Obstructive Lung Diseases Quiz

Obstructive Lung Disease

• Obstructive lung diseases are characterized by air trapping, slow airflow out, and decreased airflow out
• Reduced FEV1 is a key indicator of slow airflow out
• Reduced FVC indicates less air is able to flow out
• Reduced FEV1/FVC is a hallmark of obstructive lung disease

Residual & Total Lung Volume

• Residual and total lung volume increase in obstructive lung diseases, caused by trapped air
• They decrease in restrictive lung diseases because less air fills the lungs due to restriction

Obstructive Lung Diseases - Examples

• Chronic bronchitis
• Emphysema
• Asthma
• Bronchiectasis

Chronic Bronchitis

• Persistent cough, productive of sputum
• At least three months over two years
• No other cause of cough
• Strongly associated with smoking

Chronic Bronchitis - Other Details

• Hypertrophy of mucous secreting glands
• Reid Index: >50% in chronic bronchitis
• Mucous plugging of lungs
• Increased risk of lung infections
• Poor ventilation of lungs
• Increased CO2
• Decreased O2
• Hypoxic vasoconstriction
• Pulmonary hypertension
• Right heart failure (cor pulmonale)
• Cough
• Wheezing
• Crackles
• Dyspnea
• Cyanosis (shunting)

Emphysema

• Smokers' lung disease
• Too many proteases created
• Upper lung damage, lower lung damage
• Alpha 1-antitrypsin deficiency
• Ineffective anti-proteases
• Destruction of alveoli
• Smoke activates macrophages
• Recruitment of neutrophils
• Release of proteases
• Loss of elastic recoil
• Small airways collapse on exhalation
• Air trapped in lungs
• Dyspnea (less sputum than chronic bronchitis)
• Hyperventilation
• Weight loss
• Cor pulmonale
• Barrel Chest

Acinus

• Acinus = bronchiole + alveoli
• Smokers = centriacinar damage
• Alpha 1-antitrypsin deficiency = panacinar

Asthma

• Reversible bronchoconstriction, usually due to allergic stimulus (type I hypersensitivity)
• Airways are hyperresponsive
• Commonly seen in children
• Associated with other atopic conditions (e.g., rhinitis, eczema)
• May have family history of allergic reactions

Asthma Triggers

• Upper respiratory infections (URIs)
• Allergens (animal dander, dust mites, mold, pollen)
• Stress
• Exercise
• Cold
• Aspirin

Aspirin Exacerbated Respiratory Disease (AERD)

• Asthma, chronic rhinosinusitis, nasal polyposis
• Chronic asthma/rhinosinusitis symptoms
• Acute exacerbations after ingestion of aspirin or NSAIDs
• Dysregulation of arachidonic acid metabolism
• Overproduction of leukotrienes
• Treatment: Leukotriene receptor antagonists (Montelukast, Zafirlukast)

Asthma Symptoms

• Episodic symptoms (dyspnea, wheezing, cough)
• Hypoxia during episodes
• Decreased I/E ratio
• Reduced peak flow
• Mucous plugging (airway obstruction/shunt)
• Death: Status asthmaticus

Asthma Diagnosis

• Usually classic history/physical exam
• Muscarinic challenge with methacholine
• Administer increasing amounts of nebulized drug
• Spirometry after each dose
• Look for dose at which FEV1 falls significantly
• If dose is low —> positive test

Asthma Pathology

• Recurrent episodes
• Smooth muscle hypertrophy
• Inflammation
• Classic sputum findings include Curschmann's spirals and Charcot-Leyden crystals

Pulsus Paradoxus

• Most frequent non-cardiac causes are asthma/COPD

Bronchiectasis

• Result of chronic, recurrent airway inflammation
• Airways permanently dilated
• Obstruction: large airways dilated, small/medium airways thickened bronchial walls
• Recurrent infections
• Cough, excessive sputum (foul smelling)
• Hemoptysis
• Cor pulmonale
• Amyloidosis
• Etiologies include obstruction (tumor), smoking, cystic fibrosis, Kartagener's syndrome, allergic bronchopulmonary aspergillosis

Primary Ciliary Dyskinesia

• Cilia unable to beat, beat normally, or absent
• Inherited (autosomal recessive)
• Gene mutations dynein structure/formation
• Dynein = motor protein creates movement
• Clinical features include chronic sinusitis, bronchiectasis, male infertility, and situs inversus

Kartagener's Syndrome

• Chronic sinusitis
• Bronchiectasis (chronic cough, recurrent infections)
• Male infertility
• Situs inversus

Allergic Bronchopulmonary Aspergillosis (ABPA)

