• SYMBICORT for asthma patients ≥12 years of age
  • SYMBICORT is NOT a rescue medication and does NOT replace fast-acting inhalers to treat acute symptoms.

SPEED AND CONTROL

See Asthma Safety Profile in asthma patients 12 years and older.

The majority of patients’ FEV1 improvement occurred at 15 minutes in asthma1-3

In patients ≥12 years of age with asthma taking SYMBICORT 160/4.5* (n=124) in Study 1, 79% of 2-hour postdose FEV1 improvement occurred at 15 minutes on day of randomization, 89% at week 2, and 90% at end of treatment1-3

Sustained improvement in lung function was demonstrated in asthma patients ≥12 years of age in a 12-week efficacy and safety study2,3

Patients saw sustained effect over 12 weeks2-3

Study 1: A 12-week efficacy and safety study of patients with moderate to severe asthma

SYMBICORT 160/4.5* significantly improved predose FEV1† (P <.05 vs budesonide, formoterol, and placebo) averaged over the course of the study, and also improved 12-hour average postdose FEV1† (P <.001 vs budesonide, formoterol, and placebo at week 2), coprimary endpoints3; 2-hour postdose FEV1† over 12 weeks was a secondary endpoint2

*Administered as 2 inhalations twice daily.

†As compared to baseline; baseline defined as the predose FEV1 value on day of randomization.

The most common adverse reactions ≥3% reported in asthma clinical trials included nasopharyngitis, headache, upper respiratory tract infection, pharyngolaryngeal pain, sinusitis, influenza, back pain, nasal congestion, stomach discomfort, vomiting, and oral candidiasis.

Study 1: A 12-week, double-blind, placebo-controlled study comparing SYMBICORT 160/4.5 mcg, budesonide 160 mcg, formoterol 4.5 mcg, the free combination of budesonide 160 mcg plus formoterol 4.5 mcg in separate inhalers, and placebo, each administered as 2 inhalations twice daily. A total of 596 patients (124 randomized to receive SYMBICORT) ≥12 years of age were evaluated. The study included a 2-week run-in period with budesonide 80 mcg, 2 inhalations twice daily. Most patients had moderate to severe asthma and were using moderate to high doses of inhaled corticosteroids (ICSs) prior to study entry. This study was designed to assess 2 primary endpoints. The first was predose FEV1 averaged over 12 weeks, and the second was 12-hour average postdose FEV1 at Week 2. Secondary efficacy variables included daytime and nighttime asthma symptom scores and daily rescue medication use (both recorded by patients in the electronic diary).

COMPARATOR ARMS

Mean change in 2-hour postdose FEV1 (mL/%) over 12 weeks:

Day of randomization

SYMBICORT 160/4.5 mcg: 420 mL/20.0%

Budesonide 160 mcg: 100 mL/4.4%

Formoterol 4.5 mcg: 420 mL/19.9%

Budesonide 160 mcg + formoterol 4.5 mcg: 410 mL/19.4%

Placebo: 90 mL/4.4%

2 weeks

SYMBICORT 160/4.5 mcg: 380 mL/18.6%

Budesonide 160 mcg: 120 mL/5.6%

Formoterol 4.5 mcg: 270 mL/12.8%

Budesonide 160 mcg + formoterol 4.5 mcg: 370 mL/18.0%

Placebo: 10 mL/1.2%

End of treatment

SYMBICORT 160/4.5 mcg: 420 mL/20.2%

Budesonide 160 mcg: 140 mL/6.5%

Formoterol 4.5 mcg: 260 mL/12.3%

Budesonide 160 mcg + formoterol 4.5 mcg: 410 mL/19.5%

Placebo: -10 mL/0.4%

FAST SYMPTOM CONTROL WITH SYMBICORT1,4

MEAN CHANGE FROM BASELINE* IN ALBUTEROL USE (%)

Change in Albuterol Use

Study 1: A 12-week efficacy and safety study of patients ≥12 years of age with moderate to severe asthma

SYMBICORT 160/4.5† provided a 70% reduction in albuterol use vs baseline within 1 day of the first dose and a 57% reduction over 12 weeks1,4

