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Asthma and HIV

for Health Care Providers

Asthma

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary. Consult VA pharmacists for alternatives.

Key Points

  • Asthma is characterized by airway hyperresponsiveness, inflammation, and reversible obstruction.
  • Stepwise, multimodal treatment of asthma may decrease symptoms.
  • Patients should know their baseline peak expiratory flow rate (PEFR) measurements and their PEFR thresholds for seeking medical care.
  • Drug-drug interactions between PIs and certain medications may affect treatment.

Background

  • Asthma is a chronic inflammatory disorder of the airways that causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough, particularly at night and in the early morning.
  • These symptoms are associated with airflow limitation that typically is reversible and responsive to bronchodilator therapy, unlike chronic obstructive pulmonary disease (see COPD).
  • In asthma, airflow limitation is secondary to airway hyperresponsiveness and narrowing (increased resistance to flow) caused by inflammation and edema. In contrast, in COPD (particularly in the case of emphysema), airflow limitation is primarily caused by lung tissue destruction and loss of recoil, and is largely irreversible.
  • Asthma is best distinguished from COPD (emphysema and chronic bronchitis) by clinical features such as:
    • Marked variability in symptoms
    • No history of cigarette smoking (although some asthmatics may smoke)
    • Onset early in life (although asthma may present in adulthood)
    • History of allergies such as hay fever

Because COPD may demonstrate partially reversible airflow obstruction, the response to a bronchodilator, particularly a single administration in the pulmonary function laboratory, may not reliably distinguish asthma and COPD.

Epidemiology

  • The prevalence of asthma in the United States is approximately 6-11%, depending on the population surveyed (higher prevalence among people living in the inner city).
  • 75% of patients with asthma are diagnosed before the age of 7, although asthma may develop at any age.
  • A small cross-sectional study of 83 HIV-infected children and young adults showed that 34% of the subjects carried a clinical diagnosis of asthma, and 42% were using rescue bronchodilators.

Veterans with HIV*

Asthma: 6%

*Veterans in the VA HIV Clinical Case Registry in care in 2007 who had an ICD-9 code corresponding to this condition

Evaluation

Clinical Signs and Symptoms

Risk factors
  • Atopy
  • Passive smoking
  • Upper respiratory tract infections
  • Beta-blockers (including ophthalmic formulations)
HistoryFavoring diagnosis of asthmaFavoring other diagnosis (especially COPD)
  • Wheezing
  • Cough often worse at night
  • Shortness of breath
  • Chest tightness
  • Episodic symptoms: hours to days
  • Triggers: exercise (after 10-15 minutes), cold air, exposure to allergens (dust, molds, furry animals, cockroaches, pollens), GERD, aspirin or NSAIDs
  • Personal or family history of atopy (including allergic rhinitis)
  • Asthmatic symptoms as a child
  • Onset of symptoms at age >50
  • History of cigarette smoking
  • Sputum production
  • Lack of marked improvement after beta-agonist inhaler or oral steroids
Physical examination
  • Normal between exacerbations
  • Wheezes (nonspecific, and may not be present)
  • Rhonchi
  • Prolonged expiration
    • In severe exacerbations (status asthmaticus):
    • Use of accessory muscles
    • Tachypnea
    • Tachycardia
    • Prolonged expiratory phase
    • Disappearance of wheezing as airflow diminishes (suggests impending respiratory arrest)
Imaging
  • Chest X ray usually normal; may show hyperinflation in severe disease
Pulmonary function tests
  • Spirometry is the preferred way to measure airflow limitation (see below)
  • Peak flow rate assessment can aid in diagnosis and monitoring (see below)
Differential diagnosis
  • COPD
  • Diffuse bronchiectasis
  • Allergic bronchopulmonary aspergillosis
  • Constrictive bronchiolitis
  • Eosinophilic bronchitis
  • Postviral bronchiolitis (usually reversible with time but not bronchodilators)
  • Upper airway obstruction (tumors)
  • Congestive heart failure

