Obstructive lung disease Notes

NOTES NOTES OBSTRUCTIVE LUNG DISEASE GENERALLY, WHAT IS IT? PATHOLOGY & CAUSES ▪ Obstruction of airflow from lungs ▪ Increased resistance to airflow → airtrapping ▪ Classifications ▫ Narrowing of lumen wall (e.g. asthma, chronic bronchitis) ▫ Increasing pressure external to airway/loss of lung parenchyma (e.g. emphysema) ▫ Obstruction of airway lumen (e.g. bronchiectasis, chronic bronchitis) COMPLICATIONS ▪ Cor pulmonale, right ventricular hypertrophy SIGNS & SYMPTOMS ▪ Cough, thick mucus, dyspnea, wheezing DIAGNOSIS DIAGNOSTIC IMAGING Chest X-ray/CT scan LAB RESULTS ▪ Sputum culture ▪ Arterial blood gas (ABGs) 886 OSMOSIS.ORG OTHER DIAGNOSTICS Spirometry/pulmonary function test (PFTs) ▪ Tidal volume (TV) ▫ Volume of air inspired, expired during quiet breathing ▪ Residual volume (RV) ▫ Volume of air left in lung after maximal expiration ▪ Forced vital capacity (FVC) ▫ Maximum volume of air that can be expired after maximal inspiratory effort ▪ Forced expiratory volume (FEV) ▫ Volume of air forcibly exhaled per unit of time ▪ Peak expiratory flow rate (PEFR) ▫ During FEV, maximum flow of expiration ▪ Functional residual capacity (FRC) ▫ Volume of air left in lungs after quiet expiration TREATMENT ▪ See individual diseases

Chapter 126 Obstructive Lung Disease ALPHA 1-ANTITRYPSIN (A1AT) DEFICIENCY osms.it/a1at-deficiency PATHOLOGY & CAUSES ▪ Autosomal dominant (codominant) genetic disorder ▫ Decreased production/absence of A1AT → overaction of proteases → damaged alveoli → damaged lungs, liver ▪ Lungs ▫ Damaged alveoli inflammation → neutrophils secrete elastase → absence of/decreased A1AT → elastase overacts, inflames → increased breakdown of elastin → alveoli lose elasticity, integrity → chronic obstructive pulmonary disease (COPD) ▪ Liver ▫ Genetic mutation → misfolded A1AT build up in endoplasmic reticulum of hepatocytes → kill hepatocytes → cirrhosis CAUSES ▪ Smoking ▫ Earlier onset of COPD in individuals with A1AT deficiency ▪ Genetics ▫ Serine protease inhibitor, clade A, member 1 (SERPINA1) encodes A1AT protein, located on long arm of chromosome 14 ▪ Pi*M ▫ Normal allele ▪ Pi*Z (most common) ▫ Mutated/diseased allele ▫ Misfolded A1AT proteins aggregate → stick in endoplasmic reticulum of hepatocytes → kill hepatocytes ▪ PiMZ ▫ Heterozygous (one normal allele, one diseased allele) ▫ Mutated gene contributes 10% normal amounts A1AT proteins ▫ Heterozygous individuals have 60% normal levels (enough to protect lungs in non-smokers) ▫ Increased risk of lung/liver disease ▪ PiZZ ▫ Homozygous ▫ Individuals only have 15–20% normal levels ▫ Much higher risk of lung/liver disease ▫ Can live without lung/liver disease if environmental exposures minimal ▫ Infants can develop liver failure during first years of life ▫ Individuals with no production of A1AT = no liver disease COMPLICATIONS ▪ COPD (emphysema, bronchiectasis, chronic bronchitis), hepatocellular carcinoma, liver cirrhosis, chronic hepatitis SIGNS & SYMPTOMS ▪ COPD: shortness of breath, wheezing, mucus production, chronic cough ▪ Liver damage, cirrhosis, impaired liver function: inability to make coagulation factors, hepatic encephalopathy, portal hypertension, esophageal varices, jaundice, hepatocellular carcinoma OSMOSIS.ORG 887

