Recovery of smell sense loss by mepolizumab in a patient allergic to Dermatophagoides and affected by chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) frequently presents with dysfunction or loss of the sense of smell, resulting in a significant impairment in quality of life. The medical treatments currently available may improve the olfactory function in patients with CRSwNP, but such an outcome is generally only transitory. We report the case of a patient with CRSwNP who completely recovered from smell sense loss by treatment with mepolizumab. CASE PRESENTATION: The patient was a 62-year-old female who has severe asthma induced by allergy to Dermatophagoides and concomitant CRSwNP. Any treatment for the latter, including oral and injective corticosteroids, was unsuccessful in the loss of smell. Due to the satisfaction of admission criteria to mepolizumab treatment for severe asthma, treatment was initiated on March 2018, resulting in good clinical control of both asthma and CRSwNP, and particularly in complete recovery of the smell loss after 4 months of treatment and still persisting. CONCLUSION: In this case report, the treatment with mepolizumab in a patient allergic to Dermatophagoides and affected by CRSwNP was associated with an improvement of anosmia. That finding may be explained by a reduction of the nasal obstruction by nasal polyps.

Epicutaneous immunotherapy in rhino-conjunctivitis and food allergies: a review of the literature.

BACKGROUND: Epicutaneous immunotherapy (EPIT) is a new way of allergen administration that has a high rate of adherence and safety. The aim of this manuscript is to review clinical trials on EPIT for respiratory and food allergies published in the last 10 years, taking into account how different variables (i.e., dose, patch application duration, skin preparation, and efficacy and safety evaluation) have influenced study results. MAIN BODY: From a review of the literature, we identified eight placebo-controlled, double-blind trials conducted on children and adults, including four studies on grass pollen rhino-conjunctivitis, one on cow's milk allergy and three on peanut allergy. Different methods for skin pre-treatment, such as skin abrasion and tape stripping or stratum corneous hydration by an occlusive system, different endpoints and cumulative allergen doses, and different durations of patch application and tape stripping, were used in the rhino-conjunctivitis studies. A visual analogue system was used for the efficacy evaluation. Several local skin reactions (eczema) and some systemic adverse reactions were reported at higher rates in the active group compared to placebo in one study, but this was not shown by other authors. Local eczema reactions were correlated to the times for applying the tape stripping, while systemic side effects were correlated to the deepness of scraping. In the food allergy trials, differences in the food challenge thresholds, endpoints and allergen sites of the cutaneous patch application influenced the study results. A slight dose-dependent efficacy was found in the peanut allergy studies, which was confirmed by a more significant increase in the following progressive open study. Few adverse events and high adherence in all of the food allergen trials were reported. CONCLUSIONS: Overall, the EPIT study results, even if they were affected by great heterogeneity among the methodologies applied, have shown not only the high safety and adherence with this kind of immunotherapy but also suggested the possibility for obtaining definitive evidence of the efficacy of EPIT, especially for food allergies.

The Role of the Microbiome in Asthma: The Gut⁻Lung Axis.

Asthma is one of the most common chronic respiratory diseases worldwide. It affects all ages but frequently begins in childhood. Initiation and exacerbations may depend on individual susceptibility, viral infections, allergen exposure, tobacco smoke exposure, and outdoor air pollution. The aim of this review was to analyze the role of the gut⁻lung axis in asthma development, considering all asthma phenotypes, and to evaluate whether microbe-based therapies may be used for asthma prevention. Several studies have confirmed the role of microbiota in the regulation of immune function and the development of atopy and asthma. These clinical conditions have apparent roots in an insufficiency of early life exposure to the diverse environmental microbiota necessary to ensure colonization of the gastrointestinal and/or respiratory tracts. Commensal microbes are necessary for the induction of a balanced, tolerogenic immune system. The identification of commensal bacteria in both the gastroenteric and respiratory tracts could be an innovative and important issue. In conclusion, the function of microbiota in healthy immune response is generally acknowledged, and gut dysbacteriosis might result in chronic inflammatory respiratory disorders, particularly asthma. Further investigations are needed to improve our understanding of the role of the microbiome in inflammation and its influence on important risk factors for asthma, including tobacco smoke and host genetic features.

Allergen immunotherapy and respiratory infections in children: an encouraging experience.

