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Asthmaby: Tooba Momen
MD.Sub specialty inAllergy @ Immunology
Definition
-Defined by the Global Initiative on Asthma as follows:
a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. The chronic inflammation is associated with airway hyperresponsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness and coughing, particularly at night or early in the morning. These episodes are usually associated with widespread, but variable, airflow obstruction within the lung that is often reversible either spontaneously or with treatment.’
In patients with suggestive symptoms the diagnosis of asthma requires the demonstration of the disease's main physiological characteristics, such as variable airway obstruction or hyperresponsiveness.
Prevalence-However, the overall prevalence has been estimated to be around 300
million worldwide.-The survey found that nearly 1 out of 10 (9.2%) American children 18 years
of age and younger currently suffer from asthma
-Boys (14% vs 10% girls) and children in poor families (16% vs 10% not poor) are more likely to have asthma. Approximately 80% of all asthmatics report disease onset prior to 6 yr of age.
-The prevalence of asthma is higher in children than in adults.
-higher in young boys than in young girls. -In both adolescents and adults it is more prevalent in females. -Asthma is more frequent in economically developed countries with a
‘Western lifestyle’ than in less developed regions, and also is more common in urban areas
ETIOLOGY
- a combination of environmental exposures and inherent biological genetic vulnerabilities.
- environment include inhaled allergens respiratory viral infections chemical and biological 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.
Genetic
More than 22 loci on 15 autosomal chromosomes have been linked to asthma.
-asthma has been consistently linked with loci containing pro-allergic, 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).
PATHOGENESIS
Airflow obstruction in asthma is the result of numerous pathologic processes.
bronchoconstriction of bronchiolar muscular bands restricts or blocks airflow.
A cellular inflammatory infiltrate and exudates: eosinophils ,neutrophils, monocytes,
lymphocytes, mast cells, basophils → epithelial damage and desquamation.
T lymphocytes and other immune cells that produce pro-allergic, proinflammatory cytokines
(IL-4, IL-5, IL-13) and chemokines (eotaxin) mediate this inflammatory process.
All processes that contribute to airflow obstruction .
airways edema
basement membrane thickening
subepithelial collagen deposition
smooth muscle hypertrophy
mucous gland hypertrophy, and mucus hyper secretion
RISK FACTORS FOR ASTHMA
DEVELOPMENT
Allergic sensitization Gender Reduced Lung Function Upper respiratory Tract Infections RSV, Rhinovirus, Influenza, Parainfluenza, Metapneumovirus Genetics Socioeconomic Factor Psychological Factor
Asthma Predictive IndexMajor criteria Minor Criteria Parental history of asthma Physician diagnosed atopic
dermatitis Allergic sensitization to at least
one aeroallergen
Children with wheezing and either one major or 2 minor criteria→ 4-7 times Low sensitivity ( 15-57%)High negative predictive value
Allergic sensitization to milk, egg, or peanut
Wheezing unrelated to colds
Blood Eosinophilia ≥ 4 %
Phenotype @ Risk FactorsIdentifying phenotypes of pediatric asthma and the
associated risk factors with each phenotype may help predict long-term outcomes and identify high-risk children who might benefit from secondary prevention interventions.
Transient early wheezing-Recurrent episodes of wheezing mainly in the first year of life and is the mostprevalent form of early wheezing. -Some 60% of children who wheeze in the first 3 years of life have resolution of
their symptoms by 6 years of age.- It has no significant relationship to atopy and maternal smoking-less than one-quarter of transient wheezers continued to wheeze during
adolescence -Other risk factors : include infants with school-aged oldersiblings, day-care attendance,house-dust endotoxinand allergenexposure, such as cockroach,male sex,and bottle-feeding.
Non-atopic persistent wheezing-is associated with the first episode of wheezing
occurring less than 1 year of age than atopic wheezing.
-represents 20% of wheezy children under age 3 and the wheezing episodes become less frequent by early teens.
Children with this phenotype have a lower level of pre-bronchodilator lung function and enhanced airway reactivity.
It is speculated that this phenotype may be caused by an alteration in the regulation of airway tone leading to viral-induced wheeze.
IgE-associated/atopic persistent wheezing
-This phenotype is found in 20% of children who wheeze during the first 3 years of life, with symptoms typically first presenting after age 1 year.
