GINA2009

	DO
	-
COPYRIGHTED	MATERIAL

				REPRODUCE!
		CHAPTER
			OR	2
		ALTER
	NOT
		DIAGNOSIS

AND

CLASSIFICATION

KEY POINTS:

CLINICAL DIAGNOSIS

• A clinical diagnosis of asthma is often prompted

A correct diagnosis of asthma is essential if approprdistinguishedate from so-called eosinophilic bronchit drug therapy is to be given. Asthma symptoms may bewhich patients have cough and sputum eoinophils but

					Medical History
by symptoms such as episodic breathlessness,
wheezing, cough, and chest tightness.					Symptoms . A clinical diagnosis of asthma is often promp
					by symptoms such as episodic breathlessness, wheez
• Measurements of lung function (spirometry or peak									1
					cough, and chest tightness. Epi odic symptoms after an
expiratory flow) provide an assessment of the severity
					incidental allergen exposure, seasonal variability of
of airflow limitation, its reversibility, and its variability,
					symptoms and a positive family history of asthma and
and provide confirmation of the diagnosis of asthma.
					atopic disease are also helpful diagnostic guides. As
					associated with rhinitis may occur intermittently
• Measurements of allergic status can help to identify
risk factors that cause asthma symptoms in					patient being entirely asymptomatic between seasons
					may involve seasonal worsening of asthma symptoms or
individual patients.
					a background of persistent asthma. The patterns of th
• Extra measures may be required to diagnose					symptoms that strongly suggest an asthma diagnosis
					variability; precipitation by non-specific irritants
asthma in children 5 years and younger and in the										REPRODUCE!
elderly, and occupational asthma.					smoke, fumes, strong smells, or exercise; worsening
					night; and responding to appropriate asthma therapy.
								OR
					Useful questions to consider when establishing a
• For patients with symptoms consistent with asthma,
					diagnosis of asthma are describedFigurein2-1 .
but normal lung function, measurement of airway
responsiveness may help establish the diagnosis.
						Figure 2-1. Questions to Consider in the Diagnosis
						of Asthma
• Asthma has been classified by severity in previous
							ALTER
reports. However, asthma severity may change over											wheezing
						• Has the patient had an attack or recurrent attacks of
time, and depends not only on the severity of the
						• Does the patient have a troublesome cough at night?
underlying disease but also its responsiveness to
treatment.						• Does the patient wheeze or cough after exercise?
				NOT
						• Does the patient experience wheezing, chest tightness, or
						cough after exposure to airborne allergens or pollutants?
• To aid in clinical management, a classification of• Do the patient's colds “go to the chest” or take more than 10
		DO				days to clear up?
asthma by level of control is recommended.-
						• Are symptoms improved by appropriate asthma treatment?
• Clinical control of asthma is defined as:
					In some sensitized individuals, asthma may be
- No (twice or less/week) daytime symptoms
					exacerbated by seasonal increases in specific
- No limitations of daily activites, inlcuding exercise2
					aeroallergens. Examples includeAlternaria,and birch,
- No nocturnal symptoms or awakening because					grass, and ragweed pollens.
of asthma
- No (twice or less/week) need for reliever treatmentCough-variant asthma.									Patients with cough-variant
	MATERIAL						3
- Normal or near-normal lung function
					asthma have chronic cough as their principal, if not on
- No exacerbations					symptom. It is particularly common in children, and i
					often more problematic at night; evaluations during t
					day can be normal. For these patients, documentation of
					variability in lung function or of airway hyperrespon
INTRODUCTION
					and possibly a search for sputum eosinophils, are
COPYRIGHTED
								4
					particularly important. Cough-variant asthma must be

	normal indices of lung function when assessed by
intermittent and their significance may be overlooked by
	spirometry and airway hyperresponsiveness.
patients and physicians, or, because they are non-specific,		5
they may result in misdiagnosis (for example of wheezy
	Other diagnoses to be considered are cough-induced by
bronchitis, COPD, or the breathlessness of old age). This
	angiotensin-converting-enzyme (ACE) inhibitors,
is particularly true among children, where misdiagnoses
	gastroesophageal reflux, postnasal drip, chronic sinus
include various forms of bronchitis or croup, and lead to
inappropriate treatment.	and vocal cord dysfunction.
	6

16 DIAGNOSIS AND CLASSIFICATION

Exercise-induced bronchoconstriction. Physical	Tests for Diagnosis and Monitoring
activity is an important cause of asthma symptoms for
most asthma patients, and for some it is the only causeMeasurements.		of lung function.	The diagnosis of

Exercise-induced bronchoconstriction typically developsasthma is usually based on the presence of characteris within 5-10 minutes after completing exercise (it symptomsrarely. However, measurements of lung function, occurs during exercise). Patients experience typicaland particularly the demonstration of reversibility o asthma symptoms, or sometimes a troublesome cough, function abnormalities, greatly enhance diagnostic which resolve spontaneously within 30-45 minutes. Someconfidence. This is because patients with asthma forms of exercise, such as running, are more potentfrequently have poor recognition of their symptoms an triggers7 . Exercise-induced bronchoconstriction may occurpoorperception of symptom severity, especially if th in any climatic condition, but it is more common whenasthmathe is long-standing10 . Assessment of symptoms such patient is breathing dry, cold air and less common inashot,dyspnea and wheezing by physicians may also be

