Effect of adjuvanted and standard sublingual immunotherapy on respiratory function in pure rhinitis due to house dust mite over a 5-year period.

BACKGROUND: Allergen-specific immunotherapy (AIT) still remains the only causal treatment for IgE mediated respiratory diseases (rhinitis/asthma) In addition to the observed clinical decrease in symptoms, AIT can provide a long-lasting and preventive effect. In particular it can modify the progression from rhinitis to asthma. METHODS: The study was observational, open, non randomized, controlled, prospective and performed in a real-life setting. Patients with pure mite-induced allergic rhinitis were followed-up, receiving adjuvanted SLIT (aSLIT), standard SLIT (sSLIT) or drug treatment alone, according to their preference starting between 2008 and 2009. The possible onset of asthma, changes in pulmonary function and bronchial hyperreactivity (BHR) were assessed over a 5-year horizon. Also the onset of new sensitizations and symptoms-medication score (SMS) were evaluated. RESULTS: One hundred forty two patients fulfilling the inclusion criteria were assessed at baseline, and 124 had the 5-year evaluation (age range 8-57, 69 male). After 5 years of treatment, new sensitizations appeared differentially among treatments with 58.1% of new sensitizations in the drug treatment group, 13.2% in the sSLIT patients, and 8.1% in the aSLIT patients. At the end of 5 years, SMS significantly changed (P < 0.001) in all groups, with a negative trend for controls, as compared to the SLIT treatments. The SMS decreased in both SLIT groups at 5 years, with no change in patients on drug treatment alone. The use of salbutamol (absent at baseline), showed an overall increase only in the group receiving drugs alone with a significant difference at 5 years (P < 0.001). Considering the MCh challenge, there was a difference among treatments (P < 0.001) in PD20 after 5 years: the control group had a lower PD20 at 5 years. No significant difference in PD20 was detected between sSLIT and aSLIT. The FEV1 significantly decreased in controls, with no change in the sSLIT group and a significant increase in aSLIT as compared to sSLIT. DISCUSSION: Despite the limitations inherent to a real-life setting study (absence of randomization and control, small sample size, lack of intermediate timepoint assessment) the results of this study evidenced that the investigated SLIT product, either adjuvanted or not, had a positive effect on the evolution of respiratory allergy due to house dust mite. CONCLUSION: In the real life setting, considering a 5-year period, aSLIT and sSLIT reduced the onset of new sensistizations and maintained intact the pulmonary function, as compared to patients receiving drug treatment alone.

OSA, metabolic syndrome and CPAP: effect on cardiac remodeling in subjects with abdominal obesity.

BACKGROUND: We evaluated whether obstructive sleep apnoea (OSA) and continuous positive airway pressure (CPAP) treatment influence left ventricular (LV) remodelling independently of abdominal obesity and metabolic syndrome (MetS). METHODS: Cardiorespiratory examination, 24-h BP monitoring and echocardiogram were performed in overweight/obese patients with increased abdominal adiposity and symptoms suggesting OSA : OSA/MetS (n.50), OSA/noMetS (n.22), noOSA/MetS (n.29), noOSA/noMets (n.16). The evaluation was repeated in 41 patients after ≥18 months of CPAP. RESULTS: Despite similar age, gender, BMI and 24-h BP, the 2 groups with MetS had greater LV remodelling (LV hypertrophy and diastolic dysfunction) than the 2 groups without MetS. From multiple regression analysis independent determinants for LV mass were MetS, 24-h systolic BP and age, for LV diastolic function were LV mass index, MetS and age. After CPAP, the 20 patients with decreased body weight showed diastolic BP decrease, LV hypertrophy regression and diastolic function improvement, whereas, despite similar respiratory improvement, BP and LV parameters were unchanged in the 21 patients with body weight unchanged/increased. CONCLUSION: In patients with increased abdominal adiposity, LV remodelling is not associated to OSA per se; chronic CPAP treatment does not influence LV remodelling whose regression is mainly linked to body weight decrease.

