Diseases of the Lungs

1. Obstructive Lung Diseases

Chronic Obstructive Pulmonary Disease (COPD)

• Major risk factor: Cigarette smoking
• Typically progressive, may lead to cor pulmonale (right-sided heart failure)
• Characterized by functional outflow obstruction due to loss of elastic tissue in alveolar walls

• Enlargement of air spaces distal to terminal bronchioles caused by destruction of elastic support structures by proteases (especially from neutrophils)
• Subtypes:
  • Centriacinar - most common; smoking-related
  • Panacinar - seen in alpha-1 antitrypsin (AAT) deficiency
• Clinical features: increased chest volume, dyspnea, relatively normal blood oxygenation at rest
• AAT serum normal range: 100-190 mg/dL; PIZZ genotype causes loss of up to 90% of serum AAT

• Defined as persistent productive cough for at least 3 consecutive months in at least 2 consecutive years
• Mucus production from hyperplasia of tracheal and large airway mucous glands
• Airway obstruction from small airway inflammation (chronic bronchiolitis)
• Histology: enlarged mucus-secreting glands, goblet cell metaplasia, inflammation, bronchiolar wall fibrosis
• Patients develop hypoxemia and hypercapnia

Asthma

• Characterized by reversible bronchoconstriction caused by airway hyperresponsiveness
• Atopic asthma: Th2 and IgE-mediated immunologic reaction to environmental allergens
  • Early-phase reaction: mast cell degranulation
  • Late-phase reaction: inflammatory cells and cytokines
  • Key cytokines: IL-4, IL-5, IL-13
• Nonatopic asthma: Triggered by viral infections, pollutants, cold, exercise
• Eosinophils are key inflammatory cells in nearly all subtypes
• Airway remodeling (subbasement membrane thickening, smooth muscle hypertrophy) may add an irreversible component

Cystic Fibrosis (CF)

• Genetic obstructive disease causing mucus retention and airway inflammation
• Chronic productive cough, crackles, and wheezing
• Bronchiectasis detectable on CT in up to 60% by age 3
• Polymicrobial colonization: Staphylococcus aureus, Pseudomonas aeruginosa, Burkholderia spp.
• Exacerbations: increased cough, dyspnea, sputum changes; FEV1 drops >10% from baseline
• Progressive upper lobe bronchiectasis over time
• Also causes pancreatic insufficiency (90% of patients), meconium ileus, fat-soluble vitamin deficiency

2. Restrictive / Interstitial Lung Diseases (ILD)

3. Pneumoconioses (Occupational Lung Diseases)

4. Infectious Lung Diseases

Community-Acquired Pneumonia (CAP)

• May be bacterial (lobar or bronchopneumonia pattern) or viral
• Lobar pneumonia stages: congestion → red hepatization → gray hepatization → resolution
• Common bacterial causes:
  • S. pneumoniae - most common CAP pathogen; lobar pattern
  • H. influenzae / M. catarrhalis - acute exacerbations of COPD
  • S. aureus - after viral respiratory infections
  • K. pneumoniae - debilitated/malnourished patients
  • P. aeruginosa - cystic fibrosis, burns, neutropenia
  • L. pneumophila (Legionella) - especially organ transplant recipients
• Viral pneumonia causes: SARS-CoV-2 (COVID-19), influenza A/B, RSV, human metapneumovirus, parainfluenza, adenovirus
  • Characterized by respiratory distress out of proportion to clinical/radiological signs; inflammation confined to alveolar septa

Tuberculosis (TB)

• Chronic granulomatous disease caused by Mycobacterium tuberculosis
• Hallmark: Caseating (caseous necrosis) granulomas
• Immunity: Th1 CD4+ T cells are central
• Primary TB: Usually asymptomatic in immunocompetent; subpleural Ghon focus + lymph node involvement
• Secondary (reactivation) TB: Cavitary lesions at lung apices; occurs when immunity is compromised
• Miliary TB: Life-threatening disseminated form seen in immunodeficiency (e.g., HIV)
• Acid-fast staining (Ziehl-Neelsen / auramine-O fluorochrome) used for diagnosis

5. Vascular Lung Diseases

Pulmonary Embolism (PE)

• Most pulmonary artery thrombi are embolic, usually from deep lower leg veins
• Risk factors: prolonged bed rest, hip/knee surgery, severe trauma, heart failure, oral contraceptives, disseminated cancer, hypercoagulable states (e.g., Factor V Leiden)
• Clinical spectrum:
  • 60-80%: clinically silent
  • 15-35%: hypoxemia, dyspnea, pleuritic chest pain, possible infarction
  • 5%: acute right-sided heart failure, shock, sudden death
• Risk of recurrence is generally high

6. Lung Cancer (Primary Pulmonary Malignancy)

• All types commonly cause paraneoplastic syndromes
• High mutation burden from tobacco carcinogens makes lung cancers responsive to immune checkpoint inhibitor therapy (PD-L1 targeting)
• PD-L1 immunohistochemistry is used to predict response to checkpoint inhibitors

Summary Classification Table