Alveolar-capillary Membrane Damage Research Articles

Immature Surfactant Protein B Increases in the Serum of Patients with Calcific Severe Aortic Stenosis.

Valvular disease is a complex pathological condition that impacts countless individuals around the globe. Due to limited treatments, it is crucial to understand its mechanisms to identify new targets. Valve disease may result in pulmonary venous hypertension, which is linked to compromised functioning of the alveolar and capillary membranes and hindered gas exchange. Nonetheless, the correlation between surfactant proteins (SPs) and valve disease remains unexplored. A total of 44 patients were enrolled in this study, with 36 undergoing aortic valve replacement and 8 needing a second aortic valve substitution due to bioprosthetic valve degeneration. Ten healthy subjects were also included. The results showed that patients who underwent both the first valve replacement and the second surgery had significantly higher levels of immature SP-B (proSP-B) compared to control subjects. The levels of the extra-lung collectin SP-D were higher in patients who needed a second surgery due to bioprosthetic valve degeneration, while SP-A levels remained unchanged. The research also showed that there was no reciprocal relationship between inflammation and SP-D as the levels of inflammatory mediators did not differ between groups. The present study demonstrates that circulating proSP-B serves as a reliable marker of alveolar-capillary membrane damage in patients with valvular heart disease.

Syndromes of gas exchange disorders in patients with pulmonary tuberculosis

Introduction. Measurement of diffusion in the lung is important in the diagnosis and management of most pulmonary diseases. The analysis of diffusion lung capac-ity (DLCO) in combination with body plethysmography is useful for the interpretation of the causes of pulmo-nary gas exchange disorders. The aim: to determine the leading syndromes of pulmonary gas exchange disorders in patients with pulmonary tuberculosis (PT). Materials and methods. 608 patients (244/364 M/W) with veri-fied PT with smoking history of less than 10 pack/years were examined. Spirometry, body plethysmography, and DLCO were performed by the single-breath breath-hold-ing method. Results. DLCO decrease was detected in the majority of patients with PT (76%): in 94% of patients with massive fibrous-cavernous PT, 79.4% with disseminated PT and more than 60% of patients with infiltrative foci, local cavities, tuberculomas. In patients without ventilation dis-orders (58.4%), DLCO decrease was caused by damage to the alveolar capillary membrane, less often by air trapping (35.1%), other cases were rare. In the obstructive variant, mixed disorders of gas exchange (38.2%) and air trapping (34.1%) were most typical. In the restrictive variant, gas exchange surface reduction (62.5%) and mixed disorders (30%) prevailed. In mixed ventilation disorders, the mixed pulmonary gas exchange disorders were most often de-tected (63.8%) and the gas exchange surface reduction was quite common (36.2%) also. Conclusion. Alveolar cap-illary membrane damage (35.1%) and air trapping (28.1%) were most common in patients with PT. The mixed variant and gas exchange surface reduction were detected less frequently (24.7 and 12.1%, respectively), but these syn-dromes led to the most significant DLCO decrease.

Ultraprotective Ventilation during CPB Protects the Alveolar-Capillary Barrier in Pulmonary Normotensive Congenital Heart Patients.

Alveolar-capillary membrane damage develops as a result of the inflammatory effect of cardiopulmonary bypass (CPB). In the presence of a healthy alveolar-capillary barrier, there is little or no surfactant in the blood. The aim of this study was to evaluate the protective effects of ultraprotective ventilation during CPB by measuring serum and bronchoalveolar lavage (BAL) surfactant protein B (SPB) values in congenital heart surgery. This prospective study was designed for 46 patients with congenital heart defects. Patients were classified into two groups: group 1 comprising pulmonary normotensive patients and group 2 consisting of pulmonary hypertensive (PH) patients. Each group was divided into two sub-groups: (a) those who received ultraprotective ventilation during CPB and (b) those who did not receive ultraprotective ventilation during CPB. Serum SPB (S-SPB) values were measured preoperatively (ST1); at the fourth hour postop (ST2); and at the 24th hour postop (ST3). BAL SPB values were measured preoperatively (BT1); and at the fourth hour postop (BT2).Results: ST1, ST2, and ST3 values of group 1a (pulmonary normotensive ventilated patients) and group 1b (pulmonary normotensive non-ventilated patients) were much lower than those of group 2a (pulmonary hypertensive ventilated patients) and group 2b (pulmonary hypertensive non-ventilated patients) (P < .05). The evaluation of ST1, ST2, and ST3 values between groups 1a and 1b did not show statistically significant differences. When comparing ST1 to ST3, a decrease in value was observed in group 1a (32.28 ± 13.27 ng/mL to 19.38 ± 7.6 ng/mL) (P = .006). In Group 1b, values increased between ST1 and ST2 before decreasing from ST2 to ST3; however, the ST3 values were still higher than their ST1 counterparts. It was recorded that there was no statistically significant difference between the ST1, ST2, and ST3 values of group 2a and group 2b. A comparison of the BT1 and BT2 values in groups also yielded no statistically significant differences.Conclusion: Although pulmonary hypertension is known to result in lung injury, this study is important as it shows that ultraprotective ventilation protects the alveolar-capillary barrier in pulmonary normotensive congenital heart patients.