• Hypersensitivity (allergic) reaction to Aspergillus fumigatus
• Lungs colonize with fungus
• Low virulence fungus
• Only infects immunocompromised or debilitated lungs
• Occurs predominantly in asthma and cystic fibrosis (CF) patients
• ABPA patients demonstrate Increased Th2 CD4+ cells, synthesis of interleukins, eosinophilia, and IgE antibody production

Obstructive/Restrictive Lung Disease Summary

• Obstructive lung disease: increased RV/FRC/TLC; decreased FEV1/FVC
• Restrictive lung disease: decreased RV/FRC/TLC; normal or increased FEV1/FVC

Restrictive Lung Disease

• Key points: difficulty getting air in → less air out
• Reduced FVC
• Reduced FEV1
• Normal (>=80%) FEV1/FVC is hallmark

Restrictive Lung Disease - Causes

• #1 Poor breathing mechanics
• #2 Interstitial lung diseases

Poor Breathing Mechanics

• Not a primary lung issue
• Under-ventilation of lungs
• Alveoli working normally (normal A-a gradient)
• Neuromuscular conditions (ALS, Polio, myasthenia gravis)
• Structural causes (scoliosis, morbid obesity)

Interstitial Lung Disease

• Bilateral, diffuse pattern
• Small, irregular opacities (reticular or nodular)
• "Honeycomb" lung appearance

Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO)

• Measures the ability of the lungs to transfer gas to RBCs
• Patient inhales a small amount of carbon monoxide
• CO uptake is diffusion limited
• Machine measures CO exhaled from the lungs
• Normal range: 75-140% predicted
• Severe disease: <40% predicted

Low DLCO Conditions

• Interstitial lung disease
• Emphysema
• Abnormal lung vasculature
• Pulmonary hypertension
• Pulmonary embolism
• Prior lung resection
• Anemia

Interstitial Diseases - Examples

• Idiopathic pulmonary fibrosis
• Systemic diseases with interstitial lung features
• Scleroderma
• Rheumatoid arthritis
• Goodpasture's syndrome
• Wegener's granulomatosis
• Sarcoidosis
• Pneumoconiosis
• Drug toxicity (amiodarone, methotrexate)
• Hypersensitivity pneumonitis

Idiopathic Pulmonary Fibrosis

• Most common type of idiopathic interstitial pneumonia
• Slow onset dyspnea
• Typically affects adults over 40

Pneumoconiosis

• Coal miner's lung
• Silicosis
• Asbestosis

Coal Miner's Lung

• Inhalation of coal dust particles
• Small, rounded, nodular opacities on CXR
• Preference for the upper lobes

Silicosis

• Inhalation of silica (quartz, granite, or sandstone)
• Most widespread pneumoconiosis in US
• Common in foundries, sandblasting, and mines
• Macrophages react to silica, resulting in inflammation, fibroblasts, and collagen
• High prevalence of tuberculosis
• High prevalence of bronchogenic carcinoma

Silicosis - X-ray Findings

• Affects the upper lobes
• Eggshell calcifications of lymph nodes

Asbestosis

• Inhalation of asbestos fibers
• Classically affects lower lobes
• Interstitial lung disease (asbestosis)
• Pleural plaques
• Lung cancer

Asbestosis - Details

• CXR: calcified pleural plaques are pathognomonic
• Pathological examination: asbestos bodies (ferruginous bodies) - asbestos fibers surrounded by a coating of iron and protein
• Bronchogenic carcinoma
• Mesothelioma (Asbestos is the only known risk factor for mesothelioma)
• Occurs decades after exposure
• Slow onset symptoms (dyspnea, cough, chest pain)
• Poor prognosis

Drug Toxicity Examples

• Bleomycin
• Busulfan
• Amiodarone
• Methotrexate

Hypersensitivity Pneumonitis

• Hypersensitivity reaction to environmental antigen (agricultural dusts, microorganisms, chemicals)
• Mixed type III/IV hypersensitivity
• Classic case is farmer's lung
• Also common in bird/poultry handlers

Hypersensitivity Pneumonitis - Further Details

• Classic presentation in farmer/bird handler: cough, dyspnea, and chest tightness, often with diffuse crackles
• Diagnosis: bronchoalveolar lavage, inhalation challenge, and lung biopsy
• Treatment: avoidance of exposure and steroids

COPD & Asthma Treatment

• Short-acting bronchodilators: albuterol, ipratropium
• Long-acting bronchodilators: salmeterol, formoterol, tiotropium
• Steroids: inhaled (beclomethasone, fluticasone, budesonide), oral (prednisone), intravenous (methylprednisolone)
• Special asthma drugs: leukotriene receptor antagonists (Montelukast, Zileuton), omalizumab, theophylline
• Special COPD drugs: roflumilast

