Vittorio Ricca

Minimal persistent inflammation is present at mucosal level in patients with asymptomatic rhinitis and mite allergy

The natural exposure to house dust mites causes sensitization in genetically susceptible patients. Persistent exposure of sensitized patients causes chronic inflammation, and consequently, hyperreactivity, thus promoting the development of clinical features. Recently, intercellular adhesion molecule-1 (ICAM-1)/CD54 expression on epithelial cells triggered by allergen has been demonstrated and related to the inflammation caused by the allergic reaction. Therefore we evaluated the possible presence of inflammation (i.e., inflammatory cell infiltrate and ICAM-1/CD54 expression on epithelium) at conjunctival and nasal levels in patients with asymptomatic allergic rhinitis caused by mites, in their relatives living in the same environment, and in healthy volunteers. In addition, the possible relationship between inflammation and house dust mite allergen exposure was evaluated. Conjunctival and nasal scrapings of allergic subjects enrolled in the study showed many inflammatory cells. A mild ICAM-1/CD54 expression on conjunctival and nasal epithelium was detectable in allergic subjects, whereas relatives and healthy volunteers showed few inflammatory cells and no ICAM-1/CD54 expression on epithelial cells. A detectable level of house dust mite, sufficient to cause sensitization, was found in all houses. This study demonstrates a minimal persistent inflammation at conjunctival and nasal levels constantly detectable in patients without symptoms who are sensitized to mites and continuously exposed to the natural allergens.

Topical azelastine reduces eosinophil activation and intercellular adhesion molecule-1 expression on nasal epithelial cells: An antiallergic activity

BACKGROUND It is well known that allergen-specific nasal challenge (ASNC) is a fruitful tool with which to evaluate antiallergic activity exerted by a drug. Azelastine is a new antihistamine also available in topical form (i.e., nasal spray). OBJECTIVE The aim of the study was to evaluate the effects of azelastine nasal spray on inflammatory changes after ASNC in both the early-phase reaction and the late-phase reaction. METHODS The study had a double-blind, placebo-controlled, randomized, and parallel-group design. Twenty patients with pollen allergy were enrolled out of pollen season. ASNC was performed at baseline (TO) and after 1 week of washout (T7). At T7, 10 patients sprayed azelastine (1 puff) into their nostrils, and 10 patients used placebo. ASNC was performed after 30 minutes. The considered parameters (evaluated during early- and late-phase reactions) were: (1) clinical signs and symptoms, (2) cytologic assessment (neutrophils and eosinophils), (3) assay-of mediators (eosinophil cationic protein and myeloperoxidase), and (4) expression of intercellular adhesion molecule-1 (ICAM-1) on nasal epithelial cells. We focused our attention on ICAM-1 because it is the natural ligand of leukocyte functional associated antigen-1 and Mac-1, expressed on eosinophils. In addition, ICAM-1 is expressed on epithelial cells only on allergen exposure (both natural and experimental). RESULTS Placebo did not exert any modification on the considered parameters. After azelastine administration, significant decreases in total symptom score, eosinophilic and neutrophilic infiltration, and ICAM-1 expression were observed during both early- and late-phase reactions. Furthermore, serum eosinophil cationic protein levels decreased during the late-phase reaction, whereas myeloperoxidase was not affected by the treatment. These findings were confirmed by the powerful Kochs split-plot statistical analysis. CONCLUSION Azelastine exerts antiallergic activity, mainly affecting eosinophil function and downregulating ICAM-1 expression, on nasal epithelial cells.

Minimal persistent inflammation is also present in patients with seasonal allergic rhinitis

BACKGROUND The allergic reaction is characterized by an inflammatory response, which is correlated to the allergen exposure, and is detectable in mite allergic patients, even when symptoms are absent. OBJECTIVE The study was aimed at assessing the presence of inflammation in patients with pollen allergy during a long observation period. METHODS Six patients, sensitized only to Betula alba, were enrolled. Evaluated parameters were (1) nasal symptoms, (2) inflammatory markers (ie, neutrophil and eosinophil number and intercellular adhesion molecule-1 expression on nasal epithelial cells), and (3) pollen count. Patients were examined during the pollen season every 4 days for 40 days and were observed 3 times after the pollen season. RESULTS A significant inflammatory reaction was evident throughout the pollen season, even during the days with a low pollen count and low or absent symptoms. CONCLUSIONS The results of this study indicate that the global therapeutic strategy for allergic rhinitis should be revised and targeted to inflammatory phenomena rather than to symptoms alone.

Continuous versus on demand treatment with cetirizine for allergic rhinitis.

BACKGROUND Cetirizine is an antihistamine used in the treatment of allergic rhinoconjunctivitis, that has antiallergic activity. OBJECTIVE The aim of this double-blind, placebo-controlled, parallel group study was to evaluate the clinical efficacy and the antiallergic activity of cetirizine, administered either continuously or on demand over a 4-week period of natural allergen exposure. METHODS Twenty patients, with allergic rhinoconjunctivitis due to grass and/or Parietaria pollen, were enrolled. They were randomized into 2 parallel groups: one group received the standard dose of 10 mg cetirizine daily and the other received placebo, all patients were allowed to take an additional daily dose of cetirizine when needed. Variables evaluated were clinical symptoms (recorded on diary cards), number of additional on demand cetirizine doses, nasal inflammatory cells, and pollen counts. RESULTS The results of the present study show that patients treated with continuous administration of cetirizine achieved significant symptomatic relief and inflammatory control (decreases in numbers of infiltrating neutrophils and eosinophils) in comparison to patients treated on demand. CONCLUSION Continuous treatment with cetirizine is more effective than on demand treatment. Continuous treatment reduces clinical and inflammatory variables more than symptomatic treatment and the on demand therapy can determine acceptable clinical control, but does not reduce allergic inflammation.