-Risk factors associated include male sex, parentalasthma, atopic dermatitis, eosinophilia at 9 months, and a history of
wheezing with lower respiratory tract infections.
-Associated with early sensitization to food or aeroallergens. Children-normal lung function in infancy but reduced lung function at age 6 years
compared with children with no history of wheezing with lower respiratory illnesses.
- Bronchial hyperreactivity is often observed and may onlybe observed after the first episode of wheezing.
Asthma Symptoms Symptoms may include: Coughing
Wheezing
Chest tightness
Shortness of breath
Excessive fatigue
Intermittent dry coughing and/or expiratory wheezing
Older children and adults → shortness of breath and chest tightness.
Respiratory symptoms can be worse at night.
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,
general fatigue (possibly due to sleep disturbance),
difficulty keeping up with peers in physical activities.
Key symptom indicators for considering a diagnosis of asthma
Wheezing
History of any following Cough Recurrent wheeze Recurrent difficulty breathing Recurrent chest tightness
Symptoms occur or worsen in presence of trigger
Symptom occur or worsen at night, waking the patient
Features isn't favor of asthma
Symptom starting at or shortly after birth
FTT
Complete failure to respond to anti asthmatic medication
Continuous wheezing
No association with typical trigger
DIAGNOSIS OF ASTHMA
History and patterns of
symptoms
Physical examination
Measurements of lung function
History
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.
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.
patient's age
History Cont…. course of onset (acute versus gradual) →Acute onset of wheezing raises the possibility of foreign body aspiration,
particularly if there is a history of choking. → distinguish between intermittent and persistent wheezing. →Persistent wheezing presenting very early in life suggests a congenital or
structural abnormality; in -contrast, paroxysmal or intermittent wheezing is a characteristic finding in patients with asthma.
→ Persistent wheezing with sudden onset is consistent with foreign body
aspiration, whereas the slowly progressive onset of wheezing may be a sign of extraluminal bronchial compression by a growing mass or lymph node . In addition, patients with interstitial lung disease can present with persistent wheezing.
A history of neonatal or perinatal respiratory problems and wheezing since birth → congenital abnormality.
Association of wheezing with feeding or vomiting → gastroesophageal reflux or impaired swallowing complicated by aspiration.
History of choking, especially with associated coughing or shortness of breath, even if this does not immediately precede onset of wheezing symptoms.
Wheezing with little cough suggests a purely mechanical cause of obstruction, and raises suspicion for foreign body aspiration. In general, cough is a prominent component of asthma in children
Cont….
Symptoms that vary with changes in position may be caused by tracheomalacia, bronchomalacia, or vascular rings.
Poor weight gain and recurrent ear or sinus infections suggest cystic fibrosis, immunodeficiency, or ciliary dysfunction.
hx of failure to thrive without feeding difficulties, electrolyte abnormalities, signs of intestinal malabsorption including frequent, greasy, or oily stools →cystic fibrosis
Asthma Triggers
Common viral infections of the respiratory tract
Aeroallergens in sensitized asthmatics 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
Physical Examination During routine clinic visits, commonly present without abnormal
signs, which stresses the importance of the medical history in diagnosing asthma.
Some may exhibit a dry, persistent cough.
The chest examination is often normal. 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 beta-agonist (SABA [albuterol]) is supportive of the diagnosis of asthma.
Physical Examination
During asthma exacerbation Expiratory wheezing and a prolonged expiratory phase
can usually be appreciated by auscultation.
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
-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.
Pulmonary Function Testing
Lung Function Abnormalities in Asthma
Airflow limitation Low FEV1 (relative to percentage of predicted norms) FEV1/FVC ratio <0.80 Bronchodilator response (to inhaled β-agonist) Improvement in FEV1 ≥12% or ≥200 mLExercise challenge Worsening in FEV1 ≥15%
Daily peak flow or FEV 1 monitoring: day to day and/or AM-to-PM variation ≥20%
RadiologyChest radiographs (posteroanterior and lateral views) in children
with asthma often appear to be normal, aside from subtle and nonspecific findings of hyperinflation (flattening of the diaphragms) and peribronchial thickening .