Acute COPD Exacerbation Treatment

• Oxygen
• Nebulized albuterol +/- ipratropium
• IV or oral corticosteroids
• Methylprednisolone 80mg IV q8hrs
• Antibiotics (severe cases/hospitalized patients) (e.g., fluoroquinolones, amoxicillin/clavulanate)

GOLD Criteria

• Classification system for COPD severity based on FEV1
• Mild (FEV1 >80%), Moderate (FEV1 50-79%), Severe (FEV1 30-49%), Very Severe(FEV1 <30%)
• Treatment varies according to GOLD stage

Chronic COPD Treatment

• Mild (FEV1 >80%): As needed short-acting bronchodilators
• Moderate (50-79%): Add long-acting bronchodilator
• Severe (30-49%): Add inhaled corticosteroids
• Very Severe ( <30%): Oxygen, possible surgery

Surgical COPD Treatment

• Lung volume reduction surgery/bullectomy
• Lung transplant

Pneumonia

• Infection of the lungs
• Three patterns:
• Lobar pneumonia
• Bronchopneumonia
• Interstitial pneumonia (atypical pneumonia)

Lobar Pneumonia

• Classic form of pneumonia (S. pneumoniae)
• Bacteria (often acquired in the nasopharynx and aerosolized) invade alveolar type II cells
• Rapid spread from one alveolus to another.
• Inflammation/consolidation of lung lobes.
• Can involve the entire lung.
• Four stages:

1. Congestion: Fluid exudate of bacteria (1-24 hours)
2. Red hepatization: fluid exudate containing RBCs and WBCs(2-3 hours)
3. Gray hepatization: fluid exudate containing more neutrophils and fibrin(4-6 days)
4. Resolution: restoration to normal (little scarring)

Bronchopneumonia

• Patchy inflammation of multiple lobules
• Primarily affects the airways and surrounding tissues
• Staphylococcus aureus is a common cause

Interstitial Pneumonia (Atypical Pneumonia)

• Inflammatory infiltrate of alveolar walls only
• More indolent course
• Common causes include viruses (e.g. respiratory syncytial virus RSV ,Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumonia)
• Milder than strep pneumonia
• Respiratory distress is rare
• Interstitial infiltrates on chest x-ray

Pneumonia - Causes (Children)

• Neonates (<4 weeks): Group B strep, E. coli
• Children (4 weeks to 18 years): Viruses (e.g., RSV ), Mycoplasma pneumoniae, Chlamydia pneumoniae, Streptococcus pneumoniae

Pneumonia - Causes (Adults)

• Streptococcus pneumoniae (most common)
• Haemophilus influenzae
• Mycoplasma pneumoniae
• Chlamydia pneumoniae
• Legionella
• Gram-negative rods (e.g., Klebsiella, E. coli, Pseudomonas)
• Staphylococcus aureus
• Anaerobes
• Viruses (e.g., influenza, RSV)

Pneumonia - Signs/Symptoms

• High fever
• Cough
• Sputum production
• Elevated white blood cell count (WBC)
• Pleuritic chest pain

Pneumonia - Diagnosis

• History and physical exam
• Chest X-ray (sometimes CT)
• Sputum culture
• Bronchoalveolar lavage

Pneumonia - Clinical Classes

• Community-acquired pneumonia (CAP): Usually Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus; sometimes mycoplasma, chlamydia, or legionella (Uncomplicated/complications)
• Nosocomial pneumonia: Often gram-negative rods (e.g., Klebsiella, E. coli, Pseudomonas), Staphylococcus aureus (including MRSA), Anaerobes (aspiration PNA; lung abscess); sometimes multidrug combinations
• Hospital-acquired pneumonia (HAP): Usually Gram-negative rods, Staphylococcus aureus, and sometimes other organisms
• Ventilator-associated pneumonia (VAP): Usually gram-negative rods, and sometimes other organisms
• Healthcare-associated pneumonia (HCAP): Usually various organisms

Pneumonia - Community Acquired PNA (Uncomplicated)

• No co-morbidities
• No recent antibiotic use
• Low community resistance rates
• Three to five day course of azithromycin, clarithromycin, or doxycycline
• Patient should be afebrile 48-72 hours and clinically stable

Pneumonia - Community Acquired PNA (Complicated)

• COPD, CKD, Diabetes, CHF, Alcoholism
• Past antibiotic use
• Levofloxacin
• Amoxicillin plus azithromycin

