Thematic module 3 Allergic diseases in children

Thematic module 3 Allergic diseases in children

Themes:

1.   Atopic dermatitis and allergic rhinitis in children. Etiology, pathogenesis, clinical features, classification, treatment and prophylactic. Atopic march.

2.   Bronchial asthma. Etiology, pathogenesis, clinical features, diagnostics, treatment and prophylactic

Asthma is a chronic inflammatory condition of the lung airways resulting in episodic airflow obstruction. This chronic inflammation heightens the twitchiness of the airways – airways hyperresponsiveness (AHR) – to provocative exposures. Asthma management is aimed at reducing airways inflammation by minimizing proinflammatory environmental exposures, using daily controller anti-inflammatory medications, and controlling co-morbid conditions that can worsen asthma. Less inflammation typically leads to better asthma control, with fewer exacerbations and decreased need for quick-reliever asthma medications.

Etiology

Although the cause of childhood asthma has not been determined, contemporary research implicates a combination of environmental exposures and inherent biologic and genetic vulnerabilities. Respiratory exposures in this causal environment include inhaled allergens, respiratory viral infections, and chemical and biologic air pollutants such as environmental tobacco smoke. In the predisposed host, immune responses to these common exposures can be a stimulus for prolonged, pathogenic inflammation and aberrant repair of injured airways tissues. Lung dysfunction (i.e., AHR and reduced airflow) develops. These pathogenic processes in the growing lung during early life adversely affect airways growth and differentiation, leading to altered airways at mature ages. Once asthma has developed, ongoing exposures appear to worsen it, driving disease persistence and increasing the risk of severe exacerbations.

Genetics

More than 100 genetic loci have been linked to asthma. Although the genetic linkages to asthma have sometimes differed between cohorts, asthma has been consistently linked with loci containing proallergic, proinflammatory genes (the interleukin [IL]-4 gene cluster on chromosome 5). Genetic variation in receptors for different asthma medications is associated with variation in biologic response to these medications (polymorphisms in the β₂-adrenergic receptor). Other candidate genes include ADAM-33 (member of the metalloproteinase family), the gene for the prostanoid DP receptor, and genes located on chromosome 5q31 (possibly IL-12).

Environment

Recurrent wheezing episodes in early childhood are associated with common respiratory viruses, including respiratory syncytial virus, rhinovirus, influenza virus, adenovirus, parainfluenza virus, and human metapneumovirus. This association implies that host features affecting immunologic host defense, inflammation, and the extent of airways injury from ubiquitous viral pathogens underlie susceptibility to recurrent wheezing in early childhood. Furthermore, injurious viral infections of the airways that manifest as pneumonia or bronchiolitis requiring hospitalization are risk factors for persistent asthma in childhood. Other airways exposures can also exacerbate ongoing airways inflammation, increase disease severity, and drive asthma persistence. Indoor and home allergen exposures in sensitized individuals can initiate airways inflammation and hypersensitivity to other irritant exposures, and are strongly linked to disease severity and persistence. Consequently, eliminating the offending allergen(s) can lead to resolution of asthma symptoms and can sometimes “cure” asthma. Environmental tobacco smoke and air pollutants (ozone, sulfur dioxide) aggravate airways inflammation and increase asthma severity. Cold dry air and strong odors can trigger bronchoconstriction when airways are irritated but do not worsen airways inflammation or hyperresponsiveness.

 

Pathogenesis

Airflow obstruction in asthma is the result of numerous pathologic processes. In the small airways, airflow is regulated by smooth muscle encircling the airways lumens; bronchoconstriction of these bronchiolar muscular bands restricts or blocks airflow. A cellular inflammatory infiltrate and exudates distinguished by eosinophils, but also including other inflammatory cell types (neutrophils, monocytes, lymphocytes, mast cells, basophils), can fill and obstruct the airways and induce epithelial damage and desquamation into the airways lumen. Helper T lymphocytes and other immune cells that produce proallergic, proinflammatory cytokines (IL-4, IL-5, IL-13), and chemokines (eotaxin) mediate this inflammatory process. Pathogenic immune responses and inflammation may also result from a breach iormal immune regulatory processes (such as regulatory T lymphocytes that produce IL-10 and transforming growth factor [TGF]-β) that dampen effector immunity and inflammation when they are no longer needed. Hypersensitivity or susceptibility to a variety of provocative exposures or triggers (Table 1) can lead to airways inflammation, AHR, edema, basement membrane thickening, subepithelial collagen deposition, smooth muscle and mucous gland hypertrophy, and mucus hypersecretion—all processes that contribute to airflow obstruction.

Table 1   — ASTHMA TRIGGERS

Common viral infections of the respiratory tract Aeroallergens in sensitized asthmatic patients:      Animal dander      Indoor allergens      Dust mites      Cockroaches      Molds Seasonal aeroallergens:      Pollens (trees, grasses, weeds)      Seasonal molds Environmental tobacco smoke Air pollutants:      Ozone      Sulfur dioxide      Particulate matter      Wood- or coal-burning smoke      Endotoxin, mycotoxins      Dust Strong or noxious odors or fumes:      Perfumes, hairsprays      Cleaning agents Occupational exposures:      Farm and barn exposures      Formaldehydes, cedar, paint fumes Cold air, dry air Exercise Crying, laughter, hyperventilation Co-morbid conditions:      Rhinitis      Sinusitis      Gastroesophageal reflux

 

 

Clinical Manifestations and Diagnosis

Intermittent dry coughing and expiratory wheezing are the most common chronic symptoms of asthma. Older children and adults report associated shortness of breath and chest tightness; younger children are more likely to report intermittent, nonfocal chest pain. Respiratory symptoms can be worse at night, especially during prolonged exacerbations triggered by respiratory infections or inhalant allergens. Daytime symptoms, often linked with physical activities or play, are reported with greatest frequency in children. Other asthma symptoms in children can be subtle and nonspecific, including self-imposed limitation of physical activities, general fatigue (possibly due to sleep disturbance), and difficulty keeping up with peers in physical activities. Asking about previous experience with asthma medications (bronchodilators) may provide a history of symptomatic improvement with treatment that supports the diagnosis of asthma. Lack of improvement with bronchodilator and corticosteroid therapy is inconsistent with underlying asthma and should prompt more vigorous consideration of asthma-masquerading conditions.

Asthma symptoms can be triggered by numerous common events or exposures: physical exertion and hyperventilation (laughing), cold or dry air, and airways irritants. Exposures that induce airways inflammation, such as infections (rhinovirus, respiratory syncytial virus, metapneumovirus, torque teno virus, parainfluenza virus, influenza virus, adenovirus, Mycoplasma pneumonia, Chlamydia pneumoniae), and inhaled allergens, also increase AHR to irritant exposures. An environmental history is essential for optimal asthma management.

The presence of risk factors, such as a history of other allergic conditions (allergic rhinitis, allergic conjunctivitis, atopic dermatitis, food allergies), parental asthma, and/or symptoms apart from colds, supports the diagnosis of asthma. During routine clinic visits, children with asthma commonly present without abnormal signs, emphasizing the importance of the medical history in diagnosing asthma. Some may exhibit a dry, persistent cough. The chest findings are ofteormal. Deeper breaths can sometimes elicit otherwise undetectable wheezing. In clinic, quick resolution (within 10 min) or convincing improvement in symptoms and signs of asthma with administration of a short-acting inhaled β-agonist (SABA; e.g., albuterol) is supportive of the diagnosis of asthma.

During asthma exacerbations, expiratory wheezing and a prolonged expiratory phase can usually be appreciated by auscultation. Decreased breath sounds in some of the lung fields, commonly the right lower posterior lobe, are consistent with regional hypoventilation owing to airways obstruction. Crackles (or rales) and rhonchi can sometimes be heard, resulting from excess mucus production and inflammatory exudate in the airways. The combination of segmental crackles and poor breath sounds can indicate lung segmental atelectasis that is difficult to distinguish from bronchial pneumonia and can complicate acute asthma management. In severe exacerbations, the greater extent of airways obstruction causes labored breathing and respiratory distress, which manifests as inspiratory and expiratory wheezing, increased prolongation of exhalation, poor air entry, suprasternal and intercostal retractions, nasal flaring, and accessory respiratory muscle use. In extremis, airflow may be so limited that wheezing cannot be heard (Table 2).

Table 2  FORMAL EVALUATION OF ASTHMA EXACERBATION SEVERITY IN THE URGENT OR EMERGENCY CARE SETTING

	MILD	MODERATE	SEVERE	SUBSET: RESPIRATORY ARREST IMMINENT
SYMPTOMS
Breathlessness	While walking	While at rest (infant—softer, shorter cry, difficulty feeding)	While at rest (infant—stops feeding)
	Can lie down	Prefers sitting	Sits upright
Talks in	Sentences	Phrases	Words
Alertness	May be agitated	Usually agitated	Usually agitated	Drowsy or confused
SIGNS
Respiratory rate	Increased	Increased	Often >30 breaths/min
Use of accessory muscles; suprasternal retractions	Usually not	Commonly	Usually	Paradoxical thoracoabdominal movement
Wheeze	Moderate; often only end-expiratory	Loud; throughout exhalation	Usually loud; throughout inhalation and exhalation	Absence of wheeze
Pulse rate (beats/min)[‡]	<100	100-120	>120	Bradycardia
Pulsus paradoxus	Absent   <10 mm Hg	May be present   10-25 mm Hg	Often present   >25 mm Hg (adult)   20-40 mm Hg (child)	Absence suggests respiratory muscle fatigue
FUNCTIONAL ASSESSMENT
Peak expiratory flow (value predicted or personal best)	≥70%	Approx. 40-69% or response lasts <2 hr	<40%	<25%[?]
Pao2 (breathing air)   and/or	Normal (test not usually necessary)	≥60 mm Hg (test not usually necessary)	<60 mm Hg; possible cyanosis
Pco2	<42 mm Hg (test not usually necessary)	<42 mm Hg (test not usually necessary)	≥42 mm Hg; possible respiratory failure
Sao2 (breathing air) at sea level	>95% (test not usually necessary)	90-95% (test not usually necessary)	<90%

 

Laboratory Findings

Airway hyperresponsiveness to nonspecific stimuli is a hallmark of asthma. These include inhaled pharmacologic agents such as histamine and methacholine as well as physical stimuli such as exercise and cold air. Airways may exhibit hyperresponsiveness or twitchiness even when pulmonary function tests are normal. Giving increasing amounts of a bronchoconstrictive agent to induce a decrease in lung function (usually a 20% drop in forced expiratory volume in 1 second [FEV1]) is the most common method of testing airway responsiveness. Hyperresponsiveness iormal children younger than age 5 years is greater than in older children. The level of airway hyperresponsiveness usually correlates with the severity of asthma.

During acute asthma exacerbations, FEV1 is diminished and the flow-volume curve shows a “scooping out” of the distal portion of the expiratory portion of the loop. The residual volume, functional residual capacity, and total lung capacity are usually increased, while the vital capacity is decreased. Reversal or significant improvement of these abnormalities in response to inhaled bronchodilator therapy alone or with anti-inflammatory therapy is observed. Increased airway resistance also results in a decreased peak expiratory flow rate (PEFR). Diurnal variation in PEFR (ie, the difference between morning and evening measurements) of greater than 15–20% has been used as a defining feature of asthma. Significant changes in PEFR may occur before symptoms become evident. In more severe cases, PEFR monitoring enables earlier recognition of suboptimal asthma control. Exercise, cold air, and methacholine or histamine challenges may help to establish a diagnosis of asthma when the history, examination, and pulmonary function tests are not definitive. Alternatively, a diagnostic trial of inhaled bronchodilators and anti-inflammatory medications may be helpful, especially in infants and young children in whom underdiagnosis and undertreatment are common. Infant pulmonary function can be measured in sedated children with compression techniques. The forced oscillation technique can be used to measure airway resistance in younger children.

Hypoxemia is present early with a normal or low PCO2 level and respiratory alkalosis. Hypoxemia may be aggravated during treatment with a 2-agonist due to ventilation–perfusion mismatch. Oxygen saturation less than 91% is indicative of significant obstruction. Respiratory acidosis and increasing CO2 tension may ensue with further airflow obstruction and signal impending respiratory failure. Hypercapnia is usually not seen until the FEV1 falls below 20% of predicted value. Metabolic acidosis has also beeoted in combination with respiratory acidosis in children with severe asthma and indicates imminent respiratory failure. A PaO2 less than 60 mm Hg despite oxygen therapy and a PaCO2 over 60 mm Hg and rising more than 5 mm Hg per hour are relative indications for mechanical ventilation in a child in status asthmaticus.

Pulsus paradoxus may be present with moderate or severe asthma. In moderate asthma in a child, this may be between 10 and 25 mm Hg, and in severe asthma between 20 and 40 mm Hg. Absence of pulsus paradoxus in a child with severe asthma exacerbation may signal respiratory muscle fatigue.

Clumps of eosinophils on sputum smear and blood eosinophilia are frequent findings. Their presence tends to reflect disease activity and does not necessarily mean that allergic factors are involved. Leukocytosis is common in acute severe asthma without evidence of bacterial infection and may be more pronounced after epinephrine administration. Hematocrit can be elevated with dehydration during prolonged exacerbations or in severe chronic disease. Potential noninvasive measures of airway inflammation include serum eosinophil cationic protein levels, exhaled nitric oxide, and induced sputum. Each test has its strengths and weaknesses.

