Pathogenesis Of Respiratory Distress Syndrome Research Articles

Budesonide and Surfactant Combination for Treatment of Respiratory Distress Syndrome in Preterm Neonates and Evaluation Outcomes

Background: Pulmonary inflammation plays a critical role in the pathogenesis of respiratory distress syndrome. The aim of this study was to compare the effectiveness of intratracheal administration combination of pulmonary surfactant (PS) and budesonide with surfactant alone in preterm neonates. Materials and Methods: This randomized clinical trial was performed in Yazd between 2020 and 2022. A total of 70 preterm neonates weighing between 800 and 1500 g were included in the study. Results: The risk of bronchopulmonary dysplasia (BPD) in infants treated with PS and budesonide was seven times lower than in the surfactant group alone (P = 0.004). Furthermore, in the intervention group, the hospitalization period (P = 0.004) and retinopathy of prematurity (P = 0.02) were significantly reduced. Conclusion: In these neonates, intratracheal administration of surfactant/budesonide combination significantly decreases the incidence of frequent apnea, BPD, continuous positive airway pressure therapy, and earlier discharge. There is a need for larger trials and an exact evaluation of side effects.

Evaluation of intratracheal salbutamol effects in addition to surfactant in the clinical course of premature neonates with respiratory distress syndrome.

In addition to surfactant deficiency, secretion of fluid from blood to the lungs and increase in the fluid content of the lung play significant roles in the pathogenesis of respiratory distress syndrome (RDS). Thus, we aimed to evaluate the effect of salbutamol (a beta-agonist) on fluid clearance from the lungs in neonates with RDS. This randomized controlled clinical trial included 82 neonates with RDS admitted to the neonatal intensive care units of Alzahra and Shahid Beheshti Hospitals of Isfahan University of Medical Science from 2017 to 2018. Patients were recruited through convenience sampling. They were randomized into two groups, using simple randomization: 42 were only treated with intra-tracheal surfactant (control group) and 40 with intra-tracheal surfactant plus salbutamol (intervention group). The two groups were compared regarding intubation surfactant administration and extubation (INSURE) failure, duration of nasal continuous positive airway pressure, intubation, oxygen therapy, morbidity, and mortality. INSURE failure leading to mechanical ventilation occurred in 3 neonates in the control group and 2 in the intervention group (P = 0.680). Mean hospital length of stay did not differ significantly between groups (P = 0.230). Comparison of controls with the intervention group regarding complications and the incidence of morbidities revealed no statistically significant difference (P > 0.05). Findings of this study were not in favor of the routine use of salbutamol in neonates with RDS as it did not improve the course of the disease among newborns.

Immunotherapy strategies and prospects for acute lung injury: Focus on immune cells and cytokines.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a disastrous condition, which can be caused by a wide range of diseases, such as pneumonia, sepsis, traumas, and the most recent, COVID-19. Even though we have gained an improved understanding of acute lung injury/acute respiratory distress syndrome pathogenesis and treatment mechanism, there is still no effective treatment for acute lung injury/acute respiratory distress syndrome, which is partly responsible for the unacceptable mortality rate. In the pathogenesis of acute lung injury, the inflammatory storm is the main pathological feature. More and more evidences show that immune cells and cytokines secreted by immune cells play an irreplaceable role in the pathogenesis of acute lung injury. Therefore, here we mainly reviewed the role of various immune cells in acute lung injury from the perspective of immunotherapy, and elaborated the crosstalk of immune cells and cytokines, aiming to provide novel ideas and targets for the treatment of acute lung injury.

Oxidative Stress and Anti-Oxidant Markers in Premature Infants with Respiratory Distress Syndrome.

BACKGROUND:Neonatal respiratory distress syndrome (RDS) caused by decreased surfactant and structural lung immaturity. The imbalance between oxidative status and antioxidant defence system was suggested to be an important trigger for lung affection with RDS.AIM:The goal of the current research was to elucidate the significance of the oxidant/ antioxidant status in the pathogenesis of RDS in preterm infants.PATIENTS AND METHODS:This controlled study included 31 preterm neonates with RDS and 36 healthy preterm neonates. Quantification level of oxidative stress biomarkers; malondialdehyde (MDA) & hydrogen peroxide (H2O2) along with antioxidant enzymes activity; catalase (CAT) & superoxide dismutase (SOD) in plasma of healthy premature neonates compared with those with RDS.RESULTS:status of oxidative stress markers (MDA & H2O2) showed a significant increase with decreased levels of antioxidant enzymes activity (CAT & SOD) in neonates with RDS when compared to healthy prematures.CONCLUSION:The results obtained in this study indicate that the increased oxidative stress accompanied by reduced antioxidant defences may play a significant role in the pathogenesis of respiratory distress in preterm newborns.