DIAGNOSIS DIAGNOSTIC IMAGING Liver ultrasound Chest X-ray/CT scan ▪ Hyperinflated/damaged lungs, basilar emphysema, panlobular emphysema ▫ Smoking: apically distributed emphysema LAB RESULTS ▪ Serum A1AT levels ▪ Family history, genetic testing ▪ Liver biopsy OTHER DIAGNOSTICS ▪ PFT ▫ Measure rate air exits lungs ▪ Periodic acid-Schiff (PAS) ▫ Diastase-resistant pink globules in liver biopsy ▫ Stains A1AT pink TREATMENT MEDICATIONS ▪ Augmentation therapy ▫ Intravenous (IV) infusions of A1AT protein from plasma donors ▫ Not curative, only slows progression ▪ Inhalers, supplemental oxygen ▫ COPD ▪ Lactulose ▫ Prevent hepatic encephalopathy ▫ For liver cirrhosis SURGERY ▪ Liver transplant ▫ Esp. homozygous infants, liver failure during first years ▪ Lung transplant Figure 126.2 A CT scan of the chest in the axial plane demonstrating panlobular emphysema as a consequence of alpha 1-antitrypsin deficiency. Figure 126.1 The histological appearance of the liver in an individual with alpha 1-antitrypsin deficiency. There are globular inclusions within periportal hepatocytes. 888 OSMOSIS.ORG

Chapter 126 Obstructive Lung Disease ASTHMA osms.it/asthma PATHOLOGY & CAUSES ▪ Hyperresponsiveness disorder, reversible airflow obstruction ▪ Chronic inflammation, narrowing of airways ▪ Acute (Type 1 hypersensitivity reaction) ▫ Initial sensitization to allergen → production of cluster of differentiation 4 (CD4), T helper 2 (Th2) cells → release interleukin 4 (IL4), interleukin 5 (IL5) → environmental trigger → eosinophils, mast cells release inflammatory mediators in bronchial walls (e.g. histamine, leukotrienes) → degradation of lipids, proteins, nucleic acids → tissue destruction → strong inflammatory reaction in bronchiolar walls → smooth muscle of bronchioles spasm, mucus in narrow airways increases → difficulty breathing ▫ Vasodilation of pulmonary vasculature, increased capillary permeability → edema ▫ Increased mucus production by goblet cells → impaired mucociliary function ▪ Chronic inflammation → scarring, fibrosis → thickening of epithelial basement membrane → permanently narrows airway ▪ Th2 cells release IL5 → attract, activate eosinophils ▪ Neutrophils release cytokines ▫ Interleukin 8 (IL8) ▫ More severe for individuals with neutrophilic asthma ▪ Triggers ▫ Air pollution, cigarette smoke, dust, pet dander, cockroaches, mold, pollen, medications (e.g. aspirin, beta-blockers) TYPES Extrinsic ▪ Type 1 hypersensitivity reaction triggered by extrinsic allergens (e.g. dust, mold) ▪ Individuals with atopic family history to allergies ▪ Atopic triad ▫ Asthma, atopic dermatitis, allergic rhinitis Intrinsic ▪ Nonimmune ▪ Viral infections, stress, exercise, smoking SIGNS & SYMPTOMS ▪ Coughing, chest tightness, dyspnea, difficulty breathing, wheezing, whistling during expiration ▪ Curschmann spirals in sputum ▫ Spiral-shaped mucus plugs ▫ Casts from small bronchi ▫ Blocks air exchange, inhaled medications from reaching inflammation ▪ Charcot–Leyden crystals in sputum ▫ Needle-shaped, formed from breakdown of eosinophils DIAGNOSIS OTHER DIAGNOSTICS ▪ Trigger test, spirometry, peak air flow ▪ Classifications based on frequency of symptoms (esp. night/morning), forced expiratory volume in one second (FEV1), PEFR, frequency of medication use (intermittent, mild persistent, moderate persistent, severe persistent) TREATMENT OTHER INTERVENTIONS ▪ No cure; treatments manage symptoms, prevent asthma attack ▪ Avoid triggers OSMOSIS.ORG 889

