CE: D.C.

; MCP/280305; Total nos of Pages: 7;

MCP 280305

REVIEW

CURRENT
OPINION Asthma diagnosis using patient-reported outcome
measures and objective diagnostic tests: now and
into the future
Safia F. Nawaz a, Mayuran Ravindran b, and Merin E. Kuruvilla c

Purpose of review
The global prevalence of asthma continues to increase; however, asthma remains under-diagnosed and
under-treated. This results in a significant burden on the healthcare system and preventable patient
morbidity and mortality. Over-diagnosis of asthma based on clinical history alone also complicates patient
management. This heightens the importance of a prompt and accurate asthma diagnosis. Therefore, a
review of the literature was performed regarding both objective diagnostic testing for asthma and using
patient-reported outcome measures.
Recent findings
The cornerstone of asthma diagnosis remains spirometry with testing for bronchodilator reversibility testing
for pediatric and adult populations. This test may need to be repeated at multiple time points due to its low
sensitivity. Peak flow measurement, fractional exhaled nitric oxide testing, and allergy testing are useful
adjuncts to the diagnosis and phenotyping of asthma. Bronchoprovocation testing is reserved for people
with high clinical suspicion for asthma, but negative spirometry. Novel noninvasive testing modalities may
play a diagnostic role in the future. The advent of remote digital health monitoring technology has resulted
in revisiting patient-reported outcome measures for the diagnosis and monitoring of asthma.
Summary
Overall, improved diagnostic tools for asthma are crucial for earlier recognition and treatment of the
disease and improved patient care outcomes worldwide.
Keywords
asthma, bronchoprovocation testing, diagnosis, fractional exhaled nitric oxide, patient-reported outcome mea-
sures, peak expiratory flow, spirometry

INTRODUCTION asthma management have been refined to facilitate

Asthma is a chronic inflammatory lung disease
characterized by airway hyper-responsiveness and
reversible obstruction. Globally prevalent and span-
ning all age groups (with an annually increasing
incidence in children), the WHO estimates that
262 million people were affected by asthma in
2019 alone [1]. Despite its prevalence, however,
asthma is often under-diagnosed and under-treated,
leading to a disproportionate burden on the health-
care system and significant preventable patient mor-
bidity and mortality.
In recent years, medical innovations and
research have led to a shift in the perception of
asthma from a discrete steroid-responsive pulmo-
nary disease to a complex syndrome with a broad
diversity of phenotypes. With this evolution of clin-
ical understanding, practice guidelines governing
disease diagnosis, and optimize patient care and
reported outcomes.
Multiple systematic approaches geared at diag-
nosing asthma have been undertaken in accordance
with advancements in medical research. Focus
groups have attempted to consolidate methods of
assessment, diagnosis, and disease mitigation. Most
recent guidelines have prioritized quality of life
a
Division of Pulmonary, Allergy & Immunology, Cystic Fibrosis, and Sleep,
Department of Pediatrics, bDepartment of Internal Medicine and cDivision
of Pulmonary, Allergy, Critical Care & Sleep Medicine, Department of
Medicine, Emory University, Atlanta, Georgia, USA
Correspondence to Merin E. Kuruvilla, MD, 1605 Chantilly Dr NE,
Atlanta, GA 30324, USA. E-mail: merin.kuruvilla@emoryhealthcare.org
Curr Opin Pulm Med 2022, 28:000–000
DOI:10.1097/MCP.0000000000000871

1070-5287 Copyright ß 2022 Wolters Kluwer Health, Inc. All rights reserved. www.co-pulmonarymedicine.com

Copyright © 2022 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
CE: D.C.; MCP/280305; Total nos of Pages: 7;
MCP 280305