Rescue use within 1 day of first dose of SYMBICORT (n=120): Baseline*: 2.12; Treatment‡: 0.911,4

Rescue use over 12 weeks with SYMBICORT (n=121): Baseline*: 2.10; Treatment Average§: 1.091,4

The primary comparison for this secondary endpoint was SYMBICORT vs placebo over 12 weeks (P <.001)4¶

Study 2: A 12-week efficacy and safety study of patients ≥12 years of age with mild to moderate asthma

SYMBICORT 80/4.5† reduced rescue medication use by 51% vs baseline within 1 day of the first dose and 67% over 12 weeks1,4

Onset of Effect Questionnaire

Study 1: A subset of patients ≥18 years of age with moderate to severe asthma completed a 5-item Onset of Effect Questionnaire

In this subset, a significantly greater percentage of patients taking SYMBICORT 160/4.5† compared with placebo patients felt their medication started working right away at week 1 (69.1% [n=65/94]) versus placebo (23.3% [n=21/90], P <0.001)5,6

Results at the end of treatment (Week 12) remained statistically significant (P <0.001)5,6

SYMBICORT is NOT a rescue medication and does NOT replace fast-acting inhalers to treat acute symptoms

*Baseline is defined as the mean of all values obtained during the run-in period. During run-in, patients received budesonide 80 mcg administered as 2 inhalations twice daily and albuterol as a rescue medication.

†Administered as 2 inhalations twice daily.

‡Treatment is the mean value in puffs/day of albuterol used within 1 day of the first dose of SYMBICORT.

§Treatment Average is defined as the mean of all values obtained during the double-blind treatment period in puffs/day of albuterol.

IIAssessed using the Onset of Effect Questionnaire.

P values based on treatment comparison of absolute mean change from baseline for SYMBICORT vs budesonide and placebo.

Study 1: A 12-week, double-blind, placebo-controlled study comparing SYMBICORT 160/4.5 mcg, budesonide 160 mcg, formoterol 4.5 mcg, the free combination of budesonide 160 mcg plus formoterol 4.5 mcg in separate inhalers, and placebo, each administered as 2 inhalations twice daily. A total of 596 patients (124 randomized to receive SYMBICORT) ≥12 years of age were evaluated. The study included a 2-week run-in period with budesonide 80 mcg, 2 inhalations twice daily. Most patients had moderate to severe asthma and were using moderate to high doses of ICS prior to study entry. This study was designed to assess 2 primary endpoints. The first was predose FEV1 averaged over 12 weeks, and the second was 12-hour average postdose FEV1 at Week 2. Secondary efficacy variables included daytime and nighttime asthma symptom scores, daily rescue medication use (both recorded by patients in the electronic diary), and percent of patients who experienced a predefined asthma event.

Study 2: A 12-week, randomized, multicenter, double-blind, double-dummy, placebo-controlled study comparing SYMBICORT 80/4.5 mcg, budesonide 80 mcg, formoterol 4.5 mcg, each administered as 2 inhalations twice daily. A total of 480 patients (123 randomized to receive SYMBICORT) ≥12 years of age were evaluated. The study included a 2-week run-in period with placebo and rescue albuterol therapy. Most patients had mild to moderate persistent asthma and were using low to moderate doses of ICS either alone or as part of combination therapy prior to study entry. This study was designed to assess 2 primary endpoints. The first was predose FEV1 averaged over 12 weeks, and the second was 12-hour average postdose FEV1 at Week 2. Secondary efficacy variables included daytime and nighttime asthma symptom scores, daily rescue medication use (both recorded by patients in the electronic diary), and percent of patients who experienced a predefined asthma event.