8	inaccurate. Measurement of lung function provides an
humid climates.
	assessment of the severity of airflow limitation,

Rapid improvement of post-exertional symptoms afterreversibility and its variability, and provides conf

inhaled2 -agonist use, or their prevention by pretreatmhentdiagnosis of asthma. Although measurements of l
with an inhaled-agonist before exercise, supports a function do not correlateREPRODUCE!strongly with symptoms or o
2		11	12
diagnosis of asthma. Some children with asthma presmeasuresnt of disease control in eitheror chiadultsdren,
	OR
only with exercise-induced symptoms. In this group,theseor measures provide complementary information abou
when there is doubt about the diagnosis, exercise testingdifferent aspects of asthma control.
is helpful. An 8-minute running protocol is easily

performed in clinical practice and can establish a fiVariousm methods are available to assess airflow limita
diagnosis of asthma.		ALTER
	but two methods have gained widespread acceptance for
9
	use in patients over 5 years of age. These are spirometr
Physical Examination	NOT
	particularly the measurement of forced expiratory vol
	in 1 second (FEV1 ) and forced vital capacity (FVC), and
Because asthma symptoms are variable, the physical	peak expiratory flow (PEF) measurement.
DO
examination of the respiratory system may be normal.
The most usual abnormal physical finding is wheezingPredictedon			values of1 FEV,FVC, and PEF based on age,
-
auscultation, a finding that confirms the presencesex,of andairflowheight have been obtained from population
MATERIAL	studies. These are being continually revised, and wi
limitation. However, in some people with asthma,
wheezing may be absent or only detected when the	exception of PEF for which the range of predicted value

person exhales forcibly, even in the presence of significanttoowide,they are useful for judging whether a given airflow limitation. Occasionally, in severe asthma is abnormal or not.

exacerbations, wheezing may be absent owing to severely

reduced airflow and ventilation. However, patients Thetermsinhisreversibilityand variabilityrefer to changes in state usually have other physical signs reflectingsymptomsthe accompanied by changes in airflow limitatio

exacerbation and its severity, such as cyanosis, drowsiness,thatoccur spontaneously or in response to treatment. T
COPYRIGHTED		is generally applied to rapid impro
difficulty speaking, tachycardia, hyperinflated chest,termreversibilityuse of
accessory muscles, and intercostal recession.	in FEV1 (or PEF), measured within minutes after inhalat
	of a rapid-acting bronchodilator—for example after 200-400

Other clinical signs are only likely to be present ifugpatientssalbutamol (albuterol)13 —or more sustained improvement are examined during symptomatic periods. Features ofover days or weeks after the introduction of effecti hyperinflation result from patients breathing atcontrollerahigher treatment such as inhaled glucocorticoster13 .

lung volume in order to increase outward retraction ofVariabilitythe refers to improvement or deterioration in airways and maintain the patency of smaller airways symptoms and lung function occurring over time. (which are narrowed by a combination of airway smooth Variability may be experienced over the course of one da muscle contraction, edema, and mucus hypersecretion)(when. it is called diurnal variability), from day to day The combination of hyperinflation and airflow limitationmonthtoinmonth, or seasonally. Obtaining a history of

an asthma exacerbation markedly increases the work	variability is an essential component of the diagnosi
of breathing.	asthma. In addition, variability forms part of the
	assessment of asthma control.

DIAGNOSIS AND CLASSIFICATION

17

Spirometryis the recommended method of measuring as the amplitude (the difference between the maximu airflow limitation and reversibility to establishandiagnostheminimumsof value for the day), expressed as a asthma. Measurements of FEV1 and FVC are undertaken percentage of the mean daily PEF value, and averaged during a forced expiratory maneuver using a spirometover. 1-2 weeks19 . Another method of describing PEF Recommendations for the standardization of spirometryvariability is the minimum morning pre-bronchodilat have been published13-15 . The degree of reversibility inover 1 week, expressed as a percent of the recent best

800	REPRODUCE!
FEV 1 which indicates a diagnosis of asthma is generally(Min%Max) (	Figure 2-2 )19 . This latter method has been

accepted as ≥ 12% and ≥ 200 ml from the pre-bronchodilator suggested to be the best PEF index of airway lability value13 . However most asthma patients will not exhibitclinical practice because it requires only a once-daily reversibility at each assessment, particularly thosereading,on correlates better than any other index with ai treatment, and the test therefore lacks sensitivityhyperresponsiveness,. and involves a simple calculati Repeated testing at different visits is advised.

measurements of PEF are not interchangeable with otherPEFmonitoring is valuable in a subset of asthmatic

Spirometry is reproducible, but effort-dependent.

