ASTHMA























  • Reference [2,15]
Differential diagnosis for asthma symptoms
0 - 11 years old
  • Allergic rhinitis and sinusitis
  • Aspiration from swallowing mechanism dysfunction or gastroesophageal reflux
  • Bronchiectasis - recurrent infections, productive cough
  • Bronchopulmonary dysplasia - preterm delivery, symptoms since birth
  • Congenital heart disease - cardiac murmurs
  • Cystic fibrosis - excessive cough and mucus production, gastrointestinal symptoms
  • Enlarged lymph nodes or tumor
  • Inhaled foreign body - sudden onset of symptoms, unilateral wheeze
  • Laryngotracheomalacia, tracheal stenosis, or bronchostenosis
  • Primary ciliary dyskinesia - recurrent infections, productive cough, sinusitis
  • Tuberculosis - chronic cough, hemoptysis, dyspnea, fatigue, fever, (night) sweats, anorexia, weight loss
  • Vascular rings or laryngeal webs
  • Viral bronchiolitis or obliterative bronchiolitis
  • Vocal cord dysfunction
≥ 12 years old
  • Allergic rhinitis and sinusitis
  • Alpha 1-antitrypsin deficiency - shortness of breath, family history of early emphysema
  • Bronchiectasis - productive cough, recurrent infections
  • Chronic upper airway cough syndrome - sneezing, itching, blocked nose, throat-clearing
  • Congenital heart disease - cardiac murmurs
  • Congestive heart failure
  • COPD - cough, sputum, dyspnea on exertion, smoking or noxious exposure
  • Cystic fibrosis - excessive cough and mucus production
  • Hyperventilation, dysfunctional breathing - dizziness, paresthesia, sighing
  • Inducible laryngeal obstruction - dyspnea, inspiratory wheezing (stridor)
  • Mechanical obstruction of the airways (benign and malignant tumors)
  • Medications (e.g., angiotensin-converting enzyme (ACE) inhibitors)
  • Parenchymal lung disease - dyspnea with exertion, non-productive cough, finger clubbing
  • Pulmonary embolism - sudden onset of dyspnea, chest pain
  • Pulmonary infiltration with eosinophilia
  • Tuberculosis - chronic cough, hemoptysis, dyspnea, fatigue, fever, (night) sweats, anorexia, weight loss
  • Vocal cord dysfunction




  • Reference [2,15]
Spirometry measures
Normal spirometry
  • FEV1 / FVC ratio
    • 8 - 19 years: 85%
    • 20 - 39 years: 80%
    • 40 - 59 years: 75%
    • 60 - 80 years: 70%
  • Predicted FEV1
    • Predicted FEV1 is based on a person's age, sex, height, weight, and ethnicity
    • An online calculator is available here - online FEV1 calculator
Asthma (reactive airway disease)
  • 1. Confirm that FEV1 and FEV1 / FVC ratio is reduced
  • 2. 10 - 15 minutes after the inhalation of a short-acting bronchodilator (e.g. albuterol, 2-4 puffs), there should be an increase in FEV1 of > 200 ml and ≥ 12% from baseline
Exercise-induced asthma (EIA)
  • For patients suspected of having exercise-induced asthma, a protocol that involves exercise before spirometry should be performed
  • These protocols typically involve around 6 - 10 minutes of exercise on a stationary bike or treadmill before testing
  • Spirometry is considered positive for EIA if the following is seen:
    • Adults: Fall in FEV1 of > 10% and > 200 ml from baseline
    • Children: Fall in FEV1 of > 12% of predicted
Bronchoprovocation test
  • Bronchoprovocation testing involves administering an agent that is known to provoke asthma symptoms before performing spirometry
  • Common provoking agents that are used include methacholine, histamine, hypertonic saline, mannitol, and cold air. Hyperventilation may also be used to provoke symptoms.
  • Spirometry is considered positive for bronchoprovocation if the following is seen:
    • Adults: Fall in FEV1 from baseline of ≥ 20% with standard doses of methacholine or histamine, or ≥ 15% with standardized hyperventilation, hypertonic saline or mannitol challenge
Patients using inhalers
  • For patients who are already using inhalers, SABA should be held for at least 4 hours before spirometry testing and LABA should be held for 12 - 24 hours depending on the duration of action

