Similarity and differences in elderly patients with fixed airflow obstruction by asthma and by chronic obstructive pulmonary disease.

BACKGROUND: Epidemiologic studies have demonstrated that elderly patients with fixed airflow obstruction can be affected by asthma or chronic obstructive pulmonary disease (COPD). METHODS: We studied 49 consecutive elderly outpatients, presenting fixed airflow obstruction, by clinical history (smoking), pulmonary function tests, blood gas analysis, and induced sputum. RESULTS: The age was not different in patients with COPD (n=28) and asthma (n=21) (70.2+/-3.9 years vs. 69.6+/-3.7 years), also the degree of fixed airflow obstruction was similar (FEV1: 58.3+/-1.5% vs. 59.0+/-1.4% of predicted). Patients with asthma had significantly more eosinophils in peripheral blood (0.43+/-0.05x10(-3)microL vs. 0.27+/-0.1x10(-3)microL, P<0.0001), and in induced sputum (5.0% [(p25th and p75th) 5.0-6.0%] vs. 1.0% [(p25th and p75th) 0.01-1.0%]; P<0.0001), as well as serum ECP (18.6+/-4.9ng/mL vs. 7.7+/-4.7ng/mL, P<0.0001) and ECP in the induced sputum (31.6+/-2.9ng/mL vs. 5.6+/-4.9ng/mL, P<0.0001). Finally, in induced sputum the eosinophils EG2+ were higher in patients with asthma than in patients with COPD (40.5 [(p25th and p75th) 39.3-44.3] MFI vs. 3.9 [(p25th and p75th) 0-11.4] MFI, P<0.0001). They also had significantly higher diffusing capacity, and a greater reversibility to steroids, after 14-day course of therapy, whereas the reversibility to 400microg of salbutamol was similar. CONCLUSION: Despite similar fixed airflow obstruction, elderly patients with asthma have distinct characteristics compared with patients with COPD.

The characteristics of different diagnostic tests in adult mild asthmatic patients: comparison with patients with asthma-like symptoms by gastro-oesophageal reflux.

BACKGROUND: Diagnosing asthma cannot be always easy. It is important to consider the validity of the diagnostic tests, and/or how much more commonly they are positive in patients with asthma compared to healthy subjects and, particularly, to patients with asthma-like symptoms. OBJECTIVE: To evaluate the validity of diagnostic tests for asthma, in terms of sensitivity, specificity, positive and negative predictive values, in patients with bronchial asthma compared to patients affected by gastro-oesophageal reflux disease (GERD) with asthma-like symptoms, and healthy control subjects without asthma and gastro-oesophageal reflux (GER). DESIGN: Single-center, cross-sectional, observational study. PATIENTS: We studied 60 patients with mild asthma, 30 patients with GERD and asthma-like symptoms and 25 healthy control subjects. MEASUREMENTS: We measured provocative concentration of methacholine causing a 20% fall in the forced expiratory volume in 1s (MCh PC(20)/FEV(1)), the amplitude percent mean of peak expiratory flow (A%M of PEF), derived from twice-daily readings for >2 weeks, the FEV(1)/forced vital capacity (FEV(1)/FVC) ratio, the eosinophil count in blood and in induced sputum and the serum eosinophil cationic protein (ECP) levels. RESULTS: FEV(1)/FVC ratio, A%M of PEF, blood eosinophils counts and serum ECP levels were less sensitive and specific when the reference population was composed of patients with asthma-like symptoms by GER. While, MCh PC(20)/FEV(1) and induced sputum eosinophils count were the most sensitive (both 90%) and specific (89% and 92%, respectively) tests. CONCLUSION: Our findings demonstrate that MCh PC(20)/FEV(1) and the induced sputum eosinophil count are the most useful objective tests in patients with mild asthma. All patients with asthma presented both an MCh PC(20)/FEV(1) <1500 microg and eosinophils count in the induced sputum >1%.

A study of serum immunoglobulin levels in elderly persons that provides new insights into B cell immunosenescence.

The literature on immunosenescence has focused mainly on T cell impairment. With the aim of gaining insight into B cell immunosenescence, we investigated the serum immunoglobulin levels in a cohort of 166 subjects (20-106 years). Serum IgG (and IgG subclasses) were quantified by the nephelometric technique, IgE by CAP system fluorescence enzyme immunoassay, and IgD by radial immunodiffusion (RID). There was an age-related increase of IgG and IgA; the IgG age-related increase was significant only in men, but IgG1 levels showed an age-related increase both in men and women, whereas IgG3 showed an age-related increase only in men. IgE levels remain unchanged, whereas IgD and IgM serum levels decreased with age; the IgM age-related decrease was significant only in women, likely due to the relatively small sample of aged men. Thus, in the elderly the B cell repertoire available to respond to new antigenic challenge is decreased. A lot of memory IgD- B cells are filling immunological space and the amount of naïve IgD+ B cells is dramatically decreased. This shift away from a population of predominantly naïve B cells obviously reflects the influences of cumulative exposure to foreign pathogens over time. These age-dependent B cell changes indicate that advanced age is a condition characterized by lack of clonotypic immune response to new extracellular pathogens. In any event, the increase of memory B cells and the loss of naïve B cells, as measured by serum IgD levels, could represent hallmarks of immunosenescence and could provide useful biomarkers possibly related to the life span of humans.

