Integrin α E ß 7 (CD103) expression in bronchoalveolar lymphocytes of patients with hypersensitivity pneumonitis.

PURPOSE: CD4+/CD8+ ratio in bronchoalveolar lavage fluid (BALF) often retrieves contradictory findings when used for diagnosis of sarcoidosis and hypersensitivity pneumonitis (HP), so CD103+ has been investigated as a possible differential marker. We aimed to compare CD103+ expression in BALF T-lymphocytes between patients with HP, sarcoidosis and other interstitial lung diseases (ILD). METHODS: An observational study carried out over a 2-year period included consecutive patients with suspected ILD who underwent BALF as part of their initial diagnostic work-up; CD103+ expression on BALF T-lymphocytes was evaluated. After a final diagnosis established according to international criteria, three patient subgroups-HP, ILD (which included idiopathic interstitial pneumonia and connective tissue disease-associated lung disorders) and sarcoidosis-were considered for further analysis. RESULTS: A total of 77 subjects were enrolled, 20 with HP, 16 with other ILD and 41 with sarcoidosis. A significantly higher number of CD4+ CD103+ and CD8+ CD103+ lymphocytes were found in HP patients. Among patients with sarcoidosis, 12 (29.3 %) presented a BALF CD4+/CD8+ <3.5, all of them with histological confirmation. Compared to these patients, also statistically significant higher CD4+ CD103+ counts in HP patients were observed (p = 0.007). Among HP patients, although bird fanciers (n = 14) presented higher percentages of both CD4+ CD103+ and CD8+ CD103+ T-lymphocytes than those with work-related HP (n = 5), the differences did not reach statistical significance. CONCLUSIONS: Patients with HP present significantly higher counts of CD103+ T-lymphocytes in BALF, both in the CD4+ and CD8+ subsets, when compared to sarcoidosis, even with sarcoidosis subgroup presenting a BALF CD4+/CD8+ <3.5. The expression of CD103 may help in the interpretation of BALF data in these diffuse granulomatous lung disorders.

Neurogenic inflammation in allergen-challenged obese mice: A missing link in the obesity-asthma association?

AIM: A number of studies have shown an association between obesity and asthma. Controversy remains on the mechanisms supporting this association. In this study we aimed to assess neurogenic inflammation in a model of diet-induced obesity and allergen-challenged mice. METHODS: High fat diet-induced (HFD) obese Balb/c mice were sensitized and challenged with ovalbumin (OVA). Glucose, insulin, OVA-specific IgE and substance P (SP), and the main tachykinin involved in neurogenic inflammation, were quantified in sera. Cell counts were performed in bronchoalveolar lavage fluid (BALF). The extent of peribronchial infiltrates was estimated on lung tissue sections and inflammation was score based on inflammatory cell counts surrounding the bronchi. RESULTS: Obesity per se and allergen-sensitization per se increased serum SP (P = .027, P = .004, respectively). Further increased was observed in obese-sensitized mice (P = .007). Obese-sensitized mice also showed higher insulin (P = .0016), OVA-specific IgE (P = .016), peribronchial inflammatory score (P = .045), and tendency for higher glycemia. The interaction of obesity and asthma on SP levels was confirmed (P = .005, R(2) = 0.710). SP was positively correlated with metabolic (glycemia, r = 0.539, P = .007) and allergic inflammation parameters (BALF eosinophils, r = 0.445, P = 0.033; BALF mast cells, r = 0.574, P = .004; peribronchial inflammation score, r = 0.661, P < .001; and OVA-specific IgE, r = 0.714, P < .001). CONCLUSIONS: Our findings provide support to the neurogenic inflammation link between obesity and asthma in mice. These two conditions independently increased SP and the presence of both pathologies further increased this level. Neurogenic inflammation may be a previously unrecognized mechanism beyond the obese-asthma phenotype. Further studies are need to confirm this role of SP in human obesity-asthma association.

Differential responses of adiposity, inflammation and autonomic function to aerobic versus resistance training in older adults.

