Inhaled triamcinolone and chronic obstructive pulmonary disease.
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Biomedical subjects
Publications and source records attributed to G W Canonica.
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BACKGROUND: Experimental data demonstrate that mite allergy is characterized by persistent chronic inflammation, even during asymptomatic periods. This suggests that long-term continuous treatment be included in the global strategy of allergy treatment. OBJECTIVE: We conducted a study to evaluate whether regularly administered cetirizine reduces allergic symptoms and drug prescriptions in children with mite allergy. METHODS: In this double-blind, randomized, placebo-controlled study, two parallel groups of 10 children with mite allergy (mean age: 6.5 years) received either cetirizine or placebo daily for 6 months. Participants were allowed to take rescue medications for rhinitis and/or mild asthma. The symptoms (nasal itching, sneezing, obstruction, rhinorrhea, conjunctival itching, lacrimation, conjunctival hyperemia, cough, wheezing, and chest tightness) were recorded on a diary card. The intake of cetirizine (as additional symptomatic treatment), antibiotics, acetaminophen, beta2-agonists, inhaled and systemic corticosteroids was also recorded. RESULTS: Symptom scores and drug consumption were significantly lower (P < 0.05) in the cetrizine-treated group versus the placebo group. The greatest reductions were in cetirizine itself, inhaled corticosteroids, beta2-agonists, and antibiotics. No side effects were reported in either group. CONCLUSIONS: In mite-allergic children, cetirizine administered daily for prolonged periods decreases symptoms of and drug prescriptions for allergic rhinitis and asthma compared with symptomatic treatment.
BACKGROUND: Allergen specific nasal challenge (ASNC) is an optimal model to study the pathophysiologic mechanisms sustaining allergic inflammation, particularly the adhesion molecules promoting cellular infiltration of nasal mucosa. Topical corticosteroids have been accepted as a highly effective anti-inflammatory therapy for allergic rhinitis. OBJECTIVE: The aim of this double-blind, randomized, placebo-controlled study was the evaluation of inflammatory events, during the late-phase, after a 2-week treatment with nasal mometasone furoate (MF), 200 microg daily, or placebo, using the model of ASNC. METHODS: A total of 42 patients with allergic rhinitis underwent nasal challenge before and after treatment. The following parameters were evaluated at baseline, and 6 hours (late-phase) after ASNC: 1) nasal symptoms (rhinorrhea, itching, sneezing, obstruction); 2) inflammatory cells (eosinophils and neutrophils); 3) eosinophil cationic protein (ECP) and tumor necrosis factor-alpha (TNF-alpha) in nasal lavage; and 4) intercellular adhesion molecule-1 expression on nasal epithelial cells. RESULTS: MF nasal spray was associated with late-phase reductions of: 1) clinical symptoms (P < 0.03); 2) eosinophil (P < 0.004) and neutrophil (P < 0.003) infiltration; 3) ECP (P < 0.001) and TNF-alpha (P < 0.05); and 4) intercellular adhesion molecule-1 expression on nasal epithelial cells (P < 0.001). CONCLUSIONS: The present results demonstrate that MF has a significant effect on late-phase events, reducing the cellular influx and activation.
BACKGROUND: Sublingual immunotherapy (SLIT) appears to be acceptably safe in clinical trials, but post-marketing data are needed to provide essential information. This study specifically evaluated the safety of commercial SLIT in adult patients in a post-marketing phase. METHODS: A total of 198 patients (83 male, 115 female, mean age 24.4 years) receiving SLIT for respiratory allergy were followed up for 3 years by a specific questionnaire for side-effects. SLIT (LAIS, Lofarma SpA, Milan, Italy), a monomeric allergoid in tablets, was administered, in association with drug therapy, pre- or pre-coseasonally for pollen and continuously for mites. The average duration was 12-36 months, and the total of doses was about 32 800. Side-effects were grouped as ocular, gastrointestinal, rhinitis, asthma, urticaria, edema of tongue/lips, and anaphylaxis. The severity was graded as low (no need for treatment or dose adjusting, no interference with activities), moderate (interference with activities/need for drugs/SLIT discontinuation), and severe (life-threatening/hospitalization/emergency care). RESULTS: Seventeen events corresponding to 7.5% of patients and 0.52 per 1000 doses were reported. Seven episodes of rhinitis (two in two patients), three of oral itching, and one of abdominal pain were self-limiting. Two cases of urticaria and two of abdominal pain/nausea were controlled by a temporary dose-adjustment, and one case of urticaria and conjunctivitis required oral antihistamines. Medical intervention was needed in six patients only during a 3-year period. CONCLUSION: The results of this study, performed in a real situation of clinical practice, confirm the satisfactory safety profile of SLIT.
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.
