María del Carmen Vennera

Effects of Omalizumab in Non-Atopic Asthma: Results from a Spanish Multicenter Registry

Aim. To evaluate the effectiveness of omalizumab in non-atopic asthma. Methods. Using data from a multicenter registry of severe asthma, we evaluated and compared the clinical outcome of 29 omalizumab-treated severe non-atopic asthmatics with 266 omalizumab-treated severe allergic asthmatics. Effectiveness was assessed by considering severe exacerbations, pulmonary function, the Global Evaluation of Treatment Effectiveness (GETE) scale, and Asthma Control Test (ACT). Results. Omalizumab demonstrated significant improvement in the clinical status of non-atopic asthmatics as measured by GETE, which rose from 1.6 ± 1.1 to 2.8 ± 0.8 at 4 months (p = .0215) to 2.9 ± 0.9 at 1 year (p = .0093) and to 3.4 ± 0.6 at 2 years (p = .0078), and by the ACT, which increased from 13.0 ± 5.5 to 17.5 ± 5.4 at 4 months (p = .0236) to 17.9 ± 4.8 at 1 year (p = .0136) and to 20.6 ± 3.9 at 2 years (p = .0024). Forced expiratory volume in 1 second (FEV1) improved from 61.0 ± 19.4% to 65.1 ± 17.2 at 4 months to 64.1 ± 24.7 at 1 year and to 67.3 ± 23.0 at 2 years, but without significant differences between initial and follow-up measurements (p = .52, .91, and .45, respectively) and exacerbations decreased from 3.1 ± 3.5 to 1.9 ± 2.8 at 1 year (p = .1709) to 1.8 ± 4.4 at 2 years (p = .2344). The results were not significantly different from those obtained in atopic asthmatics. Conclusion. Anti-IgE therapy can be effective in non-atopic severe asthma.

Omalizumab Therapy in Severe Asthma: Experience from the Spanish Registry—Some New Approaches

Objective. The efficacy of omalizumab in severe asthma has been widely demonstrated. The main objective of this study was to evaluate the efficacy and tolerability of omalizumab in a real-life setting in Spain, particularly in those patients with immunoglobulin E (IgE) levels out of range. Methods. Totally 266 uncontrolled severe asthma patients receiving high-dose inhaled corticosteroids (ICSs) plus long-acting β2-agonist (LABA) were recruited. Main efficacy outcomes were asthma exacerbation rate (AER), asthma control test (ACT), and global evaluation of treatment effectiveness (GETE). Results. AER was reduced from 3.6 (3.6) in previous year to 0.67 (1.2) at 4 months (p < .05) and to 1.04 (1.8) at 2 years (p < .05). ACT increased significantly from 14.3 (4.7) at baseline to 18.4 (4.4) at 4 months (p < .05) and to 20.3 (4.0) (p < .05) at 2 years. After 4 months, 74.6% of patients had reached a good or excellent rate on the GETE scale (p < .05). This rate continued increasing up to 81.6% at 2 years. These efficacy results were similar for patients with “off-label” IgE > 700 IU/ml. At follow-up, maintenance treatment with oral steroids was discontinued in a considerable number of patients: from 89 to 19 (p < .05). Omalizumab was discontinued because of lack of efficacy only in 28/266 (10.5%) patients. Overall, 30 patients (11.4%) reported adverse events. Severe adverse events were not observed. Conclusion. This real-life study confirms that omalizumab is very efficacious and very well tolerated in patients with uncontrolled severe asthma. Results did not vary in the subgroup of patients with IgE levels >700 IU/ml.

Efficacy of omalizumab in the treatment of nasal polyps

Omalizumab, a humanised monoclonal anti-immunoglobulin E (IgE) antibody, is indicated as adjuvant treatment in refractory allergic severe asthma.1 In both chronic rhinosinusitis (CRS) with nasal polyps (NP) and allergic rhinitis, IgE is increased in mucosal tissue and frequently in serum. The role of omalizumab has been clearly established in allergic asthma and rhinitis, but remains to be elucidated in NP.2 The only evidence for the potential efficacy of omalizumab in NP relies on case reports and small series of patients which suggest that, when NP and asthma coexist, the anti-IgE may have therapeutic value on NP.3 4 We describe the evolution of NP in 19 patients who were treated with omalizumab for severe asthma and who also had …

