Comprehensive Pulmonary Disorders Study Guide (copy)

DISORDERS OF THE AIRWAYS

• Airway disorders are categorized into upper airway disorders (above and including the vocal folds) and lower airway disorders.

Disorders of the Upper Airways

• Acute Obstruction:

  • Demands immediate relief to prevent fatal asphyxia.

  • Etiologies: Laryngeal or pharyngeal trauma, foreign body aspiration, laryngospasm, laryngeal edema or angioedema, acute allergic laryngitis, and acute infections (acute epiglottitis, Ludwig angina, pharyngeal or retropharyngeal abscess).

• Chronic Obstruction:

  • Etiologies: Goiter, pharyngeal or laryngeal carcinoma, laryngeal or subglottic stenosis, laryngeal granulomas or webs, bilateral vocal fold paralysis, and laryngomalacia (supraglottic structure collapse during inspiration).

  • Laryngeal or subglottic stenosis frequently manifests weeks to months following endotracheal intubation.

  • Clinical Findings: Inspiratory stridor, intercostal retractions on inspiration, a palpable inspiratory thrill over the larynx, and localized wheezing over the neck or trachea on auscultation.

  • Diagnostic Evaluation: Flow-volume loops indicate characteristic flow limitations; soft-tissue neck radiographs display supraglottic or subglottic narrowing; CT and MRI specify exact anatomic sites; flexible endoscopy provides diagnostic visualization (caution is required to avoid exacerbating airway edema).

• Vocal Fold Dysfunction (Inducible Laryngeal Obstruction [ILO]):

  • Definition: Transient, reversible laryngeal narrowing caused by paradoxical vocal fold adduction during inspiration, expiration, or both.

  • Clinical Presentation: Dyspnea and wheezing mimicking asthma or exercise-induced asthma.

  • Key Differentiators from Asthma: Absence of response to bronchodilators, normal spirometry immediately following an attack, flow-volume loop evidence of upper airway obstruction, and a negative bronchial provocation test.

  • Co-conditions and Triggers: Can coexist with asthma; triggered by exercise (exercise-induced laryngeal obstruction), inhalational irritants (smoke, fumes, cleaning chemicals), laryngopharyngeal reflux, or psychogenic stress.

  • Definitive Diagnosis: Direct endoscopic visualization of vocal fold adduction during inspiration.

  • Acute Management: Patient reassurance, supportive care, continuous positive airway pressure (CPAP), or helium-oxygen mixture (heliox).

  • Long-Term Prevention: Avoidance of precipitants, speech therapy, and botulinum toxin injections for refractory cases involving bilateral vocal fold hypomobility, laryngeal dystonia, or ILO.

Disorders of the Lower Airways

• Tracheal Obstruction:

  • Anatomic Classification: Intrathoracic (below the suprasternal notch) or extrathoracic.

  • Fixed Tracheal Obstruction Causes: Acquired or congenital tracheal stenosis, primary or secondary tracheal neoplasms, extrinsic compression (lung, thymus, or thyroid tumors; lymphadenopathy; congenital vascular rings; aneurysms), foreign body aspiration, tracheal granulomas or papillomas, tracheal trauma, and idiopathic subglottic stenosis.

  • Variable/Dynamic Tracheal Obstruction Causes: Tracheomalacia, foreign body aspiration, and retained secretions.

• Acquired Tracheal Stenosis:

  • Etiology: Primarily secondary to prior tracheotomy or endotracheal intubation.

  • Preventive Interventions: Daily endotracheal tube (ETT) care, continuous monitoring of cuff pressure (target range: $20-30\,\text{cm H}_2\text{O}$) to avoid mucosal ischemic injury, oral and endotracheal suctioning, and regular ETT rotation.

  • Symptom Onset: Weeks to months following decannulation or extubation.

  • Clinical Features: Dyspnea, dysphonia, dysphagia, cough, and inability to clear secretions. Physical findings (wheezing, palpable tracheal thrill, harsh breath sounds) typically remain absent until tracheal diameter is reduced by $\ge 50\%$.

  • Diagnostic Confirmation: Tracheal CT, pulmonary function testing (PFT) with flow-volume loops, or bronchoscopy.

  • Management Options: Balloon dilation, surgical resection with end-to-end reconstruction, airway stenting, laser therapy, or tracheostomy for refractory disease.

• Bronchial Obstruction:

  • Causes: Retained pulmonary secretions, aspiration, foreign bodies, bronchomalacia, bronchogenic carcinoma, extrinsic mass compression, and endobronchial metastatic tumors.

  • Manifestations: Dyspnea, cough, localized wheezing, fever, and chills (when postobstructive infection is present).

  • Clinical Suspicion Indicators: Recurrent pneumonia involving the same lobar or segmental distribution, or delayed radiographic resolution of pneumonia (> 3\,\text{months}).

  • Radiographic Findings: Localized atelectasis, postobstructive infiltrates, and localized air trapping secondary to a check-valve mechanism. CT scanning defines the precise site and cause.

  • Definitive Diagnostic Study: Bronchoscopy.

  • Therapeutic Modalities: Bronchoscopic electrocautery, argon plasma coagulation, laser ablation, and radiofrequency ablation.

ASTHMA

• Essentials of Diagnosis:

  • Respiratory symptoms (wheeze, dyspnea, cough, chest tightness) variable in time and severity.

  • Variable expiratory airflow obstruction on PFT or a positive bronchoprovocation challenge.

• General Considerations:

  • Affects $5-10\%$ of the total population.

  • Pediatric Prevalence: Higher in males ($7\%$) than females ($5.4\%$).

  • Adult Prevalence: Higher in females ($10.8\%$) than males ($6.5\%$).

  • Racial Disparities in the United States: Black individuals are $44\%$ more likely to have asthma than White individuals. Hospitalization rates are highest among Black persons and children; death rates are highest among Black individuals aged $15-24\,\text{years}$.

  • US Healthcare Burden: $\sim 10\,\text{million}$ office visits, $1.8\,\text{million}$ emergency department visits, and > 3500 deaths annually.

• Definition & Pathogenesis:

  • Chronic inflammatory disorder of the airways resulting in variable airflow limitation and bronchial hyperresponsiveness.

  • Histopathologic Features: Infiltration with eosinophils, neutrophils, and T-lymphocytes; goblet cell hyperplasia; mucus plugging of small airways; sub-basement membrane collagen deposition; bronchial smooth muscle hypertrophy; mucosal edema; mast cell activation; and epithelial denudation.

  • Immunologic Endotypes:

  • T2-High Endotype: Mediated by classic Th2 cytokines (IL-4, IL-5, IL-13); highly responsive to targeted biologic therapies.

  • T2-Low Endotype: Marked by neutrophilic or paucigranulocytic inflammation; variable response to standard inhaled corticosteroid therapies.

  • Clinical Phenotypes:

  • Allergic Asthma: Childhood onset; associated with eczema, allergic rhinitis, and food allergies. Inhaled allergen exposure triggers early (immediate) or late ($4-6\,\text{hours}$) asthmatic responses. Common triggers include house dust mites, cockroaches, cat dander, and pollens.

  • Late-Onset T2-High Asthma and Aspirin/NSAID-Associated Respiratory Disease (AERD).

  • Nonallergic Asthma: Adult onset; marked by neutrophilic airway inflammation.

  • Asthma with Persistent Airflow Limitation: Driven by structural airway remodeling.

  • Asthma with Obesity: Prominent dyspnea symptoms with minimal classic airway inflammation.

