Recognizing genetic disease: A key aspect of pediatric pulmonary care

Advancement in technology has improved recognition of genetic etiologies of disease, which has impacted diagnosis and management of rare disease patients in the pediatric pulmonary clinic. This review provides an overview of genetic conditions that are likely to present with pulmonary features and require extensive care by the pediatric pulmonologist. Increased familiarity with these conditions allows for improved care of these patients by reducing time to diagnosis, tailoring management, and prompting further investigation into these disorders.     

肺表面活性物质联合鼻塞式气道正压通气治疗新生儿呼吸窘迫综合征效果分析

目的：探讨肺表面活性物质（PS）联合鼻塞式气道正压通气（NCPAP）治疗新生儿呼吸窘迫综合征（NRDS）的临床效果。方法将72例NRDS患儿随机分为两组,各36例。两组均给予常规对症治疗,观察组在此基础上给予PS＋NCPAP治疗,对照组在此基础上给予PS＋机械通气（ MV）治疗,比较两组治疗效果、并发症发生率、氧疗时间及住院时间。结果观察组治疗总有效率为94．44％,高于对照组的77．78％（ P ＜0．05）;观察组并发症发生率为13．89％（5/36）,对照组并发症发生率为36．11％（13/36）,观察组并发症发生率低于对照组（ P ＜0．05）;观察组氧疗时间和住院时间均短于对照组（ P ＜0．01）。结论 PS联合NCPAP治疗NRDS能有效减少氧疗时间、降低并发症发生率及缩短住院时间。     

布地奈德合剂防治RDS早期疗效研究

目的探讨气管内滴入不同布地奈德合剂联合经鼻持续气道正压(NCPAP)对呼吸窘迫综合征(RDS)的早期疗效差异。方法按纳入标准随机将RDS高危早产儿91例(预防RDS28例,诊断RDS治疗63例)分为观察组(气管内滴入沐舒坦-布地奈德混合剂)和对照组(气管内滴入固尔苏-布地奈德混合剂),均予NCPAP通气,比较预防病例RDS发生率和RDS治疗病例PaO2/FiO2改善情况。结果两组均无RDS新发病例;两组RDS病例治疗前及治疗后6、12 h PaO2/FiO2无差异(P0.05),治疗后1小时观察组比对照组低(P0.01)。结论两种布地奈德混合剂及早气管内滴入均能有效预防RDS、改善RDS肺功能,但观察组显效慢。     

肺表面活性物质预防早产儿呼吸窘迫综合症的临床观察

目的对肺表面活性物质固尔苏应用于早产儿呼吸窘迫综合症的早期预防效果进行观察及分析。方法选取早产儿病例120例,根据患儿家长意愿分组为固尔苏组62例和对照组58例。在常规进行心电监测、入恒温箱、抗感染等治疗基础上,对照组不应用固尔苏,固尔苏组给予固尔苏用药治疗。结果固尔苏组患儿的平均通气时间、氧疗时间和住院时间明显短于对照组(P0.01);固尔苏组患儿呼吸机相关性肺炎、肺气漏和视网膜病变发病率明显低于对照组(P0.05);固尔苏组患儿治愈率明显高于对照组,致死率和NRDS发生率明显低于对照组(P0.01)。结论肺表面活性物质预防早产儿呼吸窘迫综合症具有较好的疗效,可快速改善患儿肺功能、提高肺顺应性,并且降低并发症的发生以及致死率。     

Nonionic surfactant attenuates acute lung injury by restoring epithelial integrity and alveolar fluid clearance

Introduction: Acute lung injury (ALI) has a great impact and a high mortality rate in intensive care units (ICUs). Excessive air may enter the lungs, causing pulmonary air embolism (AE)-induced ALI. Some invasive iatrogenic procedures cause pulmonary AE-induced ALI, with the presentation of severe inflammatory reactions, hypoxia, and pulmonary hypertension. Pulmonary surfactants are vital in the lungs to reduce the surface tension and inflammation. Nonionic surfactants (NIS) are a kind of surfactants without electric charge on their hydrophilic parts. Studies on NIS in AE-induced ALI are limited. We aimed to study the protective effects and mechanisms of NIS in AE-induced ALI.Materials and methods: Five different groups (n = 6 in each group) were created: sham, AE, AE + NIS pretreatment (0.5 mg/kg), AE + NIS pretreatment (1 mg/kg), and AE + post-AE NIS (1 mg/kg). AE-induced ALI was introduced by the infusion of air via the pulmonary artery. Aerosolized NIS were administered via tracheostomy.Results: Pulmonary AE-induced ALI showed destruction of the alveolar cell integrity with increased pulmonary microvascular permeability, pulmonary vascular resistance, pulmonary edema, and lung inflammation. The activation of nuclear factor-κB (NF-κB) increased the expression of pro-inflammatory cytokines, and sodium-potassium-chloride co-transporter isoform 1 (NKCC1). The pretreatment with NIS (1 mg/kg) prominently maintained the integrity of the epithelial lining and suppressed the expression of NF-κB, pro-inflammatory cytokines, and NKCC1, subsequently reducing AE-induced ALI.Conclusions: NIS maintained the integrity of the epithelial lining and suppressed the expression of NF-κB, pro-inflammatory cytokines, and NKCC1, thereby reducing hyperpermeability, pulmonary edema, and inflammation in ALI.     