Figure 2-2. Measuring PEF Variability*

Therefore,

proper instructions on how to perform the forced expiratory

Inhaled glucocorticosteroids

commenced

maneuver must be given to patients, and the highest value

OR

of three recordings taken. As ethnic differences in

spirometric values have been demonstrated, appropriate 700

predictive equations for1 andFEVFVC should be

600

ALTER

established for each patient. The normal range of values

is wider and predicted values are less reliable in young500

people (< age 20) and in the elderly (> age 70). Because

L/mi

PEF

400

many lung diseases may result in reduced1 , a usefulFEV

300

assessment of airflow limitation is the1 to ratio of FEV

FVC. The FEV 1 /FVC ratio is normally greater than 0.75 to

200

0.80, and possibly greater than 0.90 in children. Any

310/700

500/710

620/720

100

= 44%

= 70%

= 86%

values less than these suggest airflow limitation.

NOT

Peak expiratory flow measurements are made using a

0

-

1

0 1 2

3 4 5 6 7

8 9 10

Weeks of Inhaled Glucocorticosteroid Treatment

peak flow meter and can be an important aid in both

DO

*PEF chart of a 27-year-old man with long-standing, poorly controlled asthma, before

-

diagnosis and monitoring of asthma. Modern PEF meters

and after the start of inhaled glucocorticosteroid treatment. With treatment, PEF

levels increased, and PEF variability decreased, as seen by the increase in Min%Max

are relatively inexpensive, portable, plastic, and ideal for

(lowest morning PEF/highest PEF %) over 1 week.

patients to use in home settings for day-to-day objective

measurement of airflow limitation. However,

MATERIAL

spirometry is the preferred method of documentin

measurements of lung function such1 inaseitherFEV		patients and can be helpful:
adultsor children. PEF can underestimate the degree
16	17	• To confirm the diagnosis of asthma. Although
of airflow limitation, particularly as airflow limitation and
COPYRIGHTED

gas trapping worsen. Because values for PEF obtained	airflow limitation, a 60 L/min (or 20% or more of pre-
with different peak flow meters vary and the range of
predicted values is too wide, PEF measurements shouldbronchodilator PEF) improvement after inhalation of a
	bronchodilator, or diurnal variation in PEF of more
	20
preferably be compared to the patientis own previous best
	than 20% (with twice daily readings, more than) 10%
measurementsusing his/her own peak flow meter. The	suggests a diagnosis of asthma.	21
18

previous best measurement is usually obtained when the

patient is asymptomatic or on full treatment and serves•To improve control of asthma, particularly in patients
as a reference value for monitoring the effects of changeswith poor perception of symptoms . Asthma
	10
in treatment.	management plans which include self-monitoring o
	symptoms or PEF for treatment of exacerbations have

Careful instruction is required to reliably measure PEFbeen shown to improve asthma outcomes22 . It is easier because PEF measurements are effort-dependent. Most to discern the response to therapy from a PEF chart commonly, PEF is measured first thing in the morningthan from a PEF diary, provided the same chart format before treatment is taken, when values are often closeisto consistently23 . used

their lowest, and last thing at night when values are usually higher. One method of describing diurnal PEF variability is

18 DIAGNOSIS AND CLASSIFICATION

• To identify environmental (including occupational) Non-invasive markers of airway inflammation. The

causes of asthma symptoms. This involves the patientevaluation of airway inflammation associated with ast monitoring PEF daily or several times each day over may be undertaken by examining spontaneously produced

periods of suspected exposure to risk factors in theorhypertonichome

saline-induced sputum for eosinophili

or workplace, or during exercise or other activitiesneutrophilicthat

inflammation. In addition, levels of exhaled

30

have

may cause symptoms, and during periods of non-exposurenitric. oxide (FeNO)and carbon monoxide (FeCO)

32

31

been suggested as non-invasive markers of airway

Measurement of airway responsiveness.

For patients

inflammation in asthma. Levels of FeNO are elevated in

people with asthma (who are not taking inhaled gluco-

with symptoms consistent with asthma, but normal lung

corticosteroids) compared to people without asthma, yet

function, measurements of airway responsiveness to

these findings are not specific for asthma. Neithe

direct airway challenges such as inhaled methacholine and

eosinophilia nor FeNO have been evaluated prospectively

histamine or indirect airway challenges such as inhaled

60

as an aid in asthma diagnosis, but these measurement

mannitolor exercise challenge may help establish a

are being evaluated for potential use in determining

24

diagnosis of asthma. Measurements of airway

33,34,56

optimal treatment, although it has been shown that the

responsiveness reflect the “sensitivity” of the airways to

use of FeNo as a measure of asthma control does not

factors that can cause asthma symptoms, sometimes improve control or enableREPRODUCE!reduction in dose of inhaled

called “triggers,” and the test results are usually expressed

55

glucocorticosteroid.

as the provocative concentration (or dose) of the agonist

OR

causing a given fall (often 20%) in1 (FigureFEV 2-3 ).