Chest radiographs can be helpful in identifying abnormalities that are hallmarks of asthma masqueraders (aspiration pneumonitis, hyperlucent lung fields in bronchiolitis obliterans), and complications during asthma exacerbations (atelectasis, pneumomediastinum, pneumothorax).
Some lung abnormalities can be better appreciated with high-
resolution, thin-section chest CT scans.
Inspiratory chest radiograph in a 12-month-old boy with a 2-month history of wheezing demonstrates moderate hyperlucency and hyperexpansion of the right hemithorax
A 3 y/o girl with history of chronic wet cough & wheezing since 1 years ago
Peak flow meter
DIFFERENTIAL DIAGNOSIS
Upper airway disease Large airway
Allergic rhinitis & Sinusitis
Small airwayViral bronchiolitis or obliterative
bronchiolitisCystic fibrosisBroncho pulmonary dysplasiaHeart Disease
OthersInfection, habit cough, PNDAspiration syndromes
Foreign body in trachea or bronchusVocal cord dysfunctionVascular ring or laryngeal webLaryngotracheomalacia, tracheal stenosis, or bronchostenosisEnlarged lymph nodes or tumor
Treatment
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Asthma Therapy Goals
“The goal of asthma therapy is to control asthma so patients can live active, full lives while minimizing their risk of asthma exacerbations and other problems”
NAEPP EPR -3
TreatmentFour Components of Optimal Asthma Management
REGULAR ASSESSMENT AND MONITORING Asthma checkups Every 2–4 wk until good control is achieved 2–4 per yr to maintain good control Lung function monitoring CONTROL OF FACTORS CONTRIBUTING TO ASTHMA SEVERITIY Eliminate or reduce problematic environmental exposures Treat co-morbid conditions: rhinitis, sinusitis, gastroesophageal reflux
ASTHMA PHARMACOTHERAPY Long-term-control vs quick-relief medications Classification of asthma severity for anti-inflammatory pharmacotherapy Step-up, step-down approach Asthma exacerbation management
PATIENT EDUCATION Provide a two-part care plan Daily management Action plan for asthma exacerbations
EPR3 recommends stepwise approach to asthma therapy guided by asthma severity & level of control, including an assesment of the domains of impairment & risk
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Severity & Control are used as follows for managing asthma:
If the patient is not currently on a long-term controller at the first visit:– Assess asthma severity to determine the appropriate
medication & treatment plan.
Once therapy is initiated, the emphasis is changed to the assessment of asthma control. – The level of asthma control will guide decisions either
to maintain or adjust therapy.
Asthma Severity Classification Persistent
Category Intermittent Mild Moderate Severe
ImpairmentSymptoms ≤2 days/wk ≥2 days/wk Daily Throughout the
day
Nighttime awakening
0-4 y/o 0
≥5 y/o ≤2 /mo
≤2/ mo
3-4/mo
3-4/mo
>1/wk
>1/wk
Often 7/wk
SABA use for
symptom
≤2 days/wk ≥2 days/wk Daily Several times/day
Interference with normal
activity
None Minor limitation
Some Limitation
Extremely limitation
Lung function
nl nl FEV1 60-80 %
FEV1/FVC reduced 5%
FEV1< 60%FEV1/FVC reduced> 5%
Asthma Severity Classification
Category Intermittent Persistent
Risk 0-4 y/o
≥5 y/o
0-1/yr
0-1/yr
≥2 exacerbation/ 6 moOr
≥4 whezing episode /yr lasting > 1 day & risk factor
for persistent asthma
≥2/yr
• Consider short course of oral systemic corticosteroids,
• Step up (1 2 steps), and• Reevaluate in 2 weeks. • If no clear benefit in 4 6
weeks, consider alternative diagnoses or adjusting therapy.
• For side effects, consider alternative treatment options.
• Step up (1 step) and• Reevaluate in
2 6 weeks.• If no clear benefit in
4 6 weeks, consider alternative diagnoses or adjusting therapy.
• For side effects, consider alternative treatment options.
• Maintain current treatment.
• Regular followupevery 1 6 months.
• Consider step down if well controlled for at least 3 months.
Recommended Actionfor Treatment
(See figure 4 1a fortreatment steps.)
