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Severe asthma phenotypes

Background

Overview

Definition
Asthma is a disorder of the lower respiratory tract characterized by reversible airflow obstruction and episodic or persistent symptoms of wheezing, dyspnea, and cough.
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Pathophysiology
The cause of asthma is unknown; however, a combination of genetic factors (alterations in ORMDL3, HLAG, IRAKIM, MYB, ADAM33, FLG), epigenetic changes (alterations in DNA methylation, histone modifications, mitochondrial gene silencing) and environmental factors (air pollutants, allergens, respiratory infections) have been implicated.
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Epidemiology
The estimated prevalence of asthma in the US is 7,400 persons per 100,000 population. The incidence of adult-onset asthma is estimated at 153 cases per 100,000 person-years.
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Disease course
In patients with asthma, exposure to allergens causes airway inflammation, leading to airway obstruction, hyperresponsiveness, and airway remodeling. These changes are associated with the clinical manifestations of to wheezing, coughing, chest tightness, and dyspnea.
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Prognosis and risk of recurrence
Patients with asthma have excess all-cause mortality, with a standardized mortality rate estimated at 1.54 in males and 1.91 in females. Patients with frequent exacerbations have an annual loss of lung function approximately 2% greater than predicted.
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Guidelines

Key sources

The following summarized guidelines for the evaluation and management of severe asthma phenotypes are prepared by our editorial team based on guidelines from the National Heart, Lung, and Blood Institute (NHLBI 2020), the Canadian Thoracic Society (CTS 2017), and the European Respiratory Society (ERS/ATS 2014). ...
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Screening and diagnosis

Diagnosis: as per CTS 2017 guidelines, confirm the diagnosis of asthma based on history and objective measures of lung function in patients old enough to reliably undergo pulmonary function tests.
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Asthma Control Test (ACT)
In the past 4 weeks, how much of the time did your asthma keep you from getting as much done at work, school or at home?
All of the time
Most of the time
Some of the time
A little of the time
None of the time
During the past 4 weeks, how often have you had shortness of breath?
More than once a day
Once a day
3-6 times a week
1-2 times a week
Not at all
During the past 4 weeks, how often did your asthma symptoms (wheezing, coughing, shortness of breath, chest tightness or pain) wake you up at night or earlier than usual in the morning?
≥ 4 nights a week
2-3 nights a week
Once a week
1-2 times a week
Not at all
During the past 4 weeks, how often have you used your rescue inhaler or nebulizer medication (such as Salbutamol)?
≥ 3 times per day
1-2 times per day
2-3 times per week
≤ 1 per week
Not at all
How would you rate your asthma control during the past 4 weeks?
Not controlled at all
Poorly controlled
Somewhat controlled
Well controlled
Completely controlled
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Diagnostic investigations

Work-up
As per CTS 2017 guidelines:
Obtain total serum IgE level measurement, peripheral eosinophil count, and where available sputum eosinophils and fractional exhaled nitric oxide levels in patients with confirmed severe asthma, in order to characterize the phenotype.
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Recognize that:
sputum eosinophils may help in identifying responders to anti-IL-5 therapies but not in identifying responders to macrolides
blood eosinophil counts may help to identify patients that will experience fewer exacerbations with anti-IL-5 therapies and omalizumab
insufficient evidence for the use of fractional exhaled nitric oxide to predict response or responders to omalizumab or anti-IL-5 therapies
serum IgE does not predict response to anti-IL-5 therapies or omalizumab
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Medical management

General principles: as per ATS/ERS 2014 guidelines, consider using sputum eosinophil counts, obtained in centers experienced in using this technique, in addition to clinical criteria to guide treatment in adult patients with severe asthma.
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More topics in this section

  • ICSs and SABAs

  • ICSs and LABAs

  • LAMAs

  • Omalizumab

  • Other biologic agents

  • Allergen immunotherapy

  • Macrolides

  • Antifungal agents

  • Methotrexate

Therapeutic procedures

Bronchial thermoplasty: as per NHLBI 2020 guidelines, consider offering bronchial thermoplasty in ≥ 18 years old patients with persistent asthma placing a low value on harms (short-term worsening symptoms and unknown long-term side effects) and a high value on potential benefits (improvement in QoL, a small reduction in exacerbations).
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Patient education

Self-management counseling: as per CTS 2017 guidelines, provide comprehensive self-management asthma education in patients with suspected or confirmed severe asthma, and obtain an evaluation by an asthma specialist.
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