Pulmonary surfactant (PS) is synthesized and secreted by alveolar epithelial type II (AEII) cells, which is a complex compound formed by proteins and lipids. Surfactant participates in a range of physiological processes such as reducing the surface tension, keeping the balance of alveolar fluid, maintaining normal alveolar morphology and conducting host defense. Genetic disorders of the surfactant homeostasis genes may result in lack of surfactant or cytotoxicity, and lead to multiple lung diseases in neonates, children and adults, including neonatal respiratory distress syndrome, interstitial pneumonia, pulmonary alveolar proteinosis, and pulmonary fibrosis. This paper has provided a review for the functions and processes of pulmonary surfactant metabolism, as well as the connection between disorders of surfactant homeostasis genes and lung diseases.
ATP-Binding Cassette Transporters ; genetics ; DNA-Binding Proteins ; genetics ; Homeostasis ; Humans ; Lung Diseases ; genetics ; Pulmonary Surfactant-Associated Protein C ; genetics ; Pulmonary Surfactants ; metabolism ; Transcription Factors

To treat respiratory distress syndrome, surfactant is currently delivered via less invasive surfactant administration (LISA) or INtubation SURfactant Extubation (INSURE). The aim of this study was to compare the effect of the two delivery methods of surfactant on cerebral autoregulation. Near infrared spectroscopy monitoring was carried out to detect cerebral oxygen saturation (ScO), and the mean arterial blood pressure (MABP) was simultaneously recorded. Of 44 preterm infants included, the surfactant was administrated to 22 via LISA and 22 via INSURE. The clinical characteristics, treatments and outcomes of the infants showed no significant differences between the two groups. The correlation coefficient of ScOand MABP (r) 5 min before administration was similar in the two groups. During surfactant administration, rincreased in both groups (0.44±0.10 to 0.54±0.12 in LISA, 0.45±0.11 to 0.69±0.09 in INSURE). In the first and second 5 min after instillation, rwas not significantly different from baseline in the LISA group, but increased in the first 5 min after instillation (0.59±0.13, P=0.000 compared with the baseline in the same group) and recovered in the second 5 min after instillation (0.48±0.10, P=0.321) in the INSURE group. There were significant differences in the change rates of rbetween the two groups during and after surfactant administration. Our results suggest that cerebral autoregulation may be affected transiently by surfactant administration. The effect duration of LISA is shorter than that of INSURE (<5 min in LISA vs. 5-10 min in INSURE).
Administration, Intranasal ; adverse effects ; Brain ; metabolism ; Female ; Homeostasis ; Humans ; Infant, Newborn ; Infant, Premature ; Intubation ; adverse effects ; Male ; Oxygen Consumption ; Pulmonary Surfactants ; administration & dosage ; therapeutic use ; Respiratory Distress Syndrome, Newborn ; drug therapy ; therapy

OBJECTIVETo investigate the relationship between the recovery levels of pulmonary surfactants (PS) and lung compliance after whole-lung lavage.

METHODSPatients with pneumoconiosis in different stages (healthy subjects, stage I, and stage II, n = 10 for each group) were selected. The recovery levels of PS and lung compliance at different time points after whole-lung lavage were determined, and their relationship was analyzed.

RESULTSBefore whole-lung lavage and at 0, 10, 30, 60, 90, and 120 min after the operation, the lung compliance levels were 39.5±6.7, 28.3±5.6, 31.5±5.2, 37.6±4.4, 38.0±5.3, 38.7±5.5, and 39.2±5.3 ml/cm H2O for healthy subjects, 38.8±5.1, 25.1±6.1, 28.4±6.8, 30.5±5.9, 36.3±5.5, 37.3±5.4, 38.2±4.5, and 38.8±5.1 ml/cm H2O for patients with stage I pneumoconiosis, and 32.9±6.1, 20.3±6.0, 24.3±5.4, 25.1±5.4, 26.8±5.8, 27.8±4.8, and 32.8±4.5 ml/cm H2O were for patients with stage II pneumoconiosis. It was observed that in patients with pneumoconiosis, the lung compliance levels showed a declining trend along with the increasing stage, reaching the lowest level in stage II patients; comparison between groups indicated a significant difference (P < 0.05). For healthy subjects, 30 min was needed for restoring lung compliance to its preoperative level, while 60 and 120 min were needed for stage I and stage II patients, respectively. Compared with that at 0 min after operation, PS levels were elevated significantly at 10 min after operation in all patients (P < 0.05), whereas for stage I and stage II patients, the PS levels at 30 min after operation were significantly higher than that at 10 min (F = 4.27, P < 0.05; F = 20.40, P < 0.05). For all patients, the PS levels at 60 min after operation were significantly higher than those at 10 and 30 min (P < 0.05). After whole-lung lavage, the PS levels in all patients were restored to a large extent within 10∼30 min, but the recovery of lung compliance needed 30∼ 90 min.

