DEFINITION • Asthma: Chronic inflammatory condition of the lung airways resulting in episodic airflow obstruction. • Chronic inflammation results in airways hyperresponsiveness (AHR) to provocative exposures • Management aims: 1. Reduce proinflammatory environmental exposures and 2. DAILY anti-inflammatory medications (ie. corticosteroids) and 3. Control any comorbidities that may worsen asthma AETIOLOGY • Cause not fully determined • Combination of environmental exposures and inherent biological and genetic vulnerabilities • **Causal environments: Inhaled allergens, viral RTIs, chemical/biological air pollutants/irritants eg. tobacco smoke. o Exposure to these in predisposed host result in prolonged pathogenic inflammation and aberrant repair --> Lung dysfunction develops. o This abnormal growth and development in early life leads to abnormal airways at mature age GENETICS • More than 100 gene loci linked to asthma. • Loci contain • Other genes: ENVIRONMENT • Injurious/severe LRTI of the airways that manifest as *pneumonia and *bronchiolitis are risk factors for persistent asthma. • Other infections/Microbes • Allergens – Inhalant allergens > food allergens • Irritants/Pollutants e.g. Tobacco smoke • Stress RISK FACTORS (Must Know) See box -> (M > F) -> Lecture: “ASTHMA PREDICTIVE INDEX (API)” - Tucson cohort 1980-present - >/= 4 eps of wheeze + 1 major OR 2 minor predicts asthma APPLIES TO CHILDREN <= - *MAJOR: 1. Parental asthma, 2. Atopic dermatitis (eczema), 3. Inhalant allergen sensitization - MINOR: 1. Eosinophilia > 4%, 2. Wheezing outside of colds, 3. Food allergen sensitization, 4. Allergic rhinitis POINTS Approximately 80% of all asthmatic patients report disease onset prior to age 6!! - BUT only a minority of children who experience recurrent wheezing go on to persistent asthma - Maternal asthma is the single most important risk factor for asthma development 2 main types of childhood asthma: 1. Recurrent wheezing 2. Chronic asthma PATHOGENESIS Airway obstruction in asthma results from numerous pathologic processes: • In small airways, airflow is regulated by smooth muscle encircling the airways lumens – bronchoconstriction of these bronchiolar muscle bands restricts and blocks airflow (Parasympathetic system stimulates bronchoconstriction) • ALSO, a cellular inflammatory infiltrate AND exudates containing mainly eosinophils, can fill and obstruct airways AND induce epithelial damage and desquamation into the airways lumen. • ALSO, helper T lymphocytes (CD4) and other immune cells produce proallergenic, proinflammatory cytokines (IL-4, 5 and 13) that mediate the inflammatory process. ALL CONTRIBUTE TO AIRFLOW OBSTRUCTION (LOOK AT EACH AND JUST OBVIOUSLY SEE HOW) CLINICAL MANIFESTATIONS AND DIAGNOSIS ***NOTE FROM LECTURE: The most likely diagnosis in children with recurrent wheezing is asthma, regardless of the age of onset, evidence of atopic disease, precipitating causes, or frequency of wheezing MOST COMMON CHRONIC SYMPTOMS: • Intermittent DRY COUGHING • EXPIRATORY WHEEZE Other symptoms in older children/adults: • Shortness of breath • Chest tightness **NB**: The respiratory symptoms are WORSE AT NIGHT!! Others are subtle/nonspecific: Limited physical activity, general fatigue (may be due to sleep disturbance) • ***MUST ASK ABOUT PREVIOUS BRONCHODILATOR USE IN HISTORY!!: o Symptomatic improvement with treatment supports asthma diagnosis! o BUT lack of improvement with bronchodilator/corticosteroid therapy is inconsistent with asthma and should prompt consideration of “ASTHMA-MASQUERADING CONDITIONS” • ***MUST ASK ALL Triggers***: Physical exertion, hyperventilation (laughing), cold or dry air, airway irritants/allergens (incl smoking at home, pets etc), respiratory infection (induce airway inflammation – eg. RSV, rhinovirus, adenovirus, influenza, parainfluenza, mycoplasma pneumoniae, chlamydia pneumoniae). ENVIRONMENTAL HISTORY IS VITAL • **Ask about risk factors: SEE RISK FACTORS ABOVE AND OTHER DIFFERENTIALS OF WHEEZE From lecture: HISTORY FOR A WHEEZING PATIENT: o Age of onset o Course of onset (Acute vs. chronic) o Cough o Shortness of breath o Cyanosis o Chest pain o **Exercise-induced symptoms o Postnasal drip o Snoring o Spitting up o Greasy stool (cystic fibrosis)? o **Eczema o Choking o Triggers o Cold air o Allergic rhinitis o Weight loss o Recurrent infections o Birth history o Environmental history o Smokers at home o Number of siblings o Occupation of inhabitants at home o Pets o TB exposure o Worms o ***Family history of Atopy/Asthma o ***Past use and response to bronchodilators o Food allergies o Co-morbid conditions History suggestive of asthma o Intermittent episodes of wheezing o Seasonal variation o Family history of asthma and/or atopy o Good response to asthma medications o Positive asthma predictive index **History suggestive of a diagnosis other than asthma o Poor response to asthma medications/bronchodilators o History of neonatal or perinatal respiratory problems o Wheezing since birth - congenital abnormality o Associated with feeding or vomiting o History of choking associated with cough & SOB o Poor weight gain o Recurrent ear or sinus infections o Wheezing with little cough - Mechanical cause of obstruction- small airways, airway malacia o Symptoms vary with position (TM) o Progressive dyspnea, tachypnea, exercise intolerance & failure to thrive suggest interstitial lung disease Examination (See Notes on wheezing for general wheezing examination) • ***Chest findings are often normal!! – Ask for deeper breaths -> May elicit wheezing In extremis -> Airflow may be so limited that wheezing cannot be heard DIFFERENTIAL DIAGNOSIS [**CLASSIFY: Upper