 

 

Table 2. Differential Diagnosis of Asthma in Infants and Children.

Viral bronchiolitis

Aspiration

Laryngotracheomalacia

Vascular rings

Airway stenosis or web

Enlarged lymph nodes

Mediastinal mass

Foreign body

Bronchopulmonary dysplasia

Obliterative bronchiolitis

Cystic fibrosis

Vocal cord dysfunction

Cardiovascular disease

 

Complications

With acute asthma, complications are primarily related to hypoxemia and acidosis and can include generalized seizures. Pneumomediastinum or pneumothorax can be a complication in status asthmaticus. Recent studies point to airway wall remodeling and loss of pulmonary function with persistent airway inflammation. Childhood asthma independent of any corticosteroid therapy has been shown to be associated with delayed maturation and slowing of prepubertal growth velocity. However, attainment of final predicted adult height does not appear to be compromised.

 

Treatment

 Management of asthma should have the following components:

–         assessment and monitoring of disease activity;

–         provision of education to enhance the patient’s and family’s knowledge and skills for self-management;

–         identification and management of precipitating factors and co-morbid conditions that may worsen asthma;

–         appropriate selection of medications to address the patient’s needs.

The long-term goal of asthma management is attainment of optimal asthma control.

 

Component 1: Regular Assessment and Monitoring

Regular assessment and monitoring are based on the concepts of asthma severity, asthma control, and responsiveness to therapy.

Asthma severity is the intrinsic intensity of disease, and assessment is generally most accurate in patients not receiving controller therapy. Hence, assessing asthma severity directs the initial level of therapy. The 2 general categories are intermittent asthma and persistent asthma, the latter further subdivided into mild, moderate, and severe. Asthma severity is to be assessed only once, during a patient’s initial evaluation, and only in patients who are not yet using a daily controller agent. In contrast, asthma control refers to the degree to which symptoms, ongoing functional impairments, and risk of adverse events are minimized and goals of therapy are met. In children receiving controller therapy, asthma control is to be assessed. Assessment of asthma control is important in adjusting therapy and is categorized in 3 levels: well-controlled, not well-controlled, and very poorly controlled. Responsiveness to therapy is the ease with which asthma control is attained by treatment. It can also encompass monitoring for adverse effects related to medication use.

Classification of asthma severity and control is based on the domains of Impairment and Risk. These domains may not correlate with each other and may respond differently to treatment.

The NIH guidelines have criteria for 3 age groups—0-4 yr, 5-11 yr, and ≥12 yr—for the evaluation of both severity (Table 3) and control (Table 4). The level of asthma severity or control is based on the most severe impairment or risk category. In assessing asthma severity, impairment consists of an assessment of the patient’s recent symptom frequency (daytime and nighttime with subtle differences iumeric cutoffs between the 3 age groups), need for short-acting β₂-agonists for quick relief, ability to engage iormal or desired activities, and airflow compromise, which is evaluated with spirometry in children 5 yr and older.

Risk refers to an evaluation of the likelihood of developing asthma exacerbations for the individual patient. Of note, in the absence of frequent symptoms, persistent asthma should be considered, and therefore long-term controller therapy should be initiated for infants or children who have risk factors for asthma (see earlier) and 4 or more episodes of wheezing over the past year that lasted longer than 1 day and affected sleep, or 2 or more exacerbations in 6 months requiring systemic corticosteroids.

Table 3. Assessing asthma severity and initiating treatment for patients who are not currently taking long-term control medications

	CLASSIFICATION OF ASTHMA SEVERITY
	Intermittent	Persistent
		Mild	Moderate	Severe
COMPONENTS OF SEVERITY
Impairment
Daytime symptoms	≤2 days/wk	>2 days/wk but not daily	Daily	Throughout the day
Nighttime awakenings:
Age 0-4 yr	0	1-2/mo	3-4/mo	>1/wk
Age ≥5 yr	≤2/mo	3-4/mo	>1/wk but not nightly	Often 7/wk
Short-acting β2-agonist use for symptoms (not for prevention of exercise-induced bronchospasm)	≤2 days/wk	>2 days/wk but not daily, and not more than 1 on any day	Daily	Several times per day
Interference with normal activity	None	Minor limitation	Some limitation	Extreme limitation
Lung function:
FEV1 % predicted, age ≥5 yr	Normal FEV1 between exacerbations    >80% predicted	≥80% predicted	60-80% predicted	<60% predicted
FEV1/FVC ratio:
Age 5- 11 yr	>85%	>80%	75-80%	<75%
Age ≥12 yr	Normal	Normal	Reduced 5%	Reduced >5%
Risk
Exacerbations requiring systemic corticosteroids:   Age 0-4 yr	0-1/yr (see notes)	≥ 2 exacerbations in 6 mo requiring systemic corticosteroids or      ≥ 4 wheezing episodes/yr lasting >1 day and risk factors for persistent asthma
Age ≥ 5 yr	0-1/yr (see notes)	≥2/yr (see notes)	≥2/yr (see notes)	≥2/yr (see notes)
RECOMMENDED STEP FOR INITIATING THERAPY
All ages	Step 1	Step 2
Age 0-4 yr			Step 3	Step 3
Age 5-11 yr			Step 3, medium-dose ICS option	Step 3,  medium-dose ICS option      or      Step 4
Age ≥12 yr			Consider a short course of systemic corticosteroids	Consider a short course of systemic corticosteroids
	In 2-6 wk, evaluate level of asthma control that is achieved and adjust therapy accordingly. If no clear benefit is observed within 4-6 wk, consider adjusting therapy or alternative diagnoses.

 

FEV1, forced expiratory volume in 1 sec; FVC, forced vital capacity; ICS, inhaled corticosteroids.

 

Table 4. Assessing asthma control and adjuring therapy in children

	CLASSIFICATION OF ASTHMA CONTROL
	Well-Controlled	Not Well-Controlled	Very Poorly Controlled
COMPONENTS OF CONTROL
Impairment
Symptoms	≤2 days/wk but not more than once on each day	>2 days/wk or multiple times on ≤2 days/wk	Throughout the day
Nighttime awakenings:
Age 0-4 yr	≤1/mo	>1/mo	>1/wk
Age 5-11 yr	≤1/mo	≥2/mo	≥2wk
Age ≥12 yr	≤2/mo	1-3/wk	≥4/wk
Short-acting β2-agonist use for symptoms (not for exercise-induced bronchospasm pretreatment)	≤2 days/wk	>2 days/wk	Several times per day
Interference with normal activity	None	Some limitation	Extremely limited
Lung function:
Age 5-11 yr:
FEV1 (% predicted or peak flow)	>80% predicted or personal best	60-80% predicted or personal best	<60% predicted or personal best
FEV1/FVC:	>80%	75-80%	<75%
Age ≥ 12 yr:
FEV1 (% predicted or peak flow)	>80% predicted or personal best	60-80% predicted or personal best	<60% predicted or personal best
Validated questionnaires:
Age ≥ 12 yr:
ATAQ	0	1-2	3-4
ACQ	≤0.75	≤1.5	N/A
ACT	≥220	16-19	≤15
Risk
Exacerbations requiring systemic corticosteroids:
Age 0-4 yr	0-1/yr	2-3/yr	>3/yr
Age ≥5 yr	0-1/yr	≥2/yr (see notes)
Consider severity and interval since last exacerbation.
Treatment-related adverse effects	Medication side effects can vary in intensity from none to very troublesome and worrisome. The level of intensity does not correlate to specific levels of control but should be considered in the overall assessment of risk.
Reduction in lung growth or progressive loss of lung function	Evaluation requires long-term follow-up care.
RECOMMENDED ACTION FOR TREATMENT
	Maintain current step.   Regular follow-up every 1-6 mo to maintain control.   Consider step down if well-controlled for at least 3 mo.	Step up (1 step) and reevaluate in 2-6 wk.   If no clear benefit in 4-6 wk, consider alternative diagnoses or adjusting therapy.   For side effects, consider alternative options.	Consider short course of oral corticosteroids.   Step up (1-2 steps) and reevaluate in 2 weeks.   If no clear benefit in 4-6 wk, consider alternative diagnoses or adjusting therapy.   For side effects, consider alternative options.

Component 3: Control of Factors Contributing to Asthma Severity

Controllable factors that can significantly worsen asthma can be generally grouped as (1) environmental exposures and (2) co-morbid conditions (Table 5).

 

 

Table 5. CONTROL OF FACTORS CONTRIBUTING TO ASTHMA SEVERITY

Eliminate or reduce problematic environmental exposures:      Environmental tobacco smoke elimination or reduction:      In home and automobiles      Allergen exposure elimination or reduction in sensitized asthmatic patients:      Animal danders:      Pets (cats, dogs, rodents, birds)      Pests (mice, rats)      Dust mites      Cockroaches      Molds      Other airway irritants:      Wood- or coal-burning smoke      Strong chemical odors and perfumes (e.g., household cleaners)      Dusts Treat co-morbid conditions:      Rhinitis      Sinusitis      Gastroesophageal reflux Annual influenza vaccination (unless patient is egg-allergic)

 

Eliminating and Reducing Problematic Environmental Exposures

The majority of children with asthma have an allergic component to their disease; steps should be taken to investigate and minimize allergen exposures in sensitized asthmatic patients. For sensitized asthmatic patients, reduced exposure to perennial allergens in the home decreases asthma symptoms, medication requirements, AHR, and asthma exacerbations. The important home allergens that are linked to asthma worsening differ between locales and even between homes. Common perennial allergen exposures include furred or feathered animals as pets (cats, dogs, ferrets, birds) or as pests (mice, rats) and occult indoor allergens such as dust mites, cockroaches, and molds. Although some sensitized children may report an increase in asthma symptoms on exposure to the allergen source, improvement from allergen avoidance may not become apparent without a sustained period of days to weeks away from the offending exposure. Tobacco, wood and coal smoke, dusts, strong odors, and noxious fumes can all aggravate asthma. These airways irritants should be eliminated from or reduced in the homes and automobiles used by children with asthma. School classrooms and daycare settings can also be sites of asthma-worsening environmental exposures. Eliminating or minimizing these exposures (e.g., furred or feathered pets in classrooms of sensitized children with asthma) can reduce asthma symptoms, disease severity, and the amount of medicatioeeded to achieve good asthma control. Annual influenza vaccination continues to be recommended for all children with asthma (except for those with egg allergy), although influenza is not responsible for the large majority of virus-induced asthma exacerbations experienced by children.

Treat Co-Morbid Conditions

Rhinitis, sinusitis, and gastroesophageal reflux often accompany asthma and can mimic asthma symptoms and worsen disease severity. Indeed, these conditions with asthma are the most common causes of chronic coughing. Effective management of these co-morbid conditions may improve asthma symptoms and disease severity, such that less asthma medication is needed to achieve good asthma control.

Gastroesophageal reflux is more common, with a reported incidence of GER-related asthma symptoms in up to 64% of asthmatic patients. GER may worsen asthma through 2 postulated mechanisms: (1) aspiration of refluxed gastric contents (micro- or macro-aspiration); and (2) vagally-mediated reflex bronchospasm. Occult GER should be suspected in individuals with difficult-to-control asthma, especially patients who have prominent asthma symptoms while eating or sleeping (in a horizontal position) or who prop themselves up in bed to reduce nocturnal symptoms. GER can be demonstrated by reflux of barium into the esophagus during a barium swallow procedure or by esophageal pH monitoring. Because radiographic studies lack sufficient sensitivity and specificity, extended esophageal pH monitoring is the method of choice for diagnosing GER. If significant GER is noted, reflux precautions should be instituted (no food 2 hr before bedtime, head of the bed elevated 6 in., avoidance of caffeinated foods and beverages) and medications such as proton pump inhibitors (omeprazole, lansoprazole) or H₂-receptor antagonists (cimetidine, ranitidine) administered for 8 to 12 wk. Proton pump inhibition did not improve asthma control in one study of adults with asthma and GER.

Rhinitis is usually co-morbid with asthma, detected in ≈90% of children with asthma. Rhinitis can be seasonal and/or perennial, with allergic and nonallergic components. Rhinitis complicates and worsens asthma via numerous direct and indirect mechanisms. Nasal breathing may improve asthma and reduce exercise-induced bronchospasm by humidifying and warming inspired air and filtering out allergens and irritants that can trigger asthma and increase AHR. Reduction of nasal congestion and obstruction can help the nose to perform these humidifying, warming, and filtering functions. In asthmatic patients, improvement in rhinitis is also associated with improvement in AHR, lower airways inflammation, asthma symptoms, and asthma medication use. Optimal rhinitis management in children is similar to asthma management in regard to the importance of interventions to reduce nasal inflammation.

 

Radiographic evidence for sinus disease is common in patients with asthma. There is usually significant improvement in asthma control in patients diagnosed and treated for sinus disease. A coronal, “screening” or “limited” CT scan of the sinuses is the gold standard test for sinus disease and is often helpful if recurrent sinusitis has been suspected and treated without such evidence. If the patient with asthma has clinical and radiographic evidence for sinusitis, topical therapy to include nasal saline irrigations and possibly intranasal corticosteroids should be instituted, and a 2- to 3-wk course of antibiotics administered.

