IntroductionAsthma disease is linked to a dysbiosis. Synbiotics are a combination of probiotics and prebiotics, which are well tolerated and safe. They have been shown to have positive effects on asthma condition in in vivo models and in some studies on asthmatic patients. However, the literature focusing on their effects on asthma condition is limited and human studies are still insufficient.MethodsWe performed a double-blind randomized placebo-controlled trial to assess the impact of a synbiotic (namely Bactecal®) on asthma control, quality of life, lung function, blood and airway inflammation on uncontrolled asthmatic patients 1–3–6 months after the synbiotic intake.ResultsCompared to placebo, the synbiotic positively impacted the lung function and reduced eosinophilic airway inflammation and sputum IL-4 level.ConclusionThe synbiotic Bactecal® had a positive impact on patients with uncontrolled asthma. It improved the lung function while decreasing airway type-2 inflammation.

Asthma is associated with accelerated rate of FEV1 decline. To determine predictive factors associated with accelerated FEV1 decline in adult asthma and evaluate sputum cytokines as potential biomarkers for airflow decline. We recruited 125 asthmatics evaluated at the asthma clinic of Liège and reevaluated them at least 5 years later. Clinical, functional and inflammatory characteristics were compared between patients with accelerated decline (FEV1 decline > 0.85

Severe asthmatics often display fixed airway obstruction thought to be a consequence of accelerated lung function decline. Biologic therapies are efficacious therapies for severe type 2-high asthma. These therapies significantly decrease exacerbation rates, improve the quality of life, improve asthma control and decrease the need of oral glucocorticosteroid for severe type 2-high asthma but their effect on lung function decline is still unknown. The aim of this study was to determine if biologic therapies could prevent lung function decline in severe type 2 high asthmatics. We conducted a real life observational study on 127 severe type-2-high asthmatics patients, recruited from the University Asthma Clinic of Liege, who have been treated with biologic therapies for at least 3 years. We have compared the FEV1 post-bronchodilation before the initiation of a therapy with omalizumab (n=79) or mepolizumab (n=48) and after 3 years of treatment. In the omalizumab cohort, the mean FEV1 post-bronchodilatation was 2 268 ml before starting the biologic and 2363 ml (p = 0.48) after 3 years of treatment, which corresponds to a change from 77% and 80% predicted respectively (p = 0.74). In the mepolizumab cohort, the FEV1 post-bronchodilatation was 2100 ml before starting the biologic and 2259ml (p = 0.36) after 3 years of treatment, which corresponds to a change from 76% and 79% predicted respectively (p = 0.45). Our result support that treatment with omalizumab and mepolizumab could prevent lung function decline in severe type 2-high asthmatics.

Introduction: Mucociliary clearance(MCC) results from an effective interaction between the mucus layer and the normal coordinated ciliary beating. Ciliary dyskinesia is defined as an abnormal ciliary beat frequency(CBF) and/or ciliary beat pattern(CBP). Recent data demonstrated a ciliary dyskinesia in moderate and severe asthma, but it is unknown if this is primary, or secondary to chronic inflammation. Aims: To determine if ciliary dyskinesia is primary or secondary in severe asthma. Methods: Ciliated epithelial samples were obtained by nasal brushing from 10 adults with severe asthma. Beating cilia were recorded using digital high-speed videomicroscopy at 37°C. Ciliary functional analysis(CFA) was assessed by CBF and by the percentage of dyskinetic CBP(%DK). CFA was re-assessed after air-liquid interface(ALI) cell culture in a subset of 4 patients. Normal values for CFA were obtained from 14 healthy adults. Results: Our results confirms that ciliary dyskinesia is increased in adults with severe asthma compared with healthy subjects, with a lower CBF(11.52±0.67Hz vs 14.79±0.58Hz, p=0.001), and a higher %DK(29.3±4.23% vs 17.28±2.04%, p=0.010). However, when comparing CFA before and after ALI cell culture, there is no significant difference in CBF(11.44±2.91Hz vs 12.88±1.75Hz, p=0.269), or in the %DK(32.7±15.79% vs 24.43±13.24%, p=0.378). Conclusions: This pilot study confirms that ciliary function is impaired in patients with severe asthma, and may play a role in impaired MCC. Furthermore, our results suggest that ciliary dyskinesia may be primary and not secondary to chronic inflammation in severe asthma, as ciliary function does not improve after ALI cell culture; this must be confirmed in higher numbers of patients.

