The prevalence of nasal polyps and the corresponding urinary LTE4 levels in severe compared to mild and moderate asthma.

BACKGROUND: Several comorbid conditions may contribute to worsening asthma symptoms, including nasal polyps (NPs). Cysteinyl leukotrienes (Cys-LTs) play a crucial role in asthma pathophysiology, and specific receptors for CysLTs are reported as upregulated in nasal polyp tissues. The aim of the present study was to assess the prevalence of nasal polyps in severe vs. mild and moderate asthma, and to compare the corresponding levels of urinary Leukotriene E4 (LTE4). MATERIALS AND METHODS: A cohort of 386 asthma patients were studied: n=166 with mild, n=146 with moderate and n=74 severe asthma. All patients performed a nasal endoscopy and urine were collected in the morning for the quantitative LTE4 immunoenzimatic assay (Cayman Chemical, MI, USA). Intolerance to ASA was also assessed by means of a nasal provocation test with L-ASA. RESULTS: The prevalence of NPs was the following: 8 cases (4.8%) in mild; 14 (9.6%) in moderate, and 33 (44.6%) in severe asthma. Mean urinary LTE4 levels were increasing according to the disease severity. ASA-intolerance was assessed in 1 patient in mild asthma (0.6%), 14 in moderate asthma (9.6%) and 28 in severe asthma (37.8%). CONCLUSIONS: Nasal polyps represent a comorbid which is highly frequent in severe asthma. Both their prevalence and the corresponding mean LTE4 levels in urine proved in strict, direct relationship with asthma severity. In severe asthma, nasal polyps represent a condition which is associated with the highest excretion of urinary LTE4 and ASA intolerance.

Comprehensive effects of supplemented essential amino acids in patients with severe COPD and sarcopenia.

AIM: Aim of the study was to investigate whether or not oral supplementation of essential amino acids (EAAs) may improve body composition, muscle metabolism, physical activity, cognitive function, and health status in a population of subjects with severe chronic obstructive pulmonary disease (COPD) and sarcopenia. METHODS: Thirty-two patients (25 males) (FEV1/FVC < 40% predicted), age 75 +/- 7 years, were randomised (n = 16 in both groups) to receive 4 gr/bid EAAs or placebo according to a double-blind design. When entered the study (T0), after four (T4), and after twelve (T12) weeks of treatments, body weight, fat free-mass (FFM), plasma lactate concentration (micromol/l), arterial PaCO2 and PaO2, physical activity (n degree steps/day), cognitive function (Mini Mental State Examination; MMSE), health status (St. George's Respiratory Questionnaire; SGRQ) were measured. RESULTS: EAAs supplemented, but not patients assuming placebo, progressively improved all baseline variables overtime. In particular, at T12 of EAAs supplementation, body weight (BW) increased by 6 Kg (p = 0.002), FFM by 3.6 Kg (p = 0.05), plasma lactate decreased from 1.6 micromol/l to 1.3 micromol/l (p = 0.023), PaO2 increased by 4.6 mmHg (p = 0.01), physical activity increased by 80% (p = 0.01). Moreover, the score for cognitive dysfunction improved from 19.1 scores to 20.8 (p = 0.011), while the SRGQ score also improved from 723 to 69.6 even though this trend did not reach the statistical significance. CONCLUSIONS. A three-month EAAs supplementation may have comprehensive effects on nutritional status; muscle energy metabolism; blood oxygen tension, physical autonomy; cognitive function, and perception of health status in patients with severe COPD and secondary sarcopenia.

Inhaled corticosteroids in stable COPD patients: do they have effects on cells and molecular mediators of airway inflammation?

STUDY OBJECTIVE: To investigate possible changes in cells and molecular mediators of airway inflammation following inhaled steroid treatment of stable COPD patients. DESIGN: Six-week open preliminary prospective study. SETTING: A university respiratory disease clinic. PATIENTS: : Stable COPD patients with mild disease. INTERVENTION: Six-week treatment with inhaled beclomethasone (1.5 mg die). MEASUREMENTS: The levels of interleukin (IL)-8, myeloperoxidase, eosinophilic cationic protein and tryptase, and cell numbers in bronchial lavage specimens were determined, and the symptom score, the endoscopic bronchitis index, and functional parameters were recorded. RESULTS: After treatment there were significant reductions in the lavage levels of IL-8 ([mean +/- SEM] 1,603.4 +/- 331.2 vs 1,119.2 +/- 265.3 pg/mL, respectively; p = 0. 01) and myeloperoxidase (1,614.5 +/- 682.3 vs 511.2 +/- 144.2 microg/L, respectively; p = 0.05), in cell numbers (250.6 +/- 27.7 vs 186.3 +/- 11.5 cells x 10(3)/mL, respectively; p = 0.04), neutrophil proportion (59.7 +/- 14.3% vs 31.5 +/- 10.1%; p = 0.01), symptom score (4.5 +/- 0.6 vs 1.4 +/- 0.5; p = 0.01), and bronchitis index (8.5 +/- 0.8 vs 5.5 +/- 0.7; p = 0.007). CONCLUSIONS: In stable patients with COPD, inhaled steroid treatment may induce changes on some cellular and molecular parameters of airway inflammation.