Complications

• Sepsis
• Respiratory failure
• Lung abscesses
• Pleural effusion
• Acute respiratory distress syndrome (ARDS)

ARDS (Acute Respiratory Distress Syndrome)

• Triggered by various lung injuries
• Injury leads to release of pro-inflammatory cytokines (TNF, interleukins)
• Cytokines recruit neutrophils to the lungs
• Neutrophils release reactive oxygen species and proteases, damaging capillary endothelium and alveolar epithelium
• Protein leaks from vascular space, fluid pours into interstitium

ARDS - Triggers

• Sepsis
• Pneumonia
• Aspiration
• Trauma
• Acute pancreatitis
• Transfusion-related acute lung injury (TRALI)

ARDS Treatment

• Mechanical ventilation
• Low tidal volume
• Supportive care (fluids, nutrition)

Legionella

• First identified at American Legion convention
• Infection from inhalation of aerosolized bacteria (not airborne)
• Outbreaks at hotels with contaminated water
• Causes nosocomial pneumonia
• Initially mild pneumonia symptoms, may progress to severe pneumonia

Legionella - Symptoms

• Mild cough, fever, malaise
• Progress to severe pneumonia
• Gastrointestinal symptoms (e.g., watery diarrhea, nausea, vomiting, abdominal pain)
• Hyponatremia is common

Legionella - Diagnosis

• Special culture requirements: buffered charcoal yeast extract agar (BCYE), iron, cysteine, antibiotics, silver dyes
• Urinary antigen test
• Rapid test available in minutes

Legionella - Classic Case

• Mild cough
• Watery diarrhea
• Confusion
• Negative bacteria on gram stain

Pontiac Fever

• Mild form of Legionella infection
• Fever, malaise, chills, fatigue, headache
• No respiratory complaints
• Chest radiograph is usually normal

Mycoplasma Pneumonia

• Atypical pneumonia (no cell wall)
• College dorm outbreaks, military recruits
• Chest X-rays usually worse than symptoms
• Can cause autoimmune hemolytic anemia (IgM antibody against RBC antigen)
• "Cold" hemolytic anemia
• Stevens-Johnson syndrome

Influenza Virus

• Atypical pneumonia, caused by influenza A or B viruses
• Fever, headache, myalgias, non-productive cough
• Major complication is secondary bacterial pneumonia (Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae)
• Worsening symptoms after initial improvement

CMV (Cytomegalovirus)

• Pneumonia in transplant patients on immunosuppressive drugs
• "Owl eye" intranuclear inclusions on microscopy

RSV (Respiratory Syncytial Virus)

• Viral respiratory infection in infants
• Common cause of lower respiratory tract illness in children
• Often seasonal (November - April)
• Bronchiolitis, pneumonia, and acute respiratory failure, often starts with upper airway infection
• Runny nose, followed by cough and wheezing in a few days

RSV - Treatment

• Ribavirin inhibits guanine nucleotides
• Prevention: Palivizumab (monoclonal antibody against F protein)

Aspiration Pneumonia

• Aspiration of microorganisms from the oral cavity/nasopharynx into the lungs
• Risk factors include reduced consciousness (e.g., anesthesia, seizures), alcoholism, dysphagia (or neuromuscular weakness), debilitating illness

Aspiration Pneumonia - Causative Organisms

• Klebsiella
• Staphylococcus aureus
• Anaerobic bacteria (Peptostreptococcus, Fusobacterium, Prevotella, Bacteroides)
• Clindamycin is often first-line therapy

Klebsiella Pneumonia

• Can cause lobar pneumonia.
• Usually from aspiration.
• Marked inflammation/necrosis in lungs.
• Thick, mucoid, and blood-tinged sputum.
• "Currant jelly" sputum

Lung Abscess

• Contained, fluid-filled space in the lungs
• Usually a consequence of aspiration.
• Predominantly anaerobes (Peptostreptococcus, Prevotella, Bacteroides, Fusobacterium).
• Sometimes involves bacterial species like S.aureus, Klebsiella
• Treatment is typically clindamycin

PCP (Pneumocystis Jirovecii)

• Diffuse interstitial pneumonia.
• Typically caused by the fungus Pneumocystis jirovecii.
• Requires immunocompromise(example HIV)
• AIDS-defining illness.
• Yeast is inhaled if immune system is intact
• Usually causes no symptoms if immune system is intact
• Diagnosis by microscopy. Special stains are used.
• Treatment is usually with TMP-SMX, Dapsone, and pentamidine

Pleural Disease

• Two layers of tissue surrounding the lungs:
• Visceral pleura: attached to lungs
• Parietal pleura: attached to chest wall
• Pleural space/cavity: between the layers.
• Mesothelial lining secrets pleural fluid for lubrication
• Different types of etiologies can cause pleural effusion and other diseases.