  • NOTE: Values are for persistent asthma
  • Intermittent asthma should have normal values in between exacerbations
  • Reference [2]
Asthma severity based on spirometry findings
Ages 5 - 11 years
Mild Moderate Severe
FEV1 ≥ 80% of predicted 61 - 79% of predicted ≤ 60% of predicted
FEV1 / FVC > 80% 75 - 80% < 75%
Age ≥ 12 years
Mild Moderate Severe
FEV1 ≥ 80% of predicted 61 - 79% of predicted ≤ 60% of predicted
FEV1 / FVC normal reduced ≤ 5% reduced > 5%












  • Reference [16]
NHLBI 2020 Asthma Treatment Recommendations (0 - 4 years of age)
  • Proceed to next step if no clear benefit after 4 - 6 weeks
  • Inadequate control generally defined as increasing use of SABA or use of SABA > 2 times per week (excluding EIA)
  • See ICS dosing for low, medium, high dosing
Step Treatment
Step 1
  • SABA as needed
  • At start of URI: short course of ICS and SABA as needed
Step 2 Preferred
  • Daily low-dose ICS and SABA as needed

Alternative
  • Daily LTRA and SABA as needed
Step 3 Preferred (one of the following)
  • Daily low-dose ICS + either LABA or LTRA and SABA as needed
  • Daily medium-dose ICS and SABA as needed
Step 4 Preferred
  • Daily medium-dose ICS + LABA and SABA as needed

Alternative
  • Daily medium-dose ICS + LTRA and SABA as needed
Step 5 Preferred
  • Daily high-dose ICS + LABA and SABA as needed

Alternative
  • Daily high-dose ICS + LTRA and SABA as needed
Step 6 Preferred
  • Daily high-dose ICS + LABA + oral systemic corticosteroid and SABA as needed

Alternative
  • Daily high-dose ICS + LTRA + oral systemic corticosteroid and SABA as needed

  • Reference [16]
NHLBI 2020 Asthma Treatment Recommendations (5 - 11 years of age)
  • Proceed to next step if no clear benefit after 4 - 6 weeks
  • Inadequate control generally defined as increasing use of SABA or use of SABA > 2 times per week (excluding EIA)
  • See ICS dosing for low, medium, high dosing
Step Treatment
Step 1
  • SABA as needed
Step 2 Preferred
  • Daily low-dose ICS and SABA as needed

Alternative
  • Daily LTRA and SABA as needed
Step 3 Preferred
  • Daily and as needed combination low-dose ICS/formoterol
  • As needed ICS/formoterol is defined as 2 puffs every 4 hours as needed up to a maximum of 8 puffs per day

Alternative (one of the following)
  • Daily medium-dose ICS and SABA as needed
  • Daily low-dose ICS + LABA or LTRA and SABA as needed
Step 4 Preferred
  • Daily and as needed combination medium-dose ICS/formoterol
  • As needed ICS/formoterol is defined as 2 puffs every 4 hours as needed up to a maximum of 8 puffs per day

Alternative (one of the following)
  • Daily medium-dose ICS + LABA and SABA as needed
  • Daily medium-dose ICS + LTRA and SABA as needed
Step 5 Preferred
  • Daily high-dose ICS + LABA and SABA as needed

Alternative
  • Daily high-dose ICS + LTRA and SABA as needed
Step 6 Preferred
  • Daily high-dose ICS + LABA + oral systemic corticosteroid and SABA as needed

Alternative
  • Daily high-dose ICS + LTRA + oral systemic corticosteroid and SABA as needed