Evidence of intercellular adhesion molecule-1 expression on nasal epithelial cells in acute rhinoconjunctivitis caused by pollen exposure

Rhinoconjunctivitis caused by pollen allergy is characterized by typical signs and symptoms and mucosal infiltration by inflammatory cells during pollen season. It has been recently demonstrated that the adhesion molecule system is deeply involved in cell-to-cell interaction during inflammatory response consequent to allergic reactions. The aim of this study was to evaluate the expression of intercellular adhesion molecule-1 (ICAM-1 or CD54) on nasal epithelial cells, before and during natural seasonal exposure, in 10 allergic patients (Parietaria judaica-sensitized) and in 10 healthy volunteers, correlating this parameter with clinical and cytologic involvement. Nasal epithelial cells of allergic subjects showed a significant expression of CD54 during pollen season (p < 0.001). On the contrary, no CD54 expression was observed out of pollen season. In healthy volunteers no CD54 expression was observed both before and during pollen season. Cytologic evaluation demonstrated an infiltration by eosinophils (mainly activated [EG2+]), (p < 0.001), neutrophils (p < 0.001), and metachromatic cells (p < 0.001) during pollen season only in allergic subjects. Therefore results indicate that seasonal allergic rhinitis is characterized by an infiltration of inflammatory cells correlated with CD54 expression on nasal epithelial cells. This phenomenon is specific, being restricted only to allergic patients during pollen season.

Seasonal rhinitis and azelastine: Long- or short-term treatment☆☆☆★★★

BACKGROUND Azelastine is a topical antihistamine, clinically demonstrated to be effective in allergic rhinitis. OBJECTIVE We evaluated the clinical efficacy and the antiallergic activity of azelastine nasal spray, administered 0.56 mg per day, 0.28 mg per day, or on demand over a 3-month period during natural allergen exposure, in a double-blind, placebo-controlled fashion. METHODS Thirty patients, sensitized to grass or Parietaria pollen, were allocated to three treatment groups: those receiving the standard dosage (0.14 mg/nostril two times a day), half the dosage (0.07 mg/nostril two times a day), or placebo daily for 3 months. All patients were allowed to take additional doses of azelastine when needed. Evaluation parameters were as follows: clinical symptoms recorded on a diary card, number of additional, on-demand azelastine puffs, nasal inflammatory cell count, intercellular adhesion molecule-1 expression on nasal epithelial cells, and pollen count. RESULTS This study showed the following: (1) the half dose (0.28 mg/day) and the standard dose (0.56 mg/day) were equally effective in reducing clinical symptoms (p = NS), although the standard dosage required fewer additional puffs during times of peak pollen counts (p < 0.05); (2) both dosages were able to reduce the allergic inflammation (p < 0.05 vs placebo); and (3) on-demand use achieved acceptable clinical control but did not significantly reduce allergic inflammation. CONCLUSION Continuous treatment was more effective than on-demand use as assessed by both clinical evaluation and antiinflammatory action.

Allergen-Specific Nasal Challenge: Response Kinetics of Clinical and Inflammatory Events to Rechallenge

Allergen-specific nasal challenge is a valid and reliable tool for studying the pathophysiological mechanisms involved in allergic inflammation. Nasal challenge induces an immediate clinical response in allergic subjects and a concomitant appearance of an inflammatory infiltrate. The mucosal inflammation may persist up to 48–72 h after allergen exposure. If the subjects are rechallenged within this period the response is more pronounced: the so-defined priming effect. The aim of the study was to evaluate the effects of the nasal rechallenge, performed at different time intervals: 3 days, 1, 2 and 4 weeks after the first challenge. Forty allergic subjects underwent two nasal challenges: at baseline and after the periods mentioned above (10/group). Symptoms and inflammatory cells (eosinophils and neutrophils recovered by nasal brushing) were assessed. The 3-day-interval group showed a hyperreactive response (priming effect), the 1- and 4-week-interval groups showed a response similar to baseline, and the 2-week-interval group showed a hyporeactive response (‘tolerogenic effect’). The last phenomenon may be due to a possible immunologic response similar to that achievable during local specific immunotherapy. The present results further elucidate the kinetics of allergen-driven inflammatory events and highlight the importance of the time period chosen for rechallenge. The latter fact may be of primary importance in clinical trials involving specific challenge.

Cytokines evaluation in nasal lavage of allergic children after Bacillus clausii administration: A pilot study

Respiratory infections are very frequent in children. Bacillus clausii has been demonstrated to exert some immunomodulatory activities and to be safe. We conducted a study to investigate whether B. clausii administration in allergic children with recurrent respiratory infections might modulate cytokine pattern. Ten children (mean age 4.4 yr) attending the nursery school were enrolled at the end of school year (i.e. in the summer). Bacillus clausii spores (Enterogermina®: 2 billion spores per vial) were administered at the dosage schedule of two vials a day for 4 wk. A panel of cytokines, including interleukin (IL)‐1, IL‐3, IL‐4, IL‐6, IL‐8, IL‐10, IL‐12, interferon (IFN)‐γ, transforming growth factor (TGF)‐β, and tumor necrosis factor (TNF)‐α, was measured by immunoassay in the fluid recovered from nasal lavage, performed before and after the treatment. Bacillus clausii treatment induced a significant decrease of IL‐4 levels (p < 0.01) and a significant increase of IFN‐γ (p < 0.05), IL‐12 (p < 0.001), TGF‐β (p < 0.05), and IL‐10 (p < 0.05) levels. Other cytokines were not significantly modified. In conclusion, this study shows that the B. clausii may exert immunomodulating activity by affecting cytokine pattern at nasal level in allergic children with recurrent respiratory infections.