Asthma

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Author / Curator: Sharon McGrath, MD

Faculty Advisor: Whitney LeFevre, MD

Top Teaching Points

  • Asthma is a clinical diagnosis supported by PFTs (which generally can't be used for diagnosis until at least 5 years old).
  • Consider aspirin-exacerbated respiratory disease (AERD) in those with Samter's triad (asthma, respiratory symptoms exacerbated by aspirin, and nasal polyps).
  • A properly used inhaler with a spacer is just as effective at medication delivery as a nebulizer.[1]
  • Asthma exacerbations don't need empiric antibiotics.[2][3]
  • Cough-variant asthma is more common in children.[4]
  • Smokers have a decreased responsiveness to inhaled corticosteroids.[5]
  • In general, mild exacerbations may be managed at home, moderate should be seen in the office, and severe require hospitalization.[6]
  • Cardioselective ß-blockers are safe for use in stable asthmatics, but nonselective ß-blockers should be avoided.[7][8]

Background

Epidemiology

  • Affects ~8.3% of adults and children in the US.[9][10]
  • In children, it is more common in blacks and in males, and in adults it is more common in females.[11]
  • Responsible for 10 deaths per million in the US population in 2017.[12]

Pathophysiology

Asthma is a chronic lung disease of inflammation causing reversible narrowing and obstruction of the airway. Chronic inflammation leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing.[13]

Natural History & Complications

  • Risk factors for continuation of asthma into adulthood include frequent symptoms in first year of life, family history (especially in mother), eczema, elevated IgE levels, and maternal smoking.[14]
  • Most chronic adulthood asthma has its onset at <6 years old and about 75% of adolescent asthma will persist into adulthood[15]; however, 3 of 4 school-aged children outgrow asthma.[16]
  • Remission is less likely in adult-onset asthma. Though many cases of "new onset" asthma in adulthood are undiagnosed childhood asthma, it may be more common in females[17] and increased around menopause[18].
  • Asthma severity is unlikely to worsen in adults, in absence of other comorbidities.[16][19]
  • While asthma is characterized by reversible limitation in airflow, chronic inflammation can lead to irreversible structural changes.[20] Loss of lung function is worse in those with newly diagnosed asthma and those with more severe symptoms.[15]
  • Exacerbations are more common when asthma is uncontrolled.[4]

Diagnosis

Typical H&P should prompt confirmation with pulmonary function tests, such as spirometry.[21] The combination is used to classify severity.[22]

Diagnosis requires variable expiratory airflow limitation (preferably spirometry if ≥ 5 years old), reversible obstruction, and exclusion of alternative diagnoses. Asthma Predictive Index is a useful tool in younger children.[23]

History & Exam Findings[2]

  • Recurrent cough, wheezing, difficulty wheezing, and/or chest tightness (typically more than one of these)
  • Symptoms vary over time and in intensity, are worse at night or on waking or with viral infections
  • Symptoms often triggered by exercise, exposure to allergens/irritants, changes in weather, stress, menstrual cycles
  • Exam often normal, but may have wheezing, especially on forced expiration

Pulmonary Function Tests

  • Spirometry measuring FEV1 and FEV1/FVC can be done in the office. Normal ranges are determined by sex, age, and height.
    • FEV1 <80% predicted and FEV1/FVC <85% predicted
    • Reversibility is shown by increase in FEV1 ≥12% with bronchodilator[4]
Asthma Classification - Adapted from NHLBI guidelines for patients ≥ 12y[22]
Severity
Persistent
Components Intermittent Mild Moderate Severe
Impairment Symptoms ≤ 2 days/wk > 2 days/wk Daily Throughout day
Nighttime awakenings ≤ 2 /mo 3-4 /mo >1/wk (not nightly) Often Nightly
SABA use ≤ 2 days/wk > 2 days/wk Daily Several times per day
Interference with normal activity None Minor Some Extreme
FEV1 or PEF Normal FEV1 between exacerbations;

>80%

>80% 60-80% <60%
FEV1/FVC Normal Normal Reduced 5% Reduced >5%
Risk Exacerbations requiring OCS < 2 /yr ≥ 2 /yr
Recommended treatment Step 1 Step 2 Step 3-4

(+ consider OCS)

Step 4-5

(+ consider OCS

OCS = oral corticosteroids
Other diagnostic tests

Ancillary tests are primarily to exclude other diagnoses or identify comorbid conditions.[4]