Asthma

breath, and coughing, with expiratory wheezing

KEY POINTS on examination. Exercise intolerance and nocturnal
 Early diagnosis of asthma is crucial to expedite awakenings with lower respiratory symptoms are
treatment and improve patient care outcomes. considered pathognomonic for asthma. Symptom-
atology such as wheezing, worsening with laughter,
 There are currently a variety of subjective and objective cold air, viral upper respiratory infections, nocturnal
methods for diagnosing asthma.
awakenings, and exercise intolerance should raise
 Many objective methods for diagnosing asthma are clinical suspicion for asthma. A personal or family
technique-dependent, which limits their practicality and history of atopy and elimination of alternative diag-
lends credence to emerging subjective noses are key pieces of evidence to support this
diagnostic methods. diagnosis. However, asthma can be over-diagnosed
 Future methods of diagnosis will likely incorporate both based on clinical history alone. For this reason, the
subjective and objective tools. National Institute for Health and Care Excellence
(NICE) published guidelines on asthma diagnosis. In
addition to a clinical assessment, NICE suggested
the implementation of an algorithm with the
(QOL), cost-effective medicine, and public health sequential performance of objective testing [6]. A
outcomes. This has been demonstrated by two of the suggested pathway for the diagnosis of asthma is
leading task forces on asthma management, the outlined in Fig. 1.
Global Initiative for Asthma (GINA) and the
National Heart, Lung, and Blood Institute (NHLBI)
&& &&
[2 ,3 ]. Updated guidelines have integrated practi- Peak expiratory flow
cal strategies for asthma diagnosis. In addition, A peak flow meter (PFM) is a handheld device that
there has been a focus on contextualizing objective measures airflow. Although peak flow measures may
diagnosis modalities with newly emerging subjec- be limited by patient technique, their cost-effective-
tive/qualitative data. ness, convenience, and role in improving patient
self-awareness are undeniable assets. Guidelines rec-
ommend serial peak expiratory flow (PEF) measure-
ASTHMA DIAGNOSIS ments while at work and away from work to
The diagnosis of asthma should be first suspected by objectively confirm occupational asthma [4].
clinical history and/or assessment. This includes a Studies have investigated the ability of PEF to
history of episodic chest tightness, shortness of serve as a surrogate for spirometry in the diagnosis of

Risk factors Diagnosis of Asthma

• Contribung history of atopy
• Exposure to smoke, polluon, etc.
• Obesity
Symptom and exam-directed diagnosc workup

Concurrent atopy Objecve Subjecve

Suspected allergic sensizaon Pulmonary workup Paent-Reported Outcome Measures (PROMs)

• Allergy tesng (skin prick/in vitro) • Spirometry • Asthma control tools (ACT/ACQ)
• FeNO • Quality of life (QOL) quesonnaires
• Impulse oscillometry • Remote digital health monitoring technology

Negave Negave spirometry Posive

Tesng consistent w/ asthma

Consider other eologies (ex: GERD) • Consider other eologies
• Administer short-acng
• Consider bronchoprovocaon tesng
β₂ agonist PRN for relief
• Introduce treatment if high likelihood of
• Start an-inflammatory
asthma and repeat tesng to confirm
therapy (ex: ICS)
diagnosis at later me
• Idenfy symptomac
triggers
• Treat comorbidies

Arrange appropriate follow-up to reassess

symptomac control and treatment

FIGURE 1. Diagnosis of asthma using subjective and objective measures of testing.