vs. Middle vs. Lower respiratory tract conditions**] [ALSO: Extraluminal compression vs. Intraluminal obstruction vs. Intrinsic change in airway dimension] Also depends on the age group (see lecture) Other common causes of intermittent chronic coughing --> GER, rhinosinusitis SEE TABLE BELOW - * = More common ones DIFFERENTIAL DIAGNOSIS OF CHILDHOOD ASTHMA UPPER RT CONDITIONS MIDDLE RT CONDITIONS LOWER RT CONDITIONS - Allergic rhinitis * - Chronic rhinitis * - Sinusitis * - Adenoidal or tonsillar hypertrophy - Nasal foreign body - Laryngotracheobronchomalacia * - Laryngotracheobronchitis (e.g., pertussis) * - Chronic bronchitis from environmental tobacco smoke exposure * - Vocal cord dysfunction * - Foreign body aspiration * - Laryngeal web, cyst, or stenosis - Vocal cord paralysis - Tracheoesophageal fistula - Vascular ring, sling, or external mass compressing on the airway (e.g., tumor) - Toxic inhalations Viral bronchiolitis * Gastroesophageal reflux * Bronchopulmonary dysplasia (chronic lung disease of preterm infants) Pneumonia Pulmonary oedema (e.g., congestive heart failure) Causes of bronchiectasis: Cystic fibrosis Immune deficiency Allergic bronchopulmonary mycoses (e.g., aspergillosis) Chronic aspiration Immotile cilia syndrome, primary ciliary dyskinesia Bronchiolitis obliterans Interstitial lung diseases Hypersensitivity pneumonitis Pulmonary eosinophilia, Churg-Strauss vasculitis Pulmonary hemosiderosis Tuberculosis Medications associated with chronic cough: Acetylcholinesterase inhibitors β -Adrenergic antagonists Angiotensin-converting enzyme inhibitors LABORATORY FINDINGS 1. PULMONARY FUNCTION TESTS (Spirometry and Peak flow) POINT: ‘Forced expiratory airflow measurement’ helpful in diagnosis and monitoring efficacy of therapy A. Spirometry is helpful as an objective measure of airflow limitation o **Valid spirometry measurements depend on a patient’s ability to perform a full, forceful, prolonged expiration, usually feasible in children > 6 yrs. old. Reproducible spirometric efforts are an indicator of test validity; if the FEV 1 (forced expiratory volume in 1 sec) is within 5% on 3 attempts, then the highest FEV 1 effort of the 3 is used Normative values for FEV 1 have been determined for children on the basis of height, gender, and ethnicity o Because asthmatic patients typically have hyperinflated lungs, FEV 1 can be simply adjusted for full expiratory lung volume — the forced vital capacity (FVC) — with an FEV 1/FVC ratio. o BUT these measures alone are NOT diagnostic of asthma as numerous other conditions can cause airflow reduction Bronchodilator response to an inhaled β -agonist (e.g., albuterol) is > in asthmatics than nonasthmatics; an improvement in FEV 1 ≥ 12% or > 200 mL is consistent with asthma. IMPORTANT TABLE (NELSON’S) B. Peak expiratory flow (PEF) monitoring devices provide simple and inexpensive home-use tools to measure airflow and can be helpful in a number of circumstances. Patients must practice over 2-3 weeks to determine a “personal best”, preferably at times when they a not symptomatic • Peak flow rate monitoring can be accurately performed by most patients > 5 years • ** PEFR < 80% predicted for height/patient’s personal best should trigger the administration of an inhaled short-acting beta2 -agonist • A PEFR < 50% of the patient’s personal best should trigger both administration of an inhaled short-acting beta2 -agonist AND immediate medical attention SEE MY FULL NOTES ON PEFR NOTE WELL: PEFR and FEV1 are different. Forced expiratory volume over 1 second (FEV1) is a dynamic measure of flow used in formal spirometry. It represents a truer indication of airway obstruction than does peak flow rate. Although peak flow rate usually correlates well with FEV1, this correlation decreases in patients with asthma as airflow diminishes. 2. Radiology The findings of chest radiographs (PA 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 CXR: • Hyperinflation (Flattened ribs and diaphgram, Increased number of ribs over hemidiaphragm, Right diaphragm same level as left) • Flattened hemi-diaphragms • Peribronchial cuffing • Atelectasis 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). TREATMENT **MUST SEE ENTIRE UHWI OFFICIAL EMED DOCUMENT** • SEE GINA GUIDELINES • SEE SUMMARY OF THE STEP UP AND DOWN APPROACH FROM A CONCISE SOURCE!! • MUST SEE UHWI OFFICIAL EMED DOCUMENT AND GINA FOR MANAGEMENT OF EXACERBATION ***ASTHMA IS A CHRONIC CONDITION THAT IS OFTEN BEST MANAGED WITH DAILY ICS CONTROLLER MEDICATION as monotherapy or with adjunctive therapy*** ***NOTE WELL: Remember patient education AND control of environmental factors AND comorbidities (eg. GER, rhinitis, sinusitis etc.)*** NELSON’S: During initial patient visits, a basic understanding of the pathogenesis of asthma (chronic inflammation and AHR underlying a clinically intermittent presentation) can help children with asthma and their parents understand the importance of recommendations aimed at reducing airways inflammation. It is helpful to specify the expectations of good asthma control resulting from optimal asthma management. Explaining the importance of steps to reduce airways inflammation in order to achieve good asthma control and addressing concerns about potential adverse effects of asthma pharmacotherapeutic agents, especially their risks relative to their benefits, are essential in achieving long-term adherence with asthma pharmacotherapy and environmental control measures. GINA (GLOBAL INITIATIVE FOR ASTHMA) GUIDELINE Based on GINA guidelines, must use this table to determine level of control, which will determine when to “Step-up” management, using the table on the next page

