global strategy for asthma management and prevention

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GINA_WR_2006.qxp:GINA_WR_2006.qxp 7/20/07 4:12 PM Page 19• To identify environmental (including occupational)causes of asthma symptoms. This involves the patientmonitoring PEF daily or several times each day overperiods of suspected exposure to risk factors in the homeor workplace, or during exercise or other activities thatmay cause symptoms, and during periods of non-exposure.Measurement of airway responsiveness. For patientswith symptoms consistent with asthma, but normal lungfunction, measurements of airway responsiveness tomethacholine, histamine, mannitol, or exercise challengemay help establish a diagnosis of asthma 24 . Measurementsof airway responsiveness reflect the “sensitivity” of theairways to factors that can cause asthma symptoms,sometimes called “triggers,” and the test results areusually expressed as the provocative concentration (ordose) of the agonist causing a given fall (often 20%) inFEV1 (Figure 2-3). These tests are sensitive for adiagnosis of asthma, but have limited specificity 25 . Thismeans that a negative test can be useful to exclude adiagnosis of persistent asthma in a patient who is nottaking inhaled glucocorticosteroid treatment, but a positivetest does not always mean that a patient has asthma 26 .This is because airway hyperresponsiveness has beendescribed in patients with allergic rhinitis 27 and in thosewith airflow limitation caused by conditions other thanasthma, such as cystic fibrosis 28 , bronchiectasis, andchronic obstructive pulmonary disease (COPD) 29 .Figure 2-3. Measuring Airway Responsiveness*Non-invasive markers of airway inflammation. Theevaluation of airway inflammation associated with asthmamay be undertaken by examining spontaneously producedor hypertonic saline-induced sputum for eosinophilic orneutrophilic inflammation 30 . In addition, levels of exhalednitric oxide (FeNO) 31 and carbon monoxide (FeCO) 32 havebeen suggested as non-invasive markers of airwayinflammation in asthma. Levels of FeNO are elevated inpeople with asthma (who are not taking inhaled glucocorticosteroids)compared to people without asthma, yetthese findings are not specific for asthma. Neither sputumeosinophilia nor FeNO has been evaluated prospectivelyas an aid in asthma diagnosis, but these measurementsare being evaluated for potential use in determiningoptimal treatment 33,34 .Measurements of allergic status. Because of the strongassociation between asthma and allergic rhinitis, thepresence of allergies, allergic diseases, and allergic rhinitisin particular, increases the probability of a diagnosis ofasthma in patients with respiratory symptoms. Moreover,the presence of allergies in asthma patients (identified byskin testing or measurement of specific IgE in serum) canhelp to identify risk factors that cause asthma symptoms inindividual patients. Deliberate provocation of the airwayswith a suspected allergen or sensitizing agent may behelpful in the occupational setting, but is not routinelyrecommended, because it is rarely useful in establishing adiagnosis, requires considerable expertise and can resultin life-threatening bronchospasm 35 .Skin tests with allergens represent the primary diagnostictool in determining allergic status. They are simple andrapid to perform, and have a low cost and high sensitivity.However, when improperly performed, skin tests can leadto falsely positive or negative results. Measurement ofspecific IgE in serum does not surpass the reliability ofresults from skin tests and is more expensive. The mainlimitation of methods to assess allergic status is that apositive test does not necessarily mean that the disease isallergic in nature or that it is causing asthma, as someindividuals have specific IgE antibodies without anysymptoms and it may not be causally involved. Therelevant exposure and its relation to symptoms must beconfirmed by patient history. Measurement of total IgE inserum has no value as a diagnostic test for atopy.*Airway responsiveness to inhaled methacholine or histamine in a normal subject, andin asthmatics with mild, moderate, and severe airway hyperresponsiveness.Asthmatics have an increased sensitivity and an increased maximal broncho- constrictorresponse to the agonist. The response to the agonist is usually expressed as theprovocative concentration causing a 20% decline in FEV1 (PC20).DIAGNOSIS AND CLASSIFICATION 19
