Asthma & COPD Flashcards
obstructive lung diseases: diseases with narrowing of airways
*COPD
*asthma
obstructive lung diseases: diseases with DILATION of airways
*cystic fibrosis (CF)
*non-CF bronchiectasis
asthma - defined
*a disease of CHRONIC inflammation of the airways
*intermittent obstructive lung disease often triggered by allergens, viral URIs, and stress
asthma - variable symptoms
*variable and recurring dyspnea, wheezing, cough, and/or chest tightness
*reversible airflow obstruction (bronchodilator response)
*resolution of an exacerbation
*diurnal symptoms (worse symptoms at night) frequently present
bronchodilator reversibility in asthma
*obstruction is reversed with the use of a bronchodilator, defined by:
an increase in FEV1 or FVC by 10% predicted or more after use of a bronchodilator
asthma phenotypes
*Th2 asthma (allergic asthma)
*non-Th2 asthma (non-allergic asthma)
allergic asthma (Th2): features
*atopic (rhinitis, eczema, asthma)
*allergens: dust mites, seasonal pollens, pet dander
*occupational asthma: workplace allergens
allergic asthma: pathobiology
*Th2-driven pathobiology: allergen → stimulates an antigen presenting cell → activates Th2 cells, which release IL-4, IL-5, IL-13 → activation of eosinophils, mast cells, and B cells → release of leukotrienes, histamine, etc
*leads to atopic phenotype
*eosinophils, mast cells, and B cells are the MAIN EFFECTOR CELLS
*UNCONTROLLED INFLAMMATION LEADS TO AIRWAY REMODELING
airway inflammation in allergic asthma
*inflammation of terminal bronchioles (smooth muscles, no cartilage)
*Th2 cells are activated by an antigen → release of IL-2, IL-4, IL-5, and IL-13 → activation of eosinophils, mast cells, and IgE from B cells
*bronchial submucosal edema and smooth muscle contraction
*bronchial obstruction from edema, cellular debris, airway smooth muscle hypertrophy, bronchospasm
hypersensitivity in allergic asthma
*chronic underlying inflammation of asthma: type IV Th2 hypersensitivity
*acute exacerbation of asthma is acute inflammation in addition to chronic inflammation: type 1 (IgE-mediated) hypersensitivity
non-allergic asthma (non-Th2): features
*common triggers: viral infections, cold air, exercise, sinusitis, gastric reflux, stress
*inhaled irritants: tobacco, solvents, chemicals
non-allergic asthma: pathobiology
*not entirely known
*triggers are not allergens (they are something else)
*NEUTROPHILS play a key role as an effector cell
*uncontrolled inflammation leads to airway remodeling
airway remodeling due to chronic inflammation
*smooth muscle hypertrophy & hyperplasia
*goblet cell hyperplasia
*combined, these hypertrophies cause a narrowed lumen, causing OBSTRUCTION of airflow
diagnosis of asthma: testing airway responsiveness
*assess bronchial responsiveness to see how the airways “respond” to stimuli using:
1. short-acting beta agonist (bronchodilator): responsive = 10%+ increase in FEV1 or FVC
2. bronchoprovocation to induce hyper-responsiveness by: short-acting cholinergic (e.g. methacholine)
classic asthma symptoms
EPISODIC symptoms of:
1. COUGH (esp after exertion, breathing cold air, at night, after colds, paroxysmal)
2. WHEEZING (chest tightness, noisy breathing)
3. BREATHLESSNESS (esp if intermittent, after exertion, or at night)
physical exam: asthma (during acute exacerbation)
*tachypnea
*use of accessory muscles to breathe
*markedly prolonged expiration with wheezing
*no air movement, “silent chest”
*intercostal retractions in childen
lab studies & pathology for workup of asthma
*CBC (looking for eosinophilia)
*allergy testing
*sputum samples:
-Cruschmann spirals (mucous plugs from epithelium)
-Charcot-Leyden crystals (eosinophilic crystals)
-Creola bodies (desquamated epithelial cells)
CXR findings in asthma
*CXR rarely demonstrates any abnormalities in asthma
*advanced disease from airway remodeling or acute exacerbation can cause hyperinflation
asthma therapies: short-acting beta agonists (SABA)
*used for RESCUE (sudden onset symptoms)
*examples: albuterol, levalbuterol, pirbuterol
asthma therapies: inhaled corticosteroids
*goal: target underlying inflammation (maybe prevent airway remodeling)
