Inflammation, structural, and functional abnormalities within the airways are key features of asthma. Although these processes are well documented, their expression varies across the heterogeneous ...spectrum of asthma. Type 2 inflammatory responses are characterized by increased levels of eosinophils, FeNO, and type 2 cytokines in blood and/or airways. Presently, type 2 asthma is the best‐defined endotype, typically found in patients with allergic asthma, but surprisingly also in nonallergic patients with (severe) asthma. The etiology of asthma with non‐type 2 inflammation is less clear. During the past decade, targeted therapies, including biologicals and small molecules, have been increasingly integrated into treatment strategies of severe asthma. These treatments block specific inflammatory pathways or single mediators. Single or composite biomarkers help to identify patients who will benefit from these treatments. So far, only a few inflammatory biomarkers have been validated for clinical application. The European Academy of Allergy & Clinical Immunology Task Force on Biomarkers in Asthma was initiated to review different biomarker sampling methods and to investigate clinical applicability of new and existing inflammatory biomarkers (point‐of‐care) to support diagnosis, targeted treatment, and monitoring of severe asthma. Subsequently, we discuss existing and novel targeted therapies for asthma as well as applicable biomarkers.
Asthma is a chronic and heterogeneous disease, which is defined as severe disease whenever it requires treatment with a high dose of inhaled corticosteroids plus a second controller and/or systemic ...corticosteroids to prevent it from becoming ‘‘uncontrolled’’ or if it remains ‘‘uncontrolled’’ despite this therapy. Severe asthma is a heterogeneous condition consisting of phenotypes such as eosinophilic asthma, which is characterized by sputum eosinophilia, associated with mild to moderate increase in blood eosinophil count, frequently adult-onset, and associated with chronic rhinosinusitis with nasal polyps in half of the cases. Eosinophilic asthma is driven by T2 inflammation, characterized, among the others, by interleukin-5 production. IL-5 plays a key role in the differentiation, survival, migration, and activation of eosinophils, and it has become an appealing therapeutic target for eosinophilic asthma. In recent years two monoclonal antibodies (mepolizumab and reslizumab) directed against IL-5 and one monoclonal antibody directed against the alpha-subunit of the IL-5 receptor (benralizumab) have been developed. All these IL-5 target drugs have been shown to reduce the number of exacerbation in patients with severe asthma selected on the basis of peripheral blood eosinophil count. There are still a number of unresolved issues related to the anti-IL5 strategy in eosinophilic asthma, which are here reviewed. These issues include the effects of such therapy on airway obstruction and asthmatic symptoms, the level of baseline eosinophils that predicts a response to treatment, the relationship between blood and airway eosinophilia, and, perhaps most importantly, how to elucidate the pathogenetic role played by eosinophils in the individual patient with severe eosinophilic asthma.
Allergy in severe asthma Del Giacco, S. R.; Bakirtas, A.; Bel, E. ...
Allergy,
February 2017, Letnik:
72, Številka:
2
Journal Article
Recenzirano
Odprti dostop
It is well recognized that atopic sensitization is an important risk factor for asthma, both in adults and in children. However, the role of allergy in severe asthma is still under debate. The term ...‘Severe Asthma’ encompasses a highly heterogeneous group of patients who require treatment on steps 4–5 of GINA guidelines to prevent their asthma from becoming ‘uncontrolled’, or whose disease remains ‘uncontrolled’ despite this therapy. Epidemiological studies on emergency room visits and hospital admissions for asthma suggest the important role of allergy in asthma exacerbations. In addition, allergic asthma in childhood is often associated with severe asthma in adulthood. A strong association exists between asthma exacerbations and respiratory viral infections, and interaction between viruses and allergy further increases the risk of asthma exacerbations. Furthermore, fungal allergy has been shown to play an important role in severe asthma. Other contributing factors include smoking, pollution and work‐related exposures. The ‘Allergy and Asthma Severity’ EAACI Task Force examined the current evidence and produced this position document on the role of allergy in severe asthma.