Mean change from baseline in albuterol use within 1 day of the first dose of study treatment

SYMBICORT 160/4.5 mcg: -70% (n=120)

Budesonide 160 mcg: -14% (n=105)

Formoterol 4.5 mcg: -50% (n=117)

Budesonide 160 mcg + formoterol 4.5 mcg: -70% (n=112)

Placebo: -8% (n=122)

Mean change from baseline in albuterol use over 12 weeks

SYMBICORT 160/4.5 mcg: -57% (n=121)

Budesonide 160 mcg: -19% (n=109)

Formoterol 4.5 mcg: -22% (n=119)

Budesonide 160 mcg + formoterol 4.5 mcg: -67% (n=113)

Placebo: 29% (n=124)

Onset of Effect Questionnaire (OEQ): A subset of patients ≥18 years of age was assessed on a weekly basis using the OEQ, administered through an electronic diary to record patients’ responses to 5 statements concerning onset of medication. Responses to OEQ items were analyzed at the end of Week 1 of treatment and at end of treatment (last assessment while on treatment), with the end of Week 1 prespecified as the primary time point to assess patient perception of onset associated with treatment initiation. A responder analysis was conducted for the OEQ, with patient responses of “strongly agree” and “somewhat agree” prespecified as a yes response and responses of “neither agree or disagree,” “somewhat disagree,” and “strongly disagree” prespecified as a no response.

*Patients were considered to have experienced a “predefined asthma event” if any of the following conditions occurred at any time during the study:

  1. At any visit or follow-up visit, a decrease in morning predose FEV1 ≥20% from the Visit 2 (randomization visit) morning predose FEV1 or a decrease to <40% (Study 1) or <45% (Study 2) of predicted normal value.
  2. The use of ≥12 actuations of albuterol per day on 3 or more days within any period of 7 consecutive days after randomization.
  3. A decrease in morning PEF ≥20% from baseline (defined as the mean of all values from the 7-day period immediately preceding Visit 2 [randomization visit]) on 3 or more days within any period of 7 consecutive days after randomization.
  4. Two or more nights with an awakening due to asthma, which required the use of, rescue medication within any period of 7 consecutive days after randomization.
  5. A clinical exacerbation requiring emergency treatment, hospitalization, or use of an asthma medication not allowed by the protocol.

ASTHMA CONTROL IN SYMBICORT STUDIES1,7

In Studies 1 and 2, significantly more patients taking SYMBICORT* did not have a predefined asthma event† vs placebo over 12 weeks1,7

 
 
 
 
 
 

Individual components are combined for patients with moderate to severe asthma receiving SYMBICORT 160/4.5* in Study 1 (n=124) and for patients with mild to moderate asthma receiving SYMBICORT 80/4.5* in Study 2 (n=123)1,7

 

National institutes of health defines control in terms of risk and impairment8

For more information, click here

SYMBICORT is NOT a rescue medication and does NOT replace fast-acting inhalers to treat acute symptoms

*Administered as 2 inhalations twice daily.

†Predefined asthma event criteria were a clinically important decrease in FEV1 or PEF, increase in rescue albuterol use, nighttime awakening due to asthma, emergency intervention or hospitalization due to asthma, or requirement for asthma medication not allowed by the protocol.

‡OCS was one of the asthma medications that were not allowed by the protocol.

Study 1: A 12-week, double-blind, placebo-controlled study comparing SYMBICORT 160/4.5 mcg, budesonide 160 mcg, formoterol 4.5 mcg, the free combination of budesonide 160 mcg plus formoterol 4.5 mcg in separate inhalers, and placebo, each administered as 2 inhalations twice daily. A total of 596 patients (124 randomized to receive SYMBICORT) ≥12 years of age were evaluated. The study included a 2-week run-in period with budesonide 80 mcg, 2 inhalations twice daily. Most patients had moderate to severe asthma and were using moderate to high doses of ICS prior to study entry. This study was designed to assess 2 primary endpoints. The first was predose FEV1 averaged over 12 weeks, and the second was 12-hour average postdose FEV1 at Week 2. Secondary efficacy variables included daytime and nighttime asthma symptom scores, daily rescue medication use (both recorded by patients in the electronic diary), and percent of patients who experienced a predefined asthma event.

COMPARATOR ARMS

Percent of patients who did not have a predefined asthma event*

SYMBICORT 160/4.5 mcg: 70.2% (87/124)

Budesonide 160 mcg: 56% (61/109)

Formoterol 4.5 mcg: 44.7% (55/123)

Budesonide 160 mcg + formoterol 4.5 mcg: 79.1% (91/115)

Placebo: 32.8% (41/125)

The primary comparison was between SYMBICORT and placebo. SYMBICORT 160/4.5 mcg vs placebo (P <0.001).

