Summary Airway epithelium is emerging as a regulator of innate immune responses to a variety of insults including cigarette smoke. The main goal of this study was to explore the effects of cigarette smoke extracts (CSE) on Toll‐like receptor (TLR) expression and activation in a human bronchial epithelial cell line (16‐HBE). The CSE increased the expression of TLR4 and the lipopolysaccharide (LPS) binding, the nuclear factor‐κB (NF‐κB) activation, the release of interleukin‐8 (IL‐8) and the chemotactic activity toward neutrophils. It did not induce TLR2 expression or extracellular signal‐regulated signal kinase 1/2 (ERK1/2) activation. The LPS increased the expression of TLR4 and induced both NF‐κB and ERK1/2 activation. The combined exposure of 16‐HBE to CSE and LPS was associated with ERK activation rather than NF‐κB activation and with a further increase of IL‐8 release and of chemotactic activity toward neutrophils. Furthermore, CSE decreased the constitutive interferon‐inducible protein‐10 (IP‐10) release and counteracted the effect of LPS in inducing both the IP‐10 release and the chemotactic activity toward lymphocytes. In conclusion, cigarette smoke, by altering the expression and the activation of TLR4 via the preferential release of IL‐8, may contribute to the accumulation of neutrophils within the airways of smokers.

Elite athletes show a high prevalence of symptoms and signs of asthma, but no study has assessed the acute effects of endurance exercise on airway cells in nonasthmatic athletes. We measured exhaled nitric oxide (NO) and collected samples of induced sputum after 3% NaCl aerosol administration for 20 min in nonasthmatic middle-aged amateur runners after the Fourth Palermo International Marathon and 6--9 wk later (habitual training period) at baseline. After the marathon, exhaled NO (n = 9 subjects) was higher [27 +/- 9 parts/billion (ppb)] than at baseline (12 +/- 4 ppb; P < 0.0005). Polymorphonuclear neutrophil (PMN) counts in induced sputum were much higher in runners (91.2 +/- 3.6% of total cells postmarathon and 78.7 +/- 9.1% at baseline) than in sedentary control subjects (9.9 +/- 5.9%; P < 0.001). Expression of L-selectin and CD11b/CD18 in sputum PMNs was lower after the race than at baseline and inversely related to the amount of exhaled NO (r = -0.66 and -0.69, respectively; P < 0.05). Our data indicate that sputum PMNs are increased in nonasthmatic runners both after a marathon and at baseline and suggest that NO may modulate exercise-associated inflammatory airway changes.

BackgroundClinical presentation phenotypes of obstructive sleep apnoea (OSA) and their association with comorbidity as well as impact on adherence to continuous positive airway pressure (CPAP) treatment have not been established.MethodsA prospective follow-up cohort of adult patients with OSA (apnoea-hypopnoea index (AHI) of ≥5/h) from 17 European countries and Israel (n = 6,555) was divided into four clinical presentation phenotypes based on daytime symptoms labelled as excessive daytime sleepiness (“EDS”) and nocturnal sleep problems other than OSA (labelled as “insomnia”): 1) EDS (daytime+/nighttime-), 2) EDS/insomnia (daytime+/nighttime+), 3) non-EDS/non-insomnia (daytime-/nighttime-), 4) and insomnia (daytime-/nighttime+) phenotype.ResultsThe EDS phenotype comprised 20.7%, the non-EDS/non-insomnia type 25.8%, the EDS/insomnia type 23.7%, and the insomnia phenotype 29.8% of the entire cohort. Thus, clinical presentation phenotypes with insomnia symptoms were dominant with 53.5%, but only 5.6% had physician diagnosed insomnia. Cardiovascular comorbidity was less prevalent in the EDS and most common in the insomnia phenotype (48.9% vs. 56.8%, p<0.001) despite more severe OSA in the EDS group (AHI 35.0±25.5/h vs. 27.9±22.5/h, p<0.001, respectively). Psychiatric comorbidity was associated with insomnia like OSA phenotypes independent of age, gender and body mass index (HR 1.5 (1.188–1.905), p<0.001). The EDS phenotype tended to associate with higher CPAP usage (22.7 min/d, p = 0.069) when controlled for age, gender, BMI and sleep apnoea severity.ConclusionsPhenotypes with insomnia symptoms comprised more than half of OSA patients and were more frequently linked with comorbidity than those with EDS, despite less severe OSA. CPAP usage was slightly higher in phenotypes with EDS.