Pulmonary Function Testing

Definitions

  • Irreversible airflow obstruction: a post-bronchodilator forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) ratio of <0.70 (note: may be less specific in older people).
  • Reversible airflow obstruction: increase in post-bronchodilator FEV1 of ≥200 mL or >12% of predicted value.
  • Partially reversible airflow obstruction: post-bronchodilator FEV1/FVC <70% of predicted value despite significant bronchodilator responsiveness.
  • Spirometry: Measure FEV1, FVC, and bronchodilator response.
  • PEFR: Measure brief, forceful exhalation on a peak flow meter. Peak flow meters are inexpensive, provide objective, reproducible assessments of airflow, and may be ordered through a facility's Prosthetics Service for home use by patients.

    The test can be performed with the patient sitting or standing. Instruct the patient to breathe in maximally, put meter to mouth, seal lips around mouthpiece, and blow as hard and as fast as possible into meter.
    • Record patients' personal best PEFR when they feel well and have had a number of good trials on the meter.
    • Normal peak flow range is 80-100% of the personal best PEFR.
    • Normal variability in PEFR is 15-20%. Unchanged PEFR in the presence of symptoms suggests a diagnosis other than asthma.
    • Average PEFRs vary by age, sex, and height.

If initial pulmonary function test (PFT) results are normal or unobtainable, but asthma is still suspected:

  • Have the patient record serial PEFR measurements and symptoms in a diary to determine whether there is evidence of intermittent airflow limitation that correlates with symptoms such as dyspnea, chest tightness, or cough.
  • Repeat evaluation when patient is symptomatic.
  • Consider performing serial measurements before and after bronchodilator treatment (this is helpful only if there is baseline airflow limitation at the time of testing).
  • To diagnose occupational asthma, test before and after occupational exposures; this can be done with spirometry or PEFR. Taking repeated PEFR measurements and keeping a symptom diary are simple to do and may provide more useful information.
  • Consider performing bronchoprovocation testing (methacholine or exercise challenge) for patients with atypical symptoms, such as chronic (rather than intermittent) cough or with normal baseline pulmonary function. Provocative testing should not be performed in patients who have typical asthma symptoms.

Management

Chronic Asthma

Goals

  • ≤2 episodes/week of symptoms requiring treatment with short-acting beta-agonist (SABA) medication
  • Prevent exacerbations and need for emergency department visits
  • Minimize limitations on activity
  • Minimize toxicities
Monitoring and Intervention
  • Patients with asthma who use tobacco should be counseled to stop. (see Smoking Cessation)
  • At each visit, ask patients whether asthma has woken them from sleep, necessitated more rescue bronchodilator use than usual, necessitated urgent care or emergency room visits, or limited participation in usual activities.
  • Ask about control of triggers.
  • Provide an annual flu vaccination.
  • Instruct patients to perform serial PEFR measurements at home and workplace.
  • Determine each patient's baseline PEFR.
  • Determine each patient's PEFR threshold and symptom threshold for escalating therapy or seeking medical evaluation; see Table 2. Patients should know their baseline PEFRs and their PEFR thresholds. Written plans based on symptoms or PEFR thresholds improve disease control.
  • Review and instruct on correct use of inhalers with spacers. Patients who are unable to use spacers properly may need a nebulized formulation of a SABA.
  • Use of SABA >2 times per week generally indicates inadequate chronic control and may necessitate a "step-up" in treatment. See below.
Table 1: Chronic Asthma: Maintenance Treatment according to Severity of Symptoms
SeverityClassification CriteriaTreatment

*There are important interactions between some inhaled corticosteroids and certain ARVs. See Table 4: Potential ARV Interactions.