  • Precipitants & Triggers: URTIs, rhinosinusitis, postnasal drip, GERD, weather shifts, psychological stress, exercise, combustion products (tobacco, methamphetamine, diesel fuel), air pollution ($\text{O}_3$, $\text{SO}_2$, $\text{NO}_2$, particulates), tartrazine dyes, aspirin/NSAIDs, workplace exposures (occupational asthma), and hormonal fluctuations (catamenial asthma).

  • Exercise-Induced Bronchoconstriction (EIB): Initiates during exercise or within $3\,\text{minutes}$ post-exercise, peaks at $10-15\,\text{minutes}$, and resolves by $60\,\text{minutes}$. Driven by airway hyperosmolarity and thermal changes from hyperventilation.

  • Cough-Variant Asthma: Severe nonproductive cough serves as the primary clinical manifestation of airway hyperreactivity.

• Assessing Asthma Control (Table 9-1):

  • Evaluated over a 4-week recall period using 4 components: daytime symptoms (> 2\times/\text{week}), nighttime awakenings, interference with normal activities, and reliever use (> 2\times/\text{week}).

  • Well Controlled: 0 of these components present.

  • Partly Controlled: 1 or 2 of these components present.

  • Not Controlled: 3 or 4 of these components present.

• Clinical Findings:

  • Physical Exam Findings: Swollen nasal mucosa, nasal polyps, atopic dermatitis; expiratory wheezing and prolonged expiratory phase during quiet respiration. During critical exacerbations, airflow limitation may be severe enough to eliminate wheezing ("silent chest"), presenting with globally suppressed breath sounds, accessory muscle use, and hunched posture.

  • Diagnostic Biomarkers: Blood eosinophil count > 150-300\,\mu\text{L}^{-1} defines the eosinophilic phenotype (guiding monoclonal antibody selection). Serum IgE guides biologic therapy and aids in evaluating suspected allergic bronchopulmonary aspergillosis (ABPA).

  • Spirometry Parameters:

  • Airflow Obstruction: Reduced $\text{FEV}_1/\text{FVC}$ ratio (< 0.70 or below the lower limit of normal).

  • Bronchodilator Responsiveness: Defined by ATS/ERS as an increase in $\text{FEV}_1$ or \text{FVC} > 10\% relative to the predicted value following short-acting bronchodilator inhalation. (Historical standard: $\ge 12\%$ and $\ge 200\,\text{mL}$ increase).

  • Severe obstruction leads to air trapping (elevated residual volume [RV]), which secondary reduces $FVC$ and can mimic a restrictive defect.

  • Bronchoprovocation Testing:

  • Indicated when asthma is suspected but resting spirometry is non-diagnostic.

  • Contraindicated if baseline \text{FEV}_1 < 65\% predicted.

  • Positive Methacholine Test: $\ge 20\%$ fall in $\text{FEV}_1$ at a concentration $\le 8\,\text{mg/mL}$. Negative predictive value is $95\%$.

  • Peak Expiratory Flow (PEF) Monitoring:

  • Diurnal pattern: Lowest upon awakening, highest several hours before the waking mid-point.

  • Diurnal or day-to-day variation $\ge 20\%$ indicates uncontrolled asthma.

  • Absolute \text{PEF} < 200\,\text{L/min} signifies severe airflow obstruction.

• Asthma Management & Step Therapy (Tables 9-2, 9-3, 9-4, 9-5):

  • Treatment Goals: Eliminate chronic interfering symptoms, prevent exacerbations, avoid emergency care/hospitalization, and maintain near-normal lung function.

  • Step Therapy Outline (GINA / NAEPP Guidelines):

  • Steps 1 & 2: Low-dose ICS-formoterol as needed OR daily low-dose ICS plus SABA as needed OR concomitant low-dose ICS and SABA as needed.

  • Step 3: Low-dose combination ICS-formoterol daily and as needed (Single Maintenance and Reliever Therapy [SMART]).

  • Step 4: Medium-dose combination ICS-formoterol daily and as needed.

  • Step 5: Medium-to-high dose ICS-LABA plus long-acting muscarinic antagonist (LAMA) and as-needed SABA.

  • Step 6: High-dose ICS-LABA plus oral systemic corticosteroids and as-needed SABA.

  • Pharmacologic Classes:

  • Inhaled Corticosteroids (ICS): Beclomethasone dipropionate, Budesonide, Flunisolide, Fluticasone propionate, Fluticasone furoate, Mometasone furoate, Triamcinolone acetonide. Metabolized by hepatic CYP3A4 enzymes; co-administration with strong CYP3A4 inhibitors (ritonavir, ketoconazole) increases systemic bioactivity, potentially triggering Cushing syndrome and adrenal insufficiency.

  • Long-Acting $\beta_2$-Agonists (LABA): Formoterol ($20\,\mu\text{g}$ q12h nebulized), Salmeterol ($50\,\mu\text{g}$ q12h DPI). LABAs must NEVER be prescribed as monotherapy due to increased risks of asthma-related mortality.

  • Combined Inhalers: Budesonide/formoterol, Fluticasone/salmeterol, Fluticasone furoate/vilanterol, Mometasone/formoterol.

  • Leukotriene Receptor Antagonists (LTRA) & 5-LO Inhibitors: Montelukast ($10\,\text{mg}$ daily at bedtime), Zafirlukast ($20\,\text{mg}$ BID on an empty stomach; monitor ALT for hepatic dysfunction), Zileuton ($600\,\text{mg}$ QID 5-lipoxygenase inhibitor; monitor ALT).

  • Monoclonal Antibodies (Biologics):

    • Omalizumab: Anti-IgE antibody. Dose based on baseline serum IgE ($30-1500\,\text{IU/mL}$) and body weight. Carries a black-box warning for anaphylaxis.

    • Mepolizumab: Anti-IL-5 SC injection ($100\,\text{mg}$ q4w). Indicated for absolute eosinophil count (AEC) $\ge 150-300\,\mu\text{L}^{-1}$.

    • Reslizumab: Anti-IL-5 IV injection ($3\,\text{mg/kg}$ q4w). Target AEC $\ge 400\,\mu\text{L}^{-1}$. Carries a black-box warning for anaphylaxis.

    • Benralizumab: Anti-IL-5R$\alpha$ SC injection ($30\,\text{mg}$ q4w for 3 doses, then q8w). Direct cytotoxic apoptosis of eosinophils and basophils. Target AEC $\ge 300\,\mu\text{L}^{-1}$.

    • Dupilumab: Anti-IL-4R$\alpha$ SC injection ($200$ or $300\,\text{mg}$ q2w). Blocks IL-4 and IL-13 signaling. Target AEC $\ge 150\,\mu\text{L}^{-1}$ or FeNO $\ge 25\,\text{ppb}$.

  • Phosphodiesterase Inhibitors: Methylxanthines/Theophylline (target therapeutic serum range: $5-15\,\mu\text{g/mL}$ after $\ge 48\,\text{hours}$ of stable dosing).

• Management of Asthma Exacerbations (Table 9-6 & Figures 9-1, 9-2):

  • Severity Classification:

  • Mild-to-Moderate: Breathless walking/talking; talks in phrases/sentences; $100-120\,\text{bpm}$; $\text{PEF} \ge 50\%$ predicted/personal best; $\text{SaO}_2\,90-95\%$.

  • Severe: Dyspneic at rest; sits upright; talks in words; agitated; respiratory rate > 30/\text{min}; accessory muscle use; pulse > 120\,\text{bpm}; pulsus paradoxus > 25\,\text{mm Hg}; \text{PEF} < 50\% predicted (or < 40\%); \text{PaO}_2 < 60\,\text{mm Hg}; $\text{PaCO}_2 \ge 42\,\text{mm Hg}$; \text{SaO}_2 < 90\%.