  • Reference [18]
NHLBI 2020 Asthma Treatment Recommendations (≥ 12 years of age)
  • Proceed to next step if no clear benefit after 2 - 6 weeks
  • Inadequate control generally defined as increasing use of SABA or use of SABA > 2 times per week (excluding EIA)
  • See ICS dosing for low, medium, high dosing
Step Treatment
Step 1
  • SABA as needed
Step 2 Preferred (one of the following)
  • Daily low-dose ICS and SABA as needed
  • As needed concomitant ICS and SABA

Alternative
  • Daily LTRA and SABA as needed
Step 3 Preferred
  • Daily and as needed combination low-dose ICS/formoterol (as needed ICS/formoterol is defined as 2 puffs every 4 hours as needed up to a maximum of 10 puffs per day)

Alternative (one of the following)
  • Daily medium-dose ICS and SABA as needed
  • Daily low-dose ICS + LABA and SABA as needed
  • Daily low-dose ICS + LAMA and SABA as needed
  • Daily low-dose ICS + LTRA and SABA as needed
Step 4 Preferred
  • Daily and as needed combination medium-dose ICS/formoterol (as needed ICS/formoterol is defined as 2 puffs every 4 hours as needed up to a maximum of 10 puffs per day)

Alternative (one of the following)
  • Daily medium-dose ICS + LABA and SABA as needed
  • Daily medium-dose ICS + LAMA and SABA as needed
Step 5 Preferred
  • Daily medium-to-high dose ICS + LABA + LAMA and SABA as needed

Alternative (one of the following)
  • Daily medium-to-high-dose ICS + LABA and SABA as needed
  • Daily high-dose ICS + LTRA and SABA as needed
  • Consider adding biologic. See severe asthma below.
Step 6
  • Daily high-dose ICS + LABA + oral corticosteroids and SABA as needed
  • Consider adding biologic. See severe asthma below.

  • Reference [2,6]
Treatment recommendations for exercise-induced asthma
Step 1
  • SABA 5 - 20 minutes before exercise (effective in up to 80% of patients)
  • If symptoms not controlled during exercise, then proceed to Step 2
Step 2
  • Add one of the following:
    • Cromolyn sodium before exercise
    • Anticholinergic before exercise
    • LABAs can be protective for up to 12 hours (NOTE: LABAs will have shortened duration of effectiveness if used daily)
    • If symptoms occur daily, then proceed to Step 3
Step 3
  • Add one of the following:
    • Daily ICS +/- LABA
    • Daily LTRA (effective in up to 50% of patients)
Nonpharmacological treatment
  • A warm-up period before exercise may reduce the degree of symptoms
  • A mask or scarf over the mouth may attenuate cold-induced symptoms




  • Reference [15,16]
Allergen Mitigation Strategies
House dust mites
  • Encase bedding in impermeable covers
  • Wash bedding on hot cycle (55–60°C) Replace carpets with hard flooring
  • Acaricides and/or tannic acid Minimize objects that accumulate dust
  • Vacuum cleaners with integral HEPA filter and double-thickness bags
  • Remove, hot wash, or freeze soft toys
Pets
  • Remove cat/dog from the home
  • Keep pet from the main living areas/bedrooms
  • HEPA-filter air cleaners
  • Wash pet
  • Replace carpets with hard flooring
  • Vacuum cleaners with integral HEPA filter and double-thickness bags
Cockroaches
  • Bait plus professional extermination of cockroaches
  • Baits placed in households
Fungi
  • Remediation of dampness or mold in homes
  • Air filters, air conditioning