2 www.co-pulmonarymedicine.com Volume 28  Number 00  Month 2022

Copyright © 2022 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
CE: D.C.; MCP/280305; Total nos of Pages: 7;
MCP 280305
asthma, with mixed results. PEF measurement is
purely dependent on patient effort and in general,
the concordance between PEF, and spirometry is
highly variable [5–8]. This may result in inappropri-
ate clinical diagnoses, especially in children since
PEF is often not accurate in this population. How-
ever, a post-hoc analysis in 2019 of eight Phase 3
trials with tiotropium Respimat (Boehringer Ingel-
heim, Germany) in adolescents and adults with
asthma suggested that PEF could be a valid, and
more convenient substitute to forced expiratory
volume in 1 s (FEV1) measurement as an endpoint
in clinical trials [9].
Overall, PEF may be used by asthmatics who are
familiar with its measurement for disease monitor-
ing, but is not a valid replacement for pulmonary
function testing (PFT) in asthma diagnosis.
Pulmonary function testing
PFT is the cornerstone of asthma diagnosis in
patients 5 years or older. The most commonly used
pulmonary function test is spirometry, which mea-
sures lung volume and airflow. The first step to
confirm a diagnosis of asthma is spirometry with
testing for bronchodilator reversibility. An improve-
ment in FEV1 of at least 12% and at least 200 cc is
required for confirmation. A lack of reversibility
with bronchodilator use may suggests a diagnosis
other than asthma. However, it must be noted that
the predictive value of this criterion is not absolute
&
[10 ]. In two large cohorts of patients with high
clinical suspicion for asthma, spirometry with bron-
chodilator reversibility testing had negative predic-
&
tive values of only 39–57% [10 ,11]. A negative test
thus does not reliably rule out asthma.
Per the 2021 GINA guidelines update, a sugges-
tive history in conjunction with characteristic spi-
rometry – documented expiratory airflow
limitation in conjunction with documented exces-
sive variability in lung function – are necessary to
make a diagnosis of asthma, followed by ongoing
serial assessment of lung function at follow-up visits
&&
to predict risk of future exacerbations [3 ]. The 2020
NHLBI update, meanwhile, reiterated that lung
function does not strongly correlate with asthma
symptoms in affected patients, but concurred with
the use of spirometry in predicting exacerbation
risk. The update also confirmed with ongoing mon-
itoring of lung function to assess asthmatic control,
going so far as to suggest that more frequent spi-
&&
rometry may be of use pending disease severity [2 ].
In addition to confirming the diagnosis, PFTs are
just as vital in averting a misdiagnosis of asthma.
One-third of asthmatics receiving specific therapy
were found to not have asthma using objective
1070-5287 Copyright ß 2022 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2022 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Asthma diagnosis Nawaz et al.
measures of PFTs [12]. This can result in the possibly
harmful use of expensive asthma medications in
patients who are unlikely to derive clinical benefit.
Fractional exhaled nitric oxide
The phenotyping of asthma over time has allowed
for the personalization of treatment regimens in
afflicted patients. In severe asthmatics, differentiat-
ing between Type-2 and non-Type-2 airway inflam-
mation can allow for targeted therapy and reduced
disease burden. Fractional exhaled nitric oxide
(FeNO) is a tool that can be useful in diagnosing
Type-2 asthma. This test can help determine the
degree of airway inflammation present in patients
with allergic or eosinophilic asthma, which fall
under the umbrella of Type-2 asthma. Type-2 cyto-
kines including IL-4 and IL-13 have been shown to
induce nitric oxide synthase and thus elevate FeNO
in affected patients. FeNO has been utilized clini-
cally as a tool in predicting exacerbation risk and
guiding therapy options.
In 2020, an expert panel on behalf of the
National Asthma Education and Prevention Pro-
gram provided evidence-based recommendations
governing the utility of FeNO as a diagnostic clinical
&&
tool [2 ]. Their analysis emphasized that FeNO
should not be the sole determinant of type 2 inflam-
mation and determined that values less than 25 ppb
in adults and less than 20 ppb in children suggest a
diagnosis other than Type-2 asthma. A recommen-
dation was also made regarding the role of airway
hyperresponsiveness in FeNO measurements, with
guidance provided to stop inhaled corticosteroids at