  • Imminent Respiratory Arrest: Mute, silent chest on auscultation, bradycardia, confusion, drowsiness, paradoxical thoracoabdominal movement, \text{PEF} < 25\%.

  • Emergency Pharmacotherapy:

  • Oxygen: Titrated to maintain $\text{SaO}_2\,93-95\%$ (or > 90\%).

  • Inhaled SABAs: Albuterol MDI ($4-10$ puffs with spacer) or nebulizer ($2.5\,\text{mg}$ in $3\,\text{mL}$ saline) given every $20\,\text{minutes}$ for the first hour (at least 3 treatments).

  • Anticholinergics: Add Ipratropium bromide ($0.5\,\text{mg}$ nebulized or $8$ puffs MDI) to SABA in moderate-to-severe exacerbations to decrease hospitalization rates.

  • Systemic Corticosteroids: Outpatient burst is Prednisone/Prednisolone $0.5-1.0\,\text{mg/kg/day}$ (typically $40-60\,\text{mg}$ as a single or 2 divided doses) for $3-10\,\text{days}$. Inpatient severe exacerbations: Prednisone or Methylprednisolone $1\,\text{mg/kg}$ IV/PO q6-12h for $48\,\text{hours}$ until $\text{PEF} \ge 50\%$ predicted, then step down to $0.5\,\text{mg/kg/day}$ until $\text{PEF}$ reaches $70\%$.

  • Intravenous Magnesium Sulfate: Single dose of $2\,\text{g}$ IV infused over $20\,\text{minutes}$ for acute severe exacerbations failing initial therapy (\text{FEV}_1 < 25\% predicted).

  • Contraindicated/Unhelpful Interventions: Sedatives and anxiolytics (respiratory depressant risks), mucolytics (worsen bronchospasm), empiric antibiotics (unless overt purulent bacterial sinusitis/pneumonia exists).

  • Discharge Criteria: $\text{PEF}$ or $\text{FEV}_1 \ge 60-70\%$ of predicted or personal best sustained for at least $60\,\text{minutes}$ post-last bronchodilator treatment with minimal/absent symptoms.

CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

• Essentials of Diagnosis:

  • History of cigarette smoking or other chronic inhalational exposures.

  • Chronic cough, dyspnea, and sputum production.

  • Rhonchi, decreased breath sound intensity, and prolonged expiration on physical exam.

  • Airflow limitation on PFT that is not fully reversible and progressive.

• General Considerations:

  • Third leading cause of death worldwide.

  • Major Causes: Tobacco smoking (primary in resourced countries) and indoor biomass fuel combustion smoke (primary in developing nations). About two-thirds of COPD cases stem from direct tobacco smoke; one-third results from environmental tobacco smoke, occupational dusts/chemicals, and biomass exposure.

  • Annual $\text{FEV}_1$ Loss in Active Smokers: $66\,\text{mL/year}$ in men and $54\,\text{mL/year}$ in women (compared to $30\,\text{mL/year}$ in male quitters and $22\,\text{mL/year}$ in female quitters).

  • Genetic Risk Factor: Congenital $\alpha_1$-antitrypsin ($\alpha_1$-antiprotease) deficiency.

• Clinical Phenotypes (Table 9-7):

  • Type A: "Pink Puffer" (Emphysema Predominant):

  • Clinical Features: Severe exertional dyspnea, presentation post-age 50, thin body habitus with recent weight loss, use of accessory muscles, quiet chest without adventitious sounds, absent peripheral edema.

  • Laboratory & PFT Findings: Normal hemoglobin ($12-15\,\text{g/dL}$); resting $\text{PaO}_2$ normal to slightly reduced ($65-75\,\text{mm Hg}$) with normal $\text{SaO}_2$; normal/low $\text{PaCO}_2$ ($35-40\,\text{mm Hg}$); hyperinflation with flattened diaphragms and diminished apical vascular markings on CXR; markedly elevated TLC; reduced DLCO; increased static lung compliance; high dead-space ventilation ($\text{V}/\text{Q}$ space).

  • Type B: "Blue Bloater" (Bronchitis Predominant):

  • Clinical Features: Chronic productive cough with mucopurulent sputum, presentation in late 30s or 40s, overweight/obese, cyanotic, comfortable at rest, prominent peripheral edema, noisy chest with rhonchi and wheezes.

  • Laboratory & PFT Findings: Elevated hemoglobin ($15-18\,\text{g/dL}$ secondary to chronic hypoxemia); reduced $\text{PaO}_2$ ($45-60\,\text{mm Hg}$); elevated $\text{PaCO}_2$ ($50-60\,\text{mm Hg}$); CXR shows prominent interstitial markings ("dirty lungs") without diaphragm flattening; normal TLC and DLCO; normal static compliance; high perfusion to low $\text{V}/\text{Q}$ areas.

• Diagnostic Evaluation:

  • Spirometry Standard: Post-bronchodilator \text{FEV}_1/\text{FVC} < 0.70 confirms non-reversible airflow obstruction.

  • Lung Volumes: Increased Residual Volume (RV) and Total Lung Capacity (TLC), with elevated $\text{RV}/\text{TLC}$ ratio confirming hyperinflation and air trapping.

  • Diffusing Capacity: Single-breath DLCO reduction quantifies anatomic emphysema and correlates with exertional desaturation and pulmonary hypertension.

  • Functional Capacity: 6-minute walk distance < 350\,\text{m} correlates directly with increased all-cause mortality.

  • Arterial Blood Gases (ABGs): Indicated if $\text{FEV}_1$ or \text{DLCO} < 40\% predicted or if hypercapnia/hypoxemia is suspected clinically.

• Ambulatory Management:

  • 1. Smoking Cessation: Single most crucial intervention to alter disease trajectory. Pharmacotherapy includes Nicotine Replacement Therapy (transdermal patch, gum, lozenge, inhaler, nasal spray), Bupropion, and Varenicline (partial agonist of nicotinic acetylcholine receptors).

  • 2. Home Supplemental Oxygen Therapy:

  • Survival Benefit: Proven only in resting hypoxemia. Prescribed when resting $\text{PaO}_2 \le 55\,\text{mm Hg}$ or $\text{SpO}_2 \le 88\%$, or $\text{PaO}_2\,56-59\,\text{mm Hg}$ ($\text{SpO}_2\,89\%$) with dependent edema/heart failure, P pulmonale on ECG, or hematocrit > 56\%.

  • Administration: Continuous oxygen ($24\,\text{hours/day}$) achieves a 36-month survival rate of $65\%$ vs $45\%$ with nocturnal-only oxygen. Nasal cannula flow must be maintained for $\ge 15\,\text{hours/day}$ (target flow $1-3\,\text{L/min}$ to keep \text{PaO}_2 > 55\,\text{mm Hg}).

  • Medicare Coverage Guidelines summarized in Table 9-8.

  • 3. Inhaled Bronchodilators:

  • Short-Acting Bronchodilators: SAMAs (Ipratropium bromide $2-4$ puffs q6h) or SABAs (Albuterol $2$ puffs q4-6h).

  • Long-Acting Bronchodilators: LAMAs (Tiotropium, Aclidinium, Umeclidinium, Glycopyrrolate) and LABAs (Salmeterol, Formoterol, Indacaterol, Arformoterol, Vilanterol, Olodaterol).

  • GOLD 2024 Guidelines: Recommends early initiation of dual LAMA + LABA therapy for stable symptomatic COPD over LAMA monotherapy.