  • Reference [15,16,17]
Asthma immunomodulator therapy recommendations
Therapies
Indications for IL-5 inhibitor therapy
  • ATS - Blood eosinophil count ≥ 150 cells/mcL and prior exacerbations
  • GINA - Blood eosinophil count ≥ 300 cells/mcL and exacerbations in last year
  • Manufacturer package insert/studies
    • Benralizumab (Fasenra®) - blood eosinophil count ≥ 300 cells/mcL
    • Mepolizumab (Nucala®) - blood eosinophils ≥ 150 cells/mcL within 6 weeks of dosing or ≥ 300 cells/mcL within 12 months of enrollment
    • Reslizumab (Cinqair®) - blood eosinophil count ≥ 400 cells/mcL
Indications for IgE inhibitor therapy
  • ATS - Blood eosinophil count ≥ 260 cells/mcL or FeNO ≥ 19.5 ppb
  • GINA - Sensitization on skin prick testing or specific IgE + total serum IgE and weight within dosage range + exacerbations in the last year
  • Omalizumab (Xolair®) package insert - patients who have a positive skin test or in vitro reactivity to a perennial aeroallergen and whose symptoms are inadequately controlled with inhaled corticosteroids
Indications for IL-4/IL-13 inhibitor therapy
  • ATS - adult patients with severe eosinophilic asthma, and for those with severe corticosteroid-dependent asthma regardless of eosinophil levels
  • GINA - Blood eosinophils ≥ 150 cells/mcL or FeNO ≥ 25 ppb + exacerbations in the last year
  • Dupilumab (Dupixent®) package insert - asthma with eosinophilic phenotype or oral corticosteroid dependent asthma


















ICS/LABA AS NEEDED STUDIES
Budesonide-formoterol as needed vs Daily Budesonide and Terbutaline as needed, Lancet (2019) [PubMed abstract]
  • Design: Randomized open-label trial (N=890 | length = 52 weeks) in adults with asthma
  • Treatment: Budesonide 200 μg-formoterol 6 μg one inhalation as needed vs Budesonide 200 μg one inhalation twice daily plus terbutaline 250 μg as needed
  • Primary outcome: Number of severe exacerbations per patient per year (severe exacerbations defined as use of systemic corticosteroids for at least 3 days because of asthma, or admission to hospital or an emergency department visit because of asthma requiring systemic corticosteroids
  • Results:
    • Primary outcome: Budesonide-formoterol - 0.119/patient/year, Budesonide-terbutaline - 0.172/patient/year (p=0.49)
  • Findings: In adults with mild to moderate asthma, budesonide-formoterol used as needed for symptom relief was more effective at preventing severe exacerbations than maintenance low-dose budesonide plus as-needed terbutaline. The findings support the 2019 Global Initiative for Asthma recommendation that inhaled corticosteroid-formoterol reliever therapy is an alternative regimen to daily low-dose inhaled corticosteroid for patients with mild asthma.

Albuterol as needed vs Budesonide daily/Albuterol as needed vs Budesonide/Formoterol as needed in adults with mild asthma, NEJM (2019) [PubMed abstract]
  • Design: Randomized, open-label trial (N=668 | length = 52 weeks) in adults with mild asthma
  • Treatment: Albuterol as needed vs Budesonide Turbuhaler 200 mcg twice daily + Albuterol as needed vs Budesonide 200 mcg/Formoterol 6 mcg as needed
  • Primary outcome: Annualized rate of asthma exacerbations defined as worsening asthma that required any one of the following: urgent medical care, hospitalization, systemic steroids, ≥ 16 actuations of albuterol or ≥ 8 actuations of budesonide–formoterol over the course of 24 hours
  • Results:
    • Primary outcome (exacerbations/yr): Albuterol PRN - 0.40, Budesonide daily/Albuterol PRN - 0.175, Budesonide/Formoterol PRN - 0.195 (Albuterol vs others p <0.001 | Budesonide/Albuterol vs Budesonide/Formoterol p=0.65)
  • Findings: In an open-label trial involving adults with mild asthma, budesonide–formoterol used as needed was superior to albuterol used as needed for the prevention of asthma exacerbations.

