Randomized open comparison of montelukast and sublingual immunotherapy as add-on treatment in moderate persistent asthma due to birch pollen.

BACKGROUND: No studies have directly compared the effects of immunotherapy and antileukotrienes due to the long time required to appreciate the clinical effects of immunotherapy. We compared the effect of montelukast (MK) and SLIT added to standard therapy in moderate asthma over 5 years. METHODS: Open randomized controlled trial. Patients with moderate asthma (and rhinitis) solely due to birch pollen were randomized to receive either MK (10 mg/d) or birch sublingual immunotherapy (SLIT) in the pollen seasons, in addition to formoterol/fluticasone. All the patients also received salbutamol and cetirizine as rescue medications. Asthma and rhinitis symptoms were recorded on diary cards from February to May at baseline and after 3 and 5 years of study. In-season nasal eosinophils and bronchial hyperresponsiveness were also evaluated. RESULTS: Thirty-three adult patients were enrolled and 29 completed the study. The groups were homogeneous at baseline. Bronchial and nasal symptom scores were lower at 3 and 5 years compared to baseline in the SLIT group. Bronchial hyperresponsiveness and bronchodilator use decreased significantly in both groups at 5 years, but only in the SLIT group at 3 years. In the SLIT group there was a significant decrease in nasal eosinophils compared to baseline and to the MK group. CONCLUSION: In patients with birch pollen-induced moderate asthma and rhinitis, the addition of SLIT provides a greater clinical benefit than that of MK.

Lower respiratory tract inflammation in chronic bronchitis. Evaluation by bronchoalveolar lavage and changes associated with treatment with Immucytal, a biological response modifier.

Chronic bronchitis (CB) is characterized by inflammatory changes in the bronchial tissue and by recurrent bronchitis exacerbations. In addition, defective systemic and local immune mechanisms have been demonstrated and biologic response modifiers (BRMs) have been recently introduced for clinical use in patients with CB. We studied 24 patients with CB by bronchoalveolar lavage (BAL), before and after a 4-week treatment protocol with inhaled Immucytal (Pierre-Fabre Pharma Srl, Milan, Italy), a BRM composed of bacterial ribosomal fractions and membrane proteoglycans. Compared with normal controls (NC), before treatment BAL in patients with CB contained increased proportions of neutrophils (NC, 0.8 +/- 0.2 percent; CB, 3 +/- 1 percent), of eosinophils (NC, 0.1 +/- 0.02 percent; CB, 0.6 +/- 0.2 percent); and of lymphocytes (NC, 6 +/- 1 percent; CB, 13 +/- 2 percent; p < 0.01 each comparison) with higher percentages of CD3+ and CD8+ lymphocytes (p < 0.01 each comparison). In BAL from patients with CB there were also higher levels of albumin and of the ratio IgG/albumin (p < 0.01 and p < 0.05, respectively, compared with NC). After Immucytal treatment, the proportions of lymphocytes in BAL in patients with CB were decreased (13 +/- 2 percent before, 6 +/- 1 percent after; p < 0.01). In addition, the posttreatment BAL samples contained significantly fewer neutrophils per milliliter of BAL (3.7 +/- 0.8 x 10(3) neutrophils per milliliter of BAL before, 1.5 +/- 0.5 x 10(3) neutrophils per milliliter after; p < 0.05). No differences were seen for the proportions of lymphocyte subpopulations and for the protein levels between the BAL obtained before and after Immucytal treatment. These data demonstrate the presence of a lower respiratory tract inflammation in patients with CB and suggest that treatment of patients with CB with a BRM may change the proportions of inflammatory cells present in BAL.

Distribution of bronchial nonspecific reactivity in the general population.

We investigated 654 subjects of a small Lombardy (Italy) town between 15 and 64 years of age who were representative of the general population. By clinical examination, the sample included 535 normal subjects (164 normal smokers, 341 normal nonsmokers, 30 normal subjects with acute upper respiratory illness within 30 days before the challenge), 50 with chronic bronchitis, 26 with asthma, and 43 with allergic rhinitis. Subjects whose FEV1 was 75 percent or more than the predicted value (654) underwent methacholine bronchial challenge by means of 1 percent metered-dose solution. The test result was considered positive at a drop of more than 15 percent in FEV1 (compared with buffer). Normal smokers and all of the groups with disease had a significantly different distribution of reactivity compared with normal nonsmokers. The difference between asthmatic and these "normal" subjects was highly significant; nevertheless, a clear cut-off between the two groups does not appear to exist.

