DOWNLOAD PDF CH. 5. THE DIFFERENTIAL DIAGNOSIS OF ASTHMA IN CHILDHOOD

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1 Chapter 1 : Signs of Asthma in Children. Asthma Symptoms. Patient Patient The suspicion of an alternative diagnosis beyond asthma is heightened in the wheezing infant less than six months of age. The incidence of wheezing induced by allergically mediated disease increases progressively after age 2 years. The classic symptoms are shortness of breath, wheezing, and chest tightness. Type 2 brittle asthma is background well-controlled asthma with sudden severe exacerbations. Exercise-induced bronchoconstriction Exercise can trigger bronchoconstriction both in people with or without asthma. Occupational asthma Asthma as a result of or worsened by workplace exposures is a commonly reported occupational disease. A few hundred different agents have been implicated, with the most common being: The employment associated with the highest risk of problems include: Alcohol-induced respiratory reactions Alcohol may worsen asthmatic symptoms in up to a third of people. There is negative skin test to common inhalant allergens and normal serum concentrations of IgE. Often it starts later in life, and women are more commonly affected than men. Usual treatments may not work as well. In children, other upper airway diseases such as allergic rhinitis and sinusitis should be considered as well as other causes of airway obstruction including foreign body aspiration, tracheal stenosis, laryngotracheomalacia, vascular rings, enlarged lymph nodes or neck masses. In both populations vocal cord dysfunction may present similarly. After the age of 65, most people with obstructive airway disease will have asthma and COPD. In this setting, COPD can be differentiated by increased airway neutrophils, abnormally increased wall thickness, and increased smooth muscle in the bronchi. However, this level of investigation is not performed due to COPD and asthma sharing similar principles of management: This plan should include the reduction of exposure to allergens, testing to assess the severity of symptoms, and the usage of medications. The treatment plan should be written down and advise adjustments to treatment according to changes in symptoms. If trigger avoidance is insufficient, the use of medication is recommended. Pharmaceutical drugs are selected based on, among other things, the severity of illness and the frequency of symptoms. Specific medications for asthma are broadly classified into fast-acting and long-acting categories. In those with occasional attacks, no other medication is needed. If mild persistent disease is present more than two attacks a week, low-dose inhaled corticosteroids or alternatively, an leukotriene antagonist or a mast cell stabilizer by mouth is recommended. For those who have daily attacks, a higher dose of inhaled corticosteroids is used. In a moderate or severe exacerbation, corticosteroids by mouth are added to these treatments. The most common triggers include allergens, smoke tobacco and other, air pollution, non selective beta-blockers, and sulfite-containing foods. Corticosteroids are generally considered the most effective treatment available for long-term control. The spacer is a plastic cylinder that mixes the medication with air, making it easier to receive a full dose of the drug. A nebulizer may also be used. Nebulizers and spacers are equally effective in those with mild to moderate symptoms. However, insufficient evidence is available to determine whether a difference exists in those with severe disease. For emergency management other options include: Effects beyond one year are unknown. Evidence is insufficient to support the usage of vitamin C. Page 1

2 Chapter 2 : Acute Asthma World Allergy Organization Differential Diagnosis in Children In children, chronic cough is a problem, which needs differentiation between asthma and not asthma. Chronic productive cough with purulent sputum is a reason for concern in children and is not usually a symptom of asthma. Strong emotional expression laughing or crying hard Airborne chemicals or dusts Menstrual cycles Symptoms occur or worsen at night, awakening the patient. Physical findings that increase the probability of asthma are listed below. The absence of these findings does not rule out asthma, because the disease is by definition variable, and signs of airflow obstruction are often absent between attacks. Hyperexpansion of the thorax, especially in children; use of accessory muscles; appearance of hunched shoulders; and chest deformity. Sounds of wheezing during normal breathing or a prolonged phase of forced exhalation typical of airflow obstruction. Wheezing may only be heard during forced exhalation, but it is not a reliable indicator of airflow limitation. These measurements help to determine whether there is airflow obstruction, its severity, and whether it is reversible over the short term. These tests can aid diagnosis or confirm suspected contributors to asthma morbidity