Drugs Aging (2017) 34:157–162

DOI 10.1007/s40266-017-0437-y

THERAPY IN PRACTICE

Late-Onset Asthma: A Diagnostic and Management Challenge

Charlotte Suppli Ulrik1,2

Published online: 6 February 2017

Ó Springer International Publishing Switzerland 2017

Abstract Late-onset asthma is common, associated with
poor outcome, underdiagnosed and undertreated, possibly
due to the modifying effect of ageing on disease expres-
sion. Although the diagnostic work-up in elderly individ-
uals suspected of having asthma follows the same steps as
in younger individuals (case history and spirometry), it is
important to acknowledge that elderly individuals are
likely to have diminished bronchodilator reversibility and
some degree of fixed airflow obstruction. Elderly individ-
uals, therefore, often require further objective tests,
including bronchial challenge testing, to objectively con-
firm asthma. If necessary, a trial of oral or inhaled corti-
costeroid might be necessary. Asthma can be diagnosed
when increased airflow variability is identified in a symp-
tomatic patient, and if the patient does not have a history of
exposure, primarily smoking, known to cause chronic
obstructive pulmonary disease, the diagnosis is asthma
even if the patient does not have fully reversible airflow
obstruction. Pharmacological therapy in patients with late-
onset asthma follows international guidelines, including
treatment with the lowest effective dose of inhaled corti-
costeroid to minimize the risk of systemic effects. How-
ever, most recommendations are based on extrapolation
from findings in younger patients. Comorbidities are very
common in patients with late-onset asthma and need to be
taken into account in the management of the disease. In
conclusion, late-onset asthma is poorly recognized and sub-
optimally treated, the latter not least because elderly
patients are excluded from most randomized controlled
trials. Future studies should focus on the development of
evidence-based guidelines for diagnosis and the pharma-
cological therapy of asthma in the elderly, including late-
onset asthma.
Key Points
Diagnosing new-onset asthma in the elderly is a
challenge.
The diagnostic procedures in elderly patients with
possible asthma should acknowledge the impact of
concomitant diseases.
Management of late-onset asthma follows
international guidelines, although the evidence has
been obtained largely from studies of non-elderly
patients.
Diagnostic algorithms and evidence-based
management guidelines are needed for patients with
late-onset asthma.
1 Introduction

