Sublingual immunotherapy and regulatory T cells.
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Administration, Sublingual↗
Biomedical subjects
M Milanese
Publications and source records attributed to M Milanese.
CCR5 promoter polymorphisms and HIV-1 perinatal transmission in Brazilian children.
The frequencies of four CCR5 promoter polymorphisms, and of the Delta32 deletion, have been evaluated in Brazilian HIV-1 positive (HIV+) and HIV-1 negative (HIV-) children, both born from HIV-1 positive mothers and healthy controls (HC), with the aim of investigating whether CCR5 polymorphisms could be associated to vertical transmission of HIV-1. One hundred and six HIV-1 positive children and 70 HIV-1 negative children were enrolled from impoverished areas of Recife (Brazil). We recruited also as healthy controls 104 uninfected children from the same ethnic background, matched for age and known to be not at risk for HIV-1 infection. CCR5 polymorphisms were detected by PCR amplification and direct sequencing. Although no significative divergence was found for CCR5 Delta32, CCR5-59356-C/T and CCR5-59653 C/T polymorphisms, the frequency of CCR5-59353-T/C and CCR5-59402-A/G genotypes differed among HIV+, HIV- and HC children. The presence of the CCR5-59353-TT genotype indicated a trend for increased risk of vertical transmission of HIV-1 infection in Brazilian children, while the presence of the CCR5-59402-AA genotype is suggestive for a protective effect against HIV-1 vertical transmission.
Brazil↗
Eosinophils, specific hyperreactivity and occurrence of late phase reaction in allergic rhinitis.
BACKGROUND: Eosinophil infiltration may be considered characteristic of nasal allergic inflammation. However, a mild inflammatory infiltrate may be present in asymptomatic subjects exposed to specific allergen. OBJECTIVE: We investigated the relationship between inflammation, specific hyperreactivity and clinical late phase reactions in allergic subjects using the ASNC model. METHODS: Sixty allergic subjects (aged from 18 to 47 years) were enrolled among those sensitized to pollens (n=20) and those to house dust mite with (n=20) or without (n=20) known clinical nasal LPR. All subjects were asymptomatic. TNSS and eosinophil number were assessed at baseline, 30 min (early phase) and 6 hours (late phase) after ASNC. RESULTS: Eosinophil number was higher in LPR+ rhinitics than in other groups, at baseline and during the early and late phase (p<0.001). ATD was lower in LPR+ rhinitics than in other groups (p<0.001). In LPR+ rhinitics, at baseline there was a significant correlation between eosinophils and ATD (r=0.56, p=0.009). After allergen challenge, TNSS was significantly higher in LPR+ rhinitics than in other groups, both during early and late phase (p<0.001 for all comparisons). CONCLUSIONS: In house dust mite sensitised subjects, LPR occurrence after allergen challenge is associated with higher inflammation and lower ATD at baseline. Therefore, in house dust mite allergy minimal persistent inflammation without symptoms can drive different clinical responses to allergen challenge.
Adolescent↗
Time-course of diastolic dysfunction in different stages of chronic HCV related liver diseases.
AIM: A hyperdynamic circulatory pattern in advanced liver disease is known since a long time. The first studies evaluating cardiac function in cirrhosis were performed in patients with alcoholic liver disease and thus this condition was attributed to the toxic effects of ethanol. A reduced performance of the left ventricle after physical and pharmacological strains along with an altered diastolic function has been demonstrated also in postviral cirrhosis. Many factors are involved in advanced cirrhosis whereas little is known in the earlier stages of disease. METHODS: To this aim we have investigated patients with different stages of hepatitis C virus (HCV)-related liver disease to detect the time-course of diastolic dysfunction. An impaired relaxation and increased thickness of left ventricular walls along with an altered pattern of transmitral flow can be easily detected by means of echocardiography. RESULTS: In chronic hepatitis diastolic function is preserved but increased thickness of left ventricle parietal walls can be detected in patients with fibrosis on liver biopsy. The typical pattern of diastolic dysfunction is observed in Child A cirrhotic patients and in Child C ascitic patients but thickness of parietal walls is more relevant in the former group. Chronic aldosterone blockade could exert favourable effects in heart remodeling suggesting a potential role of these drugs in cirrhotic cardiomyopathy. CONCLUSIONS: The presence of increased thickness of left ventricle parietal walls in chronic hepatitis C in the precirrhotic stage point to a putative role of HCV in this heart structural abnormality that can become a co-factor in the more advanced stages of cirrhosis when portal hypertension and its deleterious effects on systemic hemodynamics, cardiac function and structure become manifest.
