Serum Surfactant Protein Levels in Patients Admitted to the Hospital with Acute COPD Exacerbation.

Surfactant proteins (SPs) have been studied in COPD patients as biomarkers of disease severity and as predictive factors of unfavorable outcomes. The aim of this exploratory study was to evaluate serum levels of SP-A, SP-B, SP-C, and SP-D in patients with COPD both during AECOPD and in stability and to test their possible associations with disease severity and with the development of new exacerbation events. 20 consecutive COPD patients hospitalized for AECOPD were included. Serum SP levels were measured on admission, at discharge, and on stability. SP-A levels were significantly lower both on admission and at discharge in patients with early relapse compared to those with late or no relapse (29.2 ± 9.1 vs. 43.9 ± 16.9 ng/ml, p = 0.037, and 24.3 ± 2.8 vs. 39.3 ± 14.2 ng/ml, p = 0.011, respectively). SP-B levels were found to have a trend to be higher at discharge and significantly higher on stability in patients experiencing an early relapse compared to those with late or no relapse (52.5 ± 31.6 vs. 31.4 ± 32.3 ng/ml, p = 0.052 and 64.8 ± 32.6 vs. 32.8 ± 25.6 ng/ml, p = 0.024, respectively). Finally, the ROC analysis showed that serum SP-A, SP-B, and SP-C levels at discharge, seemed to be significant predictors of early relapse. Our conclusion is that serum levels of SPs might be related to disease outcomes in COPD patients.

In vitro and in vivo comparison between poractant alfa and the new generation synthetic surfactant CHF5633.

BACKGROUND: CHF5633 is a new generation synthetic surfactant containing both SP-B and SP-C analogues developed for the treatment of respiratory distress syndrome. Here, the optimal dose and its performance in comparison to the animal-derived surfactant poractant alfa were investigated. METHODS: In vitro surfactant activity was determined by means of the Wilhelmy balance and the capillary surfactometer. The dose-finding study was performed in preterm rabbits with severe surfactant deficiency. CHF5633 doses ranging from 50 to 300 mg/kg were used. Untreated animals and animals treated with 200 mg/kg of poractant alfa were included for comparison. RESULTS: In vitro, minimum surface tension (γmin) was decreased from values above 70 to 0 mN/m by both surfactants, and they formed rapidly a film at the air-liquid interface. In vivo studies showed a clear dose-dependent improvement of lung function for CHF5633. The pulmonary effect of CHF5633 200 mg/kg dose was comparable to the pulmonary response elicited by 200 mg/kg of poractant alfa in preterm rabbits. CONCLUSION: CHF5633 is as efficient as poractant alfa in our in vitro and in vivo settings. A clear dose-dependent improvement of lung function could be observed for CHF5633, with the dose of 200 mg/kg being the most efficient one.

Relationship between surfactant proteins B and C and obstructive sleep apnea: is serum SP-B concentration a potential biomarker of obstructive sleep apnea?

BACKGROUND: Surfactant proteins B and C are mainly synthesized, secreted by alveolar type II cells, and affected by hypoxia and mechanical stretches. We hypothesized that their serum levels might be altered by intermittent hypoxia and swing of intrathoracic pressure of obstructive sleep apnea (OSA). METHODS: Consecutive 140 middle-aged males, suspicious of OSA determined by polysomnography, were studied. Surfactant proteins B and C were determined by ELISA. RESULTS: Surfactant protein B (41.39 ± 6.01 vs 44.73 ± 7.62 ng/L, p = 0.005), not C (32.60 ± 6.00 vs 32.43 ± 6.44 ng/L, p = 0.61), significantly lowered in moderate to severe OSA subjects than in non to mild OSA subjects. Severity of OSA is inversely correlated with serum surfactant protein B. Adjusting age, body mass index, and smoking history, compared to subjects with surfactant protein B (SP-B) ≥43.35 ng/L, those with SP-B <43.35 ng/L showed significantly increased 1.528-fold risk for moderate to severe OSA (p = 0.009), whereas no association between surfactant protein C and OSA was observed. Prevalence of moderate to severe OSA in lower SP-B group is higher than that in higher SP-B group (62.7 vs 38.4 %, p = 0.003). Serial and parallel tests on Epworth sleep scale (ESS) and SP-B evaluation can be complementary and prove helpful with high specificity (94.44 %) and sensitivity (84.48 %) to detect moderate to severe OSA. CONCLUSIONS: Serum surfactant protein B, rather than C, is decreased in some individuals with moderate to severe OSA, compared to non to mild OSA subjects. Serum surfactant protein B might be a potential biomarker to diagnose OSA.

Surfactant protein C metabolism in human infants and adult patients by stable isotope tracer and mass spectrometry.

Surfactant protein C (SP-C) is deemed as the surfactant protein most specifically expressed in type II alveolar epithelial cells and plays an important role in surfactant function. SP-C turnover in humans and its meaning in the clinical context have never been approached. In this study, we used mass spectrometry to investigate SP-C turnover in humans. We studied four infants and eight adults requiring mechanical ventilation. All patients had no lung disease. Patients received a 24-h continuous infusion of (13)C-leucine as precursor of SP-C, and serial tracheal aspirates and plasma samples were obtained every 6 h till 48 h. SP-C was isolated from tracheal aspirates by sorbent-phase chromatography. (13)C-leucine SP-C enrichment could be successfully measured in three infant and in four adult samples by using mass spectrometry coupled with a gas chromatographer. Median SP-C fractional synthesis rate, secretion time, and peak time were 15.7 (14.1-27.5)%/day, 6.0 (4.7-11.5) h, and 24 (20-27) h. In conclusion, this study shows that it is feasible to accurately determine SP-C turnover in humans by stable isotopes.

[A case of acute exacerbation of interstitial pneumonia after appendectomy managed with spinal anesthesia].

An 88-year-old woman was admitted with acute appendicitis. She had been treated with prednisolone and home oxygen therapy for interstitial pneumonia. Her respiratory state on admission was Grade 2 of Hugh-Jones' classification, and plasma KL-6 and SP-D levels were high. Seven days after the admission, appendectomy was performed under spinal anesthesia. Spinal anesthesia was initiated by injecting 0.5% hyperbaric bupivacaine 2.0ml into L3-4 interspace, and achieved block level was up to T4. During the operation, her respiratory state was stable, but after the operation, dry cough, increase of body temperature, and dyspnea were observed. Chest roentgenogram revealed severe ground glass appearance and reticular shadows bilaterally. Steroid therapy for acute exacerbation of interstitial pneumonia was initiated, but she died on the 13th POD. This case teaches us to take a lot of care in the management of a patient with high plasma level of KL-6 and SP-D.