least 2 weeks (though a longer washout period may
be necessary depending on the type of inhaled
corticosteroid) prior to collecting FeNO in cases
where a diagnosis of asthma is questionable; it
was also noted that this may be useful in identifying
nonadherence with medication regimens and
potentially in predicting future exacerbation risk
[13].
FeNO is influenced by diet and medications
such as inhaled corticosteroids, as well as demo-
graphic factors such as gender and ethnicity [14].
This has provoked concerns regarding its reliability
as a clinical tool. The 2020 NHLBI update condition-
ally recommended the use of FeNO in patients
5 years or older with equivocal presentations, such
as ambiguous clinical history or inability to perform
spirometry, but emphasized the importance of not-
ing concurrent allergic disease as a potential con-
founder when interpreting FeNO levels. The update
identified FeNO levels greater than 50 ppb in adults
and 35 ppb in children as consistent with Type-2
asthma. The update recommended against FeNO
www.co-pulmonarymedicine.com 3
CE: D.C.; MCP/280305; Total nos of Pages: 7;
MCP 280305
Asthma
measurement in those 4 years or younger, and
against FeNO usage in isolation to diagnose asthma.
In summary, FeNO was deemed a useful adjunct to
clinical history, physical exam, and spirometry in
&&
guiding therapy for asthma [2 ].
Bronchoprovocation testing
The threshold criteria for spirometry with broncho-
dilator reversibility have a low sensitivity for ruling
out asthma. In patients with intermittent or exer-
cise-induced bronchoconstriction in particular, spi-
rometry is often normal poorly predictive of
underlying asthma. Confirmatory bronchoprovoca-
tion testing is recommended in this scenario to
measure bronchial hyperresponsiveness and also
as a marker of its severity [15].
Bronchial hyperresponsiveness may be mea-
sured using direct inhalational challenges or
indirect challenges.
Direct bronchoprovocation testing
Direct inhalational challenges use direct stimulants
such as methacholine or histamine for bronchopro-
vocation. Direct challenges are highly sensitive with
a high negative predictive value for excluding
asthma [16]. Methacholine challenge testing
(MCT) is widely used to detect bronchial hyperreac-
tivity. However, there is considerable divergence in
recommendations regarding MCT thresholds that
are diagnostic for asthma. It is also important to
note that several factors affect the reliability of MCT,
such as concomitant use of controller inhalers.
The American Thoracic Society recommends a
cutoff provocation concentration that causes a 20%
decrease in FEV1 (PC20) as 8 mg/ml using a tidal
breathing method [17]. However, redefining the
normal PC20 as more than 16 mg/ml significantly
&
increases test sensitivity [10 ].
The European Respiratory Society recommends
that MCT results are reported as the provocation
dose that causes a 20% decrease in FEV1 (PD20)
rather than the concentration [18]. A PD20 more
than 400 mg (equivalent to PC20 16 mg/ml) is
considered normal.
Indirect bronchoprovocation testing
Indirect challenges use stimulants such as exercise,
eucapnic voluntary hyperpnea (EVH), hypertonic
saline, or mannitol. Indirect challenges are more
specific and better correlate with eosinophilic
airway inflammation.
In patients with a chief diagnosis of exercise
induced bronchoconstriction (EIB), EVH has been
hailed as an optimal method to secure the diagnosis.
An at least 10% decrease from baseline FEV1 is
4 www.co-pulmonarymedicine.com
Copyright © 2022 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
considered a positive challenge. EVH is the standard
set for diagnosis of EIB by the International Olympic
Committee, but is not typically applied in other set-
tings [19,20]. A recent systematic reviews, however,
demonstrated wide heterogeneity in EVH with regard
to patient demographic data and an overall lack of
sensitivity and specificity [21]. EVH is also limited by
cost and dependence on skilled technicians.
Allergic evaluation
In patients in whom a diagnosis of Type-2 asthma is
likely, allergic evaluation via serum or skin prick
testing may prove key in identifying modifiable risk
factors. The 2020 NHLBI update recommended mul-
ticomponent allergen-specific mitigation interven-
tions in patients exposed to specific allergens with a
suggestive clinical history and/or documented aller-
&&
gies based on testing [2 ].
Impulse oscillometry
Finally, impulse oscillometry (IOS) is a very recent