 

Component 4: Principles of Asthma Pharmacotherapy

The current version of NIH asthma guidelines (2007) proposes an expanded stepwise treatment approach to assist, not replace, the clinical decision-making required to meet individual patient needs. The recommendations vary by age groups and are based on current evidence. The goals of therapy are to reduce the components of both impairment (e.g., preventing chronic and troublesome symptoms, allowing infrequent need of quick-reliever medications, maintaining “normal” lung function, maintaining normal activity levels including physical activity and school attendance, meeting families’ expectations and satisfaction with asthma care) and risk (e.g., preventing recurrent exacerbations, reduced lung growth, and medications’ adverse effects). The choice of initial therapy is based on assessment of asthma severity, and for patients who are already using controller therapy, modification of treatment is based on assessment of asthma control and responsiveness to therapy. A major objective of this approach is to identify and treat all “persistent” and uncontrolled asthma with anti-inflammatory controller medication. Daily controller therapy is not recommended for children with “intermittent asthma.” Management of intermittent asthma is simply the use of a short-acting inhaled β-agonist as needed for symptoms and for pre-treatment in those with exercise-induced bronchospasm (Step 1 therapy; see Table 6).

 

Table 6    STEPWISE APPROACH FOR MANAGING ASTHMA IN CHILDREN

AGE	THERAPY	INTERMITTENT ASTHMA	PERSISTENT ASTHMA: DAILY MEDICATION
		Step 1	Step 2	Step 3	Step 4	Step 5	Step 6
0-4 yr	Preferred	SABA prn	Low-dose ICS	Medium-dose ICS	Medium dose ICS + either LABA or LTRA	High-dose ICS + either LABA or LTRA	High-dose ICS + either LABA or LTRA and Oral corticosteroid
	Alternative		Cromolyn or montelukast
5-11 yr	Preferred	SABA prn	Low dose ICS	Either low-dose ICS ? LABA, LTRA, or theophylline   or   Medium-dose ICS	Medium-dose ICS + LABA	High-dose ICS + LABA	High dose ICS + LABA and Oral corticosteroid
	Alternative		Cromolyn, LTRA, nedocromil, or theophylline		Medium-dose ICS + either LTRA or Theophylline	High-dose ICS + either LTRA or Theophylline	High-dose ICS + either LTRA or Theophylline and Oral corticosteroid
≥12 yr	Preferred	SABA prn	Low-dose ICS	Low-dose ICS + LABA or Medium-dose ICS	Medium-dose ICS + LABA	High-dose ICS + LABA and Consider omalizumab for patients with allergies	High-dose ICS + LABA + oral co ticosteroid and Consider omalizumab for atients with allergies
	Alternative		Cromolyn, LTRA, nedocromil, or theophylline	Low-dose ICS + LTRA, theophylline, or zileuton	Medium-dose ICS + LTRA, theophylline, or zileuton
	Each step: Patient education, environmental control, and management of comorbidities. Age ≥5 yr: Steps 2-4: Consider subcutaneous allergen immunotherapy for patients who have allergic asthma.
	QUICK-RELIEF MEDICATION FOR ALL PATIENTS
	SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms: up to 3 treatments at 20-min intervals as needed. Short course of oral systemic corticosteroids may be needed. Caution: Use of SABA >2 days/wk for symptom relief (not prevention of exercise-induced bronchospasm) generally indicates inadequate control and the need to step up treatment. For ages 0-4 yr: With viral respiratory infection: SABA q4-6h up to 24 hr (longer with physician consult). Consider short course of systemic corticosteroids if exacerbation is severe or patient has history of previous severe exacerbations.

 

ICS, inhaled corticosteroid; LABA, inhaled long-acting β2-agonist; LTRA, leukotriene receptor antagonist; prn, as needed; SABA, inhaled short-acting β2-agonist.

 

Transfer

 

The preferred treatment for all patients with persistent asthma is daily ICS therapy, as monotherapy or in combination with adjunctive therapy. The type(s) and amount(s) of daily controller medications to be used are determined by the asthma severity and control rating. Alternative medications for Step 2 therapy include a leukotriene receptor antagonist (montelukast), nonsteroidal anti-inflammatory agents (cromolyn and nedocromil), and theophylline (for youths). For young children (≤4 r of age) with moderate or severe persistent asthma, medium-dose ICS monotherapy is recommended (Step 3); combination therapy is recommended only as a Step 4 treatment for uncontrolled asthma.

Along with medium-dose ICSs, combination therapy with an ICS plus any of the following adjunctive therapies (depending on age group) is recommended as Step 4 treatment for moderate persistent asthma, or as step-up therapy for uncontrolled persistent asthma: long-acting inhaled β₂-agonists (LABAs), leukotriene-modifying agents, cromones, and theophylline. Children with severe persistent asthma (Treatment Steps 5 and 6) should receive high-dose ICS, an LABA, and long-term administration of oral corticosteroids if required. In addition, omalizumab can be used in older children (≥12 yr old) with severe allergic asthma. A rescue course of systemic corticosteroids may be necessary at any step. For children 5 yr and older with allergic asthma requiring Steps 2-4 care, allergen immunotherapy can be considered.

“Step-Up, Step-Down” Approach

The NIH guidelines emphasize initiating higher-level controller therapy at the outset to establish prompt control, with measures to “step down” therapy once good asthma control is achieved. Initially, airflow limitation and the pathology of asthma may limit the delivery and efficacy of ICS such that stepping up to higher doses and/or combination therapy may be needed to gain asthma control. Furthermore, ICS requires weeks to months of daily administration for optimal efficacy to occur. Combination pharmacotherapy can achieve relatively immediate improvement while also providing daily ICS to improve long-term control.

Asthma therapy can be stepped down after good asthma control has been achieved and ICS has had time to achieve optimal efficacy, by determining the lowest number or dose of daily controller medications that can maintain good control, thereby reducing the potential for medication adverse effects. If a child has had well-controlled asthma for at least 3 months, the guidelines suggest decreasing the dose or number of the child’s controller medication(s) to establish the minimum required medications to maintain well-controlled asthma. Regular follow-up is still emphasized because the variability of asthma’s course is well recognized. In contrast, if a child has not well-controlled asthma, the therapy level should be increased by 1 step and close monitoring is recommended. For a child with very poorly controlled asthma, the recommendations are that treatment go up 2 steps and/or a short course of oral corticosteroid therapy be given, with evaluation within 2 wk. As step-up therapy is being considered at any point, it is important to check inhaler technique and adherence, implement environmental control measures, and identify and treat comorbid conditions.

Atopic dermatitis.

   Patients with atopic dermatitis: Milk crust

Allergy is a companion of civilization, and the frequency and prevalence of allergic diseases is a medical condition human health in adverse environmental conditions . According to specialists of the XXI century will be characterized further spread of allergic diseases. Background allergic skin diseases in children is increasing every year, requiring the development of specialized care for children.
Significant expansion and continuous increase in the frequency of allergic diseases in children worldwide and attracted attracted the attention of scientists as previous generations, and our contemporaries. The growth rate and early manifestation of atopic disease during the last years of serious concern among pediatricians. With the development of industry and technological progress as new and aggressive adverse environmental factors that promote growth proliferation atopy, in connection with which this pathology becomes unmanageable.

Significant prevalence of allergic diseases and the annual growth of this disease around the world have turned the issue of allergies in the medical-social problem. Today atopy is regarded as systemic pathology, clinical shock is determined by the authority. Systematic destruction distinctly manifested in childhood. Stages of development of sensitization, expanding beachhead allergies with age explain the appearance of a new term – “atopic march”. Infants with AD are predisponsed to developing allergic rhinitis and/ or asthma later in childhood, the so-called“atopic march”. For young children is the most significant food allergy with primary cutaneous manifestations of clinical symptoms. After two years against the preservation of food allergy, the role aeroalergens, especially tick-borne allergens house dust, epidermal, and later – pollen. Atopic dermatitis (AD) in most cases begins in the first year of life and is the first of atopic disease. Maximum development of asthma acquired in 5-6 years, and the peak of allergic rhinitis accounted for prepubertal and pubertal periods.

     In other words – atopic dermatitis may serve as the initial stage for the development of other, more severe allergies, especially – asthma. Controlling the flow with AD, scholars and practitioners rely prevent “atopic march” .

Atopic dermatitis (AD) – a systemic chronic allergic disease that occurs in people with an inherited predisposition to atopy and characterized by typical morphological changes of the skin with itching, lesions of the central and autonomic nervous system, endocrine and immune systems with hyper Ig E.

     AD is an important problem of modern pediatrics, which is primarily due to the spread of disease. Epidemiological studies carried out under standardized protocols international program ISSAC (International Study of Astma and Allergy in Childhood) in Europe, Asia and Africa as well – America and Australia showed that the prevalence of AD according to various sources ranging from 1 to 46%. Prevalence of AD among children population is the highest in Japan and 24% in the Americas – 17.2% Europe – 15.6%, in Russia – from 5.2 to 15.5% . The prevalence of AD in Ukraine is 3.9%, but in recent years it has been steadily increasing . According to WHO, about 15% of the child population in Europe suffer from allergic disease, traced a clear tendency to increase these numbers 213.

   

There are claims that 60% of children with AD manifestations sometimes disappear completely, the other 40% – worried about relapsing disease for a long time 333. It is believed that children who are sick in the first year of life, have a more favorable prognosis . However, one caot ignore the fact that the earlier debut and runs harder than DR, the higher the chance of his persistent flow, especially when combined with other atopic diseases.

According to the results of epidemiological studies carried out in different countries, the prevalence of allergic dermatoses varies over a wide range – from 3% to 73%. Data above research and analysis reports allergic offices, centers of clinical allergy and immunology in different regions of Russia showed the incidence of allergic dermatoses in children with allergic diseases much higher one that actually recorded. Similar studies of domestic scholars also argue that BP has a leading position in the structure of allergic diseases in children – up to 50-75% and is more than 1 / four chronic diseases, which affects the skin.

 

Atopic dermatitis is often combined with other allergic diseases (so-called allergy syndrome) – with asthma – in 34% of allergic rhinitis – in 25%, recurrent laryngotracheitis – 10% of hay fever – in 8% of 100.

According to some scholars 112 in the structure of atopic disease sprinkled `Janka and angioedema angioedema occurs with a frequency of 3% to 35%, severe atopic syndrome – from 0.2% to 1.5%, acute toxic-allergic reactions – from 0.1% to 1.5%, Stevens-Johnson syndrome – from 0.05% to 0.1%; contact dermatitis – from 0.1% to 0.2%; Lyell syndrome – from 0.01% to 0 1%, but the most common is the DR, which is registered with a frequency of 10% to 73%.

    Priority importance is the complexity of studying epidemiological indicators of AD, which is due to the lack of pathognomonic tests and criteria for verification of its. The need for in-depth study of this issue lies in the lack, until recently approved classification blood pressure, which reduces vigilance precinct pediatricians, thereby causing delayed diagnosis and an increasing number of complicated forms in the structure of this pathology. Developments undertaken in this direction  prove that the actual incidence is much higher among traffic being registered.

    Summarizing the above it should be noted that AD is a fairly common problem multifaceted and requires further in-depth study of the causes of development and methods of prevention.

1.2 Etiology and pathogenesis of atopic dermatitis

Further consideration of the problem shows that AD belongs to the multifactorial polygenic disease with burdened heredity. This means that the disease required a combination of damaging factors of the microorganism and environmental conditions. The basis of AD is genetic predisposition to abnormally elevated immune response to a wide range of common environmental factors – allergens. Total component of all these factors – chronic allergic inflammation, localized in a “target organ” which is the skin in AD 303.
Leading role in the etiology and pathogenesis belongs heredity. AD occurs in 56% of probands with burdened heredity on one of the parental lines in 81% of children with complicated pedigree on both lines. Conducted in this field studies have shown that 80% of children suffer from AD, weighed a history of allergies, and in most cases the maternal line – up to 70% and only 18 – 22% on the paternal side. The analysis shows the importance of heredity that if both parents suffer from atopic disease, the risk of AD in children ranges from 60 to 80% if one parent is sick chances are reduced to 45 – 59% and in healthy parents such risk is 10 – 12%. Pressing issue is to study the possible participation of 26 genes in the development of atopy, many of them established relationship with symptoms and atopy defined localization.

    Atopy gene linked to a specific locus on the long arm of chromosome 11 and is transmitted primarily through the maternal line.

Analyzing the work affecting the immune mechanisms of the pathogenesis of AD, the undisputed fact is that the main pathogenetic link in the development of the disease are Ig E – dependent reaction , it is generally well Th1/Th2 concept. In VI International Symposium on DR dealt differences immune response and not atopic atopic type, defined function of T-cell populations. The population of memory cells in antigen stimulation may send CD 4 T cells to Th1 or Th2 path, respectively, the first type of immune response observed ieatopikiv, and the second – in the presence of atopy. Th type 1 cells synthesize interleukin (IL) -2, γ-interferon, tumor necrosis factor – a  and others – these cytokines cause delayed reactions. Th type 2 cells produce IL-4, 5, 10, 13, responsible for the development of atopic reactivity . Cytokines synthesized by Th 2 cells are in dynamic opposition to Th 1 cells and vice versa.