>3/year2 3/year0 1/yearExacerbations requiring
oral systemic corticosteroids
Risk
Several times per day>2 days/week2 days/weekShort-acting
beta2-agonist usefor symptom control
(not prevention of EIB)
Extremely limitedSome limitationNoneInterference with normal activity
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.
Classification of Asthma Control (0 4 years of age)
Impairment
Components of Control
Treatment-related adverse effects
>1x/week>1x/month1x/monthNighttime awakenings
Throughout the day>2 days/week2 days/weekSymptoms
Very Poorly ControlledNot Well Controlled
WellControlled
Assessing Control & Adjusting Therapy Children 0-4 Years of Age
Lowest level of treatment required to maintain control
Classification of Asthma Severity
Intermittent
Persistent
Step 1
Mild Moderate
Severe
Step 2
Step 3 or 4
Step 5 or 6
IntermittentAsthma
Persistent Asthma: Daily MedicationConsult asthma specialist if step 3 care or higher is required.Consider consultation at step 2
Step 1
Preferred
SABA PRN
Step 2PreferredLow dose ICSAlternative Montelukast or Cromolyn
Step 3
PreferredMedium Dose ICS
Step 4
PreferredMedium Dose ICS
AND
Either:Montelukast or LABA
Step 5
PreferredHigh Dose ICS
AND
Either:Montelukast or LABA
Step 6
PreferredHighDose ICS
AND
Either:Montelukast or LABA
ANDOral corticosteroid
Patient Education and Environmental Control at Each Step
Stepwise Approach for Managing Asthma in Children 0-4 Years of Age
Quick-relief medication for ALL patients -SABA as needed for symptoms.With VURI: SABA every 4-6 hours up to 24 hours. Consider short course of corticosteroids with (or hx of) severe exacerbation
Step down if possible
(and asthma is well controlled at least 3 months)
Assess control
Step up if needed
(first check adherence, environmental control)
IntermittentAsthma
Persistent Asthma: Daily MedicationConsult asthma specialist if step 4 care or higher is required.Consider consultation at step 3
Patient Education and Environmental Control at Each Step
Stepwise approach for managing asthma in children 5-11 years of age
Quick-relief medication for ALL patientsSABA as needed for symptoms.Short course of oral corticosteroids maybe needed.
Step down if possible
(and asthma is well controlled at least 3 months)
Assess control
Step up if needed
(first check adherence, environmental control, and comorbid conditions)
Preferred
SABA PRN
Step 1
Preferred
Low dose ICS
AlternativeLTRA, CromolynNedocromil orTheophylline
Step 2 PreferredEitherLow Dose ICS + LABA, LTRA, or Theophylline
OR
Medium Dose ICS
Step 3 Preferred
Medium Dose ICS + LABA
AlternativeMedium dose ICS + either LTRA, or Theophylline
Step 4 Preferred
High Dose ICS + LABA
AlternativeHigh dose ICS + either LTRA, or Theophylline
Step 5 Preferred
High Dose ICS + LABA + oral corticosteroid
AlternativeHigh dose ICS + either LTRA, or Theophylline + oral corticosteroid
Step 6
Long-Term Controller Medications INHALED CORTICOSTEROIDS (ICS): -choice for all patients with persistent asthma -Fluticasone propionate, mometasone furoate and, to a lesser extent,
budesonide are considered “2nd-generation” ICSs in that they have increased anti-inflammatory potency and reduced systemic bioavailability for potential adverse effects, owing to extensive first-pass hepatic metabolism.
LONG-ACTING INHALED β-AGONIST (LABA): -the addition of LABA to ICS to be superior to doubling the dose of ICS,
especially on day and nocturnal symptoms. There are also controller formulations that combine ICS with LABA (fluticasone/salmeterol, budesonide/formoterol).
LEUKOTRIENE-MODIFYING AGENTS: - LTRAs have bronchodilator and targeted anti-inflammatory properties and
reduce exercise-, aspirin-, and allergen-induced bronchoconstriction. -an alternative treatment for mild persistent asthma and as an “add-on”
medication to ICS for moderate persistent asthma.
NONSTEROIDAL ANTI-INFLAMMATORY AGENTS : - Cromolyn and nedocromil - alternative anti-inflammatory drugs for children with mild persistent
asthma. Although largely devoid of adverse effects, these medications must be administered frequently (2–4 times/day) and are not nearly as effective daily controller medications as ICSs and leukotriene-modifying agents .