RESPIRATORY DISTRESS SYNDROME IN ACUTE PANCREATITIS (EXPERIMENTAL STUDY)

Aim. To assess the role of lipid metabolism disorders and coagulation-lytic changes of lung tissue structures in the pathogenesis of respiratory distress syndrome in acute pancreatitis. Material and Methods. The study is based on experiments on adult mongrel dogs. The model is acute pancreatitis by V.M. Buyanov et al. (1989). In target dates blood sample, bronchoalveolar lavage and biopsy of lung tissue were analyzed. We investigated free-radical processes, phospholipase and protease activity, qualitative and quantitative composition of lipids, coagulation-lytic state of tissues, functional state of surfactant and transcapillary fluid exchange. Results. It was found that acute pancreatitis is associated with significant disorders of transcapillary exchange of fluid in lungs, function and composition of surfactant, that led to respiratory impairment. Lipid metabolism disorders and coagulation-lytic changes in lungs are main pathogenetic mechanisms of respiratory distress syndrome. Metabolic changes in lungs are associated with endogenous intoxication. Conclusion. Pulmonary lipid metabolism changes and tissue coagulation-lytic system modification occur in acute pancreatitis due to endogenous intoxication, increased phospholipase and proteolytic activity, intensification of lipid peroxidation. These disorders leads to violation of transcapillary fluid exchange, functional state of surfactant followed by respiratory distress syndrome development.excessive intensification of lipid peroxidation, increased activity of phospholipases and proteases.

The fascinating story of surfactant.

The fascinating story of surfactant.

Clinical features of respiratory distress syndrome in neonates of different gestational ages

To study clinical features of respiratory distress syndrome (RDS) in neonates of different gestational ages (GA). According to GA, 133 neonates with RDS were classified into GA <34 weeks group (n=66), GA 34-36 weeks group (late preterm neonates; n=31), and GA ≥37 weeks group (full-term neonates; n=36). The mothers' medical history during pregnancy and the condition of the neonates at birth were retrospectively analyzed, and the clinical data were compared between groups. Prenatal corticosteroids supplementation in the GA <34 weeks group was more common than that in the GA 34-36 weeks group (P<0.05). Compared with the GA ≥37 weeks group and the GA 34-36 weeks group, the GA <34 weeks group showed a significantly lower rate of primary diseases, a significantly later time of the development of dyspnea (P<0.05), and a higher rate of intraventricular hemorrhage (P<0.05). Serum albumin levels in the GA <34 weeks group were significantly lower than in the GA ≥37 weeks group (P<0.05). The GA ≥37 weeks group and the GA 34-36 weeks group showed a significantly higher reuse rate of pulmonary surfactant (P<0.05). Use of high-frequency oscillatory ventilation was more common in the GA ≥37 weeks group compared with the GA <34 weeks group (P<0.05). The clinical features of RDS are different across neonates of different GA, suggesting that the pathogenesis of RDS may be different in neonates of different GA.

Neonatal Respiratory Diseases in the Newborn Infant: Novel Insights from Stable Isotope Tracer Studies

Respiratory distress syndrome is a common problem in preterm infants and the etiology is multifactorial. Lung underdevelopment, lung hypoplasia, abnormal lung water metabolism, inflammation, and pulmonary surfactant deficiency or disfunction play a variable role in the pathogenesis of respiratory distress syndrome. High-quality exogenous surfactant replacement studies and studies on surfactant metabolism are available; however, the contribution of surfactant deficiency, alteration or dysfunction in selected neonatal lung conditions is not fully understood. In this article, we describe a series of studies made by applying stable isotope tracers to the study of surfactant metabolism and lung water. In a first set of studies, which we call ‘endogenous studies', using stable isotope-labelled intravenous surfactant precursors, we showed the feasibility of measuring surfactant synthesis and kinetics in infants using several metabolic precursors including plasma glucose, plasma fatty acids and body water. In a second set of studies, named ‘exogenous studies', using stable isotope-labelled phosphatidylcholine tracer given endotracheally, we could estimate surfactant disaturated phosphatidylcholine pool size and half-life. Very recent studies are focusing on lung water and on the endogenous biosynthesis of the surfactant-specific proteins. Information obtained from these studies in infants will help to better tailor exogenous surfactant treatment in neonatal lung diseases.