BACKGROUND: Allergic inflammation may promote respiratory infections (RI). House dust mite (HDM) sensitization is common in childhood. Allergen immunotherapy may cure allergy as it restores a physiological immune and clinical tolerance toward the causal allergen and exerts anti-inflammatory activity. This study retrospectively investigated whether 3 year high-dose HDM-sublingual immunotherapy (SLIT) could affect respiratory infections in children with allergic rhinitis. METHODS: Globally, 33 HDM allergic children (18 males, mean age 9.3 years) were subdivided in 2 groups: 20 treated with symptomatic drugs alone (group 1) and 13 by high-dose SLIT, titrated in mcg of major allergens (group 2) for 3 years. RESULTS: SLIT-treated children had significantly (P=0.01) less RI episodes (3.6) than symptomatically-treated children (5.4). In addition, SLIT-treated children had less fever (P<0.01) and took fewer medications, such as antibiotics (P<0.05) and fever-reducers (P<0.01), than symptomatically-treated children. CONCLUSIONS: This preliminary study suggests that high-dose 3-year SLIT might lessen RI in allergic children.

Allergic rhinitis phenotypes based on mono-allergy or poly-allergy.

BACKGROUND: Allergic rhinitis (AR) is characterized by typical symptoms that are dependent on inflammation. Poly-allergy is a frequent phenomenon. Phenotyping AR represents an up-to-date issue. OBJECTIVE: The aim of this study was to evaluate whether the number of allergies is able to define different phenotypes in patients with AR. METHODS: 83 patients (43 males, mean age 34.7 years) suffering from AR were evaluated. Sensitization, VAS for nasal symptoms perception, and nasal cytology were evaluated. RESULTS: Poly-allergic patients perceived more severe nasal obstruction than mono-allergic ones (p = 0.0006) as well as they had more frequent sneezing (p < 0.0001). Moreover, poly-allergic patients had a more intense inflammatory infiltrate, concerning both eosinophils (p = 0.0005) and mast cells (p = 0.0001), than mono-allergic patients. CONCLUSIONS: The present study demonstrates that the presence of poly-allergy could define a distinct AR phenotype in comparison with mono-allergy. It could be clinically relevant as poly-allergic patients have more intense inflammation and more severe symptoms than mono-allergic ones.

A survey of clinical features of allergic rhinitis in adults.

BACKGROUND: Allergic rhinitis (AR) has high prevalence and substantial socio-economic burden. MATERIAL/METHODS: The study included 35 Italian Centers recruiting an overall number of 3383 adult patients with rhinitis (48% males, 52% females, mean age 29.1, range 18-45 years). For each patient, the attending physician had to fill in a standardized questionnaire, covering, in particular, some issues such as the ARIA classification of allergic rhinitis (AR), the results of skin prick test (SPT), the kind of treatment, the response to treatment, and the satisfaction with treatment. RESULTS: Out of the 3383 patients with rhinitis, 2788 (82.4%) had AR: 311 (11.5%) had a mild intermittent, 229 (8.8%) a mild persistent, 636 (23.5%) a moderate-severe intermittent, and 1518 (56.1%) a moderate-severe persistent form. The most frequently used drugs were oral antihistamines (77.1%) and topical corticosteroids (60.8%). The response to treatment was judged as excellent in 12.2%, good in 41.3%, fair in 31.2%, poor in 14.5%, and very bad in 0.8% of subjects. The rate of treatment dissatisfaction was significantly higher in patients with moderate-to-severe AR than in patients with mild AR (p<0.0001). Indication to allergen immunotherapy (AIT) was significantly more frequent (p<0.01) in patients with severe AR than with mild AR. CONCLUSIONS: These findings confirm the appropriateness of ARIA guidelines in classifying the AR patients and the association of severe symptoms with unsuccessful drug treatment. The optimal targeting of patients to be treated with AIT needs to be reassessed.

Ranking in importance of allergen extract characteristics for sublingual immunotherapy by Italian specialists.

The efficacy of allergen immunotherapy (AIT) is well supported by evidence from trials and meta-analyses. However, its actual performance in daily practice may be diminished by several pitfalls, including inappropriate patient selection, and, especially, the use of allergen extracts of insufficient quality. We performed a survey, the Allergen Immunotherapy Decision Analysis, to evaluate which criteria specialists use to choose products for sublingual immunotherapy (SLIT) in adult patients suffering from allergic respiratory disease. We surveyed a total of 169 Italian allergists randomly chosen from a database belonging to a market research company (Lexis Ricerche, Milan, Italy). The survey was performed between October and November 2012 under the aegis of the European Center for Allergy Research Foundation and consisted of a questionnaire-based electronic survey prepared by a scientific board of 12 AIT experts. The questionnaire comprised two parts, the first of which contained 14 items to be ranked by each participant according to the importance assigned to each when choosing SLIT products. The physicians' rankings assigned major importance to the level of evidence-based validation of efficacy and safety, standardization of the product, efficacy based on personal experience, and defined content(s) of the major allergen(s) in micrograms. The results of this survey show that Italian allergists rank the quality-related characteristics of allergen extracts as highly important when choosing products for AIT. The allergists' preference for high-quality products should be addressed by regulatory agencies and by producers.