Pneumothorax

• Air in the pleural space.
• Two types:
• Spontaneous pneumothorax (primary/secondary)
• Tension pneumothorax
  • Primary: rupture of subpleural blebs common in tall, thin young males
  • Secondary: Older patients with underlying pulmonary disease (e.g., COPD)
• Treatment: 100% oxygen; chest tube insertion

Tension Pneumothorax

• Often from trauma
• Air enters the pleural space but can't escape
• Medical emergency
• Emergent thoracentesis/chest tube placement
• Trachea deviates away from affected side

Pleural Effusion

• Accumulation of fluid in the pleural space.
• Three general etiologies:
• Transudative
• Exudative
• Lymphatic

Transudative Effusion

• Something driving fluid into pleural space -- High pressure (e.g., CHF)
• Nephrotic syndrome
• Cirrhosis
• Little protein in effusion
• Treat underlying cause (no drainage)

Exudative Effusion

• Fluid leaking into pleural space -- High vascular permeability
• Many causes (malignancy, pneumonia)
• More protein in pleural fluid compared to transudative effusion
• Usually requires drainage

Transudate vs. Exudate - Light's Criteria

• Thoracentesis to obtain fluid sample and test for protein and LDH
• Exudate is likely if:
• Pleural protein/serum protein > 0.5
• Pleural LDH/serum LDH > 0.6
• Pleural LDH > 2/3 upper limit of normal

Lymphatic Effusions ("Chylothorax")

• Lymphatic fluid effusion from thoracic duct obstruction/injury
• Malignancy most common cause
• Trauma (often surgical)
• Milky-appearing fluid
• Very high triglycerides (TG usually > 110mg/dL)

Other Pleural Effusions

• Hemothorax (high Hct in fluid)
• Empyema (infected pleural fluid, pus, putrid odor; positive culture)
• Malignant effusion (positive cytology)

Mesothelioma

• Pleural tumor
• Asbestos exposure is the only known risk factor
• Imaging: pleural thickening and pleural effusion
• Slow onset symptoms
• Poor prognosis
• Median survival with and without treatment varies

Lung Cancer

• Common cancers include breast, prostate, lung (most deadly), and colorectal
• Risk factors: cigarette smoking (polycyclic aromatic hydrocarbons), radiation therapy, exposure to environmental toxins(asbestos), and radon.

Lung Cancer - Symptoms

• Usually advanced at presentation
• Cough, dyspnea, rarely hemoptysis
• Often leads to imaging

Lung Cancer - Diagnosis

• Pulmonary nodule ("coin lesion") on imaging
• Compare with prior imaging
• Biopsy

Benign Pulmonary Nodules

• Granulomas (80% benign nodules)
• Hamartomas (composed of lung tissue and cartilage)

Granulomas - Causes

• Fungi (e.g., histoplasmosis, coccidioidomycosis)
• Mycobacteria (e.g., tuberculosis)

Lung Cancers - Types

• Small cell lung cancer
• Non-small cell lung cancers (Squamous Cell Carcinoma, Adenocarcinoma, Large Cell Carcinoma, Bronchioloalveolar Carcinoma, Carcinoid tumor)

Small Cell Lung Cancer

• Poorly differentiated small cells
• Classic in male smokers
• Neuroendocrine tumor
• Central tumor
• Poor prognosis -- often metastic at time of diagnosis

Small Cell Lung Cancer - Paraneoplastic Syndromes

• ACTH: Cushing syndrome (progressive obesity, hyperglycemia)
• ADH: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) -- hyponatremia (confusion)
• Antibodies against pre-synaptic Ca channels in neurons (e.g., Lambert-Eaton syndrome) -- main symptom is weakness

Non-Small Cell Lung Cancers

• Squamous cell carcinoma
• Adenocarcinoma
• Large cell carcinoma
• Bronchioloalveolar carcinoma
• Carcinoid tumor

Squamous Cell Carcinoma

• Hilar mass arising from bronchus
• Keratin production ("pearls")
• Intercellular desmosomes ("intercellular bridges")
• Male smokers
• Can produce PTHrP -- hypercalcemia, stones, bones, and groans; psychiatric overtones; bone and abdominal pain; confusion

Adenocarcinoma

• Glandular tumor
• Common in non-smokers/females
• Peripheral

Large Cell Carcinoma

• Poorly differentiated
• Lacks glandular or squamous differentiation
• Lacks small cells
• Smokers' cancer
• Central or peripheral
• Poor prognosis