Effectiveness of intratracheal salbutamol in addition to surfactant on the clinical course of newborns with respiratory distress syndrome: a clinical trial.

BackgroundIn addition to surfactant deficiency, increase of lung fluid content and secretion of fluid derived from the blood participate in the pathogenesis of RDS in newborns.We hypothesized that the administration of salbutamol (β-agonist) to increase lung fluid absorption would decrease the INSURE failure rate in newborns with respiratory distress syndrome (RDS) treated with intratracheal surfactant.MethodsDesignBlinded, randomized clinical trial study.Setting/populationLevel III NICU, premature infants with RDS requiring intratracheal Surfactant.Forty Eight newborns with RDS treated with intratracheal Surfactant were randomized into two groups as Group A, Normal saline (as control group) and Group B (intervention group), Salbutamol were administered intratracheally in addition to Surfactant. Intubation-Surfactant administration- Rapid Extubation (INSURE) failure rate as primary outcome and secondary outcome as follow: duration of the need to NCPAP, mechanical ventilation and oxygen therapy; complications (patent ductus arteriosus, pneumothorax); mortality (respiratory or prematurity related complication) and the duration of hospitalization were assessed.ResultsTwenty Four patients in each group were studied. INSURE failure was seen in16 (66.7 %) and 10 (41.7 %) of normal saline and salbutamol groups respectively (p = 0.082). The duration of NCPAP in control group was 69.5 ± 54.9 h while in Salbutamol group was 51.6 ± 48.7 h (p = 0.316). All of deaths were related to respiratory failure. No differences in mortality or complications of RDS were observed. The duration of hospitalization was longer in control group than interventional group, 28.3 ± 18.1 and 18.6 ± 8.6 days, respectively. (p = 0.047).ConclusionSalbutamol may improve the clinical course of newborns with RDS requiring Surfactant.Trial registration numberIRCT2014072714215N1

Genetic research progress of respiratory distress syndrome in preterm infants

Respiratory distress syndrome(RDS)is a critical respiratory disease and commonly occurs in preterm infants.Preterm RDS is mainly due to the deficiency of lung surfactant.However, recent studies have indicated that genetic susceptibility may involve in the pathogenesis of RDS in preterm infants.In this paper, recent research progresses of genetic susceptibility and related candidate genes of RDS in preterm infants at home and abroad are reviewed. Key words: Respiratory distress syndrome; Preterm infants; Genetics

Intrafetal glucose infusion alters glucocorticoid signaling and reduces surfactant protein mRNA expression in the lung of the late-gestation sheep fetus.

Increased circulating fetal glucose and insulin concentrations are potential inhibitors of fetal lung maturation and may contribute to the pathogenesis of respiratory distress syndrome (RDS) in infants of diabetic mothers. In this study, we examined the effect of intrafetal glucose infusion on mRNA expression of glucose transporters, insulin-like growth factor signaling, glucocorticoid regulatory genes, and surfactant proteins in the lung of the late-gestation sheep fetus. The numerical density of the cells responsible for producing surfactant was determined using immunohistochemistry. Glucose infusion for 10 days did not affect mRNA expression of glucose transporters or IGFs but did decrease IGF-1R expression. There was reduced mRNA expression of the glucocorticoid-converting enzyme HSD11B-1 and the glucocorticoid receptor, potentially reducing glucocorticoid responsiveness in the fetal lung. Furthermore, surfactant protein (SFTP) mRNA expression was reduced in the lung following glucose infusion, while the number of SFTP-B-positive cells remained unchanged. These findings suggest the presence of a glucocorticoid-mediated mechanism regulating delayed maturation of the surfactant system in the sheep fetus following glucose infusion and provide evidence for the link between abnormal glycemic control during pregnancy and the increased risk of RDS in infants of uncontrolled diabetic mothers.