Study 2: A 12-week, randomized,multicenter, double-blind, double-dummy, placebo-controlled study comparing SYMBICORT 80/4.5 mcg, budesonide 80 mcg, formoterol 4.5 mcg, each administered as 2 inhalations twice daily. A total of 480 patients (123 randomized to receive SYMBICORT) ≥12 years of age were evaluated. The study included a 2-week run-in period with placebo and rescue albuterol therapy. Most patients had mild to moderate persistent asthma and were using low to moderate doses of ICS either alone or as part of combination therapy prior to study entry. This study was designed to assess 2 primary endpoints. The first was predose FEV1 averaged over 12 weeks, and the second was 12-hour average postdose FEV1 at Week 2. Secondary efficacy variables included daytime and nighttime asthma symptom scores, daily rescue medication use (both recorded by patients in the electronic diary), and percent of patients who experienced a predefined asthma event.

COMPARATOR ARMS

Percent of patients who did not have a predefined asthma event*

SYMBICORT 80/4.5 mcg: 81.3% (100/123)

Budesonide 80 mcg: 78.5% (95/121)

Formoterol 4.5 mcg: 57.9% (66/114)

Placebo: 43.4% (53/122)

The primary comparison was between SYMBICORT and placebo. SYMBICORT 80/4.5 mcg vs placebo (P <0.001).

*Patients were considered to have experienced a “predefined asthma event” if any of the following conditions occurred at any time during the study:

  1. At any visit or follow-up visit, a decrease in morning predose FEV1 ≥20% from the Visit 2 (randomization visit) morning predose FEV1 or a decrease to <40% (Study 1) or <45% (Study 2) of predicted normal value.
  2. The use of ≥12 actuations of albuterol per day on 3 or more days within any period of 7 consecutive days after randomization.
  3. A decrease in morning PEF ≥20% from baseline (defined as the mean of all values from the 7-day period immediately preceding Visit 2 [randomization visit]) on 3 or more days within any period of 7 consecutive days after randomization.
  4. Two or more nights with an awakening due to asthma, which required the use of, rescue medication within any period of 7 consecutive days after randomization.
  5. A clinical exacerbation requiring emergency treatment, hospitalization, or use of an asthma medication not allowed by the protocol.

SAFETY PROFILE FOR SYMBICORT IN ASTHMA

SYMBICORT for asthma patients ≥12 years of age uncontrolled on an ICS

SYMBICORT is NOT a rescue medication and does NOT replace fast-acting inhalers to treat acute symptoms.

Adverse reactions in clinical studies1 asthma patients ≥12 years of age

Adverse reactions occurring at an incidence of ≥3% and more commonly than placebo in the SYMBICORT groups1

Adverse Reactions in Asthma Studies in patients 12 years and olderAdverse Reactions in Asthma Studies in patients 12 years and older

*The incidence of adverse reactions in this table is based upon pooled data from three 12-week, double-blind, placebo-controlled US asthma clinical trials in patients aged 12 years and older.

†All treatments were administered as 2 inhalations twice daily.

LEARN ABOUT SYMBICORT FOR PEDIATRIC ASTHMA PATIENTS 6 TO <12 YEARS UNCONTROLLED ON AN ICS

LEARN ABOUT SYMBICORT FOR PEDIATRIC ASTHMA PATIENTS 6 TO <12 YEARS UNCONTROLLED ON AN ICS

See COPD safety profile

SYMBICORT 160/4.5 for maintenance treatment of COPD, and for reducing COPD exacerbations

