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December 2013
Kevin R. Murphy, MD
Key Points
Asthma and chronic obstructive pulmonary disease (COPD) are both common obstructive
lung diseases and, despite sharing some key symptoms, are distinct in terms of pathogenesis
and management
Review of the 2009 Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines for the Pharmacological
Management of Chronic Obstructive Pulmonary Disease
Original Publish Date = 6/29/2010
Available at: http://advanceweb.com/web/focus_on_copd/article2.html
Reversibility of Airflow Obstruction in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Original Publish Date = 2/11/2011
Available at: http://advanceweb.com/web/AstraZeneca/reversibility_of_airflow_obstruction/focus_on_copd_issue2.html
Devices for Aerosol Delivery in the Treatment of Adults With Asthma and Chronic Obstructive Pulmonary Disease
(COPD) in the United States
Original Publish Date = 7/22/2011
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Introduction
Asthma and chronic obstructive pulmonary disease (COPD) are respiratory diseases that share key symptoms,
such as dyspnea and wheezing, but are etiologically distinct. Both asthma and COPD are characterized by airflow
limitation. Asthma is a chronic inflammatory disease of hyper-reactive airways, in which episodes are often
associated with specific triggers, such as allergens [1]. In contrast, COPD is a progressive disease characterized
by persistent airflow limitation due to chronic inflammatory response of the lungs to noxious particles or gases,
primarily caused by cigarette smoking. These differences in pathology are matched by different treatment
strategies; therefore, differential diagnosis is essential.
In addition to medical history, physical examination, and spirometry, questionnaire tools can aid diagnosis,
classification of severity, and monitoring of asthma and COPD. The basics of understanding spirometry can be
reviewed at http://www.advanceweb.com/web/AstraZeneca/reversibility_of_airflow_obstruction
/spirometry_module.html. Questionnaire tools include screenings for COPD (COPD Population Screener
[COPD-PS] [2], the Clinical COPD Questionnaire [CCQ] [3], and Lung Function Questionnaire [LFQ] [4]); tools to
assess the severity of asthma (National Asthma Education and Prevention Program [NAEPP] [5]); tools to monitor
disease progression and control (Asthma Control Test [ACT] [6], pediatric Test for Respiratory and Asthma Control
in Kids [TRACK] [7]); and tools to help differentiate between asthma and COPD [8, 9].
The measurement of forced expiratory volume in 1 second (FEV1) with a spirometer can also facilitate the
monitoring of both asthma and COPD in primary care. Handheld digital spirometers for office use are an
alternative to conventional spirometry for the routine monitoring of lung function. These devices have acceptable
accuracy, are easy to use, and require minimal storage space [10]. Additionally, emerging tools, such as exhaled
nitric oxide (eNO), are available and can be used in the diagnosis of asthma and differentiation between asthma
and COPD [11]. Because both asthma and COPD are highly prevalent, Nurse Practitioners are at the forefront of
diagnosing, managing, and differentiating between asthma and COPD [1].
Mark is a 48-year-old white man who is rarely seen in the clinic. However, he is becoming increasingly
worried about episodes of breathlessness, which occur 13 times a year. He shows no sign of acute
respiratory distress as he talks through his recent medical history, which includes cutting down on a
15pack year history of smoking from 1 pack per day to 12 cigarettes per week. He remembers something
from his childhood about "athletes asthma" but does not have a recent history of use of inhalers. On
questioning, he mentions an uncle with asthma.
Diagnosis of Asthma
An accurate diagnosis of asthma is based on a combination of medical history, physical examination, and
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spirometry [5]. A thorough medical history should include pattern of occurrence; precipitating or aggravating
factors; exacerbation type, severity, and frequency; family and social history; and the patients own assessment of
their illness.