innovation that has proven useful in early detection
of asthma. This method of forced oscillation is
noninvasive and does not depend on patient tech-
nique. It is also more sensitive than spirometry in
detecting small airway disease. Most significantly, it
can also be used to differentiate small airway
obstruction from large airway obstruction [22]. As
IOS can be used in patient populations that cannot
perform spirometry, including young children, the
elderly, and neurologically compromised patients, it
may be a more useful clinical tool than spirometry,
but extensive data and reference values are lacking.
IOS can also be cost-prohibitive. Further honing of
this potentially very beneficial tool could lead to a
viable clinical supplement and/or alternative
to spirometry.
CLINICALLY RELEVANT PATIENT-
REPORTED OUTCOME MEASURES IN
ASTHMA
There has been increasing emphasis on using
patient-reported outcome measures (PROMs) as an
adjunct to routine PFT to monitor patient percep-
tion of current symptom control, for instance prior
to and following a medical intervention to assess
efficacy [23–25]. Current asthma PROMs have been
shown to lack standardization, with retrospective
studies demonstrating the broad variability among
asthma-related PROMs. Objectives to establish stan-
dard definitions and methodologies have been
established by the Asthma Outcomes Workshop, a
consortion with the National Institute of Health, in
Volume 28  Number 00  Month 2022
CE: D.C.; MCP/280305; Total nos of Pages: 7;
MCP 280305
2010 – an evolving area of study that will likely
continue to gain traction in coming years [26].
PROMs are categorized into generic or disease-
specific assessments. A recent head-to-head qualita-
tive comparison demonstrated that generic mea-
sures, such as the EuroQol-5-dimension-5-level,
are less sensitive to patient-perceived disease impact
[27]. Generic assessments are also inferior with
respect to content validity and patient acceptability,
compared with asthma-specific PROMs. These
shortcomings suggest a benefit to using asthma-
specific instruments to prioritize clinically meaning-
ful data, but there are over 15 available options to
choose from [28]. When comparing existing
asthma-specific PROMs, it is important to optimize
the following criteria: sensitivity to changes in clin-
ical condition, content validity, and ease of admin-
istration [28].
Quality-of-life questionnaires
As previously mentioned, asthma-specific QOL
questionnaires have historically been considered a
useful tool in the assessment of asthma control and
management. While they can allow for greater
patient input in the capacity of shared decision-
making, their subjectivity can often be called into
question. One 1997 study evaluated the clinical
utility of the Asthma Quality of Life Questionnaire
(AQLQ) on low-income adult asthmatic patients
and found positive correlations between AQLQ,
spirometry, and symptoms, suggesting sufficient
reliability and validity [29]. A more recent study
in 2016 examined patient insight into the Sydney
AQLQ along with two of the other most commonly
used asthma-specific QOL questionnaires – the Liv-
ing With Asthma Questionnaire and Juniper AQLQ
– to assess their relevance. The study noted a wide
breadth of patient perceptions to the different ques-
tionnaires, overall reporting that each of the ques-
tionnaires posed varying limitations. Patients found
the QOL questionnaires to be lacking in scope,
redundant, focused on emotions rather than symp-
toms, and most concerningly, often too open to
interpretation [30]. These findings suggest that
while there is a role for QOL questionnaires in the
clinical management of asthma, they must be
weighed in comparison with other testing and fol-
low-up modalities for asthma.
Asthma control tools
A recent review article summarizing aggregate data
from systematic reviews on nine of the most preva-
lent asthma-specific instruments showed the
Asthma Control Test (ACT) and Asthma Control
1070-5287 Copyright ß 2022 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2022 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Asthma diagnosis Nawaz et al.
Questionnaire (ACQ) displayed the best evidence
for use in clinical settings based on the above criteria
[16].
STRENGTHS AND LIMITATIONS OF
ASTHMA-SPECIFIC PATIENT-REPORTED
OUTCOME MEASURES IN SYMPTOM
CONTROL, RISK STRATIFICATION, AND
MEDICATION ADHERENCE
Symptom control
The ACT and ACQ have demonstrated strong, sta-
tistically significant score correlations with one
another. Both composite and interval score changes