Aged↗
Airway function and nasal inflammation in seasonal allergic rhinitis and asthma.
BACKGROUND: Allergic rhinitis (AR) and asthma are frequently associated and characterized by a Th2-dependent inflammation. Nasal and bronchial obstruction may be objectively measured. OBJECTIVE: The aim of this study was to evaluate the relationships among upper and lower airway function and nasal inflammation in subjects with seasonal allergic rhinitis (SAR) and asthma. METHODS: Twenty out-patients (12 males and eight females, mean age: 23.4+3.6 years) with SAR and asthma were evaluated during the pollen season. All of them showed a moderate-severe grade of nasal obstruction. Total symptom score, rhinomanometry, spirometry, nasal lavage, and nasal scraping were obtained in all subjects. Eosinophils were counted by conventional staining; IL-4 and IFN-gamma were measured by immunoassay on fluids recovered from nasal lavage. RESULTS: Functional parameters, i.e. nasal airflow and forced expiratory volume in 1 s (FEV(1)), were correlated with nasal eosinophils (R(2)>0.83, P<0.001). Inflammatory parameters, i.e. eosinophils were correlated with immunological parameters, i.e. IL-4 and IFN-gamma levels (R(2)=0.93, P<0.001). Nasal symptoms were correlated with nasal airflow (rho=-0.71, P< or =0.01) and eosinophils (rho=0.72, P<0.01). Nasal airflow was correlated with FEV(1) (r=0.89, P<0.0001). CONCLUSIONS: This study demonstrates the close connection between Th2 cytokines and eosinophil infiltration in the nose. There is also clear evidence concerning the relationships between eosinophils infiltration and cytokines levels. Nasal eosinophils can be regarded as the most important predictors of upper and lower airway functions. These findings constitute first evidence of a relationship among nasal Th2-related inflammation and nasal and bronchial airflow in patients with SAR and asthma.
Adult↗
Prevention of MRSA pneumonia by oral vancomycin decontamination: a randomised trial.
This study was undertaken to assess whether oropharyngeal vancomycin may control oropharyngeal carriage and lower airway infection due to methicillin-resistant Staphylococcus aureus (MRSA) acquired in the intensive care unit (ICU). Secondary endpoints were the emergence of vancomycin-resistant enterococci, vancomycin-intermediate S. aureus and vancomycin consumption. A total of 84 patients, admitted to a medical/surgical ICU and mechanically ventilated for >72 h, were randomly assigned to control (n=42) or test (n=42) group. Both groups received the protocol of selective decontamination of the digestive tract, including polymyxin E, tobramycin and amphotericin B. Patients in the test group received 0.5 g of a 4% vancomycin gel at 6-h intervals in the oropharynx. Lower airway infections due to MRSA acquired on the ICU were reduced in the test group, as was oropharyngeal carriage. Neither vancomycin-resistant enterococci nor vancomycin-intermediate S. aureus were isolated from either surveillance or diagnostic samples during the study period. The vancomycin costs were lower in the test group. This study demonstrates that oropharyngeal vancomycin, which controls intensive care unit-acquired lower airway infections and secondary carriage due to methicillin-resistant Staphylococcus aureus, is cost-effective and safe in terms of vancomycin-resistant enterococci and vancomycin-intermediate Staphylococcus aureus.
Administration, Oral↗
Cetirizine reduces cytokines and inflammatory cells in children with perennial allergic rhinitis.
Cetirizine has been demonstrated able of reducing nasal inflammatory infiltration in children with allergic rhinitis and cytokine production in in vitro studies. The aim of this double-blind, placebo-controlled, and randomized study was to evaluate cytokine pattern and inflammatory cells in children with perennial allergic rhinitis, before and after treatment with cetirizine or placebo. Twenty children with perennial allergic rhinitis were evaluated, 13 males and 7 females (mean age 13.4 years). Inflammatory cells and cytokines were evaluated by scraping and nasal lavage, before and after 2-weeks administration of cetirizine or placebo. IL4 and IL8 were measured by immunoassay and inflammatory cells were counted by conventional staining. Cetirizine treatment induced a significant decrease of IL4 (p<0.01) and IL8 levels (p=0.01). A significant reduction of the inflammatory cells was detected in actively-treated children, both concerning neutrophils and eosinophils (p<0.01). Moreover, cetirizine significantly reduced nasal obstruction score (p=0.007). This study shows the cetirizine effectiveness in exerting anti-inflammatory activity by modulating cytokine pattern and by reducing inflammatory infiltration in children with perennial allergic rhinitis.
Adolescent↗
Nasal eosinophils correlate with FEV1 in patients with perennial allergic rhinitis associated to asthma.
