Asthma

Asthma

A leading cause of chronic illness in childhood.

Asthma is the most frequent admitting diagnosis in children's hospitals

10–15% of boys and 7–10% of girls may have asthma at some time during childhood.

Asthma can lead to severe psychosocial disturbances in the family.

With proper treatment, however, satisfactory control of symptoms is usually possible.

It may be regarded as a diffuse, obstructive lung disease with

            (1) Hyper reactivity of the airways to a variety of stimuli and

            (2) reversibility of the obstructive process occurs either spontaneously or because of treatment.

Other names -reactive airway disease, wheezy bronchitis, viral-associated wheezing, and atopic-related asthma.

Bronchoconstriction and inflammation are the pathophysiologic factors. Mast cells, eosinophils, activated T lymphocytes, macrophages, and neutrophils have key roles in the inflammation of asthma.

Both large (>2 mm) and small (<2 mm) airways may be involved

Hyper reactivity of the airways, appears to be an intrinsic part of the disease and is present in almost all asthmatic individuals.

This hyperresponsiveness manifests

            As bronchoconstriction following exercise;

            On natural exposures to strong odors or irritant fumes such as sulfur dioxide, tobacco smoke, or cold air

            On intentional exposures in the laboratory to inhalations of histamine or parasympathomimetic agents

Airway hyperreactivity relates to the severity of the disease.

             increased reactivity occurs

                                                               i.      during viral respiratory infections,

                                                             ii.      following exposure to air pollutants and allergens

                                                            iii.      to occupational chemicals in sensitized individuals,

                                                           iv.      following administration of b-receptor antagonists.

An acute decrease in airway irritability follows administration of b-receptor agonists, theophylline, and anticholinergics, and decreased irritability follows chronic administration of cromolyn, nedocromil, or systemic or inhaled corticosteroids.

A child with one affected parent has about a 25% risk of having asthma;

the risk increases to about 50% if both parents are asthmatic.

genetic predisposition combined with environmental factors may explain most cases of childhood asthma.

EPIDEMIOLOGY.

onset at any age;

30% of patients are symptomatic by 1 yr of age,

80–90% of asthmatic children have their first symptoms before 4–5 yr of age.

Occasional attacks of slight to moderate severity,

Some experience severe, intractable asthma, -interferes with school attendance, play activity, and day-to-day functioning.

most severely affected children have an onset of wheezing during the first yr of life and a family history of asthma and other allergic diseases (particularly atopic dermatitis).

These children may have

1. growth retardation unrelated to corticosteroid administration (although ultimate height attainment usually is normal),
2. chest deformity secondary to chronic hyperinflation,
3. persistent abnormalities on pulmonary function testing.

The prognosis for young asthmatic children is good.

remission depends on growth in the cross-sectional diameter of the airways.

Risk factors for asthma

1. poverty,
2. maternal age less than 20 yr at the time of birth,
3. birthweight less than 2,500 g,
4. smoking by adult member
5. small home size and over crowding

PATHOPHYSIOLOGY.

1. bronchoconstriction,
2. hypersecretion of mucus,
3. mucosal edema,
4. cellular infiltration,
5. desquamation of epithelial and inflammatory cells.

 inhaled allergens (dust mites, pollens, molds, cockroach, cat or dog allergens), vegetable proteins, viral infection, cigarette smoke, air pollutants, odors, drugs (nonsteroidal anti-inflammatory agents, b-receptor antagonists, metabisulfite), cold air, and exercise.

The pathology of severe asthma

1. bronchoconstriction,
2. bronchial smooth muscle hypertrophy,
3. mucous gland hypertrophy,
4. mucosal edema,
5. infiltration of inflammatory cells (eosinophils, neutrophils, basophils, macrophages),
6. desquamation.
7. Pathognomonic findings include Charcot-Leyden crystals (lysophospholipase from eosinophil membranes), Curschmann spirals (bronchial mucous casts), and Creola bodies (desquamated epithelial cells).

Mediators of inflammation  are released from local mucosal mast cells following stimulation by allergens -.

Mediators such as histamine, leukotrienes C4 , D4 , and E4 , and platelet-activating factor initiate bronchoconstriction, mucosal edema, and the immune responses (see Chapter 141).

The early immune response results in bronchoconstriction, is treatable with b2 -receptor agonists, and may be prevented by mast cell-stabilizing agents (cromolyn or nedocromil).

The late-phase reaction occurs 6–8 hr later, produces a continued state of airway hyperresponsiveness with eosinophilic and neutrophilic infiltration, can be treated and prevented by steroids, and can be prevented by cromolyn or nedocromil.

Obstruction is most severe during expiration because the intrathoracic airways normally become smaller during expiration.

airway obstruction is diffuse but not uniform throughout the lungs.

Segmental or subsegmental atelectasis may occur, aggravating mismatching of ventilation and perfusion

Hyperinflation causes decreased compliance, with consequent increased work of breathing.

Increased transpulmonary pressures, necessary for expiration through obstructed airways, may cause further narrowing or complete premature closure of some airways during expiration, thus increasing the risk of pneumothorax.