The Efficacy of Platelet-Rich Plasma in the Treatment of Rib Fractures.

Background Rib fracture is the most common result of thoracic traumas. Intrapulmonary shunt, alveolar capillary membrane damage, intra-alveolar hemorrhage, and hypoxia may develop following rib fractures. Therefore, prompt treatment is important. The aim of this experimental study was to analyze the effects of platelet-rich plasma (PRP) on rib fractures to secure a speedier and more efficient treatment method. Materials and Methods The study involved 18 New Zealand white rabbits, randomly divided into three groups as Group 1, the sham group with no surgical intervention; Group 2, the control group in which simple rib fractures were applied and no treatment; and Group 3, in which rib fractures were applied and then PRP treatment was administered. Results The mean recovery plate thickness measurements were found to be statistically significantly higher in the PRP group compared with the other groups (p < 0.005). A thicker fibrotic cell proliferation and the formation of many capillaries were observed around the growth plate in the PRP group compared with the other groups. These structures were lesser in the control group compared with the PRP group and at the lowest level in the sham group. Larger and distinct callus formation was observed and a new intramedullary field in the PRP group. Conclusions PRP is a reliable and effective autologous product with minimal side effects, which can be considered as an alternative treatment in patients with rib fractures and used easily in pseudoarthrosis, surgical fracture, or flail chest.

AB0818 Nitric oxide diffusion and pulmonary capillary blood volume measurement in scleroderma patients

BackgroundCarbon monoxide diffusing capacity test (DLCO) is a non invasive diagnostic method for interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH), frequent and severe complications of systemic sclerosis (SSc)....

Acute high-altitude exposure reduces lung diffusion: Data from the HIGHCARE Alps project

The causes and development of lung fluid, as well as the integrity of the alveolar-capillary membrane at high altitude, are undefined. This study was conceived to see whether fluid accumulates within the lung with acute high altitude exposure, and whether this is associated with alveolar capillary membrane damage. We studied lung carbon monoxide diffusion (DLCO), its components – membrane diffusion (DM) and capillary volume (VC) and alveolar volume (VA) measured in 43 healthy subjects in Milan (122m) and after 1 and 3 days at Capanna Regina Margherita (4559m). DLCO measurement was adjusted for hemoglobin and inspired oxygen. We also measured plasma surfactant derived protein B (SPB) and Receptor of Advanced Glycation End-products (RAGE) as markers of alveolar-capillary membrane damage, and ultrasound lung comets as a marker of extravascular lung water. 21 subjects received acetazolamide and 22 placebo.DLCO was lower at Capanna Regina Margherita (day 1: 24.3±4.7 and day 3: 23.6±5.4mL/mmHg/min), than in Milan (25.8±5.5; p<0.001 vs. day 1 and 3) due to DM reduction (Milan: 50.5±14.6mL/mmHg/min, Capanna Regina Margherita day 1: 45.1±11.5mL/mmHg/min, day 3: 43.2±13.9mL/mmHg/min; p<0.05 Milan vs. day 3) with a partially compensatory VC increase (Milan: 96±37mL, Capanna Regina Margherita day 1: 152±66mL, day 3: 153±59mL; p<0.001 Milan vs. day 1 and day 3). Acetazolamide did not prevent the fall in DLCO albeit, between day 1 and 3, such a trend was observed. Regardless of treatment lung comets increased from 0 to 7.2±3.6 (p<0.0001). SPB and RAGE were unchanged. Lung fluid increased at high altitude without evidence from plasma measurements, supporting alveolar-capillary damage.

Pulmonary Complications of Congenital Heart Disease

Cardiac and pulmonary pathophysiologies are closely interdependent, which makes the management of patients with congenital heart disease (CHD) all the more complex. Pulmonary complications of CHD can be structural due to compression causing airway malacia or atelectasis of the lung. Surgical repair of CHD can also result in structural trauma to the respiratory system, e.g., chylothorax, subglottic stenosis, or diaphragmatic paralysis. Disruption of the Starling forces in the pulmonary vascular system in certain types of CHD lead to alveolar-capillary membrane damage and pulmonary oedema. This in turn results in poorly compliant lungs with a restrictive lung function pattern that can deteriorate to cause hypoxemia. The circulation post single ventricle palliative surgery (the so called "Fontan circulation") poses a unique spectrum of pulmonary pathophysiology with restrictive lung function and a low pulmonary blood flow state that predisposes to thromboembolic complications and plastic bronchitis. As the population of patients surviving post CHD repair increases, the incidence of pulmonary complications has also increased and presents a unique cohort in both the paediatric and adult clinics.