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Chapter 126 Obstructive Lung Disease Figure 126.3 A chest radiograph demonstrating hyperinflation in an individual with chronic asthma. There is a pneumothorax in the right lower zone. BRONCHIECTASIS osms.it/bronchiectasis PATHOLOGY & CAUSES ▪ Chronic inflammation → permanent dilation of bronchi, bronchioles → destruction of airways ▫ Damage to mucociliary “elevator” → mucus, bacteria accumulates CAUSES Chronic inflammation ▪ Primary ciliary dyskinesia ▫ Absence of dynein arm in cilia → cilia move abnormally → mucus stuck in airways → bacteria in mucus multiply → pneumonia → chronic inflammation ▪ Cystic fibrosis (most common) ▫ Mucus too sticky → hard for cilia to sweep → mucus accumulates → recurrent pneumonias → chronic inflammation, infection Airway obstruction ▪ E.g. tumor inside/outside airway, lodged foreign object ▪ Blockage prevents mucociliary escalator from clearing mucus → recurrent pneumonias → chronic inflammation Infections ▪ E.g. aspergillosis, tuberculosis, adenovirus, Haemophilus influenzae, Staphylococcus aureus; hypersensitivity response → inflammation ▫ Chronic inflammation → immune cells, cytokines damage cilia, elastin fibers → airways dilated, clogged with mucus → fibroblasts deposit collagen → loss of elastin, buildup of collagen → lungs less elastic → more difficult for air to move smoothly → lung function declines → hypoxia → pulmonary arterioles constrict to divert blood away from damaged areas of lung → increased OSMOSIS.ORG 891

pulmonary vascular resistance → right ventricular hypertrophy → cor pulmonale → inflammation of pleura SIGNS & SYMPTOMS ▪ Wheezing, productive cough, foul smelling mucus, dyspnea, hemoptysis, recurrent/ persistent pneumonia, basilar crackles ▪ Long term hypoxia ▫ Digital clubbing DIAGNOSIS DIAGNOSTIC IMAGING CT scan ▪ Dilated bronchi/bronchioles Chest X-ray ▪ Increased bronchial markings at lung periphery LAB RESULTS ▪ Sputum culture ▪ Genetic testing Figure 126.4 The gross pathological appearance of the lungs in a case of severe bronchiectasis. OTHER DIAGNOSTICS ▪ Spirometry ▫ FEV1 decreased, FEV1/FVC ratio decreased ▪ Sweat test TREATMENT MEDICATIONS ▪ Bronchodilators; beta-2 agonists (e.g. albuterol) ▪ Inhaled corticosteroids (e.g. fluticasone ▪ Antibiotics ▫ Recurrent pneumonias OTHER INTERVENTIONS ▪ Percussion, postural drainage ▫ Recurrent pneumonias ▪ Pulmonary hygiene ▪ Adequate hydration 892 OSMOSIS.ORG Figure 126.5 The histological appearance of bronchiectasis complicated by fungal colonisation. There is a heavily dilated bronchus containing an aggregation of fungus known as an aspergilloma.

Chapter 126 Obstructive Lung Disease CHRONIC BRONCHITIS osms.it/chronic-bronchitis PATHOLOGY & CAUSES ▪ Preventable, progressive pulmonary disease ▫ Chronic airway inflammation, limited airflow ▫ Bronchial tubes in lungs inflame → productive cough ▪ Subset of COPD ▪ Exposure to irritants → hypertrophy/ hyperplasia of bronchial mucous glands, goblet cells in bronchioles, cilia less mobile → increased mucus production, less movement → mucus plugs → obstruction in bronchioles → air-trapping → productive cough ▪ Blocked airflow, air-trapping → increased partial pressure of CO2 in lungs → less O2 reaches blood → cyanosis (if severe); individuals referred to as “blue bloaters” RISK FACTORS ▪ Smoking (primary cause), cystic fibrosis, sulfur, nitrogen dioxide, dust, silica, family history, genetic predisposition COMPLICATIONS ▪ Pulmonary hypertension, increased workload of right ventricle, cor pulmonale, infections distal to mucus blockages, fibrosis of terminal bronchioles, compensatory polycythemia SIGNS & SYMPTOMS ▪ Wheezing (due to mucus, narrow airway), crackles/rales (small airways pop open during air movement due to narrow passageway) ▪ Hypoxemia, hypercapnia (due to mucus plugs blocking air flow) → cyanosis → tissue hypoxia DIAGNOSIS DIAGNOSTIC IMAGING Chest X-ray ▪ Large, horizontal heart, increased bronchial markings LAB RESULTS ▪ ABGs ▫ Respiratory acidosis (arterial PCO2 > 45mmHg, bicarbonate > 30mEq/L) OTHER DIAGNOSTICS ▪ Productive, mucinous cough ▫ At least three months over two consecutive years ▪ PFTs ▫ Increased TLC, air-trapping; decreased FVC1/FVC ratio ▪ Postmortem measurement ▫ Reid index (measure ratio of thickness of bronchial mucinous glands, total thickness of airway, epithelium to cartilage) ▫ > 40% (due to hyperplasia, hypertrophy of glands) TREATMENT MEDICATIONS ▪ Supplemental oxygen, bronchodilators, inhaled steroids, antibiotics ▫ Manage symptoms ▪ Prophylactic vaccination against influenza, Streptococcus pneumoniae (S. pneumoniae) OTHER INTERVENTIONS ▪ Smoking cessation, pulmonary rehabilitation OSMOSIS.ORG 893