GINA_WR_2006.qxp:GINA_WR_2006.qxp 7/20/07 4:12 PM Page 20DIAGNOSTIC CHALLENGES ANDDIFFERENTIAL DIAGNOSISThe differential diagnosis in patients with suspectedasthma differs among different age groups: infants,children, young adults, and the elderly.Children 5 years and YoungerThe diagnosis of asthma in early childhood is challengingand has to be based largely on clinical judgment and anassessment of symptoms and physical findings. Sincethe use of the label “asthma” for wheezing in children hasimportant clinical consequences, it must be distinguishedfrom other causes persistent and recurrent wheeze.Episodic wheezing and cough is very common even inchildren who do not have asthma and particularly in thoseunder age 3 36 . Three categories of wheezing have beendescribed in children 5 years and younger:• Transient early wheezing, which is often outgrown inthe first 3 years. This is often associated withprematurity and parental smoking.• Persistent early-onset wheezing (before age 3). Thesechildren typically have recurrent episodes of wheezingassociated with acute viral respiratory infections, haveno evidence of atopy 37 and, unlike children in the nextcategory of late onset wheezing/asthma, have no familyhistory of atopy. The symptoms normally persistthrough school age and are still present at age 12 in alarge proportion of children. The cause of the episodeis usually the respiratory syncytial virus in childrenyounger than age 2, while other viruses predominate inolder preschool children.• Late-onset wheezing/asthma. These children haveasthma which often persists throughout childhood andinto adult life 38, 39 . They typically have an atopicbackground, often with eczema, and airway pathologyis characteristic of asthma.The following categories of symptoms are highlysuggestive of a diagnosis of asthma: frequent episodes ofwheeze (more than once a month), activity-induced coughor wheeze, nocturnal cough in periods without viralinfections, absence of seasonal variation in wheeze, andsymptoms that persist after age 3. A simple clinical indexbased on the presence of a wheeze before the age of 3,and the presence of one major risk factor (parental historyof asthma or eczema) or two of three minor risk factors(eosinophilia, wheezing without colds, and allergic rhinitis)has been shown to predict the presence of asthma in laterchildhood 38 . However, treating children at risk with inhaledglucocorticosteroids has not been shown to affect thedevelopment of asthma 40 .Alternative causes of recurrent wheezing must beconsidered and excluded. These include:• Chronic rhino-sinusitis• Gastroesophageal reflux• Recurrent viral lower respiratory tract infections• Cystic fibrosis• Bronchopulmonary dysplasia• Tuberculosis• Congenital malformation causing narrowing of theintrathoracic airways• Foreign body aspiration• Primary ciliary dyskinesia syndrome• Immune deficiency• Congenital heart diseaseNeonatal onset of symptoms (associated with failure tothrive), vomiting-associated symptoms, or focal lung orcardiovascular signs suggest an alternative diagnosis andindicate the need for further investigations.A useful method for confirming the diagnosis of asthma inchildren 5 years and younger is a trial of treatment withshort-acting bronchodilators and inhaled glucocorticosteroids.Marked clinical improvement during the treatment anddeterioration when treatment is stopped supports adiagnosis of asthma. Use of spirometry and othermeasures recommended for older children and adultssuch as airway responsiveness and markers of airwayinflammation is difficult and several require complexequipment 41 making them unsuitable for routine use.However, children 4 to 5 years old can be taught to use aPEF meter, but to ensure reliability parental supervision isrequired 42 .Older Children and AdultsA careful history and physical examination, together withthe demonstration of reversible and variable airflowobstruction (preferably by spirometry), will in mostinstances confirm the diagnosis. The following categoriesof alternative diagnoses need to be considered:• Hyperventilation syndrome and panic attacks• Upper airway obstruction and inhaled foreign bodies 43• Vocal cord dysfunction 44• Other forms of obstructive lung disease, particularly COPD• Non-obstructive forms of lung disease (e.g., diffuseparenchymal lung disease)• Non-respiratory causes of symptoms (e.g., leftventricular failure)20 DIAGNOSIS AND CLASSIFICATION
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