Comparison of topical tacrolimus 0.1 % in pectin ointment with clobetasol 0.5% ointment in adults with moderate to severe desquamative gingivitis: A 4-week, randomized, double-blind clinical trial.

BACKGROUND: Desquamative gingivitis (DG) is a clinical condition characterized by red, painful, glazed, and friable gingiva, which might be a manifestation of some autoimmune mucocutaneous diseases. The time from the development of initial signs of DG to diagnosis can vary from months to years. Based on a literature search, no data concerning patients with DG without signs of autoimmune disease were available. OBJECTIVE: The aim of this trial was to compare the efficacy and tolerability of monotherapy with topical tacrolimus 0.1% in pectin ointment versus clobetasol propionate 0.5% ointment in adults affected by DG. METHODS: This randomized, double-blind clinical trial was conducted at the Dipartimento di Medicina Clinica e Sperimentale, Universita di Verona, Verona, Italy. Patients aged > or =18 years were selected using the department's electronic medical records based on a clinical diagnosis of moderate to severe DG. After a 2-week washout period, patients were randomly assigned to receive 2 mL of tacrolimus 0.1% in pectin (equivalent to 0.2 mg of tacrolimus) or 2 mL of clobetasol propionate 0.5% ointment (equivalent to 1 mg of clobetasol) QD for 4 weeks. Evaluations were performed before treatment (baseline), after the treatment period (week 4), and at 2 follow-up visits at weeks 6 and 8. The signs of DG (ie, erythema [atrophy] and desquamation [erosions/ulceration]) were quantified by a blinded investigator using a calculated score based on their surface extension, using a drawing in which the areas of various zones of the mouth were indicated as a percentage of the whole oral mucosa. Severity of erythema and desquamation was rated on a 4-point scale (0 = absent; 1 = involvement of <5% of surface [mild]; 2 = 5%-15% [moderate]; and 3 = >15% [severe]). The primary end point was the number of patients who achieved remission (severity score of 0) in either sign; the secondary end point was the proportions of patients achieving improvement (severity score of 0 or 1) in either sign. Before and after treatment, we measured the serum concentrations of tacrolimus and its metabolites with an immunoenzymatic assay kit. Tolerability was assessed using hematology, biochemistry, urinalysis, measurements of systolic/diastolic blood pressure and heart rate, patient interview, and spontaneous reporting. RESULTS: A total of 24 patients (18 women, 6 men; all white of Italian origin; age range, 21-65 years; 12 patients per treatment group) were enrolled in the study. In the tacrolimus group, 11 (91.7%) patients achieved remission of erythema and/or desquamation at weeks 4 and 6; at week 8, these rates were 9 (75.0%) and 8 (66.7%), respectively; none of the patients in the clobetasol group achieved remission of either sign at any time point (all, P < 0.001). At weeks 4, 6, and 8, significantly greater proportions of patients treated with tacrolimus had improved erythema and desquamation compared with those treated with clobetasol (all, P < 0.001). At week 4, all patients had undetectable serum tacrolimus concentrations (<1.5 microg/L). Six (50.0%) patients in the tacrolimus group reported a mild oral burning sensation, and 6 (50.0%) patients in the clobetasol group reported mild mouth dryness. No other adverse events were reported. CONCLUSIONS: The results of this small study suggest that topical tacrolimus 0.1 % in pectin was more effective compared with clobetasol propionate 0.5% ointment in the treatment of DG. Both treatments were generally well tolerated in the population studied.

Food allergy in gastroenterologic diseases: Review of literature.

Food allergy is a common and increasing problem worldwide. The newly-found knowledge might provide novel experimental strategies, especially for laboratory diagnosis. Approximately 20% of the population alters their diet for a perceived adverse reaction to food, but the application of double-blind placebo-controlled oral food challenge, the "gold standard" for diagnosis of food allergy, shows that questionnaire-based studies overestimate the prevalence of food allergies. The clinical disorders determined by adverse reactions to food can be classified on the basis of immunologic or nonimmunologic mechanisms and the organ system or systems affected. Diagnosis of food allergy is based on clinical history, skin prick tests, and laboratory tests to detect serum-food specific IgE, elimination diets and challenges. The primary therapy for food allergy is to avoid the responsible food. Antihistamines might partially relieve oral allergy syndrome and IgE-mediated skin symptoms, but they do not block systemic reactions. Systemic corticosteroids are generally effective in treating chronic IgE-mediated disorders. Epinephrine is the mainstay of treatment for anaphylaxis. Experimental therapies for IgE-mediated food allergy have been evaluated, such as humanized IgG anti-IgE antibodies and allergen specific immunotherapy.