Short-acting beta 2 agonists

Salbutamol (albuterol), terbutaline.

Long-acting beta 2 agonists

Salmeterol, Formoterol.

Anti-cholinergics

Ipratropium bromide.

ICS

Inhaled corticosteroids such as Budesonide, Beclomethasone, and Fluticasone.

Oral steroids

Prednisone, known for its side effects.

Methylxanthines

Theophylline and Aminophylline, now rarely used in children.

Leukotriene receptor antagonists

Montelukast and Zafirlukast.

CNS complications of steroid therapy

Sleep disturbances, Mood swings, Behavioral changes, Anxiety, Depression, Euphoria, Psychosis.

EYES complications of steroid therapy

Blurred vision, Retinopathy, Glaucoma, Cataract.

ORAL complications of steroid therapy

Thrush.

RESPI complications of steroid therapy

Hoarseness.

CARDIO complications of steroid therapy

Hypertension due to sodium retention, Edema.

GASTRO complications of steroid therapy

Decrease appetite, Vomiting, Peptic ulcers, Hematemesis, Colitis.

MSK complications of steroid therapy

Muscle weakness.

BONES complications of steroid therapy

Osteopenia, Osteoporosis.

SKIN complications of steroid therapy

Hyper/Hypo-pigmentation, Rash, Acne, Easy bruising, Increased hair.

What are the side effects of Prednisone?

Variety of side effects including sleep disturbances, mood swings, and gastrointestinal issues.

What is the purpose of bronchodilators?

To relax and widen the airways to improve breathing.

Name a short-acting beta 2 agonist.

Salbutamol (albuterol).

What are the long-acting beta 2 agonists?

Salmeterol and Formoterol.

What is a common anti-cholinergic used for respiratory issues?

Ipratropium bromide.

What is an ICS used to treat inflammation?

Budesonide.

Which drug class do Montelukast and Zafirlukast belong to?

Leukotriene receptor antagonists.

What is a notable side effect of prolonged steroid use?

Osteoporosis.

How does steroid therapy affect the eyes?

It can cause blurred vision, retinopathy, glaucoma, and cataracts.

What are common respiratory effects of steroid therapy?

Hoarseness.

What is the primary function of leukotriene receptor antagonists?

To block the action of leukotrienes that cause inflammation and bronchoconstriction.

What side effect can steroids cause related to skin?

Rash, acne, easy bruising, hyper/hypo-pigmentation.

What effect do steroids have on muscle strength?

They can cause muscle weakness.

What gastrointestinal issues can be caused by steroid therapy?

Decrease appetite, vomiting, peptic ulcers.

Which steroid is commonly prescribed for short-term management of severe asthma?

Prednisone.

What are some reasons for the rare use of methylxanthines in children?

Their side effects and less efficacy compared to other treatments.

What condition can occur as a result of steroid-induced sodium retention?

Hypertension.

Name a short-acting bronchodilator.

Albuterol.

What is the main action of long-acting beta-agonists?

To provide prolonged bronchodilation.

What condition are the side effects of steroid therapy often related to?

Chronic inflammatory diseases such as asthma.

What is one common side effect of long-term steroid use on the bones?

Osteopenia.

What therapeutic class does Budesonide belong to?

Inhaled corticosteroids.

What is a common side effect of anti-cholinergics like Ipratropium bromide?

Dry mouth.

What is the mechanism of action of beta-agonists?

They stimulate beta-2 adrenergic receptors leading to airway dilation.