Cefepime versus ceftazidime in the treatment of lower respiratory tract infections.

The objective of the study was to compare the safety and efficacy of cefepime and ceftazidime in the treatment of community acquired lower respiratory tract infections of moderate intensity. Eighty-six patients were randomized at a 2:1 ratio to receive respectively cefepime 1 g b.i.d. or ceftazidime 1 g t.i.d. The drugs were well tolerated and the occurrence of adverse events in each group was comparable. The rates of satisfactory clinical response were 96% (49/51) for cefepime and 89% (24/27) for ceftazidime. A total of 73 pathogens were isolated and pathogen eradication rates were 98% and 96% respectively for the cefepime and ceftazidime treatment groups. In conclusion, the data confirmed that cefepime could be a good alternative to ceftazidime.

Myocardial injury induced by a single dose of adriamycin: an electron microscopic study.

Adriamycin cardiomyopathy has been studied under the electron microscope using myocardial ventircular cells of CRF mice, previously treated with 10 mg/kg body weight of the drug given in a single intravenous injection. Within 10 min myocardial cell nucleoli show a nucleolonema fragmentation, and during the following 3 hours they acquire the nucleolar segregation pattern. Fourteen hours after drug injection, nucleolar morphology again becomes normal, while areas of focal degeneration, characterized by damaged mitochondria and enlarged smooth reticulum cisternae, appear in the sarcoplasm. One to 3 days later the degeneration process involves the myofibrillar component, and after 50 days the great majority of myocardial ventricular cells is damaged. The early appearance and the functional significance of nucleolar segregation support the hypothesis that adriamycin cardiotoxicity might be dependent on its ability to bind to myocardial cell DNA. The consequent failure of RNA and protein synthesis, impairing the continuous renewal of myofibrillar and mitochondrial components of the cell, might explain the progressive myocardial damage.

Ultrastructural study of leukemic cell phagocytosis using the myeloperoxidase reaction.

The phagocytosis (in the absence of serum factors) of zymosan particles by peripheral leukocytes isolated from ten patients with acute leukemia (AMbL, AMoL, AMML, AUL, ALL and CML-BC) was studied at the electron microscope. An evident phagocytic activity was observed only in the cells in which cytochemical and ultrastructural features suggested that the blast elements belonged to the monocytic series. However, no phagocytosis by unclassifiable leukemic blasts was observed, even though they had some submicroscopic characteristics of the monocytic series. These findings suggest that phagocytic capacity develops during the course of cell differentiation, becoming striking only when the blast cell acquires the ultrastructural features of the pro-monocytic stage. Using the myeloperoxidase reaction, this study also demonstrates a morphological alteration in the degranulation process after the ingestion of zymosan particles in both the blasts and the mature PMN cells of leukemic patients. This defect could be related to the susceptibility to severe infections usually found in subjects with hematological malignancies.

Ultrastructural alterations of atrial myocardium induced by adriamycin in chronically treated animals.

The clinical use of adriamycin (AM) is limited by a possible dose-dependent myocardiopathy. Severe lesions of ventricular myocardium widely described by electron microscopy have been correlated to irreversible congestive heart failure. On the other hand, the atrial contractile elements which differ from the ventricular ones because of the presence of the so-called specific granules have rarely been considered. In the work described in this paper, adriamycin was injected into rabbits and mice according to schedules of chronic toxicity. At the end of the treatment the atrial myocells presented diffuse ultrastructural lesions of mitochondria, sarcoplasmic reticulum and myofibrillar bundles. These alterations might be caused by the ribonucleoprotein synthesis inhibition, by a direct drug toxicity or by an energetic crisis due to early mitochondrial lesions. Besides, adriamycin produces a decrease of the specific atrial granules that play a hypothetic role in the metabolism of myocardial cells. However, lack of information about the contents and the exact function of atrial granules does not allow us to conclude that their decrease in treated animals has a pathogenetic significance in myocardiopathy induced by adriamycin.

Selective mitochondrial alterations induced by a single dose of daunorubicin or 4-demethoxydaunorubicin in mouse ventricular myocardium.

