BRONCHIAL ASTHMA IN CHILDREN Department of pediatrics Definition

BRONCHIAL ASTHMA IN CHILDREN Department of pediatrics

Definition �Asthma is a chronic disease involving the respiratory system in which the airways occasionally constrict, become inflammated, and are lined with excessive amounts of mucus often in response to one or more triggers.

Epidemiology �Bronchial asthma (BA) is one from the most frequent chronic diseases in children and its incidence continues to increase in the last years. Conformable to ISAAC data (International Study of Asthma and Allergy in Children), BA affects 5 -20% of children on the earth globe, this index varying in different countries (in USA - 5 -10%, in Canada, UK - 25 -30%, in Greece, China – 3 -6%).

Risk factors for BA development in children �Familial antecedents of BA and other allergic diseases. �Contact with home dust containing dust mite: Dermatophagoides pteronyssinus. �Contact with fur-bearing animals (cat, dog, etc. ). �Contact with mould (species of fungi Alternaria, Aspergillus, Candida, Penicillium). �Contact with the pollen of different plants. �Smoke of cigarettes, after woods burning. �Presence of cockroaches.

Risk factors for BA development in children �Alimentary (fish, egg, cow’s milk etc. ) and drug allergens �Meteorological factors (cold air, fog). �Physical activity �Environmental pollution �Presence of gastroesophageal reflux. �Drugs and vaccines (antibiotics – penicillin, cephasoline, tetracycline etc. , sulfonamides, NSAID, colorants, etc. ) �Viral infections �Stress factors

Clinical classification of bronchial asthma �Atopic (allergic) asthma �Nonatopic (nonallergic) asthma �Status asthmaticus

Particular forms of bronchial asthma �BA provoked by physical effort �Cough variant of BA �Aspirinic BA

Classification of BA in function of severity Type of BA Exacerbations of Nocturnal BA accesses PEF and PEF variability Intermittent < 1 time per week ≤ 2 times per Asymptomatic, month normal PEF between accesses >80% <20% Mild persistent >1 time per week, > 2 times per but <1 time per month day. Exacerbations can affect the activity >80% 20 – 30% Moderate persistent Daily. Exacerbations affect the activity >1 time per week 60 -80% >30% Severe persistent Permanently. Limited physical activity Frequent <60% >30%

Clinical picture of BA Anamnesis Which questions must be given in the case of BA suspicion: �Had the patient episodes of wheezing, inclusively repeated? �Has the patient nocturnal cough? �Has the patient cough and wheezing after physical effort? �Had the patient episodes of wheezing and cough after the contact with aeroallergens and pollutants? �Had the patient episodes of wheezing after supported respiratory infection? �Is decreasing the degree of symptoms expression after antiasthmatic drugs receiving?

Recommendations for personal and hereditary antecedents assessment: �Presence of dyspnea, wheezing, cough and thorax oppression episodes, with evaluation of duration and conditions of improving. �Familial antecedents of bronchial asthma. �Risk factors �Asthmatic symptoms are manifesting concomitantly (the thoracic oppression is less constant) and have common: - Variability in time (are episodic); - Preferentially nocturnal appearance; - Appearance due to trigger factor (physical effort, exposition to allergens, strong laugh, etc. ). - Personal, familial and environmental factors.

Characteristics of asthmatic attacks: �Quick appearance with expiratory dyspnea, prolonged expiration and wheezing, pronounced sensation of thoracic oppression, lack of air (sensation of suffocation). �Duration from 20 – 30 min until a few hours. �Spontaneous disappearance or at administration of ß 2 -adrenomymetics with short action. �They appear more frequently in night. �The attacks appear suddenly and end also suddenly with tormenting cough with elimination of mucous, viscous, “pearl” sputum in small quantity.

Suggestive symptoms for bronchial asthma diagnosis in children: �Frequent episodes of wheezing (more than 1 episode per month); �Cough ± wheezing induced by physical activity; �Nocturnal cough out of viral infection periods; �Lack of wheezing seasonal variations.

There are 3 categories of wheezing: � Precocious transitory wheezing; is associated with presence of such risk factors as prematurity, smoking parents, dyspnea until 3 years; � Persistent wheezing with precocious onset (until 3 years); recurrent episodes of wheezing associated with acute viral infections (predominantly with respiratory syncitial virus, in children under 2 years, and other viruses, in older children), without atopic manifestations or familial antecedents of atopy; the symptoms persist until the school age and can be present in 12 years old children in significant proportion; � Wheezing (asthma with tardy onset, after 3 years age); in this group asthma evolves in childhood period and even in adults; children present signs of atopy (most frequent – atopic dermatitis) and air pathways pathology characteristic for asthma.

