S. Buscaglia

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.

Cetirizine reduces inflammatory cell recruitment and ICAM-1 (or CD54) expression on conjunctival epithelium in both early- and late-phase reactions after allergen-specific challenge ☆ ☆☆ ★ ★★

BACKGROUND Allergen-specific conjunctival challenge (ASCC) is a safe and reproducible experimental model of allergic conjunctivitis and a useful tool in the evaluation of effectiveness and possible mechanisms of action of drugs commonly used in the treatment of allergic diseases. OBJECTIVE The protective effect of cetirizine on inflammatory changes after ASCC was assessed in 12 patients with rhinoconjunctivitis caused by Parietaria judaica in a double-blind study. METHODS After a screening ASCC was performed, patients were randomized into two treatment groups; each patient was given cetirizine (oral tablets) 10 mg twice daily, or matching placebo for 3 1/2 days in off-pollen season. Clinical evaluation (itching, hyperemia, lacrimation, and swelling of eyelids) and cytologic assessment (number of inflammatory cells in conjunctival scraping and evaluation of intercellular adhesion molecule-1 (ICAM-1)/CD54 expression on epithelial cells) were performed at baseline, 30 minutes (i.e., early-phase reaction [EPR]), 6 hours, and 24 hours (i.e., late-phase reaction [LPR]) after ASCC, before and after treatment. RESULTS The EPR clinical events and the EPR total number of inflammatory cells were significantly reduced by cetirizine compared with placebo. The LPR clinical events and inflammatory cell recruitment were reduced by cetirizine in a similar manner. Both eosinophil and neutrophil numbers were decreased by active drug in EPR and LPR. Furthermore, ICAM-1/CD54 expression was significantly reduced by cetirizine in both the EPR and LPR compared with placebo. CONCLUSIONS This study shows that cetirizine has a protective effect on clinical and cellular EPR and LPR events (including ICAM-1/CD54 expression on epithelium) induced by ASCC.

Allergic subjects express intercellular adhesion molecule — 1 (ICAMA or CD54) on epithelial cells of conjunctiva after allergen challenge

BACKGROUND Allergic inflammation can be experimentally reproduced in vivo in humans, by means of the conjunctival provocation test with allergen. The allergen stimulation triggers an early clinical response and an almost simultaneous cellular infiltrate. Among the factors that can contribute to the local cellular recruitment, we postulate a possible early involvement of CD54 in the development of inflammation caused by the allergic reaction. METHODS We used a sensitive immunocytochemical immunoenzymatic alkaline phosphatase-monoclonal antialkaline phosphatase technique to detect the possible expression of CD54 molecule on epithelial cells of conjunctiva in 15 allergic subjects and in 15 healthy individuals in basal conditions and after allergen challenge (Parietaria judaica) during the off-pollen season. RESULTS At baseline all studied individuals did not evidence CD54 expression on epithelial cells; 30 minutes after allergen challenge, all the allergic individuals showed a marked expression of CD54 on conjunctival epithelium, whereas none of healthy subjects showed any CD54 expression. First, CD54 expression on conjunctival epithelium after specific provocation test appeared as a specific phenomenon occurring only in sensitized subjects; moreover, it is an immediate event concomitant with the local inflammatory infiltrate. Therefore conjunctival epithelium unexpectedly appeared to be more than a bystander in the allergic reaction; it may be perceived as an active participant interacting with the inflammatory infiltrate. CONCLUSIONS These findings indicate that CD54 may play a central role in the allergic inflammation and strongly support the concept that maneuvers designed to interact with the adhesion machinery expressed on inflammatory cells and epithelium may be a helpful therapeutic approach.

ICAM-1 on epithelial cells in allergic subjects: a hallmark of allergic inflammation.

Allergen-specific challenge was first shown to induce ICAM-1 expression on epithelial cells (ECs) of conjunctiva in allergic patients. The data have also been confirmed in the nose. We then checked for the presence of ICAM-1 consequent to natural exposure to allergens. For both conjunctivitis and rhinitis due to pollen we confirmed, during the pollen season, the presence of ICAM-1 on ECs. We demonstrated the endogenous source of ICAM-1 by in situ hybridization both in vitro and in vivo. ICAM-1 could be an activation marker on ECs, or could, enhanced EC susceptibility to bind offending cells such as eosinophils (LFA-1+). ICAM-1 is also a receptor for the vast majority of rhinoviruses, which are known to provoke, mainly in children, asthma attacks. Since we found that mite allergens can induce ICAM-1 on ECs, even during clinical latency, allergy may be considered as a primary event leading to asthma (through rhinovirus infection) and non-specific hyperreactivity.

