There has been no documented deterioration in pulmonary function with
BT, and no significant structural ab-normalities have been seen on high-resolution computed tomography.56,58
Both GINA 2016 and ERS/ATS support the use of BT in the context of
adults with severe asthma, calling for
more long-term studies to address
delayed benefits and safety.
A multicenter, double-blind, 26-week
study of 11,693 patients randomized to ICS + LABA (budesonide/
formoterol) vs ICS (budesonide)
alone has shown no increased AEs
in either arm. The study found that
treatment with budesonide/for-moterol was associated with lower
risk of asthma exacerbations than
using budesonide alone ( 16.5%;
P = .002).62
The safety of adding a LABA to
fluticasone also has been evaluated
recently. A 2016 study of almost
12,000 patients (aged > 12 years)
compared fluticasone proprionate
alone vs fluticasone with salmeterol.63
There were no asthma-related deaths,
but 2 patients in the fluticasone-only group were intubated with
asthma complications. The risk of a
severe asthma exacerbation seemed
to be lower in the combination
group (8% vs 10%; P < .001).63
A 2014 Cochrane Review supported the view that LABAs in
adults seem to be safe when used
concurrently with an ICS with a A-level recommendation, based on
consistent good-quality, patient-oriented evidence.64 Multiple organizations have issued guidelines
to this effect in the past, but previous results of studies showed that
asthma deaths and a small increase
in nonfatal serious AEs were noted
in those using LABA monotherapy
NAEPP (EPR- 3) and ERS/ATS
recommend stepwise increases in
the dose of ICS in combination with
a LABA. The GINA guidelines recommend controller therapy to include combination IHS and LABA
but with the consideration of higher
doses of ICS than are routinely recommended for general use.
Inhaler and Inhaler Combinations
Many different inhalers of ICS alone
and ICS/LABA combinations exist
on the market today. There are differences in delivery that affect patient
preference but these differences have
not been found to improve delivery.
Small particle ICS therapy could possibly correlate with improved delivery to the small airways.65 There are
3 preparations of inhaled steroids
that fit in to this group, including
beclomethasone, ciclesonide, and
flunisolide. Other inhaled steroid
formulations include budesonide,
fluticasone propionate, fluticasone
furoate, and mometasone.
Combination therapy (ICS +
LABA) inhalers also are widely
available. They include budesonide/
formoterol, fluticasone proprionate/
and the newer fluticasone furoate/
vilanterol, a once-daily combination
approved for those aged ≥ 18 years.
The treatment of severe asthma has
progressed from simple manipulation
of avoidance, bronchodilators, and
corticosteroids to include many other
treatments that have improved QOL
for patients with refractory asthma.
Although many of these options are
delivered in coordination with an allergy and pulmonary specialist, it is
important for the PCP to have a good
knowledge base and awareness of additional treatments that are currently
The authors report no actual or potential conflicts of interest with regard to
The opinions expressed herein are those
of the authors and do not necessarily
reflect those of Federal Practitioner,
Frontline Medical Communications
Inc., the U.S. Government, or any of its
agencies. This article may discuss unlabeled or investigational use of certain
drugs. Please review the complete prescribing information for specific drugs
or drug combinations—including indications, contraindications, warnings,
and adverse effects—before administering pharmacologic therapy to patients.
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