Ultra-fine particles in induced sputum as a biomarker for lung inflammatory and functional state: a cross sectional study.

Background

The exposure to ambient particulate matter (PM) is associated with increased morbidity and mortality from respiratory, cardiovascular, and other causes. A major contribution to this adverse effect is attributed to particles at the nanoscale range (ultrafine particles [UFP] particles < 100 nm). Most of the information about human exposure to PM has been collected by environmental monitoring of inhaled particles.

Objectives

To evaluate the use of direct measuring of UFP in the sputum as a biomarker for lung inflammation and functional impairment.

Methods

The study population included 121 patients who underwent an induced sputum (IS) test as a part of a clinical evaluation for respiratory symptoms. Cell differential count was performed, and the UFP content was measured in each IS sample. The UFP content in the sputum was compared among patients with different inflammatory phenotypes based on IS granulocytes levels: eosinophilic inflammation (EI) IS eosinophils > 2.7%, neutrophilic inflammation (NI) IS neutrophils > 65%, and mixed granulocytic inflammation (MGI) including both IS eosinophils > 2.7% and IS neutrophils > 65%. The association between the IS-UFP content and pulmonary function test (PFT) parameters was also tested.

Results

Patients with MGI had a distinct profile of particles in IS, which was characterized by the highest percentage of UFP (relative to larger particles) compared to patients with EI, NI, or normal IS cell count. Furthermore, EI and NI were found to have an interaction effect regarding the IS-UFP profile, as demonstrated by the significantly different IS-UFP profile of patients with MGI compared to the profile associated with EI and NI independently. Last, the profile of UFP in the IS samples was also correlated with patient PFT. Reduced forced mid-expiratory flow (FEF) 25-75 or FEV1 were correlated with a higher IS-UFP mean size. Reduced FEF25-75 was correlated with a lower IS-UFP concentration and percentage relative to larger particles.

Conclusions

To the best of my knowledge, this study is the first to report a distinct IS-UFP profile in patients with MGI, which suggest an interaction effect of EI and NI on the IS-UFP content. This finding may further support the consideration of MGI as a distinct inflammatory phenotype, beyond the simple combination of EI and NI independently. In addition, reduced PFT parameters were associated with a specific change in the IS-UFP profile. The results of this study may shed light on the use of IS-UFP content as a biomarker for lungs inflammation and functional impairment. Further prospective studies are needed to establish a cause and effect relationship between lungs inflammation and functional impairment to the IS-UFP content.