BACKGROUND: Increased body fat, autonomic dysfunction and low-grade chronic inflammation are interrelated risk factors implicated in the etiology of several chronic conditions normally presented by older adults. OBJECTIVE: This study aims to assess the effectiveness of different training protocols on reducing body fat, improving autonomic function, and decreasing low-grade systemic inflammation in community-dwelling elderly adults. METHODS: Fifty participants (11 men, 68±5.5years) were randomly allocated into resistance or aerobic training or control groups. Evaluations were done at baseline and following the 8-month intervention period on their body composition (assessed by DXA), inflammatory biomarkers (high-sensitivity C-reactive protein [hs-CRP], tumor necrosis-alpha [TNF-α], interferon-gamma [IFN-γ], interleukins-6 and -10 [IL-6, IL-10]), lipoproteic profile, fasting glycemia, blood pressure, heart rate variability (HRV; frequency and time domains) and aerobic fitness (assessed by six-minute walk distance [6MWD]). A paired t-test was used to detect changes (%Δ=[(post-test score-pretest score)/pre-test score]×100) within groups, while between-group differences were analyzed using the one-way ANOVA or General Linear Models. RESULTS: A significant change (Δ%) both in total (-5.4±6.3% and -3.3±2.9%, respectively) and central body fat (8.9±11.3% and -4.8±4.5%) was observed in resistance and aerobic training groups, respectively; along with a change in resting systolic and diastolic blood pressures (-9.2±9.8% and -8.5±9.6%), heart rate (-4.6±6.5%), hs-CRP (-18.6±60.6%), and 6MWD (9.5±6.9%) in response to aerobic training. CONCLUSIONS: The present findings provide further evidence for the benefits of aerobic and resistance training on reducing body fat. Aerobic training was demonstrated to reduce hs-CRP and blood pressure in community-dwelling elderly participants with no serious medical conditions.

Diagnostic value of CD103 expression in bronchoalveolar lymphocytes in sarcoidosis.

BACKGROUND: Pulmonary sarcoidosis is frequently characterized by a CD4(+)/CD8(+) ratio ≥3.5 in bronchoalveolar lavage fluid (BALF), although up to 40% of the cases present a normal or even decreased ratio, pointing out its variability and limitation as a diagnostic marker for sarcoidosis. Lung lymphocytes within the bronchial epithelium, the alveolar walls, and BALF express the integrin CD103. Our aim was to compare the expression of CD103 in BALF T-lymphocytes between sarcoidosis and other interstitial lung diseases (ILD) and to evaluate its relevance as a BALF diagnostic marker for sarcoidosis. METHODS: A total of 86 patients with ILD (mean age ± standard deviation, 42.6 ± 16.6 years; 60.5% female), who underwent BALF as part of their initial diagnostic work-up, were enrolled into 2 groups: sarcoidosis (n = 41) and other ILD (n = 45). Area under the receiver operating characteristic (ROC) curve (AUC) was used to describe the performance of CD103 for sarcoidosis diagnosis. RESULTS: Sarcoidosis patients presented a significantly reduced CD103 expression in BALF T-lymphocytes, more pronounced in the CD4(+) subset. The BALF CD103(+)CD4(+)/CD4(+) ratio for a cutoff point of 0.45 was associated with a better diagnostic performance for sarcoidosis (AUC: 0.86 [95% confidence interval (95% CI): 0.78-0.94]; sensitivity: 81%; specificity: 78%), even for those with a CD4(+)/CD8(+) ratio <3.5 (AUC: 0.79 [95% CI: 0.64-0.93]; sensitivity: 75%; specificity: 78%). CONCLUSIONS: Assessment of CD103 expression in BALF CD4(+) T-lymphocytes may be a reliable tool for sarcoidosis diagnosis, independently of CD4(+)/CD8(+) ratio, pointing out the relevance of evaluating the CD103(+)CD4(+)/CD4(+) ratio in the ILD diagnostic work-up.

Airway vascular damage in elite swimmers.

We postulated that high level swimming can promote airway inflammation and thus asthma by enhancing local vascular permeability. We aimed to test this hypothesis by a cross-sectional study comparing swimmers (n = 13, 17 ± 3 years, competing 7 ± 4 years, training 18 ± 3 h per week), asthmatic-swimmers (n = 6, 17 ± 2 years, competing 8 ± 3 years, training 16 ± 4 h per week), and asthmatics (n = 19, 14 ± 3 years). Subjects performed induced sputum and had exhaled nitric oxide, lung volumes, and airway responsiveness determined. Airway vascular permeability index was defined as the ratio of albumin in sputum and serum. Results from the multiple linear regression showed each unit change in airway vascular permeability index was associated with an increase of 0.97% (95%CI: 0.02 to 1.92; p = 0.047) in sputum eosinophilis, and of 2.64% (95%CI:0.96 to 4.31; p = 0.006) in sputum neutrophils after adjustment for confounders. In a general linear model no significant differences between airway vascular permeability between index study groups existed, after controlling for sputum eosinophilis and neutrophils. In conclusion, competitive swimmers training in chlorine-rich pools have similar levels of airway vascular permeability than asthmatics. Although competitive swimming has been associated with asthma, airway inflammation and airway hyperesponsiveness do not seem to be dependent on increased airway vascular permeability.