Increased intrathoracic pressure may interfere with venous return and reduce cardiac output, which may be manifested as a pulsus paradoxus.

Mismatching of ventilation with perfusion, alveolar hypoventilation, and increased work of breathing cause changes in blood gases

Hyperventilation of some regions of the lung compensates for the higher carbon dioxide tension in blood that perfuses poorly ventilated regions.

it cannot compensate for hypoxemia while breathing room air because of the patient's inability to increase the partial pressure of oxygen and oxyhemoglobulin saturation. Further progression of airway obstruction causes more alveolar hypoventilation, and hypercapnia

Hypoxia interferes with conversion of lactic acid to carbon dioxide and water, causing metabolic acidosis.

Hypercapnia increases carbonic acid, which dissociates into hydrogen ions and bicarbonate ions, causing respiratory acidosis.

Hypoxia and acidosis can cause pulmonary vasoconstriction,

cor pulmonale resulting from sustained pulmonary hypertension is not a common complication of asthma.

Hypoxia and vasoconstriction may damage type II alveolar cells, diminishing production of surfactant, which normally stabilizes alveoli. Thus, this process may aggravate the tendency toward atelectasis.

ETIOLOGY.

Asthma involves - autonomic, immunologic, infectious, endocrine, and psychologic factors

Neural bronchoconstrictor activity is mediated through the cholinergic portion of the autonomic nervous system.

Vagal sensory endings - termed cough or irritant receptors, depending on their location, initiate the afferent limb of a reflex arc, which at the efferent end stimulates bronchial smooth muscle contraction.

Vasoactive intestinal peptide neurotransmission initiates bronchial smooth muscle relaxation. Vasoactive intestinal peptide may be a dominant neuropeptide involved in maintaining airway patency.

Humoral factors favoring bronchodilation include the endogenous catecholamines that act on b-adrenergic receptors to produce relaxation in bronchial smooth muscle.

Locally produced adenosine, may contribute to bronchoconstriction.

Methylxanthines – deriphylline- are antagonists of adenosine.

Asthma may be due to abnormal beta-adrenergic receptor–adenylate cyclase function, with decreased adrenergic responsiveness.

decreased numbers of beta-adrenergic receptors on leukocytes - may provide a structural basis for hyporesponsiveness to b-agonists.

Immunologic Factors.

extrinsic or allergic asthma, exacerbations follow exposure to -dust, pollens, and danders.

such patients have increased concentrations of both total IgE

intrinsic --- no evidence of IgE involvement;

skin test results are negative

IgE concentrations low.

in the first 2 yr of life and in older adults (late-onset asthma

increased IgE levels may be due to atopy,

Viral agents - respiratory syncytial virus (RSV) and parainfluenza virus are most often involved; in older children rhinoviruses. Influenza virus - with increasing age.

Viral agents -- stimulation of afferent vagal receptors of the cholinergic system in the airways. An IgE response to RSV can occur in infants and children with RSV-associated wheezing - Wheezing with RSV infection may unmask a predisposition to asthma.

Endocrine Factors.

Asthma may worsen in relation to pregnancy and menses, especially premenstrually,

may have its onset in women at menopause.

improves in some children at puberty.

Thyrotoxicosis increases the severity of asthma; the mechanism is unknown.

Psychologic Factors.

Emotional factors can trigger symptoms

effects of severe chronic illness such as asthma on children's views of themselves, their parents' views of them, or their lives in general can be devastating.

Emotional or behavioral disturbances are related to poor control of asthma

CLINICAL MANIFESTATIONS.

acute or insidious.

Acute episodes - exposure to irritants such as cold air and noxious fumes (smoke, wet paint) or exposure to allergens or simple chemicals,

Exacerbations precipitated by viral respiratory infections are slower in onset, with gradual increases in severity of cough and wheezing over a few days.

Because airway patency decreases at night, many children have acute asthma at night. The signs and symptoms

            cough, which sounds tight and is nonproductive early in the course of an attack;

            wheezing,

            tachypnea,

            dyspnea with prolonged expiration and use of accessory muscles of respiration;

            cyanosis;

            hyperinflation of the chest;

            tachycardia and pulsus paradoxus,

            Cough may be present without wheezing,

            wheezing may be present without cough;

            tachypnea also may be present without wheezing.

in extreme respiratory distress, wheezing—may be absent

child has difficulty walking , talking.

hunched-over, tripod-like sitting position that makes it easier to breathe.

Expiration is typically more difficult

children complain of inspiratory difficulty also

Abdominal pain is common, due to the use of abdominal muscles and the diaphragm.

The liver and spleen may be palpable because of hyperinflation of the lungs.

Vomiting is common - followed by slight relief of symptoms.

sweat profusely;

low-grade fever

fatigue may be severe.

barrel chest deformity is a sign of chronic, airway obstruction

Harrison sulci, = anterolateral depression of the thorax at the insertion of the diaphragm, - in children with recurrent severe retractions.