& Charlotte Suppli Ulrik Previous studies of the prevalence of asthma among adults
csulrik@dadlnet.dk have shown considerable differences between countries,
1
Department of Respiratory Medicine, Hvidovre Hospital, with estimates up to 16% in young adults and up to 10% in
2650 Hvidovre, Denmark adults over 65 years [1, 2]. The trend of enhanced long-
2
Institute of Clinical Medicine, University of Copenhagen, evity worldwide means that the number of older people
Copenhagen, Denmark with asthma will continue to rise for decades to come, and,
158
furthermore, children from the asthma epidemic in the
1980s are growing older and will add substantially to the
number of older adults with asthma [3, 4].
In spite of an increase in the proportion of elderly
individuals presenting with symptoms suggesting a diag-
nosis of asthma [5], asthma in the elderly remains under- or
misdiagnosed [6]. This is probably mainly due to the
erroneous belief that asthma is a disease with childhood
onset [7], and, therefore, asthma symptoms occurring at
older ages may be attributed to other diseases, including
chronic obstructive pulmonary disease (COPD). Further-
more, recognizing age of onset in elderly patients with
asthma symptoms is very important as it may allow health
professionals to distinguish between truly late-onset dis-
ease and relapsing disease, as long-standing asthma
recently has been shown to differ from late-onset asthma
with regard to clinical and physiological characteristics, as
well as outcome [8].
Unfortunately, advanced age is an exclusion criterion in
the vast majority of randomized controlled trials (RCTs),
and, therefore, our knowledge of asthma in the elderly with
regard to pharmacological therapy is limited. The frequent
occurrence of comorbidities in elderly patients with asthma
also contributes to exclusion of this subgroup of patients
from RCTs. In line with this, it has previously been shown
that asthma patients enrolled in RCTs are not representa-
tive of real-life patients [9]. The consequence is that elderly
patients with asthma are very likely to receive pharmaco-
logical therapy that has not been tested in this subgroup.
1.1 Aims and Definitions
The primary aims of this review are to provide an update
on current knowledge of diagnostic challenges, including
the differentiation between asthma and COPD, and man-
agement strategies, including pharmacological therapy, in
elderly patients presenting with symptoms suggesting a
diagnosis of asthma.
In accordance with the Preferred Reporting Items for
Systematic Reviews and Meta-Analyses (PRISMA)
guidelines, MEDLINE and the Cochrane Library were
searched using the terms ‘asthma’ and/or ‘pathophysiol-
ogy’, ‘diagnosis’, ‘management’, ‘therapy’, ‘outcome’,
‘morbidity’ and ‘mortality’, in combination with
‘elderly’, ‘late-onset’, ‘aging’ or ‘older’. Publications
within the last 5 years from peer-reviewed journals in
English were largely selected, but high-quality and fre-
quently referenced older publications were also included.
Reviews were only included, to a limited extent, to
provide the reader with more detailed background
information (which could not be more extensively
addressed in the present review).
C. S. Ulrik
2 Definitions
The term ‘late-onset asthma’ refers to a person with onset
of asthma-like symptoms who is aged 60 years or older,
defined on the basis of chronological age.
Asthma is regarded as a disease characterized by vari-
able airflow limitation leading to episodic symptoms of
cough, wheeze and dyspnoea, with the main therapeutic
targets being airway inflammation and airway wall
remodelling–.
The clinical diagnosis of asthma requires objective
assessment of lung function, preferably spirometry, and
demonstration of variability by bronchodilator or corti-
costeroid reversibility, airway hyperresponsiveness, e.g. to
inhaled mannitol, or increased diurnal variability in lung
function, e.g. in peak expiratory flow rate.
Chronic obstructive pulmonary disease (COPD) is
regarded as a disease characterized by chronic airflow
limitation caused by exposure to noxious particles or gas-
ses leading to symptoms of cough, sputum, dyspnoea and
exercise limitation.
Asthma–COPD overlap refers to patients with co-ex-
isting features of asthma, e.g. bronchodilator reversibility,
and COPD, with the latter including chronic airflow limi-
tation and relevant exposure, e.g. smoking.
3 Diagnosing Late-Onset Asthma
Asthma is diagnosed on the basis of symptoms and
objective assessment of variable airflow obstruction irre-
spective of the age of the individual suspected to be suf-
fering the disease. However, underdiagnosis of asthma
remains a problem, as up to half of elderly individuals with
asthma are undiagnosed [2, 10].
Elderly patients often exhibit atypical symptoms and
may also have altered perception of their symptoms, and
one of the crucial issues related to late-onset asthma is
proper recognition of the disease. The question is, there-
fore, whether the traditional diagnostic algorithm can be
applied in individuals with late-onset symptoms. On the
other hand, it appears likely that underdiagnosis of late-
onset asthma would be lower if objective assessment,
including spirometry, were more widely used [11].
Although spirometry seems to be effective for identi-
fying patients with late-onset severe asthma [3], it may be
difficult to obtain a conclusive diagnosis not least in cases
of mild and moderate asthma [12]. Furthermore, perform-
ing spirometry in the elderly may be difficult because of the
