Comparison of exacerbation phenotypes among patients with severe asthma

2020 ◽  
Vol 41 (4) ◽  
pp. e67-e79
Author(s):  
Karina Ruth Soenjoyo ◽  
Nivedita Nadkarni ◽  
Mariko Siyue Koh

Background: Exacerbation phenotypes among patients with severe asthma have been largely characterized during stable periods. Little is known about severe asthma patients during exacerbation periods. Objective: To compare persistently frequent exacerbators (PFE), non‐persistently frequent exacerbators (NPFE), and infrequent exacerbators (IFE) among patients with severe asthma during stable and exacerbation periods. Methods: Patients with severe asthma who were admitted for asthma exacerbations from 2011 to 2017 and on follow up at Singapore General Hospital were recruited and categorized as PFEs (two or more exacerbations per year over 2 consecutive years), NPFEs (two or more exacerbations in 1 year only), or IFEs (fewer than two exacerbations per year over 2 consecutive years). Demographic, clinical, and laboratory data were collected at baseline and during exacerbation periods. Results: The participants were categorized as the following: 20 PFEs, 36 NPFEs, and 57 IFEs, with no significant demographic differences. The participants as PFEs (versus NPFEs and IFEs) were characterized by having a higher prevalence of psychiatric disorders (25% versus 8% versus 5%; p = 0.046), more comorbidities (7 versus 4 versus 2; p < 0.001), and a higher steroid burden per year (1150 versus 456 versus 350 mg; p < 0.001). The participants who were PFEs (versus IFEs) had a higher total immunoglobulin E (IgE) level (625 versus 232 IU/mL; p = 0.046) and longer duration of admission stay (3 versus 2 days; p = 0.009). All three groups had higher blood neutrophil counts during exacerbation periods than during stable periods (p = 0.008 versus p < 0.001 versus p = 0.004). Conclusion: The participants categorized as PFEs were characterized by comorbidities, higher steroid burden, IgE levels, and longer hospital stays. Exacerbations in the participants with severe asthma, regardless of exacerbation phenotype, were characterized by neutrophilia. These findings provided insights into potential therapeutic strategies to reduce exacerbations in patients with severe asthma.

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mohsen Sadatsafavi ◽  
Amir Khakban ◽  
Hamid Tavakoli ◽  
Solmaz Ehteshami-Afshar ◽  
Larry D. Lynd ◽  
...  

Abstract Background Oral corticosteroids are important components of pharmacotherapy in severe asthma. Our objective was to describe the extent, trends, and factors associated with exposure to oral corticosteroids (OCS) in a severe asthma cohort. Methods We used administrative health databases of British Columbia, Canada (2000–2014) and validated algorithms to retrospectively create a cohort of severe asthma patients. Exposure to OCS within each year of follow-up was measured in two ways: maintenance use as receiving on average ≥ 2.5 mg/day (prednisone-equivalent) OCS, and episodic use as the number of distinct episodes of OCS exposure for up to 14 days. Trends and factors associated with exposure on three time axes (calendar year, age, and time since diagnosis) were evaluated using Poisson regression. Results 21,144 patients (55.4% female; mean entry age 28.7) contributed 40,803 follow-up years, in 8.2% of which OCS was used as maintenance therapy. Maintenance OCS use declined by 3.8%/calendar year (p < 0.001). The average number of episodes of OCS use was 0.89/year, which increased by 1.1%/calendar year (p < 0.001). Trends remained significant for both exposure types in adjusted analyses. Both maintenance and episodic use increased by age and time since diagnosis. Conclusions This population-based study documented a secular downward trend in maintenance OCS use in a period before widespread use of biologics. This might have been responsible for a higher rate of exacerbations that required episodic OCS therapy. Such trends in OCS use might be due to changes in the epidemiology of severe asthma, or changes in patient and provider preferences over time.


2018 ◽  
Vol 39 (01) ◽  
pp. 091-099 ◽  
Author(s):  
Kian Fan Chung

AbstractSevere therapy-resistant asthma has been defined as “asthma which requires treatment with high dose inhaled corticosteroids (ICSs) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming ‘uncontrolled’ or which remains ‘uncontrolled’ despite this therapy”. Patients who usually present with ‘difficult-to-treat asthma’ should first be assessed to determine whether he/she has asthma with the exclusion of other diagnoses and if so, whether the asthma can be classified as severe therapy-resistant. This necessitates an assessment of adherence to medications, confounding factors, and comorbidities. Increasingly, management of severe therapy-resistant asthma will be helped by the determination of phenotypes to optimize responses to existing and new therapies. Severe asthma patients are usually on a combination of high dose ICS and long-acting β-agonist (LABA) and, in addition, are often on a maintenance dose of oral corticosteroids. Phenotyping can be informed by measuring blood eosinophil counts and the level of nitric oxide in exhaled breath, and the use of sputum granulocytic counts. Severe allergic asthma and severe eosinophilic asthma are two defined phenotypes for which there are efficacious targeted biologic therapies currently available, namely anti-immunoglobulin E (IgE) and anti-interleukin (IL)-5 antibodies, respectively. Further progress will be realized with the definition of noneosinophilic or non-T2 phenotypes. It will be important for patients with severe asthma to be ultimately investigated and managed in specialized severe asthma centers.