    However, the skin in AD is not only a target organ, but also actively participate in the formation of atopy. The concept of the immune system of the skin revealed in studies that demonstrate the value of cells located in the dermis – mast cells, macrophages, B-lymphocytes, endothelium of blood and lymph vessels. Research has identified a number of authors lead lymphoid tissue associated with the skin, in the initiation of the immune response in AD. Indicative is the work of J. Banchereau, M. Ralph , which proved that after transplantation of skin, when access to the regional lymph nodes was interrupted by ligation of afferent vessels, the immune response to a skin graft and contact allergens is developed.

   Unity mechanisms of AD, asthma and allergic rhinitis scientists noted long ago – in 1993 these diseases have been grouped under the name “atopic triad”, but the pathophysiologic link between them has been proven only in recent years. Some researchers suggest that dermal sensitization precedes the sensitization of the respiratory tract .

Among other immunological mechanisms, but I (reaginovomu, Ig E-dependent) type classification Gell and Coombs noted the reaction cell-mediated (type IV) [229]. Also, there are reactions of type II (cytotoxic), type III (immunocompetent) and V – stimulating type hypersensitivity reactions. Sufficient attention is given to researchers as Pathochemical phase allergic reactions and nonimmune (pseudoallergy) mechanisms of pathogenesis of AD.

    Among the most prominent damaging exogenous factors important role as allergens play food, household factors (house dust, especially mites Dermatophagoides), fungal, physical irritants, contact allergens animal (pet dander) and plant origin (pollen grass and trees), and a number of nonspecific factors – climate change, neblahopryyemni environmental impacts, smoke, psycho-emotional stress.

Food allergens are the most important in the structure of sensitization with infancy. This age period is characterized by morphological, enzymatic, and immunological enterohormonalnoyu imperfect safeguard the barrier of the small intestine, which is easily affected and influenced the significant penetration of immunogenic components of food.

Diagnostics. For the estimation of AD diagnosis the combination of not less 3 essential and 3 additive criteria is necessary.

1.     Essential criteria: itch, rush elements`, typical morphology and localication: flexor surface of extremities in adults (lichinefication), extensor surfaces and face in children (eczema), chronic recurrent course, atopic diseases in personal and family anamnesis (bronchial asthma, allergic rhinitis).

2.     Additive criteria: skin dryness, ichthyosis, skin picture increasing, keratosis, folicularis, positive skin hypersensitivity reactions of an immediate type with allergens, high level of general Ig E in blood, appearance of diseases in early age (under 2 years), tendency to infections of the skin mainly of staphylococcic and herpetic etiology, nonspecific dermatitis of hands and foots, nipples` eczema, cheilitis, reccurent conjunctivitis, keratoconus, subcapsular front cataract, white dermographism, dark circles under the eyes, folds on the frontal surface of neck, face skin paleness of redness, itch in sweating, dermatosis` clinical dynamics dependence on environmental and emotional factors, allergy for wood and lipids` solvents, food allergy.

 

 

 

 

 

Atopic dermatitis (AD), often called eczema (pronounced “EK-zema”) or atopic eczema is a very common skin disease. It affects around 10% of all infants and children. The exact cause is not known, but AD results from a combination of family heredity and a variety of conditions in everyday life that triggers the red, itchy rash. How do we know if it’s atopic dermatitis? TIME OF ONSET. This type of eczema usually begins during the first year of life and almost always within the first five years. It’s seldom present at birth, but it often comes on during the first six weeks. Other rashes also can start at any time, but most rashes disappear within a few days to weeks. AD tends to persist. It may wax and wane, but it keeps coming back. ITCHING. Atopic dermatitis is a very itchy rash. Much of the skin damage comes from scratching and rubbing that the child cannot control. THE LOCATION OF THE RASH can also help us recognize AD. In babies, the rash usually starts on the face or over elbows and knees, places that are easy to scratch and rub. It may spread to involve all areas of the body, although moisture in the diaper region protects the skin barrier. Later in childhood, the rash is typically in the elbow and knee folds. Sometimes it only affects the hands, and at least 70% of people with AD have hand eczema at some time in their life. Rashes on the feet, scalp or behind the ears are other clues that might point to AD. Be advised, though, that these symptoms may also indicate other conditions, such as seborrheic dermatitis.   THE APPEARANCE OF THE RASH is probably the least helpful clue, because it may be very different from one person to another. Scratch marks are often seen, along with scaly dry skin. The skin may become infected and show yellow crusts or little, pinpoint, pus-containing bumps. The skin also may thicken from long-term scratching and rubbing.

HEREDITY. If other family members or relatives have AD, asthma or hay fever, the diagnosis of AD is more likely.

THE BOTTOM LINE: Be sure to get your child diagnosed by a physician before assuming that the condition is atopic dermatitis.

The Atopic Triad

AD falls into a category of diseases called Atopy, a term originally used to describe the allergic conditions asthma and hay fever. AD was included in the atopic category because it often affects people who either suffer from asthma and/or hay fever or have family members who do. Physicians often refer to these three conditions as the “atopic triad.”

Does it run in families?

AD is a familial disease, though the exact way it passes from parents to children is unclear. If one parent has AD, or any of the other atopic diseases (asthma, hay fever), the chances are about 50% that the child will have one or more of the diseases. If both parents are atopic, chances are even greater that their child will have it. However, the connection is not an absolute one: As many as 30% of the affected patients have no family members with any of these allergic disorders.

What causes atopic dermatitis?

AD is not contagious. People with AD cannot “give” it to someone else.

AD inflammation results from too many reactive inflammatory cells in the skin. Research is seeking the reason why these cells over-react. Patients with AD (asthma or hay fever) are born with these over-reactive cells. When something triggers them, they don’t turn off as they should. We try to control AD by controlling the trigger factors that “turn on” inflamed skin, or by “damping the flames” with anti-inflammatory therapies.

What are trigger factors?

Trigger factors may be different in different people. Most children get worse when they get a cold or other infection. Most have worse problems in the winter; but others simply cannot stand the sweating during hot, humid summer weather. Let’s look at the trigger factors that seem to affect every child with AD.

DRY SKIN. The skin’s main function is to provide a barrier against dirt, germs and chemicals from the outside. We don’t notice this barrier unless it gets dry, and then it’s scaly rough and tight. Dry skin is brittle – moist skin is soft and flexible. People with AD have a defect in their skin so it won’t stay moist. It is especially bad in winter when the heat is on in the house and the humidity drops. Other things that dry the skin are too much bathing without proper moisturizing. The challenge: Prevent skin dryness.

IRRITANTS. Irritants are any of the substances outside the body that can cause burning, redness, itching or dryness of the skin. The challenge: Avoid irritating substances.

STRESS. Emotional stress comes from many situations. People with AD often react to stress by having red flushing and itching. Special problems for children with AD include frustration, anger or fear. And, of course, AD itself, and its treatments, are a source of stress! The challenge: Recognize stress and reduce it.

HEAT AND SWEATING. Most people with atopic dermatitis notice that when they get hot, they itch. They have a type of prickly heat that doesn’t occur just in humid summertime but anytime they sweat. It can happen from exercise, from too many warm bedclothes, or rapid changes in temperature from cold to warm.

INFECTIONS. Bacterial “staph” infections are the most common, especially on arms and legs. Such infections might be suspected if areas are weeping or crusted or if small “pus-bumps” are seen. A common virus infection of children, Molluscum sp., tends to be more severe in children with AD. Molluscum infections look like small bumps, often with a central white core. Herpes infections (such as fever blisters or cold sores) and fungus (ringworm or athlete’s foot) can also trigger AD. If some lesions look different ask your doctor. If they turn out to be infected, they can be treated with antibiotics or other, effective medications. These are generally benign, superficial infections for AD patients and they do not seem to be especially contagious for other people. The challenge: Recognize and treat pustules or crusted lesions in consultation with a physician.

ALLERGENS. Allergens are materials (such as pollen, pet dander, foods, or dust) that cause allergic responses. Allergic diseases such as asthma and hay fever, which flare quickly, are easy to tie to allergens. Allergic symptoms, such as itching and hives, appear soon after exposure to airborne allergens and last only briefly. But the slower, continuing, chronic eczema of AD may be difficult to tie to specific allergens. Food allergies can trigger flares, especially for children with moderate to severe AD. Pollens, dust mites, and pets can seldom be shown to trigger eczema in young children. Of the available tests for allergy, scratch tests and RAST tests are only brief reactions and do not diagnose allergen-triggered eczema. Patch tests, by contrast, can diagnose eczema response in some cases such as allergies to skin care products.

Are there other trigger factors?

Children with AD will be helped by reducing the major trigger factors described above. But individuals may be subject to other trigger factors, and it is important to be alert for these as well.

How can you avoid trigger factors?

1.     Keep the skin barrier intact. MOISTURIZE!

2.     Wear soft clothes that “breathe.” Avoid fabrics of wool, nylon, or stiff material.

3.     If sweating causes itching, find ways to keep cooler: Reduce exertion, especially during times of flare. Layer clothing and adjust to temperature change. Don’t overheat rooms, especially the bedroom. Use light bedclothes.

4.     When itching from sweating, dust, pollen or other exposures, take a cooling shower or tub bath, and don’t forget to moisturize afterwards, within 3 minutes after the child has been gently toweled. Refer to the NEA Bathing & Moisturizing educational brochure for more information.

5.     Learn to recognize signs of infection and treat early.

6.     If you suspect food allergy, be systematic. Likely offenders are eggs, milk, peanuts, soy, wheat and seafood, but any food can do it. Can you exclude the most likely offender for a week? Substitute hydrolysate (e.g. Alimentum® or Nutramagen®) for cow’s milk formula. Keep a food diary. When the skin clears up, try the food. Watch for signs of itching or redness over the next two hours. Eliminate a food group if it causes hives or face swelling. Don’t exclude multiple food groups at the same time – it’s rare to have more than one or two food allergies that impact the eczema, and your child can get malnourished with prolonged avoidance of many foods. Always make sure that any food manipulation is performed with the advice of a physician.

7.     With allergy-prone kids furry animals are a risk. If you must have pets, keep them outside or at least off beds, rugs and furniture where the child plays. Dust mites collect in bedroom carpets and bedding. Simple control measures include coverings for pillows and mattresses, removing bedroom carpets and frequent washing of bedclothes in hot water.

8.     Think about stress-causing events and ways to cope with them. Review problems with your doctor or a mental health professional. Consider clinicians who specialize in approaches including mindfulness. Try to make AD treatments part of a daily, family routine. Encourage children with AD to do what they can on their own.

 

Treatment of AD in the first place was to normalize the day, establishing hypoallergenic life, elimination diet and nutrition according to age, enriched with vitamins.

  Medical therapy consisted in prescribing antihistamines, with preference given to selective H1-receptor blockers (loratadine (Claritin), desloratadine (Aerius), cetirizine). In the case of the presence of severe itching fenistil intended for oral use. Noted on course intake of drugs with changes every 10-14 days. In patients with AD, which was combined with asthma, for further outpatient treatment used ketotifen (zadyten), which belongs to the tricyclic benzaheptatiofeniv mukozalnyy layer protects the stomach from entering food allergens in patients with food allergy symptoms and suppresses the development of bronchial hyperresponsiveness.

   Particular attention was attached to conduct rehabilitation centers chronic infection (treatment of dental, otolaryngeal pathology).
Important role in the treatment of AD given sedatives containing plant components (novopasyt, sedasen – forte).
Given psevdoalergy mechanisms AD, intended hepatoprotective drugs (Hofitol, Gepabene, Flamini). The reason for the appointment of pancreatic enzymes (mezim forte) was the presence of dyspankreatyzm.

 

Local therapy AD applied individually to each clinical case considering anatomical and morphological and functional characteristics of the skin of children, with preference given to herbal. Exterior treatment was aimed at reducing and eliminating subjective sensations (itching, pain), reduction and elimination of dry skin, elimination of biologically active substances and destructive substances, protecting skin from the adverse effects of the environment, and – treatment of secondary infections.

   Attention parents appealed that before applying external medicines skin sick child must cleaned of manure crusts, scales, balances used drugs that irritate the skin. Cleaning the skin promoted closer contact with them drugs and thus allowed to achieve the desired effect. Children are encouraged to conduct daily hygienic bathrooms that clean and moisturize the skin, increase the penetration of external agents, create a sense of comfort and bring your child fun.

      To resolve acute inflammation when exudation and weeping used lotion with tri-color and violet dyes (fukortsyn – local antyseptic) who contributed to the elimination of fluid and destructive elements of cells from the skin and simultaneously prevent secondary infection of the affected area. To eliminate bacterial infection in one case used tetracycline ointment, a predefined sensitivity to it.

      In order to reduce dryness of skin, from which suffered most patients applied Calendula ointment – emollient that supports the elasticity and softness of the skin. In patients with pronounced itching used fenistyl Gel – antihistamine gel on a basis that provides a gradual selection of components for a long time.

    When the first symptoms, as well as in cases of persistent disease and frequent exacerbations as a prophylactic intended kalbtsynevrynu inhibitors – a class nonhormonal skin-selective inhibitor of inflammatory cytokines. At the Ukrainian market, the group of pharmacological agents represented cream “Elidel”. Tactics use the means was applied in applications with a thin layer on the affected area 2 times a day.
An important aspect in the treatment of AD was the appointment of sorption drugs significantly reduced the cutaneous manifestations of the syndrome after 2-3 days of application. Among them – “Enterosgel” that was intended dose of 0.5 – 1.0 g per 1 kg of body weight per day, “polisorb” a daily dose of 100 mg per 1 kg of weight and carbon sorbents “Karbolonh”, “Karbosfer “100-200 mg per 1 kg child per day. Preparations intended short course of 5-7 days due to the absence of selective adsorption steps.

