BACKGROUND: Bronchiectasis is a common comorbidity in patients with asthma and is associated with increased disease severity. In patients with severe eosinophilic asthma, biologics targeting IL-5... Show moreBACKGROUND: Bronchiectasis is a common comorbidity in patients with asthma and is associated with increased disease severity. In patients with severe eosinophilic asthma, biologics targeting IL-5/5Ra have beneficial effects on oral corticosteroid (OCS) use and exacerbation frequency. However, how coexisting bronchiectasis affects the response to such treatments is unknown.OBJECTIVE: To evaluate the real-world effectiveness of anti-IL-5/5Ra therapy in patients with severe eosinophilic asthma and comorbid bronchiectasis on exacerbation frequency and daily maintenance and cumulative OCS dose.METHODS: This real-world study evaluated data from 97 adults with severe eosinophilic asthma and computed tomographyeconfirmed bronchiectasis from the Dutch Severe Asthma Registry, who initiated anti-IL5/5Ra biologics (mepolizumab, reslizumab, and benralizumab) and had follow-up data for 12 months or greater. The analysis was performed for the total population and subgroups with or without maintenance OCS use.RESULTS: Anti-IL-5/5Ra therapy significantly reduced exacerbation frequency in patients with maintenance OCS use as well as in those without it. In the year before biologic initiation, 74.5% of all patients had two or more exacerbations, which decreased to 22.1% in the follow-up year (P < .001). The proportion of patients on maintenance OCS decreased from 47% to 30% (P < .001), and in the OCS-dependent patients (n [ 45) maintenance OCS dose decreased from median (interquartile range) of 10.0 mg/d (5-15 mg/d) to 2.5 mg/d (0-5 mg/d) after 1 year (P < .001).CONCLUSIONS: This real-world study shows that anti-IL-5/ 5Ra therapy reduces exacerbation frequency and daily maintenance as well as the cumulative OCS dose in patients with severe eosinophilic asthma and comorbid bronchiectasis. Although it is an exclusion criterion in phase 3 trials, comorbid bronchiectasis should not preclude anti-IL-5/5Ra therapy in patients with severe eosinophilic asthma. (c) 2023 American Academy of Allergy, Asthma & Immunology (J Allergy Clin Immunol Pract 2023;11:2724-31) Show less
Have, L. ten; Visser, E.; Meulmeester, F.L.; Bendien, S.A.; Braunstahl, G.J.; Broeders, M.E.A.C.; ... ; Brinke, A. ten 2023
Background: Many patients with severe asthma are overweight or obese, often attributed to unintentional weight gain as a side effect of oral corticosteroids (OCSs). Anti-IL-5/5Ra biologics... Show moreBackground: Many patients with severe asthma are overweight or obese, often attributed to unintentional weight gain as a side effect of oral corticosteroids (OCSs). Anti-IL-5/5Ra biologics significantly reduce OCS use, but their long-term effects on weight are unknown.Objectives: To examine (1) weight change up to 2 years after anti-IL-5/5Ra initiation in subgroups on the basis of maintenance OCS use at start of treatment and (2) whether cumulative OCS exposure before or changes in OCS exposure during treatment are related to weight change.Methods: Real-world data on weight and cumulative OCS dose from adults included in the Dutch Registry of Adult Patients with Severe asthma for Optimal DIsease management before and at least 2 years after starting anti-IL-5/5Ra were analyzed using linear mixed models and linear regression analyses.Results: For the included 389 patients (55% female; mean body mass index, 28 +/- 5 kg/m(2); 58% maintenance OCS), mean weight decreased -0.27 kg/y (95% CI, -0.51 to -0.03; P = .03), with more weight loss in patients with maintenance OCS use than in those without maintenance OCS use (-0.87 kg/y [95% CI, -1.21 to -0.52; P < .001] vs +0.54 kg/y [0.26 to 0.82; P < .001]). Greater weight loss at 2 years was associated with higher cumulative OCS dose in the 2 years before anti-IL-5/5Ra initiation (beta = -0.24 kg/g; 95% CI, -0.38 to -0.10; P < .001) and, independently, greater reduction in cumulative OCS dose during follow-up (beta = 0.27 kg/g; 95% CI, 0.11 to 0.43; P < .001).Conclusions: Anti-IL-5/5Ra therapy is associated with long-term weight reduction, especially in patients with higher OCS exposure before treatment and those able to reduce OCS use during treatment. However, the effect is small and does not apply to all patients, and so additional interventions seem necessary if weight change is desired. Show less
Background Bronchial Thermoplasty (BT) is an endoscopic treatment for severe asthma using radiofrequency energy to target airway remodeling including smooth muscle. The correlation of pulmonary... Show moreBackground Bronchial Thermoplasty (BT) is an endoscopic treatment for severe asthma using radiofrequency energy to target airway remodeling including smooth muscle. The correlation of pulmonary function tests and BT response are largely unknown. Forced Oscillation Technique (FOT) is an effort-independent technique to assess respiratory resistance (Rrs) by using pressure oscillations including small airways. Aim To investigate the effect of BT on pulmonary function, assessed by spirometry, bodyplethysmography and FOT and explore associations between pulmonary function parameters and BT treatment response. Methods Severe asthma patients recruited to the TASMA trial were analyzed in this observational cohort study. Spirometry, bodyplethysmography and FOT measurements were performed before and 6 months after BT. Asthma questionnaires (AQLQ/ACQ-6) were used to assess treatment response. Results Twenty-four patients were analyzed. AQLQ and ACQ improved significantly 6 months after BT (AQLQ 4.15 (+/- 0.96) to 4.90 (+/- 1.14) and ACQ 2.64 (+/- 0.60) to 2.11 (+/- 1.04), p = 0.004 and p = 0.02 respectively). Pulmonary function parameters remained stable. Improvement in FEV1 correlated with AQLQ change (r = 0.45 p = 0.03). Lower respiratory resistance (Rrs) at baseline (both 5 Hz and 19 Hz) significantly correlated to AQLQ improvement (r = - 0.52 and r = - 0.53 respectively, p = 0.01 (both)). Borderline significant correlations with ACQ improvement were found (r = 0.30 p = 0.16 for 5 Hz and r = 0.41 p = 0.05 for 19 Hz). Conclusion Pulmonary function remained stable after BT. Improvement in FEV1 correlated with asthma questionnaires improvement including AQLQ. Lower FOT-measured respiratory resistance at baseline was associated with favorable BT response, which might reflect targeting of larger airways with BT. Show less
Around 5-10% of patients with asthma do not respond adequately to inhaled steroids and long-acting bronchodilators and become difficult-to-treat; they remain symptomatic, have recurrent... Show moreAround 5-10% of patients with asthma do not respond adequately to inhaled steroids and long-acting bronchodilators and become difficult-to-treat; they remain symptomatic, have recurrent exacerbations or persistent airflow limitation. This thesis focuses on the mechanisms that may explain why these patients become difficult-to-treat and investigate biomarkers that can predict the development of specific asthma phenotypes. The different studies describe the possible role of alpha- antitrypsin in the development of persistent airflow limitation, the relationship between severity of asthma and the degree of peripheral airway inflammation and dysfunction, the clinical and inflammatory characteristics of obese patients with difficult-to-treat asthma, risk factors of lung function decline and the consistency of the eosinophilic phenotype Show less