Carbon-nanoparticle-triggered acute lung inflammation and its resolution are not altered in PPARγ-defective (P465L) mice.

BackgroundThe alveolar macrophage (AM) - first line of innate immune defence against pathogens and environmental irritants - constitutively expresses peroxisome-proliferator activated receptor γ (PPARγ). PPARγ ligand-induced activation keeps the AM quiescent, and thereby contributes to combat invaders and resolve inflammation by augmenting the phagocytosis of apoptotic neutrophils and inhibiting an excessive expression of inflammatory genes. Because of these presumed anti-inflammatory functions of PPARγ we tested the hypothesis, whether reduced functional receptor availability in mutant mice resulted in increased cellular and molecular inflammatory response during acute inflammation and/or in an impairment of its resolution.MethodsTo address this hypothesis we examined the effects of a carbon-nanoparticle (CNP) lung challenge, as surrogate for non-infectious environmental irritants, in a murine model carrying a dominant-negative point mutation in the ligand-binding domain of PPARγ (P465L/wt). Animals were instilled intratracheally with Printex 90 CNPs and bronchoalveolar lavage (BAL) was gained 24 h or 72 h after instillation to investigate its cellular and protein composition.ResultsHigher BAL cell numbers - due to higher macrophage counts - were found in mutants irrespective of treatment. Neutrophil numbers in contrast were slightly lower in mutants. Intratracheal CNP instillation resulted in a profound recruitment of inflammatory neutrophils into the alveolus, but genotype related differences at acute inflammation (24 h) and resolution (72 h) were not observed. There were no signs for increased alveolar-capillary membrane damage or necrotic cell death in mutants as determined by BAL protein and lactate-dehydrogenase content. Pro-inflammatory macrophage-derived cytokine osteopontin was higher, but galectin-3 lower in female mutants. CXCL5 and lipocalin-2 markers, attributed to epithelial cell stimulation did not differ.ConclusionsDespite general genotype-related differences, we had to reject our hypothesis of an increased CNP induced lung inflammation and an impairment of its resolution in PPARγ defective mice. Although earlier studies showed ligand-induced activation of nuclear receptor PPARγ to promote resolution of lung inflammation, its reduced activity did not provide signs of resolution impairment in the settings investigated here.

Surfactant phospholipids, surfactant proteins, and inflammatory markers during acute lung injury in children

To explore the pathophysiology of acute lung injury in children. Prospective cohort study. Regional University Hospital, pediatric intensive care unit. Children without a preexisting lung injury who developed acute lung injury and were intubated were eligible for the study. Children without lung injury and intubated for minor surgical procedures acted as controls. Bronchoalveolar lavage fluid and blood were collected on days 1 to 4, weekly, and immediately before extubation during acute lung injury. Molecular species compositions of phosphatidylcholine were determined by electrospray ionization mass spectrometry of lipid extracts of bronchoalveolar lavage fluid supernatants. Surfactant proteins A, B, and D and interleukin-8 were measured in bronchoalveolar lavage fluid and plasma by enzyme-linked immunosorbent assay and Western blotting. Eighteen children with acute lung injury were enrolled in the study and compared with eight controls. In children with acute lung injury, there were significant changes in the bronchoalveolar lavage fluid phosphatidylcholine species. Bronchoalveolar lavage fluid dipalmitoyl phosphatidylcholine (PC 16:0/16:0) and palmitoyl-myristoyl phosphatidylcholine (PC 16:0/14:0) significantly deceased during acute lung injury (p < .001 and p < .001, respectively), whereas oleoyl-linoleoyl PC (18:1/18:2), palmitoyl-linoleoyl PC (16:0/18:2) and stearoyl-linoleoyl PC (18:0/18:2) characteristic of plasma PC were significantly increased (p < .05, p < .02, and p < .05 respectively), as well as palmitoyl-oleoyl PC (16:0/18:1), and stearoyl-arachidonoyl PC (18:0/20:4) which are characteristic of cell membranes (p < .02, and p < .02, respectively). There were no significant changes to bronchoalveolar lavage fluid, surfactant protein A or B levels compared with controls during acute lung injury, whereas bronchoalveolar lavage fluid, surfactant protein D, and interleukin-8 levels significantly increased (p < .05 and p < .02, respectively). In plasma during acute lung injury, there were significant increases in surfactant proteins A, B, and D, and interleukin-8 (p < .001, p < .001, p < .05, and p < .001, respectively). Changes to the phosphatidylcholine profile, surfactant proteins, and inflammatory markers of bronchoalveolar lavage fluid and plasma in children with acute lung injury are consistent with an alveolar/blood leakage and inflammatory cell membrane degradation products. These changes are due to alveolar capillary membrane damage and cellular infiltration.