e. Reasons for Additional Tests Patient has symptoms but spirometry is normal or near normal Assess diurnal variation of peak flow over 1 to 2 weeks Refer to a specialist for bronchoprovocation with methacholine, histamine, or exercise; negative test may help rule out asthma Suspect infection, large airway lesions, heart disease, or obstruction by foreign object Chest X-ray Suspect coexisting chronic obstructive pulmonary disease, restrictive defect, or central airway obstruction Additional pulmonary function studies Suspect other factors contribute to asthma these are not diagnostic tests for asthma. Use the chart below to help you assign a severity level to your patient, based on the domains of impairment and risk. Spirometry is the preferred method for measuring lung function to classify severity. Peak flow has not been found to be a reliable variable for classifying severity, but it may serve as a useful tool for monitoring trends in asthma control over time. Assessment of the risk of future adverse events requires careful medical history, observation, and clinician judgment. Documentation of warning signs and adverse events will be necessary when a patient is felt to be at increased risk. Assessing the risk of exacerbations is through questions regarding the use of medications, particularly oral corticosteroids, or urgent care visits. Low FEV1 is associated with increased risk for severe exacerbations. Assessment of the risk of progressive loss of lung function, or, for children, the risk of reduced lung growth measured by prolonged failure to attain predicted lung function values for age requires longitudinal assessment of lung function, preferably using spirometry. Assessment of the risk of side effects from medication s does not directly correspond to the varying levels of asthma control. For example, a patient might have well-controlled asthma with high doses of ICS and chronic oral corticosteroids but is likely to experience some adverse effects from this intense therapy. The risk of side effects can vary in intensity from none to very troublesome and worrisome. The next step in caring for your patient with asthma is to develop a treatment plan that addresses their medication needs and avoidance strategies based on current level of severity. Learn more about the stepwise approach recommended by the NIH for the management of asthma in adults and children over 12 years old. Page 2

3 Chapter 3 : Asthma Diagnosis blog.quintoapp.com Asthma is a common chronic disease worldwide and affects approximately 24 million persons in the United States. It is the most common chronic disease in childhood, affecting an estimated 7 million children. Despite this, in the United States alone, approximately 12 million people each year experience an acute exacerbation of their asthma, a quarter of which require hospitalization [1]. An acute exacerbation of asthma should be correctly identified from poor asthma control. In contrast, poor asthma control typically presents with a diurnal variability in airflow and is a characteristic that is usually not seen during an acute exacerbation. Various clinical symptoms and signs may assist the clinician in determining the severity of acute asthma Figure 1 [1,10]. To prevent severe exacerbations of asthma, the goals for the physician managing patients with asthma are: Recognition of patients who are at a greater risk for near-fatal or fatal asthma. Education of the patient to recognize a deterioration in their disease. Provision of an individual action plan for the patient to manage the exacerbation and to know when to seek professional help. Physical Examination Clinical estimates of severity based on an interview and a physical examination can result in an inaccurate estimation of disease severity; audible wheezing is usually a sign of moderate asthma, whereas no wheezing can be a sign of severe airflow obstruction. Symptoms of severe asthma include severe chest tightness, cough with or without sputum, sensation of air hunger, inability to lie flat, insomnia and severe fatigue. The signs of severe asthma include use of accessory muscles of respiration, hyperinflation of the chest, tachypnea, tachycardia, sweating, diaphoresis, obtundation, apprehensive appearance, wheezing, inability to complete sentences and difficulty in lying down. Altered mental status, with or without cyanosis, is an ominous sign and immediate emergency care and hospitalization are required. A detailed examination should include examining for signs and symptoms of pneumonia, pneumothorax or a pneumomediastinum, the latter of which can be investigated by palpation for subcutaneous crepitations, particularly in the supraclavicular areas of the chest wall. Differential Diagnosis of Acute Asthma The differential diagnosis of acute asthma includes COPD, bronchitis, bronchiectasis, foreign body, extra-or intra-thoracic tracheal obstruction, cardiogenic pulmonary edema, non-cardiogenic pulmonary edema, pneumonia, pulmonary embolus, chemical pneumonitis, and hyperventilation