Alessandra Paternò

Metabolic syndrome, insulin resistance and sleepiness in real-life obstructive sleep apnoea

The metabolic syndrome shows a variable prevalence in obstructive sleep apnoea (OSA), and its association with insulin resistance or excessive daytime sleepiness in OSA is unclear. This study assessed the following in consecutive patients with newly diagnosed OSA: 1) the prevalence of metabolic syndrome; and 2) its association with insulin resistance and daytime sleepiness. Metabolic syndrome (National Cholesterol Education Program Adult Treatment Panel (NCEP-ATP) III criteria), insulin resistance (Homeostatic Model Assessment (HOMA) index, n=288) and daytime sleepiness (Epworth Sleepiness Scale) were assessed in 529 OSA patients. The prevalence of metabolic syndrome was 51.2%, which increased with OSA severity. Each metabolic syndrome component correlated with apnoea/hypopnoea index, but only blood pressure retained significance after correction for confounders. Both obesity and OSA contributed to metabolic abnormalities, with different sex-related patterns, since diagnosis of metabolic syndrome was significantly associated with neck circumference, age, body mass index and lowest arterial oxygen saturation in males, and with age and arousal index in females. The number of metabolic syndrome components increased with HOMA index (p<0.001). Prevalence of sleepiness was the same in patients with and without metabolic syndrome. The metabolic syndrome occurs in about half of “real-life” OSA patients, irrespective of daytime sleepiness, and is a reliable marker of insulin resistance.

Airway cells after swimming outdoors or in the sea in nonasthmatic athletes.

BACKGROUND Marathon runners and elite swimmers showed increased inflammatory cells in the airways at baseline. Although airway neutrophils increase further after a marathon race, the airway response to swimming is unknown. The aim of this study was to assess the effects of swimming on airway cells. To avoid the concomitant effects of chronic exposure to chlorine, the study was conducted in seven nonasthmatic swimmers [mean age (SD): 23.3 +/- 7.7 yr, training: 32 +/- 15 km.wk-1] habitually training in an outdoor pool (OP), i.e., a low-chlorine environment. METHODS Spirometry, exhaled nitric oxide (NO), induced sputum, and peripheral blood samples were obtained at baseline, after a 5-km trial in OP, and after a 5-km race in the sea (S), i.e., hypertonic airway exposure. RESULTS Airway neutrophil differential counts at baseline were higher in swimmers than in sedentary controls (N = 10), but cell counts, neutrophil elastase, and eosinophil cationic protein were unaffected by 5-km swimming. After swimming, L-selectin expression on airway cells decreased, suggesting exercise-induced cell mobilization into the airways and/or direct effects of hyperventilation on airway cells. After S, airway eosinophil differential counts increased slightly. Exhaled NO concentration was 19 +/- 6 ppb at baseline, 8 +/- 4 ppb after OP, and 21 +/- 7 ppb after S (P < 0.005 for OP vs baseline and S). CONCLUSIONS In swimmers not chronically exposed to high chlorine concentrations, data obtained at baseline suggest a direct relationship between airway neutrophilia and endurance training. The low L-selectin expression by airway cells postexercise suggests hyperventilation-induced cell recruitment or modulation of cell function. Hypertonic exposure of airways during exercise may slightly increase airway eosinophils and exhaled NO. Overall, 5-km swimming exerted smaller effects on airway cells than running a marathon.

Effects of extra‐fine inhaled beclomethasone/formoterol on both large and small airways in asthma

To cite this article: Scichilone N, Battaglia S, Sorino C, Paglino G, Martino L, Paternò A, Santagata R, Spatafora M, Nicolini G, Bellia V. Effects of extra‐fine inhaled beclomethasone/formoterol on both large and small airways in asthma. Allergy 2010; 65: 897–902.

Bronchial epithelial damage after a half-marathon in nonasthmatic amateur runners.

High neutrophil counts in induced sputum have been found in nonasthmatic amateur runners at rest and after a marathon, but the pathogenesis of airway neutrophilia in athletes is still poorly understood. Bronchial epithelial damage may occur during intense exercise, as suggested by investigations conducted in endurance-trained mice and competitive human athletes studied under resting conditions. To gain further information on airway changes acutely induced by exercise, airway cell composition, apoptosis, IL-8 concentration in induced sputum, and serum CC-16 level were measured in 15 male amateur runners at rest (baseline) and shortly after a half-marathon. Different from results obtained after a marathon, neutrophil absolute counts were unchanged, whereas bronchial epithelial cell absolute counts and their apoptosis increased significantly (P < 0.01). IL-8 in induced sputum supernatants almost doubled postrace compared with baseline (P < 0.01) and correlated positively with bronchial epithelial cell absolute counts (R(2) = 0.373, P < 0.01). Serum CC-16 significantly increased after all races (P < 0.01). These data show mild bronchial epithelial cell injury acutely induced by intense endurance exercise in humans, extending to large airways the data obtained in peripheral airways of endurance-trained mice. Therefore, neutrophil influx into the airways of athletes may be secondary to bronchial epithelial damage associated with intense exercise.