Measurements of allergic status

. Because of the strong

These tests are sensitive for a diagnosis of asthma, but

25

association between asthma and allergic rhinitis, the

have limited specificity. This means that a negative test

presence of allergies, allergic diseases, and allergic

can be useful to exclude a diagnosis of persistent asthma

in particular, increases the probability of a diagnosi

in a patient who is not taking inhaled glucocorticosteroid

asthmaALTERin patients with respiratory symptoms. Moreov

treatment, but a positive test does not always mean that a

26

the presence of allergies in asthma patients (identi

patient has asthma. This is because airway

skin testing or measurement of specific IgE in ser

hyperresponsiveness has been described in patients with

27

help to identify risk factors that cause asthma sym

allergic rhinitand ins those with airflow limitationNOTcaused

28

individual patients. Deliberate provocation of the air

by conditions other than asthma, such as cystic, fibrosis

with a suspected allergen or sensitizing agent may b

bronchiectasis, and chronic obstructive pulmonary disease

(COPD) 29 .

-DO

helpful in the occupational setting, but is not rout

recommended, because it is rarely useful in establi

diagnosis, requires considerable expertise and can re

35

in life-threatening bronchospasm.

Figure 2-3. Measuring Airway Responsiveness*

Skin tests with allergens represent the primary dia

MATERIAL

tool in determining allergic status. They are simple

COPYRIGHTED

rapid to perform, and have a low cost and high sensitivi

However, when improperly performed, skin tests can le

to falsely positive or negative results. Measuremen

specific IgE in serum does not surpass the reliabil

results from skin tests and is more expensive. The

limitation of methods to assess allergic status is

positive test does not necessarily mean that the dis

allergic in nature or that it is causing asthma, as som

individuals have specific IgE antibodies without an

symptoms and it may not be causally involved. The

relevant exposure and its relation to symptoms must

confirmed by patient history. Measurement of total I

serum has no value as a diagnostic test for atopy.

*Airway responsiveness to inhaled methacholine or histamine in a normal subject, and in asthmatics with mild, moderate, and severe airway hyperresponsiveness. Asthmatics have an increased sensitivity and an increased maximal bronchoconstrictor response to the agonist. The response to the agonist is usually expressed as the provocative concentration causing a 20% decline in FEV1 (PC20).

DIAGNOSIS AND CLASSIFICATION

19

DIAGNOSTIC CHALLENGES AND DIFFERENTIAL DIAGNOSIS

Alternative causes of recurrent wheezing must be considered and excluded. These include:

			• Chronic rhino-sinusitis
The differential diagnosis in patients with suspected• Gastroesophageal reflux
asthma differs among different age groups: infants,
children, young adults, and the elderly.			• Recurrent viral lower respiratory tract infections
			• Cystic fibrosis
Children 5 years and Younger			• Bronchopulmonary dysplasia
			• Tuberculosis
The diagnosis of asthma in early childhood is challenging
and has to be based largely on clinical judgment and an			• Congenital malformation causing narrowing of the
			intrathoracic airways
assessment of symptoms and physical findings. Since
			• Foreign body aspiration
the use of the label “asthma” for wheezing in children has
			• Primary ciliary dyskinesia syndrome
important clinical consequences, it must be distinguished
from other causes persistent and recurrent wheeze.			• Immune deficiency
			• Congenital heart disease
Episodic wheezing and cough is very common even in				REPRODUCE!
		Neonatal onset of symptoms (associated with failure t
children who do not have asthma and particularly in those
		thrive), vomiting-associated symptoms, or focal lung o
under age 36 . Three categories of wheezing have been		cardiovascular signsORsuggest an alternative diagnosi
described in children 5 years and younger:		indicate the need for further investigations.

• Transient early wheezing,which is often outgrown in

the first 3 years. This is often associated withA useful method for confirming the diagnosis of ast

	prematurity and parental smoking.			children 5 years and younger is a trial of treatment wi
	• Persistent early-onset wheezing(before age 3). These			short-actingALTERbronchodilators and inhaled glucocorticoste
				Marked clinical improvement during the treatment and
	children typically have recurrent episodes of wheezing
				deterioration when treatment is stopped supports a
	associated with acute viral respiratory infections, have
	37			diagnosis of asthma. Use of spirometry and other
	no evidence of atopyand, unlike children in the nextNOT
				measures recommended for older children and adults
	category of late onset wheezing/asthma, have no family
	history of atopy. The symptoms normally persist such as airway responsiveness and markers of airway
			DO	inflammation is difficult and several require comp
	through school age and are still present-at age 12 in a
		MATERIAL		equipmentmaking them unsuitable for routine use.
	large proportion of children. The cause of the episode					41
				However, children 4 to 5 years old can be taught to use a
	is usually the respiratory syncytial virus in children
				PEF meter, but to ensure reliability parental supervis
	younger than age 2, while other viruses predominate in
				required.
	older preschool children.				42
	• Late-onset wheezing/asthma. These children have			Older Children and Adults
	asthma which often persists throughout childhood and
	into adult life. They typically have an atopic			A careful history and physical examination, together w
	38, 39
	COPYRIGHTED
	background, often with eczema, and airway pathologythe demonstration of reversible and variable airflow
	is characteristic of asthma.			obstruction (preferably by spirometry), will in most
	The following categories of symptoms are highly			instances confirm the diagnosis. The following cat
				of alternative diagnoses need to be considered:
	suggestive of a diagnosis of asthma: frequent episodes of
	wheeze (more than once a month), activity-induced cough
	or wheeze, nocturnal cough in periods without viral			• Hyperventilation syndrome and panic attacks
				• Upper airway obstruction and inhaled foreign bodies
	infections, absence of seasonal variation in wheeze, and						43
							44
				• Vocal cord dysfunction
	symptoms that persist after age 3. A simple clinical index