BACKGROUND: Eosinophil inflammation is present in nasal and bronchial mucosa and a clear link between upper and lower airways exists. Our aim was to evaluate whether nasal inflammation correlates with lung function in patients with perennial allergic rhinitis associated with asthma. METHODS: Eighty perennial allergic rhinitics with mild asthma, aged from 18 to 46 years, were enrolled. Nasal scraping and spirometry were performed in all subjects. RESULTS: A close relationship between the nasal eosinophil number and the percentage of predicted FEV1 was demonstrated (r = -0.76; p<0.0001). CONCLUSIONS Nasal cytology may be considered a non-invasive tool to assess airway inflammation in mild asthmatics with associated allergic rhinitis.
Adolescent↗
Long-term cetirizine treatment may reduce new sensitisations in allergic children: a pilot study.
Experimental data demonstrate that mite allergy is characterized by persistent chronic inflammation. This suggests that long-term continuous treatment may be included in the global strategy of allergy management as recently reported. Moreover, most of allergic subjects show polysensitisation. We conducted a study to investigate whether a long-term cetirizine treatment may reduce the occurence of new sensitisations in children with mite allergy. This study was initially double-blind, randomized, and placebo-controlled, with two parallel groups of 10 children with mite allergy receiving either cetirizine or placebo daily. All children could assume cetirizine as rescue medication (i.e. symptomatic treatment). After six months, parents of continuously-treated children decided to continue the treatment for 3 years. Other subjects continued to assume cetirizine on symptomatic basis. All children were prospectively followed for other 3 years. Outcome measure was skin prick test, yearly performed. Cetirizine-continuously-treated group showed a significant lower incidence of new sensitisations (p = 0.002). In conclusion, cetirizine administered daily for prolonged periods (i.e. 3 years) may decrease the development of new sensitisations in monosensitised children, showing a potential effect of tertiary prevention of allergy.
Animals↗
Nasal cytokine modulation by montelukast in allergic children: a pilot study.
BACKGROUND: Allergic rhinitis and asthma are characterized by chronic inflammation due to a Th2 cytokine polarization. Leukotrienes receptor antagonists have been shown to be effective in both diseases. OBJECTIVE: Aim of the study was to evaluate the modulation by the antileukotriene montelukast on Th2 and Th1 cytokines in allergic rhinitis. METHODS: Fourteen school children affected by persistent allergic rhinitis (PAR) and exercise-induced asthma (EIA) underwent a nasal lavage before and after a two-week treatment with montelukast. A panel of cytokines, including IL4, IL13, and IFN gamma, was measured by immunoassay on nasal lavage samples. RESULTS: Montelukast treatment induced a significant decrease of IL4 and IL13 levels (p < 0.001, for both comparisons), and a significant increase of IFN gamma (p < 0.001). CONCLUSIONS: Montelukast treatment reversed a typical Th2 cytokine pattern (IL4 and IL13) toward a Th1 (IFN gamma) predominance in children with PAR and EIA. This effect could be considered relevant for long term allergic inflammation control and of interest when treating EIA with concomitant PAR.
Acetates↗
Most nosocomial pneumonias are not due to nosocomial bacteria in ventilated patients. Evaluation of the accuracy of the 48 h time cut-off using carriage as the gold standard.
A prospective observational cohort study was undertaken with two endpoints: (1) to compare the time cut-off of 48h and the carrier state criterion for classifying lower airway infections in adult and paediatric long-term ventilated patients, and (2) to evaluate the potential of optimized time cut-offs for characterizing imported and ICU-acquired lower airway infections. All patients admitted to the general and paediatric intensive care units and expected to require mechanical ventilation for a period > or = 3 days were enrolled. Surveillance cultures of throat and rectum were obtained on admission and thereafter twice weekly to distinguish micro-organisms that were imported into the unit from those acquired during the stay on the unit. A total of 130 adults and 400 children were studied. In the adult population, 70% of lower airway infections were classified as ICU-acquired by the 48 h cut-off and 48% by the criterion of carriage; on the paediatric ICU the percentages were 65% and 20%, respectively. To separate imported from ICU-acquired infections, eight days was optimal in the adult population and 10 days in the paediatric population. Sensitivity, specificity, positive predictive value and negative predictive value for a time cut-off of eight days for adults were 86, 77, 80, 83%, respectively, and using 10 days for children were 87, 62, 90, 56%, respectively. The use of the 48 h cut-off rule classifies patients as having nosocomial pneumonia, when in fact the infections are commonly caused by microorganisms carried in by the patients. In contrast, using the carriage method, the proportion of lung infections due to nosocomial bacteria was relatively small and was a late phenomenon. Although in prolonging the time cut-off the difference between the two types of classification was shorter, time cut-offs were still found to be unreliable for distinguishing imported from unit-acquired lower airway infections.