Bronchioloalveolar Carcinoma

• Subtype of adenocarcinoma
• Non-smokers; peripheral
• Mucinous types: goblet cells, nonmucinous: Clara cells or Type II pneumocytes
• Looks like PNA on CXR
• Lobar consolidation
• Excellent prognosis; surgery, radiotherapy

Carcinoid Tumor

• Neuroendocrine; Well-differentiated cells
• Chromogranin-positive
• Non-smokers
• Rarely causes carcinoid syndrome
• Serotonin secretion (flushing, diarrhea)

Lung Cancer - Complications

• Pleural effusions
• Phrenic nerve compression
• Diaphragm paralysis
• Hemidiaphragm elevation on chest X-ray
• Recurrent laryngeal nerve compression
• Hoarseness
• SVC syndrome(caused by tumor compression)
• Lung masses, mediastinal masses, thrombotic vessels, indwelling catheters, pacemaker wires
• ICP (increased intracranial pressure), headaches, confusion
• Cranial artery rupture
• Metastasis: widespread (adrenal, brain, bone, liver)

Sleep Apnea

• Breath cessation during sleep (usually > 10 seconds)
• Multiple episodes per night are typical
• Symptoms: restless sleep, daytime somnolence, loud snoring
• Types: Central sleep apnea (no effort to breathe), Obstructive sleep apnea (decreased airflow despite effort)

Central Sleep Apnea

• Hypoventilation when awake
• Fall-asleep = apnea periods
• Central nervous system diseases (e.g. encephalitis, polio, ALS)
• Severe kyphoscoliosis
• Narcotics
• Classic breathing pattern is Cheyne-Stokes

Obstructive Sleep Apnea

• Recurrent soft tissue collapse in the pharynx
• Strongest risk factor is obesity

Sleep Apnea Complications

• Hypertension (HTN)
• Pulmonary hypertension
• Arrhythmias
• Sudden death

Erythropoiesis

• Chronic hypoxia stimulates EPO release

Sleep Apnea Diagnosis

• Polysomnography ("sleep study")
• Patient monitored in a controlled setting
• EEG, eye movements, O2 level, heart rate (HR), respiratory rate
• Number of apnea episodes is recorded

Sleep Apnea Treatments

• Weight loss
• Continuous positive airway pressure (CPAP)
• Upper airway surgery

Cystic Fibrosis

• Inherited genetic disease.
• Autosomal recessive pattern.
• Both parents must be carriers.
• Results in thick, sticky mucus in the lungs and GI tract.
• Common cause of chronic lung disease in children

CFTR (Cystic Fibrosis Transmembrane Regulator)

• CFTR protein (abnormal)
• CFTR gene encodes for the abnormal protein
• ATP ion transporter; pumps Cl- out of epithelial cells against concentration gradient.
• Hydrates mucosal surfaces

CFTR Gene Mutations

• Many mutation identified.
• Most common mutation: delta F508 (deletion of 3 DNA bases, codes for the 508th amino acid: phenylalanine)
• Abnormal protein folding & prevents protein trafficking.

CF Pathophysiology (Lung Disease)

• Thick mucus in lungs; Recurrent pulmonary infections
• Chronic bronchitis; Bronchiectasis
• Pseudomonas aeruginosa is a major pathogen in CF.

CF Pathophysiology (GI/Pancreatic)

• Impaired flow of bile and pancreatic secretions
• Malabsorption especially fats; loss of fat-soluble vitamins (A, D, E, K)
• Steatorrhea (frequent, foul-smelling, oily, and greasy stools which may float).

CF Presentation

• Usually diagnosed before age 2.
• Respiratory disease (45%): productive cough, lungs hyperinflated on chest X-ray, chronic bronchitis/bronchiectasis
• Failure to thrive (28%)
• Meconium ileus (20%): first stool of newborn; very thick and sticky
• Other symptoms include biliary disease (bile duct obstruction; pale/clay-colored stools, elevated LFTs; hepatomegaly; cirrhosis; gallstones), infertility (95% of men with CF are infertile), digital clubbing, nasal polyps

CF Diagnosis

• Sweat chloride test
• Pilocarpine iontophoresis
• Chloride content is analyzed from sweat collected on filter paper.
• High chloride level suggests CF
• DNA testing is often done if sweat test is abnormal
• Rare CF patients may have negative sweat tests and usually have milder disease
• Recurrent pulmonary and sinus infections
• Measuring nasal voltage to detect abnormal sodium processing

CF Treatment

• Promote clearance of airway secretions (e.g., inhaled DNase, inhaled saline, N-acetylcysteine)
• Ivacaftor (targets patients with G551D mutation).
• Exacerbations are often treated with antibiotics
• Pancreatic enzyme replacement; Vitamins (A, D, E, and K)
• Lung transplantation in appropriate cases

Tuberculosis (TB)

• Ancient disease, found in mummies.
• Old name: Consumption.
• Tubercle = round nodule; Tuberculosis = multiple round nodules.
• Obligate aerobes; Reactivation disease prefers upper lobes; Infect macrophages

Tuberculosis (TB) - Culture

• Difficult to culture. Requires special media (Lowenstein-Jensen agar)
• Does not stain well with Gram stain, due to mycolic acids in cell wall(acid-fast).