Safety of subcutaneous and sublingual immunotherapy with allergoids in children: a real-life pharmacovigilance study.

Aims: Allergen-specific immunotherapy uses a sublingual (sublingual immunotherapy [SLIT]) or subcutaneous (subcutaneous immunotherapy [SCIT]) route. This pharmacovigilance study aimed to determine the number and type of adverse drug reactions (ADRs) for SLIT and SCIT using carbamylated monomeric allergoids (CMAs) in children. Materials & methods: This pharmacovigilance study analyzed real-world post-marketing reports collected from a safety database of Lais sublingual tablets and injective Lais-in, containing CMAs for over 10 years. Results & conclusion: From January 2009 to September 2022, 26,107 doses of Lais-in were administered in children; only two nonserious related ADRs (incidence: 0.000077%) were reported. Regarding SLIT, the results showed only 12 spontaneous nonserious ADR reports (incidence: 0.000004%). These data showed the excellent safety profile of both SLIT and SCIT CMAs.

The cure for allergic people is named allergen-specific immunotherapy (AIT). Recently, AIT uses new substances named allergoids. This study has shown that AIT with allergoids is very safe.

Association between a low IgE response to Phl p 5 and absence of asthma in patients with grass pollen allergy.

BACKGROUND: The introduction of component-resolved diagnosis was a great advance in diagnosis of allergy. In particular, molecular allergy techniques allowed investigation of the association between given molecular profiles and clinical expression of allergy. We evaluated the possible correlation between the level of specific IgE (sIgE) to single components of Phleum pratense and clinical issues such as the severity of allergic rhinitis (AR) and the presence or absence of asthma. METHODS: The study included 140 patients with rhinitis and/or asthma caused by sensitization to grass pollen. sIgE to Phl p 1, Phl p 5, Phl p 7, and Phl p 12 from Phleum pratense were measured, and the correlation between the stage of AR according to Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines and the presence of asthma was studied by multivariate logistic regression in terms of sIgE and ARIA stage, while univariate logistic regression was used for IgE and a dichotomic classification of asthma as present or absent. RESULTS: Ten patients had intermittent AR, 48 had mild persistent AR, and 82 had severe persistent AR. Asthma was present in 86 patients and absent in 54. A significant correlation was found between severe persistent AR and presence of asthma (p < 0.01). The only significant correlation between clinical data and sIgE values was that of low values of sIgE to Phl p 5 and absence of asthma (p < 0.01). CONCLUSIONS: This preliminary finding suggests that low values of sIgE to Phl p 5 are correlated with the absence of asthma in patients with grass-pollen induced allergy. The data, provided they are confirmed by further studies, could be useful when selecting patients who are candidates for allergen immunotherapy, since a higher risk of asthma could be used as a selection criterion for using this approach.

Pathophysiology, favoring factors, and associated disorders in otorhinosinusology.

The pathogenesis of rhinosinusitis (RS) is related to inflammation, caused by infections in the acute form of the disease but also by other agents in the chronic forms. Cytology allows to evaluate the defensive components, such as hair cells and muciparous cells, while the presence in the nasal mucosa of eosinophils, mast cells, bacteria and/or fungal hyphae, or spores indicates the nasal pathology. The anatomic and physiologic characteristics of the otorhinosinusal system account for the frequent concomitant involvement of the different components. The pivotal pathophysiologic sites are the ostiomeatal complex, the spheno-ethmoidal recess, and the Eustachian tube. The latter is the link with acute otitis media (AOM), which is the most common disease in infants and children and has major medical, social, and economic effects. Moreover, because of the strict relationship between upper and lower airways, nasal sinus disease may contribute to asthma and sinusitis may be considered as an independent factor associated with frequent severe asthma exacerbations. Concerning the role of allergy, the available data do not permit to attribute a central role to atopy in sinusitis and thus allergy testing should not be a routine procedure, while an allergologic evaluation may be indicated in children with OM, especially when they have concomitant rhinitis.