CONCLUSIONAfter whole-lung lavage, the lung compliance declines obviously, but recovers gradually afterwards; the higher stage suggests a longer recovery. The recovery of lung compliance needs a longer time than that of PS.

Adult ; Bronchoalveolar Lavage ; Humans ; Lung Compliance ; Male ; Middle Aged ; Pneumoconiosis ; metabolism ; physiopathology ; therapy ; Pulmonary Surfactants

INTRODUCTIONRetinopathy of prematurity (ROP) can lead to severe visual impairment. This study was conducted to determine the levels of biochemical mediators (i. e. vascular endothelial growth f actor [ VEGF] and insulin- like growth factor-1 [IGF-1]) in the blood of premature infants with proliferative ROP.

METHODSBlood samples from 71 preterm infants born at or before 32 weeks of gestation were obtained 6-8 weeks after birth. These infants were classified into two groups according to their eye examination results. The control group consisted of 41 infants who had no evidence of ROP, and the study group consisted of 30 infants with proliferative ROP at stage III or higher. Blood VEGF and IGF-1 levels were measured using enzyme-linked immunosorbent assay.

RESULTSThe mean gestational ages of the infants at birth were 28.4 ± 1.6 and 28.8 ± 1.6 weeks in the study and control groups, respectively (p = 0.259). The mean postmenstrual age of the infants at the time of blood sampling was 34.9 ± 1.2 weeks in the study group and 34.6 ± 1.3 weeks in the control group (p = 0.339). The mean blood IGF-1 (18.48 ± 11.79 µg/L and 16.75 ± 13.74 µg/L in the study and control groups, respectively; p = 0.580) and VEGF (267.35 ± 103.43 pg/mL and 237.52 ± 130.92 pg/mL in the study and control groups, respectively; p = 0.305) levels of the infants were not significantly different between the two groups.

CONCLUSIONAt 6-8 weeks after birth, blood IGF-1 and VEGF levels were not found to be significantly different between premature infants with proliferative ROP and those without.

Case-Control Studies ; Enzyme-Linked Immunosorbent Assay ; Female ; Gestational Age ; Humans ; Infant, Newborn ; Infant, Premature ; Insulin-Like Growth Factor I ; metabolism ; Intensive Care, Neonatal ; Male ; Pulmonary Surfactants ; therapeutic use ; Retinopathy of Prematurity ; blood ; Vascular Endothelial Growth Factor A ; blood

OBJECTIVETo study the changes to surfactant proteins in the serum and bronchoalveolar lavage fluids (BALF) of children with Mycoplasma pneumoniae pneumonia (MPP) and their significance.

METHODSSelf-control method was used in the study. Forty-seven MPP children were divided into single lung infected (n=32) and bilateral lung infected groups (n=15) according to lung CT results. Surfactant proteins SP-A, B, C and D were measured using ELISA in the serum and BALF in the two groups. The correlations between SP-A, B, C and D content in the serum and BALF were evaluated by Spearman correlation analysis.

RESULTSSP-A, B, C and D content in BALF from the majorly infected or infected lung were significantly higher than from the opposite lung and serum (P<0.01). SP-A, B and C content in serum was significantly lower than in BALF from the non-infected lung in the single-side infected lung group (P<0.01 or 0.05), but there was no significant difference between serum SP-D content and BALF SP-D content from the non-infected lung. There were no significant differences in SP-A, B, C and D content in serum and BALF from the minorly infected lung in the bilateral lung infected group. Serum SP-D content was positively correlated with BALF SP-D content from the majorly infected lung in the bilateral lung infected group (P<0.01).

CONCLUSIONSSerum SP-D content may serve as a biomarker for evaluating the severity of pulmonary infection in children with community-acquired pneumonia.

