An epidemiological survey on the allergological importance of some emerging pollens in Italy.

Epidemiological studies on the pollens responsible for allergic diseases throughout Italy are lacking. Routine diagnostic panels consist prevalently of grass, Parietaria, weeds, birch, olive and mugwort. Considering the great variety of Italian geographical areas and the observation of the growing allergological importance of new botanical species (e.g., ambrosia), a survey on pollen species considered "minor" was necessary. A panel of "emerging" pollens (birch, hazelnut, alder, hornbeam, cypress, ragweed) and a routine panel were used to skin prick test 2,934 consecutive outpatients with respiratory pathology of suspected allergic origin, in 21 centers across Italy. A specific questionnaire was compiled. It was found that 20.1% of patients did not react to allergens tested, 28.2% were positive for at least one emerging pollen and 51.7% did not react to emerging pollens but tested positive for at least one allergen from the routine panel. The prevalence of single pollen species was related to geographical areas. Ragweed pollen was shown to provoke asthma much more frequently than other pollens. Hitherto scarcely considered pollens play a considerable role in causing allergic diseases in Italy. In the great majority of patients, positivity for these pollens was associated with positivity to the better recognized group of pollen allergens, although in some cases they were the primary pathogenic agent. We suggest that these more recently considered allergens be included in routine diagnostic panels.

In vitro effect of lithium chloride on interleukin-15 production by monocytes from IL-breast cancer patients.

Lithium salt compounds are used to limit the degree and duration of neutropenia in patients receiving chemotherapy for cancer. Interleukin-15 (IL-15) is a cytokine which possesses promoting activities on hematopoiesis and is also involved in antitumor response, activating NK, CTL and LAK cells. In this study we analyzed IL-15 production by monocyte cultures treated with lithium chloride (LiCl). Monocytes were obtained from patients affected by non-metastatic and metastatic breast cancer. LiCl treatment induced IL-15 production by monocytes mainly from non-metastatic patients. Combined lipopolysaccharide/LiCl treatment of monocyte cultures up-regulated IL-15 release compared to those treated with LPS alone (p<0.0001). The modulation of LiCl-induced IL-15 could counteract the immunosuppression state of cancer patients, which should be taken into account when developing new immunotherapeutic strategies.

Tolerability of meloxicam in patients with histories of adverse reactions to nonsteroidal anti-inflammatory drugs.

BACKGROUND: Adverse reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) are frequent, particularly among patients with chronic urticaria or asthma. The need to identify an alternative drug that is safe and reliable is a common problem in clinical practice. OBJECTIVE: To assess the tolerability of meloxicam, a new NSAID that selectively inhibits the inducible isoform of cyclooxygenase, in a group of NSAID-sensitive patients. PATIENTS AND METHODS: We studied 177 patients who had suffered adverse reactions to one or more NSAIDs. Cutaneous reactions were reported by 83.1% of the subjects (urticaria in 55, angioedema in 52, urticaria/angioedema in 39, and maculopapular rash in 1), respiratory symptoms by 3.9%, both cutaneous and respiratory symptoms by 9%, Stevens-Johnson's syndrome by 2.3%, and anaphylactoid reactions by 1.7%. All subjects underwent a single-blind, placebo-controlled oral challenge with divided therapeutic doses of meloxicam (1.9 mg + 5.6 mg 1 hour later = cumulative dose 7.5 mg). RESULTS: Positive reactions were observed in only two cases (1.1%), both manifested exclusively by cutaneous symptoms (urticaria/angioedema in one case and maculopapular rash/facial edema in the second). CONCLUSION: Meloxicam seems to be well tolerated by NSAID-sensitive subjects whose reactions are manifested by urticaria/angioedema. Additional study is needed for a more complete assessment of its tolerability in patients with aspirin-induced asthma and other severe manifestations of NSAID sensitivity.

In vitro interleukin-8 production by monocytes treated with lithium chloride from breast cancer patients.

