Rabbit allergens: a significant risk for allergic sensitization in subjects without occupational exposure.

BACKGROUND: Although rabbits are becoming popular as pets, data about the characteristics of allergic sensitization to rabbit allergens in patients without professional exposure are scarce. AIMS OF THE STUDY: To determine the characteristics of allergic sensitization to pet rabbits, and the role of direct and indirect exposure to rabbits and rabbit allergens in non-professionally exposed patients. METHODS: From among 1124 consecutive outpatients, we selected all subjects with an immediate skin reaction to rabbit dander. A clinical history including a careful evaluation of the modality of rabbit exposure, the results of skin-prick tests (SPTs) and total/specific IgE antibodies were recorded. The prevalence of rabbit ownership in the Naples area was also calculated. RESULTS: Among 753 SPT-positive patients, 20 (2.65%) were sensitized to rabbit dander (5 patients were mono-sensitized). Fifteen patients reported direct rabbit contact (7 were rabbit owners and 8 had occasional contact outside the home); 3 patients had indirect exposure through contact with rabbit owners and 2 patients denied any direct or indirect exposure. Rabbit mono-sensitized owners of pet rabbits had persistent (moderate-severe) symptoms. The prevalence of rabbit ownership is 1.56%. CONCLUSIONS: In susceptible not professionally exposed individuals, direct rabbit contact and, in some cases, indirect or no apparent exposure, may induce allergic sensitization to rabbit allergens. A progressive increase in rabbit sensitization (also by indirect exposure) may be expected as a consequence of the increase in rabbit ownership.

Effect of formoterol/budesonide combination on arterial blood gases in patients with acute exacerbation of COPD.

BACKGROUND: Patients with severe chronic airway obstruction might suffer dangerous hypoxemia after administration of a beta-agonist despite bronchodilation. METHODS: We first compared the acute effects on gas exchange of two doses of formoterol Turbuhaler (9 and 18 microg) in 10 patients with acute exacerbation of COPD. Afterwards, we compared the acute effects of formoterol Turbuhaler 9 microug with those of formoterol/budesonide combination in a single inhaler (Turbuhaler) 9/320 microg in 10 other patients with acute exacerbation of COPD. Finally, we compared the changes in PaO(2) induced by formoterol Turbuhaler 9 microg or formoterol/budesonide combination in a single inhaler (Turbuhaler) 9/320 microg with those in FEV(1) in 10 other patients with acute exacerbation of COPD. Each agent was given on separate days, and the patients' arterial blood gases were measured at baseline and at intervals of 120 min. RESULTS: Small but statistically significant declines in PaO(2) were found after administration of both formoterol 9 and 18 microg. In the second group of patients, formoterol 9 microg alone again induced a significant decrease in PaO(2). However, the simultaneous administration of budesonide 320 microg significantly reduced the acute effect of formoterol on PaO(2). In a third group of 10 patients we confirmed a small but significant decrease in PaO(2) after formoterol alone and the reduction of this effect when budesonide was administered simultaneously. Moreover, we also documented that addition of budesonide amplified the fast onset of action of formoterol. CONCLUSIONS: These results suggest that when treating patients suffering from acute exacerbation of COPD with formoterol, it is prudent to check their arterial blood gases. In any case, combined administration of formoterol and budesonide reduces the potential for acute effects of formoterol on blood-gas tensions.

Asthma treatment must be always tailored to the individual patient.

Several studies have shown that there are notable benefits in adding a long acting beta 2-agonist to an inhaled corticosteroid. Particularly, long acting beta 2-agonists allow to reduce the amount of steroid that is required to induce a specific response and, consequently, its possible side effects. Currently the pharmaceutical market promotes, and physicians tend in any case to privilege, the use of fixed combinations for the treatment of the asthmatic patient and this also in the first phases of the illness. Nevertheless, for the majority of patients with mild to moderate asthma, it seems more reasonable to optimize the dose of the inhaled steroid before considering the addition of a long-acting beta 2-agonist, and use this latter on an 'as needed' basis if its pharmacodynamic characteristics allow it. Use of combinations is the more reasonable therapeutic choice for patients with a more severe pathological picture, who, despite the optimized dosage of the inhaled glucocorticoid, also require a long acting beta 2-agonist. After having verified the stability of the clinical control, it is possible to continue with the combined therapy provided, however, that this allows the treatment of the patient with the lowest dose of corticosteroid able to prevent, as far as is possible, exacerbations. Asthma exacerbations are less frequent with this therapy, but when they appear it is necessary to be immediately able to increase and, sometimes, also maximize the dosage of corticosteroid without being forced to double, or even triple, the dose of the long acting beta 2-agonist unless there is a real need--and which probably, rather, would induce unwanted side effects.