О Treatment continued appointment 3.5 microclysters with these drugs (with their preliminary conducting clearing enemas) frequency of 1 every week.
Do not remain without attention and correction of such comorbidities as irritable bowel syndrome (which greatly complicates the course of AD) – Duphalac administered in an initial dose of 5 to 15 ml (depending on body weight) to normalize bowel movements and the subsequent use of maintenance dose. After normalization of the bowel was appropriate correction of dysbiotic violations, which meant ten Symbiter rate and laktovit forte 1-2 capsules three times daily for 2-3 weeks.

    Physiotherapy treatment of AD consisted of ultraviolet irradiation affected skin in suberitem doses. Correction of comorbidities in patients with hepatobiliary pathology – paraffin-ozocerite on right upper quadrant, and in patients with irritable bowel syndrome – the entire abdomen. Children with biliary dyskinesia received oxygen cocktails with choleretics herbs.

What kinds of treatments help?

MOISTURIZERS. Ointments such as petroleum jelly are best unless they’re too thick and cause discomfort. Creams may be fine for moderately dry skin or in hot, humid weather. Apply them to wet skin, immediately after bathing. Lotions are not rich enough and often have a net drying effect on AD skin.

CORTICOSTEROIDS. Often called topical (“applied to the skin”) steroids, these are cortisone-like medications used in creams or ointments that your doctor may prescribe (e.g. hydrocortisone, mometasone, desonide, triamcinolone). They are not the same as the anabolic steroids some athletes misuse. Corticosteroid medicines are very helpful. Often they are the only treatment that can calm the inflamed skin. Use of steroid ointments and creams requires good judgment and careful supervision. They come in many strengths from mild to super-potent. Hydrocortisone, a very mild steroid, is quite safe. The more potent ones can cause thinned skin, stretch marks and even growth retardation or suppression of the adrenal gland if used too many days in the same areas of the body. Parents should monitor the child’s use. Ask the doctor about potency and side effects of prescribed corticosteroid medicines and follow the product insert instructions carefully.

Topical Immunomodulators (TIMs)

This family of topical medications has been available for the past 10 years. TIMs work to inhibit the skin’s inflammatory response (which is what causes the redness and also contributes to itching). At this time there are two FDA approved non-steroid drugs: tacrolimus and pimecrolimus. TIMs are not steroids and do not cause thinning of the skin but they can suppress the immune system in the skin so that the use of sun protection for the children receiving this therapy is recommended.

For children less than two years of age these medications are only used off-label and as always, with any medication, they should be used with careful supervision of a physician. Tacrolimus and pimecrolimus both currently have a “black box” warning, which is a precautionary statement given to the medication by the Food and Drug Administration.

TAR PREPARATIONS. Tar creams or bath emulsions can be helpful for mild inflammation.

ANTIBIOTICS. Oral or topical antibiotics reduce the surface bacterial infections that may accompany flares of AD.

ANTIHISTAMINES. Often prescribed to reduce itching, these medicines may cause drowsiness but seem to help some children, largely due to their sleep-inducing side effects.

When will my child outgrow 
atopic dermatitis?

For any given child, it is difficult to predict. The majority of babies with AD will lose most of the problem by adolescence, often before grade school. A small number will have severe AD into adulthood. Many have remissions that last for years. The dry skin tendency often remains. Most people learn to use moisturizers to keep their dermatitis controlled. Occasional episodes of AD may occur during times of stress or with jobs that expose the skin to irritants and wet work.

Will AD affect my child’s career choice?

Someone who has had eczema should avoid jobs that can injure the skin. Military service automatically excludes people with AD or asthma. Wet work in restaurants or hospitals is especially damaging to hands predisposed by AD to drying and cracking. Generally, it’s better to pick “clean” indoor work such as with people, computers, papers or books, given the choice.

 Asthma is a chronic inflammatory disorder of the airways characterized by an obstruction of airflow, which may be completely or partially reversed with or without specific therapy. Airway inflammation is the result of interactions between various cells, cellular elements, and cytokines. In susceptible individuals, airway inflammation may cause recurrent or persistent bronchospasm, which causes symptoms including wheezing, breathlessness, chest tightness, and cough, particularly at night or after exercise.

Airway inflammation is associated with airway hyperreactivity or bronchial hyperresponsiveness (BHR), which is defined as the inherent tendency of the airways to narrow in response to a variety of stimuli (eg, environmental allergens and irritants).

 

Approximately 500,000 annual hospitalizations (34.6% in persons  <18 y) are because of asthma. The cost of illness related to asthma is around $6.2 billion. Each year, an estimated 1.81 million people (47.8% £18 y) require treatment in the emergency department. Among children and adolescents aged 5-17 years, asthma accounts for a loss of 10 million school days and costs caretakers $726.1 million because of work absence.

Pathophysiology

Interactions between environmental and genetic factors result in airway inflammation, which limits airflow and leads to functional and structural changes in the airways in the form of bronchospasm, mucosal edema, and mucus plugs.

 

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Airway obstruction causes increased resistance to airflow and decreased expiratory flow rates. These changes lead to a decreased ability to expel air and may result in hyperinflation. The resulting overdistention helps maintain airway patency, thereby improving expiratory flow; however, it also alters pulmonary mechanics and increases the work of breathing.

Hyperinflation compensates for the airflow obstruction, but this compensation is limited when the tidal volume approaches the volume of the pulmonary dead space; the result is alveolar hypoventilation. Uneven changes in airflow resistance, the resulting uneven distribution of air, and alterations in circulation from increased intraalveolar pressure due to hyperinflation all lead to ventilation-perfusion mismatch. Hypoxic vasoconstriction also contributes to this mismatch.

In the early stages, when ventilation-perfusion mismatch results in hypoxia, hypercarbia is prevented by the ready diffusion of carbon dioxide across alveolar capillary membranes. Thus, asthmatic patients who are in the early stages of an acute episode have hypoxemia in the absence of carbon dioxide retention. Hyperventilation triggered by the hypoxic drive also causes a decrease in PaCO₂. An increase in alveolar ventilation in the early stages of an acute exacerbation prevents hypercarbia. With worsening obstruction and increasing ventilation-perfusion mismatch, carbon dioxide retention occurs. In the early stages of an acute episode, respiratory alkalosis results from hyperventilation. Later, the increased work of breathing, increased oxygen consumption, and increased cardiac output result in metabolic acidosis. Respiratory failure leads to respiratory acidosis.

Chronic inflammation of the airways is associated with increased BHR, which leads to bronchospasm and typical symptoms of wheezing, shortness of breath, and coughing after exposure to allergens, environmental irritants, viruses, cold air, or exercise. In some patients with chronic asthma, airflow limitation may be only partially reversible because of airway remodeling (hypertrophy and hyperplasia of smooth muscle, subepithelial fibrosis) that occurs with chronic untreated disease.

New insights in the pathogenesis of asthma suggest the role of lymphocytes. Airway inflammation in asthma may represent a loss of normal balance between two “opposing” populations of Th lymphocytes. Two types of Th lymphocytes have been characterized: Th1 and Th2. Th1 cells produce IL-2 and IFN-a , which are critical in cellular defense mechanisms in response to infection. Th2, in contrast, generates a family of cytokines (IL-4, -5, -6, -9, and -13) that can mediate allergic inflammation. The current “hygiene hypothesis” of asthma illustrates how this cytokine imbalance may explain some of the dramatic increases in asthma prevalence in Westernized countries. This hypothesis is based on the assumption that the immune system of the newborn is skewed toward Th2 cytokine generation. Following birth, environmental stimuli such as infections will activate Th1 responses and bring the Th1/Th2 relationship to an appropriate balance.

 

Evidence exists that the prevalence of asthma is reduced in association with certain infections (Mycobacterium tuberculosis, measles, or hepatitis A); exposure to other children (eg, presence of older siblings and early enrollment in childcare); and less frequent use of antibiotics. Furthermore, the absence of these lifestyle events is associated with the persistence of a Th2 cytokine pattern.

Under these conditions, the genetic background of the child, with a cytokine imbalance toward Th2, will set the stage to promote the production of IgE antibody to key environmental antigens (eg, dust mites, cockroaches, Alternaria, and possibly cats). Therefore, a gene-by-environment interaction occurs in which the susceptible host is exposed to environmental factors that are capable of generating IgE, and sensitization occurs. A reciprocal interaction seems to exist between the two subpopulations in which Th1 cytokines can inhibit Th2 generation and vice versa. Allergic inflammation may be the result of an excessive expression of Th2 cytokines. Alternately, the possibility that the loss of normal immune balance arises from a cytokine dysregulation in which Th1 activity in asthma is diminished has been suggested in recent studies.

In preschool children with asthma, 2 years of inhaled corticosteroid therapy did not change the asthma symptoms or lung function during a third, treatment-free year. This suggests that no disease-modifying effect of inhaled corticosteroids is present after the treatment is discontinued.

Recent evidence suggests that rhinovirus is a significant risk factor for the development of wheeze in preschool children and a frequent trigger of wheezing illnesses in children with asthma.

 

 

Frequency

•   In the US: Approximately 17.3 million Americans have asthma. The prevalence of asthma in the general population is 5%, and it has increased 40% in the past decade. Asthma accounts for more school absences and more hospitalizations than any other chronic illness. In most children’s hospitals in the United States, it is the most common diagnosis at admission.

•   Internationally: Worldwide, 130 million people have asthma. The prevalence is 8-10 times higher in developed countries (eg, United States, Great Britain, Australia, New Zealand) than in the developing countries. In developed countries, the prevalence is higher in low income groups in urban areas and inner cities than in other groups.

Mortality/Morbidity

Globally, morbidity and mortality associated with asthma have increased over the last 2 decades. This increase is attributed to increasing urbanization. Despite advancements in our understanding of asthma and the development of new therapeutic strategies, the morbidity and mortality rates due to asthma definitely increased between 1980 and 1995. In the United States, the mortality rate due to asthma has increased in all age, race, and sex strata. In the United States, the mortality rate due to asthma is more than 17 deaths per 1 million people (ie, 5000 deaths per y). From 1975-1993, the number of deaths nearly doubled in people aged 5-14 years. In the northeastern and midwestern United States, the highest mortality rate has been among persons aged 5-34 years.

Race

The prevalence of asthma is higher in minority groups (eg, blacks, Hispanics) than in other groups; however, findings from one study suggest that much of the recent increase in the prevalence is attributed to asthma in white children. About 5-8% of all black children have asthma at some time. The prevalence in Hispanic children is reported to be as high as 15%. In blacks, the death rate is consistently higher than in whites.

Sex

Before puberty, the prevalence is 3 times higher in boys than in girls. During adolescence, the prevalence is equal among males and females. Adult-onset asthma is more common in women than in men.

Age

In most children, asthma develops before they are aged 5 years, and, in more than half, asthma develops before they are aged 3 years.

Among infants, 20% have wheezing with only upper respiratory tract infections (URTIs), and 60% no longer have wheezing when they are aged 6 years. Many of these children were called “transient wheezers” by Martinez et al. They tend to have no allergies, although their lung function is often abnormal. These findings have led to the idea that they have small lungs. Children in whom wheezing begins early, in conjunction with allergies, are more likely to have wheezing when they are aged 6 and 11 years. Similarly, children in whom wheezing begins after they are aged 6 years often have allergies, and the wheezing is more likely to continue when they are aged 11 years.

 

CLINICAL MANIFESTATION

History

The National Asthma Education and Prevention Program Expert Panel Report II (EPR-2), “Guidelines for the Diagnosis and Management of Asthma,” highlights the importance of correctly diagnosing asthma. To establish the diagnosis of asthma, the clinician must establish the following: (a) episodic symptoms of airflow obstruction are present, (b) airflow obstruction or symptoms are at least partially reversible, and (c) alternative diagnoses are excluded.

The severity of asthma is classified as mild intermittent, mild persistent, moderate persistent, or severe persistent, according to the frequency and severity of symptoms, including nocturnal symptoms, characteristics of acute episodes, and pulmonary function. These categories do not always work well in children. First, lung function is difficult to assess in younger children. Second, asthma that is triggered solely by viral infections does not fit into any category. While the symptoms may be intermittent, they may be severe enough to warrant hospitalization. Therefore, a category of severe intermittent asthma has been suggested. Features of the categories include the following:

 

Patients with mild intermittent disease have symptoms fewer than 2 times a week, and pulmonary function is normal between exacerbations. Exacerbations are brief, lasting from a few hours to a few days. Nighttime symptoms occur less than twice a month. The variation in peak expiratory flow (PEF) is less than 20%.

• Patients with mild persistent asthma have symptoms more than 2 times a week but less than once a day. Exacerbations may affect activity. Nighttime symptoms occur more than twice a month. Pulmonary function test results (in age-appropriate patients) demonstrate that the forced expiratory volume in 1 second (FEV₁) or PEF is less than 80% of the predicted value, and the variation in PEF is 20-30%.

• Patients with moderate persistent asthma have daily symptoms and use inhaled short-acting beta2-agonists every day. Acute exacerbations in patients with moderate persistent asthma may occur more than 2 times a week and last for days. The exacerbations affect activity. Nocturnal symptoms occur more than once a week. FEV₁ and PEF values are 60-80% of the predicted values, and PEF varies by more than 30%.

