Effects of formoterol or salmeterol on impulse oscillometry in persistent asthma

Arvind Manoharan, Alexander von Wilamowitz-Moellendorff, Ashley Morrison, Brian J. Lipworth (Lead / Corresponding author)

Research output: Contribution to journalArticle

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Abstract

Background

Effects of small-particle long-acting β-agonists on the small airways have been poorly documented.
Objective

We used impulse oscillometry (IOS) to compare single and repeated dosing effects of small- and large-particle long-acting β-agonists.
Methods

After a 1- to 2-week run-in period, patients received either 12 μg of small-particle hydrofluoroalkane 134a–formoterol solution or 50 μg of large-particle salmeterol dry powder twice daily plus inhaled corticosteroid for 1 to 2 weeks with a 1- to 2-week washout period in between. Measurements were made over 60 minutes after the first and last doses.
Results

Sixteen patients completed the study as follows: mean age, 43 years; FEV1, 80%; forced midexpiratory flow between 25% and 75% of forced vital capacity (FEF25-75), 48%; total airway resistance at 5 Hz, 177%; peripheral airway resistance as the difference between 5 and 20 Hz, 0.18 kPa·L−1·s; Asthma Control Questionnaire score, 0.76; and inhaled corticosteroid dosage, 550 μg/d. There were significantly greater improvements with formoterol versus salmeterol in all IOS outcomes and FEF25-75, but not FEV1, at 5 minutes after the first dose, which were not sustained over 60 minutes. After the last dose, all IOS outcomes, but not FEV1 or FEF25-75, were significantly better with formoterol over the entire 60 minutes: mean difference at 60 minutes between formoterol and salmeterol in total airway resistance at 5 Hz, 7.50% (95% CI, 1.56% to 13.43%, P = .02); central airway resistance at 20 Hz, 5.37% (95% CI, 0.13% to 10.62%, P = .045); peripheral airway resistance as the difference between 5 and 20 Hz, 12.76% (95% CI, 1.28% to 24.24%, P = .03); reactance area under the curve, 19.46% (95% CI, 7.56% to 31.36%, P = .003); reactance at 5 Hz, 11.19% (95% CI, 4.62% to 17.76%, P = .002); and resonant frequency, 9.34% (95% CI, 3.21% to 15.47%, P = .005). Peak expiratory flow significantly improved to a similar degree with both drugs.
Conclusion

Significant improvements in IOS outcomes but not spirometry results occurred after chronic dosing with formoterol compared with salmeterol. This might reflect better deposition to the entire lung, including the small airways.
Original languageEnglish
Pages (from-to)727-733.e1
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume137
Issue number3
Early online date26 Jul 2015
DOIs
Publication statusPublished - Mar 2016

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Oscillometry
Airway Resistance
Asthma
HFA 134a
Vascular Resistance
Adrenal Cortex Hormones
Spirometry
Vital Capacity
Powders
Area Under Curve
Formoterol Fumarate
Salmeterol Xinafoate
Lung
Pharmaceutical Preparations