Budesonide/Formoterol as needed vs Daily Budesonide for Preventing Asthma Exacerbations, NEJM (2018) [PubMed abstract]
  • Design: Randomized, placebo-controlled trial (N=4215 | length = 52 weeks) in patients ≥ 12 years old with mild asthma
  • Treatment: Budesonide/Formoterol at signs of exacerbation vs Maintenance Budesonide
  • Primary outcome: Annualized rate of severe exacerbations
  • Results:
    • Primary outcome (exacerbation/yr): Budesonide/Formoterol - 0.11, Maintenance budesonide - 0.12
  • Findings: In patients with mild asthma, budesonide-formoterol used as needed was noninferior to twice-daily budesonide with respect to the rate of severe asthma exacerbations during 52 weeks of treatment but was inferior in controlling symptoms. Patients in the budesonide-formoterol group had approximately one quarter of the inhaled glucocorticoid exposure of those in the budesonide maintenance group.

Quintupled ICS Dose vs Maintenance Dose at Signs of Exacerbation, NEJM (2018) [PubMed abstract]
  • Design: Randomized, placebo-controlled trial (N=254 | length = 48 weeks) in children with mild-to-moderate persistent asthma on ICS maintenance therapy
  • Treatment: Quintupled ICS Dose vs Normal Dose + Placebo for 7 days at signs of exacerbation
  • Primary outcome: Rate of severe asthma exacerbations treated with systemic glucocorticoids
  • Results:
    • Primary outcome (exacerbations/yr): Quintupled dose - 0.48, Placebo - 0.37 (p=0.30)
  • Findings: In children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma exacerbations or improve other asthma outcomes and may be associated with diminished linear growth.

Open-label Quadrupling ICS Dose vs Maintenance Dose at Signs of Exacerbation, NEJM (2018) [PubMed abstract]
  • Design: Randomized, open-label, pragmatic trial (N=1922 | length = 12 months) in adults and adolescents with asthma on ICS maintenance therapy
  • Treatment: Quadrupled ICS Dose vs Maintenance Dose at signs of exacerbation
  • Primary outcome: Time to first severe asthma exacerbation, defined as treatment with systemic glucocorticoids or an unscheduled health care consultation for asthma
  • Results:
    • Primary outcome (severe exacerbation): Quadrupled dose - 45%, Maintenance dose - 52% (p=0.002)
  • Findings: In this trial involving adults and adolescents with asthma, a personalized self-management plan that included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate resulted in fewer severe asthma exacerbations than a plan in which the dose was not increased

ICS vs other

LABA/ICS vs Doubling ICS in Children with Symptomatic Asthma, Am J Respir Crit Care Med (2010) [PubMed abstract]
  • Design: Randomized, controlled trial (N=158 | length = 26 weeks) in children with symptomatic asthma on Fluticasone 100 twice a day
  • Treatment: Salmeterol/Fluticasone 50/100 twice a day vs Fluticasone 200 twice a day
  • Primary outcome: Percentage of symptom-free days during the last 10 weeks of the treatment. Change in lung function measurements
  • Results:
    • Percentage of symptom-free days during the last 10 weeks of the treatment period did not differ between treatment groups (per protocol analysis: adjusted mean difference 2.6%; 95% confidence interval, -8.1 to 13.4)
  • Findings: In our study, the efficacy on symptom control and lung function of the combination of a long-acting bronchodilator with inhaled corticosteroid is equal to doubling the dose of the inhaled corticosteroid in children still symptomatic on a moderate dose of inhaled corticosteroid.