Surfactant Production by Neoplastic Type II Pneumocytes

A bronchioloalveolar carcinoma of type II pneumo-cyte differentiation with abundant intraluminal secretion, histochemically and histologically mimicking alveolar proteinosis, is described. The tumor was of the diffuse type, involving almost the entire lower lobe of the left lung. The luminal aspect of the cells showed evidence of apocrine secretion. Ultrastructurally, the cells were characterized by the presence of cytoplasmic lamellar bodies. There were occasional cells with intranuclear tubules, and numerous rounded fragments of cytoplasm were present in the lumen as evidence of the apocrine activity. The intraalveolar secretion was composed of lamellar bodies in various stages of dissolution, tubular myelinlike networks characteristic of surfactant, and amorphous, granular material. This is the first reported instance of morphologic demonstration of surfactant secretion by a bronchioloalveolar carcinoma.     

Alveolar macrophages and emphysema in surfactant protein-D-deficient mice

Abstract:   Surfactant protein-D (SP-D) is a member of the collectin family of collagenous proteins with lectin activity. SP-D is expressed in numerous tissues, primarily in type II alveolar cells in the periphery of the lung. SP-D plays an important role in host defense of the lung. To evaluate the importance of SP-D in vivo , transgenic mice lacking SP-D (SP-D-/- mice) have been generated. Lipid accumulation and airspace enlargement were observed in the lungs of SP-D-/- mice within 3 weeks after birth, and progressed with advancing age. Airspace enlargement and abnormalities in elastin fibers supported the concept that SP-D was required to inhibit destruction of the alveoli. Alveolar macrophages from SP-D-/- mice produced more H₂O₂ and matrix metalloproteinases (MMP)-2, -9, and -12 compared with wild-type mice. In vitro studies demonstrated that oxidants derived in part from NADPH oxidase enhanced NF-κB activation and MMP production in alveolar macrophages from SP-D-/- mice. A specific inhibitor of NF-κB reduced MMP production by alveolar macrophages from SP-D-/- mice. Taken together, these data demonstrated oxidant-dependent activation of NF-κB and enhanced MMP expression by alveolar macrophages from SP-D-/- mice, a process likely to mediate airspace remodeling caused by SP-D deficiency. SP-D plays a critical role in regulating alveolar macrophage activation, oxidant production, and MMP activity that may influence the pathogenesis of various pulmonary disorders.     

The Effect of Reflux and Bile Acid Aspiration on the Lung Allograft and Its Surfactant and Innate Immunity Molecules SP-A and SP-D

Gastro-esophageal reflux and related pulmonary bile acid aspiration were prospectively investigated as possible contributors to postlung transplant bronchiolitis obliterans syndrome (BOS). We also studied the impact of aspiration on pulmonary surfactant collectin proteins SP-A and SP-D and on surfactant phospholipids--all important components of innate immunity in the lung. Proximal and distal esophageal 24-h pH testing and broncho-alveolar lavage fluid (BALF) bile acid assays were performed prospectively at 3-month posttransplant in 50 patients. BALF was also assayed for SP-A, SP-D and phospholipids expressed as ratio to total lipids: phosphatidylcholine; dipalmitoylphosphatidylcholine; phosphatidylglycerol (PG); phosphatidylinositol; sphingomyelin (SM) and lysophosphatidylcholine. Actuarial freedom from BOS was assessed. Freedom from BOS was reduced in patients with abnormal (proximal and/or distal) esophageal pH findings or BALF bile acids (Log-rank Mantel-Cox p < 0.05). Abnormal pH findings were observed in 72% (8 of 11) of patients with bile acids detected within the BALF. BALF with high levels of bile acids also had significantly lower SP-A, SP-D, dipalmitoylphosphatidylcholine; PG and higher SM levels (Mann-Whitney, p < 0.05). Duodeno-gastro-esophageal reflux and consequent aspiration is a risk factor for the development of BOS postlung transplant. Bile acid aspiration is associated with impaired lung allograft innate immunity manifest by reduced surfactant collectins and altered phospholipids.     

Electrochemical polymerization of 3,4-ethylenedioxythiophene in aqueous micellar solution containing biocompatible amino acid-based surfactant

Poly(3,4-ethylenedioxythiophene) (PEDOT) films were synthesized electrochemically by direct anodic oxidation of 3,4-ethylenedioxythiophene (EDOT) in aqueous solution containing the environmentally–friendly amino acid-based surfactant sodium N-lauroylsarcosinate (SLS), which as a mild biosurfactant has good biocompatibility, low toxicity, good solubilization, and efficient and quick biodegradability. The moderate interactions between a neutral SLS–aqueous micellar solution and EDOT monomer led to the decreased onset oxidation potential of EDOT. PEDOT films were characterized spectroscopically using Fourier transform infrared and ultraviolet–visible techniques. PEDOT films with good thermal stability and electrical conductivity of 5 S cm⁻¹ were synthesized in neutral SLS–water micellar solutions.