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Evaluation of the asthmas
Published in Vibeke Backer, Peter G. Gibson, Ian D. Pavord, The Asthmas, 2023
Vibeke Backer, Peter G. Gibson, Ian D. Pavord
Firstly, the airway trait of type-2 inflammation is measured using biomarkers such as the blood eosinophil count and FeNO. Both of these markers have been consistently linked to an increased risk of exacerbation with a combined eosinophil/FeNO measure also associated with a doubling prevalence of uncontrolled asthma. Treatment that targets type-2 inflammation is associated with fewer asthma exacerbations. FeNO can also be used to provide information on adherence which can be used to delineate refractory patients from those who are non-adherent to corticosteroid therapy. Both markers are relatively easy to perform, provide relatively rapid information and add both predictive and prognostic value. This is also an obvious entry point for the use of novel digital inhalers and connected inhaler systems, which when aligned with biomarker profiling (FeNO and blood eosinophil count) will aid decision making in the clinic prior to treatment escalation. This approach will facilitate the identification of patients who would achieve a good response with monitored adherence with inhaled treatment but also identifies patients who despite adequate treatment with high-dose ICS treatment are likely to have persisting type-2 inflammation and will probably require escalation to novel biologic therapies.
Mucosal responses to helminth infections
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
William Gause, Richard Grencis
Helminth parasites can seriously compromise host fitness in man, vertebrates in the wild, and animals used in agriculture. In humans, they remain a major global health problem contributing to morbidity and impaired childhood development. The type 2 immune response is uniquely adapted to mediate protective immunity against these relatively large multicellular eukaryotic pathogens. Although many of the same immune cell types are involved in helminth and microbial infections, their activation states can be quite different. Host-protective immune responses against helminths can mediate enhanced resistance and mitigation of tissue injury, which is particularly important as these large parasites migrate through vital organs such as the lung and intestine. However, in some cases, chronic type 2 immune responses can lead to harmful type 2 inflammation contributing to fibrosis and components of the type 2 immune response can cause immediate hypersensitivity reactions. Epidemiological studies have identified a correlation between helminth infections and reduced inflammatory and autoimmune diseases in developing countries. Helminth excretory/secretory products, an outcome of the long coevolutionary relationship with vertebrates, have numerous immunomodulatory effects. More research is needed to develop effective vaccines against helminths and to potentially harness immunomodulatory effects of these helminths to treat inflammatory diseases and enhance wound healing.
Olfactory dysfunction in chronic rhinosinusitis: insights into the underlying mechanisms and treatments
Published in Expert Review of Clinical Immunology, 2023
Jing Song, Ming Wang, Chengshuo Wang, Luo Zhang
Recently, several studies have also shown beneficial effects of biologic agents on OD in Th2-biased CRSwNP [121]. Dupilumab, a blocker of the shared IL‐4/IL‐13 receptor component, can significantly improve the smell of CRSwNP patients with comorbid non‐steroidal anti‐inflammatory drug‐exacerbated respiratory disease [122]. Surprisingly, during the treatment period of dupilumab, the proportion of patients who received treatment with sinonasal surgery was significantly lower than in the placebo group [123]. Whilst Omalizumab, an anti-IgE antibody, has been shown to have obvious benefits in the olfaction of CRSwNP patients [124], Mepolizumab selectively binds to and inactivates IL-5 to improve smell in CRSwNP patients, especially of patients with fewer previous surgeries [125]. Another monoclonal antibody that is directed against the alpha subunit of the IL-5 receptor has also been shown to reduce the difficulty with sense of smell compared to placebo in patients with CRSwNP [126]. More recently, a systematic review and network meta-analysis has shown that although multiple biologics credibly improve several patient-important outcomes, including smell, in CRSwNP patients dupilumab is the most beneficial of all and improves sense/loss of smell to a greater level compared to omalizumab, mepolizumab, benralizumab [127]. As studies involving type 2 inflammation are well ahead of studies involving non-type 2 inflammation, it is recommended that further studies should also focus on non-type 2 inflammation-targeted treatment approaches and the safety of biologics for routine clinical use [128].
Updates in the diagnosis and practical management of allergic rhinitis
Published in Expert Review of Clinical Pharmacology, 2023
Chiara Trincianti, Maria Angela Tosca, Giorgio Ciprandi
Allergic rhinitis is the most frequent IgE-mediated disease and recognizes a type 2 phenotype characterized by eosinophilic infiltrate and allergen exposure-dependent inflammation [68]. Although it is well known, and several guidelines have established precise diagnostic criteria and treatment protocols, controlling allergic rhinitis is not optimal in most patients [69]. In this regard, an attracting issue concerns the availability of simple biomarkers measuring type 2 inflammation. That is, it is well known that allergic inflammation may be present despite symptoms, such as the concept of minimal persistent inflammation [70]. In other words, the possibility of documenting the presence and severity of type 2 inflammation can modulate the use of antiallergic treatments. In fact, patients prefer to take drugs on demand, but this approach could be inappropriate, mainly if inflammation persists also without overt symptoms. In this regard, a trivial blood cell count is recommended for getting a rough idea of the degree of type 2 inflammation [71]. However, it remains desirable to also have biomarkers that can predict the response to AIT and define the efficacy so that treatment can be discontinued judiciously.
Defining response to therapy with biologics in severe asthma: from global evaluation to super response and remission
Published in Expert Review of Respiratory Medicine, 2023
Andriana I Papaioannou, Evangelia Fouka, Konstantinos Bartziokas, Maria Kallieri, Angelos Vontetsianos, Konstantinos Porpodis, Nikoletta Rovina, Stelios Loukides, Petros Bakakos
To this context, consideration of the characteristics of patients who are candidates for treatment discontinuation is of paramount importance. Firstly, it is meaningful to withdraw biologics in patients with poor symptom control, continuing exacerbations, or airflow limitation [142]. Several authors suggest that the suppression of Type 2 inflammation may be a necessary precondition to achieve clinical remission [143,144]. Moreover, patients with severe asthma often have co-existing comorbidities contributing to their symptoms, requiring a multidimensional management approach. In a Spanish real-life study, patients who successfully discontinued omalizumab tended to present fewer comorbidities such as sinusitis and nasal polyp than those who failed to withdraw biologic therapy [37]. These findings suggest that, in addition to clinical and immunological control, successful management of asthma comorbidities may be required for the discontinuation of biologics.