Predictive signs for childhood asthma (preschool, school age): �Wheezing until 3 years; �Presence of major risk factor (familial antecedents of asthma); �Two from three minor risk factors (eosinophilia, wheezing without cough, allergic rhinitis).

Physical examination: Basic principles: � The signs of respiratory system affection can be absent. � Inspection: - Sitting position (orthopnea) with accessory respiratory muscles involvement; - Tachypnea. � At percussion: - Diffuse increased sonority and down placed diaphragm. � Auscultatively: - Diminished vesicular murmur; - Dry coarse, polyphonic, disseminated crackles, predominantly at expiration, that can be heard at distance (wheezing); - Moist and subcrepitant crackles in more advanced bronchial hypersecretion.

Causes of bronchial asthma exacerbations: �Insufficient bronchodilator treatment. �Long-term defect of the basic treatment. �Viral respiratory infections. �Changes of weather �Stress �Long time exposure to triggers.

Appreciation of bronchial asthma exacerbations severity Symptom Mild Moderate Severe Dyspnea -appears during gait; The child can stay in bed -in older children it appears at speaking, in small children the crying becomes more short and slow; feeding difficulties. - the child prefers to sit down. - appears in rest; - refusal to eat; - forced position (sit down, inclined forward) Imminence of respiratory stopping

Appreciation of bronchial asthma exacerbations severity Symptom Mild Moderate Severe Speaking -propositions -expressions -words State of alertness -can be agitated -as a rule, agitated Frequency of respiration -increased -sometimes> 30/min. Participation -as a rule, of accessory absent respiratory muscles with supraclavicula r retraction -as a rule, absent -as a rule, present Imminence of respiratory stopping -inhibited or in confusion state Paradoxical thoraco- abdominal movement

Appreciation of bronchial asthma exacerbations severity Symptom Mild Moderate Severe Imminence of respiratory stopping Moist crackles Moderately expressed, often, only at expiration Sonorous Absent Frequency of cardiac contractions < 100 – 120 > 120 Bradycardia Paradoxical pulse Absent Can be present Often is present Absent

Appreciation of bronchial asthma exacerbations severity Symptoms Mild Moderate Severe PEF in % from >80% predicted after bronchodilator using 60 – 80% <60% Pa O 2 at air respiration, Pa CO 2 >60 mm Hg <60 mm Hg <45 mm Hg >45 mm Sa. O 2% (with air) >95% 91 -95% <90% Imminence of respiratory stopping

Normal frequency of respiration in children Age Frequency of respiration < 2 months <60/min 2 – 12 months <50/min 1 – 5 years <40/min 6 – 8 years <30/min

Normal frequency of cardiac contractions (FCC) in children Suckling babies 2 – 12 months <160/min Little age 1 – 2 years <120/min Preschool and school age 2 – 8 years <110/min

The diagnosis of BA in children has the following basic aspects: ● atopic background: allergic rhinitis, atopic dermatitis, alimentary allergy, atopic manifestation in family; ● clinically: paroxysmal dyspnea with wheezing; ● functionally: reversible bronchial obstruction; ● therapeutically: efficient response at short action bronchodilators and inhalator corticosteroids treatment.

The algorhythm for BA diagnosis in suckling baby and infant (by Martinez, modified) Major criteria: ● hospitalizations at severe form of bronchiolitis or wheezing; ● ≥ 3 episodes of wheezing during respiratory infections in the last 6 months; ● presence of asthma in one of parents; ●atopic dermatitis; ●sensibilization to pneumoallergens.

Minor criteria: ● rhinorrhea in the absence of flu; ● wheesing in the absence of flu; ● eosinophilia (≥ 5%); ● alimentary allergy; ● male.

Risk for persistent wheezing/asthma: �One from first 2 major criteria + another major criterion; �One from first 2 major criteria + 2 minor criteria.

PARACLINICAL INVESTIGATIONS IN BRONCHIAL ASTHMA Obligatory investigations: �PEF-metry; �Spirography; �Test with bronchodilator �Skin tests with allergens; �Pulsoxymetry; �Hemoleukogram; �General analysis of sputum; �ECG; total and specific Ig. E �X-ray chest in 2 proiections.