  • 4. Inhaled Corticosteroids (ICS): Not recommended as monotherapy or in early stages. Reserved for severe disease with frequent exacerbations ($\ge 2/\text{year}$), history of hospitalizations, blood eosinophil count $\ge 300\,\mu\text{L}^{-1}$, or concomitant asthma. (Carries an increased risk of bacterial pneumonia).

  • 5. Phosphodiesterase-4 Inhibitors: Roflumilast reduces exacerbation frequency in patients with \text{FEV}_1 < 50\% predicted, chronic bronchitis, and recurrent exacerbations.

  • 6. Prophylactic Antibiotics: Oral Azithromycin ($250\,\text{mg}$ daily or $500\,\text{mg}$ 3x/week) or Moxifloxacin reduces exacerbations in refractory disease. Requires monitoring for QT prolongation and ototoxicity.

  • 7. Replacement Therapy: Human $\alpha_1$-antitrypsin ($60\,\text{mg/kg}$ IV weekly) for PiZZ or null genotypes with serum levels < 11\,\mu\text{mol/L} (< 50\,\text{mg/dL}).

  • 8. Pulmonary Rehabilitation: Recommended for symptomatic patients to improve exercise capacity, decrease hospitalizations, and enhance quality of life.

• Management of Hospitalized Acute Exacerbations:

  • Controlled Oxygen Therapy: Titrated via nasal prongs or Venturi mask to target $\text{SaO}_2\,90-94\%$ or $\text{PaO}_2\,60-70\,\text{mm Hg}$ without precipitating severe hypercapnia.

  • Inhaled Bronchodilators: Nebulized Albuterol ($2.5\,\text{mg}$ diluted to $3\,\text{mL}$) combined with Ipratropium bromide ($500\,\mu\text{g}$) every $1-4\,\text{hours}$.

  • Systemic Corticosteroids: Prednisone $0.5\,\text{mg/kg/day}$ (or $30-40\,\text{mg}$ daily) PO for $5-7\,\text{days}$.

  • Empiric Antibiotics: Prescribed when 2 or 3 cardinal symptoms (increased dyspnea, increased sputum volume, increased sputum purulence) are present:

  • Without Pseudomonas risk: Levofloxacin ($750\,\text{mg}$ PO/IV daily), Moxifloxacin ($400\,\text{mg}$ PO/IV daily), or Ceftriaxone ($1\,\text{g}$ IV daily).

  • With Pseudomonas risk (\text{FEV}_1 < 50\%, recent hospitalization, $\ge 3$ antibiotic courses in past year): Piperacillin-tazobactam ($4.5\,\text{g}$ IV q6h), Cefepime ($1-2\,\text{g}$ IV q8h), or Ceftazidime ($2\,\text{g}$ IV q8h).

  • Noninvasive Positive-Pressure Ventilation (NIPPV): First-line intervention for acute hypercapnic respiratory failure ($\text{pH} \le 7.35$ and $\text{PaCO}_2 \ge 45\,\text{mm Hg}$); decreases intubation rates, nosocomial infections, length of stay, and mortality.

• Advanced Procedures:

  • Lung Transplantation: 2-year post-transplant survival is $75\%$.

  • Lung Volume Reduction Surgery (LVRS): Bilateral surgical resection of $20-30\%$ of hyperinflated, poorly functioning emphysematous lung tissue.

  • Endobronchial Valves: One-way duckbill valves (Zephyr, Spiration) placed endobronchially to reduce severe lung hyperinflation.

  • Bullectomy: Surgical removal of giant bullae occupying $\ge 30-50\%$ of the hemithorax.

• Prognosis & Assessment:

  • Median survival of patients with $\text{FEV}_1 \le 1\,\text{L}$ is $\sim 4\,\text{years}$.

  • BODE Index: Multidimensional tool scoring Body mass index, Airway obstruction ($\text{FEV}_1$), Dyspnea (mMRC scale), and Exercise capacity (6-minute walk distance) to predict hospitalization and death.

BRONCHIECTASIS

• Essentials of Diagnosis:

  • Chronic productive cough with copious purulent sputum, dyspnea, wheezing, and hemoptysis.

  • HRCT findings of dilated, thickened airways ("tram tracks", "end-on rings") and scattered opacities.

• Etiologies: Cystic fibrosis, recurrent pulmonary infections (TB, NTM, fungal, severe pneumonia), immunodeficiencies (hypogammaglobulinemia, CVID, HIV, myeloma), $\alpha_1$-antitrypsin deficiency, primary ciliary dyskinesia, autoimmune diseases (RA, Sjögren syndrome), allergic bronchopulmonary aspergillosis (ABPA), and focal endobronchial obstruction.

• Microbiology: Haemophilus influenzae (most common), Moraxella catarrhalis, Pseudomonas aeruginosa (marker for rapid lung function decline, frequent exacerbations, and mortality), Staphylococcus aureus, NTM, and Streptococcus pneumoniae.

• Diagnostic Standard: High-Resolution CT (HRCT) scanning of the chest.

• Management Protocols:

  • Acute Exacerbations: Antibiotics tailored to sputum culture for $10-14\,\text{days}$. Empiric options: Amoxicillin-clavulanate ($875/125\,\text{mg}$ BID), Cefpodoxime ($200\,\text{mg}$ BID), Doxycycline ($100\,\text{mg}$ BID), or Ciprofloxacin ($500-750\,\text{mg}$ BID).

  • Airway Clearance Therapies: Postural drainage, chest percussion, hypertonic ($3-7\%$) saline nebulization, and handheld flutter valve devices.

  • Chronic Suppression: For patients with $\ge 3$ exacerbations annually, long-term macrolide therapy (Azithromycin) for $6-12\,\text{months}$ or cyclical inhaled antibiotics (Tobramycin) reduces exacerbations.

  • Massive Hemoptysis Management: Bronchial artery embolization, bronchoscopic hemostasis (balloon tamponade, topical epinephrine, laser), or surgical resection.

ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS (ABPA)

• Definition: Pulmonary hypersensitivity reaction triggered by colonization of the tracheobronchial tree by Aspergillus species.

• Diagnostic Criteria:

  1. Clinical history of asthma or cystic fibrosis.

  2. Elevated total serum IgE level (> 500\,\text{IU/mL}).

  3. Elevated serum IgE specific to Aspergillus fumigatus $\ge 0.35\,\text{kU/L}$ or positive Aspergillus skin test.

  4. At least two of the following:

  • Elevated serum Aspergillus IgG antibodies.

  • Radiographic abnormalities consistent with ABPA (transient opacities, mucoid impaction, central bronchiectasis).

  • Peripheral blood eosinophil count $\ge 500\,\mu\text{L}^{-1}$.

• Treatment: Oral Prednisone $0.5-1.0\,\text{mg/kg/day}$ for 2 weeks followed by a gradual taper over months. Itraconazole or Voriconazole added for steroid-dependent disease. Biologic agents (Mepolizumab, Benralizumab, Dupilumab, Omalizumab) reduce exacerbations in refractory cases.

CYSTIC FIBROSIS (CF)

• Essentials of Diagnosis:

  • Autosomal recessive defect in the CFTR gene affecting chloride transport and fluid flux.

  • Pulmonary Manifestations: Chronic productive cough, recurrent infections, P. aeruginosa colonization, bronchiectasis, and progressive airflow obstruction.

  • Extrapulmonary Manifestations: Pancreatic insufficiency, meconium ileus, distal intestinal obstruction, biliary cirrhosis, chronic sinusitis, nasal polyposis, congenital bilateral absence of the vas deferens with azoospermia in males.