THEOPHYLLINE. -bronchodilator effects, theophylline has anti-inflammatory
properties as a phosphodiesterase inhibitor. -an alternative mono therapy controller agent for older children and
adults with mild persistent asthma, it is no longer considered a first-line agent for small children in whom there is significant variability in the absorption and metabolism of different theophylline preparations, necessitating frequent dose monitoring (blood levels) and adjustments.
-elevated theophylline levels have been associated with headaches, vomiting, cardiac arrhythmias, seizures, and death.
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Exacerbations Defined (Risk)
Are acute or subacute episodes of progressively worsening shortness of breath, cough, wheezing, and chest tightness — or some combination of these symptoms.
Are characterized by decreases in expiratory airflow that can be documented and quantified by spirometry or Peak expiratory flow. – These objective measures more reliably indicate the
severity of an exacerbation than does the severity of
symptoms.
Classifying Severity of Asthma Exacerbations in the UC or ER Setting
Severity Symptoms & Signs
Initial PEF (or FEV1)
Clinical Course
MildDyspnea only with activity (assess tachypnea in young children)
PEF 70 percent predicted or personal best
Usually cared for at home Prompt relief with inhaled SABA Possible short course of oral
systemic corticosteroids
Moderate Dyspnea interferes with or limits usual activity
PEF 4069 percent predicted or personal best
Usually requires office or ED visit Relief from freq. inhaled SABA Oral systemic corticosteroids;
some symptoms last 1–2 days after treatment is begun
SevereDyspnea at rest; interferes with conversation
PEF <40 percent predicted or personal best
Usually requires ED visit and likely hospitalization
Partial relief from frequent inhaled SABA
PO systemic corticosteroids; some symptoms last >3 days after treatment is begun
Adjunctive therapies are helpful
Subset: Life threatening
Too dyspneic to speak; perspiring
PEF <25 percent predicted or personal best
Requires ED/hospitalization; possible ICU
Minimal or no relief w/ frequent inhaled SABA
Intravenous corticosteroids Adjunctive therapies are helpful
Assess Severity Patients at high risk for a fatal attack (see figure 5–2a) require immediate medical attention
after initial treatment.
Symptoms and signs suggestive of a more serious exacerbation such as marked breathlessness, inability to speak more than short phrases, use of accessory muscles, or drowsiness (see figure 5–3) should result in initial treatment while immediately consulting with a clinician.
Less severe signs and symptoms can be treated initially with assessment of response to therapy and further steps as listed below.
If available, measure PEF—values of 50–79% predicted or personal best indicate the need for quick-relief mediation. Depending on the response to treatment, contact with a clinician may also be indicated. Values below 50% indicate the need for immediate medical care.
Initial Treatment Inhaled SABA: up to two treatments 20 minutes apart of 2–6 puffs
by metered-dose inhaler (MDI) or nebulizer treatments.
Note: Medication delivery is highly variable. Children and individuals who have exacerbations of lesser severity may need fewer puffs than suggested above.
Good ResponseNo wheezing or dyspnea(assess tachypnea in young children).
PEF 80% predicted or personal best.
Contact clinician for followup instructions and further management.
May continue inhaled SABA every 3–4 hours for 24–48 hours.
Consider short course of oral systemic corticosteroids.
Incomplete ResponsePersistent wheezing and dyspnea (tachypnea).
PEF 50–79% predicted or personal best.
Add oral systemic corticosteroid.
Continue inhaled SABA.
Contact clinician urgently (this day) for further instruction.
Poor ResponseMarked wheezing and dyspnea.
PEF <50% predicted or personal best.
Add oral systemic corticosteroid.
Repeat inhaled SABA immediately.
If distress is severe and nonresponsive to initial treatment:
—Call your doctor AND—PROCEED TO ED;—Consider calling 9–1–1
(ambulance transport).
To ED.
Managing Asthma Exacerbations At Home
Quick-Reliever Medications Short acting 2 agonists
SalbutamolLevosalbutamol
Anti-cholinergicsIpratropium bromide
systemic corticosteroids (oral, IV ) Magnesium sulfate Xanthines
Theophylline Adrenaline injections
Spacer
Dry PowderInhaler
Inhalation devices you can use
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