Tuberculosis (TB) - Acid-Fast Staining

• Cell walls impermeable to many dyes
• Stain with very concentrated dyes plus heat.
• Once stained, plate rinsed with acid decolorizer ("acid-fast stain")
• TB resists decolorization with acid solvents; some other bacteria do this (Nocardia).

Tuberculosis (TB) - Virulence Factors

• Trehalose dimycolate ("cord factor"): Helps evade immune response; Causes granuloma formation; Triggers cytokine release
• Sulfatides (glycolipids): Inhibits fusion of phagosomes/lysosomes; Resists host cell oxidation

Tuberculosis (TB) - Spread

• Through aerosols
• Coughing/sneezing of infected person is typically how the infection is spread to other people; in crowded areas, this disease can spread rapidly.

Tuberculosis (TB) - Exposure

• Most patients do not develop active disease.
• Infection can clear or remain "latent." A small proportion of patients develop active disease.

Tuberculosis (TB) - Primary TB

• Mainly a disease of childhood and chemo patients
• Ineffective immune response; gradual onset over weeks
• Fever, cough, pleuritic chest pain, fatigue
• First week: TB infects macrophages, phagocytosed
• Two to four weeks: Cell-mediated immune system controls TB; TH1 response; activation of CD4+ T cells; interferon-y secreted
• Formation of granulomas, macrophages transform to epithelioid cells, Langhan's giant cells, fibrin, collagen deposition
• Ghon foci, hilar lymphadenopathy, Ghon complex, Ranke complex

Tuberculosis (TB) - Primary TB Resolution

• Most patients (90%) control infection
• Self-limited by immune response(fibrosis forms).
• Some enter a latent phase ("walled off")
• PPD positive
• Rare cases (10%): miliary spread

Tuberculosis (TB) - Miliary TB

• Hematogenous spread of TB
• Progressive primary infection or reactivation
• Nearly any organ system can be involved (bones, liver, CNS, heart, skin, etc.)
• Potts disease (spine infection; back pain, fever, night sweats)
• Constrictive pericarditis

Tuberculosis (TB) - Reactivation TB

• Reactivation of dormant TB
• Cough, weight loss, fatigue, fever, night sweats
• Chest pain, often with cavitation (caseous and liquefective necrosis)
• Hemoptysis (erode pulmonary vasculature)
• CXR classically shows upper lobe lesions
• Can occur when immune compromise develops (e.g., HIV infection, TNF-α inhibitors used in autoimmune diseases, diabetes)

Aspergilloma

• Fungus ball, caused by Aspergillus fumigatus
• Non-invasive form of aspergillosis
• Grows in preformed cavities (often in patients with TB, lung cancer, or other lung diseases)
• Often asymptomatic; can cause hemoptysis
• Diagnosis: imaging plus sputum culture
• Treatment: observation vs. surgery.

Diagnosis of Active TB

• Usual method: 3 sputum samples (often 8 hours apart)
• Spontaneous or induced sputum collection (e.g., inhalation of aerosolized saline by nebulizer)
• Acid-fast smear and culture

Diagnosis - Active TB - Hospitalization

• Not necessary to hospitalize just for suspected TB infection in all cases
• Outpatients: Remain at home, avoid visitors, mask
• Inpatients: Respiratory isolation in a private room (negative air pressure); persons entering must wear a respirator; tight seal over nose and mouth

Diagnosis of Latent TB

• Identification of latent TB crucial to infection control
• Diagnosis: tuberculin skin testing (TST)
• SC injection of purified protein derivative (PPD)
• 5 tuberculin units (0.1 ml)
• Measure diameter of induration (not erythema) after 48 hours

PPD (Purified Protein Derivative) Testing

• Induration <5mm = Negative, >5mm = positive if HIV/Immunocompromised
• Induration >10mm = Positive High risk individuals (e.g., silicosis, CKD, DM, IV drug users, homeless, prison employees, others)
• Induration >15mm = Positive Healthy patients older than 4 years