relatively high prevalence of cognitive impairments.
However, previous studies have shown that most elderly
individuals are able to perform acceptable and reproducible
Late-Onset Asthma: A Diagnostic and Management Challenge
spirometries [13, 14], although health professionals may
consider using forced expiratory volume in 6 s (FEV6) as a
surrogate for forced vital capacity (FVC), as the manoeuvre
requires less physical effort [15, 16], or a lower cut-off for
the FEV1/FVC ratio [12].
The structural changes in the aging lung are associated
with some degree of persistent airflow limitation, and the
interpretation of spirometric curves in the elderly may
therefore be challenging, not least in borderline cases.
These structural changes also account for the loss of
reversibility, and this means that a bronchodilator
reversibility test may not be useful for diagnosing late-
onset asthma [10, 17].
The fraction of exhaled nitric oxide (FENO) is a marker
of eosinophilic airway inflammation, and findings from a
recent study by Godinho Netto et al. [18] suggest that FE-
NO measurements might be helpful in the diagnosis of late-
onset asthma. However, routine measurement of FENO
may not be clinically valuable in elderly patients with
asthma, as some patients may have some degree of neu-
trophilic airway inflammation related to tobacco exposure
or a non-eosinophilic phenotype [19–21].
Compared with younger individuals, it is, therefore,
likely that elderly individuals require further objective
tests, including bronchial challenge testing, to objectively
confirm a diagnosis of asthma. Unfortunately, no studies
have been published so far addressing the use of bronchial
challenge testing for diagnosing asthma exclusively in
elderly individuals, although it has previously been shown
in a group of adults with suspected asthma referred to a
university hospital that direct, e.g. methacholine, and
indirect, e.g. mannitol, challenge tests differ with regard to
specificity and sensitivity for the diagnosis [22].
In the diagnostic work-up in elderly patients suspected
of having asthma, it may, therefore, be necessary to pro-
ceed with a trial of oral or inhaled corticosteroids (ICS),
not least in patients with post-bronchodilator airflow
obstruction.
Asthma can be diagnosed when increased airflow vari-
ability is identified in a symptomatic patient, and if the
patient does not have a history of exposure, primarily
smoking, known to cause COPD, the diagnosis is asthma
even if the patient does not have fully reversible airflow
obstruction.
4 Distinguishing Late-Onset Asthma from COPD
Unfortunately, smoking history is not a clear-cut feature to
distinguish asthma from COPD, as a substantial proportion
of patients with asthma are current or ex-smokers [23, 24].
The distinction between asthma and COPD should not
be based on the response to a short-acting bronchodilator.
159
Some patients with late-onset asthma may also, due to age-
related structural changes, not have reversible airflow
limitation. Furthermore, some patients with COPD,
although having fixed airflow limitation, do have some
degree of reversibility [25, 26].
Although atopy is more common among elderly indi-
viduals with asthma compared with in age-matched indi-
viduals without asthma, evaluation of atopy is likely not
useful in differentiating between asthma and COPD, not
least because the absence of atopy clearly does not rule out
a diagnosis of asthma [27, 28].
Emphysema is not a feature of asthma, and diffusion
capacity for carbon monoxide should be normal and, by
that, support a diagnosis of asthma and not COPD [27]. As
it might be difficult to obtain valid measures of diffusion
capacity in elderly individuals, adding low-dose chest
computed tomography to exclude emphysema to the
diagnostic procedures is likely to be helpful [29, 30].
The clinical implication of these considerations is that
an elderly individual with overall characteristics pointing at
a diagnosis of asthma should be classified, and managed, as
a patient with asthma regardless of the presence of non-
reversible airflow obstruction.
5 Management of Late-Onset Asthma
Although recent Global Initiative for Asthma (GINA)
guidelines have allocated a section for the management of
asthma in elderly patients [3], the lack of clinical evidence
on the efficacy of therapeutic agents obtained from elderly
patients is a major challenge in the management of late-
onset asthma. Therapeutic decisions in patients with late-
onset disease will, therefore, largely have to be based on
clinical experience, illustrating the major gap between
current available evidence and real-world practice in
patients with late-onset asthma.
The best efficacy-to-safety ratio for many drugs used for
the treatment of asthma is obtained by drug delivery by the
inhaled route. However, inadequate inhaler device technique
is a substantial problem that may lead to poor disease control
[31], not least in elderly patients [32]. Furthermore, inade-
quate inhaler technique has also been shown to be associated
with cognitive impairment and reduced lung function [31].
However, after detailed specific instructions, which need to be
repeated, the majority of elderly patients with asthma can
acquire and retain adequate device technique.
Chronic airway inflammation is a key feature of the dis-
ease, and ICS is, therefore, also the cornerstone of pharma-
cotherapy in patients with late-onset asthma. Although not
based on evidence from clinical trials, low-dose ICS is
considered to be effective and safe also in elderly patients