AIMS AND BACKGROUND: Since interleukin-8 (IL-8) has a suppressive effect on hematopoiesis, lithium induces leukocytosis and granulocytosis and mononuclear cells are defective in patients affected by neoplastic disease, we analyzed IL-8 production by monocytes obtained from patients with nonmetastatic breast cancer (BCaM0) and metastatic breast cancer (BCaM1) and the effect of lithium chloride (LiCl) on these cells. Lithium salt compounds are used to limit the degree and duration of neutropenia in patients receiving chemotherapy for cancer and acute leukemia. Lithium influences the hematopoietic system, which is known to be regulated by numerous cytokines including IL-8. METHODS: We selected three groups of subjects (15 per group): patients affected by BCaM0, BCaM1 and healthy donors (HD) matched for sex and age. IL-8 release was assessed in supernatants of lipopolysaccharide (LPS) and/or LiCl-treated monocyte cultures. RESULTS: Monocytes from BCaM1 released higher IL-8 levels than monocytes from BCaM0 (P <0.0001); the IL-8 levels of both groups were significantly higher (P <0.0001) than those of HD. In vitro LiCl treatment reduced IL-8 production by monocytes obtained from all subjects compared to the same cells when untreated or LPS treated. The suppressive effect of LiCl on IL-8 production by monocytes from breast cancer patients was particularly marked in monocytes from BCaM0 with respect to those from BCaM1. LPS treatment increased the IL-8 production more in BCaM1 monocytes than in BCaM0 monocytes. Moreover, combined LPS/LiCl treatment of monocytes significantly (p <0.0001) downregulated the release of IL-8 compared to treatment with LPS alone. CONCLUSIONS: Our data demonstrate that monocytes from BCaM0 release larger amounts of IL-8 than monocytes from BCaM0 and from HD. Lithium was able to downregulate IL-8 production by monocytes from different subgroups. Further studies are needed to clarify if the improvement of the hematopoietic system in vivo observed following lithium therapy could reside, at least in part, in the ability of lithium to downregulate this chemokine.

Evidence for a lipid transfer protein as the major allergen of apricot.

BACKGROUND: Apricots are widely grown in Europe, and allergic reactions are becoming more common, especially oral allergy syndrome. Apricot belongs to the botanical subfamily of Prunoideae, which includes peach, the major allergen of which was identified as a 9-kd protein, a lipid transfer protein (LTP). OBJECTIVE: The aim of the study was to evaluate the IgE reactivity pattern to an apricot extract in subjects with allergic reactions to apricot, as demonstrated by a positive oral challenge response. METHODS: Thirty patients were investigated. All the patients displayed oral allergy syndrome (2 with systemic reactions) to apricot, with positive open food challenge responses, skin prick test responses, and serum-specific IgE antibodies to apricot. The IgE reactivity pattern to apricot extract was identified by using SDS-PAGE and immunoblotting. The major allergen, a 9-kd protein, was then purified by HPLC and characterized by periodic acid-Schiff stain, isoelectric point determination, and N-terminal amino acid sequencing. RESULTS: The sera from all patients allergic to apricot recognized the 9-kd protein, whereas none of the other allergens, with molecular weights from 15 to 80 kd, acted as a major allergen. The 9-kd allergen has an isoelectric point of 8.7 and is not glycosylated. Determination of the N-terminal 34 amino acid sequence showed that it belongs to the LTP family, with a 94% homology with the LTP from peach. IgE blotting of the apricot extract was completely inhibited by the 9-kd purified LTP from peach. CONCLUSIONS: The major allergen of apricot is an LTP, which is highly cross-reactive with the LTP from peach.

Evaluation of interleukin-18 production by in vitro differentiated monocytes from breast cancer patients.

Interleukin-18 (IL-18) is a multifunctional cytokine which may play an important role in cancer. In previous studies it has been reported that mononuclear cells from breast cancer patients were defective in cytokine production. In this report we examined in vitro IL-18 release by monocytes (Mo) and differentiated monocytes (Mphi) for 6 or 12 days from healthy donors (HD) and nonmetastatic breast cancer (BCa) patients prior to chemo-, hormonal or radiotherapy. Our results show no production of this cytokine by Mo and Mphi for 6 days in all the experimental conditions. HD Mphi cultured for 12 days were responsive to lipopolysaccharides only after 24 h of treatment, while significantly (p<0.05) lower amounts of IL-18 were produced by BCa Mphi cultures in the same experimental conditions. Since BCa Mphi are defective in IL-18 production, and this cytokine elicits in vivo protective antitumor effects, we hypothesize a future possibility for the use of IL-18 in cancer therapy.

Interleukin-12 and interleukin-10 production by mononuclear phagocytic cells from breast cancer patients.