Parenteral antibiotic therapy in the treatment of lower respiratory tract infections. Strategies to minimize the development of antibiotic resistance.

Antibiotic use is often imputed for increases in the prevalence of infections due to antibiotic-resistant bacteria. Resistance depends on the variety of genotypes in the large bacterial population and also on the selective pressures that are produced along the antibiotic concentration gradients in the body. In effect, at certain selective concentrations the antibiotic eliminates the susceptible majority, leaving a selected remainder intact. Therefore, the choice of antibiotics for the treatment of lower respiratory tract infections should take into consideration not only their effectiveness but also the pharmacokinetics of each agent and its delivery schedule. In fact, the potential therapeutic efficacy of an antibiotic depends not only on its spectrum of action, but also on the concentration it reaches at the site of infection. Most infections occur in the tissues of the body rather than in the blood and that it is accepted that appropriate antibiotic therapy requires the maintenance of significant concentrations of antibiotics at the site of infection in the lung long enough to eliminate the invading pathogen. Thus, the development of dosing schedules for most antimicrobials has been based on the postulate that drug levels need to be above the minimal inhibitory concentration (MIC) at this site for most or all the dosing interval. The selection of antimicrobial resistance appears to be strongly associated with suboptimal antimicrobial exposure, defined as an AUIC(0-24)/MIC ratio of less than 100O125. Antimicrobial regimens that do not achieve these values cannot prevent the selective pressure that leads to overgrowth of resistant bacterial subpopulations. It has been suggested that resistance can be avoided with attention to dosing, since dosing which provides an AUIC(0-24)/MIC ratio of at least 100 appears to reduce the rate of the development of bacterial resistance. Unfortunately, very different serum or lung concentration profiles can result in the same AUIC(0-24)/MIC. High doses administered sufficiently may often completely prevent any possibility of attaining a selective concentration. Alternatively, an antibiotic which has good bactericidal potency and maintains tissue and/or serum concentrations greater than the MIC or, better, minimal bactericidal concentration (MBC) throughout the dosing interval is equally effective in minimizing the development of antibiotic resistance.

Comparison of the effects of single oral doses of nebivolol and celiprolol on airways in patients with mild asthma.

OBJECTIVE: The respiratory effects of nebivolol, a new selective ss(1)-adrenergic blocking agent, and celiprolol, a ss-blocker possessing strong ss(1)-adrenoceptor antagonist and mild ss(2)-agonist properties, were investigated in 12 patients with mild asthma. DESIGN: Changes in several spirometric indexes (FVC, FEV(1), and forced expiratory flow rate at 50% of FVC) were measured. The interaction with the bronchodilator effect of the ss(2)-adrenoceptor-selective agonist albuterol also was investigated. RESULTS: The effect of both nebivolol and celiprolol on FEV(1) was considered to be significant (p < 0.05). The administration of nebivolol and celiprolol, but not of placebo, elicited a decrease in FEV(1): mean maximum difference for nebivolol, -0.272 L (95% confidence interval [CI], -0.402 to -0.142); mean maximum difference for celiprolol, -0.193 L (95% CI, -0.316 to -0.071); mean maximum difference for placebo, -0.0001 L (95% CI, -0.087 to 0.085). The inhalation of albuterol, up to a dose of 800 microg, significantly (p < 0.05) improved FEV(1), but the values after nebivolol and celiprolol administration were lower than the initial values. Both ss-blockers caused equal changes in heart rate, systolic BP, and diastolic BP. CONCLUSIONS: There were no significant differences between the respiratory actions of the two active drugs.

Effects of formoterol, salmeterol or oxitropium bromide on airway responses to salbutamol in COPD.