with asthma. High-dose ICS therapy is associated with
160
systemic effects [33] and, across age groups, is only rec-
ommended for up to 6 months, unless it has been clearly
shown that better asthma control is achieved on high-dose
therapy [3]. This highlights the importance of treating with
the lowest effective dose of ICS in patients with late-onset
asthma, not least to reduce the risk for osteoporosis. ICS
therapy has been associated with a higher risk of pneumonia
in patients with COPD [34], but the question of pneumonia
risk in patients with late-onset asthma has not been addressed
in prospective studies.
Fixed-combination therapy with ICS and a long-acting
b2-agonist (LABA) is recommended if patients with
asthma do not achieve disease control on ICS alone,
although in elderly patients, this is based on very limited
evidence [35]. Fixed-combination therapy, i.e. ICS and
LABA in the same inhaler, is recommended based on a
post hoc analysis of the Salmeterol Multicenter Asthma
Research Trial (SMART) showing that the increased risk of
poor outcome was only observed among participants who
were not on concomitant ICS at baseline [36] and reported
differences in adherence with ICS and LABA prescribed in
separate inhalers [37].
Add-on tiotropium to fixed-combination therapy with
ICS and LABA in patients with poor asthma control has
been shown to be effective [38], and may also be used in
patients with late-onset asthma, although direct clinical
evidence is lacking. However, in a post hoc analysis of data
from the same studies, Kerstjens et al. reported that the
effect of tiotropium on asthma control is independent of
age and age at onset of asthma [39]. Further, re-assuring
evidence with regard to treating elderly patients with long-
acting anti-muscarinic agents comes from the large Tio-
tropium Safety and Performance in Respimat (TIOSPIR)
study of patients with COPD over the age of 40 years [40].
Approximately 50% of the patients included in the study
were 65? years, and the study did not reveal any major
long-term safety concerns [40].
In contrast to previous studies where a very limited
clinical effect of adding a leukotriene modifier to ICS was
found in elderly patients with asthma [41], a recent
12-week study of 140 elderly patients (60? years) with
mild asthma revealed that add-on montelukast to low-dose
ICS had similar efficacy to that of doubling the dose of ICS
[42]. Furthermore, it has also been shown that adding a
leukotriene to ICS can improve outcomes in elderly
patients with severe asthma [43]. Further studies in elderly
patients with asthma are needed, but leukotriene modifiers
may be a good option in this group of patients, also because
of the safety profile and method of administration.
Biologic therapy, e.g. treatment with omalizumab or
mepolizumab, for patients with late-onset asthma may be
an important step forward in the management of severe
C. S. Ulrik
late-onset asthma. So far, only a few post hoc or pooled
analyses of omalizumab therapy in elderly patients with
severe allergic asthma have been published [44–46].
However, RCTs will be necessary to establish the clinical
efficacy and safety profile of biologic therapy in patients
with late-onset asthma.
6 Co-morbidities in Patients with Late-Onset
Asthma
The patient with late-onset asthma is, almost by defini-
tion, characterized by comorbidity, and the concomitant
number of diseases increases with age. Previously, it has
been shown that more than 50% of individuals 65? years
have at least three concomitant diseases [47]. Based on
data from the UK General Practice Research Database,
Soriano et al. [48] reported that the pattern of comor-
bidities in elderly patients with asthma resembles that of
COPD, with ischaemic heart diseases, cataract and
osteoporosis being the most prevalent concomitant dis-
eases. In patients with late-onset asthma, concomitant
rhinitis, gastro-oesophageal reflux, ischaemic heart dis-
ease, arrhythmias, diabetes and osteoporosis should be
treated according to guidelines.
Apart from cognitive impairment, depression and anxi-
ety are very common in elderly patients with asthma.
Recognition and treatment of depression and anxiety in
patients with late-onset asthma is important, as depression
is associated with poor outcome, including higher exacer-
bation rate and mortality [49, 50].
Taking comorbidities into account in the manage-
ment of patients with late-onset asthma is of upmost
importance, as a high number of prescribed medications
may worsen adherence with controller medication for
asthma and increase the risk of drug interactions and,
therefore, have a negative impact on efficacy, safety
and outcome.
7 Conclusions
Late-onset asthma is underdiagnosed, undertreated and
associated with poor outcome. Furthermore, only very
limited evidence is available to support therapeutic deci-
sions in patients with late-onset asthma, as this group of
patients have been excluded from the majority of con-
trolled clinical trials of asthma therapies, including bio-
logics. More research is clearly needed that focuses
specifically on this vulnerable, growing group of patients
with asthma, so that future diagnostic and therapeutic
algorithms can become evidence based.
Late-Onset Asthma: A Diagnostic and Management Challenge
Compliance with Ethical Standards
Conflict of interest CSU has no conflict of interest in relation to this
manuscript.
Funding No sources of funding were used to support the writing of
this manuscript.
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