Because endurance exercise causes release of mediators and growth factors active on the bone marrow, we asked whether it might affect circulating hematopoietic progenitor cells (HPCs) in amateur runners [ n = 16, age: 41.8 ± 13.5 (SD) yr, training: 93.8 ± 31.8 km/wk] compared with sedentary controls ( n = 9, age: 39.4 ± 10.2 yr). HPCs, plasma cortisol, interleukin (IL)-6, granulocyte colony-stimulating factor (G-CSF), and the growth factor fms-like tyrosine kinase-3 (flt3)-ligand were measured at rest and after a marathon (M; n = 8) or half-marathon (HM; n = 8). Circulating HPC counts (i.e., CD34+ cells and their subpopulations) were three- to fourfold higher in runners than in controls at baseline. They were unaffected by HM or M acutely but decreased the morning postrace. Baseline cortisol, flt3-ligand, IL-6, and G-CSF levels were similar in runners and controls. IL-6 and G-CSF increased to higher levels after M compared with HM, whereas cortisol and flt3-ligand increased similarly postrace. Our data suggest that increased HPCs reflect an adaptation response to recurrent, exercise-associated release of neutrophils and stress and inflammatory mediators, indicating modulation of bone marrow activity by habitual running.

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The European Respiratory Society (ERS) Research Seminar entitled "Pulmonary vascular endothelium: orchestra conductor in respiratory diseases - highlights from basic research to therapy" brought together international experts in dysfunctional pulmonary endothelium, from basic science to translational medicine, to discuss several important aspects in acute and chronic lung diseases. This review will briefly sum up the different topics of discussion from this meeting which was held in Paris, France on October 27-28, 2016. It is important to consider that this paper does not address all aspects of endothelial dysfunction but focuses on specific themes such as: 1) the complex role of the pulmonary endothelium in orchestrating the host response in both health and disease (acute lung injury, chronic obstructive pulmonary disease, high-altitude pulmonary oedema and pulmonary hypertension); and 2) the potential value of dysfunctional pulmonary endothelium as a target for innovative therapies.

The role of the arterial baroreflex in the cardiovascular changes associated with the obstructive sleep apnea syndrome (OSAS), and the effect of nasal continuous positive airway pressure (CPAP) treatment on baroreflex function during sleep are unknown. Baroreflex control of heart rate was studied in 29 normotensive patients with OSAS under no treatment, in 11 age-matched control subjects, and in 10 patients at CPAP withdrawal after 5.5 +/- 3.7 (range 3-14) months of treatment. Baroreflex control of heart rate was assessed by "sequence method" analysis of continuous blood pressure recordings (Finapres) obtained during nocturnal polysomnography. In untreated OSAS, baroreflex sensitivity (BRS) was low during wakefulness and non-rapid eye movement (REM) stage 2 sleep compared with control subjects, and correlated inversely with mean lowest Sa(O(2)) and the blood pressure increase after apneas. After CPAP treatment, the apnea-hypopnea index was lower, and mean lowest Sa(O(2)) higher than before treatment. After CPAP, patients were more bradycardic, blood pressure and its standard deviation decreased as Sa(O(2)) improved in non-REM stage 2 sleep, and BRS increased (nocturnal wakefulness: +59%; non-REM stage 2 sleep: +68% over pretreatment values). Our data suggest that baroreflex dysfunction in OSAS may be at least partly accounted for by nocturnal intermittent hypoxemia, and can be reversed by long-term CPAP treatment.

In spite of some differences among protocols, triathletes showed significant E during incremental exercise tests. Spontaneous E appeared to slightly improve ventilatory efficiency during CE and increasing GRADE protocols.