Allergen immunotherapy in asthma: current evidence and future requirements.

The role of allergen-specific immunotherapy in asthma (AIT) is still a matter of debate. Actually, many controlled clinical trials have proved efficacy and safety of AIT in asthma, and some published meta-analyses, despite some methodological weaknesses, have confirmed these findings, the most recent and convincing being a meta-analysis on injection AIT studies. For sublingual AIT evidences do exist, but SLIT meta-analyses are mostly questioned due to some biases and inconsistencies. Most of these arise from methodological problems in single studies, usually small, underpowered and carried out with mixed populations. The main need, therefore, is to perform AIT clinical studies only in patients with asthma and following standardized protocols, as recommended by international Guidelines. Studies of AIT in asthma should also focus more on the long term and preventive effects of the treatment, rather than considering only the immediate efficacy on allergic symptoms. Furthermore, specific asthma features, such as lung function, bronchial reactivity, asthma control and exacerbations, should be included among the study outcomes.

Bronchial hyperresponsiveness is a common feature in patients with chronic urticaria.

BACKGROUND: Chronic urticaria (CU) is a skin disorder characterized by long-lasting release of histamine, and sometimes leukotrienes, from both mast cells and basophils. Although both these substances are potent inductors of contraction of airway smooth muscle, pulmonary function and airway hyperresponsiveness have not been systematically investigated in patients with CU. OBJECTIVE: To assess pulmonary function and airway hyperresponsiveness in patients with CU. METHODS: Twenty-six clinically well-characterized adult patients with CU (M/F 8/18; mean age 47 years) underwent pulmonary function tests and methacholine provocation during a phase of moderate activity of their disease. Twenty-six adult asthmatic patients submitted to methacholine provocation were used as controls. RESULTS: Two patients (8%) had overt asthma on baseline pulmonary function tests. Twenty (77%) patients with a normal baseline pulmonary function showed significant bronchial hyperresponsiveness on methacholine provocation. Altogether, 22/26 (85%) patients had asthma or abnormal bronchial reactivity. Airway hyperresponsiveness was not associated with gender, disease duration, intolerance to NSAID, positive autologous serum skin test or respiratory allergy. On average, asthmatic controls showed a much severer airway hyperresponsiveness than urticaria patients (p < 0.01). CONCLUSION: Patients with CU frequently show bronchial hyperresponsiveness. Prospective studies are needed to assess whether they are at risk for bronchial asthma.

Long-term and preventive effects of sublingual allergen-specific immunotherapy: a retrospective, multicentric study.

There is now an increasing body of evidence to support the practice of allergen-specific sublingual-swallow immunotherapy (SLIT) in the treatment of IgE-mediated respiratory allergies. Recent studies on traditional injection therapy have pointed out that this form of treatment is not only capable to decrease actual allergic symptoms, but may also have long-term clinical and preventive effects and may influence atopy natural history. In the year 2000, our group published a retrospective, multicenter study showing the efficacy and safety of SLIT in a survey of 302 patients. We now carried out a second study on the same patients, with the aim of investigating long-term and preventive effects of SLIT. Beside the well-known safety and efficacy of this treatment (80.8% of patients reported clinical benefits), SLIT proved also to elicit long term clinical effects: over a mean follow-up of 11.6 months after the end of treatment, 80.8% of patients still maintained the previously achieved benefits. During the follow-up period, only 1% of non-asthma patients reported an onset of respiratory symptoms, and only 9.6% of patients undergoing new skin tests showed new sensitizations. All the clinical benefits were strongly linked to the length of treatment: patients with long-lasting benefits were treated for a mean length of 29.1 months, while patients showing a return to pre-SLIT condition were treated for a mean 13.3 months. SLIT can obtain long-term and preventive effects so far attributed to injection immunotherapy.

Safety and efficacy evaluation of sublingual allergen-specific immunotherapy a retrospective, multicenter study.

