Serum Levels of Surfactant Proteins in Patients with Combined Pulmonary Fibrosis and Emphysema (CPFE)

Abstract

IntroductionEmphysema and idiopathic pulmonary fibrosis (IPF) present either per se or coexist in combined pulmonary fibrosis and emphysema (CPFE). Serum surfactant proteins (SPs) A, B, C and D levels may reflect lung damage. We evaluated serum SP levels in healthy controls, emphysema, IPF, and CPFE patients and their associations to disease severity and survival.Methods122 consecutive patients (31 emphysema, 62 IPF, and 29 CPFE) and 25 healthy controls underwent PFTs, ABG-measurements, 6MWT and chest HRCT. Serum levels of SPs were measured. Patients were followed-up for 1-year.ResultsSP-A and SP-D levels differed between groups (p = 0.006 and p<0.001 respectively). In post-hoc analysis, SP-A levels differed only between controls and CPFE (p<0.05) and CPFE and emphysema (p<0.05). SP-D differed between controls and IPF or CPFE (p<0.001 for both comparisons). In IPF SP-B correlated to pulmonary function while SP-A, correlated to the Composite Physiological Index (CPI). Controls current smokers had higher SP-A and SP-D levels compared to non-smokers (p = 0.026 and p = 0.023 respectively). SP-D levels were higher in CPFE patients with extended emphysema (p = 0.042). In patients with IPF, SP-B levels at the upper quartile of its range (≥26 ng/mL) presented a weak association with reduced survival (p = 0.05).ConclusionIn conclusion, serum SP-A and SP-D levels were higher where fibrosis exists or coexists and related to disease severity, suggesting that serum SPs relate to alveolar damage in fibrotic lungs and may reflect either local overproduction or overleakage. The weak association between high levels of SP-B and survival needs further validation in clinical trials.

Prognosis of combined pulmonary fibrosis and emphysema: comparison with idiopathic pulmonary fibrosis alone

“…Twelve trials reported the 1-year SR comparison of CPFE versus IPF alone. 8–15,17–20 There were no statistically significant differences in the 1-year SR between the CPFE group and the IPF alone group (RR = 0.98, 95% CI: 0.94–1.03, p = 0.47). Heterogeneity was not evident, as assessed by the statistics ( I 2 = 19%, p = 0.26) (Figure 2).…”

“…The 13 studies contained a total of 1710 participants (603 in the CPFE group and 1107 in the IPF alone group) published between 2009 and 2017. Two of the trials were conducted in Europe, 18,20 two in North America, 8,11 and the remaining nine trials in east Asia. 9,10,12–17,19 The number of participants in each study ranged from 17 to 365 individuals.…”

Lipid–Protein and Protein–Protein Interactions in the Pulmonary Surfactant System and Their Role in Lung Homeostasis

“…The finding that elderly people show reduced levels of SP-A in the lungs [109,110] suggests that ageing may aggravate the clinical consequences of surfactant deficiency, particularly in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis [111]. On the other hand, since lung collectins levels are usually reduced in the lung because of protein leakage towards the vascular compartment, serum levels of these proteins are considered biomarkers of disease severity and predictive factors of unfavorable disease outcome [112][113][114][115].…”

Matrix remodeling in chronic lung diseases

“…Finally, in smokers, development of upper lobe emphysema and lower lobe fibrosis, or combined pulmonary fibrosis and emphysema (CPFE), is a defined endotype that portends a poor prognosis [69, 70]. Little is known about the pathophysiological responses to cigarette smoke that can promote emphysema and fibrosis, but in one study that compared smokers with IPF, emphysema, or CPFE, serum SP-A and SP-D levels were higher in patients with fibrosis irrespective of emphysema and which also correlated with disease severity [71].…”