Asthma

A heterogeneous disease characterized as chronic inflammation of the airway  (1)

Common triggers: exercise, allergen-irritant exposure, change in weather, laughter, or viral respiratory infections

Patient may experience symptoms-free periods alternating with sporadic flare-up (exacerbations).

Most common asthma phenotypes:

• Allergic asthma: usually present since childhood and has strong family history of allergic diseases

• Nonallergic asthma

• Late-onset asthma: more common in females

• Asthma with fixed airflow limitation: due to airway remodeling

• Asthma with obesity

Asthma severity is assessed retrospectively from treatment required to control symptoms.

• Mild asthma: well controlled with Step 1 or 2 treatment (i.e., with as-needed ICS-formoterol alone or with low-intensity maintenance controller treatment)

• Moderate asthma: well controlled with Step 3 or 4 treatment (i.e., low or medium dose ICS-LABA)

• Severe asthma: remains "uncontrolled" with optimized treatment with high dose ICS-LABA or that requires high dose ICS-LABA to prevent it from becoming "uncontrolled"

455,000 deaths worldwide reported in 2019 (2)

African Americans are three times more likely to die from asthma

Asthma affects about 10% of children ages 5 to 18 years in the United States.

Asthma prevalence is greater in boys than girls; however, in adults, women are more affected.

Obesity is associated with increased prevalence and incidence of asthma.

Rate of asthma deaths largest among those aged 65 and older

Host factors: genetic predisposition, sex, obesity, preterm or small for gestational age (SGA)

Environmental: viral infections, animal and airborne allergens, tobacco smoke exposure, e-cigarette use, pollution, stress

Aspirin or NSAIDs hypersensitivity 

Persons with food allergies and asthma are at increased risk for fatal anaphylaxis from those foods.

Atopy: eczema, allergic conjunctivitis, allergic rhinitis

Obesity (associated with higher asthma rates)

Gastroesophageal reflux disease (GERD)

Obstructive sleep apnea (OSA)

More than one symptom such as wheeze, SOB, cough, chest tightness

Symptoms worse at night, vary in time and intensity, worse with common triggers

May be normal

Focus on

• Use of accessory muscles

• Rhinitis, nasal polyps, swollen nasal turbinates

• Expiratory wheezing, prolonged expiratory phase. Note: Wheezing may be absent in severe exacerbation due to severely reduced airflow.

• Skin: eczema

In children

• Upper airway diseases (allergic rhinitis or sinusitis)

• Large airway obstruction (foreign body aspiration, vocal cord dysfunction, vascular ring or laryngeal web, laryngotracheomalacia, enlarged lymph nodes, or tumor)

• Small airway obstruction (viral bronchiolitis, cystic fibrosis, bronchopulmonary dysplasia, heart disease, primary ciliary dyskinesia, bronchiectasis)

• Other causes (recurrent cough, chronic upper airway cough syndrome, aspiration/GERD)

In adults

• Chronic obstructive pulmonary disease, bronchiectasis, heart failure, pulmonary embolism, tumor, pulmonary infiltration with eosinophilia, Churg-Strauss syndrome, medication-induced cough (ACE inhibitors), vocal cord dysfunction

Blood tests are not required but may find eosinophilia or elevated serum IgE levels (allergic asthma).

Documented variable expiratory airflow limitation:

• Spirometry with methacholine challenge: Normal test does not rule out asthma; measures the FVC and the FEV₁; a reduced predicted ratio of FEV₁/FVC with reversibility (increase of 200 mL and 12% of FEV₁/FVC from baseline) after using a short-acting bronchodilator (SABA)

• Excessive variability in twice daily peak expiratory flow (PEF) in 2 weeks (daily PEF variability >10%)

• Bronchial challenge test: used mainly in adults, positive when there is a fall in FEV₁ >20% with methacholine or histamine; or >15% with hypertonic saline or mannitol challenge

• Exercise challenge test: fall in FEV₁ >10% and 200 mL from baseline

• Significant increase in lung function after 4 weeks of anti-inflammatory treatment

Chest x-ray is used to exclude alternative diagnoses.