Asthma is a chronic inflammatory disease of the airways. Classification of asthma in different phenotypes has therapeutic implications and may lead to personalized medicine. Induced sputum is the gold standard for asthma phenotyping but is complex, time-consuming and not widely available. The combination of different biomarkers such as exhaled nitric oxide, blood eosinophils and total serum IgE levels allows the prediction of inflammatory phenotype in 58% of asthmatic patients when sputum is not available. We recently demonstrated the interest of measuring volatile organic compounds in exhaled breath to phenotype asthma. These compounds could play an important role in the future to predict the response to expensive biologicals available in severe asthma to reduce exacerbations and the use of systemic corticosteroids.

Background Elderly asthmatics represent an important group that is often excluded from clinical studies. In this study we wanted to present characteristics of asthmatics older than 70 years old as compared to younger patients. Methods We conducted a retrospective analysis on a series of 758 asthmatics subdivided in three groups: lower than 40, between 40 and 70 and older than 70. All the patients who had a successful sputum induction were included in the study. Results Older patients had a higher Body Mass Index, had less active smokers and were more often treated with Long Acting anti-Muscarinic Agents. We found a significant increase in sputum neutrophil counts with ageing. There was no significant difference in blood inflammatory cell counts whatever the age group. Forced expiratory volume in one second (FEV 1 ) and FEV 1 /FVC values were significantly lower in elderly who had lower bronchial hyperresponsiveness and signs of air trapping. We found a lower occurrence of the allergic component in advanced ages. Asthmatics older than 70 years old had later onset of the disease and a significant longer disease duration. Conclusion Our study highlights that asthmatics older than 70 years old have higher bronchial neutrophilic inflammation, a poorer lung function, signs of air trapping and lower airway variability. The role of immunosenescence inducing chronic low-grade inflammation in this asthma subtype remains to be elucidated.

Background. - Eosinophilic inflammation has long been associated with asthma. Looking at systemic and airway eosinophilia, we have recently identified a group of patients exhibiting diffuse eosinophilic inflammation. Among the mechanisms governing eosinophilic inflammation, IgE-mediated mast cell activation is a key event leading to eosinophilia in atopic asthmatics. Methods. - We conducted a retrospective study on our asthma clinic database containing more than 1500 patients and identified 205 asthmatics with successful sputum induction and concordant eosinophilic phenotype. This phenotype was defined as a sputum eosinophil count >= 3% and a blood eosinophils concentration >= 400 cells/mm(3). IgE-high atopic phenotype was characterized by the presence of at least one positive specific IgE (> 0.35 kU/L) to common aeroallergens and a raised total serum IgE (>= 113 kU/L). Results. - The largest group of asthmatics displaying concordant eosinophilic phenotype had a raised total serum IgE and atopy (45%). IgE-low non-atopic concordant eosinophilic asthma was a predominantly late onset disease, exhibited a more intense airway eosinophilic inflammation (P < 0.05), required more often maintenance treatment with oral corticosteroids (P < 0.05) but, surprisingly, had a reduced level of bronchial hyperresponsiveness to methacholine (P < 0.05) despite similar baseline airway calibre impairment. Conclusion. - The more severe airway eosinophilic inflammation in IgE-low non-atopic asthmatics despite similar treatment with ICS and a higher burden of OCS points to a certain corticosteroid resistance in this asthma phenotype.

Asthma is a chronic heterogeneous airway disease. There are different asthma inflammatory phenotypes with various responses to treatment and different disease severities. When asthma requires chronic systemic corticosteroids or hospitalizations despite maximal inhaled therapies in asthmatic patients in whom comorbidities have been managed and who are considered as compliant, the pulmonologist may propose biological treatment to reduce exacerbations and the dose of systemic corticosteroids. During the last ten years, the number of biologics for the management of type-2 severe asthma has increased. Anti-IgE monoclonal antibodies (omalizumab) are available for more than ten years and recommended in severe allergic asthma. New biologics are now available to block IL-5 (mepolizumab, reslizumab) or its receptor (benralizumab). These treatments allow a reduction of exacerbations and of the dose of systemic corticosteroids, an improvement in asthma control, in asthma quality of life and for some of them, an increase in lung function. New biologics will soon be available in Belgium for the management of severe asthma. In addition to the improvement of asthma control in severe asthma, biological treatments have improved the understanding of the mechanisms leading to severe asthma.

