AJTCCM VOL. 29 NO. 2 2023 41
EDITORIAL
In this issue of AJTCCM, Manyeruke etal.[1] provide a retrospective
review of 110 acute asthma exacerbations requiring mechanical
ventilation (103 patients) in the respiratory intensive care unit (ICU)
at Groote Schuur Hospital, Cape Town, South Africa (SA), over a
6-year period (2014 - 2019). eoretically, all hospital admissions for
asthma represent failure of one or more aspects of management of this
common chronic disease – timely and correct diagnosis, avoidance
of precipitating factors, smoking cessation, appropriate drug therapy,
proper inhaler use technique, adherence to therapy, patient education,
and regular review.
e striking ndings were: (i) only 60.0% of the patients were
using inhaled corticosteroids (ICSs), although 91.8% were using
short-acting beta-agonists (SABAs); (ii) the median partial pressure
of carbon dioxide (PaCO2) on admission to the ICU was 9.09 kPa
(68.2 mmHg); (iii) the median pH was 7.22; (iv) 7 patients (6.4%) had
had a previous ICU admission; (v) 10.9% were using long-term oral
corticosteroids (OCSs); (vi) 36.4% were current smokers; and (vii)
14.5% admitted to illicit drug abuse.
Current practice mandates ICSs as the mainstay of asthma drug
therapy, since these drugs address the underlying pathogenesis of
airway inammation. ICS use in asthma has been shown to control
symptoms, decrease exacerbations and hospitalisations, and even
reduce mortality.[2] In 2019, the Global Initiative for Asthma (GINA)
instituted a paradigm change by advocating that SABA monotherapy
should never be prescribed in the treatment of asthma, even in mild
disease, as this was associated with an increased risk of exacerbations
and asthma-related mortality.[3]
While there is incontrovertible evidence for the value of ICSs, these
drugs demonstrate at dose-response curves for their benecial clinical
eects, with 80 - 90% of the maximum benet obtained with ‘low-
dose’ ICSs (uticasone propionate 100 - 250 μg daily or equivalent).[4]
In contrast, the higher the dose of ICSs, the greater are the systemic
side-eects, a phenomenon that does not plateau. Notably, a large real-
world study employing two electronic UK medical record databases
showed that increasing the dose of ICSs in poorly controlled asthmatics
to dosages considered ‘high dose’ was associated with a higher risk of
exacerbations and a reduced time to rst exacerbation.[5] We also now
recognise that the magnitude of response to corticosteroids varies
between dierent asthma phenotypes and endotypes.[6]
Even in patients co-prescribed an ICS, SABA overuse (>2 standard
canisters per year) is coupled with increased asthma exacerbations and
poorer asthma control. A positive relationship between the number of
SABA canisters prescribed per patient per year and these unfavourable
outcomes was evident in the SABINA studies.[7,8] It is sobering
to note that of 24 countries across four continents surveyed in the
SABINA III study, SA fared worst, with 74.9% of mild or moderate-
to-severe asthmatics prescribed ≥3 SABA canisters per year and 56.5%
prescribed ≥10 canisters per year.[7]
How do the features and outcomes of this SA study compare with
the developed world? A large study of patients with asthma admitted
to ICUs from 2014 - 2015 that compared Australian and New Zealand
(ANZ) patients with those in the USA was reported by Abdelkarim
etal.[9] Seven hundred and thirty patients were intubated (ANZ n=544,
USA n=186). Comparing the intubated patients in the ANZ cohort
with those in the US cohort, the median age was 45 and 41 years,
respectively, most were female (62.3% and 64.0%), the median PaCO2
was 54 and 46 mmHg, the median pH was identical (7.35), ICU length
of stay (LoS) was 3.1 and 2.5 days, and ICU mortality was 2.0% and
5.4%. Manyeruke etal.’s patients were much younger (median age
33.5 years) and had more severe hypercapnia and acidosis. Despite
the more severely deranged blood gas parameters, suggesting delayed
presentation and/or greater severity of exacerbations, the ICU LoS was
similar (median 3 days) and the ICU mortality comparable (4.5%).
ere was also a female predominance (53.6%).
Asthma patients are not immune to tobacco addiction. In a
nationally representative telephonic survey of 12339 asthmatics in
the USA (21.8% of whom were current smokers) who had visited the
emergency department (ED) over the past year,[10] the odds of current
smokers having visited the ED was 1.82 compared with never smokers.