A study of age-related IgE pathophysiological changes.

The literature on immunosenescence has focused mainly on T cell impairment. However, it is well known that B function is also profoundly affected. In particular, several studies have shown age-related changes in immunoglobulin serum levels. Concerning allergic diseases, the incidence of onset of allergic symptoms, as well as their severity, seems to decrease with age. So, the decline of onset of allergic symptoms observed in ageing might result from a decrease of serum total IgE due to an unbalance of cytokines and soluble factors involved in its production. To gain insight into the mechanisms of age related incidence of onset of allergic symptoms, as well as their severity, in this study we have evaluated in a sample of young (12 females and 15 males, range 20-64 years) and old (42 females and 20, males range 70-93 years) individuals serum values of IgE and sCD23 and in vitro Type 2 cytokine production. Total serum IgE levels were quantified by CAP-system fluorescence enzyme immunoassay. Serum CD23 levels were measured by a sandwich enzyme-linked immunoassay. Enzyme immunoassay tests have been used to quantify IL-4, IL-10 and IL-13 on mitogen-stimulated cultures. Serum total IgE and sCD23 in the two groups of young and old subjects were not significantly different. No detectable levels of IL-4, IL-10 and IL-13 were observed in supernatants from unstimulated cultures in all the subjects tested. After 48 h stimulation with PHA, cytokine amounts became detectable in all subjects. However, the values of the cytokines under study were not significantly different between young and old subjects. In our study, we have not been able to show no impairment in the afferent (type 2 cytokine production) and in the central (serum IgE and sCD23 levels) branch of allergic responses. Previous studies have shown that the efferent branch, at least studied as basophil releasability and bronchial responsiveness, is not impaired in elderly. In conclusion, as suggested from the present and previous papers it is questionable whether there is sufficient information to validate the statement that the incidence of allergic diseases decreases with age.

Relationship between human leucocyte antigen class I and class II and chronic idiopathic urticaria associated with aspirin and/or NSAIDs hypersensitivity.

BACKGROUND: HLA genes play a role in the predisposition of several diseases. The aim was to analyze the prevalence of HLA class I phenotypes and HLA-DRB1* genotype in patients with CIU associated with ASA and NSAIDs hypersensitivity (AICU). METHODS: 69 patients with AICU, and 200 healthy subjects. RESULTS: Subjects with HLA-B44 and HLA-Cw5 antigens were more represented in patients with AICU than in control group. Subjects with HLA-A11, HLA-B13, HLACw4, and HLA-Cw7 antigen were more represented in control group than in patients with AICU. Multiple logistic regression demonstrated an association of HLA-Cw4 and HLA-Cw7 with a lower risk of AICU, whereas carriers of HLA-B44 phenotype had a higher risk of AICU. No differences were found between patients and controls as regards to HLA-DRB1* genotype. CONCLUSIONS: We observed an association between some HLA class-I antigens and AICU. To the best of our knowledge this is the first description of such association.

Food-additive-induced urticaria: a survey of 838 patients with recurrent chronic idiopathic urticaria.

BACKGROUND: Recurrent chronic idiopathic urticaria (RCIU) is a common skin condition that affects 0.1-3% of the population in the USA and Europe and accounts for nearly 75% of all 'ordinary' chronic urticaria (CU) cases. METHODS: We studied 838 consecutive patients with RCIU referred to hospital between 1998 and 2003. Patients with known causes of CU were excluded. Clinical history, physical examination, and symptom diaries were evaluated during two periods, a diet-free period (1 week) and a food-additive-free diet (FAFD) period (4 weeks), respectively, and two double-blind placebo-controlled (DBPC) challenges of six food additives were administered. The first DBPC challenge included a mixture of the six food additives (DBPCmixed) given to all patients. The second DBPC challenge comprised the single food additives, administered at increasing doses (DBPCsingle) to patients with a positive DBPCmixed test and 105 patients with a negative DBPCmixed test, as a control. RESULTS: The DBPCmixed challenge was positive in 116 patients. None of the 105 control patients had a positive DBPCsingle test. Only 31 DBPCsingle tests were positive in patients with positive DBPCmixed challenge. Twenty-four of the 116 patients showing a positive DBPCmixed challenge also had a positive DBPCsingle result. CONCLUSIONS: Our results confirmed that food additive hypersensitivity reactions occurred in few RCIU patients using DBPCsingle challenge. The combination of the results of FAFD and DBPCmixed challenge seems to be of considerable practical interest for allergists, internists and dermatologists, rather than the data of clinical history and the results of DBPCsingle challenge, in patients with RCIU.