CYSTIC FIBROSIS (CF) osms.it/cystic-fibrosis PATHOLOGY & CAUSES ▪ Autosomal-recessive multisystem disorder ▫ Affects lungs, digestive system, reproductive system, sweat glands ▪ Caused by CFTR gene defect (located on long arm of chromosome 7) ▫ Encodes cyclic adenosine monophosphate–regulated chloride channel cystic fibrosis transmembrane conductance regulator (CFTR) ▫ Various mutations: including lack of protein production; protein trafficking defect, degradation within cellular endoplasmic reticulum, Golgi body ▪ Genetic defect → impaired sodium, chloride transport across epithelial cell surface → thick, tenacious secretions ▫ Classic triad: ↑ sweat chloride levels, chronic sinopulmonary disease, pancreatic insufficiency ▪ Bronchi effects ▫ Goblet cell hyperplasia, submucosal gland hypertrophy → production of viscous mucus, mucus plugging → airway inflammation → elastase released from neutrophils → tissue destruction → ↑ thickness of airway walls, bronchiectatic cysts, ventilationperfusion mismatch → hypoxemia RISK FACTORS ▪ Family CF history; especially carrier parents ▪ ↑ incidence in white people of Northern, Central European descent COMPLICATIONS ▪ Chronic respiratory tract infections ▫ Common bacteria: Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae (especially younger children) ▫ Invasive fungal disease may occur → allergic bronchopulmonary aspergillosis 894 OSMOSIS.ORG (ABPA) ▪ Sinusitis ▫ Related to chronic inflammation ▪ Significant hemoptysis ▫ Related to enlarged, tortuous bronchial arteries ▪ Bronchiectasis ▫ Due to mucus plugging ▪ Pneumothorax ▫ Related to ruptured emphysematous bullae ▪ Secondary pulmonary hypertension ▫ Related to small pulmonary artery hypertrophy ▪ Nasal polyps ▫ Related to chronic inflammation ▪ Respiratory failure ▪ Non-pulmonary complications ▫ Cirrhosis; gallstones; pancreatitis; heat exhaustion, dehydration; hypochloremic alkalosis (excessive salt-loss in sweat); rectal prolapse; infertility (azoospermia); fat-soluble vitamin deficiency; anemia; nail clubbing SIGNS & SYMPTOMS ▪ Highly variable presentation ▫ Related to specific mutation, gene penetrance, environmental factors ▪ Specific pulmonary manifestations ▫ Chronic, productive cough; dyspnea; ↑ anterior-posterior chest diameter; digital clubbing; basilar crackle; expiratory wheeze; generalized hyperresonance

Chapter 126 Obstructive Lung Disease DIAGNOSIS DIAGNOSTIC IMAGING Prenatal ultrasound ▪ May detect hyperechogenic bowel, meconium peritonitis Chest X-ray ▪ Hyperinflation, air trapping, atelectasis, flattened diaphragm, peribronchial thickening, bronchovascular markings, peribronchial cuffing, parallel lines (related thickened bronchial walls—”tram tracks”) CT scan ▪ Inspissated bronchial secretions; detects degree of bronchiectasis LAB RESULTS ▪ Genetic testing ▪ CFTR mutation identification ▪ Sweat chloride test ▫ ↑ sweat chloride concentration ▫ Pilocarpine administered → stimulate sweat; collected, analyzed for chloride content Figure 126.6 A plain chest radiograph demonstrating tram-track opacities and ring shadows in an individual with cystic fibrosis. They are particularly well demonstrated in the left upper zone. OTHER DIAGNOSTICS ▪ Newborn screening ▫ Detects CF in neonatal period; initiate early intervention ▪ Pulmonary function tests ▫ ↓ FEV1 FEV1/FVC ▫ ↑ residual volume to total lung capacity (RV/TLC) ratio ▫ ↓ total lung capacity ▫ ↓ vital capacity TREATMENT MEDICATIONS Figure 126.7 A CT scan of the chest in the coronal plane demonstrating bilateral widespread bronchiectasis in a twenty five year old female with cystic fibrosis. ▪ CFTR modulators ▪ Medications to clear respiratory secretions; inhaled hypertonic saline ▪ Anti-inflammatory medications (e.g. glucocorticoids) ▪ Antibiotics ▫ Infections ▪ Bronchodilators ▫ ↓ airflow obstruction ▪ Prevention ▫ Annual influenza vaccine; pneumococcal vaccine OSMOSIS.ORG 895