	based on the presence of a wheeze before the age of 3,	• Other forms of obstructive lung disease, particularl
		• Non-obstructive forms of lung disease (e.g., diff
	and the presence of one major risk factor (parental history

of asthma or eczema) or two of three minor risk factors parenchymal lung disease)

(eosinophilia, wheezing without colds, and allergic rhinitis)• Non-respiratory causes of symptoms (e.g., left has been shown to predict the presence of asthma in laterventricular failure)

childhood38 . However, treating children at risk with Becauseinhaledasthma is a common disease, it can be found in glucocorticosteroids has not been shown to affect theassociation with any of the above diagnoses, which

development of asthma.	complicates the diagnosis as well as the assessment
40

20 DIAGNOSIS AND CLASSIFICATION

severity and control. This is particularly true whenimportantasthma to confirm the diagnosis objectively. Thi is associated with hyperventilation, vocal cord dysfunction,beachieved by specific bronchial provocation46 , testing or COPD. Careful assessment and treatment of both thealthough there are few centers with the necessary f asthma and the comorbidity is often necessary to establishforspecific inhalation testing. Another method is

the contribution of each to a patientis symptoms.	monitor PEF at least 4 times a day for a period of 2 weeks
	when the patient is working and for a similar period aw
symptoms are consistent with either asthma or left			REPRODUCE!
The Elderly	from work . The increasing recognition that occupation
		47-50
	asthma can persist, or continue to deteriorate, even in
Undiagnosed asthma is a frequent cause of treatableabsence of continued exposure to the offending,				agent
			51

respiratory symptoms in the elderly, and the frequemphasizesnt the need for an early diagnosis so that presence of comorbid diseases complicates the diagnosisappropriate. strict avoidance of further exposure and Wheezing, breathlessness, and cough caused by leftpharmacologic intervention may be applied. Recent ventricular failure is sometimes labeled “cardiac publicationsasthma,” provide an evidence-based approach to the

a misleading term, the use of which is discouragedidentification.The of occupational asthma and compare spec

presence of increased symptoms with exercise and inhalation challenge testing with alternative test
night may add to the diagnostic confusion because theseconfirming the responsible .agents
		52,61
		OR
ventricular failure. Use of beta-blockers, even topicallyDistinguishing Asthma from COPD
(for glaucoma) is common in this age group. A careful	ALTER

history and physical examination, combined with an ECGBoth asthma and COPD are major chronic obstructive and chest X-ray, usually clarifies the picture. In theairwayselderly,diseases that involve underlying airway

distinguishing asthma from COPD is particularly difinficullammat,ion. COPD is characterized by airflow limitat and may require a trial of treatment with bronchodilatorsthatis not fully reversible, is usually progressiv

and/or oral/inhaled glucocorticosteroids.	associated with an abnormal inflammatory response of t
	NOT
	lungs to noxious particles or gases. Individuals wi

Asthma treatment and assessment and attainment ofasthma who are exposed to noxious agents (particularly control in the elderly are complicated by several factors:cigarette smoking) may develop fixed airflow limitat poor perception of symptoms, acceptance of dyspnea as a mixture of “asthma-like” inflammation and “COPD-like” being “normal” in old age, and reduced expectations ofinflammation. Thus, even though asthma can usually b

mobility and activity.	DO	distinguished from COPD, in some individuals who dev
	-	chronic respiratory symptoms and fixed airflow limi
	MATERIAL
Occupational Asthma		it may be difficult to differentiate the two disea
		symptom-based questionnaire for differentiating CO

Asthma acquired in the workplace is a diagnosis thatandisasthma for use by primary health care professionals frequently missed. Because of its insidious onset,isavailable53,54 .

occupational asthma is often misdiagnosed as chronic

bronchitis or COPD and is therefore either not treated at all

or treated inappropriately. The development of new COPYRIGHTED

CLASSIFICATION OF ASTHMA

symptoms of rhinitis, cough, and/or wheeze particularly in

Etiology non-smokers should raise suspicion. Detection of asthma

of occupational origin requires a systematic inquiry about

work history and exposures. The diagnosis requiresMany attempts have been made to classify asthma defined history of occupational exposure to known oraccording to etiology, particularly with regard to

environmental sensitizing agents. However, such a suspected sensitizing agents; an absence of asthma

classification is limited by the existence of pati symptoms before beginning employment; or a definite

whom no environmental cause can be identified. Despi worsening of asthma after employment. A relationship

between symptoms and the workplace (improvement inthis, an effort to identify an environmental cause f

asthma (for example, occupational asthma) should be part symptoms away from work and worsening of symptoms on

of the initial assessment to enable the use of avoida returning to work) can be helpful in establishing a link

between suspected sensitizing agents45 .and asthmastrategies in asthma management. Describing patient having allergic asthma is usually of little benefit

treatment, unless a single specific trigger agent Since the management of occupational asthma frequently

identified. requires the patient to change his or her job, the diagnosis

carries considerable socioeconomic implications and it is

DIAGNOSIS AND CLASSIFICATION

21

Phenotype	to achieve and maintain control for prolonged64periods
	with due regard to the safety of treatment, potential

