Diagnosis and Management of Severe Asthma

Abstract

Severe 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.

Asthma and/or hay fever as predictors of fertility/impaired fecundity in U.S. women: National Survey of Family Growth

“…Immune deviation from a T2-high asthma to a T2-low asthma/T1 endotype is characterized by biomarkers of neutrophil recruitment e.g., IL-1alpha, IL-6, IL-8 43 , innate immune response dysregulation e.g., IL-23, TNF alpha, interferon, IL-17 44–48 , and includes neutrophilic noneosinophilic asthma 49 . Neutrophilic asthma is significantly increased in smokers with asthma compared to nonsmokers with asthma 50 and in previous smokers with severe asthma compared to never smokers with severe asthma 51 .…”

“…IL-8 is a biomarker of uncontrolled asthma and is associated with increased blood 122 and bronchoalveolar lavage (BAL) neutrophils 123 , oral/parenteral glucocorticoid unresponsiveness 122 , and reduced pulmonary function 122,123 . Endotypes of treatment resistant severe asthma include neutrophilic T2-low asthma 43,49,124 e.g., T2-low/Th17-low 43 , T1/Th17 125,126 which are associated with subclinical bronchial infection, increased IL-8 43 , lower airway dysbiosis 127 , and systemic inflammation 128 .…”

Severe asthma and eligibility for biologics in a Brazilian cohort

“…Many of the patients in ProAR recognized as having uncontrolled asthma may not truly have SA, as there may be modifiable factors worsening the disease (31). One of these factors is the presence of other chronic morbidities in addition to asthma (32,33), of which there was a high incidence among the individuals with ERS/ATS 2014 SA, corroborating the findings of Hekking (34).…”

“…This study showed a higher proportion of patient (78%) that had at least one asthma exacerbation in the previous year. Indeed, the literature also points to a high number of SA patients experiencing exacerbations in other cohorts, with 41% to 83% of SA patients reporting at least one exacerbation in the last year in these studies (22)(23)(24)28,32). Although the frequency reported varied among studies, probably because of methodological differences and definition of exacerbations, all studies report that these patients are experiencing a high frequency of exacerbations, highlighting what is still an unmet need for these patients.…”

2020 Brazilian Thoracic Association recommendations for the management of asthma

“…A thorough investigation of all of the factors associated with difficult-to-control asthma in every asthma patient is unnecessary. 31 However, in cases of difficult-to-control asthma, which affects 17.4% of all adult asthma patients and 74.1% of those in treatment classified as GINA step 4 or 5, 32 a systematic investigation must be performed to identify, minimize, or eliminate comorbidities (such as gastroesophageal reflux, obesity, vocal cord dysfunction, chronic rhinosinusitis, nasal polyposis, anxiety, depression, sleep apnea, COPD, allergic bronchopulmonary aspergillosis, and bronchiectasis) and to avoid asthma being caused or worsened by occupational exposure, among other things that can impair the disease control.…”