• Genetics & Molecular Classes:

  • Over 2000 CFTR variants identified; $\Delta\text{F508}$ is the most prevalent.

  • Classes: Class I (defective protein synthesis), Class II (defective processing/folding [$\Delta\text{F508}$]), Class III (defective regulation/gating), Class IV (defective conduction), Class V (reduced functional CFTR quantity).

• Diagnostic Criteria (Must satisfy 1 item from category A and 1 from category B):

  • Category A: Typical CF clinical features OR family history of CF in a sibling OR positive newborn screen.

  • Category B: Elevated sweat chloride concentration (> 60\,\text{mEq/L} on two occasions) OR presence of 2 disease-causing CFTR gene mutations OR abnormal nasal potential difference.

• Comprehensive Management:

  • CFTR Modulators:

  • Triple Modulator Therapy (Elexacaftor/Tezacaftor/Ivacaftor): Recommended for patients $\ge 2\,\text{years}$ old with at least one $\Delta\text{F508}$ allele.

  • Dual Modulator Therapy (Tezacaftor/Ivacaftor): Recommended for children 1 to < 2\,\text{years} old.

  • Monotherapy (Ivacaftor): Approved down to 1 month of age for gating mutations.

  • Airway Clearance Agents: Inhaled recombinant human deoxyribonuclease (dornase alfa / rhDNase) and hypertonic ($7\%$) saline nebulization coupled with flutter valve or chest physiotherapy.

  • Chronic Antimicrobial Therapy: Inhaled Tobramycin, Aztreonam, Colistin, or Levofloxacin given in alternating 28-day cycles for chronic P. aeruginosa infection. Oral Azithromycin ($250-500\,\text{mg}$ 3x/week) for anti-inflammatory benefit.

  • Inhaled Bronchodilators: Albuterol prescribed for patients demonstrating $\ge 12\%$ bronchodilator reversibility in $\text{FEV}_1$.

BRONCHIOLITIS

• Essentials of Diagnosis: Insidious cough and dyspnea, irreversible airflow obstruction and air trapping on PFTs, minimal CXR findings with air trapping on CT.

• Clinical Subtypes:

  • 1. Acute Bronchiolitis: Rare in adults; follows acute viral URTIs.

  • 2. Constrictive Bronchiolitis (Obliterative Bronchiolitis / Bronchiolitis Obliterans):

  • Etiologies: Inhalation of toxic fumes (ammonia, welding fumes), rheumatoid arthritis, drug toxicity (busulfan, penicillamine, gold), and chronic graft rejection following lung or hematopoietic stem cell transplantation (Bronchiolitis Obliterans Syndrome).

  • Features: Irreversible obstructive deficit with air trapping on CT. Unresponsive to corticosteroids. Azithromycin may slow functional decline in post-lung transplant recipients.

  • 3. Proliferative Bronchiolitis (Cryptogenic Organizing Pneumonia [COP] / BOOP):

  • Etiologies: Post-infectious, aspiration, ARDS, connective tissue diseases, organ transplants.

  • Features: Restrictive ventilatory defect; patchy consolidation and ground-glass opacities on CT. Highly responsive to systemic corticosteroids (Prednisone $1\,\text{mg/kg/day}$ for 1-3 months, then tapered over 3-6 months).

  • 4. Follicular Bronchiolitis: Associated with RA, Sjögren syndrome, HIV, or CVID. Displays centrilobular/peribronchial lymphoid nodules on CT. Treated with underlying disease control, steroids, and azithromycin.

  • 5. Respiratory Bronchiolitis: Most common form in adult smokers; centrilobular ground-glass nodules on CT. Managed via smoking cessation.

  • 6. Diffuse Panbronchiolitis: Predominantly diagnosed in Japan; strong male predominance; nonsmokers with chronic pansinusitis. PFTs show severe obstruction. Treated effectively with long-term low-dose macrolide antibiotics (Azithromycin).

PULMONARY INFECTIONS: PNEUMONIA

Community-Acquired Pneumonia (CAP)

• Essentials of Diagnosis:

  • Fever/hypothermia, tachypnea, cough with/without purulent sputum, dyspnea, pleuritic chest discomfort.

  • Inspiratory crackles, rhonchi, or bronchial breath sounds on chest auscultation.

  • Parenchymal pulmonary opacity on CXR or CT scan.

  • Acquisition outside of a healthcare facility or within 48 hours of hospital admission.

• Epidemiology & Pathogenesis:

  • Affects $4-5\,\text{million}$ US adults annually; $25\%$ require hospitalization. Overall inpatient mortality is $10-12\%$.

  • Common Bacterial Pathogens: Streptococcus pneumoniae (accounts for $\sim 2/3$ of bacterial isolates), Haemophilus influenzae, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Staphylococcus aureus, Moraxella catarrhalis, Klebsiella pneumoniae, and Legionella species.

  • Common Viral Pathogens: SARS-CoV-2, Influenza, Respiratory Syncytial Virus (RSV), Adenovirus, Parainfluenza.

• Diagnostic Testing:

  • Sputum Gram Stain & Culture: Recommended for hospitalized patients with severe CAP or risk factors for MRSA/P. aeruginosa.

  • Urinary Antigen Tests: Available for Legionella pneumophila (serogroup 1) and S. pneumoniae. Recommended in severe CAP or outbreaks.

  • Rapid Molecular Assays: Multiplex PCR on respiratory specimens identifies bacterial/viral pathogens and resistance genes rapidly.

  • MRSA Nasal PCR Screening: High negative predictive value (> 95\%); guides rapid de-escalation of empiric vancomycin/linezolid.

• Empiric Treatment Strategies (Table 9-10):

  • Outpatient, Healthy, No Risk Factors for Resistant Organisms:

  • Amoxicillin $1\,\text{g}$ PO TID OR

  • Doxycycline $100\,\text{mg}$ PO BID OR

  • Macrolide (Azithromycin $500\,\text{mg}$ day 1, then $250\,\text{mg}$ daily for 4 days; or Clarithromycin $500\,\text{mg}$ BID) ONLY in regions with $\text{S. pneumoniae}$ macrolide resistance rates < 25\%.

  • Outpatient, With Comorbidities (Heart, lung, liver, or renal disease; diabetes; alcoholism; malignancy; asplenia; immunosuppression; or recent antibiotic use within 90 days):

  • Combination Therapy: Oral $\beta$-lactam (Amoxicillin-clavulanate $875/125\,\text{mg}$ BID or $2000/125\,\text{mg}$ BID; Cefpodoxime $200\,\text{mg}$ BID; or Cefuroxime $500\,\text{mg}$ BID) PLUS a Macrolide or Doxycycline OR

  • Monotherapy: Respiratory Fluoroquinolone (Levofloxacin $750\,\text{mg}$ daily, Moxifloxacin $400\,\text{mg}$ daily).

  • Inpatient Non-Severe CAP:

  • IV/PO Respiratory Fluoroquinolone (Levofloxacin $750\,\text{mg}$ daily, Moxifloxacin $400\,\text{mg}$ daily) OR

  • Combination Therapy: IV $\beta$-lactam (Ceftriaxone $1-2\,\text{g}$ IV daily, Ampicillin-sulbactam $1.5-3\,\text{g}$ IV q6h, Cefotaxime $1-2\,\text{g}$ IV q8h, or Ceftaroline $600\,\text{mg}$ IV q12h) PLUS Azithromycin or a Respiratory Fluoroquinolone.

  • Inpatient Severe CAP (ICU Care Required):

  • IV $\beta$-lactam (Ceftriaxone, Ampicillin-sulbactam, Cefotaxime) PLUS IV Azithromycin or Respiratory Fluoroquinolone.