Long-lasting effects of sublingual immunotherapy according to its duration: a 15-year prospective study.

BACKGROUND: Data on the long-term effects of sublingual immunotherapy (SLIT) are sparse, and the optimal duration of treatment is a matter of debate. OBJECTIVE: We sought to prospectively evaluate the long-term effect of SLIT given for 3, 4, or 5 years and to compare the effect of those different durations. METHODS: In this prospective open controlled study we followed up patients with respiratory allergy who were monosensitized to mites for 15 years. The subjects were divided in 4 groups receiving drug therapy alone or SLIT for 3, 4, or 5 years. Clinical scores, skin sensitizations, methacholine reactivity, and nasal eosinophil counts were evaluated every year during the winter months. The clinical effect was considered to persist until clinical scores remained at less than 50% of the baseline value, and then patients underwent another course of SLIT. RESULTS: Seventy-eight patients were enrolled, and 59 completed the study. In the 12 control subjects no relevant change in clinical scores was seen throughout the study. In the patients receiving SLIT for 3 years, the clinical benefit persisted for 7 years. In those receiving immunotherapy for 4 or 5 years, the clinical benefit persisted for 8 years. New sensitizations occurred in all the control subjects over 15 years and in less than a quarter of the patients receiving SLIT (21%, 12%, and 11%, respectively). The second course of vaccination induced a benefit more rapidly than the first course. The behavior of bronchial hyperreactivity and nasal eosinophils paralleled the clinical score. CONCLUSION: Under the present conditions, it can be suggested that a 4-year duration of SLIT is the optimal choice because it induces a long-lasting clinical improvement similar to that seen with a 5-year course and greater than that of a 3-year vaccination.

Long-term comparison of sublingual immunotherapy vs inhaled budesonide in patients with mild persistent asthma due to grass pollen.

BACKGROUND: Few studies have compared the effects of immunotherapy and inhaled steroids. The main limitation of such studies is the long duration required to fully appreciate the effects of immunotherapy. OBJECTIVE: To compare the effects of inhaled budesonide and sublingual immunotherapy (SLIT) in mild persistent asthma for up to 5 years. METHODS: Patients with mild persistent asthma and rhinitis due to grass pollen were enrolled in an open randomized controlled trial. After a run-in season, they were randomized to either budesonide, 800 microg/d, in the pollen season or continuous grass SLIT for 5 years. All patients received rescue medications. Symptoms were evaluated by diary cards filled out from May to July at baseline and after 3 and 5 years. In-season nasal eosinophils and bronchial hyperresponsiveness were also assessed. RESULTS: Fifty-one patients were enrolled and 46 completed the study. The bronchial symptom scores and the use of bronchodilators decreased significantly in both groups, but the improvement was greater in the SLIT patients at 3 and 5 years. The nasal symptom score and the intake of nasal steroids decreased only in the SLIT group, and the difference vs the budesonide group was always significant. In the SLIT group vs the budesonide group, a statistically significant decrease of nasal eosinophils was found at 3 and 5 years (P < .01). The bronchial hyperresponsiveness improved significantly only in the SLIT group. CONCLUSION: In patients with grass pollen-induced asthma, in the long term SLIT was equally effective as inhaled budesonide in treating bronchial symptoms and provided an additional benefit in treating rhinitis symptoms and bronchial hyperresponsiveness.

Preventive effects of sublingual immunotherapy in childhood: an open randomized controlled study.