syndrome []. Risk Factors for Acute Asthma Particular risk factors for asthma exacerbations can be identified from the clinical history. The patient interview should include questions about recent events including [1,4]: Upper or lower respiratory tract infections Cessation or reduction of medication Concomitant medication, e. The history should include a review of previous episodes of near-fatal asthma and whether the patient has experienced multiple emergency room visits or hospitalizations, particularly those requiring admission to an intensive care unit, involving respiratory failure, intubation and mechanical ventilation. A history of allergic asthma and other known or suspected allergic symptoms should be obtained. For example, Nelson et al. Compliance with medical treatments should be reviewed; poor compliance with prescribed therapies is a major risk factor. Recent withdrawal of oral corticosteroids OCS suggests that the patient is at greater risk for a severe exacerbation. Limited access of the patient to appropriate health care and lack of education about appropriate management strategies are additional risk factors. Socioeconomic factors associated with severe asthma exacerbations include the non-compliant adolescent or elderly asthmatics living in inner city environments. Certain ethnic groups within a population may have a higher incidence of severe asthma [4,11]. Physiological and Laboratory Parameters Serial measurements of lung function facilitate quantification of the severity of airflow obstruction and response to therapy. A peak expiratory flow PEF rate provides a simple, quick, and cost effective assessment of the severity of airflow obstruction. While standing, the patient takes a deep breath to maximum inspiration, briefly holds the breath, and with lips sealed around a mouthpiece blows out as hard and fast as possible. The best of three recordings is logged as the PEF and compared to predicted normal values based on gender, age and height or to previous determinations. Patients can be supplied with an inexpensive PEF meter and taught to perform measurements at home to detect Page 3

4 deterioration of their asthma. In non-acute settings, assessment of PEF and spirometry before and after administration of a bronchodilator can indicate the likely degree of improvement in lung function which can be achieved by adequate therapy. Initial treatment with a SABA via nebulizer or metered dose inhaler MDI should be administered as puffs every 20 minutes for up to 1 hour and then as needed every hours. The forced expiratory volume in one second FEV1 is measured by spirometry to assess the volume of air exhaled over time and is the most sensitive test for airflow obstruction. While sitting, the patient is asked to forcibly exhale from the point of maximal inhalation into the spirometer, ideally over 6 seconds. Three determinations should be obtained, if possible, with the best being recorded, and severity of assessment is made by comparison to predicted normal values for the gender, height and age of the patient or to a previous value. Chest radiographs are not usually necessary for the diagnosis of acute asthma if the examination of the chest reveals no abnormal findings other than the expected clinical signs and symptoms associated with an acute exacerbation of asthma. If a complication is suspected, such as pneumonia, pneumothorax, pneumomediastinum, or atelectasis secondary to mucous plugging, a chest X-ray should be obtained [11]. Originally published as Figure in the Expert Panel Report 3. Management of Asthma Exacerbations: Treatment Treatment is based not only on assessment of lung function parameters but on clinical findings and the efficacy of previous treatment. A seasonal exacerbation of asthma in a pollen-sensitive patient is more easily treatable than an exacerbation triggered by a viral infection. Physician knowledge of an individual patient will suggest whether a systemic corticosteroid is required or whether an exacerbation can be managed on very high doses of inhaled corticosteroids [3,11,16]. Recommended treatment choices in order of introduction in the acute setting are listed below and depicted in Table 3. Primary treatment choices include: Emergency Department and Hospital-Based Care. Originally published as Fig in the Expert Panel Review 3. Nebulized albuterol is given at a dose of 0. Nebulized albuterol is administered at a dose of 2. Treatment should be continued until the patient has stabilized or a decision to hospitalize is made. Nebulizer treatment may be preferred in patients who are unable to cooperate effectively using an MDI because of the severity of acute asthma, age or agitation. Additionally, continuous nebulization should be considered in very severe asthma exacerbations based on evidence of reduced admissions and improved pulmonary function [11, ]. Levalbuterol R-albuterol nebulizer solution can be given in a similar fashion and at doses ranging from 0. Notably, levalbuterol administered at one-half the mg dose