*examples: fluticasone, budesonide, mometasone, flunisolide, etc
asthma therapies: leukotriene modifier therapies
*Montelukast [a leukotriene (LTD4) receptor (CysLT1) antagonist)
asthma therapies: biologic therapies for severe eosinophilic asthma
*monoclonal antibodies (omalizumab, reslizumab, mepolizumab, benralizumab)
aspirin-induced asthma
*patient with a history of asthma takes aspirin
*aspirin inhibits COX-1
*less COX-1 activity → decreased arachidonic acid metabolism via COX → less PGE2 (anti-inflammatory)
*increase in leukotrienes and more inflammation of the submucosa
*increased bronchial constriction/hyper-responsiveness
status asthmaticus - overview
*extreme, life-threatening asthma exacerbation
*does NOT respond to bronchodilators
status asthmaticus - clinical features
*tachypnea, hypoxemia, cyanosis
*signs of respiratory arrest, pulsus paradoxus (exaggerated drop in systolic BP with inspiration)
status asthmaticus - diagnosis
*CBC (look for infection)
*arterial blood gas (look for increased PCO2, hypoxemia, low pH)
*peak expiratory flow measurement (FEV1 < 50% warrants ICU admission)
*CXR
*EKG
status asthmaticus - management
*bronchodilation
*systemic steroids
*IV magnesium
*O2
*non-invasive ventilation or intubation
*INDICATIONS OF INTUBATION: NORMALIZATION OF PCO2 (PCO2 starts low, but then starts rising/becomes elevated)
chronic obstructive pulmonary disease (COPD) - risk factors
*SMOKING
*genetic etiologies
*other
chronic obstructive pulmonary disease (COPD) - definition
*characterized by PERSISTENT (CHRONIC) AIRFLOW OBSTRUCTION [FEV1/FVC is < 0.70]
*frequently progressive and disabling
*associated with a chronic inflammatory response in airways/lungs to noxious particles or gases
*damage to small airways
chronic obstructive pulmonary disease (COPD) - phenotypes
- chronic bronchitis
- emphysema
PFT findings in COPD
*FEV1/FVC: < 0.7 or less than LLN
*FVC: normal or decreased
*FEV1: DECREASED (used to determine severity of disease)
*RV: increased if air trapping is present
*TLC: normal or increased
*DLCO: normal (chronic bronchitis) vs. decreased (emphysema)
*NO reversal of obstruction with bronchodilator
DLCO PFT findings of COPD: chronic bronchitis vs. emphysema
*if DLCO is normal: chronic bronchitis
*if DLCO is decreased: emphysema
pathophysiology of COPD
*COPD is a disease of chronic inflammation
*increased NEUTROPHILS, macrophages, and lymphocytes
*goblet cell hyperplasia
*hypersecretion and impaired ciliary function
*smooth muscle hyperplasia
*loss of parenchyma (in emphysema - due to unopposed proteases)
COPD: chronic bronchitis - overview & clinical definition
*“blue bloaters”
*defined by: sputum production most days for 3 months for 2 consecutive years of more (excessive mucociliary dysfunction, increased goblet cell secretion)
*most commonly caused by smoking
COPD: chronic bronchitis - mechanism
*progressive obstruction → hypoventilation and V/Q mismatch → progressive respiratory acidosis and hypoxemia (BLUE)
*alveolar hypoventilation → pulmonary artery vasoconstriction → right heart failure (cor pulmonale) → fluid retention (BLOATER)
COPD: chronic bronchitis - Reid index
*ratio between the thickness of the submucosal mucous secreting glands and the thickness between the epithelium and the cartilage
*ratio > 0.4 is consistent with chronic bronchitis
COPD: emphysema - overview and clinical definition
*“pink puffers”
*defined by: destruction of alveoli, alveolar duct, and/or respiratory bronchioles
*DECREASED DLCO on PFTs
*INCREASED COMPLIANCE due to loss of elastic fibers and less lung recoil
*leads to barrel chest, air trapping, and hyperinflation
COPD: emphysema - mechanism
*alveolar macrophages release proteases and cytokines → recruit neutrophils secrete elastase and proteases
*both terminal bronchioles/alveoli with associated capillary beds destroyed
*match V/Q deficit: HYPOXEMA & HYPERCAPNIA
*attempts hyperventilation due to hypercapnia → air trapping develops and decreased cardiac output → increasing V/Q mismatch (poor perfusion in areas of good ventilation)
*cachexia is mutifactorial: hyperventilation, increased work of breathing (PINK PUFFER), inflammatory cytokines