PPD - False Negatives

• Immunosuppressive drugs (e.g., corticosteroids, TNF-α inhibitors)
• Immunocompromised (e.g., HIV infection, CKD, malnutrition)
• Diseased lymph system; Sarcoidosis; Some Lymphomas and Leukemias

BCG Vaccine

• Bacille Calmette-Guérin (BCG)
• Live strain of Mycobacterium bovis: effective in children exposed to TB

Treatment of Latent TB

• Most patients with latent TB will not develop active disease.
• Prophylaxis with Isoniazid (INH) for 9 months reduces risk of reactivation.
• Further PPD testing is not typically indicated; pt will remain PPD positive for life

Treatment of Active TB

• Requires multidrug regimens, often for 6-9 months

• Common regimen includes Isoniazid, Rifampin, Pyrazinamide, Ethambutol (sometimes Streptomycin)

• Requires sometimes direct observation therapy (DOT)

• Risks of multidrug-resistant (MDR) TB.

• Isoniazid (INH) Mechanism

• Blocks mycolic acid synthesis.

• Bacteria lose their acid fastness.

• Converted INH to the active form by katG-encoded catalase-peroxidase.

• Mutations in katG gene lead to INH resistance. Monotherapy produces resistance

Isoniazid (INH) Side Effects

• Neurotoxic (e.g., neuropathy, ataxia, paresthesia)
• Pyridoxine (vitamin B6) is often co-administered to prevent this side effect.
• Hepatotoxic (check liver function tests – LFTs)
• Drug-induced lupus

Rifampin Mechanism

• Inhibits bacterial RNA polymerase.
• Blocks RNA synthesis.
• Side effects: liver, GI upset, & discoloration of bodily fluids (red/orange).

Rifampin - Other Uses

• Leprosy prophylaxis
• Meningococcal prophylaxis
• Chemoprophylaxis in contacts of children with Hib (hemophilus influenzae B)

Pyrazinamide - Mechanism

• Unknown mechanism.
• May be active in acidic environment inside macrophages.
• Can increase liver function tests - LFTs.
• Competes with urate for renal excretion (can raise uric acid levels -- hyperuricemia; gout exacerbations)

Ethambutol

• Inhibits arabinosyl transferase
• Polymerizes arabinose (a component of mycobacterial cell walls)
• Side effects: optic neuropathy (red-green color blindness)
• Reversible

Streptomycin

• Older aminoglycoside drug
• Inhibits bacterial 30S ribosomal subunit. Prevents protein synthesis.
• Lots of resistance; mutations of ribosomal protein genes

Sarcoidosis

• Granulomatous disease, granulomas form in many parts of the body
• Immune-mediated, possibly with immune cells playing a major role
• Unknown cause
• Hallmark: widespread non-caseating granulomas, tightly packed central area of macrophages, epithelioid cells, and multinucleated giant cells surrounded by lymphocytes, monocytes, mast cells, and fibroblasts, and high CD4:CD8 helper T-cell ratio.

Sarcoidosis - Pathology

• Cell-mediated immune process
• Accumulation of TH1 CD4+ helper T cells.
• Secrete IL-2 and interferon-γ
• IL-2 stimulates TH1 proliferation.
• IFN-γ activates macrophages; Granuloma formation
• Key players include CD4 T cells, IL-2, and IFN-γ

Sarcoidosis - Organ Involvement

• Lungs (most common)
• Skin
• Heart (conduction disease, cardiomyopathy)
• Many other systems rarely involved (kidneys (renal failure), CNS (neurosarcoidosis, Bell's palsy, motor loss))

Sarcoidosis - Lung Involvement

• Classic finding is hilar lymphadenopathy.
• Cough and dyspnea are common symptoms.
• Can cause lung infiltrates and pulmonary fibrosis

Sarcoidosis - Skin Involvement

• Many lesions possible (plaques, maculopapules, subcutaneous nodules).
• Classic lesion: erythema nodosum (tender red nodules on shins).

Sarcoidosis - Eye Involvement

• Can involve many eye structures, but uveitis is the classic presentation.
• Uvea: Iris, ciliary body, choroid
• Anterior uveitis; Posterior uveitis.
• Often associated with mild symptoms (dry eye, blurry vision).
• Can be detected on routine examination.

Sarcoidosis - Other Features

• Hypercalcemia (elevated 1-alpha hydroxylase activity in alveolar macrophages;

Test your knowledge on obstructive lung diseases, including key measurements, symptoms, and specific conditions associated with these disorders. This quiz covers topics ranging from chronic bronchitis to cystic fibrosis and sleep apnea. Challenge yourself to determine what defines these diseases and their implications.