BACKGROUND: Sublingual immunotherapy (SLIT) has been proved to be effective in allergic rhinitis and asthma, but there are few data on its preventive effects, especially in children. OBJECTIVE: To evaluate the clinical and preventive effects of SLIT in children by assessing onset of persistent asthma and new sensitizations, clinical symptoms, and bronchial hyperreactivity. METHODS: A total of 216 children with allergic rhinitis, with or without intermittent asthma, were evaluated and then randomized to receive drugs alone or drugs plus SLIT openly for 3 years. The clinical score was assessed yearly during allergen exposure. Pulmonary function testing, methacholine challenge, and skin prick testing were performed at the beginning and end of the study. RESULTS: One hundred forty-four children received SLIT and 72 received drugs only. Dropouts were 9.7% in the SLIT group and 8.3% in the controls. New sensitizations appeared in 34.8% of controls and in 3.1% of SLIT patients (odds ratio, 16.85; 95% confidence interval, 5.73-49.13). Mild persistent asthma was less frequent in SLIT patients (odds ratio, 0.04; 95% confidence interval, 0.01-0.17). There was a significant decrease in clinical scores in the SLIT group vs the control group since the first year. The number of children with a positive methacholine challenge result decreased significantly after 3 years only in the SLIT group. Adherence was 80% or higher in 73.8% of patients. Only 1 patient reported systemic itching. CONCLUSIONS: In everyday clinical practice, SLIT reduced the onset of new sensitizations and mild persistent asthma and decreased bronchial hyperreactivity in children with respiratory allergy.

Effects of sublingual immunotherapy for multiple or single allergens in polysensitized patients.

BACKGROUND: Sublingual immunotherapy (SLIT) has proven efficacy in treating respiratory allergy. OBJECTIVE: To compare the clinical and functional effects and the effect on nasal eosinophils of SLIT with either single or combination allergens. METHODS: We performed an open-labeled, controlled, 4 parallel-group randomized study with 58 patients sensitized to birch and grasses only who had rhinitis and bronchial hyperreactivity in both pollen seasons. Patients were recruited for the study from January 1, 1999, to June 30, 2001. The patients received SLIT for birch, SLIT for grass, SLIT for birch and grass, or drugs only. Symptom and medication scores, forced expiratory volume in 1 second, bronchial hyperreactivity, and nasal eosinophil counts were evaluated in both pollen seasons at baseline and after 2 and 4 years. RESULTS: Ten patients dropped out and 48 completed the study. No change in all the considered parameters vs baseline was seen in patients treated with drugs only. Those patients receiving SLIT for grass or birch had a significant clinical improvement and nasal eosinophil reduction vs baseline and vs patients who did not receive SLIT in the target season (P < .01) but also in the unrelated pollen season (P < .05). The patients receiving SLIT for grass and birch improved as well, and their improvement in clinical symptoms and inflammation was significantly greater than in patients treated with SLIT for the single allergens. Minor changes were seen in the forced expiratory volume in 1 second, since it remained within the reference range in the whole population. CONCLUSION: In patients sensitized to grass and birch, SLIT with the 2 allergens provided the best clinical results. Nevertheless, SLIT with birch only or grass only also provided a measurable improvement in the grass season and birch season, respectively.

Long-lasting effects of sublingual immunotherapy for house dust mites in allergic rhinitis with bronchial hyperreactivity: A long-term (13-year) retrospective study in real life.

BACKGROUND: Subcutaneous immunotherapy for respiratory allergy has shown a long lasting efficacy after its discontinuation, whereas evidence in the case of sublingual immunotherapy (SLIT) is weak. This retrospective study evaluates whether SLIT exerts a long-lasting effect and whether it relates to its duration. METHODS: Sixty-five patients allergic to mite and positive to methacholine challenge 13 years ago were studied. Twelve (control group, SLIT 0) were treated for 4 years only with standard pharmacological therapy (SPT), while 53 received SLIT and SPT. Among these, four groups were identified according to SLIT duration. Fifteen patients were treated for 1 year (SLIT 1), 10 for 2 (SLIT 2), 14 for 3 (SLIT 3) and 14 for 4 years (SLIT 4). Clinical parameters (symptom monthly score, SMS), bronchial reactivity and FEV1 were evaluated in 1992 (run-in), 1993 (baseline) and every 2 years from 1997 to 2005. RESULTS: Two to 3 years after the treatment ended, a positive effect on SMS, but not methacholine challenge and FEV1, was seen in the SLIT groups versus SLIT 0. At this time interval an effect on methacholine challenge was also seen in SLIT 3. After 7-8 years a significant difference was seen for SMS, i.e., it was significantly better in SLIT 4 than in the other groups, while bronchial reactivity was still improved in SLIT 1, 3 and 4 only after 5-6 years. CONCLUSIONS: The effects of a 4-year SLIT on clinical parameters but not bronchial reactivity and FEV1 last 7-8 years after its discontinuation. SLIT shorter than 4 years yields proportionally less impressive results.