There is increasing awareness of heterogeneity inadversethe effects, and the cost of treatment required

manifestations of asthma and in its response to treatmentachieve this.

goal. Therefore, the assessment of asth

57,58

control should include not only control of the clinica

This is often described in terms of hphenotypesi,the

characteristics which result from the interactionmanifestationsbetween

(symptoms, night waking, reliever u

activity limitation, lung function), but also control

patientis genetic makeup and their environment. Several

expected future risk to the patient such as exacerba

different clinical phenotypes are recognized on the basis of

accelerated decline in lung function, and side-effe

cluster analysis of clinical and other features of asthma,

treatment. In general, the achievement of good clinica

e.g. aspirin-induced asthma, exacerbation-prone asthma

65

control of asthma leads to reduced risk of exacerbation.

and the search for distinctive pathological or molecular

However, certain patients may continue to experience

features which could explain these clinical patterns

continues. Most work has been done on inflammatory

exacerbations in spite of adequate interval control.

Smokers are less likely to achieve control and remain at

phenotypes, identified using sputum induction. Patients

66

risk of exacerbations. It should be noted that inhaled

with eosinophilic and non-eosinophilic phenotypes have

corticosteroids both improve clinical control and reduc

been shown to differ in their clinical response to inhaled

59,60

future risk, but some pharmacological agents are more

glucocorticosteroids, and at a group level, inflammatory

REPRODUCE!

effective in improving features of clinical contr

markers may be predictive of risk of exacerbation after

61

ers are relatively more effective at reducing exacerb

glucocorticosteroid reduction. Inflammatory phenotypes

OR

appear to be moderately stable over time, although data

Thus, for some patient phenotypes, treatment may be

62,63

selected to address the predominant problem.

are limited. At present, since few clinicians have

access to qualified sputum laboratories, identification of

Figure 2-4

describes the clinical characteristics of

the inflammatory phenotype is most likely to be useful for

Controlled, Partly Controlledand Uncontrolled asthma.

patients with severe asthma or in the context of research.

This isALTERa working scheme based on current opinion and

Asthma Control

has not been formally validated. However, this

classification has been shown to correlate well with

67

Asthma Control Testand with assessment of asthma

NOT

Asthma control may be defined in a variety of ways. In lay

control according to the US National Expert Panel Report

terms, control may indicate disease prevention, or even

68,69

3 guidelines. In clinical practice, this classificat

cure. However, in asthma, where neither of these are real-

DO

should be used in conjunction with an assessment o

-

istic options at present, it refers to control of the

patientis clinical condition and the potential risks a

manifestations of disease. The aim of treatment should be

fits of changing treatment.

Figure 2-4. Levels of Asthma Control

Characteristic

Controlled

Partly Controlled

Uncontrolled

(All of the following)

(Any measure present in any week)

Daytime symptoms

Twice or less/week

More than twice/week

Three or more features

MATERIAL

of partly controlled

Limitations of activities

None

Any

asthma present in

Nocturnal symptoms/awakening

None

Any

any week * †

Need for reliever/

Twice or less/week

More than twice/week

rescue treatment

Lung function (PEF or FEV 1 )‡

Normal

<80% predicted or personal best

COPYRIGHTED

(if known)

Poor clinical control, frequent exacerbations in past year, ever admission to critical care, exposureforasthma,to cigarettelowFEV

B. Assessment of Future Risk(risk of exacerbations, instability, rapid decline in lung function, side-effects) Features that are associated with increased risk of adverse events in the future include:

1

smoke, high dose medications.

* Any exacerbation should prompt review of maintenance treatment to ensure that it is adequate.

† By definition, an exacerbation in any week makes that an uncontrolled asthma week.

‡ Lung function is not a reliable test for children 5 years and younger.

22 DIAGNOSIS AND CLASSIFICATION

Several standardized measures for assessing clinicalAsthma Severity control of asthma have been developed, which score the

goals of treatment as continuous variables and provideFor patients not receiving inhaled glucocorticosteroi numerical values to distinguish different levelstreatmeof cont,rolprevious. GINA documents subdivided asthm Examples of validated instruments are the Asthma Controlbyseverity based on the level of symptoms, airflow