2020 ◽  
Vol 36 (6) ◽  
pp. 265-269 ◽  
Author(s):  
Justin P. Reinert ◽  
Kevin Burnham

Objective: To review and consider the immunomodulatory ramifications of glycopeptide and lipopeptide antibiotics in a patient with severe asthma, hyper-immunoglobulin E (IgE) syndrome, and osteonecrosis of the jaw. Case Summary: A 36-year-old male patient with a pertinent past medical history of hyper-IgE syndrome, severe asthma, and osteonecrosis of the jaw attributed to steroid use initially presented to the emergency department, where imaging of the jaw suggested an infectious process. Following months of vancomycin therapy as an outpatient, the patient was switched to daptomycin to facilitate once-daily infusions. Following this change, the patient experienced significantly less asthma exacerbations and fewer admissions to the hospital for asthma-related issues. Discussion: Though daptomycin is associated with eosinophilia, and this patient’s eosinophil counts did increase while on the drug, an inverse relationship developed concerning the number of hospital admissions for asthma exacerbations. A review of the literature indicates that select glycopeptides, such as vancomycin, have pro-inflammatory effects, while other related drugs, such as the lipopeptide daptomycin, may not result in clinical manifestations of an inflammatory process. Tumor necrosis factor-α, interleukin-1β, and interleukin-6 have been implicated in this process. This patient may have been particularly susceptible to the effects of the glycopeptides due to his diagnosis of hyper-IgE syndrome, which has been independently associated with reactive airway diseases. Conclusion: Cytokine migration and activation by select glycopeptide and lipopeptide antibiotics warrant consideration from clinicians when determining the most appropriate treatment regimens. Further research is required to elucidate whether the pro-inflammatory properties of vancomycin warrant a change in first-line therapy to daptomycin in select cases.


2020 ◽  
Vol 10 (3) ◽  
pp. 123
Author(s):  
Javier Perez-Garcia ◽  
José M. Hernández-Pérez ◽  
Ruperto González-Pérez ◽  
Olaia Sardón ◽  
Elena Martin-Gonzalez ◽  
...  

Asthma exacerbations are a major contributor to the global disease burden, but no significant predictive biomarkers are known. The Genomics and Metagenomics of Asthma Severity (GEMAS) study aims to assess the role of genomics and the microbiome in severe asthma exacerbations. Here, we present the design of GEMAS and the characteristics of patients recruited from March 2018 to March 2020. Different biological samples and demographic and clinical variables were collected from asthma patients recruited by allergy and pulmonary medicine units in several hospitals from Spain. Cases and controls were defined by the presence/absence of severe asthma exacerbations in the past year (oral corticosteroid use, emergency room visits, and/or asthma-related hospitalizations). A total of 137 cases and 120 controls were recruited. After stratifying by recruitment location (i.e., Canary Islands and Basque Country), cases and controls did not differ for most demographic and clinical variables (p > 0.05). However, cases showed a higher proportion of characteristics inherent to asthma exacerbations (impaired lung function, severe disease, uncontrolled asthma, gastroesophageal reflux, and use of asthma medications) compared to controls (p < 0.05). Similar results were found after stratification by recruitment unit. Thereby, asthma patients enrolled in GEMAS are balanced for potential confounders and have clinical characteristics that support the phenotype definition. GEMAS will improve the knowledge of potential biomarkers of asthma exacerbations.


2021 ◽  
Author(s):  
Zhizhen Hu ◽  
Jianwei Xuan ◽  
Haijin Zhao ◽  
Hangming Dong ◽  
Changhui Yu ◽  
...  

