Elevated serum IgE, oral corticosteroid dependence and IL-17/22 expression in highly neutrophilic asthma

Information on the clinical traits associated with bronchial neutrophilia in asthma is scant, preventing its recognition and adequate treatment. We aimed to assess the clinical, functional and biological features of neutrophilic asthma and identify possible predictors of bronchial neutrophilia.The inflammatory phenotype of 70 mild-to-severe asthma patients was studied cross-sectionally based on the eosinophilic/neutrophilic counts in their bronchial lamina propria. Patients were classified as neutrophilic or non-neutrophilic. Neutrophilic asthma patients (neutrophil count cut-off: 47.17 neutrophils·mm−2; range: 47.17–198.11 neutrophils·mm−2; median: 94.34 neutrophils·mm−2) were further classified as high (≥94.34 neutrophils·mm−2) or intermediate (47.17– <94.34 neutrophils·mm−2). The effect of smoking ≥10 pack-years was also assessed.Neutrophilic asthma patients (n=38; 36 mixed eosinophilic/neutrophilic) had greater disease severity, functional residual capacity, inhaled corticosteroid (ICS) dose and exacerbations, and lower forced vital capacity (FVC) % pred and forced expiratory volume in 1 s (FEV1) reversibility than non-neutrophilic asthma patients (n=32; 28 eosinophilic and four paucigranulocytic). Neutrophilic asthma patients had similar eosinophil counts, increased bronchial CD8+, interleukin (IL)-17-F+ and IL-22+ cells, and decreased mast cells compared with non-neutrophilic asthma patients. FEV1 and FVC reversibility were independent predictors of bronchial neutrophilia in our cohort. High neutrophilic patients (n=21) had increased serum IgE levels, sensitivity to perennial allergens, exacerbation rate, oral corticosteroid dependence, and CD4+ and IL-17F+ cells in their bronchial mucosa. Excluding smokers revealed increased IL-17A+ and IL-22+ cells in highly neutrophilic patients.We provide new evidence linking the presence of high bronchial neutrophilia in asthma to an adaptive immune response associated with allergy (IgE) and IL-17/22 cytokine expression. High bronchial neutrophilia may discriminate a new endotype of asthma. Further research is warranted on the relationship between bronchoreversibility and bronchial neutrophilia.

The Role of Histamine in the Pathophysiology of Asthma and the Clinical Efficacy of Antihistamines in Asthma Therapy

Mast cells play a critical role in the pathogenesis of allergic asthma. Histamine is a central mediator released from mast cells through allergic reactions. Histamine plays a role in airway obstruction via smooth muscle contraction, bronchial secretion, and airway mucosal edema. However, previous clinical trials of H1 receptor antagonists (H1RAs) as a treatment for asthma were not successful. In recent years, type 2 innate immunity has been demonstrated to be involved in allergic airway inflammation. Allergic asthma is defined by IgE antibody-mediated mast cell degranulation, while group 2 innate lymphoid cells (ILC2) induce eosinophilic inflammation in nonallergic asthma without allergen-specific IgE. Anti-IgE therapy has demonstrated prominent efficacy in the treatment of severe allergic asthmatics sensitized with specific perennial allergens. Furthermore, recent trials of specific cytokine antagonists indicated that these antagonists were effective in only some subtypes of asthma. Accordingly, H1RAs may show significant clinical efficacy for some subtypes of allergic asthma in which histamine is deeply associated with the pathophysiology.

