positive response to methacholine (endpoint concentration, < or = 8 mg/ml) was observed in 89.5% (17/19) of patients with BPD, but a positive response to AMP (endpoint concentration, < or = 200 mg/ml) was observed only in 21.1% (4/19). All patients with asthma responded positively to methacholine, and most (23/25, 92.0%) of them also responded positively to AMP. The majority of controls were unresponsive to both challenges. BHR to methacholine is a frequent finding in preschool-age survivors of BPD, but is usually not accompanied by BHR to AMP. This suggests that most patients with BPD do not have the inflammatory airway response which is characteristic of asthmatic patients.     

支气管肺发育不良患儿气管抽吸物单核细胞检测的临床意义研究

目的观察支气管肺发育不良(BPD)患儿气管抽吸物中单核细胞亚型的变化,借此探讨其与BPD的相关性。方法选取我院2018年1月至2019年6月需要机械通气治疗的呼吸窘迫综合征(RDS)早产儿62例,其中BPD组(氧依赖超过28天)24例,对照组38组。流式细胞仪检测患儿气管抽吸物中单核细胞亚型M1和M2所占的比例,ELISA法检测TNF-α、IL-1和IL-10表达。结果两组早产儿气管抽吸物中单核细胞比例差异无显著性(P>0.05),BPD组M1占7.65±1.28%,显著高于对照组的3.57±0.54%(P<0.01),BPD组M2占3.38±0.44%,显著低于对照组的7.35±1.32%(P<0.01)。BPD组早产儿气管抽吸物中TNF-α和IL-1表达显著高于对照组(P<0.01),BPD组IL-10表达显著高于对照组(P<0.01)。结论BPD患者单核细胞M1亚型比例显著升高,M2亚型比例显著减低。     

Rethinking furosemide use for infants with bronchopulmonary dysplasia

Diuretics are commonly administered to infants with bronchopulmonary dysplasia (BPD) to improve respiratory function despite the absence of prospective data demonstrating long term benefits. While many potentially adverse effects of furosemide are known to clinicians, its direct and indirect impact on multiple pathophysiological processes need to be understood. While furosemide likely has a role in the management of infants with BPD, clinicians are encouraged to recognize these potential complications associated with furosemide administration. Specifically, a deeper understanding of the impact of diuretics on sodium metabolism neurohumoral regulation of cardiopulmonary physiology is required.