• Patients with severe persistent asthma have continuous or frequent symptoms, limited physical activity, and frequent nocturnal symptoms. FEV₁ and PEF values are less than 60% of the predicted values, and PEF varies by more than 30%.

• Disease with any of their features is assigned to the most severe grade. The presence of one severe feature is sufficient to diagnose severe persistent asthma. The characteristics in this classification system are general and may overlap because asthma is highly variable. The classification may change over time. Patients with asthma of any level of severity may have mild, moderate, or severe exacerbations. Some patients with intermittent asthma have severe and life-threatening exacerbations separated by episodes with almost normal lung function and minimal symptoms; however, they are likely to have other evidence of increased BHR (exercise or challenge testing) due to ongoing inflammation.

• Symptoms of asthma may include wheezing, coughing, and chest tightness, among others.

• Wheezing 

• A musical, high-pitched, whistling sound produced by airflow turbulence is one of the most common symptoms.

• In the mildest form, wheezing is only end expiratory. As severity increases, the wheeze lasts throughout expiration. In a more severe asthmatic episode, wheezing is also present during inspiration. During a most severe episode, wheezing may be absent because of the severe limitation of airflow associated with airway narrowing and respiratory muscle fatigue.

• Asthma can occur without wheezing when obstruction involves predominantly the small airways. Thus, wheezing is not necessary for the diagnosis of asthma. Furthermore, wheezing can be associated with other causes of airway obstruction, such as cystic fibrosis and heart failure.

• Patients with vocal cord dysfunction have a predominantly inspiratory monophonic wheeze (different from the polyphonic wheeze in asthma), which is heard best over the laryngeal area in the neck. Patients with bronchomalacia and tracheomalacia also have a monophonic wheeze.

• In exercise-induced or nocturnal asthma, wheezing may be present after exercise or during the night, respectively.

• Coughing: Cough may be the only symptom of asthma, especially in cases of exercise-induced or nocturnal asthma. Usually, the cough is nonproductive and nonparoxysmal. Also, coughing may be present with wheezing. Children with nocturnal asthma tend to cough after midnight, during the early hours of morning.

• Chest tightness: A history of tightness or pain in the chest may be present with or without other symptoms of asthma, especially in exercise-induced or nocturnal asthma.

• Other nonspecific symptoms: Infants or young children may have history of recurrent bronchitis, bronchiolitis, or pneumonia; a persistent cough with colds; and/or recurrent croup or chest rattling. Most children with chronic or recurrent bronchitis have asthma. Asthma is the most common underlying diagnosis in children with recurrent pneumonia. Older children may have a history of chest tightness and/or recurrent chest congestion.

• During an acute episode, symptoms vary according to the severity.

• Symptoms during a mild episode: Patients may be breathless after physical activity such as walking. They can talk in sentences and lie down, and they may be agitated.

• Symptoms during a moderate severe episode: Patients are breathless while talking. Infants have feeding difficulties and a softer, shorter cry.

• Symptoms during a severe episode: Patients are breathless during rest, are not interested in feeding, sit upright, talk in words (not sentences), and are usually agitated.

• Symptoms with imminent respiratory arrest (in addition to the aforementioned symptoms): The child is drowsy and confused. However, adolescents may not have these symptoms until they are in frank respiratory failure.

Physical

• The clinical picture varies. Symptoms may be associated with URTIs, nocturnal or exercise-induced asthmatic symptoms, and status asthmaticus. Status asthmaticus, or an acute severe asthmatic episode that is resistant to appropriate outpatient therapy, is a medical emergency that requires aggressive hospital management. This may include admission to an ICU for the treatment of hypoxia, hypercarbia, and dehydration and possibly for assisted ventilation because of respiratory failure.

• Physical findings vary with the absence or presence of an acute episode and its severity, as follows:

• Physical examination in the absence of an acute episode (eg, during an outpatient visit between acute episodes)

• The physical findings vary with the severity of the asthma. During an outpatient visit, it is not uncommon for a patient with mild asthma to have normal findings at physical examination. Patients with more severe asthma are likely to have signs of chronic respiratory distress and chronic hyperinflation.

• Signs of atopy or allergic rhinitis, such as conjunctival congestion and inflammation, ocular shiners, a transverse crease on the nose due to constant rubbing associated with allergic rhinitis, and pale violaceous nasal mucosa due to allergic rhinitis, may be present.

• The anteroposterior diameter of the chest may be increased because of hyperinflation. Hyperinflation may also cause an abdominal breathing pattern.

• Lung examination may reveal prolongation of the expiratory phase, expiratory wheezing, coarse crackles, or unequal breath sounds.

• Clubbing of the fingers is not a feature of straightforward asthma and indicates a need for more extensive evaluation and work-up to exclude other conditions, such as cystic fibrosis.

• Physical examination during an acute episode may reveal different findings in mild, moderately severe, and severe episodes and in status asthmaticus with imminent respiratory arrest.

• Mild episode: The respiratory rate is increased. Accessory muscles of respiration are not used. The heart rate is less than 100 beats per minute. Pulsus paradoxus is not present. Auscultation of chest reveals moderate wheezing, which is often end expiratory. Oxyhemoglobin saturation with room air is greater than 95%.

• Moderately severe episode: The respiratory rate is increased. Typically, accessory muscles of respiration are used, and suprasternal retractions are present. The heart rate is 100-120 beats per minute. Loud expiratory wheezing can be heard. Pulsus paradoxus may be present (10-20 mm Hg). Oxyhemoglobin saturation with room air is 91-95%.

• Severe episode: The respiratory rate is often greater than 30 breaths per minute. Accessory muscles of respiration are usually used, and suprasternal retractions are commonly present. The heart rate is more than 120 beats per minute. Loud biphasic (expiratory and inspiratory) wheezing can be heard. Pulsus paradoxus is often present (20-40 mm Hg). Oxyhemoglobin saturation with room air is less than 91%.

• Status asthmaticus with imminent respiratory arrest: Paradoxical thoracoabdominal movement occurs. Wheezing may be absent (associated with most severe airway obstruction). Severe hypoxemia may manifest as bradycardia. Pulsus paradoxus noted earlier may be absent; this finding suggests respiratory muscle fatigue.

Causes

In most cases of asthma in children, multiple triggers or precipitants exist, and the patterns of reactivity may change with age. Treatment can also change the pattern. Certain viral infections, such as respiratory syncytial virus (RSV) bronchiolitis in infancy, predispose the child to asthma.

• Respiratory infections: Most commonly, these are viral infections. In some patients, fungi (eg, allergic bronchopulmonary aspergillosis), bacteria (eg, mycoplasmata, pertussis), or parasites may be responsible. Most infants and young children who continue to have a persistent wheeze and asthma have high immunoglobulin E (IgE) production and eosinophilic immune responses (in the airways and in circulation) at the time of the first viral URTI. They also have early IgE-mediated responses to local aeroallergens.

• Allergens: In patients with asthma, 2 types of bronchoconstrictor responses to allergens exist.

• Early asthmatic responses occur via IgE-induced mediator release from mast cells within minutes of exposure and last for 20-30 minutes.

• Late asthmatic responses occur 4-12 hours after antigen exposure and result in more severe symptoms that can last for hours and contribute to the duration and severity of the disease. Inflammatory cell infiltration and inflammatory mediators play a role in the late asthmatic response. Allergens can be foods, household inhalants (eg, animal allergens, molds, fungi, roach allergens, dust mites), or seasonal outdoor allergens (eg, mold spores, pollens, grass, trees).

• Irritants: Tobacco smoke, cold air, chemicals, perfumes, paint odors, hair sprays, air pollutants, and ozone can initiate BHR by inducing inflammation.

• Weather changes: Asthma attacks can be related to changes in atmospheric temperature, barometric pressure, and the quality of air (eg, humidity, allergen and irritant content).

• Exercise: Exercise can trigger an early asthmatic response. Mechanisms underlying exercise-induced asthmatic response remain somewhat uncertain. Heat and water loss from the airways can increase the osmolarity of the fluid lining the airways and result in mediator release. Cooling of the airways results in congestion and dilatation of bronchial vessels. During the rewarming phase after exercise, the changes are magnified because the ambient air breathed during recovery is warm rather than cool.

• Emotional factors: In some individuals, emotional upsets clearly aggravate asthma.

• Gastroesophageal reflux (GER): The presence of acid in the distal esophagus, mediated via vagal or other neural reflexes, can significantly increase airway resistance and airway reactivity.

• Allergic rhinitis, sinusitis, and chronic URTI: Inflammatory conditions of the upper airways (eg, allergic rhinitis, sinusitis, or chronic and persistent infections) must be treated before asthmatic symptoms can be completely controlled.

• Nocturnal asthma: Multiple factors have been proposed to explaiocturnal asthma. Circadian variation in lung function and inflammatory mediator release in the circulation and airways (including parenchyma) have been demonstrated. Other factors, such as allergen exposure and posture-related irritation of airways (eg, GER, sinusitis), can also play a role. In some patients, abnormalities in CNS control of the respiratory drive may be present, particularly in patients with a defective hypoxic drive and obstructive sleep apnea

Laboratory Studies

• Pulmonary function test (PFT) results are not reliable in patients younger than 5 years. In young children (3-6 y) and older children who can’t perform the conventional spirometry maneuver, newer techniques, such as measurement of airway resistance using impulse oscillometry system, are being tried. Measurement of airway resistance before and after a dose of inhaled bronchodilator may help to diagnose bronchodilator responsive airway obstruction.

• Spirometry: In a typical case, an obstructive defect is present in the form of normal forced vital capacity (FVC), reduced FEV₁, and reduced forced expiratory flow over 25-75% of the FVC (FEF 25-75). The flow-volume loop can be concave. Documentation of reversibility of airway obstruction after bronchodilator therapy is central to the definition of asthma. FEF 25-75 is a sensitive indicator of obstruction and may be the only abnormality in a child with mild disease. In an outpatient or office setting, measurement of the peak flow rate by using a peak flow meter can provide useful information about obstruction in the large airways. Take care to ensure maximum patient effort. However, a normal peak flow rate does not necessarily mean a lack of airway obstruction.

• Plethysmography: Patients with chronic persistent asthma may have hyperinflation, as evidenced by an increased total lung capacity (TLC) at plethysmography. Increased residual volume (RV) and functional residual capacity (FRC) with normal TLC suggests air trapping. Airway resistance is increased when significant obstruction is present.

• Bronchial provocation tests: Bronchial provocation tests may be performed to diagnose BHR. These tests are performed in specialized laboratories by specially trained personnel to document airway hyperresponsiveness to substances (eg, methacholine, histamine). Increasing doses of provocation agents are given, and FEV₁ is measured. The endpoint is a 20% decrease in FEV₁ (PD20).

• Exercise challenge: In a patient with a history of exercise-induced symptoms (eg, cough, wheeze, chest tightness or pain), the diagnosis of asthma can be confirmed with the exercise challenge. In a patient of appropriate age (usually >6 y), the procedure involves baseline spirometry followed by exercise on a treadmill or bicycle to a heart rate greater than 60% of the predicted maximum, with monitoring of the electrocardiogram and oxyhemoglobin saturation. The patient should be breathing cold, dry air during the exercise to increase the yield of the study. Spirographic findings and the PEF rate (PEFR) are determined immediately after the exercise period and at 3, 5, 10, 15, and 20 minutes after the first measurement. The maximal decrease in lung function is calculated by using the lowest postexercise and highest preexercise values. The reversibility of airway obstruction can be assessed by administering aerosolized bronchodilators.

• Blood testing: Eosinophil counts and IgE levels may help when allergic factors are suspected.

• Recent evidence suggests the usefulness of measuring the fraction of exhaled nitric oxide (FeNO) as a noninvasive marker of airway inflammation, in order to adjust the dose of inhaled corticosteroids treatment. Currently FeNO measurement, due to high cost of equipment, is used primarily as a research tool.

Imaging Studies

• Chest radiography: Include chest radiography in the initial workup if the asthma does not respond to therapy as expected. In addition to typical findings of hyperinflation and increased bronchial markings, a chest radiograph may reveal evidence of parenchymal disease, atelectasis, pneumonia, congenital anomaly, or a foreign body. In a patient with an acute asthmatic episode that responds poorly to therapy, a chest radiograph helps in the diagnosis of complications such as pneumothorax or pneumomediastinum.

• Paranasal sinus radiography or CT scanning: Consider using these to rule out sinusitis.

 

Other Tests

• Allergy testing: Allergy testing can be used to identify allergic factors that may significantly contribute to the asthma. Once identified, environmental factors (eg, dust mites, cockroaches, molds, animal dander) and outdoor factors (eg, pollen, grass, trees, molds) may be controlled or avoided to reduce asthmatic symptoms. Allergens for skin testing are selected on the basis of suspected or known allergens identified from a detailed environmental history. Antihistamines can suppress the skin test results and should be discontinued for an appropriate period (according to the duration of action) before allergy testing. Topical or systemic corticosteroids do not affect the skin reaction.

