Surfactant Protein A in particles in exhaled air (PExA), bronchial lavage and bronchial wash - a methodological comparison

Annelie F Behndig, Ekaterina Mirgorodskaya, Anders Blomberg, Anna-Carin Olin, Annelie F Behndig, Ekaterina Mirgorodskaya, Anders Blomberg, Anna-Carin Olin

Abstract

Introduction: At present, there are few methods available for monitoring respiratory diseases affecting distal airways. Bronchoscopy is the golden standard for sampling the lower airways. The recently developed method for collecting non-volatile material from exhaled air - PExA (Particles in Exhaled air) is a promising new tool, but no direct comparison between the two methods has yet been performed. The aim of the present study was to compare sampling using PExA with bronchial wash (BW) representing the larger more proximal airways and broncho-alveolar lavage (BAL) representing the distal airways.

Methods: 15 healthy non-smoking subjects (7 female/8 male), age 28 ± 4 years, with normal lung function were included in the study. PExA-sampling (2 × 250 ng particles) and bronchoscopy with BW (2 × 20 ml) and BAL (3 × 60 ml sterile saline) was performed. Albumin and Surfactant Protein A (SP-A) were analyzed with ELISA, and analyses of correlation were performed.

Results: A significant association was found between BAL-fluid albumin and PExA-albumin (rs:0.65 p = 0.01). There was also an association between SP-A in PExA and BAL, when corrected for albumin concentration (rs:0.61, p = 0.015). When correlating concentrations of albumin and SP-A in bronchial wash and PExA respectively, no associations were found.

Conclusions: This is the first direct comparison between the bronchoscopy-based BW/BAL-fluids and material collected using the PExA methodology. Both albumin and albumin-corrected SP-A concentrations were significantly associated between BAL and PExA, however, no such association was found in either marker between BW and PExA. These results indicate that the PExA method samples the distal airways. PExA is thus considered a new promising non-invasive assessment for monitoring of the distal airways.

Conflict of interest statement

Anna-Carin Olin is a founder of PExA AB, and also a board-member and chair-holder of PExA AB.

Figures

Fig. 1
Fig. 1
Associations between albumin and surfactant protein A concentrations measured in PExA and bronchoscopy samples from healthy individuals. a There was a significant association between albumin in BAL-fluid and PEx. b-d There was no significant association between SP-A in PEx and BAL or between albumin or SP-A between PEx and BW and BAL respectively. Spearman’s correlation. A p-value <0.05 was considered significant
Fig. 2
Fig. 2
Associations between Surfactant Protein A collected with PExA and bronchoscopy (BW and BAL-fluid) after correction for albumin. a There was a significant association between SP-A in PEx and in BAL-fluid. b Again, no significant association was found between SP-A in PEx and in BW. Spearman’s correlation. A p-value <0.05 was considered significant

References

    1. Mead J. The lung's "quiet zone". N Engl J Med. 1970;282(23):1318–1319. doi: 10.1056/NEJM197006042822311.
    1. Hoyte FCL, Gross LM, Katial RK. Exhaled nitric oxide: An Update. Immunol Allergy Clin North Am. 2018;38(4):573–585. doi: 10.1016/j.iac.2018.06.001.
    1. Heijkenskjold-Rentzhog C, et al. Alveolar and exhaled NO in relation to asthma characteristics--effects of correction for axial diffusion. Allergy. 2014;69(8):1102–1111. doi: 10.1111/all.12430.
    1. Bos LD, Sterk PJ, Fowler SJ. Breathomics in the setting of asthma and chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2016;138(4):970–976. doi: 10.1016/j.jaci.2016.08.004.
    1. Almstrand AC, et al. Airway monitoring by collection and mass spectrometric analysis of exhaled particles. Anal Chem. 2009;81(2):662–668. doi: 10.1021/ac802055k.
    1. Almstrand AC, et al. Effect of airway opening on production of exhaled particles. J Appl Physiol. 2010;108(3):584–588. doi: 10.1152/japplphysiol.00873.2009.
    1. Larsson P, et al. Surfactant protein a and albumin in particles in exhaled air. Respir Med. 2012;106(2):197–204. doi: 10.1016/j.rmed.2011.10.008.
    1. Almstrand AC, et al. TOF-SIMS analysis of exhaled particles from patients with asthma and healthy controls. Eur Respir J. 2012;39:59–66. doi: 10.1183/09031936.00195610.
    1. Bredberg A, et al. Exhaled endogenous particles contain lung proteins. Clin Chem. 2012;58(2):431–440. doi: 10.1373/clinchem.2011.169235.
    1. Nathan N, et al. Surfactant protein a: a key player in lung homeostasis. Int J Biochem Cell Biol. 2016;81:151–155. doi: 10.1016/j.biocel.2016.11.003.
    1. Larstad M, et al. Surfactant protein a in exhaled endogenous particles is decreased in chronic obstructive pulmonary disease (COPD) patients: a pilot study. PLoS One. 2015;10(12):e0144463. doi: 10.1371/journal.pone.0144463.
    1. Ericson PA, et al. Low levels of exhaled surfactant protein a associated with BOS after lung transplantation. Transplant Direct. 2016;2(9):e103. doi: 10.1097/TXD.0000000000000615.
    1. Emilsson OI, et al. Respiratory symptoms, sleep-disordered breathing and biomarkers in nocturnal gastroesophageal reflux. Respir Res. 2016;17(1):115. doi: 10.1186/s12931-016-0431-7.
    1. Larsson P, et al. Exhaled particles as markers of small airway inflammation in subjects with asthma. Clin Physiol Funct Imaging. 2017;37:489–497. doi: 10.1111/cpf.12323.
    1. Soares M, et al. Particles in exhaled air (PExA): non-invasive phenotyping of small airways disease in adult asthma. J Breath Res. 2018;12(4):046012. doi: 10.1088/1752-7163/aad9d1.
    1. Phelps DS, et al. Increased surfactant protein-a levels in patients with newly diagnosed idiopathic pulmonary fibrosis. Chest. 2004;125(2):617–625. doi: 10.1378/chest.125.2.617.
    1. Betsuyaku T, et al. Effects of ageing and smoking on SP-A and SP-D levels in bronchoalveolar lavage fluid. Eur Respir J. 2004;24(6):964–970. doi: 10.1183/09031936.04.00064004.

Source: PubMed

3
Abonner