of albuterol is found to deliver comparable efficacy and safety. However, the efficacy of continuous nebulization has not been evaluated [11]. Nebulized levalbuterol is given at a dose of 0. Nebulized levalbuterol is given at a dose of 1. Continuous administration of albuterol via large volume nebulizers may be more efficacious when compared to intermittent administration in patients with severe asthma exacerbations. Continuous administration of nebulized albuterol should be given at a dose of 0. At this time, there is no proven advantage of use of systemic therapy over aerosol treatment. If there is no immediate response to epinephrine treatment should be discontinued and the patient hospitalized [11]. Ipratropium Bromide Ipratropium bromide is a quaternary derivative of atropine sulfate available as a nebulizer solution. It provides competitive inhibition of acetylcholine at the muscarinic cholinergic receptor, thus relaxing smooth muscle in large central airways. It is not a first line therapy, but can be added in severe asthma particularly when albuterol is not optimally beneficial. It can be given with albuterol or levalbuterol and may be used for up to 3 hours in the initial management of acute asthma. Ipratropium bromide may be administered by nebulizer to children at a dose of 0. Children should receive puffs and adults 8 puffs, every 20 minutes for up to 3 doses, and then continued as needed for up to 3 hours [11]. Corticosteroids There are no substantial data for the immediate usefulness of corticosteroids in the acute setting because effectiveness of action is not seen for hours after administration. High dose ICS may be initiated in selected patients. Current evidence suggests equivalence in treatment of mild asthma exacerbations with oral corticosteroids. However, due to limited data, high dose ICS should be reserved for patients with mild asthma and those who refuse or cannot tolerate OCS, e. Current guidelines recommend at least quadrupling the recommended dose of ICS. Treatment should be started before the patient becomes too ill to manage their disease at home. Inhaled therapy reduces the risk of Page 4

5 unwanted effects associated with oral corticosteroid treatment, e. Short courses of OCS are effective to establish control of flare-ups of asthma or during a period of gradual deterioration of asthma not responding to increased doses of an inhaled corticosteroid. Higher doses result in increased side effects and no appreciable increased therapeutic benefit [11, 23]. Improvement may be seen between 5 to 14 days, although patients whose asthma is corticosteroid-resistant may take weeks to show a response. It is not necessary to taper OCS after a course of less than three weeks, but after use for longer than 3 weeks, it is advisable to taper the medication over one to two weeks to decrease withdrawal side effects such as adrenal insufficiency, fatigue, myalgias and joint pain [11,23]. Intramuscular IM or intravenous IV corticosteroids may be used in the initial treatment of acute asthma, but there is no evidence that giving corticosteroids IM or IV results in a more rapid onset of action than oral administration. Poorly controlled asthmatics treated with intermittent or continuous OCS or high-dose ICS pose the greatest risk for the development of osteoporosis. However, the effect of ICS on bone metabolism and subsequent osteoporosis still remains controversial. The American College of Rheumatology recommends that patients initiating treatment with OCS should be screened for osteoporotic fracture risk, lifestyle modifications, and potential treatment with a bisphosphonate. The Fracture Risk Assessment Tool FRAX may be used to calculate the risk of a major osteoporotic bone fracture and assists in categorizing these patients into one of three groups: The quantitative risks of oral corticosteroid related adverse events AE was evaluated by Ledford et al. Results demonstrat ed that an increase in cumulative SCS exposure is associated with an increased risk for AE including diabetes mellitus, skeletal conditions osteoporosis, fractures, mania, depression, opportunistic infections, pneumonia, hypertension, and lipid disorders, with the highest risk associated with skeletal conditions and infections. Magnesium Sulfate Magnesium sulfate has both immediate bronchodilator effects and mild anti-inflammatory effects. Heliox â Driven Albuterol The role of heliox - driven albuterol in the treatment of acute exacerbations continues to be a controversial topic. Many limitations remain that complicate the understanding of the current literature. Despite these uncertainties, heliox â driven albuterol should be considered in both children and adults who exhibit severe life-threatening exacerbations and those who remain in the severe category after 1 hour of intensive conventional therapy [11,24]. Hospitalization Failure to respond to treatment necessitates hospitalization. Hydration in young infants and children may be essential as these patients are at increased risk