Serum specific IgE: Biomarker for specific immunotherapy responsiveness?

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A prospective Italian survey on the safety of subcutaneous immunotherapy for respiratory allergy.

BACKGROUND: Subcutaneous immunotherapy is effective for the treatment of respiratory allergy, and it is largely used in Italy, but no systematic safety assessment has been carried out so far. OBJECTIVE: To assess prospectively the safety of injection immunotherapy in a multicentre, real-life survey. METHODS: Eleven Italian allergy departments recorded the clinical characteristics of systemic reactions (SRs) due to immunotherapy. Vaccines were prescribed according to guidelines; only standardized depot extracts were used. SRs were graded according to the EAACI recommendations, and were classified as immediate or delayed. RESULTS: One thousand seven hundred and thirty-eight patients (847 males, age range 5-71) received immunotherapy from eight different manufacturers, for a total of 2038 courses (300 patients received two extracts). A total of 60 785 injections were given over a mean immunotherapy duration of 3 years. Overall, 95 reactions were observed in 57 patients (3.28%), corresponding to 4.7% of the courses and 1.56/1000 injections. Twenty-five patients experienced more than one adverse event. There were 34 grade 2, 60 grade 3 and one grade 4 reactions and no fatality. SRs occurred more frequently in patients with asthma than in patients with rhinitis alone (4.1% vs. 1.1%), and were equally distributed between the build-up and the maintenance phase. Ragweed and grass extracts caused significantly more side effects than other allergens. CONCLUSION: In this large prospective study, the rate of SRs was low, thus confirming that injection immunotherapy has an acceptable risk/benefit ratio when prescribed and carried out according to recommendations.

Reference values for IgG and IgG4 serum levels specific for inhalant allergens in non-atopic subjects.

The IgG response to allergens is well-known, however few studies have investigated IgG and IgG4 production in normal subjects. Therefore, total IgG and IgG4 serum levels specific for 6 common inhalant allergens were measured in 282 non-allergic subjects to establish reference values at different ages and sex. Thus, 282 subjects were studied (141 female and 141 male) ranging from pre-school to adult age, all living in Northern Italy at the time of the study. Family history of first degree relatives and personal history were negative for allergic diseases. The findings obtained in this study indicate that: i) reference values for specific IgG4 and IgG levels against the allergen studied should take into account both the sex and age of the subject evaluated; ii) there is a difference in trend for age between seasonal and perennial allergens and iii) the relationships between age and specific IgG4 and IgG levels have different slopes. In conclusion, relevant differences exist in the distribution of IgG and IgG4 levels in normal subjects.

Characteristics of patients with allergic polysensitization: the POLISMAIL study.

BACKGROUND: The natural history of respiratory allergy is commonly characterized by a worsening of symptom severity, frequent comorbidity of rhinitis and asthma, and polysensitization to aeroallergens. The polysensitization phenomenon starts since childhood and is rare to find monosensitized adult patients. However, there are few studies investigating the characteristics of polysensitized patients. METHODS: This study was performed on a large cohort of patients with allergic rhinitis (assessed by ARIA criteria) and/or mild to moderate asthma (assessed by GINA). The kind and the number of sensitizations, their patterns, and the relation with quality of life (QoL) measured by the Juniper's RQLQ guestionnaire, were evaluated. RESULTS: Globally 418 patients (50.2% males, 49.8% females, mean age 26.4 years, range 3.5-65 years, 64 smokers, 371 non-smokers) were enrolled: 220 had allergic rhinitis alone, and 198 allergic rhinitis and asthma. The mean number ofsensitizations was 2.6. Three hundred-five patients (73%) had persistent rhinitis (PER), 220 of them with moderate-severe form. There was no significant derence in rate of rhinitis and asthma in monosensitized or polysensitized patients. Most patients were sensitized to pollens, whereas only 24.2% of them were sensitized to perennial allergens. Polysensitization was significantly associated with some issues of QoL, confirming previous findings, but not with number ofsensitizations. CONCLUSIONS: This study provides data confirming for poly-sensitized patients the relevance of ARIA classification of AR. PER is the most common form of AR in this cohort, symptoms are frequently moderate-severe, and asthma is present in about the half of patients with AR.

