Bacterial infection as an important triggering factor in bronchial asthma.

It is very surprising that in recent decades, the bacterial infection factor has been so overlooked in the causal treatment of bronchial asthma. Emphasis is put in the viral infection, but the bacterial infection usually associated with it is ignored. In several publications, we have insisted on the importance of the bacterial infection factor in the etiopathogenesis of bronchial asthma. It is alarming that even in the international consensus on its treatment this aspect is overlooked. In the first decades of this century, great importance had already been put on bacterial infection in the triggering of bronchospasm. In this review, we insist on this role of bacterial infection, which comes as a result of our extensive experience in this area, and the fact that in the last 10 years many authors have proven its responsibility at a bronchial mucosa level. In due time, we may be able to prove that the bacterial antigens can potentiate the action of inhalant allergens. Some authors have even proven that the action of these bacterial antigens even more energetically increases the number of intraepithelial dendritic cells in the bronchial mucosa after inhalation of bacterial lipopolysaccharide. Bystander respiratory bacterial infections can also directly modulate T helper 1 and 2 selection parallel to the immune response to inhalant allergens. Recent studies have also proven that in respiratory infection, bacterial antigens hold the main responsibility in the inflammatory and bronchospastic response in the etiopathogenesis of bronchial asthma. Therefore, a consequent treatment of the infection is required, by means of wide spectrum antibiotics, as well as prescription of bacterial immunotherapy, as we have emphasized on other occasions. In conclusion, we must try to cure asthmatic patients and not to maintain them with inhalers and unnecessary corticosteroid therapy, since increasing reactions to corticosteroids are witnessed every day.

Eosinophil soluble protein levels, eosinophil peroxidase and eosinophil cationic protein in asthmatic patients.

Eosinophil granular proteins are useful eosinophil activation markers in asthmatic patients. In this study, eosinophil peroxidase (EPO) and eosinophil cationic protein (ECP) levels were assessed in different stages of bronchial asthma in 123 patients suffering from intrinsic (n = 42) and extrinsic (n = 81) asthma, with the aim of evaluating the difference in the protein levels between both types of asthma and their importance as a severity marker of the disease. The geometric mean serum level of EPO was 12.3 +/- 2.17 ng/ml (mean +/- SD) in controls, and 38.6 +/- 3.4 ng/ml in the asthmatic patients. Mean ECP levels were 13.22 +/- 1.11 ng/ml in controls and 30.5 +/- 2.38 ng/ml in patients. Depending on the asthma severity, the EPO levels were 30.4 +/- 4.35, 38.7 +/- 5.29, and 54.46 +/- 9.46 ng/ml in mild, moderate and severe asthmatics, respectively, with the differences being significant between the groups of patients with mild and severe asthma (p < 0.001). ECP levels were 24.23 +/- 3.37 in mild, 31.69 +/- 4.21 in moderate, and 37.61 +/- 4.52 ng/ml in severe asthma. There were significant differences in ECP levels between mild and moderate asthma (p < 0.001) and between mild and severe asthma (p < 0.001). Peripheral eosinophil count was 157 +/- 20 eosinophils/mm3 in controls, 334 +/- 35 eosinophils/mm3 in mild asthmatics, 510 +/- 87 eosinophils/mm3 in moderate asthmatics and 658 +/- 72 eosinophil/mm3 in severe asthmatics, with significant differences between all groups (p < 0.05-p < 0.001). Serum EPO and ECP levels and peripheral eosinophil count were significantly greater in patients with active asthma than in patients with silent asthma (p < 0.001). Significant negative correlations (p < 0.001) were found between serum EPO levels and FEV1 (rs = -0.30), MEF25-75 (rs = -0.33), MEF50 (rs = -0.34). There was also a significant (p < 0.001) and negative correlation between ECP levels and FEV1 (rs = -0.31), MEF25-75 (rs = -0.31), MEF50 (rs = -0.32). A good positive correlation was found between peripheral eosinophil count and EPO levels (rs = 0.80, p < 0.001), and ECP levels (rs = 0.67, p < 0.001). We also found a significant positive correlation between clinical score and peripheral eosinophil count (rs = 0.54, p < 0.001), EPO levels (rs = 0.46, p < 0.001) and ECP levels (rs = 0.52, p < 0.001).

Importance of IgG4 determination in in vitro immunotherapy follow-up of inhalant allergens.

Choosing the right parameters to recommend immunotherapy in allergologic diagnosis is very important. Therefore, other parameters which are independent of the improvement of clinical manifestations and which indicate the evolution of asthma are very useful. Although a decrease in skin reactions was observed in 20% to 25% of patients in previous studies, since the in vitro techniques appeared, their evolution has been observed. Total and antigen-specific IgE evolution, as well as histamine release from basophils, in immunotherapy were followed as we had presented in previous studies. In this work, we studied 151 patients with asthma and rhinosinusitis, 70 of whom were sensitive to Lolium perenne and 81 to Dermatophagoides pteronyssinus. The parameters mentioned above were used, and the patients underwent immunotherapy at three different concentrations depending on the degree of sensitization. The standard concentration was used in the first group; those patients with very high values in radioallergosorbent test (RAST) and histamine release test (HRT) were given the concentration 1:2; and lastly, the largest group of patients, who presented the highest sensitization both in vivo and in vitro, were given the concentration 1:10. As a complement to the mentioned in vitro techniques, the antigen-specific IgG4 determination (blocking antibody) was also evaluated. As we observed in previous studies, skin test, total IgE, antigen-specific IgE and HRTs showed no significant modifications in any of the three groups, in spite of the very positive clinical evolution over the 6 years. Regarding IgG4 follow-up in pollinic patients, a very significant increase was observed, reaching its highest value after 6 years, at standard concentration and with an increase of 49.4%. In conclusion, we think that antigen-specific IgG4 is the only easily available and suitable parameter existing for immunotherapy follow-up.