Summary
Nasal cytology is an easy, cheap, non‐invasive and point‐of‐care method to assess nasal inflammation and disease‐specific cellular features. By means of nasal cytology, it is possible to ...distinguish between different inflammatory patterns that are typically associated with specific diseases (ie, allergic and non‐allergic rhinitis). Its use is particularly relevant when other clinical information, such as signs, symptoms, time‐course and allergic sensitizations, is not enough to recognize which of the different rhinitis phenotypes is involved; for example, it is only by means of nasal cytology that it is possible to distinguish, among the non‐allergic rhinitis, those characterized by eosinophilic (NARES), mast cellular (NARMA), mixed eosinophilic‐mast cellular (NARESMA) or neutrophilic (NARNE) inflammation. Despite its clinical usefulness, cheapness, non‐invasiveness and easiness, nasal cytology is still underused and this is at least partially due to the fact that, as far as now, there is not a consensus or an official recommendation on its methodological issues. We here review the scientific literature about nasal cytology, giving recommendations on how to perform and interpret nasal cytology.
Bronchiectasis is a complex respiratory disease characterised by permanent dilatation of bronchi. Vitamin D plays a role in infective disease by modulating the inflammation. Patients affected by ...bronchiectasis are frequently Vitamin D deficient and it correlates with lung function decline. We want to understand if there is a correlation between Vitamin D and clinical and radiological severity of bronchiectasis.
We included 57 patients (17 males/40 female with mean age 60 ± 12 years) between October 2017 and March 2018. We excluded patients with cystic fibrosis, traction bronchiectasis and reporting Vitamin D supplementation. Bronchiectasis severity index (BSI) and Bhalla score were calculated, blood inflammatory markers and Vit. D were measured and lung function tests were performed.
Vitamin D is deficient in 64% of patients, sufficient in 36% and normal in 7%. Mean BSI is 7.5 ± 5 and mean Bhalla score is 16 ± 4. Vitamin D levels correlate with Bhalla score (R2 = 0.68, p < 0.001) and BSI (R2 = 0.58, p < 0.0001). The correlation appears to be stronger than other markers of inflammation such as ESR and CRP R2 = 0.33, p = 0.001 and R2 = 0.39, p = 0.001 respectively.
We consider Vitamin D as a good predictor of clinical and radiological severity of bronchiectasis.
•Vitamin D deficiency was found in the majority of patients with bronchiectasis despite sufficient sun exposure.•Vitamin D levels correlated with extension and severity of bronchiectasis, and with lung function decline.•These correlations were stronger than those found for other inflammatory markers.•Vitamin D is a good predictor of clinical-radiological severity of bronchiectasis irrespectively of the underlying etiology.
Take home message: Vitamin D deficiency is common in patients affected by bronchiectasis and it correlates to clinical and radiological severity, regardless of latitude.
Pulmonary rehabilitation (PR) may improve respiratory symptoms and skeletal muscle strength in patients with COPD. We aimed to evaluate changes in ultrasound (US) measurements of diaphragmatic ...mobility and thickness after PR in COPD patients and to test its correlation with PR outcomes.
Twenty-five COPD patients were enrolled and underwent a diaphragm US assessment before and after a 12-week PR program.
We found a correlation between the intraindividual percentage of change in the diaphragmatic length of zone of apposition at functional residual capacity (ΔLzapp%) and the change in 6-minute walking distance (6MWD) after PR (rho=0.49,
=0.02). ΔLzapp% was significantly higher in patients with improved 6MWD and COPD Assessment Test (CAT) score (mean rank=12.03±2.57 vs 6.88±4.37;
=0.02). A ΔLzapp% of ≥10% was able to discriminate among patients with improved 6MWD, with a sensitivity of 83% and a specificity of 74%. The area under the receiver operating characteristic curve for ΔLzapp% was 0.83. A cutoff value of ≥9% of ΔLzapp% had a positive predictive value in discriminating a reduction in ≥2 points of CAT score after PR, with a sensitivity and a specificity of 80% and 62%, respectively.
Diaphragm US assessment represents a useful prognostic marker of PR outcomes in COPD patients.
Increasing evidence is available about the presence of increased serum concentration of immunoglobulin (Ig) free light chains (FLCs) in both atopic and non-atopic inflammatory diseases, including ...severe asthma, providing a possible new biomarker of disease.
We analyzed clinical and laboratory data, including FLCs, obtained from a cohort of 79 asthmatic subjects, clinically classified into different GINA steps. A control group of 40 age-matched healthy donors (HD) was considered. Particularly, HD have been selected according to the absence of monoclonal components (in order to exclude paraproteinemias), were tested for total IgE (that were in the normal ranges) and were negative for aeroallergens specific IgE. Moreover, no abnormality of common inflammatory markers (i.e., erythrocyte sedimentation rate and C-reactive protein) was detectable.
