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Peripheral airway inflammation and dysfunction are key elements in the pathogenesis of COPD. The exhaled alveolar fraction of nitric oxide (CANO) is an indirect biomarker of lung peripheral inflammation. We tested whether inhaled long-acting bronchodilators (LABA) can affect CANO and we evaluated correlations with lung mechanics in patients with COPD. Two-centre, randomised, double blind, crossover study including COPD patients with moderate-to-severe airflow obstruction. Following a pharmacological washout, multi-flow exhaled fraction of NO (FENO), plethysmography, lung diffusion (DLCO), single breath nitrogen washout test and dyspnoea were measured in a crossover manner at baseline and 30, 60 and 180 min following administration of salmeterol (Sal) or formoterol fumarate (FF). (ClinicalTrials.gov, number NCT01853787). Fort-five patients were enrolled (median age: 71.8 years; 84.4% males). At baseline, CANO correlated with airway resistances (r = 0.422), residual volume/total lung capacity (RV/TLC; r = 0.375), transfer factor (r= -0.463) and forced expiratory volume in 1 s (FEV1; r= -0.375, all P < 0.01). After LABA administration, we found a significant reduction of FENO that reached statistical significance at 180'; no difference was found between FF and S. Consistently, a significant reduction of CANO was documented at 60' and 180' compared to baseline for both FF and S (P < 0.01 and P < 0.05, respectively). Changes in CANO were correlated with changes in vital capacity (r=-44; P < 0.001) and RV/TLC (r = 0.56; P < 0.001), but not FEV1. In COPD, direct correlations were found between the levels of CANO and the magnitude of peripheral airway dysfunction. LABA reduced CANO levels. The reduction was associated with improvement in functional parameters reflecting air trapping., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Small airways represent the key factor of chronic obstructive pulmonary disease (COPD) pathophysiology. The effect of different classes of bronchodilators on small airways is still poorly understood and difficult to assess. Hence the acute effects of tiotropium (18 µg) and indacaterol (150 µg) on closing volume (CV) and ventilation inhomogeneity were investigated and compared in 51 stable patients (aged 70 ± 7 yr, mean ± SD; 82% men) with moderate to very severe COPD. Patients underwent body plethysmography, arterial blood gas analysis, tidal expiratory flow limitation (EFL), dyspnea assessment, and simultaneous recording of single-breath N 2 test and transpulmonary pressure-volume curve (P L -V), before and 1 h after drug administration. The effects produced by indacaterol on each variable did not differ from those caused by tiotropium, independent of the severity of disease, assessed according to the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) scale and the presence of EFL. Bronchodilators significantly decreased the slope of phase III and CV (-5 ± 4 and -2.5 ± 2.1%, respectively, both P < 0.001), with an increase in both slope and height of phase IV and of the anatomical dead space. Arterial oxygen pressure and saturation significantly improved (3 ± 3 mmHg and 2 ± 2%, respectively, both P < 0.001); their changes negatively correlated with those of phase III slope ( r  = -0.659 and r  = -0.454, respectively, both P < 0.01). The vital capacity (VC) increased substantially, but the P L -V/VC curve above CV was unaffected. In conclusion, bronchodilators reduce the heterogeneity of peripheral airway mechanical properties and the extent of their closure, with minor effects on critical closing pressure. This should lessen the risk of small-airway damage and positively affect gas exchange. NEW & NOTEWORTHY This is the first study investigating in stable chronic obstructive pulmonary disease patients the acute effects of two long-acting bronchodilators, a β-agonist and a muscarinic antagonist, on peripheral airways using simultaneous lung pressure-volume curve and single-breath N 2 test. By lessening airway mechanical property heterogeneity, both drugs similarly reduced ventilation inhomogeneity and extent of small-airway closure, as indicated by the decrease of phase III slope, increased oxygen saturation, and fall of closing volume, often below expiratory reserve volume., (Copyright © 2017 the American Physiological Society.)

Objectives: Fibromyalgia (FM) is characterised by chronic musculoskeletal pain, autonomic nervous system (ANS) dysfunction, and disturbed sleep. The aim of this study was to evaluate the influence of ANS dysfunction on the genesis of sleep disorders., Methods: Fifty female FM patients and 45 healthy subjects matched for age, gender and body mass index underwent a clinical, polysomnographic and autonomic profile evaluation at rest and during a tilt test in order to determine muscle sympathetic nerve activity (MSNA), plasma catecholamine levels, and the spectral indices of cardiac sympathetic (LFRR) and vagal (HFRR) modulation computed by means of the spectrum analysis of RR during sleep., Results: The FM patients had a higher heart rate (HR), more MSNA and a higher LF/HF ratio, and lower HFRR values at rest (p<0.05), and showed no increase in MSNA, a smaller decrease in HFRR, and an excessive rate of syncope (46%) during the tilt test. Their sleep was less efficient (p<0.01), and they had a higher proportion of stage 1 non-REM sleep (p<0.001), experienced many arousals and periodic limb movements (PLMs) per hour of sleep (p<0.001) and a high proportion of periodic breathing (PB%) (p<0.0001). Their cyclic alternating pattern (CAP) rate was significantly increased (p<0.001). During sleep, they had a higher HR and LF/HF ratio, and a lower HFRR (p<0.001). The number of tender points, CAP rate, PB% and PLMI correlated positively with HR and the LF/HF ratio, and negatively with HFRR during sleep., Conclusions: Our findings seem to show that sleep causes the same effects as a stressful test in FM patients. A vicious circle is created during sleep: pain increases sympathetic cardiovascular activation and reduces sleep efficiency, thus causing lighter sleep, a higher CAP rate, more arousals, a higher PLMI, and increasing the occurrence of PB, which gives rise to abnormal cardiovascular neural control and exaggerated pain sensitivity.