Interleukin-10 (IL-10) and Interleukin 12 (IL-12) generation may be regulated by a complex monocyte and macrophage-derived cytokine network and an impairment of the immune system can be observed in neoplastic disease. In this study, we examined the production of these cytokines by phagocytic cells, obtained from breast cancer (BCa)-bearing patients. Our results suggest that an increased IL-10 formation may represent an important regulatory pathway of IL-12 production by BCa mononuclear cells. In this report, we show that mononuclear cells of patients affected by breast cancer have a defective IL-12 production capability while generating higher amounts of IL-10.

Prevalence of sensitization to Alternaria in allergic patients in Italy.

BACKGROUND: The actual prevalence of sensitization to Alternaria is not known, partly due to the unreliability of diagnostic extracts. OBJECTIVE: To assess skin positivity to extracts of Alternaria in a wide population of Italian patients suffering from respiratory symptoms using a biologically standardized extract. METHODS: A total of 2942 patients were skin prick tested with Alternaria, and a panel of common inhalant allergens. Blood samples for specific IgE quantitation were taken both from patients positive and from patients negative (control group) to Alternaria extract. RESULTS: Three hundred six patients (10.4%, ranging from 1.8% in Turin to 29.3% in Cagliari) were positive to Alternaria; 37 were sensitized to only this mold, while the remaining 269 were sensitized to at least one other allergen. Of the Alternaria-positive patients, 79.7% suffered from rhinitis and 53.3% from asthma, either alone or associated with other symptoms. CONCLUSIONS: We suggest that, at least in Italy and in countries with similar climatic and environmental situations, standardized Alternaria extract should be included in the panel commonly used in investigating the allergen responsible in patients suffering from respiratory allergy.

Comparative study between fluticasone propionate and cetirizine in the treatment of allergic rhinitis.

Among the most frequently used drugs in the treatment of allergic rhinitis we have to mention topical nasal corticosteroids and H1 antihistamines used both systemically and topically. The present study focused the effectiveness and tolerability of cetirizine and fluticasone propionate in seasonal allergic rhinitis. 54 patients, divided into three homogeneous groups, underwent the following different treatments: Group 1: Placebo of fluticasone (2 puff per nostril once daily by aerosol) + cetirizine (10 mg/die per os) for 60 days. Group 2: Fluticasone (100 mg per nostril once daily by aerosol) + placebo of cetirizine (per os) for 60 days. Group 3: Cetirizine (10 mg/die per os) for 60 days + fluticasone (100 mg per nostril once daily by aerosol) for 20 days. The patients reported nasal symptoms (sneezing, obstruction, itching, rhinorrea) on a clinical diary. ECP levels in nasal secretions were investigated in all patients to determine the anti-inflammatory activity of both treatments. Cetirizine resulted very effective in the treatment of sneezing, itching and acqueous rhinorrea whereas not much effective on nasal obstruction. On the contrary, fluticasone, which acted effectively on nasal obstruction, resulted inefficacious on the other symptoms. The third group of patients achieved the best results on all four symptoms, including obstruction, which continued even after interrupting the treatment with fluticasone. The ECP levels were significantly reduced by both treatments. The side effects in all 3 groups were rare and not serious. From these results we can assert that the synergic action of the two drugs, achieves the best effectiveness, that the fluticasone treatment can be limited to 20 days cycles and finally that both molecules are well tolerated.

Long-term tolerability of nimesulide and acetaminophen in nonsteroidal antiinflammatory drug-intolerant patients.

BACKGROUND: Oral challenges are used to identify alternative nonsteroidal antiinflammatory drugs (NSAIDs) for patients who react adversely to drugs of this class, but challenge conditions often differ from those in which the drug will actually be used. OBJECTIVE: To determine whether the results of oral challenges with nimesulide or acetaminophen, using cumulative administration of a single therapeutic dose while the patient is in good health, can predict the response to multiple doses of the drug during future illness. METHODS: Follow-up interviews were conducted with 248 NSAID-intolerant subjects who had tolerated oral challenges with nimesulide and/or acetaminophen 1 to 3 years earlier. We analyzed the adverse reaction rate in light of the febrile/non-febrile nature of the condition treated and the number of doses consumed. RESULTS: Nimesulide was tolerated by 115/122 (94.2%) of the patients who had tried it; acetaminophen by 71/75 (94.6%). A total of 8/159 (5%) patients had experienced reactions (seven urticarial and one asthmatic) to one or both drugs. Intolerance was unrelated to the nature of the condition treated or the number of doses administered, but all four patients who failed to tolerate acetaminophen and 3/7 of those who reacted to nimesulide had histories of chronic urticaria. CONCLUSIONS: Oral challenges can reliably predict long-term NSAID tolerability in patients with previous adverse reactions to other drugs of this class, except for patients with chronic urticaria.

