The contribution of sublingual immunotherapy to the achievement of control in birch-related mild persistent asthma: A real-life randomised trial

Background: Asthma control represents the main goal of asthma management and different strategies aim to avoid the long term downsides of inhaled corticosteroids. We investigated in real-life conditions the contribution of sublingual immunotherapy in achieving the control of birch-related mild persistent asthma compared to two usual step-up therapeutic options. Methods: A three-year open randomised study included 84 asthmatics, uncontrolled during the previous birch pollen season, despite a treatment with budesonide 400 μg/day. Patients randomly received budesonide 800 μg/day, budesonide 1600 μg/day, budesonide 400 μg/day plus montelukast 10 μg/day and budesonide 400 μg/day plus carbamylated allergoid of betulaceae pre-coseasonally. Asthma Control test, combined allergy symptoms and medications score, albuterol consumption, lung function, nasal eosinophils and nasal steroids usage were assessed as changes from the first to last pollen season. Result: Seventy-six patients concluded the study. All options, except budesonide 800 μg/day, produced an improvement of mean monthly Asthma Control test (p < 0.05). Patients undergoing low-dose budesonide plus immunotherapy achieved, after three years, an appreciable control (ACT mean score 24). A significant improvement was seen in all groups for allergy symptoms plus medications and bronchial reactivity. Albuterol consumption and lung function improved in all but the first group. Only budesonide plus immunotherapy reduced nasal eosinophils and nasal steroids usage. Two mild self-resolving adverse events were reported. Conclusions: For patients with respiratory allergy due to birch pollen and mild persistent asthma, sublingual immunotherapy added to low-dose inhaled corticosteroids appears effective in maintaining long-term seasonal asthma control, representing a safe opportunity to reduce the cumulative amount of delivered corticosteroids (AU)

The contribution of sublingual immunotherapy to the achievement of control in birch-related mild persistent asthma: a real-life randomised trial.

BACKGROUND: Asthma control represents the main goal of asthma management and different strategies aim to avoid the long term downsides of inhaled corticosteroids. We investigated in real-life conditions the contribution of sublingual immunotherapy in achieving the control of birch-related mild persistent asthma compared to two usual step-up therapeutic options. METHODS: A three-year open randomised study included 84 asthmatics, uncontrolled during the previous birch pollen season, despite a treatment with budesonide 400µg/day. Patients randomly received budesonide 800µg/day, budesonide 1600µg/day, budesonide 400µg/day plus montelukast 10µg/day and budesonide 400µg/day plus carbamylated allergoid of betulaceae pre-coseasonally. Asthma Control test, combined allergy symptoms and medications score, albuterol consumption, lung function, nasal eosinophils and nasal steroids usage were assessed as changes from the first to last pollen season. RESULT: Seventy-six patients concluded the study. All options, except budesonide 800µg/day, produced an improvement of mean monthly Asthma Control test (p<0.05). Patients undergoing low-dose budesonide plus immunotherapy achieved, after three years, an appreciable control (ACT mean score 24). A significant improvement was seen in all groups for allergy symptoms plus medications and bronchial reactivity. Albuterol consumption and lung function improved in all but the first group. Only budesonide plus immunotherapy reduced nasal eosinophils and nasal steroids usage. Two mild self-resolving adverse events were reported. CONCLUSIONS: For patients with respiratory allergy due to birch pollen and mild persistent asthma, sublingual immunotherapy added to low-dose inhaled corticosteroids appears effective in maintaining long-term seasonal asthma control, representing a safe opportunity to reduce the cumulative amount of delivered corticosteroids.

Children passive smoking jeopardises the efficacy of standard anti-allergic pharmacological therapy, while sublingual immunotherapy withstands

Background: The association between genetic predisposition and environmental risk factorssuch as passive smoke in determining respiratory allergies is still uncertain; even less is known about the role played by passive smoking in influencing the success of therapy for rhinitis and allergic asthma. Objective: The purpose of this prospective, randomised study was to determine whether passive smoking influences the outcome of therapies in paediatric patients with allergic respiratory diseases. Methods: The study included 68 children (mean age 11.51 years; range: 5-17) suffering from perennial rhinitis and intermittent asthma monosensitised to Dermatophagoides. Thirty-foursubjects were exposed to daily passive smoking in their families, 34 were not. The two groups have been then randomised to receive continuous treatment with cetirizine or SLIT for three years. Results: There were 3/34 (8.8%) dropouts in the SLIT arm and 4/34 (11.7%) in the cetirizine arm. After three years, the patients exposed to passive smoking showed higher nasal eosinophilia, aworse clinical-symptomatic and pharmacological score with a worsened bronchial reactivity and functional indices of persistent asthma, regardless of how they had been treated. Nevertheless, SLIT prevented the worsening of all the clinical parameters more than the antihistamine alone either among the children exposed to smoking or not. Conclusions: Exposure to passive smoking in children suffering from respiratory allergies dueto Dermatophagoides decreased the clinical response to both drug therapy and SLIT. Nonetheless, while the children submitted to drug therapy worsened or did not show any significant improvement, the ones treated with SLIT improved (AU)

Children passive smoking jeopardises the efficacy of standard anti-allergic pharmacological therapy, while sublingual immunotherapy withstands.

