This study provides evidence that male smokers without severe airway symptoms develop an increasing systemic inflammation during a 6-year period. The study forwards both direct and indirect evidence that MPO may be an early marker of this systemic inflammation. However, our study also forwards indirect evidence that ongoing tobacco smoking may "drive" the level of systemic HNL and lysozyme. The origin of the increased MPO and its value as an easily measured predictor for future COPD deserves to be further evaluated.

In healthy, elderly never-smokers a low extent of various HRCT findings has to be considered normal. Emphysema, parenchymal nodules, and ground-glass opacities are indicative of smoking-induced disease. Further progress may cease if smoking is stopped.

A current hot topic in COPD is that two “fixed triple” combinations of an inhaled corticosteroid (ICS), a long-acting β 2 -agonist (LABA) and a long-acting muscarinic antagonist (LAMA) in a single inhaler have become available for patients with COPD, and a third triple therapy is in advanced development with the first large randomised clinical trial (RCT) recently published in Lancet Respiratory Medicine [1]. The triple therapies available in a single inhaler are: beclomethasone-dipropionate/formoterol/glycopyrronium (BDP/FF/G); fluticasone-furoate/vilanterol/umeclidinium (FLF/VI/UMEC); and budesonide/glycopyrronium/formoterol (B/G/F).

We examined whether systemic cytokine signaling via interleukin (IL)-17 and growth-related oncogene-α (GRO-α) is impaired in smokers with obstructive pulmonary disease including chronic bronchitis (OPD-CB). We also examined how this systemic cytokine signaling relates to bacterial colonization in the airways of the smokers with OPD-CB. Currently smoking OPD-CB patients (n=60, corresponding to Global initiative for chronic Obstructive Lung Disease [GOLD] stage I–IV) underwent recurrent blood and sputum sampling over 60 weeks, during stable conditions and at exacerbations. We characterized cytokine protein concentrations in blood and bacterial growth in sputum. Asymptomatic smokers (n=10) and never-smokers (n=10) were included as control groups. During stable clinical conditions, the protein concentrations of IL-17 and GRO-α were markedly lower among OPD-CB patients compared with never-smoker controls, whereas the asymptomatic smoker controls displayed intermediate concentrations. Notably, among OPD-CB patients, colonization by opportunistic pathogens was associated with markedly lower IL-17 and GRO-α, compared with colonization by common respiratory pathogens or oropharyngeal flora. During exacerbations in the OPD-CB patients, GRO-α and neutrophil concentrations were increased, whereas protein concentrations and messenger RNA for IL-17 were not detectable in a reproducible manner. In smokers with OPD-CB, systemic cytokine signaling via IL-17 and GRO-α is impaired and this alteration may be linked to colonization by opportunistic pathogens in the airways. Given the potential pathogenic and therapeutic implications, these findings deserve to be validated in new and larger patient cohorts.