Intermittent
  • Symptoms ≤2 days/week
  • Nighttime awakenings ≤2/month
  • SABA use ≤2 days/week
  • No interference with normal activity
  • FEV1>80% predicted or PEFR >80% personal best; FEV1/FVC normal
  • 0-1 exacerbations requiring oral steroids per year
Step 1:
  • SABA, (eg, albuterol, levalbuterol, pirbuterol)
Mild Persistent
  • Symptoms >2 days/week
  • Nighttime awakenings 3-4/month
  • SABA >2 days/week but not daily
  • Minor limitation with normal activity
  • FEV1 or PEFR ≥80%; FEV1/FVC normal
  • ≥2 exacerbations requiring oral steroids per year
Step 2:
  • Low-dose inhaled corticosteroid (ICS)* (use lowest effective dosage; see medication chart for details)
  • SABA, as needed
Alternatives: cromolyn, leukotriene receptor antagonist (montelukast, zafirlukast), nedocromil, theophylline
Moderate Persistent
  • Symptoms daily
  • Nighttime awakenings >1/week but not daily
  • SABA daily
  • Some limitation with normal activity
  • FEV1 or PEFR >60% and <80%, or FEV1/FVC reduced 5%
  • ≥2 exacerbations requiring oral steroids per year
Step 3:
  • Low-dose ICS* and long-acting beta-agonist (LABA) (eg, salmeterol or formoterol)
OR
  • Medium-dose ICS*
  • Consider short course of oral steroids (eg, prednisone 40 mg QD for 5 days) when initiating treatment
  • SABA, as needed
Alternatives: low-dose ICS* with leukotriene receptor antagonist, theophylline, or zileuton
Severe Persistent
  • Symptoms throughout the day
  • Nighttime awakenings daily
  • SABA several times per day
  • Extreme limitation with normal activity
  • FEV1 or PEFR <60%, or FEV1/FVC reduced >5%
  • ≥2 exacerbations requiring oral steroids per year
Step 4:
  • High-dose ICS* and LABA
  • Combination ICS and LABA options include budesonide/formoterol and fluticasone/salmeterol*
Step 5 (add to above):
  • Consider omalizumab for patients with allergies, as evaluated by an immunologist

Print table

When to Refer
  • Disease severity moderate persistent or greater: refer to Pulmonary
  • Atypical symptoms: refer to Pulmonary
  • Elevated IgE levels: refer to Pulmonary or Allergy/Immunology
Table 2: Acute Asthma Exacerbation: Treatment according to Severity of Symptoms
SeveritySigns and SymptomsTreatment
Mild
  • Dyspnea with activity
or
  • PEFR ≥80% personal best/predicted
  • Can be managed at home
  • SABA
  • Possible short course of oral systemic corticosteroids (5 days)
Moderate
  • Dyspnea limits usual activity
or
  • PEFR 60-80% personal best/predicted
  • Usually requires emergency department or office visit
  • Frequent SABA
  • Reassess after 1-2 hours; a good response includes a normal exam, no distress, PEFR>70%, O2 saturation >90%, and a sustained response for 60 minutes after the last treatment
  • Oral steroids (40-80 mg QD) until PEFR >70% personal best/predicted
Severe
  • Dyspnea at rest, or lack or response to treatments for moderate-severity acute asthma
or
  • PEFR <60% personal best/predicted
  • Usually requires emergency department or office visit
  • Frequent nebulized SABA with reassessments
  • Oral steroids (40-80 mg QD) until PEFR >70% personal best/predicted
Life Threatening
  • Too dyspneic to speak, drowsy or confused
  • Requires emergency department visit, usually hospitalization
  • Nebulized SABA and ipratropium hourly or continuous
  • PO or IV steroids
  • Consider magnesium sulfate infusion (2 g), heliox delivered albuterol
  • Consider intubation in patients with persistent hypercapnia, exhaustion, depressed mental status

Print table

Table 3: Medications and Other Therapies
For acute symptoms and exacerbations

(Print table)