BACKGROUND: The association between genetic predisposition and environmental risk factors such as passive smoke in determining respiratory allergies is still uncertain; even less is known about the role played by passive smoking in influencing the success of therapy for rhinitis and allergic asthma. OBJECTIVE: The purpose of this prospective, randomised study was to determine whether passive smoking influences the outcome of therapies in paediatric patients with allergic respiratory diseases. METHODS: The study included 68 children (mean age 11.51 years; range: 5-17) suffering from perennial rhinitis and intermittent asthma monosensitised to Dermatophagoides. Thirty-four subjects were exposed to daily passive smoking in their families, 34 were not. The two groups have been then randomised to receive continuous treatment with cetirizine or SLIT for three years. RESULTS: There were 3/34 (8.8%) dropouts in the SLIT arm and 4/34 (11.7%) in the cetirizine arm. After three years, the patients exposed to passive smoking showed higher nasal eosinophilia, a worse clinical-symptomatic and pharmacological score with a worsened bronchial reactivity and functional indices of persistent asthma, regardless of how they had been treated. Nevertheless, SLIT prevented the worsening of all the clinical parameters more than the antihistamine alone either among the children exposed to smoking or not. CONCLUSIONS: Exposure to passive smoking in children suffering from respiratory allergies due to Dermatophagoides decreased the clinical response to both drug therapy and SLIT. Nonetheless, while the children submitted to drug therapy worsened or did not show any significant improvement, the ones treated with SLIT improved.

The clinical efficacy of a sublingual monomeric allergoid at different maintenance doses: a randomized controlled trial.

Sublingual immunotherapy is widely recognized as a viable treatment for allergic rhinitis and asthma, but the optimal dosage is still under debate, especially with modified allergens. We assessed the clinical effects of a monomeric allergoid across 3 different maintenance doses in mite-monosensitized patients with rhinitis and intermittent asthma. Eighty-nine patients allergic to HDM were randomized to 3 maintenance doses of monomeric allergoid (Lais, Lofarma) or medications only. All the patients recorded their symptoms and rescue drug consumption in a diary card from November to February. Additionally, nasal eosinophil count, spirometry and methacholine bronchial challenge were performed at the beginning of the study and after 3 years. The symptom scores showed a clear improvement in all the three active arms versus baseline and versus the controls, irrespective of the dose. Likewise, a similar improvement versus baseline was seen for nasal inflammation and bronchial hyperreactivity. The SLIT with monomeric allergoids produces clinically significant results across a wide range of doses. The absence of significant side effects, even at high doses, is probably due to their low level of allergeni city.

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.

Sublingual immunotherapy for allergic respiratory disease in elderly patients: a retrospective study.

BACKGROUND: Very few studies have evaluated the effects of sublingual immunotherapy (SLIT) in elderly adults with either rhinitis or bronchial asthma. The aim of this study was to ascertain whether SLIT is effective in these patients. METHODS: One hundred and sixty seven patients (aged 18-65 years) with persistent rhinitis and mild asthma, selected from 573 subjects allergic to house-dust mites, were treated with either standard chronic pharmacotherapy or SLIT plus drugs on demand. Monthly symptom/drug scores, respiratory function, methacholine (MCh) challenge and eosinophil count were scheduled at the beginning and end of the study. RESULTS: We analysed two age groups (18-28 years, 49 patients) and 55-65 years, 40 patients). There were no differences between the groups at baseline but MCh sensitivity was lower in the older patients. At the end of treatment, SLIT achieved improvement in all variables (p< 0.001) in both age groups, but the global symptoms were lower in the younger patients (p=0.0002). There were also fewer new sensitizations in the SLIT groups (p=0.03) than in the "control"patients given standard pharmacotherapy, but with no relation to age. Asthma became worse only in the control groups, regardless of age. CONCLUSIONS: SLIT reduces symptoms, drug consumption and the progression of the disease in both young and elderly subjects allergic to house-dust mites, with persistent rhinitis and mild bronchial asthma.