Cross-reactivity of Olea europaea with other Oleaceae species in allergic rhinitis and bronchial asthma.

Cross-reactivity between pollen extracts of four species of Oleaceae was studied: olive (Olea europaea), ash (Fraxinus excelsior), privet (Ligustrum vulgare), and lilac (Syringa vulgaris). Thus, 51 patients and 13 atopic controls were studied, by means of intracutaneous skin tests, histamine-release tests against the four extracts, and specific IgE to O. europaea. The proteic content of the four extracts was assessed by SDS-PAGE and immunoblotting, and similarity of all the extracts studied was observed after electrophoresis and immunodetection. Six common bands were found to be responsible for the cross-reactivity, with apparent molecular weights of 49.6, 40, 36.7, 19.7, 16.7, and 14 kDa, respectively. The cross-reactivity was also corroborated by immunoblotting inhibition and FEIA inhibition. The patients had a similar response to the four allergenic extracts used, although the response to Olea was greatest. When the patients were compared by their geographic origin (northern or southern Spain, according to the distribution of areas of olive pollen influence), there were no significant differences between the two groups in skin reactivity, but a higher histamine release was observed for the four extracts in the southern group, although it was significant only for Fraxinus and Ligustrum. This work corroborated the practicality of the diagnostic methods used and the cross-reactivity between the four species studied, as demonstrated by the different methods used. Therefore, we suggest that only O. europaea extract be used in diagnosis and immunotherapy in Oleaceae pollen allergy.

Serum eosinophil peroxidase (EPO) levels in asthmatic patients.

Eosinophil granular proteins are a useful eosinophilic activation marker in asthmatic patients. In this study, the eosinophil peroxidase (EPO) levels were assessed in different stages of bronchial asthma, in 123 patients suffering from asthma, classified as mild (n =49), moderate (n = 49), and severe (n = 25), according to the International Consensus Report of Diagnosis and Treatment of Asthma, as well as in 27 healthy controls, with the aim of evaluating the importance of this protein as a severity marker in bronchial asthma, and its possible correlation with parameters such as anamnesis, respiratory function tests, and peripheral blood eosinophil count, and also with some allergologic diagnostic tests, both in vivo and in vitro. The geometric mean serum level of EPO was 9.3 +/- 11.3 ng/ml (median +/- SD) in controls, 28 +/- 37.8 ng/ml in the asthmatic patients. Depending on the asthma severity, the EPO levels were 25 +/- 30.5; 29 +/- 37.1, and 41 +/- 47.3 ng/ml in mild, moderate, and severe asthmatics, respectively, being the significant differences between the group of patients with mild and severe asthma (P < 0.001). The number of eosinophils (eos) in peripheral blood was 157 +/- 20 eos/mm3 in the controls, 334/35 eos/mm3 in mild asthmatics, 510 +/- 87 eos/mm3 in moderate asthmatics, and 658 +/- 72 eos/mm3 in severe asthmatics, with significant differences between all groups (from P < 0.05 to P < 0.001). Both the serum levels of EPO and the number of eosinophils were greater in patients with active asthma patients with inactive asthma (P < 0.001). Significant negative correlations (P < 0.001) were found between serum levels of EPO and FEV1 (rs = 0.30), MEF25-75 (rs = -0.33) and MEF50 (rs = -0.34), and a good positive correlation (rs = 0.80, P < 0.001) was found between EPO levels and the number of eosinophils in peripheral blood. We also found a significant positive correlation between eosinophil number and clinical score (rs = 0.54, P < 0.001) and between EPO levels and the mentioned score (rs = 0.46, P < 0.001).

Serum ECP levels in asthmatic patients: comparison with other follow-up parameters.

In recent years, eosinophil cationic protein (ECP) has been considered as a useful eosinophilic activation marker in asthmatic patients. In this study, serum ECP levels in different stages of bronchial asthma were evaluated. We studied 123 patients suffering from asthma, which was classified as mild (n = 49), moderate (n = 49), severe asthma (n = 25), and also 31 healthy controls. Serum ECP levels were 13.22 +/- 1.11 ng/mL (mean +/- s.e.m.) in controls, and 30.15 +/- 2.38 ng/mL in asthmatic patients. By subgroups, ECP levels were 24.23 +/- 3.37 ng/mL, 31.69 +/- 4.21 ng/mL and 37.61 +/- 4.52 ng/mL, in mild, moderate and severe asthmatic patients, respectively, being the differences among the three groups statistically significant (P < 0.01-P < 0.001). Peripheral blood eosinophil numbers were 157 +/- 20 eos/mm3 in controls, and 334 +/- 35 eos/mm3, 510 +/- 87 eos/mm3, and 658 +/- 72 eos/mm3, in mild, moderate, and severe asthmatic patients, respectively, with significant differences among all groups (P < 0.05-P < 0.001). The serum ECP levels as well as the eosinophil numbers were higher in symptomatic patients than in the asymptomatic ones (P < 0.01). Moderate negative correlations, although highly significant (P < or = 0.001), were found between serum ECP levels and forced vital capacity (FVC) (rs = -0.27), FEV1, MEF25-75 (rs = -031), and MEF50 (rs = -0.32). There was also a good positive correlation between ECP levels and peripheral blood eosinophil numbers (rs = 0.67, P < 0.001).