Expression of Pulmonary Surfactant-Associated Protein B in Neonatal Respiratory Distress Syndrome

Summary Background: The aim of this study was to investigate the role of pulmonary surfactant-associated protein B (SP-B) expression in the pathogenesis of neonatal respiratory distress syndrome (RDS) via detecting the protein and mRNA expression of SP-B. Methods: A total of 60 unrelated neonates who died of RDS were chosen as the RDS group and then subgrouped into ≤32 weeks group, 32∼37 weeks group and ≥37 weeks group (n=20). Sixty neonates who died of other diseases were enrolled as controls and subdivided into 3 matched groups based on the gestational age. Western blot assay and RT-PCR were employed. Results: In the RDS group, SP-B protein expression was reduced or deficient in 8 neonates of which 6 had no SP-B protein expression. In the control group, only 1 had reduced SP-B protein expression. The reduced or deficient SP-B protein expression in 9 neonates of both groups was noted in the ≥37 weeks group. In the RDS group, the SP-B mRNA expression was significantly lower than that in the control group. In the ≤37 weeks group, SP-B mRNA expression was comparable between the RDS group and control group. In the 32∼37 weeks group, the SP-B mRNA expression in the RDS group was significantly reduced when compared with the control group. In the ≥37 weeks group, the SP-B mRNA expression in the RDS group was dramatically lower than that in the control group. Conclusions: Alteration of SP-B expression is present at transcriptional and translational levels. Reduction of SP-B mRNA and protein expression is involved in the pathogenesis of RDS.

Respiratory distress syndrome (RDS) in premature infants is underscored by the magnitude of Th1 cytokine polarization

Respiratory distress syndrome (RDS) is a common problem and the leading cause of death in premature infants (PI). The introduction of surfactant treatment for RDS management has lowered mortality and morbidity; nevertheless, some neonates do not improve and are at increased risk of pulmonary hemorrhage. Inflammation, not only local but also systemic, seems to play an important role in the pathogenesis of RDS. To determine whether cytokine patterns characterize RDS and its outcome, we measured type-1 (IL-2, TNF-α, IFN-γ, IL-6) and type-2 (IL-4, IL-5, IL-10, TGF-β1) serum cytokines of 47 PI with established RDS and a control group of 30 healthy, appropriate for gestational age, full-term neonates. Cord blood samples were obtained at the time of delivery from PI and controls. Venous blood samples were collected from PI who received surfactant treatment and/or developed pulmonary hemorrhage. Significantly elevated cord blood cytokine levels were observed in PI at time of delivery, compared to controls, except for IL-5 and TNF-α levels that were within control range. The type-1/type-2 cytokine ratio was significantly increased in PI vs controls. Neonates who developed pulmonary hemorrhage between 2 and 3days of life and/or died, presented the strongest Th1 and type-1 cytokine polarization that was mainly due to increased IFN-γ and TNF-α, and decreased TGF-β1. The majority of these PI were female with very low gestational age. Overall, PI with RDS present a Th1/type-1 cytokine polarization, which persists irrespective of the treatment provided, and is amplified when complications appear. Th1 polarization is associated with poor prognosis.

The molecular basis of pulmonary surfactant – lessons from newborn infants

Major scientific advances in prenatal and neonatal physiology have provided the basis for improved outcomes for preterm and other infants with disorders causing respiratory failure. Critical for the improved diagnosis and treatment of preterm infants was the recognition of the importance of the pulmonary surfactant system in the pathogenesis of respiratory distress syndrome in preterm infants. Dr Whitsett and colleagues in the Division of Neonatology, Perinatal and Pulmonary Biology, with many collaborators worldwide, have focused their attention on the molecular basis of lung formation, maturation and function for more than three decades. Initial questions regarding the regulation of surfactant synthesis and secretion in newborn infants led to the identification and study of the structure and function of the surfactant proteins (SP-A, SP-B, SP-C and SP-D) and the genes encoding them. The critical and distinct roles of each of the surfactant proteins in surfactant homeostasis and innate immunity were systematically explored and, in particular, their important role in surfactant replacement preparations used to treat newborn infants was elucidated. Reagents, including peptides, antibodies and transgenic mouse models, were developed for general use by the field of pulmonary biology for the study of common and idiopathic lung diseases. Molecular tools to add, mutate or delete genes selectively, in the respiratory epithelium of transgenic mice, enabled the development of models of human disease. Basic advances made in understanding the molecular basis of surfactant homeostasis, lung formation and function have provided the tools and strategies for the diagnosis and treatment of pulmonary diseases that were previously termed ‘idiopathic’.