The ventricular myocardium of CD1 mice given a single high dose (LD50) of daunorubicin (DNR) or its derivative, 4-demethoxydaunorubicin (4DD), was studied under the electron microscope. Severe degenerative alterations were observed, but only in the mitochondria in myocardial tissue samples taken 3 and 7 days after treatment. This suggests that mitochondrial lesions might play an important role in the pathogenesis of anthracycline myocardipathy. Furthermore, the nucleolar segregation phenomenon, already described in experimental doxorubicin myocardiopathy, was not observed in the myocardial samples taken 1 and 3 h after DNR or 4DD injection: this fact may be interpreted, without excluding a possible DNA-mediated toxic mechanism, as the result of different kinetic behaviour of DNR and 4DD compared to doxorubicin.

[Unequal ventilation: phenomenon of trapped helium]. / Ventilazione ineguale: fenomeno dell'He intrappolato

The results of preliminary research designed to prepare a method for using mouth measurements to identify alveolar air trapping phenomena which cannot be detected by normal techniques are reported. With a present rapid thermoconductivity CO2/He analyser, it was shown that even after the completion of a standard He wash-out process, it is possible to reveal the persistence in the expiratory air of bronchiolostenotic patients of residual traces of inert gases alongside CO2 originating from normally ventilating sectors. The information obtained from the mouths of patients corresponds with the results of measurements taken inside the lung. Finally it is shown that with adequate therapy the trapping phenomenon may be reversed.

The immotile-cilia syndrome. Functional and ultrastructural alterations.

Literature was critically reviewed on the grounds of the ultrastructural and clinical observations made on three subjects carriers of Kartagener's syndrome. The relationship between the various ultrastructural aspects (lack of dynein arms and casual orientation of the central microtubular doublet) and the clinical evidence elicited in all the sites lined with ciliated epithelia (auditory apparatus, vestibular apparatus, genital organs and central nervous system). Attribution of the genesis of situs viscerum inversus to lack of ciliar motion was brought up for discussion again.

Inhalation anti-asthma therapy with spacers: technical aspects.

Inhalation is the method of choice for delivering therapeutic agents to the lung. The advent of metered-dose inhalers (MDIs) has made inhalation easier, less expensive and more efficient. However, 20-50% of patients are unable to use MDIs correctly. The main problems are: 1) impact of aerosol particles in the mouth (responsible for side-effects); 2) poor co-ordination between firing the MDI and breathing; 3) and too fast an inspiration. Various spacer devices have been designed to overcome these problems. These are: large volume devices, which reduce the oral impact and select the respirable particles; devices equipped with a one-way valve that reduces co-ordination problems; indication of too rapid an inspiration by a high-flow mark. The introduction of these devices has resulted in an improved bronchial/oral deposition rate and a reduced incidence of side-effects. Training and education of patients is fundamental in ensuring the correct use of inhalers.

Allergy to ragweed in northern Italy and prevention strategies.

Ragweed is spreading in Europe and in northern Italy, particularly in the Lombardia and Friuli areas. It constitutes a cause of significant morbidity for asthma and rhinoconjuntivitis involving as much as 12% of the general population in those countries most at risk. The public campaign to fight ragweed promoted in 1999 by the Lombardia Region failed to achieve significant results since the count of ragweed pollen in the subsequent years is similar to the previous and reached peaks of 700 pollens per m3.

Short and long-term evaluation of two structured self management programmes on asthma.

In recent years education programmes for adults have been developed focusing on improving patient self-management. The aim of this study was to evaluate the efficacy of two different educational programmes on asthma at one year (short-term efficacy) and three years (long-term efficacy). Changes in pulmonary function (FEV1), knowledge of disease and skill concerning inhalation technique were evaluated to determine the efficacy of the educational programme. Forty patients were randomly assigned to the two different educational programmes. Twenty subjects (mean age 49 +/- 11 yrs; FEV1 79% +/- 15 of predicted) were assigned, to a basic educational programme, while the others (mean age 44 +/- 11 yrs; FEV1 79% +/- 14 of predicted) were assigned to an "asthma school" programme. In both "basic" and "asthma school" groups there was a significant increase from baseline to one year (p < 0.05) and three years (p < 0.05) in FEV1, number of correct answers to the knowledge questionnaire, and number of correct steps during the inhalation procedure. No significant differences were found between the two groups at baseline, one year and three years for all three variables studied. This study confirms that both educational programmes determine in asthmatics an improvement in lung function, knowledge of disease and skill for inhalation technique at one year and three years following commencement of the programme. A "basic" educational programme is as effective as an "asthma school" one.

Reliability of a questionnaire for evaluating the understanding of asthma.

