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Association between the surfactant protein A (SP-A) gene locus and respiratory-distress syndrome in the Finnish population.

ABSTRACT: Respiratory-distress syndrome (RDS) in the newborn is a major cause of neonatal mortality and morbidity. Although prematurity is the most-important risk factor for RDS, the syndrome does not develop in many premature infants. The main cause of RDS is a deficiency of pulmonary surfactant, which consists of phospholipids and specific proteins. The genes underlying susceptibility to RDS are insufficiently known. The candidate-gene approach was used to study the association between the surfactant protein A (SP-A) gene locus and RDS in the genetically homogeneous Finnish population. In the present study, 88 infants with RDS and 88 control infants that were matched for degree of prematurity, prenatal glucocorticoid therapy, and sex were analyzed for SP-A genotypes. We show that certain SP-A1 alleles (6A2 and 6A3) and an SP-A1/SP-A2 haplotype (6A2/1A0) were associated with RDS. The 6A2 allele was overrepresented and the 6A3 allele was underrepresented in infants with RDS. These associations were particularly strong among small premature infants born at gestational age <32 wk. In infants protected from RDS (those that had no RDS, despite extreme prematurity and lack of glucocorticoid therapy), compared with infants that had RDS develop despite having received glucocorticoid therapy, the frequencies of 6A2 (.22 vs.71), 6A3 (.72 vs.17), 6A2/1A0 (.17 vs.68), 6A3/1A1 (.39 vs.10), and 6A3/1A2 (.28 vs.06) in the two groups, respectively, were strikingly different. According to the results of conditional logistic-regression analysis, diseases associated with premature birth did not explain the association between the odds of a particular homozygous SP-A1 genotype (6A2/6A2 and 6A3/6A3) and RDS. In the population evaluated in the present study, SP-B intron 4 variant frequencies were low and had no detectable association with RDS. We conclude that the SP-A gene locus is an important determinant for predisposition to RDS in premature infants.

SUBMITTER: Ramet M

PROVIDER: S-EPMC1378016 | biostudies-other | 2000 May

REPOSITORIES: biostudies-other

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Association between the surfactant protein A (SP-A) gene locus and respiratory-distress syndrome in the Finnish population.

Rämet M M Haataja R R Marttila R R Floros J J Hallman M M

American journal of human genetics 20000404 5

Respiratory-distress syndrome (RDS) in the newborn is a major cause of neonatal mortality and morbidity. Although prematurity is the most-important risk factor for RDS, the syndrome does not develop in many premature infants. The main cause of RDS is a deficiency of pulmonary surfactant, which consists of phospholipids and specific proteins. The genes underlying susceptibility to RDS are insufficiently known. The candidate-gene approach was used to study the association between the surfactant pr ...[more]

PMID: 10762543

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Project description:ObjectivesEffective treatment options for surfactant therapy in acute respiratory distress syndrome and coronavirus disease 2019 have not been established. To conduct preclinical studies in vitro and in vivo to evaluate efficiency, particle size, dosing, safety, and efficacy of inhaled surfactant using a breath-synchronized, nebulized delivery system in an established acute respiratory distress syndrome model.DesignPreclinical study.SettingResearch laboratory.SubjectsAnesthetized pigs.InterventionIn vitro analysis included particle size distribution and inhaled dose during simulated ventilation using a novel breath-synchronized nebulizer. Physiologic effects of inhaled aerosolized surfactant (treatment) were compared with aerosolized normal saline (control) in an adult porcine model (weight of 34.3 ± 0.6 kg) of severe acute respiratory distress syndrome (Pao2/Fio2 <100) with lung lavages and ventilator-induced lung injury during invasive ventilation.Measurements and main resultsMass median aerosol diameter was 2.8 µm. In vitro dose delivered distal to the endotracheal tube during mechanical ventilation was 85% ± 5%. Nebulizers were functional up to 20 doses of 108 mg of surfactant. Surfactant-treated animals (n = 4) exhibited rapid improvement in oxygenation with nearly full recovery of Pao2/Fio2 (~300) and end-expiratory lung volumes with nominal dose less than 30 mg/kg of surfactant, whereas control subjects (n = 3) maintained Pao2/Fio2 less than 100 over 4.5 hours with reduced end-expiratory lung volume. There was notably greater surfactant phospholipid content and lower indicators of lung inflammation and pathologic lung injury in surfactant-treated pigs than controls. There were no peridosing complications associated with nebulized surfactant, but surfactant-treated animals had progressively higher airway resistance post treatment than controls with no differences in ventilation effects between the two groups.ConclusionsBreath-synchronized, nebulized bovine surfactant appears to be a safe and feasible treatment option for use in coronavirus disease 2019 and other severe forms of acute respiratory distress syndrome.

Project description:BACKGROUND:Improved understanding of the relationship between patient age and acute respiratory distress syndrome (ARDS) development and mortality following traumatic injury may help facilitate generation of new hypotheses about ARDS pathophysiology and the role of novel treatments to improve outcomes across the age spectrum. METHODS:We conducted a retrospective cohort study of trauma patients included in the National Trauma Data Bank who were admitted to an intensive care unit from 2007 to 2016. We determined ARDS incidence and mortality across eight age groups for the entire 10-year study period and by year. We used generalized linear Poisson regression models adjusted for underlying mortality risk (injury mechanism, Injury Severity Score, admission Glasgow Coma Scale score, admission heart rate, and admission hypotension). RESULTS:Acute respiratory distress syndrome occurred in 3.1% of 1,297,190 trauma encounters. Acute respiratory distress syndrome incidence was lowest among pediatric patients and highest among adults aged 35 to 64 years. Acute respiratory distress syndrome mortality was highest among patients 80 years or older (43.9%), followed by 65 to 79 years (30.6%) and 4 years or younger (25.3%). The relative risk of mortality associated with ARDS was highest among the pediatric age groups, with an adjusted relative risk (aRR) of 2.06 (95% confidence interval [CI], 1.72-2.70) among patients 4 years or younger compared with an aRR of 1.51 (95% CI, 1.42-1.62) for the entire cohort. Acute respiratory distress syndrome mortality increased over the 10-year study period (aRR, 1.03 per year; 95% CI, 1.02-1.05 per year), whereas all-cause mortality decreased (aRR, 0.98 per year; 95% CI, 0.98-0.99 per year). CONCLUSIONS:While ARDS development following traumatic injury was most common in middle-aged adults, patients 4 years or younger and 65 years or older with ARDS experienced the highest burden of mortality. Children 4 years or younger were disproportionately affected by ARDS relative to their low underlying mortality following trauma that was not complicated by ARDS. Acute respiratory distress syndrome-associated mortality following trauma has worsened over the past decade, emphasizing the need for new prevention and treatment strategies. LEVEL OF EVIDENCE:Prognostic/epidemiological study, level III.

Dataset Information

Association between the surfactant protein A (SP-A) gene locus and respiratory-distress syndrome in the Finnish population.

Publications

Association between the surfactant protein A (SP-A) gene locus and respiratory-distress syndrome in the Finnish population.

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