Total antioxidant capacity and total oxidant status after surfactant treatment in preterm infants with respiratory distress syndrome

Oxidative damage is important in the pathogenesis of respiratory distress syndrome (RDS). However, data on the effect of surfactant therapy on oxidative stress in vivo are limited. We aimed to evaluate the oxidant/antioxidant status in preterm infants with RDS via measurement of total antioxidant capacity (TAC) and total oxidant status (TOS), to determine the effect of surfactant on oxidant/antioxidant balance and to assess the association between TAC, TOS and clinical outcomes of the patients. Sixty-nine infants with RDS were included. Blood samples for determining TAC and TOS were collected before and 48 h after surfactant treatment. TAC and TOS levels were analysed in serum. Patients were followed up until discharge or death. Post-surfactant TAC levels were significantly higher than pre-surfactant TAC levels (P = 0.029). TAC/TOS ratio significantly increased after surfactant treatment (P = 0.018). Infants <28 weeks of gestational age had lower levels of baseline TAC than those ≥28 weeks of gestational age (P = 0.020), whereas TOS levels were similar. Baseline TAC/TOS ratio was lower in infants who died in the study period than those who survived (P = 0.023). After controlling gestational age, baseline TAC levels were significantly and inversely correlated with the duration of total respiratory support (r = -0.343; P = 0.009) and hospitalization (r = -0.341; P = 0.009). TAC or TOS levels were not associated with the development of bronchopulmonary dysplasia or other complications as determined during the investigation period. Oxidant-antioxidant balance shifts in favour of the antioxidant system after surfactant treatment. Lower TAC/TOS ratio in preterm infants may be associated with increased mortality.

Digoxin for preventing or treating neonatal respiratory distress syndrome.

Lendrum 1955 suggested that pulmonary edema secondary to congestive heart failure may contribute to neonatal respiratory distress syndrome (RDS). Based on this hypothesis, investigators began to use digitalis glycosides to improve myocardial contractility and decrease congestive heart failure. The first use of digitalis glycosides in infants with RDS was reported by Stahlman 1959. Stahlman reported a reduction in mortality in an uncontrolled trial of digitalis in infants with RDS. To assess the effect of digoxin on mortality in premature infants at risk for or with RDS. Searches were made of the Oxford Database of Perinatal Trials, Medline (MeSH terms: digoxin; limits: age groups, newborn infants; publication type, clinical trial), previous reviews including cross references, abstracts, conference and symposia proceedings, expert informants, and journal handsearching in the English language.When updated in December 2008, the search was expanded to include Medline, CINHAL, and Embase (MeSH terms and text words: digoxin or digitalis; limits: age group, all infants; publication type: clinical trial). Randomized and quazi-randomized controlled trials of digoxin in either the prevention or treatment of RDS are included in this overview. Data regarding clinical outcomes were excerpted from the trial reports by one review author (RS) and checked by the second review author (EO). Data were analyzed according to the standards of the Cochrane Neonatal Review Group. Two randomized controlled trials have studied the effects of digoxin in the prevention and treatment of RDS. No improvement in respiratory status or mortality was noted. Meta-analysis of the effect of digoxin given to infants at risk of or with RDS on mortality does not suggest any benefit of digoxin treatment (typical relative risk 1.27 95% CI 0.78 to 2.07; typical risk difference 0.06, 95% CI -0.06 to 0.17). Although hemodynamic disturbances play a role in the overall pathogenesis of respiratory distress syndrome, the specific contribution of early congestive heart failure (unrelated to hemodynamically significant patent ductus arteriosus) does not appear to be a significant factor in RDS. Treatment with digoxin has no proven value in infants solely affected with RDS.

Surfactant protein B gene polymorphism in preterm babies with respiratory distress syndrome

The etiology of respiratory distress syndrome (RDS) is multifactorial and multigenic. Studies have suggested that polymorphisms and mutations in the surfactant protein B (SP-B) gene are associated with the pathogenesis of RDS. The objectives of this study were to determine and compare the frequencies of SP-B gene polymorphisms in preterm babies with and without RDS. We studied 151 neonates: 79 preterm babies without RDS and 72 preterm newborns with RDS. The following four SP-B gene polymorphisms were analyzed: A/C at -18, C/T at 1580, A/G at 9306, and G/C at nucleotide 8714. The polymorphisms were detected by PCR amplification of genomic DNA and genotyping. The genotypes were determined using PCR-based converted restriction fragment length polymorphisms. The control group consisted of 42 (53%) girls and 37 (47%) boys. Weight ranged from 1170 to 3260 g and mean gestational age (GA) was 33.9 weeks (range: 29 to 35 weeks and 6 days). The RDS group consisted of 31 (43%) girls and 41 (57%) boys. Weight ranged from 614 to 2410 g and mean GA was 32 weeks (range: 26 to 35 weeks). The logistic regression model showed that GA was the variable that most contributed to the occurrence of RDS. The AG genotype of the A/G polymorphism at position 9306 of the SP-B gene was a protective factor in this population (OR = 0.1681; 95%CI = 0.0426-0.6629). We did not detect differences in the frequencies of the other polymorphisms between the two groups of newborns.