Measurement of inflammatory mediators of eosinophils and lymphocytes in blood in acute asthma: serum levels of ECP influence the bronchodilator response.

The aim of this study was to assess the relevance of immunoinflammatory markers on the response to short acting beta(2)-agonist in acute asthma exacerbation. Thus, we measured serum eosinophil cationic protein (ECP) levels and sIL-2R at acute exacerbation in 52 adult patients with atopic asthma, and assessed forced expiratory volume in 1 s (FEV(1)) before and after the administration of aerosolized salbutamol. After a cumulative dose of salbutamol causing a 10% improvement in FEV(1) from baseline [CD10, i.e. cumulative doses of salbutamol (800 microg) causing an improvement in FEV(1) from baseline to 10%] the patients were divided into two groups: group A with CD <10 and group B with CD >10. The bronchodilator response, as defined by a DeltaFEV(1) (percentage of predictive value of FEV(1)) of > or =10 predictive value, was shown by 40% of the patients. After 200, 400 and 800 microg of salbutamol, significant differences of FEV(1) with respect to baseline values were, respectively, p = 0.049, 0.0039 and 0.0014. In contrast, no significant difference of the means of FEV(1) between the doses of salbutamol was observed. Significant differences of DeltaFEV(1) between 200 and 400 microg (p = 0.0002) and between 200 and 800 microg (p < 0.0001) were observed, but not between 400 and 800 microg of salbutamol. There were significant correlations between baseline values of predictive FEV(1) and serum ECP levels (rho = -0.60, p < 0.0001) and sIL-2R levels (rho = -0.35, p = 0.01) respectively. Besides, a correlation between DeltaFEV(1) and serum ECP levels (rho = -0.53, p < 0.0001) was observed, whereas no correlation was found between DeltaFEV(1) and sIL-2R. By analyzing differences between the two groups (A and B) for serum ECP levels, sIL-2R and blood eosinophil count, a significant difference was found for serum ECP levels. We conclude that subjects with acute exacerbation of asthma show high serum levels of ECP and sIL-2R and, more interestingly, that the response to brochodilator was higher in patients with lower serum ECP levels.

Randomized placebo-controlled trial comparing desloratadine and montelukast in monotherapy and desloratadine plus montelukast in combined therapy for chronic idiopathic urticaria.

BACKGROUND: H 1 -receptor antagonists are considered to be particularly effective in reducing pruritus, and they are therefore recommended as first-line treatment in patients with chronic idiopathic urticaria (CIU). Recently, antileukotriene receptors have been used in patients with CIU, either administered as monotherapy or combined with H 1 -receptor antagonists. OBJECTIVE: We compared the clinical efficacy of 5 mg of desloratadine administered once daily either as monotherapy or combined with a leukotriene antagonist, 10 mg of montelukast daily, and 10 mg of montelukast administered daily as monotherapy for the treatment of patients affected by CIU with placebo. METHODS: One hundred sixty patients aged 18 to 69 years (mean +/- SD, 43.9 +/- 13.4 years) with a history of moderate CIU were selected. A randomized, double-blind, double-dummy, placebo-controlled, parallel-group study design was used. Patients were treated with 5 mg of desloratadine once daily (n = 40), 10 mg of montelukast once daily (n = 40), 5 mg of desloratadine (n = 40) in the morning plus montelukast in the evening, or matched placebo (n = 40). Assessment of treatment efficacy was based on scores of daily cutaneous symptoms evaluated reflectively and instantaneously. RESULTS: Only the group treated with desloratadine as monotherapy or as combined therapy concluded the whole study. Twenty-seven of the 40 patients in the montelukast group and 35 of the 40 patients in the placebo group discontinued the treatment. As reflective evaluation, all groups showed significant differences compared with the placebo group in terms of total symptom score, number of hives, and size of largest hive. In addition to the pruritus, only the groups treated with desloratadine as monotherapy or combined therapy showed significant differences compared with those receiving placebo, whereas there were no differences between the montelukast and placebo groups. Finally, no differences were found between the desloratadine group and the desloratadine plus montelukast group. The instantaneous evaluation demonstrated similar results regarding the desloratadine group and the desloratadine plus montelukast group versus the placebo group, whereas there were no significant differences between the group treated with montelukast alone and the placebo group for pruritus and size of largest hive. No differences were found between the group treated with desloratadine alone and the desloratadine plus montelukast group. CONCLUSIONS: The results of this comparative study demonstrate that desloratadine is highly effective for the treatment of patients affected by CIU. In addition, the regular combined therapy of desloratadine plus montelukast does not seem to offer a substantial advantage with respect to desloratadine as monotherapy in patients affected by moderate CIU.