Predominant TH1 cytokine pattern in peripheral blood from subjects with chronic obstructive pulmonary disease.

BACKGROUND: Previous studies have provided evidence for an inflammatory process in the large airways of subjects with chronic obstructive pulmonary disease (COPD), consisting predominantly of activated T cells. No data are available on the TH1 /TH2 T-cell cytokine pattern in this disease. OBJECTIVE: We sought to characterize the TH1 /TH2 T-cell cytokine pattern in subjects with COPD. METHODS: We examined the IFN-gamma and IL-4 expression in peripheral blood CD4+ and CD8+ T cells from 20 patients with COPD and 25 control subjects by using a flow cytometric method of intracellular cytokine detection. We also examined the expression of 2 surface activation markers (CD25 and HLA-DR) on peripheral blood CD4+ and CD8+ T cells. RESULTS: There was an increased percentage of IFN-gamma-producing cells (30.3% [range, 12.9% to 60.4%] vs 19.1% [range, 4% to 31.2%], P =.003) and a decreased percentage of IL-4-producing cells (4.55% [range, 0.6% to 11.3%] vs 9.5% [2.1% to 21.3%], P =.0008) among peripheral blood CD4+ T cells from the patients with COPD compared with control subjects. There was no significant difference between the 2 groups in the percentage of peripheral blood CD8+ T cells producing IFN-gamma or IL-4 or in the percentage of peripheral blood CD4+ and CD8+ T cells expressing CD25 and HLA-DR. CONCLUSION: These findings provide evidence for a TH1 -like immune response of peripheral blood CD4+ T cells in subjects with COPD.

Neutrophils infiltrating bronchial epithelium in chronic obstructive pulmonary disease.

In order to characterize neutrophil and eosinophil presence in the airways of patients with chronic obstructive pulmonary disease (COPD), bronchoscopy with bronchial washings and bronchial biopsies was performed in 12 smoking stable COPD subjects and 18 normal non-smoking control subjects. Bronchial biopsies were examined by light microscopy using plastic embedding and histochemical techniques to identify different cell types. Bronchial washing fluid of COPD patients was characterized by a predominance of neutrophils (P = 0.001), and a slight, but significant (P = 0.03), increase of eosinophil fraction. Subjects with COPD had higher number of neutrophils in the epithelium (P = 0.01), and eosinophils in the lamina propria (P = 0.01) than did control subjects. The thickness of reticular basement membrane was increased for COPD patients in comparison to control subjects (P = 0.01). The present study provides evidence of neutrophil infiltration both in bronchial washing and bronchial epithelium of patients with COPD, suggesting that the source of neutrophils in airway lumen may be the bronchial mucosa. Although less common than in asthma, airways of COPD subjects reveal eosinophil presence and airway remodelling.

Inflammatory cells and mediators in bronchial lavage of patients with chronic obstructive pulmonary disease.

Cigarette smoking is the most important cause of chronic obstructive pulmonary disease (COPD). Although the precise sequence of events that leads a smoker to experience airway obstruction is not completely clear, airway inflammation is a relevant factor. To investigate airway inflammation, 12 nonatopic smoking COPD patients with a forced expiratory volume in one second (FEV1) < or = 75% predicted and 10 normal nonsmoking subjects (NS) were studied with bronchoscopy and bronchial lavage (BL). Serum immunoglobulin (Ig)E levels of COPD patients correlated with the smoking history (r=0.7, p=0.008). In BL of COPD patients there was an increase of neutrophils (median, range) (COPD 62.6x10(3), 1.2-323, NS 1.35, 0-19.2, p=0.001), eosinophils (COPD 1.6, 0-6.9, NS 0.15, 0-3.7, p=0.035), the levels of interleukin (IL)-8 (COPD 1079 pg x mL(-1), 121-2,500, NS 20.4, 7.2-59, p=0.001), myeloperoxidase (MPO) (COPD 752 microg x L(-1), 11-5,500, NS 22.1, 8-70, p=0.001) and eosinophil cationic protein (ECP) (COPD 21.5 microg x L(-1), 1.8-161, NS 2, 1.8-4.9, p=0.001). Significant correlations were found in BL of COPD patients between IL-8 and neutrophils (p=0.02), MPO and neutrophils (p=0.02), IL-8 and MPO (p=0.0001) and ECP and eosinophils (p=0.02). In addition, the ratios between the BL levels of MPO and the number of neutrophils and between ECP levels and eosinophils were higher in COPD patients than in NS (p=0.03 and 0.01, respectively). These data suggest that cigarette smoke is associated with increased amounts of airway interleukin-8, a chemotactic factor for neutrophils and eosinophils. Recruited neutrophils and eosinophils are activated and they release increased amounts of inflammatory mediators capable of damaging the bronchial tissue.