Cite this

Manoharan, Arvind ; von Wilamowitz-Moellendorff, Alexander ; Morrison, Ashley ; Lipworth, Brian J. / Effects of formoterol or salmeterol on impulse oscillometry in persistent asthma. In: Journal of Allergy and Clinical Immunology. 2016 ; Vol. 137, No. 3. pp. 727-733.e1.
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title = "Effects of formoterol or salmeterol on impulse oscillometry in persistent asthma",
abstract = "BackgroundEffects of small-particle long-acting β-agonists on the small airways have been poorly documented.ObjectiveWe used impulse oscillometry (IOS) to compare single and repeated dosing effects of small- and large-particle long-acting β-agonists.MethodsAfter a 1- to 2-week run-in period, patients received either 12 μg of small-particle hydrofluoroalkane 134a–formoterol solution or 50 μg of large-particle salmeterol dry powder twice daily plus inhaled corticosteroid for 1 to 2 weeks with a 1- to 2-week washout period in between. Measurements were made over 60 minutes after the first and last doses.ResultsSixteen patients completed the study as follows: mean age, 43 years; FEV1, 80{\%}; forced midexpiratory flow between 25{\%} and 75{\%} of forced vital capacity (FEF25-75), 48{\%}; total airway resistance at 5 Hz, 177{\%}; peripheral airway resistance as the difference between 5 and 20 Hz, 0.18 kPa·L−1·s; Asthma Control Questionnaire score, 0.76; and inhaled corticosteroid dosage, 550 μg/d. There were significantly greater improvements with formoterol versus salmeterol in all IOS outcomes and FEF25-75, but not FEV1, at 5 minutes after the first dose, which were not sustained over 60 minutes. After the last dose, all IOS outcomes, but not FEV1 or FEF25-75, were significantly better with formoterol over the entire 60 minutes: mean difference at 60 minutes between formoterol and salmeterol in total airway resistance at 5 Hz, 7.50{\%} (95{\%} CI, 1.56{\%} to 13.43{\%}, P = .02); central airway resistance at 20 Hz, 5.37{\%} (95{\%} CI, 0.13{\%} to 10.62{\%}, P = .045); peripheral airway resistance as the difference between 5 and 20 Hz, 12.76{\%} (95{\%} CI, 1.28{\%} to 24.24{\%}, P = .03); reactance area under the curve, 19.46{\%} (95{\%} CI, 7.56{\%} to 31.36{\%}, P = .003); reactance at 5 Hz, 11.19{\%} (95{\%} CI, 4.62{\%} to 17.76{\%}, P = .002); and resonant frequency, 9.34{\%} (95{\%} CI, 3.21{\%} to 15.47{\%}, P = .005). Peak expiratory flow significantly improved to a similar degree with both drugs.ConclusionSignificant improvements in IOS outcomes but not spirometry results occurred after chronic dosing with formoterol compared with salmeterol. This might reflect better deposition to the entire lung, including the small airways.",
author = "Arvind Manoharan and {von Wilamowitz-Moellendorff}, Alexander and Ashley Morrison and Lipworth, {Brian J.}",
note = "Supported by an unrestricted educational grant from Chiesi UK. B.J.L. has received funding from Chiesi UK for attending advisory boards. A.M. has received support from Chiesi UK to attend the 2014 European Respiratory Society Congress. Also, this study was supported by an unrestricted educational grant from Chiesi UK, who also supplied the small-particle formoterol and large-particle beclomethasone inhalers for the study",
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Effects of formoterol or salmeterol on impulse oscillometry in persistent asthma. / Manoharan, Arvind; von Wilamowitz-Moellendorff, Alexander; Morrison, Ashley; Lipworth, Brian J. (Lead / Corresponding author).

In: Journal of Allergy and Clinical Immunology, Vol. 137, No. 3, 03.2016, p. 727-733.e1.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effects of formoterol or salmeterol on impulse oscillometry in persistent asthma

AU - Manoharan, Arvind

AU - von Wilamowitz-Moellendorff, Alexander

AU - Morrison, Ashley

AU - Lipworth, Brian J.

N1 - Supported by an unrestricted educational grant from Chiesi UK. B.J.L. has received funding from Chiesi UK for attending advisory boards. A.M. has received support from Chiesi UK to attend the 2014 European Respiratory Society Congress. Also, this study was supported by an unrestricted educational grant from Chiesi UK, who also supplied the small-particle formoterol and large-particle beclomethasone inhalers for the study