Asthma action plan: Patients monitor their own symptoms and/or peak flow measurements. Reassess action plan every 3 to 6 months.

Assess asthma symptoms control with simple screening tools, such as consensus-based Global Initiative for Asthma (GINA) symptom control tool or Primary Care Asthma Control Screening Tool (PACS). Use the review, assess, adjust method of ongoing management.

Allergy skin testing is not useful for diagnosis of asthma but may be to evaluate atopic triggers.

Measurement of fractional concentration of exhaled nitric oxide (FENO) suggests eosinophilic airway inflammation.

Focus on symptom control and prevention of exacerbations.

Use of holding chambers (“spacers”) with inhaled agents improves clinical outcomes.

Written asthma self-management action plan

Encourage physical activity, weight loss, smoking cessation, avoidance of irritants, emotional stress.

Avoidance of occupational exposure

Annual influenza vaccine; Pneumococcal vaccine recommended for high-risk patients

Patients at risk for anaphylaxis carry EpiPen.

Controller medications: used for regular maintenance, reduce airway inflammation, control symptoms, and reduce risk of exacerbations:

Inhaled corticosteroids (ICS)

Long-acting β-agonist (LABA) (formoterol, salmeterol)

The ICS can be delivered by regular daily treatment or, in mild well-controlled asthma, by as-needed low dose ICS-formoterol.

Treatment of asthma with SABAs alone is no longer recommended by the GINA Guidelines for adults and adolescents.

• ICS therapy is essential to reduce risk of death and severe exacerbations.

Reliever (rescue medication) provided to all patients for as-needed relief of breakthrough symptoms

• SABA–albuterol /levalbuterol

Add-on therapies for patients with severe asthma, when patients persist with symptoms despite optimized treatment with high-dose controller medications (ICS + LABA)

Tiotropium is not indicated in children <12 years.

Reliever for all management steps in children 6–11 years is as-needed SABA.

School-based programs including asthma self-management reduce emergency department visits, hospitalizations, and days of reduced activity.

Stepwise approach for asthma treatment for adolescents (>12 years) and adults:

• Step 1: symptom driven treatment:

  • First: symptom driven as-needed low dose ICS-formoterol​​​​; controller alternatives: low-dose ICS whenever SABA taken; preferred reliever: ICS-formoterol

• Step 2: low-dose controller + as needed reliever:

  • First: low-dose ICS + SABA; controller alternatives: LTRA or low-dose ICS whenever SABA taken (separate or combined)

• Step 3: one or two controllers + as needed reliever:

  • First (adults/adolescents): low-dose ICS-LABA; controller alternatives: medium-dose ICS or low-dose ICS with LRTA. Preferred reliever: as-needed low-dose ICS/formoterol as both controller + reliever for those on maintenance therapy; first (ages 6 to 11 years) and second alternative (adults/adolescents): medium-dose ICS + SABA; third: low-dose ICS + LTRA

• Step 4: two or more controllers + as-needed reliever:

  • First (adults/adolescents): medium-dose ICS-LABA as controller; controller alternatives: high-dose ICS, add-on tiotropium or LTRA. Consider house dust mite SLIT for sensitized patient with normal spirometry and allergic rhinitis; preferred reliever low-dose ICS-formoterol for those prescribed bud-form/BDP-form maintenance and reliever therapy, otherwise SABA reliever when on other ICS-LABA

• Step 5: High-dose ICS-LABA, referral for phenotype assessment and consider add-on therapy (i.e., LAMA, anti-IgE, anti-IL5/5R, anti-IL4, tiotropium) or add low-dose OCS while considering risks versus benefits

Combination therapy with a LABA + ICS resulted in fewer asthma exacerbations than treatment with ICS alone.​

COVID-19 special considerations

• Patients with asthma should continue taking their prescribed asthma medications, particularly ICS-containing medication and oral corticosteroids if prescribed.