ICS vs ICS/LABA vs ICS/LTRA in Children with Uncontrolled Asthma, NEJM (2010) [PubMed abstract]
  • Design: Randomized, crossover trial (N=182 | length = 16 weeks on each regimen) in children with uncontrolled asthma on Fluticasone 100 twice daily
  • Treatment: Fluticasone 250 twice daily vs Salmeterol/Fluticasone 50/100 twice daily vs Fluticasone 100 twice daily + Montelukast 5 - 10 mg once daily
  • Primary outcome: The primary outcome was the differential response to each of the three step-up therapies on the basis of fixed threshold criteria for the following three asthma-control measures: the need for treatment with oral prednisone for acute asthma exacerbations, the number of asthma control days, and the FEV1.
  • Results:
    • Salmeterol/Fluticasone was more likely to be the best response when compared to Fluticasone (p-value=0.002) and Fluticasone + Montelukast (p-value=0.004)
    • There was no significant difference between Fluticasone and Fluticasone + Montelukast
    • White race predicted a better response to Salmeterol/Fluticasone
    • Black patients were least likely to have a best response to Fluticasone + Montelukast
  • Findings: Nearly all the children had a differential response to each step-up therapy. LABA step-up was significantly more likely to provide the best response than either ICS or LTRA step-up. However, many children had a best response to ICS or LTRA step-up therapy, highlighting the need to regularly monitor and appropriately adjust each child's asthma therapy.

LAMA studies

LABA + ICS vs LABA + ICS + LAMA in Uncontrolled Asthmatics, Lancet (2019) [PubMed abstract]
  • Design: Randomized, controlled trial (N=2291 | length = 52 weeks) in adults with uncontrolled asthma
  • Treatment: LABA + ICS vs LABA + ICS + LAMA
  • Primary outcome: Pre-dose FEV1 at week 26 and rate of moderate and severe exacerbations over 52 weeks
  • Results:
    • Rate of moderate and severe exacerbation per person: LABA + ICS - 2.07, LABA + ICS + LAMA - 1.79 (p=0.0083)
  • Findings: In uncontrolled asthma, addition of a long-acting muscarinic antagonist to inhaled corticosteroid plus long-acting β2-agonist therapy improves lung function and reduces exacerbations

LABA vs LAMA added to ICS in Black Adults with Asthma, JAMA (2015) [PubMed abstract]
  • Design: Randomized, open-label trial (N=1070 | length = 18 months) in black adults with moderate to severe asthma
  • Treatment: Once-daily Tiotropium vs Twice-daily LABA in patients using an ICS
  • Primary outcome: Time to asthma exacerbation, defined as a worsening asthma event requiring oral or parenteral corticosteroids
  • Results:
    • Primary outcome (mean exacerbation/person-year): Tiotropium - 0.37, LABA - 0.42 (p=0.31)
    • There was no difference in change in FEV1 at 12 months
  • Findings: Among black adults with asthma treated with ICS, adding a LABA did not improve time to asthma exacerbation compared with adding tiotropium. These findings were not affected by polymorphisms at the Arg16Gly locus of ADRB2. These findings do not support the superiority of LABA + ICS compared with tiotropium + ICS for black patients with asthma.

LAMA vs Placebo Added to ICS/LABA in Uncontrolled Asthma, NEJM (2012) [PubMed abstract]
  • Design: Two randomized, placebo-controlled trials (N=912 | length = 48 weeks) in adults with uncontrolled asthma who were receiving an ICS and LABA
  • Treatment: Tiotropium 5 mcg once daily vs Placebo
  • Primary outcomes: Peak FEV1 response and the trough FEV1 response at week 24 and time to the first severe asthma exacerbation
  • Results:
    • The mean change in the peak FEV1 from baseline was greater with tiotropium than with placebo in the two trials: a difference of 86±34 ml in trial 1 (p=0.01) and 154±32 ml in trial 2 (p<0.001)
    • The addition of tiotropium increased the time to the first severe exacerbation (282 days vs. 226 days), with an overall reduction of 21% in the risk of a severe exacerbation (hazard ratio 0.79, p=0.03)
  • Findings: In patients with poorly controlled asthma despite the use of inhaled glucocorticoids and LABAs, the addition of tiotropium significantly increased the time to the first severe exacerbation and provided modest sustained bronchodilation.