Clubbing of the fingers is rare

Clubbing suggests other causes of chronic obstructive lung disease such as cystic fibrosis.

DIFFERENTIAL DIAGNOSIS.

1. congenital malformations (of the respiratory, cardiovascular, or gastrointestinal systems),
2. foreign bodies in the airway or esophagus,
3. infectious bronchiolitis,
4. cystic fibrosis,
5. immunologic deficiency diseases,
6. hypersensitivity pneumonitis,
7. allergic bronchopulmonary aspergillosis,
8. a variety of rarer conditions that compromise the airway, including endobronchial tuberculosis, fungal diseases, and bronchial adenoma ,
9. alpha-1 antitrypsin deficiency
10. tropical eosinophilia and other parasitic infections

ASTHMA IN EARLY LIFE.

Wheezing in the infant -

anatomic and physiologic peculiarities

(1) a decreased amount of smooth muscle in the peripheral airways compared with adults may result in less support;

(2) mucous gland hyperplasia in the major bronchi compared with adults favors increased intraluminal mucus production;

(3) disproportionately narrow peripheral airways up to 5 yr of age result in decreased conductance relative to adults and render the infant and young child vulnerable to disease affecting the small airways;

(4) decreased static elastic recoil of the young lung prediposes to early airway closure during tidal breathing and results in mismatching of ventilation and perfusion and hypoxemia;

(5) highly compliant rib cage and mechanically disadvantageous angle of insertion of diaphragm to rib cage (horizontal vs. oblique in the adult) increase diaphragmatic work of breathing;

(6) decreased number of fatigue-resistant skeletal muscle fibers in the diaphragm leave the diaphragm poorly equipped to maintain high work output;

(7) deficient collateral ventilation with the pores of Kohn and the Lambert canals deficient in number and size.

development of atelectasis distal to obstructed airwaysis easier in child

The clinical, roentgenographic, and blood gas findings in asthma and bronchiolitis are similar.

bronchiolitis caused by RSV peaks during the first 6 mo of life,

during the cold weather months,

second and third attacks are uncommon.

Previously well infants or young children develop -cough, tachypnea, and wheezing

require hospitalization.

recurrent episodes of coughing and wheezing with bacterial infections should be investigated for cystic fibrosis or immunologic deficiency.

Chronic aspiration caused by swallowing dysfunction (usually in developmentally delayed children) or gastroesophageal reflux also may cause recurrent cough and wheezing in early life. Symptoms of respiratory distress often occur with or shortly after feeding, and a chest roentgenogram is commonly abnormal.

obliterative bronchiolitis (usually a sequela of a severe viral insult, most often adenovirus) and bronchopulmonary dysplasia

food allergy - during early life is controversial.

Positive skin test to foods are unusual in asthmatic infants, - usually milk, wheat, or egg

Eczema is associated with the subsequent appearance of asthma.

Eosinophilia greater than 400 cells/mm3 (and especially greater than 700 cells/mm3 ) and high serum IgE concentrations predict continuing respiratory tract problems.

TREATMENT.

avoiding allergens,

improving bronchodilation,

reducing mediator-induced inflammation.

Systemic or topical inhaled medications are used,

 minimizing exposure to irritants such as tobacco smoke, smoke from wood-burning stoves, and fumes from kerosene , wet paint and disinfectants,

avoiding ice-cold drinks and rapid changes in temperature and humidity.

Pharmacologic therapy

 Oxygen by mask or nasal prongs at 2–3 L/min

epinephrine = 0.01 mL/kg of the 1:1,000 (1.0 mg/mL)

repeat the same dose once or twice at intervals of 20 min

side effects of epinephrine (pallor, tremor, anxiety, palpitations, and headache)

Terbutaline, a more selective b2 -agonist, is available in an injectable form and is an alternative to epinephrine.

The dose of 0.01 mL/kg of the 1:1,000 (1 mg/mL) - longer duration of activity, up to 4 hr. The maximal dose of terbutaline by subcutaneous injection is 0.25 mL; this dose may be repeated once, if necessary, after 20 min.

Inhalation of bronchodilator aerosols

 less drug is given than would be required by the subcutaneous route;

side effects of injected drugs such as epinephrine are avoided.

aerosol therapy is more effective than epinephrine in reversing bronchoconstriction. Salbutamol solution is safe and effective at a dose of 0.15 mg/kg (maximum 5 mg) followed by 0.05–0.15 mg/kg at intervals of 20–30 min until response is adequate.

available as a 0.5% solution (5 mg/mL) to be diluted with 2–3 mL normal saline Nebulization with oxygen at 6 L/min prevents hypoxemia

metered-dose inhaler, 3 to 10 puffs per dose, with a spacer

doses of 6 to 10 puffs

nebulized ipratropium bromide, 250–500 mg,

Both can be administered safely at intervals of 20 min for three doses and subsequently at intervals of 2 to 4 hr if necessary.

Theophylline

aminophylline = 5 mg/kg for 5–15 min

intravenous dose should be held until the theophylline level is known.

Steroid therapy reduces the relapse and hospitalization rates.