Questionnaire (ACQ) (www.qoltech.co.uk/Asthma1.htm),	limitation, and lung function variability into four
70

the Asthma Control Test (ACT)			REPRODUCE!
			Intermittent, Mild Persistent, Moderate Persistent,
(www.asthmacontrol.com), the Childhood Asthma Control			Severe Persistent, although this classification was
Test (C-ACT)		71	erroneously applied to patients already on treatment. A
	72		79
Questionnaire (ATAQ) (www.ataqinstrument73.com), and			copy of this classification system is archived at
the Asthma Control Scoring System. Few of these			www.ginasthma.com. It is important to recognize,
		74

instruments include a measure of lung function.however,Theyarethat asthma severity involves both the sever being promoted for use not only in research but for patienttheunderlying disease and its responsiveness to care as well, even in the primary care setting. Some aretreatment80 . Thus, asthma could present with severe suitable for self-assessment of asthma control bysymptoms and airflow obstruction, but become complete

patients, and some are available in many languages, on	controlled with low-dose treatment. In addition, sever
75

the Internet, and in paper form and may be completed bynot a static featureORof an individual patientis asthm patients prior to, or during, consultations with theirmay chheangelth over months or years. The main limitation of care provider. They have the potential to improve the this previous method of classification of asthma se assessment of asthma control, providing a reproduciblewas its poor value in predicting what treatment would objective measure that may be charted over time (weekrequiredby and what a patientis response to that treatmen week or month by month) and representing an might be. For this reason, an assessment of asthma

improvement in communication between patient and control at initial presentation and periodically durin
health care professional. Their value in clinical use,treatmentasdisis more relevant and useful.
NOT	81
tinct from research settings, has yet to be demonstratedALTER

but will likely become evident in coming years. AllInofviewtheseof these limitations, asthma severity is no tools are subject to copyright restrictions, and someconsensushave classified on the basis of the intensit

fees associated with their use in research.	treatment required to achieve good asthma control.
	79,80
	Mild asthma is asthma that can be well-controlled with
There is considerable interest in controlling not onlyintensitythe treatment such as low-dose inhaled
-	glucocorticosteroids, leukotriene modifiers or cromon
clinical manifestations of asthma, but alsoDOthe
MATERIAL

inflammatory and patho-physiological features of theSevere asthma is asthma that requires high intensi disease. There is evidence that reducing inflammationtreatment, e.g. GINA Step 4, to maintain good control, or with controller therapy achieves good clinical controlwhereand good control is not achieved despite high inten

reduces the risk of exacerbations. In addition, treatment. It is recognized that different asthma
82
inflammatory and patho-physiological markers may be prephenotypes-	may have different levels of responsiven

dictors of future risk of exacerbations and declineconventionalinlung treatment. As phenotype-specific treatm function, independent of the patientis level of clinicalbecomes available, asthma which was previously

control66,76 . Biomarker-guided treatment appears, primarily,considered to be severe could become mild. to be of value in asthma phenotypes in which there is

unavailabilityCOPYRIGHTEDof tests such as endobronchial biopsyprofessionalsand communicate clearly how the words are measurement of sputum eosinophils and exhaled nitricused in the context of asthma.

dissociation between measures of clinical control Terminologyand around asthma severity is confusing bec airway inflammation. For example, treatment based on “stheverity” is also used to describe the magnitude of proportion of eosinophils in sputum has resulted inobstructiona or the intensity of symptoms. Patients reduction of exacerbations or minimization of dosesoften perceive their asthma as severe if they have in inhaled glucocorticosteroids in patients with uncontorfrolledequent symptoms, but it is important to convey t

77,78	this may merely represent inadequate treatment. Becau
asthma in spite of moderate levels of treatment.
	the terms “control” and “severity” are used in other
However, in primary care, because of the cost and/or	contexts in lay language, it is important that health

oxide30-34 , the current recommendation is that treatment should be aimed at controlling the clinical features of disease, including lung function abnormalities.

DIAGNOSIS AND CLASSIFICATION

23

16. Sawyer G, Miles J, Lewis S, Fitzharris P, Pearce N, Beasley R. Classification of asthma severity: should the internatio lines be changed?Clin Exp Allergy1998;28(12):1565-70.

REFERENCES

1. Levy ML, Fletcher M, Price DB, Hausen T, Halbert RJ, Yawn

BP. International Primary Care Respiratory Group (IPCRG)

17. Eid N, Yandell B, Howell L, Eddy M, Sheikh S. Can peak Guidelines: diagnosis of respiratory diseases in primary care.

Prim Care Respir J2006;15(1):20-34. expiratory flow predict airflow obstruction in children w asthma? Pediatrics2000;105(2):354-8.