Immunological effects of sublingual immunotherapy: clinical efficacy is associated with modulation of programmed cell death ligand 1, IL-10, and IgG4.

Sublingual immunotherapy (SLIT) is an alternate route of administration of allergen-specific immunotherapy with an improved safety profile; to clarify the immune mechanisms elicited by this therapy, we analyzed the clinical and immunologic effects of SLIT in patients with a clinical history of ragweed sensitization. To analyze possible difference among immunotherapeutic protocols, we also compared patients receiving preseasonal, seasonal, or prolonged sublingual therapy (≥ 3 y); patients receiving symptomatic therapy alone were enrolled as well in the study. Clinical and immunological parameters were measured twice in and out of the pollination period. Clinical benefits, as measured by the visual analog scale for symptoms and for use of drugs, were evident in all three groups of individuals receiving immunotherapy, but were significantly better in patients undergoing prolonged SLIT. Immunologically, SLIT resulted in increased IL-10 production, programmed cell death ligand 1 expression, and concentration of allergen-specific IgG4, as well as in the reduction of CD80 and CD86 expression and IL-4 production. SLIT, thus, is associated with modulation of programmed cell death ligand 1 expression and IL-10 synthesis and favors the production of allergen-specific IgG4. These effects are evident from the first pollen season, independently from therapeutic regimen (preseasonal or seasonal) even if a prolonged treatment is necessary to obtain full clinical efficacy. A more detailed understanding of the interaction of allergen and APCs within the oral mucosa will allow improved targeting of allergy vaccine.

Specific IgE response to different grass pollen allergen components in children undergoing sublingual immunotherapy.

BACKGROUND: Grass pollen is a major cause of respiratory allergy worldwide and contain a number of allergens, some of theme (Phl p 1, Phl p 2, Phl p 5, and Phl 6 from Phleum pratense, and their homologous in other grasses) are known as major allergens. The administration of grass pollen extracts by immunotherapy generally induces an initial rise in specific immunoglobulin E (sIgE) production followed by a progressive decline during the treatment. Some studies reported that immunotherapy is able to induce a de novo sensitisation to allergen component previously unrecognized. METHODS: We investigated in 30 children (19 males and 11 females, mean age 11.3 years), 19 treated with sublingual immunotherapy (SLIT) by a 5-grass extract and 11 untreated, the sIgE and sIgG4 response to the different allergen components. RESULTS: Significant increases (p < 0.001) were detected for Phl p 1, Phl p 2, Phl p 5, and Phl p 6, while sIgE levels induced in response to Phl p 7 and Phl p 12 were low or absent at baseline and unchanged following SLIT treatment; no new sensitisation was detected. As to IgG4, significant increases were found for Phl p2 and Phl p 5, while the increase for Phl p 12 was not significant. In the control group, no significant increase in sIgE for any single allergen component was found. CONCLUSIONS: These findings confirm that the initial phase of SLIT with a grass pollen extract enhances the sIgE synthesis and show that the sIgE response concerns the same allergen components which induce IgE reactivity during natural exposure.

Real-Life Effectiveness of Subcutaneous Immune Therapy with Carbamylated Monomeric Allergoids on Mite, Grass, and Pellitory Respiratory Allergy: A Retrospective Study.

Background: real-life studies are encouraged to evaluate the effectiveness and safety of allergen immunotherapy (AIT). In this context, a retrospective cohort study was conducted to assess the effectiveness and safety of carbamylated monomeric allergoid subcutaneous immunotherapy (MA-SCIT), along with patient satisfaction. Methods: a total of 291 patients with rhinoconjunctivitis with or without asthma with inhalant (house dust mite, grass, and pellitory) allergies were enrolled in this study. Perceived efficacy and perceived satisfaction with MA-SCIT, symptom score by VAS, ARIA classification of rhinitis, drug consumption, number of asthma worsening episodes, and asthma symptom control were evaluated by questionnaires before, after one year, at the end of treatment, and after one or two years of MA-SCIT. Results: the overall symptom score significantly decreased over the years of MA-SCIT, irrespective of specific sensitization (p < 0.01). There was a substantial amelioration of rhinitis severity, with a significant reduction (p < 0.01) in drug use. A significant reduction was observed in the asthma symptom VAS score and asthma-worsening episodes requiring systemic steroids. None of the patients reported any severe adverse reactions. Finally, 90% of the patients reported full satisfaction with the treatment. Conclusions: the study showed that AIT with carbamylated monomeric allergoids of grass, pellitory, and mites was effective and well tolerated by patients.