provide meaningful data that can support clinical
decision-making to initiate or adjust asthma ther-
apy. For example, higher scores are associated with
less frequent rescue inhaler and oral corticosteroid
use as well as fewer asthma exacerbations. Statisti-
cally significant reductions in unscheduled asthma-
related outpatient clinic visits, emergency depart-
ment visits, and urgent healthcare utilization under-
score the utility of tracking and optimizing PROM
scores as a valid measure of symptom control
[24,25,31,32]. Moreover, improvements in ACT
scores have been associated with improved
patient-reported QOL, sleep quality, work produc-
tivity, and activity levels [24,31,32].
Medication adherence
PROMs are insufficient at tracking asthma medica-
tion adherence compared with objective measures,
such as prescription refill rates. In a systematic
review of 14 PROMs designed to evaluate inhaler
medication adherence in adults with asthma, there
was no evidence that they could detect changes in
adherence scores over time [33]. Thus, these tools
cannot fully distinguish whether uncontrolled
symptoms are caused by medication nonadherence
versus truly refractory disease.
Correlation with spirometry
There is mixed evidence when it comes to the rela-
tionship between PROM scores and objective spi-
rometry findings. Multiple studies have weak
relationships between improvement in adult ACT
scores and FEV1 and FEV1/Forced vital capacity
(FVC), with correlation coefficients ranging from
0.177 to 0.518 [31,34,35]. For instance, in a retro-
spective analysis of survey responses and spirometry
in adolescents and adults, a weak and statistically
insignificant correlation was noted between spirom-
etry and ACQ responses [36].
www.co-pulmonarymedicine.com 5
CE: D.C.; MCP/280305; Total nos of Pages: 7;
MCP 280305
Asthma
In contrast, a large discrepancy has been noted
between child ACT scores and FEV and FEV1/FVC.
Recent studies demonstrate 31–46% of children
categorized as well controlled had abnormal spirom-
etry findings, with neither ACT nor ACQ scores
proving to be a reliable predictor of FEV1 less than
80% [32,34]. Furthermore, individuals with similar
ACT scores but obstructed lung function had an 87%
increase in unplanned healthcare utilization over
6 months compared with those with normal spi-
rometry [34].
These results highlight the limitations of using
PROMs to identify asthma patients with risk factors
for poor outcomes. These tools can over-estimate
levels of asthma control and should ideally be used
in conjunction with objective testing.
EXPLORING AUTONOMOUS PATIENT-
REPORTED OUTCOME MEASURES AND
THE POTENTIAL FOR DIGITAL AT-HOME
ASTHMA MONITORING
The sensitivity of PROMs at detecting airway
obstruction is lower compared with objective lung
testing; however, they are more practical and afford-
able for routine asthma monitoring [37]. PROMs
that align with the language that patients use to
describe their symptoms are increasingly being
adopted by providers [31]. A recent prospective,
single-center observational study compared patient
self-administered with physician administered ACT
scores in a sample of 97 adult patients. There was no
significant difference in composite ACT scores,
although lower education levels were associated
with a statistically significant underestimation of
nighttime symptoms and global judgment of
asthma control [37].
The growth of remote digital health monitoring
technology has promising applications for asthma
patients. Self-administered, digital remote PROMs
have successfully been able to differentiate between
well controlled versus poorly controlled asthma
[23]. Similar to clinic-based PROMs, digital moni-
toring serves as an adjunct to objective lung testing
to inform discussion and shared decision-making.
They are feasible to implement for certain popula-
tions and have shown good retention and engage-
ment [23,38]. However, there are still challenges to
integrating data into provider workflows and ensur-
ing data quality validation.
Ultimately, PROMs improve the sensitivity in
diagnosing uncontrolled asthma and are most effec-
tive when used in conjunction with objective spi-
rometry. The development of novel digital remote
monitoring may expand the role of PROMs as prac-
tical home-based asthma monitoring tools.
6 www.co-pulmonarymedicine.com
Copyright © 2022 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
CONCLUSION
While current guidelines for asthma diagnosis allow
for some provider-dependent and region-dependent