Pulmonary manifestations of inflammatory bowel disease

bronchial suppuration had appeared between 3 and 13 years after the onset of IBD. Since then, all respiratory complaints in IBD patients that cannot be explained by other causes have been defined as pulmonary manifestations of the disease. Extraintestinal manifestations of IBD have been described in almost all organs. Their incidence, which ranges from 21% to 41%, increases with the duration of the intestinal disease, and they are more common in Crohn’s disease than in ulcerative colitis. 3 The coincidence of multiple extraintestinal manifestation of IBD in the same individual is higher than that expected by chance. This has led to the suggestion that they may have pathogenic mechanisms in common. 4 Greenstein et al 5 distinguish 3 groups of extraintestinal manifestations: a) those that are associated with the inflammatory process of IBD and can respond to its treatment; b) those that persist even when IBD is no longer present; and c) those that are due to nonspecific mechanisms (less frequent). In Spain the incidence of IBD, now considered a disease of industrialized countries, has increased in the last 30 years in line with changes in the standard of living. It is currently estimated that 65 000 Spaniards suffer from this disease, but that the figure could triple within 10 years. In 1990, Hinojosa et al 6 reported an overall incidence of 9.07 cases per 100 000 personyears and an overall prevalence of 28.87 per 100 000 population. In 1992, the Catalan IBD group 7 published a survey undertaken between 1978 and 1987 that showed a prevalence of 19 cases per 100 000 population in Barcelona and 18 per 100 000 in Gerona. In the last 10 years, many advances have been made in the understanding of the genetic contribution to IBD. Ethnic predominance (Ashkenazi Jews), higher frequency in members of the same family, and higher concordance between monozygotic twins are 3 clear indications of the central role of genetic factors in the pathogenesis of the disease. Recently, the detailed map of chromosome 16 has allowed the identification of a gene that codes for a cytoplasmic protein called NOD2, also known as CARD15. This protein, expressed by macrophages, represents a very important discovery for the understanding of IBD. 8

Manifestaciones pulmonares de las enfermedades inflamatorias intestinales

Desde la década de los cincuenta se conocen descripciones bibliográficas de la asociación entre enfermedades pulmonares y enfermedades inflamatorias intestinales (EII), en particular, la colitis ulcerosa (CU) y la enfermedad de Crohn (EC)1. Fue en 1976 cuando Kraft et al2 describieron en 6 pacientes la presencia de supuraciones bronquiales crónicas que habían aparecido entre 3 y 13 años después del inicio de la EII. A partir de entonces quedaron definidas como manifestaciones pulmonares de las EII todas aquellas afecciones respiratorias que no pudieran explicarse por otra causa. Las manifestaciones extraintestinales de la EII se han descrito en casi todos los órganos de la economía. Su incidencia, que oscila entre el 21 y el 41%, aumentan con la duración de la enfermedad intestinal y son más frecuentes en la EC que en la CU3. La coincidencia de más de una manifestación extraintestinal en un mismo individuo con EII es mayor que lo esperado debido al azar, lo que ha llevado a plantear que podrían tener mecanismos patogénicos comunes4. Greenstein et al5 distinguen 3 grupos de manifestaciones extraintestinales: a) las que se asocian al proceso inflamatorio de la EII y pueden responder al tratamiento de ésta; b) las que persisten aunque la EII no esté presente, y c) las que responden a mecanismos inespecíficos (menos frecuentes). En España la incidencia de la EII ha ido aumentando en los últimos 30 años con los cambios en el nivel de vida. Hoy día se considera una enfermedad de los países industrializados. Se calcula que actualmente 65.000 españoles presentan esta enfermedad, pero esta cifra podría triplicarse en 10 años. En 1990 Hinojosa et al6 comunicaron una incidencia y una prevalencia globales de 9,07/100.000 y 28,87/100.000, respectivamente. En 1992, el grupo catalán de EII7 publicó una revisión realizada entre 1978 y 1987 con una prevalencia de 19/100.000 en Barcelona y 18/100.000 en Gerona. En los últimos 10 años se han producido muchos avances en el conocimiento de la contribución genética a la EII. El predominio étnico (judíos askenazíes), la mayor frecuencia entre miembros de una misma familia y la mayor concordancia entre gemelos monocigóticos son 3 pruebas evidentes del papel central de los factores genéticos en la patogenia de la enfermedad. Recientemente el mapeo detallado del cromosoma 16 ha permitido el hallazgo de un gen que codifica para una proteína citoplásmica designada como NOD2, también conocida como CARD15. Esta proteína, que se expresa en los macrófagos, constituye un descubrimiento muy importante para el conocimiento de la enfermedad8.