SURGERY ▪ Lung transplantation ▪ Respiratory support ▫ Respiratory failure → invasive ventilation OTHER INTERVENTIONS ▪ Address complications ▪ Chest physiotherapy ▫ Mobilize retained secretions ▪ Respiratory support ▫ Supplemental oxygen ▫ Positive-pressure ventilation EMPHYSEMA osms.it/emphysema PATHOLOGY & CAUSES ▪ COPD subset ▫ Exposure to irritants → degrades elastin in alveoli, airways → air-trapping, poor gas exchange. ▪ Irritants (e.g. cigarette smoke) → attraction of inflammatory cells → release leukotrienes, chemical mediators (e.g. B4; IL8; TNF alpha/proteases, elastases/ collagenases) → destroy collagen, elastin → lose elasticity → low pressure during expiration pulls walls of alveoli inward → collapse → air-trapping distal to collapse → septa breaks down → neighboring alveoli coalesce into larger air spaces → decreased surface area available for gas exchange ▫ Loss of elastin → lungs more compliant (lungs expand, hold air) ▫ Alveolar air sacs permanently enlarge, lose elasticity → exhaling difficult TYPES Centriacinar/centrilobular emphysema ▪ Most common ▪ Damage to central/proximal alveoli of acinus sparing distal alveoli ▫ Individuals who smoke (irritants can’t reach distal alveoli); upper lobes of lungs Panacinar emphysema ▪ Entire acinus uniformly affected ▫ A1AT deficiency; lower lobes of lungs 896 OSMOSIS.ORG Paraseptal emphysema ▪ Distal alveoli most affected ▫ Lung tissue on periphery of lobules near interlobular septa ▫ Ballooned alveoli on lung surface rupture → pneumothorax CAUSES ▪ Smoking, A1AT deficiency COMPLICATIONS ▪ Hypoxic vasoconstriction → cor pulmonale ▫ Poor gas exchange → vessels vasoconstrict to shunt blood to better gas exchange → pulmonary hypertension → increased workload for right heart → right ventricular hypertrophy → cor pulmonale ▪ Hypoxemia ▪ Pneumothorax SIGNS & SYMPTOMS ▪ Barrel chest (air-trapping, hyperinflation of lungs), apparent respiratory distress with use of accessory muscles, tripod positioning, weight loss, exhaling slowly through pursed lips (“pink puffers”), hyperventilation ▪ Pursing lips increases pressure in airway → keeps airway from collapsing → weight loss ▪ Dyspnea, cough (with less sputum)

Chapter 126 Obstructive Lung Disease DIAGNOSIS DIAGNOSTIC IMAGING Chest X-ray ▪ Increased anterior-posterior diameter, flattened diameter, increased lung field lucency (air-trapping) OTHER DIAGNOSTICS ▪ Increased TLC ▪ FVC decreased (esp. FEV1) TREATMENT MEDICATIONS ▪ Bronchodilators ▪ Inhaled steroids ▪ Combination inhalers ▫ Bronchodilators + inhaled steroids ▪ Oral steroids ▫ Adverse effects: oral candidiasis, weight gain, diabetes, osteoporosis ▪ Antibiotics (e.g. azithromycin prevents exacerbations) ▪ Supplemental oxygen Figure 126.8 The gross pathological appearance of emphysema. There are numerous dilated airspaces in a peripheral distribution. SURGERY ▪ Lung volume reduction ▫ Removal of areas of damaged lung tissue to create extra space in chest cavity for healthy lung tissue to expand ▫ Can improve quality of life and prolong survival ▪ Lung transplant ▪ Bullectomy ▫ Removal of bullae (large air spaces) to improve air flow OTHER INTERVENTIONS ▪ Pulmonary rehabilitation program ▫ Customized education plan consisting of exercising training, nutrition advice, and lifestyle counseling Figure 126.9 The histological appearance of emphysema There are numerous hyperexpanded alveoli. OSMOSIS.ORG 897

MNEMONIC: P vs. B Emphysema vs. Bronchitis EmPhysema: Pink Puffer Chronic Bronchitis: Blue Bloater 898 OSMOSIS.ORG