Treatable Traits in Pregnant Women with Asthma.

BACKGROUND: Asthma is the most common chronic respiratory disease in pregnancy, affecting approximately 8-10% of pregnant women. Uncontrolled asthma is associated with adverse perinatal outcomes, including low birth weight, preterm birth, and maternal complications such as pre-eclampsia. SUMMARY: A current approach to the management of chronic airway diseases is based on targeting treatable traits. The aim of this review was to define treatable traits in pregnant women with asthma based on recent literature and to determine personalized treatment options according to these traits. Traits addressed in this review that may improve asthma control and pregnancy outcomes are fractional exhaled nitric oxide-based asthma monitoring and treatment, medication adherence and inhalation technique, impaired lung function, smoking cessation and comorbidity including psychological conditions (depression and anxiety), obesity, rhinitis, gastroesophageal reflux disease, chronic rhinosinusitis with or without nasal polyps, and sleep apnea. KEY MESSAGES: All the treatable traits discussed have the potential to improve asthma control and pregnancy outcomes in pregnant women with asthma. Further research is needed to determine which management approaches are best to improve asthma control during pregnancy, to identify other relevant treatable traits, and to determine whether the treatable trait approach is feasible and beneficial in pregnant women with asthma.

Summary of the Dutch Multidisciplinary Practice Guideline on Asthma and Pregnancy.

Asthma is the most common chronic respiratory disease in women of childbearing age and during pregnancy. This paper presents a summary of the Dutch multidisciplinary guideline on asthma and pregnancy. The aim of this guideline is to provide structured, where possible, evidence-based recommendations to optimize the management of asthma during pregnancy. The main topics covered in this guideline are preconception counseling, the safety of asthma medications during pregnancy and breastfeeding and risk assessment and monitoring of asthma during pregnancy. Because many caregivers are involved and a uniform approach is desirable, this guideline has been developed in collaboration with all relevant health care providers and patient representatives.

Long-Term Weight Changes After Starting Anti-IL-5/5Ra Biologics in Severe Asthma: The Role of Oral Corticosteroids.

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 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/m2; 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 (ß = -0.24 kg/g; 95% CI, -0.38 to -0.10; P < .001) and, independently, greater reduction in cumulative OCS dose during follow-up (ß = 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.

Real-World Effectiveness of IL-5/5Ra Targeted Biologics in Severe Eosinophilic Asthma With Comorbid Bronchiectasis.

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-5/5Ra 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 tomography-confirmed 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.

Real-World Effectiveness of Reslizumab in Patients With Severe Eosinophilic Asthma - First Initiators and Switchers.

BACKGROUND: Reslizumab, a biologic targeting IL-5, has been shown to reduce asthma exacerbations and maintenance oral corticosteroid use in randomized controlled trials and pre-post studies in patients with severe eosinophilic asthma. However, real-world effectiveness data of reslizumab are scarce, and it is unknown whether reslizumab has added value after switching from another type 2 biologic. OBJECTIVE: To evaluate (1) the real-world effectiveness of reslizumab on severe asthma exacerbations, maintenance oral corticosteroid use, and overall treatment response, both in biologic-naive patients who initiated reslizumab and in those who switched from another type 2 biologic; and (2) physicians' experience with reslizumab treatment. METHODS: This observational real-world study evaluated data from 134 adults with severe eosinophilic asthma included in the Dutch severe asthma registry (RAPSODI), who initiated reslizumab treatment (4-weekly infusions, 0.3 mg/kg) before April 2020 and had follow-up data for 6 months and greater. Clinical asthma experts completed surveys on their experience with reslizumab treatment. RESULTS: Overall, reslizumab reduced the exacerbation rate (odds ratio [95% CI] = 0.10 [0.05-0.21]; P < .001), oral corticosteroid use (OR [95% CI], 0.2 [0.0-0.5]; P < .001), and maintenance dose (median [CI], 5.0 [0.0-10.0] to 0.0 [0.0-5.0]; P < .001), with comparable results in biologic-naive reslizumab initiators and switchers. The overall response to reslizumab was graded good or excellent in 59.2% of patients. The additive effectiveness of reslizumab after switching from another biologic was reflected in physicians' surveys. CONCLUSIONS: Real-world data show that reslizumab reduces severe asthma exacerbations and oral corticosteroid use in patients with severe eosinophilic asthma, both in biologic-naive reslizumab initiators and in those who switched from another type 2 biologic. This additional value of reslizumab was recognized by clinical asthma experts.

Alpine altitude climate treatment for severe and uncontrolled asthma: An EAACI position paper.