PY - 2016/3

Y1 - 2016/3

N2 - BackgroundEffects of small-particle long-acting β-agonists on the small airways have been poorly documented.ObjectiveWe used impulse oscillometry (IOS) to compare single and repeated dosing effects of small- and large-particle long-acting β-agonists.MethodsAfter a 1- to 2-week run-in period, patients received either 12 μg of small-particle hydrofluoroalkane 134a–formoterol solution or 50 μg of large-particle salmeterol dry powder twice daily plus inhaled corticosteroid for 1 to 2 weeks with a 1- to 2-week washout period in between. Measurements were made over 60 minutes after the first and last doses.ResultsSixteen patients completed the study as follows: mean age, 43 years; FEV1, 80%; forced midexpiratory flow between 25% and 75% of forced vital capacity (FEF25-75), 48%; total airway resistance at 5 Hz, 177%; peripheral airway resistance as the difference between 5 and 20 Hz, 0.18 kPa·L−1·s; Asthma Control Questionnaire score, 0.76; and inhaled corticosteroid dosage, 550 μg/d. There were significantly greater improvements with formoterol versus salmeterol in all IOS outcomes and FEF25-75, but not FEV1, at 5 minutes after the first dose, which were not sustained over 60 minutes. After the last dose, all IOS outcomes, but not FEV1 or FEF25-75, were significantly better with formoterol over the entire 60 minutes: mean difference at 60 minutes between formoterol and salmeterol in total airway resistance at 5 Hz, 7.50% (95% CI, 1.56% to 13.43%, P = .02); central airway resistance at 20 Hz, 5.37% (95% CI, 0.13% to 10.62%, P = .045); peripheral airway resistance as the difference between 5 and 20 Hz, 12.76% (95% CI, 1.28% to 24.24%, P = .03); reactance area under the curve, 19.46% (95% CI, 7.56% to 31.36%, P = .003); reactance at 5 Hz, 11.19% (95% CI, 4.62% to 17.76%, P = .002); and resonant frequency, 9.34% (95% CI, 3.21% to 15.47%, P = .005). Peak expiratory flow significantly improved to a similar degree with both drugs.ConclusionSignificant improvements in IOS outcomes but not spirometry results occurred after chronic dosing with formoterol compared with salmeterol. This might reflect better deposition to the entire lung, including the small airways.

AB - BackgroundEffects of small-particle long-acting β-agonists on the small airways have been poorly documented.ObjectiveWe used impulse oscillometry (IOS) to compare single and repeated dosing effects of small- and large-particle long-acting β-agonists.MethodsAfter a 1- to 2-week run-in period, patients received either 12 μg of small-particle hydrofluoroalkane 134a–formoterol solution or 50 μg of large-particle salmeterol dry powder twice daily plus inhaled corticosteroid for 1 to 2 weeks with a 1- to 2-week washout period in between. Measurements were made over 60 minutes after the first and last doses.ResultsSixteen patients completed the study as follows: mean age, 43 years; FEV1, 80%; forced midexpiratory flow between 25% and 75% of forced vital capacity (FEF25-75), 48%; total airway resistance at 5 Hz, 177%; peripheral airway resistance as the difference between 5 and 20 Hz, 0.18 kPa·L−1·s; Asthma Control Questionnaire score, 0.76; and inhaled corticosteroid dosage, 550 μg/d. There were significantly greater improvements with formoterol versus salmeterol in all IOS outcomes and FEF25-75, but not FEV1, at 5 minutes after the first dose, which were not sustained over 60 minutes. After the last dose, all IOS outcomes, but not FEV1 or FEF25-75, were significantly better with formoterol over the entire 60 minutes: mean difference at 60 minutes between formoterol and salmeterol in total airway resistance at 5 Hz, 7.50% (95% CI, 1.56% to 13.43%, P = .02); central airway resistance at 20 Hz, 5.37% (95% CI, 0.13% to 10.62%, P = .045); peripheral airway resistance as the difference between 5 and 20 Hz, 12.76% (95% CI, 1.28% to 24.24%, P = .03); reactance area under the curve, 19.46% (95% CI, 7.56% to 31.36%, P = .003); reactance at 5 Hz, 11.19% (95% CI, 4.62% to 17.76%, P = .002); and resonant frequency, 9.34% (95% CI, 3.21% to 15.47%, P = .005). Peak expiratory flow significantly improved to a similar degree with both drugs.ConclusionSignificant improvements in IOS outcomes but not spirometry results occurred after chronic dosing with formoterol compared with salmeterol. This might reflect better deposition to the entire lung, including the small airways.

U2 - 10.1016/j.jaci.2015.06.012

DO - 10.1016/j.jaci.2015.06.012

M3 - Article

VL - 137

SP - 727-733.e1

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 3

ER -