Adhesion molecules of allergic inflammation: recent insights into their functional roles

Canonica GW, Ciprandi G, Buscaglia S, Pesce G, Bagnasco M. Adhesion molecules of allergic inflammation: recent insights into their functional roles.

Azelastine eye drops reduce and prevent allergic conjunctival reaction and exert anti‐allergic activity

Background Azelastine is a selective H1‐receptor antagonist, which has previously been demonstrated to be effective in the treatment of allergic rhinitis. We have recently demonstrated that nasal azelastine inhibits the clinical and intlammatory events following nasal allergen challenge. Particularly, we focused our attention on ICAM‐1 expression on epithelial cells, since it is the natural ligand of LFA‐1, an adhesion molecule expressed by leucocytes, including eosinophils.

Drug treatment of allergic conjunctivitis. A review of the evidence.

SummaryAllergic conjunctivitis, unlike several other ocular diseases, is seldom followed by permanent visual impairment; nevertheless, it is important because of both its frequency and its severity. Two major forms, seasonal and perennial, are considered in this review.To recognise the hallmarks of allergic conjunctivitis, clinicians have need of a thorough knowledge of its pathophysiological aspects and clinical features, enabling them to choose the best and most suitable therapy among the alternatives. The aims of treatment vary according to the symptoms, severity and characteristics of the allergic reactions; in general, treatment is based mainly on environmental control, pharmacotherapy and (sometimes) specific immunotherapy.Topical vasoconstrictors, decongestant compounds, standard antihistamines or combinations of these drugs have been used for a number of years to treat the acute and/or persistent symptomatology, and in order to prevent the side effects of a prolonged treatment with topical glucocorticosteroids. Nevertheless, the latter represent the most powerful anti-inflammatory drugs, and are particularly recommended in short term treatment (5 to 7 days) in severe acute symptomatology. Orally administered ‘classic’ antihistamines, i.e. histamine H1-receptor antagonists, are effective and very convenient in either short or long term treatment, largely because the new compounds also act on the inflammatory process secondary to the allergic events.Recently, other topical compounds such as sodium cromoglycate (cromolyn sodium), nedocromil and nonsteroidal anti-inflammatory drugs (NSAIDs) [i.e. piroxicam, aspirin] have become available. Sodium cromoglycate and nedocromil act as prophylactic compounds, able to prevent the allergic reaction; NSAIDs represent a valid and effective alternative to glucocorticosteroids in several situations.

Protective Effect of Loratadine on Late Phase Reaction Induced by Conjunctival Provocation Test

The protective effect of Loratadine, a new generation, non-sedating antihistamine, on clinical and cellular events during the early phase reaction (EPR) and late phase reaction (LPR) of the allergen-specific conjunctival provocation test (CPT) was assessed out of the pollen season in 20 seasonally allergic rhino-conjunctivitis patients. After a screening CPT, selected patients were randomized to Loratadine (10 mg OD) or matching placebo for 7 days. CPT was repeated following treatment. Clinical and cellular responses were evaluated by a symptom score and cell counting in conjunctival scrapings before, and 30 min and 6 h after challenge with allergen (one eye) or placebo (control eye). Conjunctival symptom severity following CPT was reduced at 30 min (EPR) and 6 h (LPR) after CPT in the Loratadine group compared to placebo group (p < 0.01), as was the total number of inflammatory cells (p < 0.001). In conclusion, Loratadine protects against the clinical and cellular EPR and LPR events consequent to CPT, showing antiallergic properties.

Protective effect of loratadine on specific conjunctival provocation test.

The protective effect of loratadine (anti-H1 antagonist) on clinical and cellular processes following the early phase of specific conjunctival provocation test was assessed in 20 patients affected by seasonal allergic rhinoconjunctivitis, in a double-blind, randomized, placebo-controlled, parallel-group study. Patients were randomly assigned to two treatment groups, each being given a single daily dose of loratadine 10 mg or placebo, for 7 days, out of pollen season. Pretreatment with Loratadine resulted in a significant higher allergen threshold dose than placebo (p less than 0.01). Patients treated with loratadine experienced a significant reduction (p less than 0.01) in conjunctival symptom severity as compared with placebo, following conjunctival challenge. Finally, the number of inflammatory cells was lower in the loratadine-treated patients compared to the placebo group (p less than 0.01). In conclusion, loratadine exerts a significant protective effect on the early phase cellular and clinical events of conjunctival reaction induced by allergen challenge in atopic patients.

Topical ocular levocabastine reduces ICAM-1 expression on epithelial cells both in vivo and in vitro

Background Levocabastine is a selective topical H1 antagonist, effective in the treatment of seasonal allergic rhinitis and conjunctivitis.