In another study, 35% of 1 847 patients who presented to the ED
with acute asthma were current smokers (median 10 pack-years).[11]
Interestingly, only 4% of these subjects considered this acute episode
to be related to their smoking habit, although 50% acknowledged that
cigarette smoke was a triggering factor for their asthma.
Asthmatics who are also cannabis users are known to have poorer
asthma control and more frequent exacerbations. is association is
complex, as many are also tobacco users, have poor socioeconomic
circumstances and are poorly adherent to treatment. In a case-control
observational study, 44% of asthmatics who presented to the ED with
an acute exacerbation either admitted to use of illicit drugs or had a
positive urine test for illicit drugs.[12] Smoked cannabis has been shown
to cause bronchodilation lasting ~60 minutes,[13] probably mediated
via CB1 receptor stimulation in airway parasympathetic nerves that
leads to inhibition of acetylcholine release. Despite isolated reports
of cannabis improving asthma control,[14] a Norwegian study based
on asthma prescriptions suggests that current cannabis smoking
may be a risk factor for asthma.[15] A laboratory-based study suggests
that smoking cannabis decreases the conversion of beclomethasone
dipropionate (BDP) to its active metabolite, beclomethasone-17-
monopropionate.[16] e clinical signicance of possible interactions
between inhaled cannabis and BDP or other ICSs has not been studied.
Cannabis has been reported to cause allergic manifestations,[17,18]
including asthma, allergic rhinitis, eczema and even anaphylaxis.
Sensitivity may be related to exposure to pollen or seeds of the
Cannabis sativa plant, recreational use or occupational exposure.
In Manyeruke etal.’s study, 10.9% of the patients were using chronic
OCSs. e mean daily dose was not stated. Low-dose systemic steroids
(prednisone ≤7.5 mg/d) is an option in step 5 of the GINA guideline,
but only ‘as a last resort’.[19] In a systematic review of the use of systemic
corticosteroids prescribed for asthma,[20] long-term corticosteroid use
ranged from 1.2% to 30.9% in patients with any degree of asthma
severity. Long-term OCS use was associated with a 3.6-fold increase
in steroid-related side-eects compared with no use. e risks of
adverse eects are related to the cumulative dose, so even patients
prescribed frequent courses of short-term OCSs are predisposed to
these unintended consequences.
Ventilating my thoughts on severe asthma exacerbations
42 AJTCCM VOL. 29 NO. 2 2023
EDITORIAL
Of concern is that only 61.5% of survivors in Manyeruke etal.’s study
returned for a follow-up visit to the respiratory clinic at Groote Schuur
Hospital. A history of substance abuse was a signicant risk factor for
defaulting.
e World Asthma Day 2023 theme for 2 May was ‘Asthma care
for all’. SA remains far from addressing asthma, one of the most
common chronic respiratory diseases, in an adequate manner. Despite
having world experts in asthma and comprehensive national asthma
guidelines in our country, translation at grassroots level remains
woefully poor. Cape Town is a thriving metropolis with arguably
the best primary healthcare infrastructure in the country, yet the
statistics for severe asthma exacerbations do not reect this. Like
most chronic diseases, diagnosis and management of asthma extend
beyond scientically based guidelines. Important aspects beyond our
control include political commitment and support, improved access
to healthcare and emergency services, availability and cost of drugs,
transport, socioeconomic deprivation, pollution control, and tobacco
and illicit drug use.
Things we can do to improve the situation are education (of
the lay public, patients with asthma, medical students, primary
healthcare providers, general practitioners, specialists), ensuring that
all asthmatics are prescribed an ICS, advocacy for drugs and newer
formulations to be available and at lower cost (including biological
agents), checking inhaler technique at every visit, promotion of
smoking cessation, regular follow-up, and earlier interventions in
acute exacerbations. We have a lot of work to do.
M L Wong, MB BCh, FCP (SA), FCCP, FRCP (Lond)
Division of Pulmonology, Department of Medicine, Chris Hani
Baragwanath Academic Hospital and Faculty of Health Sciences,
University of the Witwatersrand, Johannesburg, South Africa
michelle.wong@wits.ac.za
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