Currently available European Alpine Altitude Climate Treatment (AACT) programs combine the physical characteristics of altitude with the avoidance of environmental triggers in the alpine climate and a personalized multidisciplinary pulmonary rehabilitation approach. The reduced barometric pressure, oxygen pressure, and air density, the relatively low temperature and humidity, and the increased UV radiation at moderate altitude induce several physiological and immunological adaptation responses. The environmental characteristics of the alpine climate include reduced aeroallergens such as house dust mites (HDM), pollen, fungi, and less air pollution. These combined factors seem to have immunomodulatory effects controlling pathogenic inflammatory responses and favoring less neuro-immune stress in patients with different asthma phenotypes. The extensive multidisciplinary treatment program may further contribute to the observed clinical improvement by AACT in asthma control and quality of life, fewer exacerbations and hospitalizations, reduced need for oral corticosteroids (OCS), improved lung function, decreased airway hyperresponsiveness (AHR), improved exercise tolerance, and improved sinonasal outcomes. Based on observational studies and expert opinion, AACT represents a valuable therapy for those patients irrespective of their asthma phenotype, who cannot achieve optimal control of their complex condition despite all the advances in medical science and treatment according to guidelines, and therefore run the risk of falling into a downward spiral of loss of physical and mental health. In the light of the observed rapid decrease in inflammation and immunomodulatory effects, AACT can be considered as a natural treatment that targets biological pathways.

Management of allergic diseases in pregnancy.

Allergic diseases like asthma, allergic rhinitis, food allergy, hymenoptera allergy, or atopic dermatitis are highly prevalent in women of childbearing age and may affect up to 30% of this age group. This review focuses on the management of allergic diseases during pregnancy. Furthermore, we discuss the challenges of counseling women with allergic diseases in the reproductive age, including considerations relevant to the ongoing SARS-CoV-2 pandemic. To create the optimal milieu for the unborn child, a multitude of immunological changes occur during pregnancy which may favor type 2 responses and aggravate disease phenotypes. In co-occurrence with suboptimal preconception disease control, this elevated Th2 responses may aggravate allergic disease manifestations during pregnancy and pose a risk for mother and child. Due to limitations in conducting clinical trials in pregnant women, safety data on anti-allergic drugs during pregnancy are limited. The lack of information and concerns among pregnant patients demands counseling on the benefits of anti-allergic drugs and the potential and known risks. This includes information on the risk for mother and child of disease aggravation in the absence of treatment. By doing so, informed decisions and shared decision-making can take place.

Biologicals in atopic disease in pregnancy: An EAACI position paper.

Biologicals have transformed the management of severe disease phenotypes in asthma, atopic dermatitis, and chronic spontaneous urticaria. As a result, the number of approved biologicals for the treatment of atopic diseases is continuously increasing. Although atopic diseases are among the most common diseases in the reproductive age, investigations, and information on half-life, pharmacokinetics defining the neonatal Fc receptors (FcRn) and most important safety of biologicals in pregnancy are lacking. Given the complex sequence of immunological events that regulate conception, fetal development, and the intrauterine and postnatal maturation of the immune system, this information is of utmost importance. We conducted a systematic review on biologicals in pregnancy for indications of atopic diseases. Evidence in this field is scarce and mainly reserved to reports on the usage of omalizumab. This lack of evidence demands the establishment of a multidisciplinary approach for the management of pregnant women who receive biologicals and multicenter registries for long-term follow-up, drug trial designs suitable for women in the reproductive age, and better experimental models that represent the human situation. Due to the very long half-life of biologicals, preconception counseling and healthcare provider education are crucial to offer the best care for mother and fetus. This position paper integrates available data on safety of biologicals during pregnancy in atopic diseases via a systematic review with a detailed review on immunological considerations how inhibition of different pathways may impact pregnancy.

Bronchiectasis in Severe Asthma: Does It Make a Difference?

BACKGROUND: Asthma and bronchiectasis are 2 heterogeneous diseases that frequently coexist, particularly in severe asthma. Recognition of this co-diagnosis may importantly affect treatment decisions and outcome. Previous studies in asthma with bronchiectasis show inconsistent outcomes, probably due to the heterogeneity of the included asthma cohorts. OBJECTIVES: We hypothesized that bronchiectasis contributes to asthma severity and that patients with severe asthma and bronchiectasis present with distinct characteristics resulting in different treatable traits. In addition, we explored whether bronchiectasis in severe asthma is more common in a specific phenotype. METHODS: This is a single-center study consecutively including patients with severe asthma from a tertiary referral center. Severe asthma was diagnosed according to the ATS/ERS guidelines. Asthma and infectious exacerbations were defined by the attending specialist as respiratory symptoms requiring treatment with systemic steroids or antibiotics, respectively. Two independent blinded radiologists evaluated each CT. RESULTS: 19% of patients with severe asthma showed bronchiectasis on CT. Patients with bronchiectasis had a lower FEV1% predicted (p = 0.02) and FEV1/FVC (p = 0.004) and more infectious exacerbations (p = 0.003) compared to patients without bronchiectasis. Bronchiectasis is more common in patients with a longer duration of asthma, sensitization to A. fumigatus or a positive sputum culture. Sputum cultures of patients with severe asthma and bronchiectasis revealed more P. aeruginosa, S. maltophilia, H. parainfluenzae, and A. fumigates compared to the non-bronchiectasis group. The adult-onset, eosinophilic asthma phenotype showed the highest prevalence of bronchiectasis (29.4%). CONCLUSIONS: Patients with severe asthma and coexisting bronchiectasis were found to represent a distinct group, in terms of disease severity, microbiology, and asthma phenotype. Performing (HR)CT and sputum cultures can help to identify these patients. These results can possibly contribute to early recognition and targeted treatment of this patient group.