SABA (eg, albuterol, levalbuterol)
  • Mainstay of therapy for intermittent disease
  • Via nebulizer (eg, 0.083% albuterol solution) or metered-dose inhaler (MDI) (90 mcg/puff)
  • For symptoms: PRN
  • For exacerbation: 4-8 puffs every 20 min x 3, then Q1-4H PRN
Anticholinergic bronchodilators (eg, ipratropium)
  • Adjunct to beta-agonists
  • Via nebulizer (0.03% solution), or MDI (18 mcg/puff,
    2 puffs), 4-8 puffs every 20 minutes for up to 3 hours
Systemic corticosteroids (prednisone or equivalent)
  • For mild exacerbation, prednisone 40-60 mg QD for 5-10 days
  • For more severe exacerbations, prednisone 40-80 mg QD until PEFR reaches 70% personal best/predicted
  • Methylprednisolone 60-125 mg IV Q6-12H for severe exacerbations
For long-term control
Inhaled corticosteroids (ICS); in order of increasing potency (on mg per mg basis):
  • Triamcinolone = flunisolide
  • Beclomethasone = budesonide
  • Fluticasone
  • Mainstay of therapy for mild disease or greater
  • See Pharmacy Benefits Management for dosing summary
  • Start with beclomethasone 200 mcg BID or equivalent
  • Use lowest dose consistent with disease control
  • Adding LABA is superior to doubling ICS dose
  • Caution with PIs: see chart below for interactions
LABA (eg, formoterol, salmeterol)
  • Not appropriate for monotherapy; may mask exacerbation
  • Administer via dry powder inhaler (DPI)
  • Dosage: formoterol 12 mcg Q12H; salmeterol 50 mcg Q12H
Leukotriene receptor antagonists (eg, montelukast, zafirlukast)
  • Potential alternative to low-dose ICS for patients with mild asthma unable to use MDI or DPI, or as adjunct to ICS for patients with moderate persistent asthma
  • Montelukast has not been shown to inhibit CYP 3A4, whereas zafirlukast may inhibit CYP 3A4 and 2C9, potentially interacting with PIs
Mast cell inhibitors (cromolyn, nedocromil)
  • Potential alternative to low-dose ICS for patients with mild asthma unable to use MDI or DPI, or as adjunct for ICS in patients with moderate persistent asthma
  • Dosage: 2 puffs QID
Theophylline
  • Use discouraged because of drug-drug interactions and narrow therapeutic index
  • Use only with patients who are refractory to other recommended treatments and show clinical benefit
  • Dose using extended-release form; follow levels closely (target level 5-15 mcg/mL)
  • Initial dosage: 300 mg QD in 2-3 divided doses; a dose increase of 1 mg/kg will increase levels by 2 mcg/mL
  • Decrease by 50% in patients with liver dysfunction
Omalizumab
  • Reserved for patients with elevated serum IgE
  • Use restricted to Pulmonary or Allergy/Immunology services
Oral corticosteroids
  • 7.5-60 mg QD (or dosed QOD to decrease adrenal suppression)
For prevention of exercise-induced bronchospasm
  • Use SABA just before exercise; alternatively, use LABA 15 minutes (formoterol) or 30 minutes (salmeterol) before exercise
Table 4: Potential ARV Interactions

(Print table)

Inhaled Corticosteroids

Fluticasone:

  • PIs: caution: ↑ serum fluticasone levels; can cause systemic corticosteroid side effects, including Cushing syndrome
    • Avoid (or limit) use with RTV, particularly in the LPV/r, ATV/r, and DRV/r combinations
    • Even boosting dosages of RTV (eg, 100 mg BID) may ↑ serum fluticasone Cmax by 2,500%
    • ATV: can ↑ fluticasone levels - use with caution
    • It is unclear whether significant interactions occur between other inhaled steroids and PIs
  • NRTIs, NNRTIs: no significant interactions expected

Long-Acting Beta Agonists

  • CYP 3A4 inhibitors such as RTV may ↑ salmeterol levels

Theophylline

  • RTV: ↓ theophylline AUC
  • IDV: small ↑ in theophylline AUC
  • Monitor and adjust theophylline dosing as needed

Leukotriene receptor antagonists

  • Zafirlukast may inhibit CYP 3A4 and 2C9, potentially interacting with PIs (no formal studies); monitor clinically for adverse effects. Montelukast has not been shown to inhibit CYP 3A4.

References