FLC-k levels were significantly increased in the asthmatic population, compared to the control group. Despite the absence of statistically significant differences in FLC-λ levels, the FLC-k/FLC-λ ratio displayed remarkable differences between the two groups. A positive correlation between FLC-κ and FLC-λ levels was found. FLC- λ level displayed a significant negative correlation with the FEV1 value. Moreover, the FLC-κ /FLC- λ ratio was negatively correlated with the SNOT-22 score and a positive correlation was observed between FLCs and Staphylococcus Aureus IgE enterotoxins sensitization.
Our findings confirmed the role of FLCs in asthma as a potential biomarker in an inflammatory disease characterized by different endotypes and phenotypes. In particular, FLC-κ and FLC-k/FLC-λ ratio could be a qualitative indicator for asthma, while FLC-λ levels could be a quantitative indicator for clinical severity parameters.
To address uncertainties in the prevention and management of influenza in people with asthma, we performed a scoping review of the published literature on influenza burden; current vaccine ...recommendations; vaccination coverage; immunogenicity, efficacy, effectiveness, and safety of influenza vaccines; and the benefits of antiviral drugs in people with asthma. We found significant variation in the reported rates of influenza detection in individuals with acute asthma exacerbations making it unclear to what degree influenza causes exacerbations of underlying asthma. The strongest evidence of an association was seen in studies of children. Countries in the European Union currently recommend influenza vaccination of adults with asthma; however, coverage varied between regions. Coverage was lower among children with asthma. Limited data suggest that good seroprotection and seroconversion can be achieved in both children and adults with asthma and that vaccination confers a degree of protection against influenza illness and asthma‐related morbidity to children with asthma. There were insufficient data to determine efficacy in adults. Overall, influenza vaccines appeared to be safe for people with asthma. We identify knowledge gaps and make recommendations on future research needs in relation to influenza in patients with asthma.
Dupilumab, an anti-IL-4 receptor a monoclonal antibody, was recently approved for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate-to-severe asthma. Onset of its ...clinical effects is rapid. CRSwNP is characterized by extended type 2 inflammatory involvement that can be assessed using extended nitric oxide analysis. We investigated whether dupilumab was associated with a rapid improvement in extended nitric oxide parameters, lung function, and clinical outcomes in patients with CRSwNP.
Consecutive patients with CRSwNP and an indication for dupilumab were evaluated for extended nitric oxide analysis (exhaled, FeNO; bronchial, JawNO; alveolar, CalvNO; nasal, nNO) and lung function 15 and 30 days after initiation of treatment and for clinical outcomes (nasal polyps score NPS, quality of life questionnaires, visual analog scale VAS for the main symptoms, and the Asthma Control Test ACT) 30 days after initiation of treatment.
We enrolled 33 patients. All extended nitric oxide and lung function parameters improved significantly after 15 days of treatment, remaining stable at 30 days. Scores on the NPS, VAS for the main RSwNP symptoms, quality of life questionnaires, and the ACT improved significantly 30 days after initiation of treatment.
Dupilumab is associated with very rapid improvement in type 2 inflammation in all airway areas. This is associated with improved lung function and clinical parameters in patients with CRSwNP.
The numerous links between allergic rhinitis and asthma have been extensively explored in the last two decades, gaining great concern within the scientific community. These two conditions frequently ...coexist in the same patient and share numerous pathogenetic and pathophysiological mechanisms.
We reviewed major pathophysiological, epidemiological, and clinical links between allergic rhinitis and asthma. We also provided a comprehensive discussion of allergic rhinitis treatment according to current guidelines, with a particular focus on the relevance of allergic rhinitis therapies in patients with comorbid asthma.
We believe that there are several unmet needs for our patients, however, there are promising advances forecasted for the future. Although allergic rhinitis is a recognized risk factor for asthma, a proper asthma detection and prevention plan in allergic rhinitis patients is not available. Allergen immunotherapy (AIT) represents a promising preventive strategy and may deserve an earlier positioning in allergic rhinitis management. A multidisciplinary approach should characterize the journey of patients with respiratory allergies, with an adequate referral to specialized Allergy/Asthma centers. Molecular Allergy Diagnosis may provide support for optimal AIT use. Finally, a possible evolution of biological treatment can be envisaged, mainly if biosimilars decrease such therapies' costs.
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