• Covid-19 vaccination is recommended for people with asthma.

Specialized testing (e.g., bronchoprovocation)

Specialized treatments (e.g., immunotherapy)

Poorly controlled asthma, frequent exacerbation, or multiple emergency department visits

Occupational asthma due to legal implications​​​​​​.

Exercise-induced bronchoconstriction (EIB): pharmacotherapy show to reduce symptoms, SABA prior exercise, or LTRA/chromones.

Allergen immunotherapy when clear relationship between symptoms and exposure

Management of acute exacerbation of asthma

• Outpatient:

  • Mild: speak in full sentence, HR <120 bpm, oxygen saturation 90–95%, and peak flow >50% of predicted can be managed as outpatient in clinic; should start SABA with ICS or formoterol/ICS and prednisolone; if symptoms resolve within 1 hour, could be discharge home with close follow-up

  • Severe symptoms: not able to speak in full sentence, HR >120 bpm, oxygen saturation <90%, peak flow <50% predicted, drowsy, confused, or silent chest; transfer to inpatient facility.

• Treatment for severe:

  • Oxygen: to maintain saturation 93–95%

  • SABA: within 1 hour of arrival, initially around the clock followed by on demand

  • Systemic steroids: Oral is as effective as IV. 50 mg prednisolone (morning dose) or 200 mg hydrocortisone divided in doses. Duration should be 5 to 7 days.

  • Epinephrine: only when asthma is associated with angioedema or anaphylaxis

  • Avoid sedative.

  • Vital signs, pulse oximetry, response and duration of response to SABA, a lung function such as PEF or FEV₁

  • Asthma education

• Discharge criteria

  • Minimal or absent asthma symptoms, Hypoxia has resolved, FEV₁ or PEF ≥70% predicted or personal best, Bronchodilator response sustained ≥60 minutes

Identify triggers and control exposures.

Consider stepping down treatment once symptoms are controlled for 3 months.

American Academy of Allergy, Asthma & Immunology: 800-822-2762 or http://www.aaaai.org/

Asthma and Allergy Foundation of America: 800-727-8462 or http://www.aafa.org/

Atelectasis, pneumonia, medication-specific side effects/adverse effects/interactions

Respiratory failure; death: ~50% of asthma deaths occur in the elderly (age >65 years)

J45.20 Mild intermittent asthma, uncomplicated

J45.52 Severe persistent asthma with status asthmaticus

J45.51 Severe persistent asthma with (acute) exacerbation

J45.902 Unspecified asthma with status asthmaticus

J45.901 Unspecified asthma with (acute) exacerbation

J45.90 Unspecified asthma

J45.50 Severe persistent asthma, uncomplicated

J45.909 Unspecified asthma, uncomplicated

J45.21 Mild intermittent asthma with (acute) exacerbation

J45.9 Other and unspecified asthma

J45.30 Mild persistent asthma, uncomplicated

J44.0 Chronic obstructive pulmonary disease with (acute) lower respiratory infection

J45.5 Severe persistent asthma

J45.2 Mild intermittent asthma

J45.31 Mild persistent asthma with (acute) exacerbation

J45.42 Moderate persistent asthma with status asthmaticus

J45.3 Mild persistent asthma

J45.32 Mild persistent asthma with status asthmaticus

J45 Asthma

427295004 Moderate persistent asthma

426656000 Severe persistent asthma

195949008 Chronic asthmatic bronchitis

427679007 Mild intermittent asthma

195967001 Asthma

409663006 Cough variant asthma

31387002 Exercise-induced asthma

389145006 Allergic asthma

426979002 Mild persistent asthma

266361008 Intrinsic asthma

SABA plus ICS or formoterol/ICS is the most effective rescue therapy for acute asthma symptoms.

Holding chambers should be used by all.

ICSs are the preferred long-term control therapy for patients of all ages.