Allergic Rhinitis, Conjunctivitis, and Sinusitis

Allergic rhinitis is an IgE-mediated inflammatory response in the nose to foreign substances known as allergens. It can be classified as seasonal or perennial, depending on the allergens triggering the reaction. This characterization is good for identifying allergen triggers but is limited because it is based on the duration of outdoor exposure (e.g., grass pollinates for 2 months in Chicago and nearly 11 months in Texas). Also, some perennial allergens, such as dust mites, have seasons. The Allergic Rhinitis in Asthma (ARIA) classification was developed to focus on therapy. It assumes that exposure to perennial and to seasonal allergen leads to the same immunologic response. ARIA places patients into the categories of mild intermittent, mild persistent, moderate/severe intermittent, and moderate/severe persistent to recommend treatment and emphasizes the link between allergic rhinitis and asthma. This review contains 5 figures, 9 tables, and 56 references. Key Words: Sinusitis, infection, allergy, antibiotic, decongestant, antihistamine

Allergic Rhinitis, Conjunctivitis, and Sinusitis

Allergic rhinitis is an IgE-mediated inflammatory response in the nose to foreign substances known as allergens. It can be classified as seasonal or perennial, depending on the allergens triggering the reaction. This characterization is good for identifying allergen triggers but is limited because it is based on the duration of outdoor exposure (e.g., grass pollinates for 2 months in Chicago and nearly 11 months in Texas). Also, some perennial allergens, such as dust mites, have seasons. The Allergic Rhinitis in Asthma (ARIA) classification was developed to focus on therapy. It assumes that exposure to perennial and to seasonal allergen leads to the same immunologic response. ARIA places patients into the categories of mild intermittent, mild persistent, moderate/severe intermittent, and moderate/severe persistent to recommend treatment and emphasizes the link between allergic rhinitis and asthma.1 This review contains 5 figures, 9 tables, and 56 references. Key Words: Sinusitis, infection, allergy, antibiotic, decongestant, antihistamine

Allergic Rhinitis, Conjunctivitis, and Sinusitis

Allergic rhinitis is an IgE-mediated inflammatory response in the nose to foreign substances known as allergens. It can be classified as seasonal or perennial, depending on the allergens triggering the reaction. This characterization is good for identifying allergen triggers but is limited because it is based on the duration of outdoor exposure (e.g., grass pollinates for 2 months in Chicago and nearly 11 months in Texas). Also, some perennial allergens, such as dust mites, have seasons. The Allergic Rhinitis in Asthma (ARIA) classification was developed to focus on therapy. It assumes that exposure to perennial and to seasonal allergen leads to the same immunologic response. ARIA places patients into the categories of mild intermittent, mild persistent, moderate/severe intermittent, and moderate/severe persistent to recommend treatment and emphasizes the link between allergic rhinitis and asthma.1 This review contains 5 figures, 9 tables, and 56 references. Key Words: Sinusitis, infection, allergy, antibiotic, decongestant, antihistamine

Practice parameters for sublingual immunotherapy

The efficacy and safety of sublingual immunotherapy (SLIT) are currently supported by clinical trials, metaanalysis and post-marketing surveys. Practice parameters for clinical use of SLIT are proposed here by a panel of Italian specialists, with reference to evidence based criteria. Indications to SLIT include allergic rhinoconjunctivitis, asthma, and isolated conjunctivitis (strength of recommendation: grade A). As to severity of the disease, SLIT is indicated in moderate/severe intermittent rhinitis, persistent rhinitis and mild to moderate asthma (grade D). SLIT may be safely prescribed also in children aged three to five years (grade B), and its use in subjects aged more than 60 years is not prevented when the indications and contraindication are ascertained (grade D). The choice of the allergen to be employed for SLIT should be made in accordance with the combination of clinical history and results of skin prick tests (grade D). Polysensitisation, i.e. the occurrence of multiple positive response does not exclude SLIT, which may be done with the clinically most important allergens (grade D). As to practical administration, co-seasonal, pre co-seasonal, and continuous schedules are available, being the latter recommended for perennial allergens or for pollens with particularly prolonged pollination, such as Parietaria (grade D). For pollens with relatively short pollination, such as grasses and trees (cypress, birch, alder, hazelnut, olive) the pre coseasonal and perennial schedules are preferred (grade C). The build-up phases suggested by manufacturers can be safely used (grade A), but they can be modified according to the patient’s tolerance (grade C). A duration of SLIT of 3-5 years is recommended to ensure a long-lasting clinical effect after the treatment has been terminated (grade C).