In recent years, several controlled studies have proved the efficacy and safety of sublingual specific immunotherapy, as a possible alternative to the classic subcutaneous route of administration. This alternative option has been officially confirmed by the recent WHO position paper "Allergen Immunotherapy: Therapeutic Vaccines for Allergic Diseases'". Since sublingual immunotherapy has now been widely used for years, we carried out an open, multicentric, retrospective study to investigate the efficacy and safety of this form of treatment in a large number of patients. To this end, we studied 302 subjects undergoing sublingual immunotherapy for at least three months with different allergen compositions. Notwithstanding the obvious limitations due to the study design, this survey has confirmed the high efficacy and safety of this form of treatment, as already reported in previous controlled studies. Sublingual immunotherapy appears to be a simple, well-tolerated and effective method of treatment of allergen-specific diseases.

MR889, a neutrophil elastase inhibitor, in patients with chronic obstructive pulmonary disease: a double-blind, randomized, placebo-controlled clinical trial.

We investigated whether MR889, a synthetic cyclic thiolic elastase inhibitor, administered for a period of 4 weeks to chronic obstructive pulmonary disease (COPD) patients, is well-tolerated, and whether it modifies biochemical indices of lung destruction. The study was a double-blind, randomized, placebo-controlled clinical trial in COPD patients. Thirty subjects were administered MR889 orally at a dose of 500 mg b.i.d. for 4 weeks, and 30 received placebo following the same schedule. In addition to safety parameters, MR889 efficacy was checked by a pretreatment/postreatment evaluation of levels of plasma elastin-derived peptides and urinary desmosine. There were no statistically significant differences between pretreatment and posttreatment efficacy parameter levels either in the control group or in the treated group. However, in a subset of treated patients with a short disease duration, the level of urinary desmosine dropped significantly with respect to pretreatment values (p = 0.004). We conclude that MR889 is safe to administer to COPD patients for a period of at least 4 weeks. During this time, MR889 does not modify biochemical markers of lung destruction in unselected COPD patients. Nevertheless, a subset of treated patients with fairly short disease duration showed a post-treatment reduction of desmosine urine levels, thus justifying the need for further studies to prove the efficacy of MR889 in modulating indices of lung destruction in COPD.

Seasonal increase of bronchial reactivity in allergic rhinitis.

Twenty-seven patients with hay fever had a carbachol inhalation challenge both out of season and during the pollen season. Eight patients with allergic asthma were used as a control group. Only three patients (11.1%) demonstrated a value of a provocative dose causing a 20% fall in FEV1 in the asthmatic range out of pollen season, but during pollen exposure, the number of positive responses significantly increased to 13 (48.1%). We observed differences regarding mean age, age of onset of symptoms, sex, and family history between patients with positive responses and patients who failed to react to inhalation challenge. It appears reasonable that an aspecific bronchial provocation test, performed during the pollen season, can detect with greater sensitivity patients with hay fever at risk of developing asthma in the future, and it also appears reasonable that these patients should be treated differently from subjects with "pure" allergic rhinitis. We expect the ongoing follow-up to clarify the prognostic value to be attributed to these findings.

T-cell subsets in sarcoidosis: an immunocytochemical investigation of blood, bronchoalveolar lavage fluid, and prescalenic lymph nodes from eight patients.

T-lymphocyte subsets in peripheral blood, bronchoalveolar lavage fluid, and prescalenic lymph nodes from eight patients with sarcoidosis were evaluated with monoclonal antibodies. Both in lung and lymph nodes significant increases in helper T cells were demonstrated, except in patients with stage III pulmonary disease or with unaffected lymph nodes. A good statistical correlation was observed between the activity of the disease (expressed by an increased ratio of helper to suppressor/cytotoxic T cells) in bronchoalveolar fluid and in lymph node cell suspensions from each patient. A three-step immunoperoxidase staining reaction, performed on lymph node frozen sections, showed a prevalence of helper T cells both inside and around the granulomas. These findings confirm that sarcoidosis is characterized by increased activity of cell-mediated immunity in its different localizations.