for dehydration due to poor oral intake and an increased respiratory rate. The patient should be monitored continuously with pulse oximetry and telemetry. Blood gases should be obtained until the patient is stable. The patient should be treated with continuous nebulized albuterol or levalbuterol, with or without ipratropium bromide, and a corticosteroid, e. If the patient is not responding and is deteriorating a decision should be made to assist ventilation before the patient has a respiratory arrest. Viral respiratory tract infections are more common in acute asthma exacerbation and therefore antibiotics should be reserved for patients who present with evidence of a co-existing bacterial infection, i. The EPR3 does not recommend the use of methylxanthines, mucolytics, sedation or chest physiotherapy for treatment in acute asthma [1, 11,25]. Conclusion Patient education is important to ensure that the patient understands that asthma is mostly a chronic disease and necessitates the avoidance of allergens, prevention of infections, compliance with routine vaccinations, management of comorbid conditions and adherence to treatment regimens. The importance of taking an ICS on a regular basis and limiting bronchodilator use cannot be over emphasized. An individual management plan should include how to recognize an impending exacerbation and provide an incremental therapy regimen to be implemented according to the degree of severity and when to seek medical care. Page 5

6 Chapter 4 : Asthma - Wikipedia Asthma, which occurs in adult and pediatric patients, is a chronic inflammatory disorder of the airways characterized by an obstruction of airflow. Among children and adolescents aged years, asthma accounts for a loss of 10 million school days annually and costs caretakers $ Your doctor may use several tests to determine how well your lungs are working. Spirometry This is the main test doctors generally use to diagnose asthma in people 5 years or older. To help determine how well your lungs are working pulmonary function, you take a deep breath and forcefully breathe out exhale into a tube connected to a spirometer. This records both the amount volume of air you exhale and how quickly you exhale. If certain measurements are below normal for a person your age, it may indicate asthma has narrowed your airways. After taking lung test measurements, your doctor may ask you to inhale an asthma drug to open air passages, and then do the test again. Showing significant improvement after taking the medication could mean you have asthma. Challenge test If your spirometer results are normal or near normal, your doctor might try to trigger asthma symptoms by having you inhale a substance that causes the airways to narrow in people with asthma, such as methacholine meth-uh-ko-leen. If you appear to have asthma triggered by exercise exercise-induced asthma, you may be asked to do physical activity to see whether it triggers symptoms. Lung tests in children Doctors seldom do lung tests in children under age 5. It can be especially difficult to diagnose asthma in young children because there are many conditions that cause asthma-like symptoms in this age group. Exhaled nitric oxide test You breathe into a tube connected to a machine that measures the amount of nitric oxide gas in your breath. Nitric oxide gas is produced by the body normally, but high levels in your breath can mean your airways are inflamed â a sign of asthma. Ruling out conditions other than asthma If your doctor suspects you have a condition in addition to or other than asthma, you may need tests such as: Chest and sinus X-rays Computerized tomography CT scans of the lungs Gastroesophageal reflux assessment Examination of the phlegm in your lungs sputum induction and examination for signs of a viral or bacterial infection Your doctor may also want to see whether you have other conditions that often accompany asthma and can worsen symptoms. These can be skin tests, blood tests or both. Although not used to diagnose asthma, allergy tests can help identify an allergic condition, such as hay fever, that may be causing your symptoms or worsening existing asthma. For some people, diagnosing the cause of breathing problems is a challenge. It can be difficult to differentiate asthma from other conditions â particularly in young children. When asthma coexists with another condition that affects breathing, it can further complicate diagnosis. It may take time â and patience â to get the correct diagnosis and determine the best course of treatment. Page 6