  • Pathogen-Specific Coverage Add-ons:

  • MRSA Risk: Add Vancomycin ($15-20\,\text{mg/kg}$ IV q8-12h, target trough $15-20\,\mu\text{g/mL}$) or Linezolid ($600\,\text{mg}$ IV/PO q12h).

  • Pseudomonas aeruginosa Risk: Add Piperacillin-tazobactam ($4.5\,\text{g}$ IV q6h), Cefepime ($2\,\text{g}$ IV q8h), Meropenem ($1\,\text{g}$ IV q8h), Imipenem ($500\,\text{mg}$ IV q6h), or Aztreonam ($2\,\text{g}$ IV q8h).

  • Duration of Antibiotic Therapy: 5 days minimum; patient must demonstrate clinical stability (< 37.8^\circ\text{C}, \text{HR} < 100, \text{RR} < 24, $\text{SBP} \ge 90$, $\text{SaO}_2 \ge 90\%$) for $\ge 48\,\text{hours}$ prior to cessation. Minimum 7 days required for MRSA or P. aeruginosa.

• Triage & Prediction Rules:

  • Pneumonia Severity Index (PSI): 20-variable risk tool stratifying 30-day mortality across classes I-V.

  • CURB-65 Criteria: 1 point each for Confusion, Uremia ($\text{BUN} \ge 20\,\text{mg/dL}$), Respiratory rate $\ge 30/\text{min}$, Blood pressure (\text{SBP} < 90\,\text{mm Hg} or $\text{DBP} \le 60\,\text{mm Hg}$), Age $\ge 65\,\text{years}$. Score $\ge 2$ suggests hospitalization; score $\ge 3$ warrants ICU evaluation.

  • ICU Admission Criteria: Requires 1 major criterion (septic shock needing vasopressors or respiratory failure needing mechanical ventilation) OR $\ge 3$ minor criteria ($\text{RR} \ge 30$, $\text{PaO}_2/\text{FiO}_2 \le 250$, multilobar infiltrates, confusion, $\text{BUN} \ge 20\,\text{mg/dL}$, \text{WBC} < 4000\,\mu\text{L}^{-1}, \text{platelets} < 100{,}000\,\mu\text{L}^{-1}, core temperature < 36.0^\circ\text{C}, hypotension needing fluid resuscitation).

• Adjunctive Hydrocortisone: Hydrocortisone ($200\,\text{mg/day}$ IV continuous infusion for 4-7 days) reduces 28-day mortality in severe CAP admitted to the ICU.

• Pneumococcal Vaccination Guidelines:

  • Recommended for all adults $\ge 50\,\text{years}$ and adults $19-49\,\text{years}$ with chronic comorbidities or immunocompromising conditions.

  • Regimens: Single dose of PCV20 or PCV21 OR single dose of PCV15 followed by PPSV23 $\ge 1\,\text{year}$ later ($\ge 8\,\text{weeks}$ later if immunocompromised).

Nosocomial Pneumonia (HAP & VAP)

• Definitions:

  • Hospital-Acquired Pneumonia (HAP): Develops $\ge 48\,\text{hours}$ after hospital admission, excluding infections incubating at entry.

  • Ventilator-Associated Pneumonia (VAP): Develops > 48\,\text{hours} after endotracheal intubation and mechanical ventilation.

• Microbiology: S. aureus (MSSA and MRSA), P. aeruginosa, Gram-negative bacilli (ESBL-producing Klebsiella, Enterobacter, E. coli), Acinetobacter species, and Stenotrophomonas maltophilia.

• Risk Factors for Multidrug-Resistant (MDR) Pathogens (Table 9-11): Prior IV antibiotic use within 90 days, septic shock at time of VAP, ARDS preceding VAP, $\ge 5\,\text{days}$ of hospitalization prior to HAP/VAP, acute renal replacement therapy prior to VAP onset.

• Empiric Treatment Protocols (Table 9-12):

  • Low Risk for Mortality and No MDR/MRSA Risk: Monotherapy with Piperacillin-tazobactam ($4.5\,\text{g}$ IV q6h), Cefepime ($2\,\text{g}$ IV q8h), Levofloxacin ($750\,\text{mg}$ IV daily), or Meropenem ($1\,\text{g}$ IV q8h).

  • High Risk for Mortality or MDR/MRSA Risk: Dual anti-pseudomonal coverage (e.g., Cefepime plus Levofloxacin or Tobramycin) PLUS an anti-MRSA agent (Vancomycin $15-20\,\text{mg/kg}$ IV q8-12h targeting trough $15-20\,\mu\text{g/mL}$ or Linezolid $600\,\text{mg}$ IV q12h).

  • Treatment Duration: 7 days standard.

Anaerobic Pneumonia & Lung Abscess

• Predispositions: Conditions impairing deglutition or consciousness (alcohol/drug abuse, seizures, stroke, general anesthesia) coupled with severe periodontal disease.

• Microbiology: Polymicrobial anaerobic flora (Prevotella melaninogenica, Peptostreptococcus, Fusobacterium nucleatum, Bacteroides species).

• Clinical Manifestations: Indolent constitutional symptoms (fever, weight loss, malaise), cough productive of foul-smelling ("putrid") purulent sputum, and poor dentition.

• Radiographic Imaging: Solitary thick-walled cavity with an air-fluid level located in dependent pulmonary segments (posterior segments of upper lobes, superior segments of lower lobes) surrounded by parenchymal consolidation.

• Treatment: Ampicillin-sulbactam ($3\,\text{g}$ IV q6h) or Amoxicillin-clavulanate ($875/125\,\text{mg}$ PO BID) or a Carbapenem. Alternative: Ceftriaxone plus Metronidazole. Antibiotic therapy is continued for at least 3 to 6 weeks or until complete radiographic resolution of the abscess cavity. (Caution: Thoracostomy tube drainage of an unruptured lung abscess is contraindicated due to risk of bronchopleural fistula formation).

PULMONARY TUBERCULOSIS

• Essentials of Diagnosis:

  • Chronic constitutional symptoms: Fatigue, weight loss, low-grade fever, night sweats, anorexia.

  • Chronic productive cough, hemoptysis, and apical post-tussive rales.

  • Epidemiologic risks: Household contact, incarceration, homelessness, travel/residence in endemic countries.

  • Diagnostic confirmation via acid-fast bacilli (AFB) smear, nucleic acid amplification test (NAAT), or culture isolation of Mycobacterium tuberculosis.

• Pathogenesis & Transmission:

  • Transmitted via inhaled airborne droplet nuclei containing M. tuberculosis.

  • Enters alveolar spaces -> phagocytosed by alveolar macrophages -> primary TB (usually asymptomatic).

  • Contained inside noncaseating/caseating granulomas driven by cell-mediated T-cell immunity -> Latent TB Infection (LTBI). Latent TB is non-communicable.

  • Lifetime reactivation risk: $5-15\%$ in immunocompetent individuals (half occurring within 2 years of primary infection).

• Drug-Resistance Definitions:

  • Monoresistant TB: Resistant to 1 first-line drug (Isoniazid or Rifampin).

  • Multidrug-Resistant TB (MDR-TB): Resistant to at least Isoniazid AND Rifampin.

  • Pre-Extensively Drug-Resistant TB (pre-XDR-TB): Resistant to Rifampin PLUS any fluoroquinolone.

  • Extensively Drug-Resistant TB (XDR-TB): Resistant to Rifampin PLUS any fluoroquinolone PLUS Bedaquiline or Linezolid.