Adult↗
Allergic inflammation and airway smooth muscle function.
It is widely accepted that airway smooth muscle (ASM) contraction plays a key role in asthmatic attacks. Whether abnormalities of contractility or autonomic regulation exist in the asthmatic ASM is still debated. Studies based on isometric contraction failed to show differences in the force-generation capability between asthmatic and normal ASM. Recent studies in vitro have shown that sensitized ASM: (1) shortens more and more rapidly than normal ASM; and (2) develops a myogenic response to stretching. The increased velocity of shortening may compromise in vivo the ability of tidal cycling to reduce airway tone, which would result in an enhanced response to bronchoconstrictor stimuli. The myogenic response may result in a sustained bronchospasm after a deep inhalation, a maneuver that in normal individuals causes bronchodilatation. Although there is no evidence that neural or humoral abnormalities in the autonomic regulation of ASM tone are central to the pathogenesis of bronchial asthma, recent data suggest that ASM receptor dysfunction may develop secondary to airway allergic response. It has been shown that exposure of passively sensitized human bronchi to allergens in vitro causes M2- and beta2-receptor dysfunction. Impairment of pre-junctional M2-autoreceptors may result in an enhancement of neurally mediated bronchoconstrictor responses, whereas beta2-receptor dysfunction may reduce the sensitivity to bronchodilator treatment. Airway inflammation, which is a characteristic feature of bronchial asthma, may alter both the contractile properties and the autonomic regulation of ASM. These changes may contribute to the severity of asthma, as they may cause an, imbalance between factors favoring and opposing airway narrowing.
Asthma↗
Inhibitory effect of aluminum on dopamine beta-hydroxylase from bovine adrenal gland.
Aluminum is a well known neurotoxic agent that is overaccumulated in the substantia nigra of patients affected by Parkinson's disease as well as in certain cerebral areas of other neurodegenerative pathologies such as Alzheimer's disease. Although the role of aluminum in neurodegenerative diseases is yet to be clearly understood, the metal ion is known to substantially alter the activity of several key enzymes in the central nervous system. The present paper reports data on the effect of aluminum on the activity of dopamine-beta-hydroxylase from bovine adrenaL gland utiLized as a model study. The metal ion inhibited the activity of this enzyme with a mixed type mechanism following the Michaelis-Menten equation. In the absence of Al, the enzyme exhibited a Km and Vmax of 2.56 mM of 4.12 pmol/min respectively, while in the presence of Al its Km and Vmax were 3.85 mM and 2.86 pmol/min respectively. The potential implications of aluminum in the etiopathogenesis of neurological disorders are discussed.
Adrenal Glands↗
Fexofenadine reduces nasal congestion in perennial allergic rhinitis.
BACKGROUND: Nasal congestion is the predominant symptom in perennial allergic rhinitis (PAR), and it seems to be mainly related to the late-phase inflammatory events. The present pilot study aimed to evaluate the therapeutic effect exerted by fexofenadine in patients with PAR due to mite allergy. METHODS: This study was a parallel, double-blind, randomized, three-arm (1:1:1), placebo-controlled study. Thirty-one subjects with PAR were enrolled and received double-blind medication: fexofenadine 120 or 180 mg, or placebo, once a day for 28 days. RESULTS: The total symptom score was reduced by fexofenadine (both dosages) at V2 (P=0.007), whereas placebo did not modify it. Nasal congestion decreased after 1 week of treatment with fexofenadine 120 (P=0.027) and 180 (P=0.01), but not with placebo (P=NS). At V3, fexofenadine (both dosages) significantly reduced nasal congestion (P=0.011 and P=0.007, respectively), by placebo did not show any significant effect. CONCLUSIONS: This pilot study represents the first evidence of the efficacy of fexofenadine in PAR, and also the control of the nasal congestion. We suggest performing larger trials to confirm these preliminary findings.
Adolescent↗
Inflammatory and mechanical factors of allergen-induced bronchoconstriction in mild asthma and rhinitis.