variability, the importance of improving current
modalities of diagnosis remains clear. Future meth-
ods of diagnosis will likely call for a mix of subjective
and objective confirmatory testing. While current
PROMs for asthma vary across practices and thus far
have been limited, honing patient questionnaires to
be standardized will likely improve their reliability
and validity.
From an objective standpoint, many of our
current testing methods, including peak flow mea-
sures, PFT, and FeNO, are technique-dependent,
which renders them unusable in certain patient
populations such as very young children. Novel
noninvasive testing modalities such as multiple-
breath washout are the target of many current
research studies and may play a diagnostic role in
the future [28]. Finally, emerging objective mea-
sures may hone in on the noninvasive and efficient
exploration of small airway disease to allow for
earlier detection of asthma and thereby earlier
intervention. Overall, improved diagnostic tools
for asthma are crucial for earlier recognition and
treatment and improved patient care outcomes
worldwide.
Acknowledgements
None.
Financial support and sponsorship
None.
Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED
READING
Papers of particular interest, published within the annual period of review, have
been highlighted as:
& of special interest
&& of outstanding interest
1. Vos T, Lim S, Abbafati C, et al., GBD 2019 Diseases and Injuries Collabora-
tors. Global burden of 369 diseases and injuries in 204 countries and
territories, 1990–2019: a systematic analysis for the Global Burden of
Disease Study 2019. Lancet 2020; 396:1204–1222.
2. Expert Panel Working Group of the National Heart, Lung, and Blood Institute.
&& 2020 Focused updates to the asthma management guidelines: a report from
the National Asthma Education and Prevention Program Coordinating Com-
mittee Expert Panel Working Group. J Allergy Clin Immunol 2020;
146:1217–1270.
National Asthma Education and Prevention Program (NAEPP) guidelines –
recently updated and should be compared/contrasted with Global Initiative for
Asthma (GINA) guidelines.
3. Reddel HK, Bacharier L, Bateman E, et al. Global Initiative for Asthma (GINA)
&& strategy 2021 – executive summary and rationale for key changes. J Allergy
Clin Immunol Pract 2022; 205:17–35.
GINA guidelines – recently updated and should be compared/contrasted with
NAEPP guidelines.
Volume 28  Number 00  Month 2022
CE: D.C.; MCP/280305; Total nos of Pages: 7;
MCP 280305
4. Burge CB, Moore VC, Pantin C, et al. Diagnosis of occupational asthma from
time point differences in serial PEF measurements. Thorax 2009;
64:1032–1036.
5. Aggarwal AN, Gupta D, Jindal SK. The relationship between FEV1 and peak
expiratory flow in patients with airways obstruction is poor. Chest 2006;
130:1454–1461.
6. Brand PL, Duiverman EJ, Waalkens HJ, et al. Peak flow variation in childhood
asthma: correlation with symptoms, airways obstruction, and hyperrespon-
siveness during long-term treatment with inhaled corticosteroids. Dutch
CNSLD Study Group. Thorax 1999; 54:103–107.
7. Pothirat C, Chaiwong W, Phetsuk N, et al. Peak expiratory flow rate as a
surrogate for forced expiratory volume in 1 s in COPD severity classification in
Thailand. Int J Chron Obstruct Pulmon Dis 2015; 10:1213–1218.
8. Llewellin P, Sawyer G, Lewis S, et al. The relationship between FEV1 and PEF
in the assessment of the severity of airways obstruction. Respirology 2002;
7:333–337.
9. Halpin DMG, Meltzer E, Wendelgard P, et al. Peak expiratory flow as an
endpoint for clinical trials in asthma: a comparison with FEV1. Respir Res
2019; 20:159.
10. Selvanathan J, Aaron S, Sykes J, et al. Performance characteristics of
& spirometry with negative bronchodilator response and methacholine chal-
lenge testing and implications for asthma diagnosis. Chest 2020;
158:479–490.
The study highlights the fallibility of current diagnostic standards.
11. Tomita K, Sano H, Chiba Y, et al. A scoring algorithm for predicting the
presence of adult asthma: a prospective derivation study. Prim Care Respir J
2013; 22:51–58.
12. Aaron SD, Vandemheen KL, Fitzgerald JM, et al. Reevaluation of diagnosis in
adults with physician-diagnosed asthma. JAMA 2017; 317:269–279.
13. Lipworth B, Kuo CR, Chan R. 2020 Updated asthma guidelines: clinical utility
of fractional exhaled nitric oxide (FeNO) in asthma management. J Allergy Clin
Immunol 2020; 146:1281–1282.
14. Rupani H, Kent BD. Using FeNO measurement in clinical asthma manage-
ment. Chest 2021. [Online ahead of print]