We examined whether a pretreatment with formoterol, oxitropium bromide, or salmeterol might modify the dose-response curves to inhaled salbutamol in patients with stable and partially reversible chronic obstructive pulmonary disease (COPD). Sixteen outpatients with partially reversible, stable COPD received 24 microg formoterol, 50 microg salmeterol, 200 microg oxitropium bromide, or placebo on four non-consecutive days. Spirometric testing was performed immediately before inhalation of treatment and after 2 h. A dose-response curve to inhaled salbutamol was then constructed using doses of 100, 100, 200 microg and 400 microg--that is, a total cumulative dose of 800 microg. Dose increments were given at 20 min intervals with measurements being made 15 min after each dose. Formoterol, salmeterol, or oxitropium bromide elicited a significant increase in forced expiratory volume in one second (FEV1) compared with placebo (mean differences (L) = placebo 0.05; formoterol 0.34; salmeterol 0.27; oxitropium bromide 0.23). Dose-dependent increases in FEV1 were seen (mean values (L) before salbutamol and after a cumulative dose of 100, 200, 400, and 800 microg = placebo: 1.06, 1.28, 1.35, 1.39, 1.41; formoterol: 1.33, 1.37, 1.41, 1.44, 1.44; salmeterol: 1.30, 1.33, 1.36, 1.39, 1.42; oxitropium bromide: 1.27, 1.34, 1.37, 1.41, 1.40). Statistical analysis revealed no significant differences in FEV1 and forced vital capacity (FVC) responses to salbutamol after therapy with formoterol, salmeterol, or oxitropium bromide compared with placebo. This study clearly shows that a pretreatment with a conventional dose of formoterol, salmeterol, or oxitropium bromide does not preclude the possibility of inducing a further bronchodilation with salbutamol in patients suffering from partially reversible chronic obstructive pulmonary disease.

[Correlation between pulmonary pharmacokinetics and pharmacodynamics support the hypothesis of the usefulness of ceftazidime at a single 1g daily dose in the treatment of bacterial exacerbation of chronic obstructive bronchopneumonia with moderate functional damage]. / Le correlazioni esistenti tra farmacocinetica polmonare e farmacodinamica permettono di ipotizzare l'utilizzo del ceftazidime alla dose di 1 g una sola volta al giorno nel trattamento delle riacutizzazioni batteriche della broncopneumopatia cronica ostruttiva con danno funzionale moderato.

INTRODUCTION AND BACKGROUND: Experimental studies have shown that cephalosporins have an antibacterial effect in vivo even when their levels are above MIC for only 40-50% of dosing intervals, whereas maximum killing is obtained when concentrations are above MIC for 60-70% of the time. Since most patients treated with antibiotics have neutrophils and other natural defence mechanisms, it is likely that a bacteriostatic effect should be sufficient to induce an effective therapeutic response. METHODS: Given that in the potential sites of lung infection ceftazidime reaches significantly higher levels than the MIC of the most commonplace respiratory pathogens, even 8-12 hours after the administration of 1 g i.m., the authors evaluated the efficacy of treatment of renewed acute episodes of COPD using this antibiotic at a dose of 1 g once a day. In order to do this, 20 outpatients were enrolled in the study, half of whom presented moderate bronchial obstruction (FEV1 = 50-70% of theoretical) whereas the remainder presented marked bronchial obstruction (FEV1 = < 50% of theoretical). RESULTS: The 10 patients with moderate obstruction at the time of enrollment, who presented Haemophilus influenzae, Streptococcus pneumoniae or Moraxella catarrhalis as causal agents in the sputum (Escherichia coli was only isolated in one patient), showed a marked improvement following treatment with 1 g ceftazidime one a day. A real or presumed eradication of the causal microorganism was observed in all subjects. Treatment with ceftazidime at the dose of 1 g/die once a day was much less effective in patients with marked bronchial obstruction. Treatment was successful in 7 out of 10 subjects, but 2 of them relapsed within 2 weeks. In this second group, Pseudomonas aeruginosa was found in the sputum of 3 patients; one of the patients showed a persistence of the bacterium after ceftazidime treatment, and another presented reinfection 12 days after the end of treatment. The two patients in whom Staphylococcus aureus was isolated did not benefit from ceftazidime treatment at this dosage. One subject who initially presented Streptococcus pneumoniae in his sputum and was then thought to have recovered, underwent a new acute episode caused by Moraxella catarrhalis 2 weeks after the suspension of ceftazidime treatment. CONCLUSIONS: The therapeutic responses observed during this study suggest the possibility of using ceftazidime in a single daily dose of 1 g i.m. to treat those patients with exacerbations of COPD who only present moderately impaired functional symptoms. On the contrary, this type of therapeutic approach must be used with extreme caution in subjects with marked functional damage, although a satisfactory clinical response may be obtained in some cases. However, the small number of patients included in this study does not allow firm conclusions to be drawn. Only a study involving a larger group of patients could provide the necessary information to confirm the hypothesis for treatment put forward by the authors.

Oral allergy syndrome (OAS) in pollinosis patients after eating pistachio nuts: two cases with two different patterns of onset.