Efectos preventivos de la inmunoterapia sublingual en niños: un estudio abierto, aleatorizado y controlado / Preventive effects of sublingual immunotherapy in childhood: an open randomized controlled study

Objetivos. Evaluar los efectos clínicos y preventivos de la inmunoterapia sublingual (SLIT) con respecto a la aparición de asma persistente, nuevas sensibilizaciones, síntomas clínicos e hiperreactividad bronquial (HRB). Los objetivos secundarios fueron: evaluar la magnitud del efecto clínico y el efecto sobre la HRB; ver la seguridad y adhesión a la SLIT. Material y métodos: Participaron 216 niños, de ambos sexos, entre 5 y 17 años, pacientes del Hospital Cuasso al Monte, Varese, Italia, con rinitis alérgica de al menos 2 años de evolución, con o sin síntomas de asma intermitente, y con diagnóstico de etiología alérgica confirmado para ácaros, gramíneas, árboles y malezas. Se excluyeron pacientes con asma persistente o VEF1 <80%, uso previo de inmunoterapia, anormalidades anatómicas de las vías aéreas superiores, enfermedades sistémicas crónicas (malignas o autoinmunes) y sensibilizaciones a epitelios y hongos anemófilos. Para los diagnósticos de rinitis y asma se emplearon las guías actuales (ARIA, GINA). Se realizaron prick test con panel estándar de alérgenos relevantes (ALK Abelló), histamina 1% y control negativo al principio y al final del estudio. Las pruebas de función pulmonar consistieron en espirometría computarizada con cabina pletismográfica y prueba de provocación no específica con metacolina con dosis progresivas desde 30 a 1.290 µg, durante el período de máxima exposición alérgenica según sensibilidad de cada paciente, al inicio y al final del estudio. A los pacientes con prueba negativa (descenso del VEFI <20%) se los consederaba con diagnóstico de rinitis exclusivamente. El estudi tuvo un período basal de 1 año de observación y luego una fase de aleatorización de 3 años de tratamiento abierto con dos ramas. Un grupo de pacientes utilizó drogas exclusivamente, y otro grupo drogas más SLIT (con una distribución 1/2).

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.

Rhinitis and asthma co-morbidity in respiratory allergy due to house dust mite: results of an observational open controlled parallel group study in real-life setting.

BACKGROUND: Some aspects of allergic progression still need to be addressed. To prevent the onset of the progression is not, at present, a very realistic aim, although therapeutic instruments are available to delay and, if possible, to stop it. We attempted to clarify these points in an observational open controlled three-parallel group study in a real-life setting. METHODS: 3838 patients with respiratory allergy due to house dust mite have been enrolled in this observational study. 2200 patients with rhinitis and/or intermittent or mild persistent asthma, poorly responsive to standard pharmacological therapy (SPT) were treated for three years with SPT associated or not with specific immunotherapy (SIT). Symptom medication scores, pulmonary function test (PFT) and methacholine (MCh) challenge were performed at the beginning and at the end of the study. 1638 pure rhinitics, responsive to SPT, enrolled as a control group, used self-medication (SM) on demand to assess the incidence of asthma in non-treated patients with standard therapeutic protocols. RESULTS: 694 patients have been treated with SPT+SIT, 1506 with SPT and 1638 with SM. Co-morbidity rhinitis-asthma incidence was higher in the SM group (an overall 69.27% including asthma and bronchial hyperreactivity). Persistent rhinitis proved more often to be associated with asthma than intermittent rhinitis. Likewise, the moderate-severe forms compared to the mild ones. The addition of SIT to SPT reduced the allergic progression in all patients. CONCLUSIONS: In everyday clinical practice too, SIT proves its efficacy in the treatment of allergic march. Patients with moderate-severe persistent rhinitis appear as the ideal candidates for this therapy.

Randomized controlled open study of sublingual immunotherapy for respiratory allergy in real-life: clinical efficacy and more.