BACKGROUND: The clinical safety of sublingual immunotherapy (SLIT) has been repeatedly confirmed; nevertheless, the possible onset of local oral symptoms is still a concern, and nothing is known about the pathogenesis of this effect. We aimed to determine whether the administration of SLIT in allergic children can evoke an IgE-mediated reaction, by measuring the levels of sublingual tryptase and ECP. METHODS: Thirty children (7-12 years old) with allergic rhinitis/asthma due to grass pollen were prescribed SLIT. In these children, an allergen-specific nasal challenge was performed, and nasal tryptase and ECP were measured before and after. Sublingual ECP and tryptase were also assessed before the SLIT, after 1 month, and after 6 months of treatment. Ten matched allergic children and 10 healthy ones served as controls for the baseline levels of sublingual ECP and tryptase. RESULTS: The levels of nasal tryptase and ECP significantly increased after nasal challenge (P<0.001), whereas no change during the SLIT course (at the beginning, after 1 month, and after 6 months) could be detected in sublingual tryptase either before or after SLIT administration. The sublingual ECP significantly decreased after 6 months of SLIT. The baseline levels of nasal tryptase and ECP were significantly higher in allergic subjects than in healthy controls, as was the level of sublingual ECP. CONCLUSIONS: In the presence of an IgE-mediated reaction (ASNC), a significant increase of tryptase and ECP can be seen. When SLIT is administered, such a phenomenon does not occur; therefore, SLIT does not elicit any IgE reaction in the mouth. It is noteworthy that allergic subjects display higher levels of nasal ECP and tryptase than healthy subjects, even when symptom-free, and these observations may indicate the presence of subclinical inflammation.
BACKGROUND: Allergic rhinitis is an inflammatory disease often associated with bronchial asthma. Intranasal corticosteroids and oral antihistamines are the first-choice drugs. Patient training is relevant to asthma management, but little is known about its impact on rhinitis. We evaluated the role of patient training in the treatment of allergic rhinitis and its effects on nasal and bronchial symptoms. METHODS: One hundred and one patients (M/F = 62/39, age range 12-62 years) with pollen-induced rhinitis (32 with concomitant mild asthma) were enrolled. They were randomized into three groups: A (n = 30) with drug therapy alone, B (n = 35) with drug therapy plus training on the use of nasal spray, and C (n = 36) the same as B plus a lesson on rhinitis and asthma. All patients received mometasone furoate nasal spray for 8 weeks as regular therapy, plus rescue medications on demand. Symptoms and drug consumption were evaluated during the pollen season. RESULTS: The rate of noncompliance/dropout was highest in the untrained patients (P = 0.001). No difference in nasal symptoms was seen among the three groups. On the other hand, group C had significantly fewer asthma symptoms (P = 0.02) and less albuterol use (P = 0.005) than group A. Moreover, the trained group globally used less rescue medication than the other groups (P = 0.02). CONCLUSIONS: Detailed training of patients seems to improve compliance with treatment, reduce concomitant asthma symptoms, and reduce the use of symptomatic drugs.
BACKGROUND: In health-related quality of life (HRQL) studies on allergic rhinitis, both disease-specific and generic questionnaires have been extensively used. Seasonal allergic rhinitis (SAR) has been studied mainly by focusing on symptomatology. The present study aimed to evaluate the SAR-HRQL by means of two questionnaires, the Medical Outcome Study Short Form Health Survey (SF-36) and a new instrument examining satisfaction in 32 aspects of daily life: the Satisfaction Profile (SAT-P). METHODS: Thirty-three patients with SAR (aged 33.5+/-8.5 years; 12 men, 21 women) were evaluated during and 2 months after the pollen season. Data were compared with reference samples by t-test, and baseline and follow-up HRQL scores were compared by a matched-pair test. RESULTS: Patients' HRQL scores collected during the pollen season were significantly lower than reference sample data in many SF-36 scores and in one SAT-P item. No differences emerged between SF-36 and SAT-P scores collected outside the pollen season and reference sample scores. Compared to baseline, outside the pollen season, patients reported significantly higher scores in the following SF-36 scales: physical functioning (P=0.002), physical role (P=0.00001), bodily pain (P=0.01), and vitality (P=0.008); and significantly higher scores in only two SAT-P items (physical well-being [P=0.009] and resistance to stress [P=0.01]). CONCLUSIONS: Our data confirm the utility of using symptomatologic and health-status questionnaires in evaluating the HRQL of SAR patients. More general quality of life questionnaires may prevent the symptomatologic and functional problems from being adequately recognized and managed. SAT-P can be a fruitful additional tool in HRQL evaluation.
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BACKGROUND AND OBJECTIVE: Little is known about the pharmacokinetics of allergens for local immunotherapy. Thus, we studied the pharmacokinetics in allergic volunteers of a commercial allergenic vaccine in orosoluble tablets (LAIS(R), Lofarma S.p.A). METHODS: The carbamylated monomeric allergoid derived from Parietaria judaica major allergen (Par j 1), characterized by maintenance of the original molecular size, and the native allergen, were radiolabelled with 123I, then incorporated into the commercial soluble tablets and administered to allergic subjects. Early sequential and late static scintigraphic acquisitions were performed, and plasma radioactivity was measured at different time intervals. RESULTS: No difference in local pharmacokinetics was observed between the allergen and the allergoid: part of the tracer was retained in the mouth for at least 2 h after swallowing. No direct absorption through the oral mucosa could be detected, as plasma radioactivity increased only after swallowing and peaked at 2 h. However, the plasma peak attained with the allergoid in tablets was significantly higher with respect to the native allergen. Finally, some undegraded allergoid, but not the allergen, could be constantly detected in the bloodstream at plasma peak. CONCLUSIONS: The results showed a similar behaviour of the allergoid and the allergen in tablets as far as their local kinetics are concerned, whereas plasma peak was higher with the allergoid than with the allergen. Therefore we conclude that the chemical modification of the allergen may affect its pharmacokinetics, by making it less susceptible to enzymatic degradation.