BACKGROUND:Omalizumab arose as a therapeutic option in patients suffering from moderate to severe refractory allergic asthma. It acts as a humanized monoclonal antibody neutralizing circulating IgE antibodies. Randomized clinical trials and real life clinical studies have already confirmed benefits, cost-effectiveness and applicability of the medication. METHOD:Our study retrospectively reports on the clinical outcomes and airway inflammation in 157 severe allergic asthmatics who were initiated with omalizumab between 2007 and 2019. RESULTS:After 4 months of therapy, 76% of the patients were judged to have benefited from omalizumab and were admitted to prolonged treatment. During follow-up, we observed an improvement in asthma control, quality of life and spirometric performance. There was also a sustained reduction in exacerbation rate over the years. As for T2 biomarkers, FeNO significantly decreased and, in a subgroup of patients who had repeated sputum inductions, there was also significant reduction in sputum eosinophils but no change in blood eosinophil count. Lastly, we found a correlation between high FeNO levels at baseline and reduction in ACQ scores at 1 year. CONCLUSION:We conclude that omalizumab shows effectiveness in severe allergic asthma in a real life setting, by reducing exacerbation rate, improving patient perspective outcomes and airway calibre, together with reducing type-2 airway inflammation.

We conducted a prospective observational study to evaluate the efficacy of yoga in poorly controlled severe asthmatic patients treated with maximal inhaled therapy and biologics. The objective of yoga was to improve breathing consciousness, exercising controlled ventilation with and without retention, abdominal breathing observation, improvement of inspiratory and expiratory muscles, opening of the chest, diaphragm exercises and relaxation. We measured exhaled nitric oxide, forced expiratory volume in one second, forced vital capacity, asthma control and quality of life questionnaires, anxiety and depression questionnaires before and after the tenth yoga course (performed twice a week). Half of the patients who were invited to participate to the study declined due to organization problems. Two patients were excluded due to bronchitis and arthralgia respectively. The analysis of the data from 12 participants revealed significant improvement in asthma control and asthma quality of life questionnaires and a reduction of anxiety.The regular practice of yoga in severe asthmatics insufficiently controlled despite maximal inhaled treatment and biotherapy seems to be an interesting complementary option to improve asthma control. Our results must be confirmed in larger randomized controlled trials.

Demonstration of bronchial hyperresponsiveness is a key feature in asthma diagnosis. Methacholine challenge has proved to be a highly sensitive test to diagnose asthma in patients with chronic respiratory symptoms and preserved baseline lung function (FEV1 > 70% pred.) but is time consuming and may sometimes reveal unpleasant to the patient. We conducted a retrospective study on 270 patients recruited from the University Asthma Clinic of Liege. We have compared the values of several lung function indices and fractional exhaled nitric oxide (FeNO) in predicting a provocative methacholine concentration <= 16 mg/ml on a discovery cohort of 129 patients (57 already on ICS) and on a validation cohort of 141 patients (66 already on ICS). In the discovery study (n = 129), 85 patients (66%) had a positive methacholine challenge with PC20M <= 16 mg/ml. Those patients had lower baseline % predicted FEV1 (92% vs. 100%; p < 0.01), lower FEV1/FVC ratio (79% vs. 82%; p < 0.05), higher RV/TLC ratio (114% vs. 100%; p < 0,0001), lower SGaw (specific conductance) (0.76 vs. 0.95; p < 0,001) and higher FeNO (29 ppb vs. 19 ppb; p < 0,01). When performing ROC curve the RV/TLC ratio provided the greatest AUC (0.74, p < 0.001), sGAW had intermediate AUC of 0.69 (p < 0.001) while FeNO, FEV1 and FEV1/FVC ratio were modestly predictive (AUC of 0.65 (p < 0.05), 0,67 (p < 0.001) and 0,63 (p < 0.001). These results were confirmed in the validation study (n = 141). Based on a logistic regression analysis, significant variables associated with positive methacholine challenge were FeNO and RV/TLC (% Pred). A combined application of FeNO and RV/TLC (% Pred) for predicting the PC20M had a specificity of 85%, a sensitivity of 59% and an AUC of 0.79. In the validation study, three variables (RV/TLC, FeNO and FEV1) were independently associated with positive methacholine challenge and the combination of these three variables yielded a specificity of 77%, a sensitivity of 39% and an AUC of 0.77. The RV/TLC ratio combined to FeNO may be of interest to predict significant methacholine bronchial hyperresponsiveness.