BACKGROUND: Some aspects of sublingual immunotherapy (SLIT) still need to be addressed: magnitude of the clinical efficacy, effect on the bronchial hyperreactivity adherence to treatment, preventive effect. We attempted to clarify these points in a randomized open, controlled, two parallel group study in a real-life setting. METHODS: Five hundred and eleven patients with allergic rhinitis with or without intermittent asthma were randomized to drugs only or drugs + SLIT (rate 2 : 3) for 3 years. The clinical score (symptoms + drug intake) was measured each year during the allergen exposure. Pulmonary function test, methacholine challenge and skin tests were performed at the beginning and at the end of the study. Adherence to treatment was assessed by measuring the consumed extract. RESULTS: Three hundred and nineteen patients received SLIT and 192 drugs only. Dropouts were 15% in the SLIT group and 12% in the controls. There was a significant improvement of clinical scores in the SLIT group: baseline 147 +/- 3.3, first year 72.9 +/- 1.3, second year 68.3 +/- 1.8, third year 54.7 +/- 2.8 (P < 0.0001 vs baseline). CONTROL GROUP: baseline 138 +/- 2.3, first year 124.1 +/- 3.7, second year 111 +/- 3.3, third year 121 +/- 3.8 (P = NS). Only four patients reported systemic itching. Adherence was >80% in 72% and >60% in 18% of patients. The number of patients with a positive MCh challenge decreased significantly after 3 years only in the SLIT group. New skin sensitizations appeared in 38% of the controls and in 5.9% of the SLIT patients (P = 0.01). CONCLUSION: Sublingual immunotherapy approximately halved the clinical scores and significantly reduced the bronchial hyperreactivity. Similarly to subcutaneous immunotherapy, SLIT displayed a preventive effect on the onset of new skin sensitizations. The adherence rate was quantitatively satisfactory.

Sublingual immunotherapy in the context of a clinical practice improvement program in the allergological setting: results of a long-term observational study.

The aim of this study was to assess the efficacy and safety of sublingual immunotherapy (SLIT) in a Clinical Practice Improvement (CPI) program carried out in allergology. The study was conducted between 1992 and 2001 using an observational type methodology in line with standard clinical practice. The program consisted of 4 basic steps: setting up of a decision-making tree; standardization of main diagnostic and therapeutic aspects; data collection; definition and evaluation of main clinical endpoints. Study patients were screened among 1508 patients with pollen and/or dust mite respiratory allergy, 350 of which, one year after having experienced a pharmacological treatment failure, were administered immunotherapy by injection (n = 111) or alternative route (n = 239). For each one of the three immunotherapy treatment groups (nasal, SLIT or injective) there was a control group of patients who, despite their poor response to pharmacological treatment, continued with pharmacological therapy alone (n = 314 in total; 68, 192 and 54 respectively). The observation of 130 SLIT patients, 106 of which were treated for at least 36 months, towards the control group evidenced that such therapy, apart from resulting efficient and particularly safe, has an unfailing protective effect against the development of asthma and new allergic sensitizations.

Clinical practice improvement program for immunotherapy of respiratory allergic diseases.

The aim of this study was to develop a clinical practice improvement (CPI) program for the allergen immunotherapy of allergic respiratory diseases. The study was conducted between 1994 and 1999, using an observational methodology in line with normal clinical practice, in a Hospital allergy center. The program comprised four basic steps: setting up a decisional tree, standardizing the main diagnostic-therapeutic aspects, recording of the data and statistical evaluation of the main clinical endpoints in a long period (36 months). A total of 256 patients were admitted, all with dust mite allergy; if pharmacological therapy failed after 12 months, they were assigned to immunotherapy (95 patients), either by subcutaneous injection or by the intranasal or sublingual route, depending on the main clinical-prognostic features taken into consideration. For each group of patients a control group was set up, given proper pharmacological therapy (40 patients). Allergen-specific immunotherapy was effective and well tolerated. Bronchial hyper-reactivity (BHR) tests indicated that subcutaneous or sublingual immunotherapy seemed to give some protection against asthma or BHR worsening. In the group only given pharmacological therapy, an increasing percentage of patients gradually became non-responders, hence potential candidates for allergen immunotherapy. The present findings, even though obtained by a non-randomized approach, are based on a large, selected case list and show that setting up a CPI program can render possible a better overall efficacy of immunotherapy, through appropriate selection and continuous follow-up of patients.

Eye closure affects flash VEP latency in dementia.

In a group of 27 demented patients (21 with DAT and 6 with MID) with normal pattern VEP (PVEP), the latencies of the main flash VEP (FVEP) components (P1, N2, P2 and N3) were assessed both with open and closed eyes. At variance from controls, demented patients showed that both P2 and N3 components are significantly delayed with closed eyes while neither P1 nor N2 timings are affected. Control studies ruled out the possibility that such an outcome might depend on a defective pupillary responsiveness and/or an impaired sensitivity to luminance changes. On these grounds it is suggested that the effect of mode of stimulation on FVEP latency in demented patients is more likely to depend on "central" than on "peripheral" mechanisms. The dependence of latency changes on closure of the eyes seems to negate the direct effect of lesions upon visual structures and suggests an impairment of the modulatory action of non-visual afferents upon the activity of the visual cortex.