PARACLINICAL INVESTIGATIONS IN BRONCHIAL ASTHMA Recommended investigations: �Bronchoscopy (at necessity); �Echo. CG; �Oxymetry of arterial blood; �Acido – basic state evaluation; �Provoking tests (effort, acetylcholine, metacholine); �Pulmonary, mediastinal CT (at necessity) �General urine analysis; �Biochemical serologic indexes (total protein, glucose, creatinin, urea, LDH, AST, ALT, bilirubin and its fractions); �Ionogram.

Spirography: �It allows to appreciate the severity and reversibility of bronchial obstruction; �It allows to differentiate from restrictive affections.

PEF-metry: �It allows the appreciation and monitoring of bronchial obstruction severity and reversibility. �The formula for calculation of PEF in% towards to predicted value in%: PEF = minimal PEF of given day/predicted PEF x 100%. � 24 hours variability of PEF is calculating after formula: 24 hours variability = 2(evening PEF – morning PEF)/(evening PEF + morning PEF) X 100%.

Pharmacological tests: �The test with ß 2 -agonist (bronchodilator test) – spirographic or PEF-metry values performed after 15 min from inhalation of short action ß 2 agonist are compared with the usual data before inhalation; increasing of PEF values ≥ 20% shows the obstruction reversibility and is suggestive for BA.

Physical effort test: �The spirography or PEF-metry is performed initially and at 5 -10 min after nonstandard physical effort (running or physical exercises), but sufficient for increase the pulse rate (until 140 – 150/min). Decreasing of PEF ≥ 20% is suggestive for asthma (effort bronchospasm).

Examination of sputum: �Eosinophils (in proportion of 10 – 90%), octoedric Charcot – Layden phospholypase crystals are suggestive for atopic asthma. �Curschmann’s spirals (agglomerations of mucus).

Hemogram and immunoglobulins �Hemogram shows eosinophilia in some cases. �Immunoglobulins: - Total serum Ig. E increased in atopic asthma. - Specific Ig. E to certain allergen are increased.

X-ray chest: �Is obligatory only in the first accesses, when the diagnosis is not clear. �In BA access – signs of pulmonary hyperinflation (flat diaphragm with reduced movements, hypertransparence of pulmonary areas, widening of retrosternal space, horizontal ribs). �It can be indicated for disease complications (pneumothorax, pneumomediastinum, atelectasis due to mucus plugs) or associated affections (pneumonias, pneumonitis etc. ) finding.

General assessment of gas exchange It is necessary in patients with signs of respiratory insufficiency, in these having Sa. O 2 less than 90%.

Allergy skin testing (skinprick test, scarification probes) It is performed by the allergologist and aims to detect Ig. E-induced allergic reactions. It is usually carried out by the method of scarification: skin scarification of 4 -5 mm with applying a drop of standard allergen in concentration of 5000 U / ml (1 unit =0. 00001 mg protein nitrogen / 1 ml).

Appreciation of allergic reaction by skin scarification test Test appreciation Conventional sign The visual image of allergic reaction Negative - It is the same as the control test Uncertain -/+ Local redness, without swelling Weakly positive + Swelling papule, 2 -3 mm diameter and peri-papular redness Positive ++ Swelling papule with a diameter >3 mm<5 mm and peri-papular redness Intense positive +++ Swelling papule with 5 -10 mm diameter and peri-papular redness Excessively positive ++++ Swelling papule with more than 10 mm diameter, peri-papular redness and pseudopodies

DIFFERENTIAL DIAGNOSIS In children less than 5 years, it is performed with another affections occuring with wheesing: � Viral bronchiolitis; � Cystic fibrosis; � Foreign body aspiration; � Upper respiratory pathways obstruction; � Bronchopulmonal displasia; � Intrathoracic respiratory pathways malformations; � Congenital cardiac diseases; � Kartagener’s syndrome; � Immune deficiencies; � Chronic sinusitis; � Gastroesophageal reflux; � Tbc; � Mediastinal adenopathies; � Tumors.

DIFFERENTIAL DIAGNOSIS In children older 5 years age, it is performed with the same affections as in big child or adult: �Cardiovascular pathology; �Upper respiratory pathways obstruction; �Foreign bodies aspiration; �Cystic fibrosis; �Syndrome of hyperventilation, panic, vocal chords dysfunction; �Pulmonary interstitial pathology; �Gastroesophageal reflux; �Rhinosinusal pathology.

Hospitalization criteria for patients with BA: �Severe access; �Inefficacity of broncholytic therapy during 1 – 2 hours; �Duration of exacerbation more than 1 – 2 weeks; �Impossibility to accord medical care at home; �Unsatisfactory living conditions; �Presence of increased risk factors for death due to BA.