The physical examination should be focused on abnormalities of the nose, throat, upper airway, skin, and chest
[5]. In terms of the latter, hyperexpansion of the thorax, use of accessory muscles, appearance of hunched
shoulders, and chest deformity should increase the suspicion of asthma. Auscultations of wheezing during normal
breathing and/or a prolonged phase of forced exhalation are typical findings associated with airflow obstruction.
However, the NAEPP notes that wheezing may only be heard during forced exhalation, but this is not a reliable
indicator of airflow limitation [5]. Signs of allergic reactions, such as increased nasal secretion, mucosal swelling,
and/or nasal polyps; atopic dermatitis/eczema; or any other manifestation of an allergic skin condition, should also
raise suspicion of asthma [5].
Spirometry, in combination with medical history and physical examination, is essential to establish the diagnosis of
asthma. Spirometry must establish reversible obstructive airflow defined as an increase in FEV1 of 12% and 200
mL after the administration of a bronchodilator [12]. The Global Initiative for Asthma (GINA) guidelines advise that
most asthma patients will not demonstrate reversibility at every assessment; therefore, repeat assessments are
recommended [12]. Importantly for the differential diagnosis of asthma and COPD, it should be noted that
persistent non-fully reversible airway obstruction, the classic hallmark of COPD, can also occur in patients with
long-standing asthma [13].
The NAEPP provides guidance on establishing the severity of asthma, which is based on 2 components:
impairment and risk of future adverse effects of the condition (such as exacerbations and decreasing lung
function). Both of these domains are based on spirometry, frequency of symptoms and their effect on normal
activity, and response to treatment [5]. Similarly, assessment of asthma control relies on the monitoring of the
effectiveness of interventions to reduce impairment and reduce the risk of future adverse events [5].
Diagnosis of COPD
Diagnosis of COPD relies on the clinical presentation of the patient, a detailed review of the patients medical
history, and spirometry. Key indicators include progressive dyspnea, chronic cough, chronic sputum production,
and exposure to risk factors for the disease (smoking in particular) [14]. Diagnosing COPD can be complicated by
the presence of comorbidities, especially age-related conditions such as congestive heart failure and cardiac
arrhythmia that can mimic COPD exacerbations [14]. Two validated COPD screening tools, the LFQ [4, 15] and
COPD-PS questionnaire [2], can help identify patients who are at high risk for airflow obstruction and should
undergo spirometry. Both tools comprise 5 questions relating to patients smoking history, age, and symptoms and
can also be used to identify adults with risk factors, such as smoking history or exposure to environmental or
occupational pollutants [2]. Figure 1 shows the COPD-PS tool [2].
Figure 1. The COPD-PS Tool [2].
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Martinez et al. COPD. 2008; 5(2):8595, copyright 2008, Informa Healthcare. Reproduced with permission of Informa
Healthcare [2].
Patients with scores that indicate possible COPD should undergo spirometry. According to the American Thoracic
Society/European Respiratory Society (ATS/ERS) [16], the following is required to establish a COPD diagnosis:
postbronchodilator FEV1/ forced vital capacity (FVC) ratio 0.7, demonstrating airflow limitation that is not fully
reversible.
Spirometry also establishes the severity of the disease. According to the Global Initiative for Chronic Obstructive
Lung Disease (GOLD) guidelines, FEV1 % of predicted postbronchodilator levels of 80, 50<80, 30<50, and <30
indicate mild, moderate, severe, and very severe COPD, respectively [16]. The COPD Foundation has established
a somewhat different guide. Consistent with GOLD, the postbronchodilator FEV1/FVC ratio must be <0.7, but
slightly different postbronchodilator FEV1 criteria are used. Table 1 compares the GOLD and COPD foundation
FEV1 criteria for mild, moderate, severe, and very severe COPD. The COPD Foundation guidelines also include
the further category of Spirometry Grade Undefined (SG U)undefined COPDthat includes patients with
FEV1/FVC ratio >0.7, but FEV1 <80% predicted. The COPD foundation suggests these characteristics are
consistent with restriction, muscle weakness, and other pathologies [17]. These spirometry outcomes are just 1 of
several severity domains that the COPD foundation uses to guide therapy.