Beneficial Effects of a Bradykinin Antagonist in a Model of Gram-Negative Sepsis

Activation of the kallikrein-kinin system in sepsis has long been recognized, but its role, beneficial or pathologic, has not been determined. Recently, however, specific bradykinin (BK) antagonists have become available and we sought to determine the effects of a BK antagonist, NPC17731, in a model of sepsis-induced acute lung injury (ALI). Anesthetized swine were studied for 5 hours, receiving a 1-hour infusion of saline (Controls) or live Pseudomonas aeruginosa (Septic untreated). Treatment groups received a 5 mg/kg bolus of NPC17731 followed by a 1 mg/kg bolus hourly commencing either just before sepsis (Pretreatment) or 30 minutes following the onset of sepsis (Posttreatment). Septic untreated animals showed a rapid, progressive decline in arterial PaO2 compared to controls, and this was significantly improved in both treatment groups. Bronchoalveolar lavage at 5 hours in both treatment groups also showed significant decreases in neutrophil (PMN) counts and protein content compared to untreated septic animals, indicating decreased PMN migration and alveolar-capillary membrane damage. Both treatment groups also showed reduced PMN sequestration in the lung compared to untreated animals, although PMNs did exhibit significant upregulation of PMN CD18 receptor expression and superoxide generation. These data imply a significant role for BK in the pathogenesis of sepsis-induced ALI. Use of a competitive BK antagonist significantly attenuated the development of ALI without inhibiting PMN activation. BK antagonists may be a useful adjunct in the armamentarium against sepsis-induced ALI.

Tumor necrosis factor-alpha blockade prevents neutrophil CD18 receptor upregulation and attenuates acute lung injury in porcine sepsis without inhibition of neutrophil oxygen radical generation.

Tumor necrosis factor (TNF alpha), both by direct action and by trafficking cells of the immune system, is implicated in cardiopulmonary derangements and PMN-mediated microvascular injury associated with gram-negative sepsis. We examined the effects of pretreatment with a monoclonal antibody to TNF alpha on PMN function, hemodynamic derangements, and alveolar capillary membrane damage in a septic porcine model. Anti-TNF alpha profoundly improved hemodynamic consequences in this model. Reduction in PMN CD11/18 receptor expression, lung myeloperoxidase activity, and attenuation of peripheral neutropenia (all P < 0.05) indicate that pretreatment significantly reduced lung sequestration of PMNs seen in septic controls. In contrast, PMN oxygen radical (O2-) generation was not significantly different from unprotected septic animals. Despite the presence of circulating PMNs primed for O2- burst, alveolar capillary membrane damage, assessed by bronchoalveolar lavage protein content and arterial PO2 was markedly attenuated in the treatment group (P < 0.05). We conclude that anti-TNF alpha suppresses systemic hemodynamic actions of TNF alpha. Further, it prevents upregulation of PMN adhesion receptors inhibiting PMN/endothelial cell interaction. This prevents formation of a "microenvironment," protected from circulating oxidant scavengers, into which sepsis-activated PMNs release their toxic products. Pretreatment with anti-TNF alpha monoclonal antibody thus affords global protection in porcine Gram-negative sepsis.

Acute cigarette smoke exposure increases alveolar permeability in rabbits.

We measured lung clearance of aerosolized technetium-labeled diethylenetriamine pentaacetic acid (99mTcDTPA) as an index of alveolar epithelial permeability in rabbits exposed to cigarette smoke. Eighteen rabbits were randomly assigned to 3 equal-size groups: control, all smoke exposure (ASE), and limited smoke exposure (LSE). Cigarette or sham smoke was delivered by syringe in a series of 5, 10, 20, and 30 tidal volume breaths with a 20-min counting period between each subset of breaths to determine 99mTcDTPA biologic half-life (T1/2). Mean T1/2 minimum (i.e., the smallest T1/2 observed) was significantly lower (p less than 0.05) for ASE and LSE rabbits than by control rabbits. We observed a significant difference at 20 and 30 breath exposures between the control and ASE group mean values (% baseline) for T1/2, arterial blood pressure, and peak airway pressure. A combination of light and electron microscopy showed focal alveolar edema and hemorrhage in the ASE and LSE groups but no alveolar-capillary membrane damage. In summary, acute cigarette smoke exposure increases alveolar permeability as measured by 99mTcDTPA clearance, but there was no detectable ultrastructural alteration of the alveolar-capillary membrane.

The adult respiratory distress syndrome. Recognition and management.

Any one of a number of physiologic insults can bring about alveolar capillary membrane damage and the adult respiratory distress syndrome. Definitive diagnosis often is delayed because symptoms and laboratory data, other than arterial blood gas values, are nonspecific. Early, vigorous therapy can prevent progressive respiratory failure.