7 Chapter 5 : Diagnosing asthma in children Australian Asthma Handbook The patients were separated into two groups according to presence of reflux and/or nocturnal symptoms. 13 patients had one of the reflux and/or nocturnal asthma symptoms (Group 1), whereas Asthma Asthma Diagnosis To diagnose asthma, your doctor will discuss your medical history with you and perform a physical exam. You may need a lung function test and maybe other tests, such as a chest or sinus X-ray. Visit a doctor immediately. Knowing what to expect during the diagnostic process may help. Additional information about asthma diagnosis can be found here. Personal and medical history. Your doctor will ask you questions to understand your symptoms and their causes. Bring notes to help jog your memory. Be ready to answer questions about your family history, the medicines you take and your lifestyle. This includes any current physical problems. Shortness of breath, wheezing, coughing and tightness in your chest may show asthma. This also includes all previous medical conditions. A history of allergies or eczema increases your chance of asthma. A family history of asthma, allergies or eczema increases your chance of having asthma, too. Tell your doctor about any home or work exposure to environmental factors that can worsen asthma. For example, these might include pet dander, pollen, dust mites and tobacco smoke. The doctor may also ask if you get chest symptoms when you get a head cold. If your doctor thinks you have asthma, they will do a physical exam. This exam may include a lung function test to detect how well you exhale air from your lungs. You may also need an X-ray of your lungs or sinuses. A physical exam then allows your doctor to review your health. To confirm asthma, your doctor may have you take one or more breathing tests known as lung function tests. These tests measure your breathing. Lung function tests are often done before and after inhaling a medicine known as a bronchodilator brahn-ko-die-ah-lay-tor, which opens your airways. If your lung function improves a lot with use of a bronchodilator, you probably have asthma. Your doctor may also prescribe a trial with asthma medicine to see if it helps. Common lung function tests used to diagnose asthma include: Page 7

8 Chapter 6 : Childhood Asthma: Diagnosis and Treatment Childhood asthma affects approximately 5% of children in the UK and the prevalence is increasing. Virus associated wheeze affects up to 20% of children at some point. Peak age of onset of childhood asthma is 5 years. Song Received Aug 5; Accepted Sep This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This article has been cited by other articles in PMC. Abstract Many children suffer from recurrent coughing, wheezing and chest tightness. In older school-aged children the majority of the children have asthma. Quality of life is affected by asthma control. Sleep disruption and exercised induced airflow limitation have a negative impact on participation in sports and social activities, and may influence family life. The goal of asthma therapy is to achieve asthma control, but only a limited number of patients are able to reach total control. This may be due to an incorrect diagnosis, co-morbidities or poor inhalation technique, but in the majority of cases non-adherence is the main reason for therapy failures. However, partnership with the parents and the child is important in order to set individually chosen goals of therapy and may be of help to improve control. Non-pharmacological measures aim at avoiding tobacco smoke, and when a child is sensitised, to avoid allergens. Introduction Asthma is a chronic disorder of the bronchial tree, characterized by completely or partially reversible airway obstruction, which may improve spontaneously or may subside only after specific therapy. Airway hyperresponsiveness is defined as the narrowing of the airways as response to a variety of stimuli, such as allergens and nonspecific triggers and infections. Asthma is a chronic disorder of both children and adults, with million individuals afflicted worldwide Global Initiative for Asthma GINA guidelines [ 1 ]. Although the prevalence of asthma has increased over the last decades, especially so in children [ 2 ], there is still no sound explanation for this increase. Asthma symptoms include recurrent wheezing, coughing, chest tightness, and dyspnea, with nightly and early morning symptoms being more prevalent, whereby quality of life is often reduced [ 3 ]. Symptoms of asthma may already occur early in life, with approximately a third of children wheezing during their first three years of life [ 4 ]. In many children, the severity of symptoms diminishes in early puberty and may even disappear altogether, especially in those with mild asthma. However, it is widely known and accepted that symptoms may remain in children with severe asthma or return in early adulthood [ 6 ]. Asthma in older children is characterised by a histopathology of a chronic inflammatory process in the conducting airways. Genetic predisposition, in combination with environmental factors, such as allergens and viral infections, may contribute to the development of asthma. Shedding of the epithelial layer is seen, with inflammation and oedema of the airway wall and infiltration of T-lymphocytes, eosinophils, and basophilic cells. This inflammatory process may lead to or is seen in association with more structural changes, such as thickening of the basal membrane and hyperplasia of