Measurement of allergen-induced skin reactions by computerized dynamic telethermography (CDTT).

Cutaneous thermic changes induced by a skin prick test reaction were measured by an infrared thermography camera (computerized dynamic telethermography, CDTT). Changes in skin temperature (T degree) detected by CDTT were compared with the mean diameter of allergen-induced skin reactions. Cutaneous thermic increase detected by CDTT correlated well with the mean wheal diameter measured in millimeters (r = 0.938, p < 0.001). Average coefficient of variation for repeated CDTT measurements was 4.6%. CDTT provides a reproducible and precise method for measuring allergen-induced skin reactions. Moreover, the continuous recording of the skin temperature represents an additional parameter for the quantification of wheal reactions.

Rush sublingual immunotherapy in Parietaria allergic patients.

Forty patients, monosensitized to Parietaria judaica with a clinical history of at least two years of rhinoconjunctivitis with or without asthma, were selected and randomly allocated in two groups. According to an open controlled experimental plan, twenty patients were submitted to sublingual immunotherapy (SLIT) with a solution of purified and biologically standardized extract of Parietaria judaica, following a preseasonal rush schedule. All patients, twenty belonging to the SLIT group and twenty belonging to the control group, were allowed to take authorized rescue drugs at need. At the end of the Parietaria pollen season. 15 patients for each group resulted to have complied with the criteria of the study. SLIT tolerance turned out to be excellent as no side effects were noticed in the group under treatment. No change could be detected in specific IgE and IgG4 in either group. According to the daily symptom and drug scores registered by each patient in a diary card, the SLIT group showed a statistically significant lower symptom score (p = 0.032) and lower drug plus symptom score (p = 0.037) during the peak pollen period (May-June 1994) in comparison to the group treated only with symptomatic drugs. Moreover, 13 out of 15 patients submitted to SLIT expressed a very favourable subjective opinion about the therapy and asked to continue the same treatment the following season. According to our results, the rush SLIT schedule, followed by maintenance during the pollen season, is simple, safe and effective for Parietaria pollen allergy and showed an excellent compliance.

Lp(a) levels and reduced risk of vascular atheromatosis in patients with alcoholic liver disease.

In a group of 80 patients (50 male and 30 female) aged between 44 and 65, affected by alcoholic liver disease (46 with steatosis and 34 with liver cirrhosis) the Authors examined the relationship between the plasma lipid, in particular of Lp(a), and the incidence of vascular atherosclerotic plaques. The results were compared with those found in the controls (50 subjects of similar age, social and working status to that of the above patients but nondrinkers without liver or other metabolic disease). In the patients with steatosis we found a moderate increase in plasma lipid fractions including total, HDL and LDL cholesterol, but low levels of Lp(a), with an incidence of arterial plaques of 10.86%. In those with liver cirrhosis the findings were characterized by low levels of lipids and in particular of Lp(a), with an incidence of arterial plaques of 8.82%, decidedly less marked than in the controls (16%). In both cases the low incidence of vascular involvement appears to be in some way linked with low levels of Lp(a) and the severity of liver disease and not with the behaviour of HDL cholesterol.

[Alcohol and idiopathic dilatated cardiomyopathy: a pathogenetic hypothesis]. / Alcool e cardiomiopatia dilatativa idiopatica: una ipotesi patogenetica.

In a group of 120 chronic alcoholics, we observed two cases of severe dilated cardiomyopathy, fatal within a year, similar to the so called "idiopathic" form, among cases of cardiovascular involvement related to alcohol abuse (63.5%) but susceptible of improvement following abstention. On the basis of their observation we believe that alcohol itself, as has already been demonstrated for certain viruses, in the presence of particular genetic factors can cause the onset of an immune reaction able to impart an autonomous course which cannot be checked even after abstention from alcohol.