Variations in serum levels of interleukin (IL)-1beta, IL-2, IL-6, and tumor necrosis factor-alpha during specific immunotherapy.

BACKGROUND: Cytokine production by T helper cells is essential for the induction and maintenance of allergic inflammation in the bronchial mucosa. According to recent views, specific immunotherapy (SIT) favors the differentiation of T lymphocytes into cells of the Th1 rather than those of the Th2 subset. OBJECTIVE: To determine whether or not SIT induces a decrease in the inflammatory reaction by studying eventual variations in the serum levels of IL-1beta, IL-2, IL-6, and TNF-alpha in allergic subjects during SIT. METHODS: Serum levels of IL-1beta, IL-2, IL-6, and TNF-alpha were determined before and after 3, 6, and 9 months of SIT by an immunoradiometric assay (IRMA) in 11 adults with perennial allergic asthma and/or rhinitis caused by house dust mites and in 6 nonatopic healthy volunteers. RESULTS: Median serum IL-1beta and TNF-alpha levels of the patients were significantly higher at baseline than those of the controls and decreased during SIT to values similar to or lower (P < .01) after 6 months of SIT for TNF-alpha than those of the controls. Median serum IL-2, significantly lower at baseline than in the controls, increased during SIT to a level similar to that of the controls. Although the median values of IL-1beta and TNF-alpha in the patients tended to decrease and those of IL-2 to increase during SIT, the differences were not significant; the correlation coefficients (r) of the serum levels of IL-1beta IL-6, and TNF-alpha versus duration of SIT were negative, while that of IL-2 was positive. CONCLUSIONS: Decreases in median serum IL-1beta and TNF-alpha levels during SIT, together with the increases in serum IL-2 and IL-6, compared with those of the controls furnish evidence supporting a reduction in the inflammatory response in the course of SIT.

Primary mediastinal seminoma.

We describe three cases of primary mediastinal seminoma, a rare neoplasm histologically similar to the testicular form, which mainly affects men between 30-60 yrs of age. Case No. 1--a 45 year old patient was treated with a combination of radiotherapy and chemotherapy. Twenty six months after the diagnosis, the patient shows a limited residual lesion, a good general health status and was asymptomatic. Case No. 2--a 56 year old patient was admitted for suspected epithelial lung cancer, with subsequent histological diagnosis of seminoma on surgical sample. The exeresis of the lesion was followed by radiotherapy and chemotherapy, the latter interrupted owing to the onset of thrombotic complications resulting in the patient's death. Case No. 3--a 35 year old patient was subjected to diagnostic and therapeutic thoracotomy, with diagnosis of primary mediastinal seminoma. The surgical therapy was followed by a cycle of radiotherapy. Five years later, the general health of the patient is good and he is still asymptomatic. In the discussion we consider the embryogenesis, clinical picture, radiological and anatomicopathological aspects, typical biomarkers of cancer, diagnostic procedures and therapeutic protocols currently followed.

[The importance of measuring plasma carcinoembryonic antigen in small-cell anaplastic carcinoma]. / Il significato del dosaggio dell'antigene carcinoembrionario plasmatico nel carcinoma anaplastico a piccole cellule.

The clinical value of the serum biomarker carcinoembryonic antigen (CEA) was evaluated prospectively in 118 patients with small cell lung cancer (SCLC) entered chemotherapy protocol between 1986 and 1992. Five quantitative categories were determined: less than 2.5 ng/ml and 2.6-5.0 ng/ml (the standard normal), 5.1-20.0 ng/ml, 20.1-100 ng/ml and greater than 100 ng/ml. 70% of patients had levels less than 5 ng/ml and only 19% had levels greater than 20 ng/ml. There was no clearcut relationship of plasma CEA level to stage of disease, in which 61% of patients with extensive disease (59 patients) had levels less than 5 ng/ml and 22% of patients with limited disease (59 patients) had levels greater than 5 ng/ml. There was a modest relationship of CEA levels to presence of metastases, in that 50% of patients with metastases had levels greater than 20 ng/ml. The average survival for the pathologic and normal category was almost similar, ranging from 13.27 to 16.81 months. The correlation between disease extent and survival was more sensitive for lactate dehydrogenase (LDH) than for CEA. So CEA as a tumor marker for SCLC must be applied in conjunction with other biomarkers, particularly LDH and neuron specific enolase (NSE) and is meaningful in only a small proportion of patients.