  • CBC - Rule out anemia, look for eosinophilia.
  • Allergy testing - Can guide avoidance strategies.
  • Bronchoprovocation testing - Can help when clinical features fit but spirometry is normal and there's no response to medications. Can be done with methacholine (high sensitivity), exercise (high specificity), or cold air.
  • Chest XR - Consider in children who do not respond to initial therapy. May show congenital malformations, aspiration or cystic fibrosis findings. Findings consistent with asthma include hyperinflation, peribronchial thickening, and mucoid impaction with atelectasis.
  • Sweat chloride test - Consider in children with other symptoms of cystic fibrosis.
  • Barium swallow - Consider if concern for swallowing dysfunction with aspiration.
Differential diagnosis: "Not all that wheezes is asthma" [4][24]
Infants and Children Adults
Upper airway disease
  • Allergic rhinitis / sinusitis / postnasal drip

Large airway obstruction

  • Foreign body
  • Vocal cord dysfunction
  • Vascular rings or laryngeal webs
  • Laryngotracheomalacia, tracheal stenosis, or bronchostenosis
  • Enlarged lymph nodes, tonsils, or tumor

Small airway obstruction

  • Viral bronchiolitis or obliterative bronchiolitis
  • Cystic fibrosis
  • Bronchopulmonary dysplasia
  • Heart disease

Other

  • Recurrent cough not due to asthma
  • Aspiration from swallowing mechanism dysfunction or GERD
  • COPD
  • CHF, pulmonary edema
  • Pulmonary embolism
  • Airway tumor
  • Pumonary infiltration with eosinophilia
  • Cough due to drugs (e.g., ACEi)
  • Vocal cord dysfunction
  • Wegener's granulomatosis

Management

Assessment components

  • Schedule every 2-6 weeks while gaining control, every 1-6 months to monitor control, and every 3 months if step-down therapy is initiated[22]
  • Measure lung function before treatment, 3-6 months later, and yearly thereafter if controlled[13]
  • Confirm correct technique for MDI / diskus, and spacer use
  • Review Asthma Action Plan
  • Evaluate and treat comorbidites that can contribute to respiratory symptoms (rhinitis, chronic rhinosinusitis, GERD, obesity, OSA, depression, anxiety)
  • Vaccines: annual influenza, PCV-13 (at age 65), PPSV-23 (once, and then repeat at age 65, at least 1 year after PCV-13 and >5 years after any PPSV-23), current Tdap[25]

Pharmacologic: Step-wise approach

Decision to utilize step-up or step-down therapy is patient-dependent. Consider step-down approach in those with significant symptoms at time of diagnosis.[26] Patients should have 3 months of good control before stepping-down.[4][27] In general, step-up is indicated if properly using rescue inhaler >2 times / week (other than as pre-treatment for exercise) and compliant with controllers.[26][27]

Table 3. Stepwise approach to asthma ≥12 yo. Adapted from NHLBI guidelines for ≥ 12 years old.[22]
Intermittent Persistent
Step 1 Step 2 Step 3 Step 4 Step 5 Step 6
Preferred SABA prn Low-dose ICS Low-dose ICS + LABA

-or-

Medium-dose ICS

Medium-dose ICS + LABA High-dose ICS + LABA High-dose ICS + LABA + OCS
+ Consider omalizumab if allergies
Alternatives Cromolyn

LTRA

Theophylline

Low-dose ICS+ (either LTRA, theophylline, or zileuton) Medium-dose ICS + (either LTRA, theophylline, or zileuton)
ICS = inhaled corticosteroids, OCS = oral corticosteroids

SABA = short-acting beta-agonist, LABA = long-acting beta-agonist

LTRA = leukotriene receptor antagonist

Non-pharmacologic: Avoidance of triggers

  • Determine triggers by asking about inhalant allergens, exposure to tobacco smoke, pollutants & irritants (dust mists, cockroaches, strong odors), workplace exposures, rhinitis, GERD, sulfite sensitivity (beer, wine, shrimp, dried fruit, processed potatoes), exercise, cold air, and medication sensitivities.
  • General guidelines: avoid smoke, use dust-mite proof pillow covers, use a dehumidifer, remove carpets, remove pest attractants, keep pets outdoors, keep windows closed

Assessing control

Validated questionnaires can help assess control: ACT, ATAQ, and ACQ.[28][29]

Peak expiratory flow rate (PEF) can be checked at home and in office.