Plasminogen Activator Inhibitor I 4G/5G Polymorphism in Neonatal Respiratory Distress Syndrome

Fibrin monomers inhibit surfactant function. 4G/5G insertion/deletion polymorphism plays an important role in the regulation of plasminogen activator inhibitor 1 (PAI-1) gene expression. To examine the genotype distribution of PAI-1 polymorphism in 60 infants with respiratory distress syndrome (RDS) and 53 controls, an allele-specific polymerase chain reaction (PCR) was used. The proportion of 4G/4G, 4G/5G, and 5G/5G genotypes did not differ statistically between the RDS and control groups (P > .05). Having PAI-1 4G/4G genotype polymorphism appears to increase the risk of RDS (odds ratio [OR] =1.5; 95% confidence interval [CI], 0.5-4.3), although it was not statistically significant. No relation was found between the PAI-1 4G/5G polymorphisms and RDS, but there was an increased risk associated with the 4G variant of the PAI-1 gene. We believe that our findings of increased 4G allele of the PAI-1 gene in infants with RDS would also help to clarify the pathogenesis of RDS.

Comparison of surfactant protein B polymorphisms of healthy term newborns with preterm newborns having respiratory distress syndrome

Polymorphisms and mutations in the surfactant protein B (SP-B) gene have been associated with the pathogenesis of respiratory distress syndrome (RDS). The objective of the present study was to compare the frequencies of SP-B gene polymorphisms between preterm babies with RDS and healthy term newborns. We studied 50 preterm babies with RDS (inclusion criteria - newborns with RDS and gestational age between 28 and 33 weeks and 6 days), and 100 healthy term newborns. Four SP-B gene polymorphisms were analyzed: A/C at nucleotide -18, C/T at nucleotide 1580, A/G at nucleotide 9306, and G/C at nucleotide 8714, by PCR amplification of genomic DNA and genotyping by cRFLP. The healthy newborns comprised 42 female and 58 male neonates; 39 were white and 61 non-white. The RDS group comprised 21 female and 29 male preterm neonates; 28 were white and 22 non-white. Weight ranged from 640 to 2080 g (mean: 1273 g); mean gestational age was 31 weeks and 2 days (range: 28-33 weeks and 6 days). When white children were analyzed separately, a statistically significant difference in the G/C polymorphism at 8714 was observed between groups (P = 0.028). All other genotype frequencies were similar for both groups when sex and race were analyzed together. Analysis of the SP-B polymorphism G/C at nucleotide 8714 showed that among white neonates the GG genotype was found only in the RDS group at a frequency of 17% and the GC genotype was more frequently found in healthy term newborns. These data demonstrate an association of GG genotype with RDS.

G protein‐coupled receptor for asthma susceptibility associates with respiratory distress syndrome

Background. Respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) have some common features with asthma.Aim. To study whether G protein‐coupled receptor for asthma susceptibility (GPRA) contributes to RDS or BPD.Methods. A haplotype association study was performed in a case‐control setting of 521 Finnish infants (including 176 preterm neonates with RDS and 37 with BPD). Immunoreactivity of GPRA isoforms A and B was determined in pulmonary samples of fetuses, term infants and preterm infants with RDS or BPD. GPRA mRNA expression was determined by quantitative real‐time polymerase chain reaction (PCR) in samples from nasal respiratory epithelium of adults, term infants and preterm infants.Results. In infants with RDS born at 32–35 weeks of gestation, GPRA haplotype H1 was significantly underrepresented in RDS, whereas haplotype H4/H5 was associated with an increased risk. As in asthma, GPRA B isoform was induced in bronchial smooth muscle cells in RDS and BPD. In nasal respiratory epithelium, relative GPRA mRNA expression was strong in adults, weak in preterm and slightly higher in term samples.Conclusions. The results suggest that near‐term RDS and asthma share the same susceptibility and protective GPRA haplotypes. Altered GPRA expression may play a role in the pathogenesis of RDS and BPD in preterm infants.