In vitro activity of flurithromycin, a novel macrolide antibiotic.

Flurithromycin is an (8,S)-8-fluoroerythromycin isolated from the fermentation broth of Streptomyces erythraeus ATCC 31772, a blocked mutant of a strain producer of erythromycin. Its in vitro antibacterial activity has been determined on recent clinical isolates of respiratory pathogens. The range of MIC for Streptococcus pneumoniae and Streptococcus beta-haemolyticus group A is from 0.0015 to 0.006 microgram/ml, for Haemophilus influenzae from 0.012 to 0.4 microgram/ml, for Staphylococcus aureus from 0.1 to 3.1 micrograms/ml. Its action is bacteriostatic and increases at alkaline pH. Among anaerobes Clostridium perfringens, Bacteroides fragilis, other species of Bacteroides and Peptostreptococcus are particularly susceptible. Flurithromycin also showed some activity on Mycobacterium bovis, M. scrofulaceum and M. phley. The determination of killing curves indicated that in most cases a killing effect was obtained at 4 X MIC. A combination of flurithromycin with ampicillin or doxycycline sometimes was synergic, but more often additive and never antagonistic. The possible interference of flurithromycin on some parameters of the natural system of defense was determined. At concentrations equal to therapeutic levels in blood and tissues, flurithromycin did not influence chemotaxis, phagocytosis, metabolic activation and the killing activity of neutrophils.

In-vitro antibacterial activity of cefotetan.

The in-vitro activity of cefotetan, a recently developed cephamycin, was investigated under various experimental conditions. The compound showed moderate activity against Staphylococcus aureus and Streptococcus pyogenes, no activity against Pseudomonas aeruginosa and Streptococcus faecalis, but a high activity against Enterobacteriaceae, including beta-lactamase-producing strains. Haemophilus influenzae also was fairly susceptible. The MBC was usually equal to or two- or fourfold higher than MIC. Medium composition, pH and inoculum size had minimal influence on its activity. About 50% of recent clinical isolates of Bacteroides fragilis were susceptible to cefotetan, but some were highly resistant. Killing curves of cefotetan against different bacterial strains indicated that it was rapidly bactericidal at concentrations equal to MIC or two- to fourfold higher. However, some strains showed regrowth after initial inhibition. Combination of cefotetan with aminoglycosides, or with cefazolin, cefotaxime, moxalactam or piperacillin resulted either in synergy, addition or indifference according to the bacterial strain and the nature of the combination. Antagonism was never observed. Human serum protein binding varied from 75 to 86% according to the assay method. Binding with horse serum protein was about 28%.

Serum and saliva levels of a trimethoprim-sulfamethopyrazine combination in man.

A combination of trimethoprim (TMP) and sulfamethopyrazine (SMP) was administered to six healthy volunteers for 8 days, according to the proposed therapeutic repeated dose schedule. The weak base TMP (pKa = 7.3) and the weak acid SMP (pKa = 6.1) were measured simultaneously in serum and saliva, both under normal conditions and after stimulation of saliva flow. The flow of saliva was stimulated by chewing plastic material in order to obtain saliva at a pH close to the normal plasma pH of 7.4. This procedure excluded pH-dependent distribution effects. Under these experimental conditions a highly significant correlation was observed between the serum and saliva concentrations of both drugs, with very small inter- and intraindividual variations. Substantial agreement was found between the saliva:serum concentration ratio and the fractions of both drugs not bound to plasma protein. Some discrepancies were noted, probably due to minor shifts in saliva pH during the collection period.