• Laboratory & Diagnostic Tests (Table 9-13):

  • Sputum AFB Smear: Requires 3 consecutive morning expectorated sputum samples collected 8 hours apart.

  • NAAT-TB & NAAT-R: Rapid molecular tests detecting M. tuberculosis DNA and gene mutations imparting rifampicin/isoniazid resistance within hours. Recommended by WHO as the initial diagnostic test.

  • Mycobacterial Culture: Liquid broth culture (10-14 days to detection) is more sensitive than solid agar culture (3-4 weeks); serves as the gold standard.

  • Tuberculin Skin Testing (TST / Mantoux) Cutoff Interpretations (Table 9-14):

  • $\ge 5\,\text{mm}$ Induration: HIV-infected individuals, close contacts of active TB cases, fibrotic apical changes on CXR, organ transplant recipients, and immunosuppressed patients ($\ge 15\,\text{mg/day}$ prednisone equivalent for $\ge 1\,\text{month}$).

  • $\ge 10\,\text{mm}$ Induration: Immigrants from high-prevalence countries (< 5\,\text{years}), injection drug users, mycobacteriology lab personnel, high-risk congregate settings (prisons, nursing homes, shelters, hospitals), high-risk medical conditions (CKD, diabetes, silicosis, gastrectomy, bypass), and children < 5\,\text{years}.

  • $\ge 15\,\text{mm}$ Induration: Persons with no known risk factors for TB.

  • Interferon-Gamma Release Assays (IGRA): In vitro blood tests (QuantiFERON, T-SPOT). Preferred over TST in individuals previously vaccinated with BCG.

• Treatment Regimens:

  • Active Drug-Susceptible Tuberculosis in Non-HIV Adults:

  • Standard 6-Month Regimen: 2 months of daily RIPE (Rifampin $10\,\text{mg/kg}$, maximum $600\,\text{mg}$; Isoniazid $5\,\text{mg/kg}$, maximum $300\,\text{mg}$; Pyrazinamide $15-30\,\text{mg/kg}$; Ethambutol $15-25\,\text{mg/kg}$) followed by 4 months of daily RI (Rifampin and Isoniazid).

  • Alternative 4-Month Regimen: 8 weeks of daily Rifapentine, Moxifloxacin, Isoniazid, and Pyrazinamide followed by 9 weeks of daily Rifapentine, Moxifloxacin, and Isoniazid.

  • Pregnancy & Lactation: Regimen consists of 2 months of INH, RIF, and EMB, followed by 7 months of INH and RIF. (Pyrazinamide is routinely omitted in the US due to uncertain teratogenicity data; Streptomycin is strictly contraindicated due to fetal ototoxicity). Supplemental Pyridoxine (Vitamin B6, $25-50\,\text{mg/day}$) must be co-administered with Isoniazid to prevent neurotoxicity.

  • Latent Tuberculosis Infection (LTBI) Regimens:

  • 3-month oral once-weekly Isoniazid plus Rifapentine.

  • 4-month oral daily Rifampin ($600\,\text{mg/day}$).

  • 3-month oral daily Isoniazid plus Rifampin.

  • 6- or 9-month oral daily Isoniazid ($300\,\text{mg/day}$) plus Pyridoxine.

NONTUBERCULOUS MYCOBACTERIA (NTM)

• Essentials of Diagnosis: Chronic cough, fatigue, parenchymal opacities/cavities/nodular bronchiectasis on CT, and isolation of NTM species from sputum or tissue.

• Common Species: Mycobacterium avium complex (MAC - M. avium, M. intracellulare), Mycobacterium kansasii, Mycobacterium abscessus, Mycobacterium fortuitum, Mycobacterium chelonae.

• Clinical Phenotypic Presentations:

  • Upper lobe fibrocavitary lesions in older male smokers.

  • Nodular bronchiectasis involving mid-lung fields (lingula, right middle lobe) in non-smoking middle-aged or older women ("Lady Windermere syndrome").

  • Hypersensitivity pneumonitis ("hot tub lung") post-environmental aerosol exposure.

• Bacteriologic Diagnostic Criteria (Immunocompetent patients):

  • Positive cultures from at least 2 separate expectorated sputum samples OR

  • Positive culture from at least 1 bronchial wash/lavage OR

  • Transbronchial/lung biopsy demonstrating granulomatous histopathology along with a positive NTM culture or positive sputum/wash culture.

• Pharmacotherapy Regimens:

  • MAC Pulmonary Disease: Combination of Macrolide (Clarithromycin $500\,\text{mg}$ BID or Azithromycin $250-500\,\text{mg}$ daily) PLUS Rifampin ($600\,\text{mg}$ daily) PLUS Ethambutol ($15\,\text{mg/kg}$ daily). Add Parenteral Amikacin or Streptomycin for severe fibrocavitary disease. Treatment is continued for 12 months after sputum culture conversion.

  • M. kansasii Disease: Rifampin, Isoniazid, and Ethambutol daily for at least 18 months (minimum 12 months post-culture conversion).

PULMONARY NEOPLASMS

Screening for Lung Cancer

• Low-Dose CT (LDCT) Screening Criteria:

  • Recommended annually for high-risk individuals: Age $50-80\,\text{years}$, $\ge 20$ pack-year smoking history, currently smoke or have quit within the past 15 years.

  • NLST Trial Evidence: LDCT screening demonstrates a $20\%$ reduction in lung cancer-specific mortality and a $6.7\%$ reduction in all-cause mortality compared to chest radiograph screening.

  • Serial annual chest x-rays provide NO mortality benefit and are not recommended.

Solitary Pulmonary Nodule (SPN)

• Definition: Single, isolated, rounded parenchymal opacity < 3\,\text{cm} in diameter outlined by normal lung, without associated atelectasis, adenopathy, or pleural effusion.

• Radiographic Risk Clues:

  • Doubling Time: Rapid progression (< 30\,\text{days}) suggests acute infection; long-term stability (> 465\,\text{days}) indicates benign etiology.

  • Calcification Patterns: Central, laminated, or popcorn calcifications reflect benign processes (granuloma, hamartoma); stippled or eccentric calcification suggests malignancy.

  • Margins: Smooth borders suggest benignity; spiculated margins, lobulation, or a peripheral halo strongly correlate with malignancy.

• Management Based on Malignancy Probability:

  • Low Probability (< 5\%): Serial HRCT scan monitoring at defined intervals.

  • Intermediate Probability ($5-60\%$): Diagnostic evaluation via Fluorodeoxyglucose (FDG)-PET scan, guided bronchoscopy, transthoracic needle aspiration (TTNA), or VATS excisional biopsy.

  • High Probability (> 60\%): Direct surgical resection following staging.

Right Middle Lobe Syndrome

• Recurrent or persistent atelectasis of the right middle lobe due to its long, narrow bronchial anatomy and acute take-off angle combined with poor collateral ventilation. Bronchoscopy is required to rule out an obstructing endobronchial lesion.

Bronchial Carcinoid Tumors

• Low-grade to intermediate-grade neuroendocrine neoplasms arising centrally within mainstem or lobar bronchi. Highly vascular pink/purple endobronchial pedunculated masses. Presentation includes hemoptysis, cough, focal wheeze, and postobstructive pneumonia. Managed via surgical resection.

Mediastinal Masses

• Anterior Mediastinum: Sternum anteriorly to pericardium posteriorly. Mass causes: Thymoma, Teratoma, Thyroid lesions, Lymphoma ("4 Ts").