Clinical, functional, and immunologic effects of sublingual immunotherapy in birch pollinosis: a 3-year randomized controlled study.

BACKGROUND: Sublingual immunotherapy (SLIT) has been proved effective in allergic rhinitis, but there are few studies assessing its effects on inflammation and on the lower airways. OBJECTIVE: We sought to evaluate at the same time the effects of SLIT on rhinitis symptoms, nasal inflammation, and lower airways function in patients with birch pollinosis. METHODS: Adult patients with rhinitis and asthma monosensitized to birch were evaluated during a run-in pollen season and then randomized to receive openly either drugs alone or drugs plus SLIT and reevaluated in the subsequent 4 pollen seasons. Rhinitis symptoms and consumption of bronchodilators were assessed by means of diary card. A nasal smear for eosinophil count was carried out in and out of pollen seasons, and pulmonary function tests with methacholine challenge were performed at each season. RESULTS: Of 79 enrolled patients, 27 dropped out, with a significantly higher rate of dropouts in the control group. There was a decrease in symptoms and bronchodilator use in the SLIT group versus the control group, becoming significant at the second and third pollen seasons, respectively ( P < .01 at all times). Nasal eosinophils decreased significantly in the active group, starting from the third pollen season ( P < .01). In the SLIT group a significant increase in FEV 1 , specific airways conductance, and maximal expiratory flow at 25% of forced vital capacity was seen starting from the second year and was associated with an increase in the methacholine threshold dose ( P < .01). The differences were significant also at the intragroup comparison over time. CONCLUSION: SLIT achieved a significant clinical benefit in birch pollinosis, reduced the eosinophil infiltration in nasal mucosa, and significantly improved pulmonary function during the pollen seasons.

The allergic march in pollinosis: natural history and therapeutic implications.

BACKGROUND: That specific immunotherapy (SIT) can slow the march of allergy has been confirmed in controlled clinical trials. However, an assessment of its effects in everyday life, in a large cohort of patients, might provide further useful information. METHODS: This observational study comprised 3,643 patients allergic to pollens; 1,620 with pure allergic rhinitis or rhinitis and intermittent or mild-persistent bronchial asthma, responding poorly to standard pharmacological therapy (SPT), were treated for 3 years with SPT alone (pure rhinitis, n = 890), or combined with continuous SIT (rhinitis and asthma, n = 730). Symptom/drug scores were recorded, respiratory function and skin tests were done, and methacholine challenge was scheduled at the beginning and end of the study. A series of 2,023 patients with pure rhinitis, responsive to SPT, were asked to 'self-medicate' as needed, serving as a control group to check the incidence of asthma. RESULTS: The incidence of rhinitis-asthma co-morbidity was highest in the self-medication group (50.8%). Persistent rhinitis was associated with asthma more often than the intermittent form, regardless of the severity of the symptoms that led to progression to asthma in patients with intermittent rhinitis. Treatment with SIT combined with SPT always slowed the allergic march which, however, was not influenced by drugs alone. CONCLUSIONS: In routine clinical practice, SIT is effective in preventing the allergic march. Patients with persistent rhinitis, who are at greatest risk of progression to asthma, appear to be the most logical candidates.