NEXT:DOSING

IMPORTANT SAFETY INFORMATION -

  • Use of long-acting beta2-adrenergic agonists (LABA) as monotherapy (without inhaled corticosteroids [ICS]) for asthma is associated with an increased risk of asthma-related death. Available data from controlled clinical trials also suggest that use of LABA as monotherapy increases the risk of asthma-related hospitalization in pediatric and adolescent patients. These findings are considered a class effect of LABA. When LABA are used in fixed dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared to ICS alone
  • SYMBICORT is NOT a rescue medication and does NOT replace fast-acting inhalers to treat acute symptoms
  • SYMBICORT should not be initiated in patients during rapidly deteriorating episodes of asthma or COPD
  • Patients who are receiving SYMBICORT should not use additional formoterol or other LABA for any reason
  • Localized infections of the mouth and pharynx with Candida albicans has occurred in patients treated with SYMBICORT. Patients should rinse the mouth after inhalation of SYMBICORT
  • Lower respiratory tract infections, including pneumonia, have been reported following the administration of ICS
  • Due to possible immunosuppression, potential worsening of infections could occur. A more serious or even fatal course of chickenpox or measles can occur in susceptible patients
  • It is possible that systemic corticosteroid effects such as hypercorticism and adrenal suppression may occur, particularly at higher doses. Particular care is needed for patients who are transferred from systemically active corticosteroids to ICS. Deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic corticosteroids to less systemically available ICS
  • Caution should be exercised when considering administration of SYMBICORT in patients on long-term ketoconazole and other known potent CYP3A4 inhibitors
  • As with other inhaled medications, paradoxical bronchospasm may occur with SYMBICORT
  • Immediate hypersensitivity reactions may occur, as demonstrated by cases of urticaria, angioedema, rash, and bronchospasm
  • Excessive beta-adrenergic stimulation has been associated with central nervous system and cardiovascular effects. SYMBICORT should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension
  • Long-term use of ICS may result in a decrease in bone mineral density (BMD). Since patients with COPD often have multiple risk factors for reduced BMD, assessment of BMD is recommended prior to initiating SYMBICORT and periodically thereafter
  • ICS may result in a reduction in growth velocity when administered to pediatric patients
  • Glaucoma, increased intraocular pressure, and cataracts have been reported following the administration of ICS, including budesonide, a component of SYMBICORT. Close monitoring is warranted in patients with a change in vision or history of increased intraocular pressure, glaucoma, or cataracts
  • In rare cases, patients on ICS may present with systemic eosinophilic conditions
  • SYMBICORT should be used with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, and in patients who are unusually responsive to sympathomimetic amines
  • Beta-adrenergic agonist medications may produce hypokalemia and hyperglycemia in some patients
  • The most common adverse reactions ≥3% reported in asthma clinical trials included nasopharyngitis, headache, upper respiratory tract infection, pharyngolaryngeal pain, sinusitis, pharyngitis, rhinitis, influenza, back pain, nasal congestion, stomach discomfort, vomiting, and oral candidiasis
  • The most common adverse reactions ≥3% reported in COPD clinical trials included nasopharyngitis, oral candidiasis, bronchitis, sinusitis, and upper respiratory tract infection
  • SYMBICORT should be administered with caution to patients being treated with MAO inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuation of such agents
  • Beta-blockers may not only block the pulmonary effect of beta-agonists, such as formoterol, but may produce severe bronchospasm in patients with asthma
  • ECG changes and/or hypokalemia associated with nonpotassium-sparing diuretics may worsen with concomitant beta-agonists. Use caution with the coadministration of SYMBICORT

IMPORTANT SAFETY INFORMATION

  • Use of long-acting beta2-adrenergic agonists (LABA) as monotherapy (without inhaled corticosteroids [ICS]) for asthma is associated with an increased risk of asthma-related death. Available data from controlled clinical trials also suggest that use of LABA as monotherapy increases the risk of asthma-related hospitalization in pediatric and adolescent patients. These findings are considered a class effect of LABA. When LABA are used in fixed dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared to ICS alone
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INDICATIONS

  1. SYMBICORT is indicated for the treatment of asthma in patients 6 years and older not adequately controlled on a long-term asthma-control medication such as an ICS or whose disease warrants initiation of treatment with both an ICS and LABA. (also see DOSAGE AND ADMINISTRATION).
  2. SYMBICORT 160/4.5 is indicated for the maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema, and to reduce COPD exacerbations.
  3. SYMBICORT is NOT indicated for the relief of acute bronchospasm.

Please see full Prescribing Information , including Patient Information.

You may report side effects related to AstraZeneca products .