COPD: emphysema - 2 locations
- centrilobular/centriacinar emphysema (occurs in respiratory bronchioles)
- panlobular/panacinar emphysema (occurs in alveoli/alveolar ducts)
centrilobular emphysema
*emphysema in the respiratory bronchioles (spares distal alveoli)
*associated with SMOKING
*commonly affects the upper lobes
panlobular emphysema
*emphysema in the alveoli/alveolar ducts
*associated with A1AT (alpha1-antitrypsin deficiency)
*commonly affects the lower lobes
chronic hypercapnic respiratory failure in COPD
*to maintain minute ventilation early in the disease, patients will take large tidal volumes and have a prolonged expiratory phase (due to obstruction)
*hypercapnia is due to INCREASED DEAD SPACE, which happens because of:
-as the disease progresses, air trapping occurs due to obstruction of the small airways and progressive worsening of FEV1; air is trapped in the alveoli, but its not well exchanged (ventilated) during respiration
-this leads to an overall decrease in tidal volume with a max respiratory rate, but the alveolar minute ventilation is inadequate → chronic hypercapnic respiratory failure
COPD - clinical presentation
*DYSPNEA (persistent, progressive, worse with exercise)
*chronic cough that may be productive,
*recurrent infections
*patients often underreport symptoms
COPD - physical exam findings
*PE is rarely diagnostic in COPD
*lung exam: hyper-resonant, wheezing, or silent chest
*cardiac exam: distant heart sounds, especially if hyperinflation is present
*physical signs of airflow limitation
COPD: treatment - 2 major goals
- symptom reduction (relieve symptoms, improve exercise tolerance, improve health)
- risk reduction (prevent progression, prevent exacerbations, reduce mortality)
COPD: non-pharmacologic treatments
*SMOKING CESSATION
*vaccinations (pneumococcal and influenza, COVID)
*supplemental oxygen
*pulmonary rehabd
COPD: pharmacologic options
- bronchodilators:
-short acting beta agonists
-short acting anticholinergics (ipratropium)
-long acting anticholinergics (tiotroprium, aclidinium, umeclidinium)
-long acting beta agonists - anti-inflammatories:
-ICS + LABA
-PDE-4 inhibitors (roflumilast)
-oral steroids
-chronic azithromycin
what genetic abnormality is associated with COPD
*alpha 1 antitrypsin deficiency (associated with panlobular emphysema)
alpha 1 antitrypsin deficiency
*genetic abnormality that is a risk factor for COPD
*Serpin superfamily (SERPINA1 gene)
*found on chromosome 14
*functions as a protease inhibitor, primarily against neutrophils elastase
clinical vignette clue for COPD due to alpha 1 antitrypsin deficiency
*COPD in someone less than 50yo
*+/- cirrhosis
*basilar emphysema (at the base of the lungs; lower lobes)
alpha 1 antitrypsin deficiency COPD - pathophysiology
*neutrophils release neutrophil elastase after stimulation
*lack of A1AT allows neutrophil elastase to breakdown elastin of the lungs (“tethers”) → destruction of alveoli → emphysema
*lower lungs are more involved
alpha 1 antitrypsin deficiency COPD - genotypes
*PiMM = normal
*PiZZ = severe deficiency
*PiZZ is associated with LIVER CIRRHOSIS (due to misfolded protein can’t be excreted and accumulated in liver cells)
*ALL COPD patients should be tested
*treatment: augmentation with donor A1AT
COPD exacerbation - defined
*an acute change in a patient’s baseline symptoms:
-increased dyspnea compared to baseline
-more frequent cough
-increased sputum production beyond day-to-day variability
-symptoms significant enough to warrant a change in therapy
etiologies of COPD acute exacerbation
*viral infections
*bacterial infections
*environmental triggers
*non-adherence to therapy
*pulmonary embolism
severity of COPD exacerbation
*assess respiratory rate, mental status, accessory muscle use, and O2 response
*MILD: no respiratory failure
-RR 20-30, no accessory muscles, normal MS, responds to O2
*MODERATE: non-life-threatening respiratory failure
-RR > 30, accessory use, normal mental status, responds to O2, elevated PCO2
*SEVERE: life-threatening respiratory failure
-moderate criteria + CHANGE IN MENTAL STATUS, no O2 response, pH < 7.25
