Exhaled and non-exhaled non-invasive markers for assessment of respiratory inflammation in patients with stable COPD and healthy smokers

Abstract

We aimed at comparing exhaled and non-exhaled non-invasive markers of respiratory inflammation in patients with COPD and healthy subjects and define their relationships with smoking habit. Forty-eight patients with stable COPD who were ex-smokers, 17 patients with stable COPD who were current smokers, 12 healthy current smokers and 12 healthy ex-smokers were included in a cross-sectional, observational study. Biochemical [prostaglandin (PG) E 2 , 15-F 2t -isoprostane, fraction of exhaled nitric oxide (F E NO)] and cellular (sputum cell counts) inflammatory outcomes and functional (spirometry) outcomes were measured in various biological matrices including exhaled breath condensate (EBC), exhaled breath, sputum supernatants, and urine. Sputum PGE 2 was elevated in both groups of smokers compared with ex-smoker counterpart (COPD: P < 0.02; healthy subjects: P < 0.03), whereas EBC PGE 2 was elevated in current (P = 0.0065) and ex-smokers with COPD (P = 0.0029) versus healthy exsmokers. EBC 15-F 2t -isoprostane, a marker of oxidative stress, was increased in current and exsmokers with COPD (P < 0.0001 for both) compared with healthy ex-smokers, whereas urinary 15-F 2t -isoprostane was elevated in both smoker groups (COPD: P < 0.01; healthy subjects: P < 0.02) versus healthy ex-smokers. F E NO was elevated in ex-smokers with COPD versus smoker groups (P = 0.0001 for both). These data suggest that the biological meaning of these inflammatory markers depends on type of marker and biological matrix in which is measured. An approach combining different types of outcomes can be used for assessing respiratory inflammation in patients with COPD. Large studies are required to establish the clinical utility of this strategy.Keywords: exhaled breath condensate, sputum, prostaglandin E 2 , 15-F 2t -isoprostane, fraction of exhaled nitric oxide, respiratory inflammation, chronic obstructive pulmonary disease Abstract word count: 252

Breathomics for Assessing the Effects of Treatment and Withdrawal With Inhaled Beclomethasone/Formoterol in Patients With COPD

“…In a breathomics multidimensional approach to assessment of drugs for COPD, we show anti-inflammatory effects of an extrafine beclomethasone/formoterol FDC pMDI vs. formoterol alone as reflected by reduced levels of sputum PGE 2 , a potent inflammatory mediator in the airways (Clarke et al, 2005; Holden et al, 2010), and EBC acetate which were found elevated in COPD patients (De Laurentiis et al, 2008, 2013; Airoldi et al, 2016; Santini et al, 2016). …”

Exhaled nitric oxide in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis

“…The sample size across studies varied from 21 to 212, with a total number of 1,669. The majority of studies were from Europe,10–12,15,18–20,22,23,26–30,33 with 1 study from Australia,17 1 study from America,13 2 studies from Africa,21,32 and 5 studies from Asia 14,16,24,25,31. In terms of diagnosis of COPD, 9 studies used doctor-diagnosis,13,15,17,21,23,29,31,32 8 studies used GOLD guideline,10,12,14,18,22,24,26,30,33 2 applied American Thoracic Society criteria,11,16 2 applied European Respiratory Society criteria,20,27 2 applied British Thoracic Society guidelines,19,28 and 1 applied Chinese Medical Association guidelines 25…”

Response of exhaled nitric oxide to inhaled corticosteroids in patients with stable COPD: A systematic review and meta‐analysis

“…Cigarette smoking is another potential confounding factor in FeNO measurements, with smoking COPD patients having lower FeNO than non‐smoking patients . We did not evaluate whether the findings differed between smokers and non‐smokers.…”