The present study was designed to evaluate the repeatability of a questionnaire developed to assess the understanding that asthma patients have of their disease and, on the basis of its variability, estimate the sample size necessary for determining the efficacy of a future structured program on asthma knowledge. The repeatability of the Asthma Questionnaire (AQ) was evaluated by asking 89 patients to complete it twice within a period of 7-10 days without the subject being exposed to any programme on asthma knowledge between the two administrations. The AQ was demonstrated to have good content and face validity. Results showed that neither age nor sex had a significant influence on total scores, and that the degree of reliability was adequate (R = 0.769). The mean percentage of correct answers was observed to be approximately 70% in both sessions, suggesting a consistent area for possible improvement which could be targeted by means of an appropriately structured programme on asthma knowledge. For comparative purposes before and after the programme, or for measuring its efficacy, the AQ should be recommended. In conclusion the Asthma Questionnaire could provide a useful tool for the general practitioner, chest physician and other health professionals, to assess what the patient really does understand or does not, concerning asthma management, and hence be the starting point for a well-tailored educational intervention.

[Acute silicosis in jewelry casting]. / Silicosi acuta nella microfusione artistica.

An accelerated silicosis case made our Occupational Health Unit focus on a pathology thought dropping so far to die out. Furthermore this event occurred in a manufacturing (lost-wax process in jewelry casting) regarded as a low-risk exposure. Besides unsuitable procedures, the user had underestimated the specific risk of that raw material (talcum-like powder at 60-80% silica crystalline level), commonly called "gypsum", inappropriately labelled since not yet adequately classified by the hazardous substances list. The widespreading of this manufacture in our area (Vicenza district) and the recent inclusion of Silica Crystalline in the Class 1 made by IARC (Jan 1997) have urged this Unit to take action in industrial hygiene investigations, instructions to the workers, mandatory directions to dealers concerning the proper hazard labelling for products containing silica crystalline and circulation of information among other Occupational Health Units involved.

[Lead poisoning caused by stonework treatment in architectural restoration]. / Intossicazione da piombo dovuta al trattamento di manufatti in pietra nell'ambito del restauro architettonico.

An unexpected lead exposure occurred among a team of masons employed in restoration work of the facade of an 18th century church in Vicenza, Italy. The unusual case of lead intoxication (PbB up to 71 micrograms/dL, PbU-EDTA 8636 micrograms/24 h after the first 1 g dose of Na2Ca EDTA) in a mason suffering from abdominal pain was reported to our unit by the local General Hospital. An investigation on the possible sources was therefore set up and the source was identified in the removal of an old paint made of white lead (basic lead carbonate) from the statues and decorative stonework of the church. An extension of the investigation confirmed that many sculptures and stonework from the same period, especially in religious buildings, were treated in the same way. The biological exposure indices of the subject's work fellows also confirmed an abnormal lead absorption. The occupational risks involved in various methods in restoration crafts are evaluated and preventive measures are suggested.

The type of sensitizing allergen can affect the evolution of respiratory allergy.

BACKGROUND: Numerous factors affect the evolution of respiratory allergy, in children, but little is known in adults. We assessed in a prospective study the influence of the type of allergen on the progression of disease. METHODS: Outpatients, with respiratory allergy underwent skin tests and pulmonary function/methacholine challenge at baseline and after 3 years. Patients were subdivided in pure rhinitis or rhinitis + bronchial hyperreactivity (BHR). In polysensitized subjects a single relevant allergen (mites, grasses, birch, Parietaria) was identified based on symptom distribution and when needed on nasal challenge. RESULTS: 6750 patients (age range 12-46) were studied. Of them, 17.8% were monosensitized but this percentage decreased to 10.4% after 3 years (P < 0.05). Subjects with pure rhinitis were 81% at the beginning and 48% at the end. After 3 years, the patients with bronchial responsiveness increased from 18% to 58% for mites, 22% to 49% for birch, 18% to 44% for grasses, 17% to 32% for Parietaria, with a significant difference among allergens (P < 0.05). Almost the same was seen in monosensitized subjects, being mites most likely to cause a worsening. All patients with BHR at baseline received immunotherapy. In these patients the onset of new sensitizations was significantly lower than in the group (pure rhinitis) receiving drugs only and lower airways symptoms disappeared more frequently. CONCLUSION: The different type of allergen influences the course of the disease, as well as the use of immunotherapy.