Criteria for hospitalization in intensive care departaments for patients with BA: �Mental deterioration; �Paradoxic pulse >15 -20 mm Hg; �Severe pulmonary hyperinflation; �Severe hypercapnia > 80 mm Hg; �Cyanosis resistant to oxygenotherapy; �Unstable hemodynamics.

General principles of drug treatment in bronchial asthma: �The inhalatory therapy is the most recommended in all children, the used devices for drug inhalation must be individualised for every case in function of its peculiarities and characteristics of used inhaler. In general lines, administration using metereddose-inhaler (MDI) with spacer versus nebulizing therapy is more preferable, due to some advantages of MDI (reduced risk of adverse effects, more decreased cost etc. ). Administration through nebulizers presents a lot of disadvantages: not precise dose, increased cost, necessity of special apparatus.

General principles of drug treatment in bronchial asthma: �Drugs administered through inhalation are preferable due to their increased therapeutic index: high concentrations of medicaments are relieved directly in respiratory pathways, with strong therapeutic effects and reduced number of systemic adverse effects.

General principles of drug treatment in bronchial asthma: �Devices for medication administered through inhalation: pressure inhalers with measured dose (MDI), dry powder inhalers, turbohalers, diskhalers, nebulizers. �Spacers (or retention camera) make easier the use of inhalers, reduce systemic absorption and secondary effects of inhaled glucocorticoids.

General principles of drug treatment in bronchial asthma: �Two types of medication help in asthma control: controlers, or drugs that prevent the symptoms and accesses, and relievers, or drugs, used for access treatment and having rapid effect. �The choice of medication depends from the control level of BA at moment and from curent medication. �If curent medication does not ensure the adequate control of BA, the indication of superior advanced step of treatment is necessary.

General principles of drug treatment in bronchial asthma: �If BA is controled 3 months, the decreasing of supporting volume for control maintaining minimal necessary dose establishing (passing to inferior step) is possible. �The therapy with adequate doses of short acting inhalatory ß 2 -agonists is recommended in accesses (if inhalers are not available, the bronchodilators can be administered per os or i/v. �In hospitals in the case of hypoxemic patient the oxygen is given.

General principles of drug treatment in bronchial asthma: �The not recommended treatment in accesses: sedatives, mucolytics, physiotherapy, hydration with high volume of liquids. �Antibiotics not treat the accesses, but are indicated in the case of concomitant pneumonias or other bacterial infections.

The key moments in the treatment of BA by steps: �Each step includes variants of therapy serving as alternative in the choice of BA control treatment, although are not similar to efficacy. �The efficacy of treatment increases from I step to V step and depends from accessibility and certainity of drug. �The steps 2 -5 include combinations of urgent medications, at necessity, of systemic control treatment. �In majority of patients with persistent BA, which anteriorly didn’t administered control treatment, is necessary to iniciate the treatment from the 2 -nd step.

The key moments in the treatment of BA by steps: �If at primary examination we determine the absence of BA control, the treatment begins from the 3 -rd step. �The patients must use relievers (short action bronchodilators) at each step. �The systemic use of urgent medication is a sign of uncontrolled BA, which indicates the necessity of control therapy volume increasing. �Reducing or absence of necessity in relievers represent the goal of treatment and, also, a criterion of efficacity.

The I step of BA treatment: � It is indicated to patients: - Which didn’t receive anteriorly control medication and which manifest episodic symptoms of BA (cough, humid crackles, dyspnoea ≤ 2 times per week, very rare with nocturnal symptoms); - In period between accesses the disease manifestations and nocturnal disturbance are absent or pulmonary function is normal. � Urgent medication: - short action inhaled ß 2 -agonists are recommended; - the inhalatory anticholinergics (ipratropium bromide, oxitropium bromide), peroral short action ß 2 -agonists (salbutamol), short action theophyllin can be the alternative medicaments. � Control medication is not necessary.

The II step of BA treatment: � It is indicated to the patients with symptoms of persistent asthma, which anteriorly didn’t administered control medication. � Urgent medication: - Recommended – inhalatory corticosteroids (ICS) in small doses; - Alternative – antileukotrienes are indicated to the following patients: -who don’t accept to use ICS; -with hard supported ICS adverse reactions; - with concomitant allergic rhinitis. � The initiation of therapy is not recommended with: - Theophylline retard, that possesses minimal antiinflammatory effect and reduced efficacy in control therapy, but has multiple adverse reactions; - Chromones (inhibitors of mast cells degranulation) having decreased efficacy, although they are distinguished by increased inoffensiveness.