airway smooth muscle and goblet cells, a process commonly known as airway remodelling. Despite observations that lung biopsy specimens from young wheezing children demonstrate the same histopathological pattern [ 7 ], little is known about the histopathology in young wheezing children. Childhood asthma often coexists with allergy and with other atopic diseases. The possible association between allergic sensitization and asthma in children led to the allergic march paradigm. However, in the years thereafter symptoms occur in other organ systems, resulting in diseases such as allergic asthma, allergic rhinitis, and allergic dermatitis. It is increasingly accepted that the phenotype of recurrent wheezing, coughing, and chest tightness also occurs in nonallergic individuals. Asthma is therefore considered a heterogeneous disease phenotype with various subphenotypes [ 8 ]. While asthma therapy has improved considerably over the last decades, we are still unable to cure the disease. A small group of children with problematic severe asthma remain the exception. This paper focuses on paediatric asthma and its treatment. Epidemiology Although much has been written about the epidemiology of asthma in children, published data are heterogeneous because a uniform definition and uniform methods of data gathering are often lacking. We Page 8

9 recently extracted data from PubMed on definitions used to diagnose asthma in paediatric cohort studies children between 6 and 18 years of age [ 9 ]. Sixty different definitions were seen in papers. The prevalence estimates varied between The need for systematic international comparisons of the prevalence of asthma, and the need of a better understanding of different causative and protective factors, led to the International Study of Asthma and Allergies in Childhood ISAAC program [ 10, 11 ]. The program aimed to elucidate the prevalence in children aged years and also in year olds. The aim was to initiate an uncomplicated and validated method to measure worldwide prevalence of asthma and allergic diseases. The initial prevalence of self-reported wheezing during the previous 12 months varied from 1. The corresponding prevalence for parent-reported wheezing in the 6- to 7-year-old children was from 0. Asthma was less prevalent in developing countries, and the highest prevalence was observed in Anglo-Saxon countries. Other conclusions could also be drawn from the study [ 12 ]. The authors found an unexpected northwest to southeast gradient in the prevalence of asthma within Europe, and this could not be explained by the recognised risk factors. In addition, asthma prevalence could not simply be explained by genetic differences: Furthermore, there were both differences and similarities in the international pattern of prevalence of asthma, allergic rhinitis, and atopic eczema. The authors found marked differences in prevalence of these three disease entities in the countries with the highest prevalence rates, while the prevalence in the countries with the lowest rates was quite similar. The differences in risk factors and time course of the various disease entities between the different countries could offer an explanation [ 12 ]. Additionally, local environmental factors seem to play an important role in the differences in prevalence. Studies of emigrant and immigrant populations, and of Germany after the reunion of East and West, suggest that environmental factors, such as allergens and lifestyle, may explain the observed differences between genetically identical populations [ 13, 14 ]. During the last two decades of the previous century, an increase in the incidence and prevalence of asthma was observed in the Western world. In, Strackan proposed a novel, albeit speculative, explanation for this increase of allergic asthma as well as other allergic diseases [ 16 ]. He observed that allergic diseases seemed to be prevented by early childhood infections, transmitted by unhygienic contact with older siblings. However, the increase in incidence and prevalence of allergic disease still remains a mystery to be solved. A cross-sectional study by Shirakawa et al. This study seemed to confirm the hypothesis and also suggested that it was possible to skew away from Th2-allergic disease through Th1-inducing infections. However, we found no effect of tuberculin skin testing in a prospective, randomised, double-blind, and placebo controlled study in Dutch children at risk for allergic disease [ 18 ]. These conflicting results may be explained by heterogeneous study designs and dissimilar genetic backgrounds, but certainly suggest that the explanation for the increase in allergic disease is not unambiguous. However, at this point the hygiene hypothesis provides the strongest epidemiological explanation for the rise in allergic disease; the probability of asthma is inversely correlated with an increasing diversity of bacterial and fungal taxa in house dust samples, and some viral infections are associated with asthma, while others seem to be protective [ 