We studied whether different bronchial responses to allergen in asthma and rhinitis are associated with different bronchial inflammation and remodeling or airway mechanics. Nine subjects with mild asthma and eight with rhinitis alone underwent methacholine and allergen inhalation challenges. The latter was preceded and followed by bronchoalveolar lavage and bronchial biopsy. The response to methacholine was positive in all asthmatic but in only two rhinitic subjects. The response to allergen was positive in all asthmatic and most, i.e., five, rhinitic subjects. No significant differences between groups were found in airway inflammatory cells or basement membrane thickness either at baseline or after allergen. The ability of deep inhalation to dilate methacholine-constricted airways was greater in rhinitis than in asthma, but it was progressively reduced in rhinitis during allergen challenge. We conclude that 1) rhinitic subjects may develop similar airway inflammation and remodeling as the asthmatic subjects do and 2) the difference in bronchial response to allergen between asthma and rhinitis is associated with different airway mechanics.
Adult↗
On the functional consequences of bronchial basement membrane thickening.
Reticular basement membrane (RBM) thickness and airway responses to inhaled methacholine (MCh) were studied in perennial allergic asthma (n = 11), perennial allergic rhinitis (n = 8), seasonal allergic rhinitis (n = 5), and chronic obstructive pulmonary disease (COPD, n = 9). RBM was significantly thicker in asthma (10.1 +/- 3.7 microm) and perennial rhinitis (11.2 +/- 4.2 microm) than in seasonal rhinitis (4.7 +/- 0.7 microm) and COPD (5.2 +/- 0.7 microm). The dose (geometric mean) of MCh causing a 20% decrease of 1-s forced expiratory volume (FEV(1)) was significantly higher in perennial rhinitis (1,073 microg) than in asthma (106 microg). In COPD, the slope of the linear regression of all values of forced vital capacity plotted against FEV(1) during the challenge was higher, and the intercept less, than in other groups, suggesting enhanced airway closure. In asthma, RBM thickness was positively correlated (r = 0.77) with the dose (geometric mean) of MCh causing a 20% decrease of FEV(1) and negatively correlated (r = -0.73) with the forced vital capacity vs. FEV(1) slope. We conclude that 1) RBM thickening is not unique to bronchial asthma, and 2) when present, it may protect against airway narrowing and air trapping. These findings support the opinion that RBM thickening represents an additional load on airway smooth muscle.
Adult↗
Role of leukotriene receptor antagonists in the management of mild-to-moderate asthma.
To date the position of Leukotriene Receptor Antagonists (LTRAs) in asthma is not yet fully established. Recent asthma guidelines consider LTRAs as 'alternative' to low doses of inhaled corticosteroids (ICS) for treatment of patients with mild persistent asthma, while in Europe LTRAs are licensed as additional therapy to ICS. Our aim in this paper is to review comparative studies between ICS and antileukotrienes in mild to moderate asthma, looking at their efficacy on asthma outcomes and on patient expectations (compliance, quality of life, and safety). Some studies report a superior efficacy of ICS, while others, in particular in patients aged < 12 years, found no differences. When considering patients' expectations LTRAs seem to be superior, with higher compliance and quality of life. Even if no differences in adverse effects have been found between ICS and LTRAs, whose safety profiles are not different from placebo, some concerns exist on long term treatment with ICS, even at low doses, in children and postmenopausal women. For this reason, even if ICS are superior to LTRAs in controlling asthma outcomes and in improving pulmonary function, in children and elderly patients LTRAs can be considered an alternative to low-dose ICS.
Adrenal Cortex Hormones↗
G(s) protein dysfunction in allergen-challenged human isolated passively sensitized bronchi.
We studied the intracellular mechanisms of allergen-induced beta(2)-adrenoceptor dysfunction in human isolated passively sensitized bronchi. Sensitization was obtained by overnight incubation of bronchial rings with serum containing a high specific IgE level to Dermatophagoides but a low total IgE level. Allergen challenge was done by incubation with a Dermatophagoides mix. The G(s) protein stimulant cholera toxin (2 microg/ml) displaced the carbachol (CCh) concentration-response curves of control and sensitized but not of challenged rings to the right. Cholera toxin (10 microg/ml) displaced the concentration-response curves to CCh of control, sensitized, and challenged rings to the right, but this effect was less in challenged rings. The effects of the G(i) protein inhibitor pertussis toxin (250 ng/ml or 1 microg/ml) on salbutamol concentration-relaxation curves did not differ significantly between challenged and sensitized rings. The adenylyl cyclase activator forskolin and the Ca(2+)-activated K(+)-channel opener NS-1619 relaxed CCh-contracted bronchial rings without significant differences between control, sensitized, and challenged rings. Neither G(i) nor G(s) alpha-subunit expression differed between control, sensitized, and challenged tissues. We conclude that G(s) protein dysfunction may be a mechanism of allergen-induced beta(2)-adrenoceptor dysfunction in human isolated passively sensitized bronchi.
Adenylyl Cyclases↗