Bronchoalveolar Lavage Fluid ; chemistry ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Pneumonia, Mycoplasma ; metabolism ; Pulmonary Surfactants ; analysis ; blood

OBJECTIVETo investigate the effect of L-Arginine (L-Arg) on pulmonary surfactant (PS) expression and alveolar macrophage (AM) in rats with pulmonary injury induced by lipopolysaccharide (LPS).

METHODSModel of acute lung injury (ALI) was made by injection (iv) with LPS 5 mg/kg in rats. Fourty-eight male SD rats were randomly divided into 3 groups(n = 16): control, model (LPS) and L-Arg groups. L-Arg (500 mg/kg ip ,L-Arg group) or saline (control and LPS group) was administrated at 3 h or 6 h after LPS injection respectively for 3 h. The expression of surfactant protein A (SP-A) mRNA in the lung tissue was detected by ISH. The total protein (TP) in the bronchoalveolar lavage fluid (BALF) was detected. Rat AM were isolated from the bronchial alveolar lavage fluid of SD rats and harvested by selective plating technique. LPS and L-Arg were added to the culture medium. The concentration of nitric oxide (NO),the activity of lactate dehydrogenase (LDH), the contents of tumor necrosis factor alpha (TNF-alpha) and interleukin- 6 (IL-6) in the culture supernatants were respectively measured.

RESULTSCompared with the control group, the expression of SP-A mRNA was significantly decreased, the TP concentration was significantly increased in LPS group. Compared with LPS group at the same time points, treatment with L-Arg at 3 h after LPS, the expression of SP-A mRNA in lung tissue was increased markedly, whereas TP concentration was decreased significantly. In cultured rat AM, LDH activity, NO, TNF-alpha and IL-6 contents in culture medium were significantly increased in LPS group to compared with those of control group. LDH activity, TNF-alpha and IL-6 contents were decreased in L-Arg group compared with those of LPS group.

CONCLUSIONL-Arg can protect the lung against LPS-induced pulmonary injury by up-regulating the expression of PS and inhibiting inflammatory transmitters from AM.

Acute Lung Injury ; chemically induced ; drug therapy ; metabolism ; Animals ; Arginine ; pharmacology ; therapeutic use ; Lipopolysaccharides ; adverse effects ; Macrophages, Alveolar ; metabolism ; Male ; Pulmonary Surfactants ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo observe the changes of pulmonary surfactant (PS) in rats with acute lung injury(ALI) induced by lipopolysaccharide (LPS) and to explore the effects of hydrogen sulfide (H2S) on PS.

METHODSFourty- eight male rats were randomly divided into six groups (n = 8). They were control group, LPS group, LPS+ NaHS low, middle, high dose groups and LPS+ PPG group. Saline was administrated in Control group. LPS was administrated in LPS group. In LPS + NaHS low, middle, high dose groups or LPS + PPG group, sodium hydrosulfide (NaHS) of different doses or DL-propargylglycine (PPG) were respectively administrated when the rats were administrated of LPS after 3 hours. All the rats were killed at 6 hours after administration of Saline or LPS. The morphological changes of alveolar epithelial type II cells (AEC-II) were respectively observed by transmission electron microscopes. The content of H2S in plasma and activity of cystathionine-gamma-lyase (CSE) in lung tissues were respectively detected. The contents of total protein (TP) and total phospholipids (TPL) in bronchoalveolar lavage fluid (BLAF) were respectively measured. The pulmonary surfactant protein A (SP-A), surfactant protein B (SP-B) and surfactant protein-C (SP-C) mRNA expressions in lung tissues were analysed.

RESULTS(1) Compared with control group, the content of H2S in plasma, activity of CSE, content of TPL, and SP-A, SP-B and SP-C mRNA expressions were respectively decreased in LPS group (P < 0.05 or P < 0.01). But the content of TP was increased in LPS group (P < 0.01); (2) Compared with LPS group, the content of H2S, activity of CSE and SP-A mRNA expression were significantly increased in LPS + NaHS low, middle and high dose groups (P < 0.05). The SP-B mRNA expression and content of TPL were significantly increased in LPS + NaHS Middle and High dose groups (P < 0.05). The content of TP was decreased in LPS + NaHS High dose group (P < 0.05). The SP-C mRNA expression was not altered in LPS+ NaHS low, middle and high dose groups (P > 0.05); (3) Compared with LPS group, the content of H2S, activity of CSE, content of TPL, and SP-A, SP-B and SP-C mRNA expressions were respectively decreased, but content of TP was increased in LPS + PPG group (P < 0.05).