Asthma is defined as a reversible airway obstruction. Airway remodeling, however, may lead to lung function decline and persistent airflow obstruction. A retrospective study was conducted in 1175 asthmatics recruited from the University Asthma Clinic of Liege. Patients with post-BD FEV1/FVC ≥70 were compared to patients with FEV1/FVC<70. Risk factors for FEV1/FVC<70 were evaluated with a multivariable logistic regression. Twenty five percent of asthmatics had an irreversible airway obstruction (FEV1/FVC<70)(n=283) in our database. These patients were statistically significantly more smokers (p<0.0001), with a later onset (p=0.045) and a longer duration (p<0.0001) of asthma, poorer asthma control (p<0.0001) and quality of life (p<0.0001), treated with higher ICS dose (p<0.0001), and had more often diffuse eosinophilic inflammation (p<0.0001) with more exacerbations (p=0.0025). The univariate model of the logistic regression showed a positive association between FEV1/FVC<70 and age (p<0.0001), male gender (p=0.0009), tobacco history (p<0.0001), PAQ-Y (p<0.0001), ACQ score (p<0.0001), ICS dose (p<0.0001), leucocytes (p<0.0001), blood neutrophils (/mm3)(p=0.0018), exacerbations(p=0.005), disease duration(p<0.0001), and diffuse eosinophilic inflammation (BEC>400&SI Eos>3%)(p<0.0001). The multivariate analysis revealed age, male gender and ACQ score as predictors of a fixed airway obstruction. These data show that poorer asthma control is associated with irreversible airway obstruction. Patients with late-onset hypereosinophilic asthma are more at risk to develop fixed airway obstruction and should be assessed more frequently in order to prevent such prognosis.

Introduction: Asthma in obese subjects is poorly understood. According to GINA guidelines, pulmonologists increase ICS in case of poor asthma control but lung volume restriction may also worsen respiratory symptoms in obese asthmatics leading to overtreatment in this subpopulation. Methods: We conducted a retrospective study on 1217 asthmatics recruited from University Hospital of Liege. 92 patients with a BMI >= 30 came at least two times at the asthma clinic (mean interval: 335 days). In this obese population, we identified predictors of good (decrease in ACQ >= 0.5) versus poor response (rise in ACQ >= 0.5) to ICS step-up therapy. Results: Obese asthmatics had a poorer asthma control and quality of life as compared to non-obese and exhibited reduced FVC, higher levels of blood leucocytes and markers of systemic inflammation. The proportion of asthma inflammatory phenotypes was similar to that observed in a general population of asthmatics. Among uncontrolled obese asthmatics receiving ICS step-up therapy, 53% improved their asthma control while 31% had a worsening of their asthma. Uncontrolled obese asthmatics showing a good response to increase in ICS had higher ACQ, lower CRP levels, higher sputum eosinophil counts and higher FeNO levels at visit 1. Uncontrolled obese asthmatics that worsened after increasing the dose of ICS had lower FVC, lower sputum eosinophil counts and higher sputum neutrophil counts. Conclusion: We observed poorer asthma control in obese asthmatics despite similar bronchial inflammation. Managing obese asthmatics according to ACQ alone seems to underestimate asthma control and the contribution of restriction to dyspnea. Increasing the dose of ICS in the absence of sputum eosinophilic inflammation or in the presence of restriction or bronchial neutrophilia led to poorer asthma control. In those patients, management of obesity should be the first choice.