Abstract Background: The prevalence of adult asthma is increasing in China. However, there are no large sample, epidemiological data describing asthma severity at the time of new diagnosis and changes during follow-up management. Thus, the purpose of this study was to use a large health care database to examine asthma severity at initial diagnosis, and changes in severity over the first year of management.Methods: Data of patients with a first diagnosis of asthma were extracted from the SuValue electronic medical database. Inclusion criteria were: 1) At least 14 years old at the time of first diagnosis; 2) Initial diagnosis from 2001 to March 2019; 3) Followed-up for at least 12 months; 4) Had a follow-up visit every 3 months. Disease severity at diagnosis and at each follow-up visit, medications prescribed, and symptoms were collected and analysed.Results: A total of 7,654 adult patients with newly diagnosed asthma from tertiary hospitals (26.38%) and secondary hospitals (73.62%) who were followed-up for at least 12 months were included. Approximately 54% were females, and the proportion of patients over 60 years old was the highest (38%). Of all patients, 53.91% were not prescribed medications to control asthma, suggesting that these patients were mild asthma. Approximately 16% of patients were prescribed oral corticosteroid and/or inhaled corticosteroid and long-acting β2-agonist combination, suggesting moderate to severe asthma. The proportions of patients with moderate and severe decreased during the first 6 months, and then the proportions remained stable. The proportion of patients with severe asthma remained stable from the 6th month onward. At the end of the year 2.7% of patients had severe asthma. Patients with mild asthma tended to continue to have mild asthma in the following 3 months (> 76.19%). However, of the patients with mild and moderate asthma at 3 months, 92.85% and 75.1%, respectively, had a reduction in severity and had mild asthma at 12 months. On the other hand, 1.26% and 3.15%, respectively, progressed to severe asthma by 12 months.Conclusion: During the first year after an initial diagnosis of asthma patients diagnosed with mild asthma tended to not progress and remained stable with mild asthma over the year. The proportions of patients diagnosed with moderate and severe asthma remained stable over the year. Further study is needed to examine the clinical features of newly diagnosed patients with severe asthma who do not experience a reduction in severity in order to target these patients for more intensive treatment and reduce the disease burden.


Thorax ◽  
2018 ◽  
Vol 73 (10) ◽  
pp. 983-985 ◽  
Author(s):  
Bruce J Kirenga ◽  
Corina de Jong ◽  
Levicatus Mugenyi ◽  
Winceslaus Katagira ◽  
Abdallah Muhofa ◽  
...  

Data on asthma treatment outcomes in Africa are limited. 449 patients with asthma (age 5–93 years) in Uganda were followed up for 2 years to determine rates of exacerbations and mortality and associated factors. During follow-up the median number of exacerbations per patient was 1 (IQR 0–5) and 17 patients died (3.7%, 27.3 deaths per 1000 person years). Considering only the first year of follow-up, 59.6% of the patients experienced at least one exacerbation, 32.4% experienced three or more exacerbations. A multivariable model showed that the likelihood of experiencing at least one exacerbation in the first year of follow-up was lower with better baseline asthma control (higher asthma control test (ACT) score), with OR 0.87 (95% CI: 0.82 to 0.93, P=0.000), and was higher with more exacerbations in the year prior to enrolment (OR for log number of exacerbations 1.28, 95% CI: 1.04 to 1.57, P=0.018). Better asthma control (OR 0.93, 95% CI: 0.88 to 0.99, P=0.021) and number of baseline exacerbations (OR 1.35,95% CI: 1.11 to 1.66, P=0.005) were also the only factors that were independently associated with experiencing three or more exacerbations during the first year of follow-up. The only factor found to be associated with all-cause mortality was FEV1, with higher recent FEV1 associated with lower all-cause mortality (OR 0.30, 95% CI: 0.14 to 0.65; P=0.002). Rates of asthma exacerbations and mortality are high in Uganda and are associated with poor asthma control. Health systems should be strengthened to care for asthma patients.


Author(s):  
Sonia Herrero Martin ◽  
Javier Hueto Perez de Heredia ◽  
Marisol Gomez ◽  
Alberto Cuesta Remon ◽  
Francisco Campano Lancharro ◽  
...  

2020 ◽  
pp. 2003051
Author(s):  
Paul M. O'Byrne ◽  
Helen K. Reddel ◽  
Richard Beasley

Inhaled corticosteroids (ICS) have been recommended as a maintenance treatment, either alone or together with long-acting inhaled β2-agonists, for all asthma patients. Short acting β2-agonists (SABA) are rapid onset bronchodilators, which provide symptom relief, but have no anti-inflammatory properties, yet are the most widely used as-needed reliever treatment for asthma, and often the only treatment prescribed. Asthma patients can find adhering to daily preventative medication with ICS difficult and will often revert to using as-needed SABA as their only treatment, increasing their risk of exacerbations. The purpose of this review was to evaluate the efficacy of reliever medications that contain an ICS when compared to SABA as a reliever, or to maintenance ICS and SABA as reliever, in mild asthma patients.Nine studies were identified which have evaluated the use of ICS as a component of an as-needed reliever in patients with mild asthma. Four of the most recent studies compared the combination of ICS/formoterol to SABA as reliever.An ICS containing reliever medication was superior to SABA as reliever alone, and was equivalent to maintenance ICS and SABA as reliever, particularly in reducing risks of severe asthma exacerbations, in studies which compared these reliever options.SABAs should not be used as a reliever without ICS. The concern about patients with mild asthma not being adherent to maintenance ICS, supports a recommendation that ICS/formoterol should be considered as a treatment option instead of maintenance ICS, to avoid the risk of patients reverting to SABA alone.


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