LTRA studies

ICS vs ICS/LABA vs ICS/LTRA in Children with Uncontrolled Asthma, NEJM (2010) [PubMed abstract]
  • Design: Randomized, crossover trial (N=182 | length = 16 weeks on each regimen) in children with uncontrolled asthma on Fluticasone 100 twice daily
  • Treatment: Fluticasone 250 twice daily vs Salmeterol/Fluticasone 50/100 twice daily vs Fluticasone 100 twice daily + Montelukast 5 - 10 mg once daily
  • Primary outcome: The primary outcome was the differential response to each of the three step-up therapies on the basis of fixed threshold criteria for the following three asthma-control measures: the need for treatment with oral prednisone for acute asthma exacerbations, the number of asthma control days, and the FEV1.
  • Results:
    • Salmeterol/Fluticasone was more likely to be the best response when compared to Fluticasone (p-value=0.002) and Fluticasone + Montelukast (p-value=0.004)
    • There was no significant difference between Fluticasone and Fluticasone + Montelukast
    • White race predicted a better response to Salmeterol/Fluticasone
    • Black patients were least likely to have a best response to Fluticasone + Montelukast
  • Findings: Nearly all the children had a differential response to each step-up therapy. LABA step-up was significantly more likely to provide the best response than either ICS or LTRA step-up. However, many children had a best response to ICS or LTRA step-up therapy, highlighting the need to regularly monitor and appropriately adjust each child's asthma therapy.

LABA vs LTRA Added to ICS in Uncontrolled Asthma, BMJ (2003) [PubMed abstract]
  • Design: Randomized, placebo-controlled trial (N=1490 | length = 52 weeks) in patients with uncontrolled asthma
  • Treatment: Fluticasone 100 mcg twice daily + Montelukast 10 mg once daily or Salmeterol 50 mcg twice daily
  • Primary outcome: The primary endpoint was the percentage of patients with at least one asthma exacerbation. Asthma exacerbation was defined as worsening asthma requiring an unscheduled visit to a doctor, emergency department, or hospital or treatment with oral, intravenous, or intramuscular corticosteroids
  • Results:
    • Primary outcome: Montelukast - 20.1%, Salmeterol - 19.1% (diff 1%, 95%CI [-3.1% to 5%])
    • The Salmeterol group had a significantly greater increase in FEV₁ than the Montelukast group (p-value<0.001)
  • Findings: The addition of montelukast in patients whose symptoms remain uncontrolled by inhaled fluticasone could provide equivalent clinical control to salmeterol

Antibiotic studies

Azithromycin vs Placebo for Acute Asthma Exacerbation, JAMA Internal Medicine (2016) [PubMed abstract]
  • Design: Randomized, placebo-controlled trial (N=199 | length = 10 days) in patients presenting to the ER with acute asthma exacerbation
  • Treatment: Azithromycin 500 mg once daily for 3 days vs Placebo
  • Primary outcome: Diary card symptom score 10 days after randomization
  • Results:
    • Baseline diary card score: Azithromycin - 4.14, Placebo - 4.18
    • Primary outcome: Azithromycin - 2.09, Placebo - 2.20 (diff −0.166, 95%CI [−0.670 to 0.337])
  • Findings: In this randomized population, azithromycin treatment resulted in no statistically or clinically significant benefit. For each patient randomized, more than 10 were excluded because they had already received antibiotics.

Azithromycin vs Placebo for the Prevention of Asthma Exacerbations, Lancet (2017) [PubMed abstract]
  • Design: Randomized, placebo-controlled trial (N=420 | length = 48 weeks) in patients with uncontrolled asthma who were receiving an ICS and LABA
  • Treatment: Azithromycin 500 mg three times a week vs Placebo for 48 weeks
  • Primary outcome: Rate of total (severe and moderate) asthma exacerbations over 48 weeks and asthma quality of life
  • Results:
    • Asthma exacerbations per patient-year: Azithromycin 1.07, Placebo - 1.86 (p <0.0001)
    • Azithromycin significantly improved asthma-related quality of life
  • Findings: Adults with persistent symptomatic asthma experience fewer asthma exacerbations and improved quality of life when treated with oral azithromycin for 48 weeks. Azithromycin might be a useful add-on therapy in persistent asthma.