The III step of BA treatment: �It is indicated to the patients with symptoms of disease showing the absence of adequate control in the treatment at the steps I and II. �Urgent medication: - Recommended - short action inhaled ß 2 -agonists (salbutamol, phenoterol).

The III step of BA treatment: �Control medication one or two drugs for disease evolution control: - Small doses of ICS in combination with long action inhaled ß 2 -agonists in one self inhaler with still fixed doses of drugs or two different inhalers; - Small doses of ICS in combination with leukotrienes (montelucast, zafirlucast); - Small doses of ICS in combination with small doses of theophylline retard; - Increasing of ICS small doses until medium doses.

The III step of BA treatment: �Small doses of ICS, as a rule, are sufficient due to additive effect of this combination, the dose is increasing, if over 3 -4 months of treatment the BA control was not obtained. �The monotherapy with formoterol and salmeterol is not recommended, they are using in combination with ICS (fluticazon, budesonid).

Note: �The using of spacers for intensifying of drugs getting into respiratory pathways and for decreasing of diverse oropharingean adverse reactions is recommended for patients receiving medium and high doses of ICS; �The patients in which the control on III step is not succeeded, need consulting of specialist with experience in BA treatment for excluding an alternative diagnosis or of cases of BA difficult to treat.

The IV step of BA treatment: �It is indicated to the patients with symptoms of disease showing the absence of control in the treatment at the 3 -rd step. � The choice of drug in therapy at IV step depends from anterior indications at 2 -nd and 3 -rd steps. �Urgent medication: �Recommended - short action inhaled ß 2 -agonists �Control medication includes two or more drugs for disease evolution control: - ICS in medium and high doses in combination with long action inhaled ß 2 -agonist; - ICS and long action inhaled ß 2 -agonist and, supplementarly, small doses of retard theophyllin.

Note: �Small and medium doses of ICS, in combination with antileukotrienes, amplify the clinical effect smaller comparatively with combination of ICS and long action inhaled ß 2 -agonist; �Increasing of ICS dose (from medium to high) in majority of patients ensures only nonsignificant increasing of clinical effect, and administration of high doses is recommended only in quality of probe with duration of 1 -3 months, when the control of BA at combination of ICS medium doses and long action inhaled ß 2 -agonist was not obtained. �Long-term administration of high doses of ICS is followed by increased risk of adverse effects.

The V step of BA treatment: � It is indicated to the patients with uncontrolled, severe BA, on the background of IV step therapy. � Urgent medication: � Recommended: short action inhaled ß 2 -agonists. � Control medication includes supplementary drugs for IV step medication for disease evolution control: - administration of CS per os can amplify the effect of treatment, but has severe adverse effects, therefore they must be given only in severe, uncontrolled forms of BA on the background of 4 -th step therapy; - administration of anti-Ig. E antibodies, supplementarly to another drugs, makes easy the control of BA, when the control of BA didn’t obtained with controller drugs, inclusively with high doses of ICS and CS per os.

Specific immunotherapy �It is indicated only in the period when the allergic BA is controlled.

THE FOLLOW-UP OF PATIENTS WITH BRONCHIAL ASTHMA - The patients return to medical consultation at I month after first visit, ulteriorly – in every 3 months. - After exacerbation, the medical visits have place after 2 – 4 weeks. - If the BA control is established, the regular maintaining visits, at 1 – 6 months, remain essential, depending from situation.

THE FOLLOW-UP OF PATIENTS WITH BRONCHIAL ASTHMA - The number of visits at physician and determining of control level depends from initial severity of patology at concret patient and from degree of patient’s knowledge about the necessary measures for BA adequate control. - The control level must be determined in certain time intervals both by physician, and by patient. - Patients who administered high doses of ICS or CS per os are included in the risk group for osteoporosis and fractures (it is necessary to perform tomodensitometry of bones and administration of biphosphates).

Continuous monitoring It is essential in realization of therapeutic goals. The schemes of treatment, the medications and level of BA control are analysed and modified during this visits.

ADEQUATE MANAGEMENT OF BRONCHIAL ASTHMA �Minimal or inexistent symptoms, including nocturnal symptoms. �Minimal episods or accesses of BA. �Absence of urgent visits at physician or hospital. �Minimal need of urgent medications. �Absence of physical activity and sport practise limitation. �Pulmonary function is about norma. �Secondary effects caused by medication are minimal or inexistent. �Prevention of deceases caused by BA.