Nasal and systemic inflammation in Chronic Obstructive Pulmonary Disease (COPD)

Nicolai Obling,Vibeke Backer,John R Hurst,Uffe Bodtger

doi:10.1016/j.rmed.2022.106774

Abstract

Systemic inflammation is a well-established feature of Chronic Obstructive Pulmonary Disease, COPD, but less is known about inflammation in the upper airways in the disease. In the current study, we investigated the inflammatory profile in the upper airway and in serum in a cohort of patients with COPD.Patients were examined with inflammatory profiles measured on material from the upper airway and in serum using a 14-plex Bioplex multiplex immunoassay containing the following cytokines: IL-1-beta, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-17, IL-18, Interferon-gamma, Tumour Necrosis Factor-alpha, Tumour Necrosis Factor beta, and GM-CSF.We evaluated COPD disease burden using the CAT questionnaire and symptoms from the upper airways with the nasal domain of the 22 items Sino Nasal Outcome Test (SNOT22nasal).We included 180 patients (female 55%, age 67 (±8) years, FEV1% 52.4 (±16.6). Using a SNOT22nasal threshold of ≥6, we divided patients into high upper airways symptoms (high UAS), n = 74 (41%) and low upper airway symptoms (low UAS), n = 106 (59%). High UAS was significantly associated with higher levels of IL-1 beta and IL-3 in nasal samples (p = 0.016 and 0.02, respectively) and higher serum levels of IL-1 beta (p = 0.003). Upper airway scores correlated positively with nasal levels of IL-3 (rho = 0.195, p = 0.01) and serum levels of IL-1 beta (rho = 0.226, p = 0.005).Patients with COPD and high upper airway symptoms displayed signs of eosinophilic and neutrophilic inflammation with elevated levels of IL-1 beta and IL-3 in the nose and elevated IL-1 beta in serum.

Highlights

Chronic Obstructive Pulmonary Disease (COPD) is widely recognized as a disease associated with local and systemic inflammation
While many mechanisms remain to be elucidated, it is known that inhalation of smoke in genetically susceptible individuals leads to activation of lung epithelial cells, which secrete proinflammatory cytokines and chemokines, which are quantitatively and qualitatively different from those without a genetic predisposition
We aim to investigate the underlying inflammatory mechanisms behind these findings, and we hypothesize that upper airway symptoms in COPD can be attributed to a specific inflammatory profile involving eosinophilic cytokines

Summary

Introduction

Chronic Obstructive Pulmonary Disease (COPD) is widely recognized as a disease associated with local and systemic inflammation. While many mechanisms remain to be elucidated, it is known that inhalation of smoke in genetically susceptible individuals leads to activation of lung epithelial cells, which secrete proinflammatory cytokines and chemokines, which are quantitatively and qualitatively different from those without a genetic predisposition. These proin flammatory mediators result in the recruitment of innate immune cells into the parenchyma and airways, where locally active enzymes degrade the lung’s connective tissues resulting in small airway obstruction and emphysema [3]

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