BACKGROUND: Upper respiratory airway diseases may induce a worsening of asthma. Sinusitis represents one of the most common chronic diseases. The association of asthma and sinusitis varies greatly in different studies, depending on diagnostic procedures. OBJECTIVE: The aims were: (i) to demonstrate that nasal endoscopy may be easily feasible in asthma at paediatric age; (ii) to evaluate the incidence of rhinosinusitis and adenoiditis in children with asthma by nasal endoscopy; (iii) to correlate inflammatory parameters such as cytology and microbiological cultures with nasal endoscopy findings. SUBJECTS AND METHODS: One hundred and forty-five asthmatic children were evaluated, 48 males and 97 females, with an average age of 7.27 years. Evaluated parameters were the incidence of rhinosinusal infections in asthmatic children, and the role of: (i) nasal endoscopy, (ii) nasal cytology, and (iii) nasal microbiology in their diagnoses. RESULTS: Nasal endoscopy was successfully performed on 128 patients. Twenty-six children had endoscopic rhinosinusitis alone, 10 had adenoiditis alone, and 35 showed endoscopic rhinosinusitis associated with adenoiditis. There were significant correlations between endoscopic rhinosinusitis and adenoiditis (P < 0.001), between clinical and endoscopic rhinosinusitis (P < 0.001), between endoscopic rhinosinusitis and adenoiditis and microbiology (P < 0.05 and P < 0.0001, respectively), and between microbiology and cytology (P < 0.05). CONCLUSION: This study shows that rhinosinusal infections are common in asthmatic children. Moreover, nasal endoscopy might represent a fruitful tool in the management of asthmatic children.
A strict relationship between allergic rhinitis and allergic asthma has been seen recently, and in many ways respiratory allergy could be seen as a single disorder of the airways. The link between rhinitis and asthma can be elucidated only by studying the natural history of the disease over long periods. We describe the follow-up of 99 allergic patients up to 10 years and the evolution of their disease. Ninety-nine patients (50 male, 49 female, mean age 31 years) out of 142, suffering from allergic rhinitis or allergic asthma, could be monitored up to 10 years after the initial diagnosis. Demographics, sensitizations and smoke habit were assumed as evaluation parameters. At baseline, 44 patients suffered from AR alone, 12 from AA alone and 43 from AR+AA. After 10 years, 31.8% of the AR patients developed developed AA and 50% of the patients with AA developed AR. Only the familial history for atopy significantly influenced the disease's evolution, whereas gender, age, smoking habit and skin sensitization did not. Sixty-five percent of patients with a single sensitization at the beginning developed new sensitizations. In conclusion, this long-term survey confirms that a relevant percentage of patients with AR alone or AA alone have a progression of the disease.
The link between upper and lower respiratory tracts has been repeatedly observed in the past 50 years but only carefully investigated during the past decade. Several clinical and experimental observations suggested the hypothesis of the unity of upper and lower airways (allergic rhinobronchitis or united airways disease). The relationships between rhinitis (and sinusitis) and asthma also include non-epidemiological aspects such as viral infections and bronchial hyperreactivity. The hypotheses have been confirmed by means of epidemiological observations, functional and immunological evidence and, indirectly, by observing the effects of drugs used mainly for rhinitis on asthma symptoms. In this article, therefore, we collected and reviewed the most relevant experimental results available to support the hypothesis for united airways disease and the studies conducted on the possible mechanisms of nose-lung interaction.
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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.
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.
BACKGROUND: We have previously shown aberrant expression of the 'leukocyte' integrin LFA-1 on epithelial cells in chronic autoimmune thyroiditis. In the present study we investigated whether conjunctival epithelial cells, which bear the adhesion molecule ICAM-1 on their surface during allergic inflammation, may also aberrantly express its natural ligand, the 'leukocyte' integrin LFA-1. METHODS: We studied 13 patients with rhinoconjunctivitis allergic to mites, chronically exposed to the allergen, 11 patients allergic to pollen tested out of the pollen season and 8 normal volunteers. Single and double immunocytochemical staining of conjunctival smears was employed. RESULTS: LFA-1 staining on epithelial cells was demonstrated in 12/13 patients allergic to mites and not in normal controls or in patients allergic to pollen tested out of the pollen season. The epithelial localization of LFA-1 was confirmed by double staining with anti-LFA-1 and anti-cytokeratin antibodies (both immunocytochemical and immunofluorescence). CONCLUSIONS: Coexpression of LFA-1 and ICAM-1 during persistent allergen stimulation may be relevant for interaction between epithelial cells and activated effector cells, such as eosinophils, which bear on their surface both ICAM-1 and its beta2 integrin ligands.