LTB4 is present in exudative pleural effusions and contributes actively to neutrophil recruitment in the inflamed pleural space.

The pleural space is a virtual compartment between the lung and chest wall that becomes filled with fluid and inflammatory cells during a variety of respiratory diseases. Here, we study the potential role of the eicosanoid metabolite leukotriene B4 (LTB4) in disparate diseases leading to acute (pneumonia) or chronic (tuberculosis, cancer) inflammation of the pleural space. LTB4 concentrations were significantly higher in pleural fluid due to pneumonia, tuberculosis and cancer with respect to congestive heart failure and correlated with neutrophil elastase, which is used as an indication of state of activation of neutrophils in the pleural space. Moreover, pleural LTB4 was biologically active, as an anti‐LTB4 antibody partially neutralized the chemotactic activity of parapneumonic, tuberculous and cancer effusions. Macrophages, neutrophils, lymphocytes, mesothelial cells and cancer cells all expressed mRNA for 5‐lipoxygenase, the enzyme that initiates leukotriene synthesis leading to the production of LTB4, in exudative pleural effusions. Upon stimulation in transudative pleural effusions, pleural macrophages produced, in a time‐dependent fashion, a significantly higher concentration of LTB4 than mesothelial cells. These studies demonstrate that different cell types are capable of producing LTB4 in the inflamed pleural space and that this mediator may play a crucial role in the recruitment of neutrophils into the pleural space.

Non-invasive markers of airway inflammation and remodeling in childhood asthma.

To evaluate the relationship between pro‐inflammatory and pro‐remodeling mediators and severity and control of asthma in children, the levels of IL‐8, MMP‐9, TIMP‐1 in induced sputum supernatants, the number of sputum eosinophils, as well as FeNO, were investigated in 35 asthmatic children, 12 with intermittent (IA) and 23 with moderate asthma (MA), and 9 controls (C). The patients with asthma were followed for 1 yr and sputum was obtained twice during the follow‐up. Biomarker levels were correlated with the number of exacerbations. We found that IL‐8, MMP‐9, TIMP‐1 and the numbers of eosinophils in induced sputum, as well as FeNO, were increased in children with IA and MA in comparison to C. The ongoing inflammation was confirmed by increased nuclear p65 NF‐κB subunit localization in sputum cells. In MA, FeNO measurements, sputum eosinophils and IL‐8 levels, positively correlated with the occurrence of disease exacerbations during a 1‐yr follow‐up. According to FeNO, sputum eosinophils and IL‐8 sputum concentrations, and the number of exacerbations, two distinct phenotypes of MA were identified. This study shows that the presence of bronchial inflammation is detectable in the airways of some IA, as well as in the airways of MA, despite the regular ICS treatment. This study also proposes the need to perform large prospective studies to confirm the importance of measuring specific biomarkers in induced sputum, concomitantly to FeNO analyses, to assess sub‐clinical airway inflammation and disease control in children with asthma.

Environmental conditions, air pollutants, and airway cells in runners: a longitudinal field study.

Abstract Runners have increased numbers of neutrophils in the airways at rest and after exercise compared with sedentary individuals. The aim of this study was to determine whether Mediterranean seasonal changes in temperature, humidity or airborne pollutants affect the airway cells of runners training outdoors in an urban environment. In nine male amateur runners, cell composition, apoptosis, and inflammatory mediators were measured in induced sputum collected at rest (baseline) and the morning after races held in the fall (21 km), winter (12 km), and summer (10 km). Concentrations of air pollutants were below the alert threshold at all times. Neutrophil differential counts tended to increase after all races (P = 0.055). Apoptosis of neutrophils increased with ozone (P < 0.005) and particulate matter <10 μm (PM10) (P < 0.05) exposure. Bronchial epithelial cell counts were low at all times and weakly correlated with ozone and PM10 concentrations. Apoptotic bronchial epithelial cells increased after all races (P < 0.05). Inflammatory mediators in induced sputum were low at baseline and after the races, and correlated with neutrophil differential counts only at rest. In conclusion, apoptosis of airway cells in runners appears to be affected by both exercise and environmental conditions. Apoptosis of neutrophils increased with exposure to environmental pollutants while apoptosis of bronchial epithelial cells increased after intense exercise. Since no relationship was observed between neutrophil counts and inflammatory mediators 20 h after races, airways inflammation at this time point appears blunted in healthy runners and little affected by exposure to mild seasonal changes and airborne pollutants.