Histologic Findings

Asthma is an inflammatory disease characterized by the recruitment of inflammatory cells, vascular congestion, increased vascular permeability, increased tissue volume, and the presence of an exudate. Eosinophilic infiltration, a universal finding, is considered a major marker of the inflammatory activity of the disease. Histologic evaluations of the airways in a typical patient reveal infiltration with inflammatory cells, narrowing of airway lumina, bronchial and bronchiolar epithelial denudation, and mucus plugs. Additionally, a patient with severe asthma may have a markedly thickened basement membrane and airway remodeling in the form of subepithelial fibrosis and smooth muscle hypertrophy or hyperplasia. 

Treatment of the patients

Medical Care

The goals of asthma therapy are to prevent chronic and troublesome symptoms, maintaiormal or near-normal pulmonary function, maintaiormal physical activity levels (including exercise), prevent recurrent exacerbations of asthma, and minimize the need for emergency department visits or hospitalizations, provide optimal pharmacotherapy with minimal or no adverse effects, and meet the family’s expectations for asthma care.

Medical care includes treatment of acute asthmatic episodes and control of chronic symptoms, including nocturnal and exercise-induced asthmatic symptoms. Pharmacologic management includes the use of control agents such as inhaled corticosteroids, inhaled cromolyn or nedocromil, long-acting bronchodilators, theophylline, leukotriene modifiers, and recently introduced strategies such as the use of anti-IgE antibodies. Relief medications include short-acting bronchodilators, systemic corticosteroids, and ipratropium. Nonpharmacologic management includes measures to improve patient compliance and adherence. For all but the most severely affected patients, the ultimate goal is to prevent symptoms, minimize morbidity from acute episodes, and prevent functional and psychological morbidity to provide a healthy (or near healthy) lifestyle appropriate to the age of child.

A step-down approach based on the asthma severity classification system emphasizes the initiation of high-level therapy to establish prompt control and then decreasing therapy (National Asthma Education and Prevention Program Expert Panel Report II, 1997). Treatment should be reviewed every 1-6 months; a gradual stepwise reduction in treatment may be possible. If control is not maintained despite adequate medication and adherence and the exclusion of contributing environmental factors, increased therapy should be considered. Long- and short-term therapy is based on the severity of asthma, as follows:

• Mild intermittent asthma 

• Long-term control: Usually, no daily medication is needed.

• Quick relief: Short-acting bronchodilators in the form of inhaled beta2-agonists should be used as needed for symptom control. The use of short-acting inhaled beta2-agonists more than 2 times a week may indicate the need to initiate long-term control therapy.

• Mild persistent asthma 

• Long-term control: Anti-inflammatory treatment in the form of low-dose inhaled corticosteroids or nonsteroidal agents (eg, cromolyn, nedocromil) is preferred. Some evidence suggests that leukotriene antagonists may be useful as first-line therapy in children. Recently, the use of montelukast was approved for children aged 2 years and older.

• Quick relief: Short-acting bronchodilators in the form of inhaled beta2-agonists should be used as needed for symptom control. Use of short-acting inhaled beta2-agonists on a daily basis or increasing use indicates the need for additional long-term therapy.

• Moderate persistent asthma

• Long-term control: Daily anti-inflammatory treatment in the form of inhaled corticosteroids (medium dose) is preferred. Otherwise, low- or medium-dose inhaled corticosteroids combined with a long-acting bronchodilator or leukotriene antagonist can be used, especially for the control of nocturnal or exercise-induced asthmatic symptoms.

• Quick relief: Short-acting bronchodilators in the form of inhaled beta2-agonists should be used as needed for symptom control. The use of short-acting inhaled beta2-agonists on a daily basis or increasing use indicates the need for additional long-term therapy.

• Severe persistent asthma 

• Long-term control 

• Daily anti-inflammatory treatment in the form of inhaled corticosteroids (high dose) is preferred. Other medications, such as a long-acting bronchodilator leukotriene antagonist or theophylline, can be added.

• Patients with moderate-to-severe asthma who react to perennial allergens despite inhaled corticosteroids may benefit from omalizumab treatment. Two 52-week pivotal Phase III clinical trials were designed to study asthma exacerbation reduction in 1071 patients with asthma (aged 12-76 y). The coprimary endpoint of each study was the number of asthma exacerbations per patient during the stable-steroid phase and the steroid-reduction phase. Patients were randomized to receive subcutaneous omalizumab or placebo every 2-4 weeks. Inhaled corticosteroid doses were kept stable over the initial 16 weeks of treatment (stable-steroid phase) and tapered during a further 12-week treatment period (steroid-reduction phase).

• In both pivotal clinical trials, when used as an add-on therapy to inhaled corticosteroids, omalizumab reduced mean asthma exacerbations (ie, asthma attacks) per patient by 33%-75% during the stable-steroid phase and 33%-50% during the steroid-reduction phase. Reduction in asthma exacerbations was confirmed by improvements in other measurements of asthma control, including symptom scores (eg, nocturnal awakenings, daytime asthma symptoms).

• Quick relief: Short-acting bronchodilators in the form of inhaled beta2-agonists should be used as needed for symptom control. The use of short-acting inhaled beta2-agonists on a daily basis or increasing use indicates the need for additional long-term therapy.

• Acute severe asthmatic episode (status asthmaticus) 

• Treatment goals are the following: 

• Correction of significant hypoxemia with supplemental oxygen: In severe cases, alveolar hypoventilation requires mechanically assisted ventilation.

• Rapid reversal of airflow obstruction by using repeated or continuous administration of an inhaled beta2-agonist: Early administration of systemic corticosteroids (eg, oral prednisone or intravenous methylprednisolone) is suggested in children with asthma that fails to respond promptly and completely to inhaled beta2-agonists.

• Reduction in the likelihood of recurrence of severe airflow obstruction by intensifying therapy: Often, a short course of systemic corticosteroids is helpful.

• Achieving these goals requires close monitoring by means of serial clinical assessment and measurement of lung function (in patients of appropriate ages) to quantify the severity of airflow obstruction and its response to treatment. Improvement in FEV₁ after 30 minutes of treatment is significantly correlated with a broad range of indices of the severity of asthmatic exacerbations, and repeated measurement of airflow in the emergency department can help reduce unnecessary admissions. Use of the peak flow rate or FEV₁ values, along with the patient’s history, current symptoms, physical findings, to guide treatment decisions is helpful in achieving the aforementioned goals. In using the PEF expressed as a percentage of the patient’s best value, the effect of irreversible airflow obstruction should be considered. For example, in a patient whose best peak flow rate is 160 L/min, a decrease of 40% represents severe and potentially life-threatening obstruction.

Consultations

Consider consultation with an allergist; ear, nose, and throat (ENT) specialist; or gastroenterologist.

• An allergist may help with further evaluation and management when the history and physical examination findings suggest significant allergies (especially systemic involvement and allergies to dietary products).

• An ENT specialist may help in managing chronic sinusitis.

• A gastroenterologist may help in excluding gastroesophageal reflux.

Diet

When a patient has major allergies to dietary products, avoidance of particular foods may help. In the absence of specific food allergies, dietary changes are not necessary. Unless compelling evidence for a specific allergy exists, milk products do not have to be avoided.

Activity

One of the goals of therapy is to adequately control exercise-induced asthmatic symptoms so that physical activity is not restricted.

Current treatment of asthma includes the use of relievers, such as beta-adrenergic agonists, systemic corticosteroids, and ipratropium, and controllers, such as cromolyn, nedocromil, inhaled corticosteroids, long-acting beta-agonists, theophylline, and leukotriene modifiers.

Drug Category: Bronchodilator, beta2-agonists

— These agents act as bronchodilators, used to treat bronchospasm in acute asthmatic episodes, and used to prevent bronchospasm associated with exercise-induced asthma or nocturnal asthma. Several studies have suggested that short-acting beta2-agonists such as albuterol may produce adverse outcomes (eg, decreased peak flow or increased risk of exacerbations) in patients homozygous for arginine (Arg/Arg) at the 16th amino acid position of beta-adrenergic receptor gene compared with patients homozygous for glycine (Gly-Gly). Recently, similar findings are reported for long-acting beta2-agonists (eg, salmeterol).

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Adult

Oral inhaler: 1-2 inhalations q4-6h; recent guidelines suggest 8-10 inhalations for more severe symptoms
 Nebulizer: Dilute 0.5 mL (2.5 mg) of 0.5% inhalation solution in 1-2.5 mL of NS solution; administer 2.5-5 mg via nebulization q4-6h, diluted in 2-5 mL sterile sodium chloride solution or water

Pediatric

Oral inhaler: 90 mcg per inhalation, 2 inhalations q4-6h; more inhalations may be used in severe, acute episodes; more frequent dosing can be used to treat acute symptoms
 Nebulizer: 2.5 mg via nebulization of 0.5% solution in 2-3 mL of sodium chloride solution q4-6h

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Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilatation; cardiovascular effects may increase with MAOIs, inhaled anesthetics, tricyclic antidepressants, and sympathomimetic agents

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Documented hypersensitivity

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Pregnancy

C – Safety for use during pregnancy has not been established.

Precautions

Large amounts (eg, those used in ICU in acute episodes) may cause muscular tremors, tachycardia, hyperglycemia, and hypokalemia; caution in hyperthyroidism, diabetes mellitus, and cardiovascular disorders

 

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Adult

Oral inhalation: 1-2 inhalations q4-6h; not to exceed 12 inhalations q24h

Pediatric

Administer as in adults

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Beta-adrenergic blockers antagonize effects; cardiovascular effects may increase with MAOIs, inhaled anesthetics, tricyclic antidepressants, and sympathomimetic agents

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Documented hypersensitivity

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Precautions

Caution in hyperthyroidism, diabetes mellitus, or cardiovascular disorders

Drug Category: Nonracemic form of the beta2-agonist albuterol

— This nonracemic form of albuterol was recently introduced. One advantage is better efficacy; hence, lower doses have a therapeutic effect, and a significant reduction in the adverse effects associated with racemic albuterol (eg, muscle tremors, tachycardia, hyperglycemia, hypokalemia) is reported. 

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Pediatric

0.63 mg by nebulizer q8h

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Decreased efficacy with beta-blockers; digoxin levels may be decreased; may potentiate the kaliuretic effects of drugs, such as, loop or thiazide diuretics; decreases serum digoxin levels by 16-22%; MAOIs may potentiate vascular constriction, extreme caution advised with coadministration

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Documented hypersensitivity

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Pregnancy

C – Safety for use during pregnancy has not been established.

Precautions

May cause muscular tremors, tachycardia, hyperglycemia, or hypokalemia (although these are less likely than with albuterol)

Drug Category: Long-acting beta2-agonist

— Long-acting bronchodilators are not used for the treatment of acute bronchospasm. They are used for the preventive treatment of nocturnal asthma or exercise-induced asthmatic symptoms, for example. Currently, 2 long-acting beta2-agonists are available in the United States: salmeterol (Serevent) and formoterol (Foradil). Salmeterol is discussed below. Salmeterol is available as a combination of salmeterol and fluticasone (Advair) in the United States. Advair has an expiration date of 30 days once the protective wrapper is removed. 

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Adult

Serevent Diskus: 1 inhalation (50 mcg) q12h

Pediatric

<12 years: Not established

>12 years: 1 inhalation of inhalation powder (50 mcg) q12h; data in children are limited

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Concomitant use of beta-blockers may decrease bronchodilating and vasodilating effects of beta-agonists such as salmeterol; concurrent administration with methyldopa may increase pressor response; coadministration with oxytocic drugs may result in severe hypotension; ECG changes and hypokalemia resulting from diuretics may worsen with coadministration

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Documented hypersensitivity; angina, tachycardia, and cardiac arrhythmias associated with tachycardia

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Pregnancy

C – Safety for use during pregnancy has not been established.

Precautions

Use only as preventive treatment, not indicated for acute asthmatic symptoms

Drug Category: Methylxanthines

— These agents are used for long-term control and prevention of symptoms, especially nocturnal symptoms. 

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Adult

200-600 mg PO q12-24h

Pediatric

Initial dose: 10 mg/kg PO sustained-release tablets and capsules; not to exceed 300 mg/d
 First dose adjustment: 13 mg/kg PO; not to exceed 450 mg/d
 Second dose adjustment: 16 mg/kg PO; not to exceed 600 mg/d

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Aminoglutethimide, barbiturates, carbamazepine, ketoconazole, loop diuretics, charcoal, hydantoins, phenobarbital, phenytoin, rifampin, isoniazid, and sympathomimetics may decrease levels; allopurinol, beta-blockers, ciprofloxacin, corticosteroids, disulfiram, quinolones, thyroid hormones, ephedrine, carbamazepine, cimetidine, erythromycin, macrolides, propranolol, and interferon may increase levels

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Documented hypersensitivity; uncontrolled arrhythmias, peptic ulcers, hyperthyroidism, uncontrolled seizure disorders

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Pregnancy

C – Safety for use during pregnancy has not been established.

Precautions

Narrow therapeutic range; serum concentration monitoring is mandatory; 10-15 mcg/mL required for maximum effectiveness; adverse effects at usual therapeutic doses include insomnia, gastric upset, aggravation of ulcer or reflux, increase in hyperactivity; dose-related acute toxicity includes tachyarrhythmia (SVT), nausea, vomiting, headache, CNS stimulation, seizures, hematemesis, hyperglycemia, hypokalemia

Drug Category: Mast cell stabilizers

 — These agents block early and late asthmatic responses, interfere with chloride channels, stabilize the mast cell membrane, and inhibit the activation and release of mediators from eosinophils and epithelial cells. They inhibit acute responses to cold air, exercise, and sulfur dioxide. 