  • Establish baseline during period of good control to compare to future readings: record 2-4 times daily for 2 weeks. Pick highest value as "personal best" PEF. Normal range for a patient is defined as 80-100% of personal best.[30]

Outpatient exacerbation management

First step at home or in office is SABA (2-8 puffs MDI or 2.5mg neb) - repeat every 20 minutes prn for first hour. AAFP's algorithms for home and ED/Inpatient management is a useful tool; in summary, however:

  • Mild exacerbation => If prompt relief in symptoms +/- PEF, can space to SABA q3-4 hrs prn; consider OCS burst
  • Moderate exacerbation => If incomplete response and PEF remains 50-79%, repeat SABA q20 min, add OCS
  • Severe exacerbation => If poor response or PEF <50%, repeat SABA, add OCS, and go to ED

Consider prescribing oral corticosteroids (OCS) for patients with frequent or severe exacerbations to have available at home.

An Asthma Action Plan can guide patients on when and how to assess for an exacerbations and guide initial self-management steps. This can be a helpful tool when counseling some patients, but there is mixed evidence of concrete benefit of using this tool. [31][32][33][34][35][36][37]

Considerations in certain populations

  • NSAID-induced asthma (AERD) - Leukotriene-modifying agents (LTRA or zileuton) should be used.[38][39]
  • Exercise-induced bronchoconstriction - Use SABA 5-15 minutes before exercise, and breathe through a scarf or mask when exercising in cold, dry conditions.[40]
  • Pregnancy - Asthma patients on average have higher perinatal mortality, preeclampsia, preterm delivery, and LBW infants. Management is essentially the same. Common Class B medications include budesonide, cromolyn, and omalizumab.[41]

When to refer

Refer if step 4 or higher is needed.[4] Consider referral when asthma is difficult to control or frequent exacerbations are occurring (such as a patient who frequently requires PO steroids), there are intolerable medication side effects, or diagnosis is uncertain and additional testing such as bronchoscopy may be needed.[13]

Trial Summaries

AMAZES (2017): Adults with persistent asthma (with symptoms despite inhaled corticosteroid and long-acting bronchodialtor) had fewer exacerbations and improved quality of life when oral azithromycin (500mg three times per week) was added to treatment for 48 weeks.[42]

AZALEA (2016): In adults with asthma exacerbations requiring systemic steroids, azithromycin added to treatment showed no statistical or clinical benefit at day 10. Of note, a large number of patients were excluded because they had already received antibiotics.[43]

BASALT (2012): Among adults with mild to moderate persistent asthma controlled with low-dose ICS therapy, the use of either biomarker-based or or symptom-based adjustment was not superior to physician assessment-based adjustment of inhaled corticosteroids in time to treatment failure.[44][WJC: BASALT]

EXTRA (2011): Omalizumab reduces asthma exacerbations in patients with uncontrolled severe allergic asthma on inhaled corticosteroids and long-acting beta agonists.[45] [WJC: EXTRA]

TALC (2010): When added to an ICS, tiotropium improved symptoms and lung function (as measured by morning PEF) in patients with inadequately controlled asthma. Its effects appeared to be equivalent to those with the addition of a LABA.[46] [WJC: TALC]

SMART (2006): Salmeterol increases the risk of respiratory-related deaths, particularly among African American patients and those not using an inhaled corticosteroid.[47] [WJC: SMART]

Ongoing controversies / New updates

  • Combination of anticholinergic with SABA (duo-nebs) in acute exacerbations seen in the ED may decrease hospitalization and return visits to the ED.[48]
  • Increased dose of inhaled glucocorticoids early in an exacerbation may reduce severity or duration of an exacerbation. However, it is not clear which characteristics predict who will benefit.[49]
  • Oral vitamin D3 offers some protection against asthma exacerbations requiring steroids in adults with mild to moderate asthma, but does not improve daily symptoms.[50][51]
  • Although LABAs increase severe attacks and asthma deaths when used alone, it is unclear whether the next best step when uncontrolled on a low-dose ICS is to increase the ICS dose or use a LABA/ICS combination.[52]
  • Children with obesity may experience more asthma symptoms.[53]

Teaching Resources

Videos:

Podcast episodes:

Core review articles / Guidelines:

Other links:

References

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