The Effect of Intranasal Corticosteroids on Asthma Control and Quality of Life in Allergic Rhinitis with Mild Asthma

Background. The mechanisms through which rhinitis affects asthma have not been completely elucidated. We explored whether the effect of nasal treatment on asthma control and respiratory-related quality of life (HRQoL) is mediated by inflammatory changes of the upper and lower airways. Methods. Allergic rhinitics with mild asthma were randomized to a 14-day treatment period with either nasal budesonide 100 μg, 1 puff per nostril twice a day, or placebo. Clinical, functional, and biological evaluations were performed before and after treatment. Results. Twenty subjects (M/F: 10/10; age: 31 ± 15 years; mean ± SD) were enrolled, and a total of 17 individuals completely participated in the study. Lung function was within the normal range. The total asthma control test (ACT) score was 20 ± 5.3 and the RHINASTHMA Global Summary (GS) was 44 ± 15. The percentage proportion of eosinophils in nasal lavage was 9.9% and significantly correlated with spirometric parameters reflecting peripheral airway function (for FEF50: r = 0.48, p = .03; for FEF25: r = 0.47, p = .03). The pH of the exhaled breath condensate (EBC) was 7.33 ± 0.4. After nasal treatment, the percentage proportion of eosinophils fell significantly (p = .002), and changes in percentage proportion of eosinophils were associated with changes both in the ACT score (r = 0.76, p = .04) and in the RHINASTHMA GS (r = 0.77, p = .02). The increase in the pH of the EBC was not associated with changes in the ACT score or with the RHINASTHMA GS. Conclusions. These findings confirm that, in subjects with allergic rhinitis with mild asthma, nasal inflammation impacts on asthma control and HRQoL. The improved control of respiratory symptoms obtained with nasal corticosteroids seems to be mediated by functional changes in the peripheral airways.

Effects of exercise training on airway responsiveness and airway cells in healthy subjects

Airway responsiveness to methacholine (Mch) in the absence of deep inspirations (DIs) is lower in athletes compared with sedentary individuals. In this prospective study, we tested the hypothesis that a training exercise program reduces the bronchoconstrictive effect of Mch. Ten healthy sedentary subjects (M/F: 3/7; mean + or - SD age: 22 + or - 3 yr) entered a 10-wk indoor rowing exercise program on rowing ergometer and underwent Mch bronchoprovocation in the absence of DIs at baseline, at weeks 5 and 10, as well as 4-6 wk after the training program was completed. Exercise-induced changes on airway cells and markers of airway inflammation were also assessed by sputum induction and venous blood samples. Mean power output during the 1,000 m test was 169 + or - 49 W/stroke at baseline, 174 + or - 49 W/stroke at 5 wk, and 200 + or - 60 W/stroke at 10 wk of training (P < 0.05). The median Mch dose used at baseline was 50 mg/ml (range 25-75 mg/ml) and remained constant per study design. At the pretraining evaluation, the percent reduction in the primary outcome, the inspiratory vital capacity (IVC) after inhalation of Mch in the absence of DIs was 31 +/- 13%; at week 5, the Mch-induced reduction in IVC was 22 + or - 19%, P = 0.01, and it further decreased to 15 + or - 11% at week 10 (P = 0.0008). The percent fall in IVC 4-6 wk after the end of training was 15 + or - 11% (P = 0.87 vs. end of training). Changes in airway cells were not associated with changes in airway responsiveness. Our data show that a course of exercise training can attenuate airway responsiveness against Mch inhaled in the absence of DIs in healthy subjects and suggest that a sedentary lifestyle may favor development of airways hyperresponsiveness.

Asthmatics with high levels of serum surfactant protein D have more severe disease

Pulmonary surfactant is a mixture of lipids and surfactant-specific proteins that covers the alveolar surface, as well as the terminal conducting airways, lowering the surface tension at the air–liquid interface during breathing. The involvement of pulmonary surfactant in the pathophysiology of asthma has been suggested [1–4]. An interesting working hypothesis is that the surface tension of the peripheral airways is altered in asthma, because the inflammatory process affects the structure and function of surfactant, leading to excessive airway narrowing and features of air trapping. We explored whether serum levels of surfactant protein D (SP-D) in asthmatics are related to the severity of the disease. In addition, we aimed to assess whether serum SP-D correlated with functional abnormalities of peripheral airways. Serum surfactant protein D could serve as a biomarker of small airways damage and severity of asthma http://ow.ly/YdeG9