15. Cockcroft DW. Methacholine challenge testing in the diagnosis of asthma.
Chest 2020; 158:433–434.
16. Leuppi JD. Bronchoprovocation tests in asthma: direct versus indirect chal-
lenges. Curr Opin Pulm Med 2014; 20:31–36.
17. Crapo RO, Casaburi R, Coates AL, et al. Guidelines for methacholine and
exercise challenge testing-1999. This official statement of the American
Thoracic Society was adopted by the ATS Board of Directors, July 1999.
Am J Respir Crit Care Med 2000; 161:309–329.
18. Coates AL, Wanger J, Cockcroft DW, et al. ERS technical standard on
bronchial challenge testing: general considerations and performance of
methacholine challenge tests. Eur Respir J 2017; 49.
19. Aggarwal B, Mulgirigama A, Berend N. Exercise-induced bronchoconstric-
tion: prevalence, pathophysiology, patient impact, diagnosis and manage-
ment. NPJ Prim Care Respir Med 2018; 28:31.
20. Anderson SD, Argyros GJ, Magnussen H, et al. Provocation by eucapnic
voluntary hyperpnoea to identify exercise induced bronchoconstriction. Br J
Sports Med 2001; 35:344–347.
1070-5287 Copyright ß 2022 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2022 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Asthma diagnosis Nawaz et al.
21. Stickland MK, Rowe BH, Spooner CH, et al. Accuracy of eucapnic hyperpnea
or mannitol to diagnose exercise-induced bronchoconstriction: a systematic
review. Ann Allergy Asthma Immunol 2011; 107:229–234.e8.
22. Chiu HY, Hsiao YH, Su KC, et al. Small airway dysfunction by impulse
oscillometry in symptomatic patients with preserved pulmonary function. J
Allergy Clin Immunol Pract 2020; 8:229–235.e3.
23. Rudin RS, Qureshi N, Foer D, et al. Toward an asthma patient-reported
outcome measure for use in digital remote monitoring. J Asthma 2021; 1–6.
24. van Dijk BCP, Svedsater H, Heddini A, et al. Relationship between the Asthma
Control Test (ACT) and other outcomes: a targeted literature review. BMC
Pulm Med 2020; 20:79.
25. Kocks JWH, Seys SF, van Duin TS, et al. Assessing patient-reported out-
comes in asthma and COPD patients: which can be recommended in clinical
practice? Curr Opin Pulm Med 2018; 24:18–23.
26. Sorkness CA. Validation studies of asthma patient-reported outcomes: ‘we
want more!’. J Allergy Clin Immunol 2014; 133:397–398.
27. Szentes BL, Schultz K, Nowak D, et al. How does the EQ-5D-5L perform in
asthma patients compared with an asthma-specific quality of life question-
naire? BMC Pulm Med 2020; 20:168.
28. Drake SM, Simpson A, Fowler SJ. Asthma diagnosis: the changing face of
guidelines. Pulm Ther 2019; 5:103–115.
29. Leidy NK, Chan KS, Coughlin C. Is the asthma quality of life questionnaire a
useful measure for low-income asthmatics? Am J Respir Crit Care Med 1998;
158:1082–1090.
30. Apfelbacher CJ, Jones CJ, Frew A, Smith H. Validity of three asthma-specific
quality of life questionnaires: the patients’ perspective. BMJ Open 2016;
6:e011793.
31. Nelsen LM, Kosinski M, Rizio AA, et al. A structured review evaluating content
validity of the Asthma Control Test, and its consistency with U.S. guidelines
and patient expectations for asthma control. J Asthma 2020; 1–15.
32. Rhee H, Love T, Mammen J. Comparing Asthma Control Questionnaire (ACQ)
and National Asthma Education and Prevention Program (NAEPP) asthma
control criteria. Ann Allergy Asthma Immunol 2019; 122:58–64.
33. Gagne M, Boulet LP, Perez N, et al. Patient-reported outcome instruments
that evaluate adherence behaviours in adults with asthma: a systematic review
of measurement properties. Br J Clin Pharmacol 2018; 84:1928–1940.
34. Lo DK, Beardsmore CS, Roland D, et al. Lung function and asthma control in
school-age children managed in UK primary care: a cohort study. Thorax
2020; 75:101–107.
35. Busby J, Khoo E, Pfeffer PE, et al. The effects of oral corticosteroids on lung
function, type-2 biomarkers and patient-reported outcomes in stable asthma:
a systematic review and meta-analysis. Respir Med 2020; 173:106156.
36. Sullivan PW, Ghushchyan VH, Marvel J, et al. Association between pulmonary
function and asthma symptoms.J Allergy Clin Immunol Pract 2019; 7:2319–2325.
37. Crimi C, Campisi R, Noto A, et al. Comparability of Asthma Control Test
scores between self and physician-administered test. Respir Med 2020;
170:106015.
38. Ainsworth B, Greenwell K, Stuart B, et al. Feasibility trial of a digital self-
management intervention ‘My Breathing Matters’ to improve asthma-related
quality of life for UK primary care patients with asthma. BMJ Open 2019;
9:e032465.
www.co-pulmonarymedicine.com 7