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What Is New In Small Airways Research

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Ves Dimov, M.D.
Allergist/Immunologist at Cleveland Clinic
Clinical Associate Professor
FAU Charles E. Schmidt College of Medicine

Forced oscillometry as an effortless test detects small airway obstruction better than spirometry in asthma

Forced oscillometry (resistance at 5, 20, and 5-20 Hz) requires passive cooperation of the patient breathing normally vs. the active participation during spirometry.

This small study from Egypt included 50 patients with stable asthma at age 50 and matched healthy controls. All patients with asthma had airway obstruction, 8% had isolated small airway obstruction, 10% had isolated large airway obstruction, and 82% had large and small airway obstruction.

By forced oscillometry, 12% had normal airway resistance, 50% had isolated small airway obstruction with frequency-dependent resistance, and 38% had large and small airway obstruction with frequency-independent resistance. There was significant difference between techniques for the detection of the site of airway obstruction (P = .012).

Forced oscillometry is an effortless test, conducted during quiet tidal breathing, and does not alter airway caliber. Forced oscillometry detected isolated small airway obstruction better than spirometry in asthma.

Source: Hafez MR, Abu-Bakr SM, Mohamed AA. Forced oscillometry track sites of airway obstruction in bronchial asthma. Annals of Allergy, Asthma and Immunology 2015; 115(1): 28-32. (doi:10.1016/j.anai.2015.04.017)


Image Source: Flow volume loop, Wikipedia, public domain


Small particle formoterol may achieve better deposition in small airways compared with large particle salmeterol

This small study from the United Kingdom used impulse oscillometry (IOS) to compare single and repeated dosing effects of small- and large-particle long-acting beta-agonists.

16 patients (mean age 43 years) received either 12 mcg of small-particle hydrofluoroalkane 134a-formoterol solution or 50 mcg 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.

At baseline, FEV1 was 80%; 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.

After the first dose, there were greater improvements with formoterol versus salmeterol in all IOS outcomes and FEF25-75, but not FEV1, at 5 minutes (these were not sustained over 60 minutes). After the last dose, all IOS outcomes, but not FEV1 or FEF25-75, were better with formoterol over the entire 60 minutes.

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.

Source: Manoharan A, von Wilamowitz-Moellendorff A, Morrison A, Lipworth BJ. Effects of formoterol or salmeterol on impulse oscillometry in patients with persistent asthma. Journal of Allergy and Clinical Immunology 2015; in press. (doi:10.1016/j.jaci.2015.06.012)

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'Extrafine' dry powder aerosols did not improve lung deposition in the small airways

There is increasing interest in the use of 'extrafine' aerosols to target the small airways in the management of asthma and COPD.

This study from The Netherlands used previously presented deposition data to assess if submicron (less than 1μm) particles can improve central and deep lung deposition. Prior data had shown that particles in the range 1-3μm are more relevant in this respect.

The following ICS/LABA combination dry powder inhalers were tested in vitro as a function of the pressure drop (2, 4 and 6kPa) across the inhaler: Symbicort Turbuhaler, Seretide Diskus, Rolenium Elpenhaler and Foster (Fostair) NEXThaler.

Obtained fine particle fractions (FPFs) <5μm (as percent of label claim) were divided into subfractions <1, 1-3 and 3-5μm. Differences of up to a factor of 4 were found between the best (Turbuhaler) and worst performing DPI (Elpenhaler), particularly for the FPF in the size range 1-3μm.

The NEXThaler, described as delivering 'extrafine' particles, did not appear to be superior in this size range.

The marked differences in amount and size distribution of the aerosols between the devices in this study likely translates into differences in the total lung dose and drug distribution over the airways.

Source: de Boer AH, Gjaltema D, Hagedoorn P, Frijlink HW. Can 'extrafine' dry powder aerosols improve lung deposition?. European Journal of Pharmaceutics and Biopharmaceutics 2015; 96: 143 –151. (doi:10.1016/j.ejpb.2015.07.016)

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Last updated: Friday, August 21st, 2015