CONCUSIONThe decrease of PS is the important physiopathologic process of ALI induced by LPS. Exogenously applied H2S could attenuate the process of ALI that possibly because H2S could adjust the compose and secretion of PS.

Acute Lung Injury ; chemically induced ; metabolism ; Animals ; Hydrogen Sulfide ; metabolism ; pharmacology ; Lipopolysaccharides ; Male ; Pulmonary Surfactants ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effects of methylprednisolone pretreatment on pulmonary lung permeability index and the content of the pulmonary surfactant dipalmitoylphosphatidylcholine (DPPC) in a rabbit model of reexpansion pulmonary edema.

METHODSTwenty-one male New Zealand white rabbits were randomly divided into control group, reexpansion, and reexpansion+methylprednisolone pretreatment groups. The rabbit model of reexpansion pulmonary edema was established using Sakaos method. A bolus dosage of methylprednisolone (3 mg/kg) in reexpansion+methylprednisolone group group or 2.0 ml/kg normal saline in the other two groups was administered intravenously 20 min before reexpansion pulmonary edema. Bronchoalveolar lavage fluid (BALF) and arterial blood samples were collected for measurement of the total protein (TP) and DPPC contents 4 h after reexpansion, and the pulmonary permeability index was calculated.

RESULTSThe pulmonary permeability index in methylprednisolone pretreatment group was significantly lower than that in the reexpansion group (0.007∓0.002 vs 0.177∓0.004, P<0.05). Methylprednisolone pretreatment significantly increased DPPC concentration in the BALF as compared with saline treatment in the reexpansion group (61.815∓28.307 vs 101.955∓24.544 µg/ml, P<0.05).

CONCLUSIONMethylprednisolone pretreatment can increase pulmonary surfactant content and improve pulmonary permeability in the rabbit model of reexpansion pulmonary edema.

1,2-Dipalmitoylphosphatidylcholine ; analysis ; Animals ; Bronchoalveolar Lavage Fluid ; Capillary Permeability ; drug effects ; Male ; Methylprednisolone ; pharmacology ; Permeability ; Pulmonary Edema ; metabolism ; physiopathology ; Pulmonary Surfactants ; metabolism ; Rabbits

OBJECTIVETo review the pathophysiology, evaluation, management, and outcomes of children with inherited disorders of surfactant metabolism due to mutations in the genes encoding surfactant proteins-B or -C (SFTPB, SFTPC), ATP binding cassette member A3 (ABCA3), and thyroid transcription factor (NKX2.1).

DATA SOURCESReview of the literature, previous work from the author's and collaborators' laboratories, St. Louis Children's Hospital Lung Transplant Database.

STUDY SELECTIONKey articles in the field, author's work.

RESULTSInherited disorders of surfactant metabolism present as acute, severe respiratory dysfunction in the neonatal period (SFTPB, ABCA3, NKX2.1) or as chronic respiratory insufficiency in later infancy and childhood which is of variable onset, severity, and course (SFTPC, ABCA3, NKX2.1). Diagnosis is established with sequencing the relevant genes; lung biopsy with electron microscopy is a useful adjunct. For surfactant protein-B and ABCA3 deficiency presenting with acute neonatal disease, treatment options are limited to lung transplantation or compassionate care. For the more chronic presentations of surfactant protein-C, ABCA3, and NKX2.1 associated disease, the natural history is variable and therefore individualized, supportive care is appropriate,

CONCLUSIONSInherited disorders of surfactant metabolism are rare, but informative diseases that provide unique opportunities for understanding mechanisms of respiratory disease in newborns and children.

ATP-Binding Cassette Transporters ; genetics ; Humans ; Infant, Newborn ; Lung Diseases ; diagnosis ; etiology ; therapy ; Lung Transplantation ; Mutation ; Pulmonary Surfactant-Associated Protein B ; deficiency ; genetics ; Pulmonary Surfactant-Associated Protein C ; genetics ; Pulmonary Surfactants ; metabolism

Adaptation, Physiological ; Animals ; Biological Transport ; Epithelial Sodium Channels ; physiology ; Extravascular Lung Water ; metabolism ; Fetus ; metabolism ; Humans ; Infant, Newborn ; Lung ; metabolism ; Pulmonary Surfactants ; metabolism