Table 1. GOLD and COPD Foundation Criteria for Establishing the Severity of COPD
GOLD
Mild
COPD Foundation
60%
Moderate
50<80%
30%<60%
Severe
30<50%
<30%
Very severe
<30%
COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity;
GOLD, Global Initiative for Chronic Obstructive Lung Disease; SG U, Spirometry Grade Undefined.
The COPD Foundation includes a further category, SG Uundefined COPDthat includes patients with FEV1/FVC ratio
>0.7, but FEV1 <80% predicted.
An accurate diagnosis requires accurate spirometry. The ATS/ERS guidelines on acceptable maneuvers
emphasize the importance of coaching the patient. This includes aspects such as ensuring a complete inhalation
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before beginning the maneuver, prompting the patient to "blast," not just "blow," the air from their lungs, and
encouraging him/her to fully exhale [18]. A summary of the within- and between-maneuver acceptability criteria is
provided in Table 2.
Obstructed mouthpiece
Between-maneuver criteria
After 3 acceptable spirograms have been obtained, apply the
following tests:
ATS, American Thoracic Society; ERS, European Respiratory Society; FEV1, forced expiratory volume in 1 second; FVC,
forced vital capacity.
This presentation has not been reviewed by European Respiratory Society prior to release; therefore the European
Respiratory Society may not be responsible for any errors, omissions or inaccuracies, or for any consequences arising
there from, in the content. Reproduced with permission of the European Respiratory Society: Eur Respir J August 2005
26:319338; doi:10.1183/09031936.05.00034805 [18].
In a minority of patients, differentiating asthma and COPD on the basis of reversibility of airway obstruction may
not be possible, especially in patients with long-standing asthma. Findings of a recent study suggested that the
association between early-onset, current clinical asthma, and irreversible airway obstruction was equivalent to a
33 pack-year history of smoking (odds ratio, 3.7; 95% CI, 1.59.3; P = 0.005) [19]. However, a detailed medical
history can help distinguish between the 2 conditions, and some key differentiating features are listed in Table 3
[1].
COPD
Onset in mid-life
Presence of comorbidities
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In addition, screening questionnaires have been developed with the specific aim of aiding differentiation between
asthma and COPD [5, 7]. A simple questionnaire based on age of onset, smoking history, atopy status, and cough
quality (Table 4) correctly classified asthma or COPD in 87.4% of cases [8]. Similarly, Tinkelman et al [9] derived a
symptom-based questionnaire including age, smoking pack-years, and 8 questions including worsening cough,
breathing-related disability or hospitalization, worsening dyspnea and phlegm quantity. This tool was reported to
have a diagnostic sensitivity and specificity of 72.0 and 82.7, respectively [9].
Table 4. 4-Item Questionnaire for Differentiating Asthma and COPD
Item
Points
Age of onset, y
<20
2040
4060
>60
Atopy
Yes
No
Smoked pack-years
>0<20
2040
>40
Cough characteristics
Dry cough
No cough
Productive cough
Scores range from 015 points, with high scores indicating COPD and low scores suggesting asthma. A cutoff score of 7
had 87.6% sensitivity and 87.2% specificity for COPD, with 87.4% classified correctly. The overlap between asthma and
COPD (score 68) comprised approximately 20% of the total population.
Marks age and smoking history raise a concern for COPD, but a score of "7" with the differentiating tool
developed by Beeh et al [8] (Table 4) suggests either coexistent disease or the need for further tests. Marks
spirometry results reveal a postbronchodilator FEV1/FVC ratio of 0.81 and FEV1 % predicted of 85.
Note: This is a hypothetical case description for teaching purposes
In difficult cases, the use of flow-volume loops may aid differential diagnosis. While spirometry reports airflow over
time, the flow-volume loop depicts airflow (in liters per second) as it relates to lung volume (in liters) during
maximal inspiration from complete exhalation and during maximum expiration from complete inhalation [18].