References:

  1. SYMBICORT [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
  2. Data on File. US-98380. AstraZeneca Pharmaceuticals LP.
  3. Rennard SI, Tashkin DP, McElhattan J, et al. Efficacy and tolerability of budesonide/formoterol in one hydrofluoroalkane pressurized metered-dose inhaler in patients with chronic obstructive pulmonary disease: results from a 1-year randomized controlled clinical trial. Drugs. 2009;69(5):549-565.
  4. Data on File, REF-4960, AZPLP.
  5. Noonan M, Rosenwasser LJ, Martin P, O’Brien CD, O’Dowd L. Efficacy and safety of budesonide and formoterol in one pressurised metered-dose inhaler in adults and adolescents with moderate to severe asthma: a randomised clinical trial. Drugs. 2006;66(17):2235-2254.
  6. Data on File, REF-4962, AZPLP.
  1. Pearlman DS, Eckerwall G, McLaren J, et al. Efficacy and safety of budesonide/formoterol pMDI vs budesonide pMDI in asthmatic children (6-<12 years). Ann Allergy Asthma Immunol. 2017;118:489-499.
  2. Data on File, REF-12860, AZPLP.
  3. SYMBICORT [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
  4. Scichilone N, Benfante A, Bocchino M, et al. Which factors affect the choice of inhaler in chronic obstructive respiratory diseases? Pulm Pharmacol Ther. 2015;31:63-67.
  5. US Department of Health and Human Services. FDA, Combination products. Jurisdictional update: metered dose inhalers, spacers and other accessories. https://www.fda.gov/combination-products/jurisdictional-updates/jurisdictional-update-metered-dose-inhalers-spacers-and-other-accessories. Updated February 12, 2020. Accessed July 31, 2023.
  1. Rennard SI, Tashkin DP, McElhattan J, et al. Efficacy and tolerability of budesonide/formoterol in one hydrofluoroalkane pressurized metered-dose inhaler in patients with chronic obstructive pulmonary disease: results from a 1-year randomized controlled clinical trial. Drugs. 2009;69(5):549-565.
  2. Data on File, REF-4960, AZPLP.
  3. SYMBICORT [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
  4. Data on File, REF-16658, AZPLP.
  5. Data on File, REF-5076, AZPLP.
  6. Data on File, REF-5103, AZPLP.
  7. Data on File, REF-61427, AZPLP.
  1. SYMBICORT [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
  2. Data on File, REF-4962, AZPLP.
  3. Noonan M, Rosenwasser LJ, Martin P, O’Brien CD, O’Dowd L. Efficacy and safety of budesonide and formoterol in one pressurised metered-dose inhaler in adults and adolescents with moderate to severe asthma: a randomised clinical trial. Drugs. 2006;66(17):2235-2254.
  4. Data on File, REF-35897, AZPLP.
  5. Kaiser H, Parasuraman B, Boggs R, Miller CJ, Leidy NK, O’Dowd L. Onset of effect of budesonide and formoterol administered via one pressurized metered-dose inhaler in patients with asthma previously treated with inhaled corticosteroids. Ann Allergy Asthma Immunol. 2008;101:295-303.
  6. Data on File, REF-4989, AZPLP.
  7. Data on File, REF-85507, AZPLP.
  8. National Heart, Lung, and Blood Institute. Expert panel report 3: guidelines for the diagnosis and management of asthma—full report 2007. August 28, 2007. https://www.nhlbi.nih.gov/sites/default/files/media/docs/EPR-3_Asthma_Full_Report_2007.pdf. Accessed July 31, 2023.
  1. SYMBICORT [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
  2. US Department of Health and Human Services. FDA, Combination products. Jurisdictional update: metered dose inhalers, spacers and other accessories.https://www.fda.gov/combination-products/jurisdictional-updates/jurisdictional-update-metered-dose-inhalers-spacers-and-other-accessories Updated February 12, 2020. Accessed July 31, 2023. 
  3. Scichilone N, Benfante A, Bocchino M, et al. Which factors affect the choice of the inhaler in chronic obstructive respiratory diseases? Pulm Pharmacol Ther. 2015;31:63-67.