19 ]. Yet, over the last 10 years, a number of studies have suggested that the rising trend in asthma prevalence might have reached a plateau, at least in Australian, Swiss, and Dutch children [ 21 â 23 ]. Possible explanations for this include a true decrease in prevalence, improved identification, and improved environmental influences such as indoor environmental factors, outdoor pollution, and changes in lifestyle, such as a shorter period of breastfeeding. On the other hand, approximately 80 percent of asthmatic patients start to have symptoms during the first 5 years of life [ 26 ]. Recurrent wheezing is frequently reported in preschool children. Usually these symptoms are triggered by the frequently occurring viral upper airway infections. These upper airway infections may occur between six and eight times per year. Unfortunately, ability to predict which children will have transient and which will have persistent problems is poor. As such, epidemiologic data such as these have limited clinical applicability. In this regard, prospective studies in which subjects were also phenotyped using a number of different clinical measures e. Therefore, at present, there are no diagnostic tools that can reliably predict the development of asthma among wheezing infants. The recognition of wheezing by parents also remains problematic. Noisy Page 9

10 breathing is certainly not uncommon among infants. It must be borne in mind that it is difficult for parents to recognize wheezing and the accurate identification of wheezing by medical history is virtually impossible: Children with physician-confirmed wheezing have higher airway resistance than children with parent-reported wheeze [ 29 ]. It is not unthinkable that physician-confirmed wheezing may be an important predictor of the development of asthma later. We observed that preschool children with an increased specific IgE, and who also wheezed, had a substantially increased chance of developing asthma by school age [ 30 ]. Unfortunately, in this study wheezing was not confirmed by a physician. Bronchial biopsies obtained from infants with confirmed wheezing have shown increased thickness of the reticular basal membrane and significantly greater eosinophilic inflammation, as compared to control subjects and even samples from children with parent-reported wheezing [ 32 ]. Early identification of asthma is mandatory in school children, since early initiation of treatment in this age group can prevent exacerbations and deterioration of lung function. However, in preschool children data are unavailable. Recent early intervention studies with ICS in young children, aimed at the prevention of asthma, have shown no beneficial results with respect to the development of asthma [ 33 â 35 ], and the results of therapeutic studies are conflicting. An explanation may be that wheezing and coughing at such a young age may be present in a number of different disease entities, with different aetiologies, and it therefore remains difficult to select an effective treatment strategy. Phenotypes in Preschool Wheezing Wheezing disorders in childhood are common and vary widely in clinical presentation and disease course. However, these phenotypes do not elucidate whether they represent distinct or different disease entities with separate aetiologies. A panel of 7 experienced clinicians from 4 European countries, working in primary, secondary, and tertiary paediatric care, found that preschool wheezing disorders consist of several phenotypes [ 40 ]. During structured discussions disease entities could be narrowed to three entities which were linked to proposed mechanisms: Both smoking during pregnancy and prematurity were considered predisposing factors for airway narrowing and therefore should not define separate disease entities. The former is defined as a phenotype where wheezing only occurs during viral colds, while the latter better resembles asthma, with wheezing also occurring without colds and during physical strain, laughing, and so forth. In addition, up to now there is no prospective validation of the two phenotypes, episodic viral wheeze and multiple trigger wheeze. It may well be that some children with episodic viral wheeze, continue to wheeze and develop asthma, while some children with multiple trigger wheeze stop wheezing by the age of six. Table 1 Characteristics of episodic viral wheeze and of multiple trigger wheeze. Chapter 7 : Asthma: Steps in testing and diagnosis - Mayo Clinic Diagnosing asthma in children under 5 is a little different. Children this age usually are not given a breathing test. Instead, the doctor asks about certain signs and symptoms and prescribes a bronchodilator if they think it might be asthma. Chapter 8 : Diagnosis of Asthma in Infants/Children Asthma Initiative of Michigan (AIM) -Symptoms respond to appropriate anti-asthma therapy. -Patient's colds "go to the chest" or take more than 10 days to clear up. -The patient also has eczema, hay fever, or a family history of asthma or atopic diseases. Page 10