به نام خدای بی همتا

1. به نام خدای بی همتا

2. Asthmaby: Tooba MomenMD.Sub specialty inAllergy @ Immunology

3. 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 hyperresponsivenessthat 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.

4. 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

5. 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.

6. 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).

8. 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

9. Risk Factors For Asthma Development

10. Allergic sensitization • Gender • Reduced Lung Function • Upper respiratory Tract Infections RSV, Rhinovirus, Influenza, Parainfluenza, Metapneumovirus • Genetics • Socioeconomic Factor • Psychological Factor

11. Asthma Predictive Index Major 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 %

12. Phenotype @ Risk Factors Identifying 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 most prevalent 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 older siblings, day-care attendance,house-dust endotoxinand allergen exposure, such as cockroach,malesex,and bottle-feeding.

13. 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.

14. 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, parental asthma, 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 only be observed after the first episode of wheezing.

15. Asthma Symptoms Symptoms may include: • Coughing • Wheezing • Chest tightness • Shortness of breath • Excessive fatigue

16. 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.

17. 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

18. 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

19. DIAGNOSIS OF ASTHMA • History and patterns of symptoms • Physical examination • Measurements of lung function

20. 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

21. 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.

22. 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

23. 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

24. 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

25. 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.

26. 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.

27. 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.

28. 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 mL Exercise challenge   Worsening in FEV1 ≥15% Daily peak flow or FEV 1 monitoring: day to day and/or AM-to-PM variation ≥20%

30. Radiology Chest 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.

32. 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

33. A 3 y/o girl with history of chronic wet cough & wheezing since 1 years ago

34. Peak flow meter

35. DIFFERENTIAL DIAGNOSIS Upper airway disease Large airway Allergic rhinitis & Sinusitis Small airway Viral bronchiolitis or obliterative bronchiolitis Cystic fibrosis Broncho pulmonary dysplasia Heart Disease Others Infection, habit cough, PND Aspiration syndromes Foreign body in trachea or bronchus Vocal cord dysfunction Vascular ring or laryngeal web Laryngotracheomalacia, tracheal stenosis, or bronchostenosis Enlarged lymph nodes or tumor

36. Treatment

37. 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

38. Treatment Four 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

39. EPR3 recommends stepwise approach to asthma therapy guided by asthma severity & level of control, including an assesment of the domains of impairment & risk

40. 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.

41. Asthma Severity Classification

43. Assessing Control & Adjusting Therapy Children 0-4 Years of Age

45. Step up if needed (first check adherence, environmental control) Step down if possible (and asthma is well controlled at least 3months) Stepwise Approach for Managing Asthma in Children 0-4 Years of Age Intermittent Asthma Persistent Asthma: Daily Medication Consult asthma specialist if step 3 care or higher is required. Consider consultation at step 2 Step 6 Preferred High Dose ICS AND Either: Montelukast or LABA AND Oralcorticosteroid Step 5 Preferred High Dose ICS AND Either: Montelukast or LABA Step 4 Preferred Medium Dose ICS AND Either: Montelukast or LABA Step 3 Preferred Medium Dose ICS Assess control Step 2 Preferred Low dose ICS AlternativeMontelukast or Cromolyn Step 1 Preferred SABA PRN Patient Education and Environmental Control at Each Step 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

46. Step 6 Step 5 Preferred High Dose ICS + LABA + oral corticosteroid Alternative High dose ICS + either LTRA, or Theophylline + oral corticosteroid Step up if needed (first check adherence, environmental control, and comorbid conditions) Preferred High Dose ICS + LABA Alternative High dose ICS + either LTRA, or Theophylline Step 4 Step 3 Preferred Medium Dose ICS + LABA Alternative Medium dose ICS + either LTRA, or Theophylline Step 2 Preferred Either Low Dose ICS + LABA, LTRA, or Theophylline OR Medium Dose ICS Preferred Low dose ICS Alternative LTRA, Cromolyn Nedocromil or Theophylline Step 1 Preferred SABA PRN Step down if possible (and asthma is well controlled at least 3 months) Stepwise approach for managing asthma in children 5-11 years of age Intermittent Asthma Persistent Asthma: Daily Medication Consult asthma specialist if step 4 care or higher is required. Consider consultation at step 3 Assess control Patient Education and Environmental Control at Each Step Quick-relief medication for ALL patients SABA as needed for symptoms. Short course of oral corticosteroids maybe needed.

47. 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.

48. 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.

49. 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.

50. Classifying Severity of Asthma Exacerbations in the UC or ER Setting