2.	Yssel H, Abbal C, Pene J, Bousquet J. The role of IgE in		18.	Reddel HK, Marks GB, Jenkins CR. When can personal best
	asthma.Clin Exp Allergy1998;28 Suppl 5:104-9.
				peak flow be determined for asthma actionThoraxplans?
3.	Corrao WM, Braman SS, Irwin RS. Chronic cough as the sole			2004;59(11):922-4.
	presenting manifestation of bronchialN EnglasthmaJ Med .		19.	Reddel HK, Salome CM, Peat JK, Woolcock AJ. Which index of
	1979;300(12):633-7.
				peak expiratory flow is most useful in the management of
4.				asthma? Am J Respir Crit Care Med 1995;151(5):1320-5.
	Gibson PG, Fujimura M, Niimi A. Eosinophilic bronchitis: clinical
	manifestations and implications forThoraxtreatment.		20.	Dekker FW, Schrier AC, Sterk PJ, Dijkman JH. Validity of peak
	2002;57(2):178-82.
				expiratory flow measurement in assessing reversibilit
5.	Gibson PG, Dolovich J, Denburg J, Ramsdale EH, Hargreave			obstructionThorax. 1992;47(3):162-6.
	FE. Chronic cough: eosinophilic bronchitis without asthma.						REPRODUCE!
			21.
	Lancet 1989;1(8651):1346-8.			Boezen HM, Schouten JP, Postma DS, Rijcken B. Distribution
				of peak expiratory flow variability by age, gender and smokin
6.	Irwin RS, Boulet LP, Cloutier MM, Fuller R, Gold PM, Hoffstein			habits in a random population sample aged 20-70 yrsEur.
	V, et al.Managing cough as a defense mechanism and as a					OR
				Respir J1994;7(10):1814-20.
	symptom. A consensus panel report of the American College of
	Chest PhysiciansChest. 1998;114(2 Suppl Managing):133S-81S.		22. Gibson PG, Powell H. Written action plans for asthma: an
				evidence-based review of the key componentsThorax .
7.	Randolph C. Exercise-induced asthma: update on			2004;59(2):94-9.
	pathophysiology, clinical diagnosis, and treatmentCurr Probl .				ALTER
	Pediatr1997;27(2):53-77.		23. Reddel HK, Vincent SD, Civitico J. The need for standardisation
				of peak flow chartsThorax. 2005;60(2):164-7.
		NOT

8.Tan WC, Tan CH, Teoh PC. The role of climatic conditions and

								24. Cockcroft DW. Bronchoprovocation methods: direct challenges.
	histamine release in exerciseinduced bronchoconstriction.
	Ann Acad Med Singapore	1985;14(3):465-9.							Clin Rev Allergy Immunol2003;24(1):19-26.
	9. Anderson SD. Exercise-induced asthma in children: a marker 25.								Cockcroft DW, Murdock KY, Berscheid BA, Gore BP. Sensitivity
						DO			and specificity of histamine PC20 determination in a random
	of airway inflammationMed J Aust.			2002;177 Suppl:S61-3.	-
									selection of young college studJ Allentsrgy Clin. Immunol
	10. Killian KJ, Watson R, Otis J, St Amand TA, O'Byrne PM.								1992;89(1 Pt 1):23-30.
	Symptom perception during acute bronchoconstrictionAm J						.	26. Boulet LP. Asymptomatic airway hyperresponsiveness: a
	Respir Crit Care Med 2000;162(2 Pt 1):490-6.
									curiosity or an opportunity to preventAmasthma?J Respir Crit
	11. Kerstjens HA, Brand PL, de Jong PM, Koeter GH, Postma DS.								Care Med 2003;167(3):371-8.
			MATERIAL
	Influence of treatment on peak expiratory flow and its relation to
	airway hyperresponsiveness and symptoms. The Dutch CNSLD27. Ramsdale EH, Morris MM, Roberts RS, Hargreave FE.
	COPYRIGHTED								Asymptomatic bronchial hyperresponsiveness in rhinitis
	Study GroupThorax.	1994;49(11):1109-15.							J Allergy Clin Immunol 1985;75(5):573-7.
	12. Brand PL, Duiverman EJ, Waalkens HJ, van Essen-Zandvliet							28. van Haren EH, Lammers JW, Festen J, Heijerman HG, Groot
	EE, Kerrebijn KF. Peak flow variation in childhood asthma:
									CA, van Herwaarden CL. The effects of the inhaled
	correlation with symptoms, airways obstruction, and
									corticosteroid budesonide on lung function and bronchial
	hyperresponsiveness during long-term treatment with inhaled
	corticosteroids. Dutch CNSLD Study GroupThorax.								hyperresponsiveness in adult patients with cystic fib
									Respir Med 1995;89(3):209-14.
	1999;54(2):103-7.
	13. Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F,							29.	Ramsdale EH, Morris MM, Roberts RS, Hargreave FE.
									Bronchial responsiveness to methacholine in chronic bronch
	Casaburi R, et al.Interpretative strategies for lung function tests.
	Eur Respir2005;26(5):948J -68.								relationship to airflow obstruction and cold air responsive
									Thorax 1984;39(12):912-8.
	14. Standardization of Spirometry, 1994 Update. American Thoracic							30. Pizzichini MM, Popov TA, Efthimiadis A, Hussack P, Evans S,
	SocietyAm. J Respir Crit Care Med			1995;152(3):1107-36.
									PizzichinietE,al.Spontaneous and induced sputum to

	measure indices of airway inflammation AminJ Respirasthma.
15. Standardized lung function testing. Official statement of the
European Respiratory SocietyEur. Respir J Suppl1993;16:1-100.	Crit Care Med 1996;154(4 Pt 1):866-9.

24 DIAGNOSIS AND CLASSIFICATION