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Flow-volume loops can show whether airflow is appropriate for a particular lung volume. Examples of normal and
abnormal flow-volume loops are shown in Figure 2 [20]. Examples of differentials that can be uncovered by
flow-volume loops include reversibility (asthma/COPD) and obstructive (asthma or COPD) versus restrictive
(pulmonary fibrosis, pneumonias, pleural effusion), or mixed (coexisting obstructive and restrictive) conditions.
Figure 2. Normal and Abnormal Flow-Volume Loops [20]
(a) A typical obstructive pattern; (b) an obstructive pattern with patchy collapse of small airways early in exhalation; (c)
example of a typical restrictive defect; and (d) example of a typical mixed (coexisting obstructive and restrictive) defect.
Solid line = predicted flow-volume curves; Dashed line = observed inspiratory and expiratory flow volume curves.
This presentation has not been reviewed by European Respiratory Society prior to release; therefore the European
Respiratory Society may not be responsible for any errors, omissions or inaccuracies, or for any consequences arising
there from, in the content. Reproduced with permission of the European Respiratory Society: Eur Respir J November 2005
26:948968; doi:10.1183/09031936.05.00035205 [20].
As shown in Figure 3, both the inspiratory and expiratory portions of the loop provide important information. In
Marks case, the expiratory portion of the loop can provide extra information. In Figure 3, the lung damage that
accompanies COPD has caused a typical angle in the slope of the expiratory phase that helps distinguish the
condition from asthma [18, 21].
With asthma, the expiratory portion of the loop curve is typically a smooth concave shape as the airway obstruction is
relatively stable throughout expiration. With COPD, the curve is typically angled as the damaged lungs in COPD collapse
with forced expiration. Y axis = flow rate; X axis = volume from full inspiration to full expiration; dotted line = normal
flow-volume curve.
Reproduced with permission from GP-training.neta GP education and training resource [21].
Biomarkers of asthma may also aid differentiation from COPD. In a recent review, biomarkers that are already in
clinical use, along with promising biomarkers in development are summarized [22]. One of the markers discussed
is eNO, which is often higher in patients with asthma versus patients without asthma or COPD [11, 23]. In 2011,
the ATS released guidelines on the use of eNO for clinic applications, and, in summary, levels >50 ppb in adults
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indicate inflammation of the airways typical of asthma [23]. This topic will be explored in more depth in a future
newsletter.
Marks flow-volume loop results demonstrated a smooth, concave expirational portion of the loop that
normalizes postbronchodilator indicative of asthma. His eNO was 60 ppb.
Note: This is a hypothetical case description for teaching purposes
As the diagnosis of asthma has now been made, it is important to think about monitoring the progression of Marks
condition over time. The emergence of user-friendly handheld spirometers with acceptable accuracy has greatly
facilitated routine monitoring of lung function [10]. In addition to routine monitoring of lung function,
questionnaire-based tools can aid the monitoring of disease progression. For asthma, the ACT, Asthma Therapy
Assessment Questionnaire control index, and the Asthma Control Questionnaire have all been validated for use in
this regard [5]. For younger patients, the child version of ACT (C-ACT) [24] and the Test for TRACK [7] are
available. If diagnosis had been COPD, the CCQ would be an appropriate questionnaire to monitor disease
progression.
Conclusions
Asthma and COPD can be challenging to differentiate, and in a proportion of patients (especially the
elderly), the conditions can coexist [25, 26]. However, a rigorous medical history, physical examination,
use of screening tools, and appropriate lung function tests can accurately differentiate between these
conditions in most patients, allowing disease-specific management.
Acknowledgements
We thank Paul Coyle, BSc, and Cherie K. Whitmore, PharmD, MBA, of Scientific Connexions (Lyndhurst, NJ) for
medical writing support funded by AstraZeneca LP (Wilmington, DE).
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