Factores asociados con el asma grave no controlada y con la percepción del control por parte de médicos y pacientes

INTRODUCTION Despite current treatments, more than half of patients with asthma are not controlled. The objective was to evaluate the correlation between control perceived by patients and physicians, compared with control evaluated according to criteria of the Spanish Guidelines for Asthma Management (GEMA), and to investigate the factors associated with that control. METHODS Multicenter, cross-sectional, observational study including 343 patients with severe persistent asthma according to GEMA criteria seen in the Department of Pulmonology and Allergology. The correlation between asthma control perceived by the patient, the physician and according to clinical judgment based on the GEMA criteria was calculated, and a multivariate analysis was used to determine variables related to the perception of asthma control. RESULTS According to GEMA criteria, only 10.2% of patients were well controlled, 27.7% had partial control and 62.1% were poorly controlled. Both the physicians and the patients overestimated control: 75.8% and 59.3% of patients had controlled asthma according to the patient and the physician, respectively, and were not controlled according to GEMA (P<.0001). Patients with uncontrolled asthma according GEMA had higher body mass index (P=.006) and physical inactivity (P=.016). Factors associated with a perceived lack of control by both physicians and patients were: nocturnal awakenings (≥ 1 day/week), frequent use of rescue medication (≥ 5 days/week) and significant limitation in activities. Discrepant factors between physicians and patients were dyspnea and emergency room visits (patients only), FEV1 ≤ 80% and a poorer understanding of the disease by the patient (physicians only). CONCLUSIONS Only 10% of patients with severe asthma evaluated in this study are controlled according to GEMA criteria. Patients and physicians overestimate control and the overestimation by patients is greater. Physical inactivity and obesity are associated with a lack of control according to GEMA.

Duration of the efficacy of omalizumab after treatment discontinuation in ‘real life’ severe asthma

Efficacy of omalizumab in severe asthma is well documented; however, the optimal duration of the treatment remains unclear. In an open prospective study, we sought to assess the persistence of response in subjects withdrawing from omalizumab treatment. We evaluated 49 patients who voluntarily accepted to discontinue omalizumab treatment after 6 years of therapy. Asthma relapse was defined as any severe asthma exacerbation associated with loss of asthma control. Twelve patients relapsed in the first year of follow-up, and 7 within 13 and 48 months. These results suggest that the effects of 6 years of omalizumab may persist after discontinuation of therapy in 60% of patients for at least 4 years.

Novel diagnostic approaches and biological therapeutics for intrinsic asthma

Intrinsic asthma has been considered as a specific disease entity for a long time, although many controversies have emerged in relation to this concept. Of note, not finding specific allergen sensitization in an asthmatic patient neither excludes an allergic component nor the essential role that immunoglobulin E may play in asthma. The diagnostic approach should be similar in any patient suspected to have asthma. The atopic status is one among many other questions. Omalizumab, the only monoclonal anti-immunoglobulin E antibody commercialized for asthma, should be tried in patients with uncontrolled severe asthma independent of their atopic status.

Influence of the diagnosis chronic rhinosinusitis on asthma response to omalizumab in severe, uncontrolled asthmatics

Background Omalizumab is a humanized anti-immunoglobulin E (IgE) monoclonal antibody that has been approved as add-on therapy for the treatment of adults with moderate-tosevere (United States) or severe (Europe) allergic asthma, inadequately controlled after treatment with high-dose inhaled corticosteroids plus long-acting b-agonists. The clinical efficacy of Omalizumab has not only been shown in the treatment of severe uncontrolled asthma, but also in the treatment of nasal polyposis and comorbid asthma. The aim of this analysis was to examine whether the diagnosis of chronic rhinosinusitis (CRS) influenced the asthma response to Omalizumab treatment.

Positive bronchodilator response is a poor predictor of future risk in well controlled asthma patients

This study was aimed to determine the ability of a positive bronchodilator response (BDR) to predict asthma loss of control in a real-life setting. Material and methods: Prospective, multicenter study. Treatment was stepped-up or stepped-down over a 12-month period to maintain asthma control. Patients who were well-controlled at baseline with a combination of inhaled corticosteroid and long-acting β 2 agonist (IC/LABA) were included. A BDT was performed at each visit (3, 6 and 12 months) and loss of control was assessed. Results: 149 patients were included (70% women, mean age 54.7 years). At baseline, mean FEV1 was 92.1%, mean Asthma Control Test score was 23.0 ± 2.1 and the exacerbation rate was 0.4 ± 0.8 per patient-year. 344 BDR measurements were made (always positive in 8.3% of the patients, intermittently positive in 41.3% and always negative in 50.4%). 59 patients (40%) lost control over the study. The area under the ROC curve of a positive BDR was 0.52 (95% CI: 0.44-0.60). Sensitivity was 23% (95% CI: 13-34%), specificity was 81% (95% CI: 76-86%), positive predictive value was 22% (95% CI: 12-32%), negative predictive value was 82% (95% CI: 78-87%), positive likelihood ratio was 1.24 (95% CI: 0.75-2.05) and negative likelihood ratio was 0.94 (95% CI: 0.82-1.09). Conclusions: A positive BDR does not predict future risk in asthma and lacks a clinical justification for its routine use.