Specific immunotherapy downregulates peripheral blood CD4 and CD8 T-lymphocyte activation in grass pollen-sensitive asthma.

Several lines of evidence indicate that specific immunotherapy may act by modifying the immune responses of T-lymphocytes to the antigen. To evaluate the effect of specific immunotherapy on the activation of T-lymphocytes by cluster of differentiation cells (CD4+ and CD8+) in peripheral blood, the expression of two surface activation markers, the p55 interleukin-2 receptor (CD25) and human leucocyte antigen (HLA)-DR, was studied prospectively on circulating CD4+ and CD8+ T-cell subsets in subjects with grass-pollen sensitive asthma before and after 1 yr of treatment with specific immunotherapy. Twenty five asthmatic patients with pollen sensitivity other than grass, studied out of their pollen season, served as the control group. Specific immunotherapy improved clinical indices of disease activity including symptom scores and medication use during the pollen season of the treatment year. It had a marked effect in reducing the expression of the two activation markers, CD25 and HLA-DR, in both CD4+ (p=0.002 and p=0.005, respectively) and CD8+ (p=0.01 and p=0.01, respectively) T-cell subsets, in parallel with a significant decrease in CD23 expression on B-cells (p=0.008) and in grass-specific immunoglobulin E levels (p=0.01) in the peripheral blood of subjects with grass pollen-sensitive asthma. The decreased T-lymphocyte activation observed in immunotherapy-treated subjects after the treatment year was significant (p=0.05) in comparison with the control group. These data add to the view that the efficacy of specific immunotherapy may be attributed to the downregulation of T-cell responses.

Inhaled beclomethasone dipropionate downregulates CD4 and CD8 T-lymphocyte activation in peripheral blood of patients with asthma.

BACKGROUND: Previous studies demonstrated a downregulation of T-lymphocyte (CD3+ cells) activation in peripheral blood after treatment with inhaled corticosteroids in patients with asthma. OBJECTIVE: This study was carried out to evaluate the effect of inhaled corticosteroids on CD4 and CD8 T-lymphocyte activation, respectively. METHODS: We examined the expression of three surface activation markers (CD25, HLA-DR, and very late activation antigen 1) on circulating CD4+ and CD8+ T-cell subsets in subjects with asthma (n = 23) before and 8 weeks after treatment with inhaled beclomethasone dipropionate dry powder (daily dose, 800 microg). RESULTS: Beclomethasone dipropionate treatment had a marked effect in reducing the expression of the activation marker CD25 (p < 0.01) in both CD4+ and CD8+ T-cell subsets in peripheral blood of patients with asthma. However, no correlation was found between the downregulation of CD4 and CD8 T-lymphocyte activation and the improvement in physiologic indices of disease activity. CONCLUSIONS: These data add to the view that CD4+ and CD8+ T lymphocytes in peripheral blood of patients with asthma are in an activated state that is downregulated by inhaled corticosteroids.

Effect of S-adenosyl-L-methionine on brain muscarinic receptors of aged rats.

The number of muscarinic receptors in the striatum and hippocampus of aged rats is significantly lower than the number measured in young animals. The treatment of aged rats for 30 days with S-adenosyl-L-methionine (SAM) restored the number of muscarinic receptors to levels found in the striatum and hippocampus from young animals. We did not observe a clear-cut difference between the dissociation constants of untreated young and untreated or SAM-treated aged rats, whereas the binding capacity varied. Moreover, in vitro addition of SAM to hippocampal membranes from aged rats resulted in a significant increase in the number of binding sites. This in vitro effect was antagonized by S-adenosyl-L-homocysteine, a specific in vitro inhibitor of methyltransferase activity. The reduction in the muscarinic receptor density could be related to a decrease in neuronal membrane fluidity induced by aging, while its increase after SAM treatment might be ascribed to the ability of this methyl donor to increase the fluidity of cell membranes by stimulating phospholipid synthesis.