We describe two uncommon cases of oral allergy syndrome (OAS) after eating pistachio nuts (p.n.) in subjects (a 54-year-old man and a 3-year-old girl) with exclusive skin prick test (SPT) positivity to Parietaria (P.) and pistachio nut (p.n.) allergens. Serologic P.- and p.n.-specific IgE determinations were also carried out. A double-blind, placebo-controlled food challenge (DBPCFC) was performed, for ethical reasons, only in the adult patient, but we observed a positive intraoral reaction only after slight scratching of the oral mucosa. Since this patient had put three whole p.n. with their shells into his mouth, breaking them with his teeth, before the onset of symptoms, we suggest that slight injury of the oral mucosa may enhance the local response. Preliminary results with SDS-PAGE and immunoblotting demonstrate the occurrence of a slight degree of cross-reactivity between these allergens, but further studies are necessary to obtain a definite conclusion.

Why are nasal and bronchial symptoms mostly perennial in patients with monosensitization to Olea europaea pollen allergens?

In the last few years interest in the clinical aspects of Olea europaea (O.e.) pollen allergy has increased. For many years we have observed in our geographical area a perennial pattern of clinical symptoms in subjects with monosensitization to O.e. allergens without any worsening during the olive pollen season. We tried to demonstrate the clinical relevance of O.e. sensitization in our patients and, moreover, to determine why this pattern is elicited. We selected a group of 26 patients with rhinitis and/or bronchial asthma and an immediate positive skin reaction only to O.e. pollen extract. Using commercially available extracts and reagents, the following diagnostic procedures were performed: Skin prick tests (SPT), specific O.e. IgE assays, nonspecific bronchial provocation tests (NsBPT) and specific nasal provocation tests (sNPT), respectively, in patients with bronchial asthma and rhinitis. Pollen counts and a statistical analysis using Spearman's correlation test were also carried out. 21 of 26 O.e. monosensitive patients showed perennial type of clinical symptoms without any particular worsening during olive pollination season. We found a high degree of statistical significance between the results of SPT/sNPT and serum specific IgE determination. Many patients exhibited a late response after sNPT. No definitive data were derived from our findings, even though the occurrence of many late reactions after sNPT could in part explain the perennial type of nasal symptoms. We would like to emphasize the necessity of better purification and standardization of diagnostic materials and, moreover, suggest further studies with a greater number of O.e. monosensitive patients living in different geographical areas.

Clinical significance of allergic sensitization to cockroaches in patients with mite related respiratory allergy.

The aim of our study was the evaluation of the clinical significance of allergic sensitization to cockroaches (C) in subjects with skin prick test (SPT) positivity only to mites, since we previously demonstrated a frequent association of SPT positivity between the allergens of these parasites. We studied 231 patients with mite related respiratory symptoms and living in the Naples area in order to obtain a highly homogeneous sample. All patients underwent anamnestic procedures, physical examination, SPT by using commercially available materials and an extract containing the whole bodies of three C. Specific C IgE assays were carried out only in C SPT positive patients. 34 of 231 subjects showed a SPT positivity to C allergens with a moderate/low degree of SPT responses and serum specific IgE levels. The results of this study confirm our previous report on the slight role of C as sensitizing agents of the respiratory tract in Southern Italy. Further studies should be carried out in subjects with a higher risk of environmental exposure by using better purified and standardized allergenic extracts. We suggest moreover to perform in vivo and in vitro diagnostic tests for C allergens in patients with perennial symptoms, especially in those with slight response to therapy, or potentially exposed to allergens of these insects.

[Allergic rhinitis due to cockroach antigenic components. An emerging pathology?]. / La rinite allergica da componenti antigenici di blatta. Una patologia emergente?

The aim of our study was the evaluation of the role of these insects as causative agents of perennial rhinitis. We studied 317 subjects of both sexes (175 F and 142 M) living in Naples area and examined consecutively in our Centre for perennial nasal symptoms of suspected IgE mediated aetiology. All patients underwent the following diagnostic procedures: anamnestic procedures by using an internal questionnaire, clinical examination, skin prick test by using commercially available allergenic extracts and an allergenic extract containing the whole bodies of Blattella germanica and orientalis, Periplaneta americana. Blood samples for specific IgE determinations and a rhinologic visit were also carried out in patients with cockroach skin Prick test positivity. 14 of 317 subjects, prevalently young males, presented a skin positivity to cockroach allergens. All patients showed a moderate low degree of cutaneous and a low degree of serologic sensitization to allergens of these insects. Our preliminary data seem to demonstrate a mild role of cockroaches as causative agents of perennial rhinitis in Naples area. Further studies are necessary for a more appropriate knowledge of this allergy.