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Adult

Cromolyn: 20 mg in 2 mL nebulizer solution q6-8h
 Nedocromil: 2-4 inhalations bid/tid; 1.75 mg/actuation

Pediatric

Cromolyn: Administer as in adults
 Nedocromil: Administer as in adults

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None reported

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Documented hypersensitivity

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Pregnancy

C – Safety for use during pregnancy has not been established.

Precautions

Do not use in severe renal or hepatic impairment; symptoms may reoccur when withdrawing drug; unpleasant taste

Drug Category: Corticosteroids

— Steroids are the most potent anti-inflammatory agents. Inhaled forms are topically active, poorly absorbed, and least likely to cause adverse effects. No study has shown significant toxicity with inhaled steroid use in children at doses less than the equivalent of 400 mcg of beclomethasone per day. They are used for long-term control of symptoms and for the suppression, control, and reversal of inflammation. Inhaled forms reduce the need for systemic corticosteroids. They block late asthmatic response to allergens; reduce airway hyperresponsiveness; inhibit cytokine production, adhesion protein activation, and inflammatory cell migration and activation; and reverse beta2-receptor downregulation and subsensitivity (in acute asthmatic episodes with long-term beta2-agonist use). 

Inhaled steroids include beclomethasone, triamcinolone, flunisolide, fluticasone, and budesonide.

 

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Adult

Low dose: 168-504 mcg/d (42 mcg/inhalation, 4-12 oral inhalations q24h)
 Medium dose: 504-840 mcg/d (42 mcg/oral inhalation, 12-20 inhalations q24h)
 High dose: >840 mcg/d (42 mcg/oral inhalation, >20 inhalations q24h)

Pediatric

Low dose: 84-336 mcg/d (42 mcg/oral inhalation, 2-8 inhalations q24h)
 Medium dose: 336-672 mcg/d (42 mcg/oral inhalations, 8-16 inhalations q24h)
 High dose: >672 mcg/d (42 mcg/oral inhalation, >16 inhalations q24h)

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None reported

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Documented hypersensitivity, bronchospasm, status asthmaticus, other types of acute episodes of asthma

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Pregnancy

C – Safety for use during pregnancy has not been established.

Precautions

Inhaled corticosteroids can cause oral thrush and hoarseness (prevented by rinsing the mouth after a dose and by using a spacer with an MDI), and large doses (>800 mcg/d) have systemic adverse effects, including growth retardation and HPA inhibition

 

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Adult

Low dose: 88-264 mcg/d (44 mcg/oral inhalation, 2-6 inhalations q24h or 110 mcg/inhalation, 2 inhalations q24h)
 Medium dose: 264-660 mcg/d (110 mcg/oral inhalation, 2-6 inhalations q24h)
 High dose: >660 mcg/d (110 mcg/oral inhalation, >6 inhalations q24h or 220 mcg/oral inhalations, >3 inhalations q24h)

Pediatric

Low dose: 88-176 mcg/d (44 mcg/oral inhalation, 2-4 inhalations q24h)
 Medium dose: 176-440 mcg/d (110 mcg/oral inhalation, 2-4 inhalations q24h)
 High dose: >440 mcg/d (110 mcg/oral inhalation, >4 inhalations q24h or 220 mcg/oral inhalation, 2 inhalations q24h)

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None reported

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Documented hypersensitivity, bronchospasm, status asthmaticus, other types of acute episodes of asthma

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Pregnancy

C – Safety for use during pregnancy has not been established.

Precautions

Inhaled corticosteroids can cause oral thrush and hoarseness (prevented by rinsing the mouth after a dose and by using a spacer with an MDI), and large doses (>800 mcg/d) have systemic adverse effects, including growth retardation and HPA inhibition; high-dose long-term therapy has been associated with HPA inhibition and might retard growth

 

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Adult

Low dose: 200-400 mcg/d (1-2 inhalations/d)
 Medium dose: 400-600 mcg/d (2-3 inhalations/d)
 High dose: >600 mcg/d (>3 inhalations/d)

Pediatric

MDI:
 Low dose: 100-200 mcg/d (1 inhalation q24h)
 Medium dose: 200-400 mcg/d (1-2 inhalation q24h)
 High dose: >400 mcg/d (>2 inhalations q24h)
 Nebulizer (inhalation susp): 0.25-0.5 mg bid; not to exceed 1 mg/d

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None reported

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Documented hypersensitivity, bronchospasm, status asthmaticus, other types of acute episodes of asthma

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Pregnancy

C – Safety for use during pregnancy has not been established.

Precautions

Inhaled corticosteroids can cause oral thrush and hoarseness (prevented by rinsing mouth after a dose or using a spacer with a MDI); large doses (>800 mcg/d) have systemic adverse effects, including growth retardation and HPA inhibition. The manufacturer recommends not mixing the nebulizer solution with any other nebulized medications. The nebulized solution must be delivered with a tight-fitting mask or mouthpiece.

Drug Category: Systemic corticosteroids

— These agents are used for short courses (3-10 d) to gain prompt control of inadequately controlled acute asthmatic episodes. They are also used for long-term prevention of symptoms in severe persistent asthma as well as for suppression, control, and reversal of inflammation. Frequent and repetitive use of beta2-agonists has been associated with beta2-receptor subsensitivity and downregulation; these processes are reversed with corticosteroids. 

Higher-dose corticosteroids have no advantage in severe asthma exacerbations, and intravenous administration has no advantage over oral therapy, provided that gastrointestinal transit time or absorption is not impaired. The usual regimen is to continue frequent multiple daily dosing until the FEV₁ or PEF is 50% of the predicted or personal best values; then, the dose is changed to twice daily. This usually occurs within 48 hours.

 

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Adult

5-60 mg/d PO qd or divided bid/qid; taper over 2 wk as symptoms resolve

Pediatric

1-2 mg/kg/d PO for 3-10 d; not to exceed 60-80 mg/d

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Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

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Documented hypersensitivity, viral infection, peptic ulcer disease, hepatic dysfunction, connective-tissue infections, fungal or tubercular skin infections, GI disease

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Pregnancy

B – Usually safe but benefits must outweigh the risks.

Precautions

Short-term use may be associated with adverse effects including reversible abnormalities of glucose metabolism, increased appetite, fluid retention, weight gain, mood alteration, hypertension, peptic ulcer, and (rarely) aseptic necrosis of femur; conditions such as tuberculosis, herpes viral infections, varicella, hypertension, and peptic ulcer, may worsen with long-term systemic corticosteroids

 

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Adult

0.5-1 mg/kg/dose IV q6h; not to exceed 5 d

Pediatric

1 mg/kg IV q6h

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Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels; phenobarbital, phenytoin, and rifampin may decrease levels (adjust dose); monitor for hypokalemia with concurrent diuretics

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Documented hypersensitivity; viral, fungal, or tubercular skin infections

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Pregnancy

C – Safety for use during pregnancy has not been established.

Precautions

Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications of glucocorticoid use

Drug Category: Leukotriene modifier

 — Knowledge that leukotrienes cause bronchospasm, increased vascular permeability, mucosal edema, and inflammatory cell infiltration leads to the concept of modifying their action by using pharmacologic agents. These are either 5-lipoxygenase inhibitors or leukotriene-receptor antagonists. 

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Adult

20 mg PO bid

Pediatric

5-11 years: 10 mg PO bid
 >12 years: Administer as in adults

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Levels decrease when administered with erythromycin, terfenadine, and theophylline; may increase risk of bleeding if administered with warfarin

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Documented hypersensitivity

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Pregnancy

B – Usually safe but benefits must outweigh the risks.

Precautions

Take on an empty stomach; potential adverse effects include reversible hepatitis; bilirubin may accumulate in liver dysfunction; Churg-Strauss vasculitis

 

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Adult

10 mg PO hs

Pediatric

12-23 months: 1 packet of 4 mg oral granules PO hs
 2-6 years: 4 mg PO hs
 6-14 years: 5 mg PO hs
 >14 years: Administer as in adults

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Phenobarbital and rifampin may reduce montelukast AUC

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Documented hypersensitivity

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Pregnancy

B – Usually safe but benefits must outweigh the risks.

Precautions

4 and 5 mg are chewable; may cause headache or dyspepsia

Drug Category: Monoclonal antibody

 — These agents bind selectively to human IgE on the surface of mast cells and basophils. 

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Adult

150-375 mg SC q2-4wk; inject slowly over 5-10 s because of viscosity; not to exceed 150 mg per injection site
 Precise dose and frequency established by serum total IgE level (IU/mL)

Pediatric

<12 years: Not established

 

Further Inpatient Care

 

• Admit patients for treatment of acute severe episodes if they are unresponsive to outpatient care (eg, they have worsening bronchospasm, hypoxia, evidence of respiratory failure).

• Once the patient is admitted, further investigations (eg, PFTs, allergy testing, and investigations to rule out other associated conditions and complications) can be performed.

Further Outpatient Care

 

• Regular follow-up visits (1-6-mo intervals) are essential to ensure control and appropriate therapeutic adjustments.

• Outpatient visits should include the following:

• Interval history of asthmatic complaints, including history of acute episodes (eg, severity, measures and treatment taken, response to therapy)

• History of nocturnal symptoms

• History of symptoms with exercise and exercise tolerance

• Review of medications, including use of rescue medications

• Review of home-monitoring data (eg, symptom diary, peak flow meter readings, daily treatments)

• Patient evaluation should include the following:

• Assessment for signs of bronchospasm and complications

• Evaluation of associated conditions (eg, allergic rhinitis)

• Pulmonary function testing (in appropriate age group)

• Address issues of treatment adherence and avoidance of environmental triggers and irritants.

• Long-term asthma care pathways that incorporate the aforementioned factors can serve as roadmaps for ambulatory asthma care and help streamline outpatient care by different providers.

• In the author’s asthma clinic, a member of the asthma care team sits with each patient to review the written asthma care plan and to write and discuss in detail a rescue plan for acute episode, which includes instructions about identifying signs of acute episode, using rescue medications, monitoring, and contacting the asthma care team. These items are reviewed at each visit.

Inpatient & Outpatient Medications

 

• Bronchodilators (short- and long-acting)

• Controlling medications (nonsteroidal, steroidal, newer agents such as leukotriene modifiers)

• Medications for the treatment of associated conditions (antiallergy medications, nasal steroids for allergic rhinitis)

• Rescue medications for use in acute episodes (short burst of steroids)

 

<!–[if !supportLists]–>·         <!–[endif]–>Any patient with a high risk of asthma should be referred to a specialist. The following may suggest a high risk:

• History of sudden severe exacerbations

• History of prior intubation for asthma

• Admission to an ICU because of asthma

• Two or more hospitalizations for asthma in the past year

• Three or more emergency department visits for asthma in the past year

• Hospitalization or an emergency department visit for asthma within the past month

• Use of 2 or more canisters of inhaled short-acting beta2-agonists per month

• Current use of systemic corticosteroids or recent withdrawal from systemic corticosteroids

• The choice between a pediatric pulmonologist and an allergist may depend on local availability and practices. A patient with frequent ICU admissions, previous intubation, and a history of complicating factors or comorbidity (eg, cystic fibrosis) should be referred to a pediatric pulmonologist. When allergies are thought to significantly contribute to the morbidity, an allergist may be helpful.

Prevention

• The goal of long-term therapy is to prevent acute exacerbations.

• The patient should avoid exposure to environmental allergens and irritants that are identified during the evaluation.

Complications

• Pneumothorax status asthmaticus with respiratory failure

• Fixed (nonreversible) airway obstruction

• Death

Prognosis

• Of infants who wheeze with URTIs, 60% are asymptomatic by age 6 years; however, children who have asthma (recurrent symptoms continuing at age 6 y) have airway reactivity later in childhood.

• Some findings suggest a poor prognosis if asthma develops in children younger than 3 years, unless it occurs solely in association with viral infections.

• Individuals who have asthma during childhood have significantly lower FEV₁ and airway reactivity and more persistent bronchospastic symptoms than those with infection-associated wheezing.

• Children with mild asthma who are asymptomatic between attacks are likely to improve and be symptom-free later in life.

• Children with asthma appear to have less severe symptoms as they enter adolescence, but half of these children continue to have asthma.

• Asthma has a tendency to remit during puberty, with a somewhat earlier remission in girls. However, compared with men, women have more BHR.

Patient Education

• Patient and parent education should include instructions on how to use medications and devices (eg, spacers, nebulizers, MDIs). The patient’s MDI technique should be assessed on every visit.

• Discuss the management plan, which includes instructions about the use of medications, precautions with drug and/or device usage, monitoring symptoms and their severity (peak flow meter reading), and identifying potential adverse effects and necessary actions.

• Write and discuss in detail a rescue plan for an acute episode. This plan should include instructions for identifying signs of an acute attack, using rescue medications, monitoring, and contacting the asthma care team.

• Parents should understand that asthma is a chronic disorder with acute exacerbations; hence, continuity of management with active participation by the patient and/or parents and interaction with asthma care medical personnel is important.

• Emphasize the importance of compliance with and adherence to treatment.

• Incorporate the concept of expecting full control of symptoms, including nocturnal and exercise-induced symptoms, in the management plans and goals (for all but the most severely affected patients).

• Avoid unnecessary restrictions in the lifestyle of the child or family. Expect the child to participate in recreational activities and sports and to attend school as usual.