Birch-apple syndrome treated with birch pollen immunotherapy.

BACKGROUND: The most common pollen-fruit cross-reaction is the birch-apple syndrome. Allergen immunotherapy (IT) is clearly effective for birch allergy, but its efficacy on apple allergy is controversial. We performed a randomized study on patients with birch-apple syndrome to evaluate the outcome of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). METHODS: Forty patients underwent IT with a birch extract (Staloral; Stallergenes, Antony, France), 20 by SCIT and 20 by SLIT. After 1 year of treatment, 15 patients (8 for SCIT and 7 for SLIT) accepted to undergo an oral apple challenge. Measurements of specific IgE to Bet v 1 and Mal d 1 and related allergens Api g 1 and Dau c 1 were obtained in 10 patients, at baseline and after IT. RESULTS: Two of 8 SCIT-treated patients (25%) and 1 of 7 SLIT-treated patients (14.2%) developed complete tolerance to apple. In the remaining patients, an increase in the provocative dose was found in 3 of the SCIT-treated (37.5%) and 2 of the SLIT-treated patients (28.6%). Changes in the levels of specific IgE to Mal d 1 were unrelated to clinical results. CONCLUSIONS: These findings suggest that different doses of birch extract may be needed in different patients to improve the associated apple allergy and that a finer diagnostic work-up in selecting patients with birch-apple syndrome who are candidates to respond to birch pollen IT also concerning apple allergy is required.

Lack of neo-sensitization to Pen a 1 in patients treated with mite sublingual immunotherapy.

BACKGROUND: Some studies reported the possible induction of food allergy, caused by neo-sensitization to cross-reacting allergens, during immunotherapy with aeroallergens, while other studies ruled out such possibility. OBJECTIVES: The aim of this study was to evaluate the development of neo-sensitization to Pen a 1 (tropomyosin) as well as the appearance of reactions after ingestion of foods containing tropomyosin as a consequence of sublingual mite immunization. MATERIALS AND METHODS: Specific IgE to Tropomyosin (rPen a 1) before and after mite sublingual immunotherapy in 134 subjects were measured. IgE-specific antibodies for mite extract and recombinant allergen Pen a 1 were evaluated using the immunoenzymatic CAP system (Phadia Diagnostics, Milan, Italy). RESULTS: All patients had rPen a 1 IgE negative results before and after mite SLIT and did not show positive shrimp extract skin reactivity and serological rPen a 1 IgE conversion after treatment. More important, no patient showed systemic reactions to crustacean ingestion. CONCLUSIONS: Patients did not show neo-sensitization to tropomyosin, a component of the extract (namely mite group 10) administered. An assessment of a patient's possible pre-existing sensitisation to tropomyosin by skin test and/or specific IgE prior to start mite extract immunotherapy is recommended. TRIAL REGISTRATION: This trial is registered in EudraCT, with the ID number of 2010-02035531.

Sublingual immunotherapy in children with allergic polysensitization.

Polysensitization is quite frequent in allergic children and may cause difficulties for the allergist in prescribing allergen-specific immunotherapy. This study aimed at evaluating the clinical effectiveness of 1 year of sublingual immunotherapy (SLIT) in a cohort of Italian allergic children with polysensitization. This open study was performed on 51 polysensitized children (34 boys; mean age, 11.8 years; range, 5.2-17.7 years) with allergic rhinitis and/or mild to moderate asthma. All of them were treated with SLIT for 1 year. The kind and the number of prescribed allergen extracts, the type of diagnosis, the severity of symptoms, and the use of drugs were evaluated at baseline and after 1 year. The adverse events to SLIT were also evaluated. Forty-two children were treated with a single extract, four with two different extracts and three with a mix of allergens. SLIT treatment induced a significant reduction in the number of sensitizations (p = 0.018); significant improvement of allergic rhinitis classification and severity; significant reduction of ocular, nasal, and bronchial symptoms (p < 0.01 for all); and drugs use (p < 0.01 for all drugs). No systemic reactions to SLIT were observed. This open study provides evidence that polysensitization is not an obstacle for prescribing SLIT in polysensitized children. Indeed, SLIT efficacy on clinical parameters is significant after 1 year and the therapy is safe.