• Middle Mediastinum: Anterior pericardium to anterior thoracic spine surface. Mass causes: Lymphadenopathy, aortic aneurysms, developmental cysts (bronchogenic, pericardial, enteric), vascular dilations.

• Posterior Mediastinum: Paravertebral region. Mass causes: Neurogenic tumors (schwannoma, neurofibroma, neurosarcoma, ganglioneuroma), esophageal tumors, hiatal hernia, extramedullary hematopoiesis.

INTERSTITIAL LUNG DISEASE (Diffuse Parenchymal Lung Disease)

• Essentials of Diagnosis: Insidious progressive dyspnea, dry cough, fine bibasilar late-inspiratory crackles, digital clubbing, restrictive defect on PFTs (reduced TLC, $\text{FEV}_1/\text{FVC}$ normal/elevated, reduced DLCO), and reticular/ground-glass opacities on CT.

• Idiopathic Interstitial Pneumonias (IIPs) Spectrum (Table 9-16):

  • Usual Interstitial Pneumonia (UIP) / Idiopathic Pulmonary Fibrosis (IPF):

  • Demographics: Age 55-60, male predominance. Subacute progressive dyspnea and dry cough.

  • HRCT Features: Subpleural, basilar-predominant reticular opacities, traction bronchiectasis, and subpleural honeycombing.

  • Histopathology: Spatial and temporal heterogeneity, collagen deposition, and actively proliferating "fibroblast foci".

  • Treatment: Corticosteroids are ineffective and harmful. Antifibrotic drugs (Nintedanib [tyrosine kinase inhibitor] and Pirfenidone) slow the rate of $\text{FEV}_1$ decline. Lung transplantation is the only definitive cure. Median survival is $\sim 3\,\text{years}$.

  • Respiratory Bronchiolitis-Associated ILD (RB-ILD) & Desquamative Interstitial Pneumonia (DIP):

  • Occurs almost exclusively in heavy smokers. Marked intra-alveolar macrophage accumulation. Excellent prognosis (> 10\,\text{year} survival) with smoking cessation.

  • Acute Interstitial Pneumonia (AIP / Hamman-Rich Syndrome):

  • Fulminant diffuse lung injury presenting as acute ARDS. High early mortality ($50-90\%$ within 2 months).

  • Nonspecific Interstitial Pneumonia (NSIP):

  • Homogeneous interstitial inflammation/fibrosis on CT (bilateral ground-glass opacities). Predominantly affects females aged 45-55. Highly responsive to systemic corticosteroids.

  • Cryptogenic Organizing Pneumonia (COP / BOOP):

  • Subacute presentation following a flu-like illness. Intra-alveolar buds of granulation tissue (Masson bodies). HRCT displays patchy subpleural consolidation. Rapidly responsive to oral Prednisone ($1\,\text{mg/kg/day}$).

SARCOIDOSIS

• Essentials of Diagnosis:

  • Systemic disease characterized by noncaseating granulomatous inflammation, most commonly involving the lungs and intrathoracic lymph nodes (> 90\%).

  • Clinical Features: Dyspnea, dry cough, fatigue, chest pain, erythema nodosum, lupus pernio, iritis/uveitis, parotid enlargement, peripheral neuropathy, and AV block/arrhythmias.

  • Löfgren Syndrome: Acute triad of erythema nodosum, bilateral hilar adenopathy, and migratory polyarthritis accompanied by fever. Excellent prognosis.

• Radiographic Staging:

  • Stage I: Bilateral hilar lymphadenopathy alone.

  • Stage II: Bilateral hilar lymphadenopathy PLUS parenchymal infiltrates.

  • Stage III: Parenchymal infiltrates alone (without hilar adenopathy).

  • Stage IV: Advanced parenchymal end-stage fibrosis (upper lobe predominant).

• Diagnostic Laboratory Findings: Elevated Serum ACE ($40-80\%$ of active cases), hypercalcemia ($5\%$), hypercalciuria ($20\%$). Histologic verification of noncaseating granulomas via transbronchial lung biopsy or node biopsy is required.

• Treatment: Oral Prednisone ($0.5-1.0\,\text{mg/kg/day}$ or $20-40\,\text{mg}$ daily) for hypercalcemia, ocular, cardiac, neurological, or progressive pulmonary involvement. Methotrexate, Azathioprine, or Infliximab used for steroid-refractory disease.

PULMONARY ALVEOLAR PROTEINOSIS (PAP)

• Accumulation of PAS-positive lipoproteinaceous surfactant material inside alveolar spaces. CT shows pathognomonic "crazy-paving" (ground-glass attenuation with interlobular septal thickening). Elevated serum anti-GM-CSF autoantibodies confirm primary autoimmune PAP. Treatment: Therapeutic whole-lung lavage and aerosolized/SC GM-CSF.

EOSINOPHILIC PULMONARY SYNDROMES

• Characterized by peripheral blood eosinophilia (> 500\,\mu\text{L}^{-1}) and pulmonary eosinophilic infiltrates.

• Acute Eosinophilic Pneumonia (AEP): Acute febrile illness with rapid hypoxic failure; marked eosinophilia on BAL, minimal early blood eosinophilia. Promptly reversed by IV corticosteroids.

• Chronic Eosinophilic Pneumonia (CEP): Subacute fever, night sweats, weight loss, asthma. CT displays peripheral dense consolidation ("photographic negative of pulmonary edema"). Marked blood and BAL eosinophilia. Highly steroid-responsive.

DISORDERS OF THE PULMONARY CIRCULATION

Pulmonary Venous Thromboembolism (PE)

• Essentials of Diagnosis:

  • Acute onset of dyspnea, pleuritic chest pain, hemoptysis, syncope, tachypnea, tachycardia, and hypoxemia.

  • Wells Clinical Prediction Score (Table 9-17):

  • Clinical signs/symptoms of DVT (+3.0 points)

  • Alternative diagnosis less likely than PE (+3.0 points)

  • Heart rate > 100\,\text{bpm} (+1.5 points)

  • Immobilization $\ge 3\,\text{days}$ or surgery in past 4 weeks (+1.5 points)

  • Previous objective PE or DVT (+1.5 points)

  • Hemoptysis (+1.0 point)

  • Malignancy treated within 6 months (+1.0 point)

  • Scoring Tiers: Low (< 2.0), Moderate ($2.0-6.0$), High (> 6.0). Dichotomous: PE Unlikely ($\le 4.0$), PE Likely (> 4.0).

  • PERC Rule for Low-Risk Patients (Table 9-18): PE excluded without imaging if ALL 8 criteria are satisfied: Age < 50\,\text{years}, \text{HR} < 100\,\text{bpm}, $\text{SaO}_2 \ge 95\%$ on room air, no prior VTE, no trauma/surgery within 4 weeks, no hemoptysis, no oral estrogen use, no unilateral leg swelling.

• Diagnostic Diagnostic Evaluation:

  • Plasma D-Dimer: High negative predictive value; excludes PE in low/intermediate pretest probability (PE Unlikely) patients when normal.

  • CT Pulmonary Angiography (CT-PA): Gold standard imaging test.

  • Ventilation-Perfusion (V/Q) Scan: Indicated when IV contrast is contraindicated (severe renal dysfunction, anaphylactic contrast allergy).

  • Venous Compression Ultrasonography: Test of choice for lower extremity DVT detection.

• Risk Stratification & Management:

  • High-Risk (Massive) PE: Sustained hypotension (\text{SBP} < 90\,\text{mm Hg} for $\ge 15\,\text{minutes}$ or requiring vasopressors). Managed with Systemic Thrombolytic Therapy (Alteplase/rt-PA $100\,\text{mg}$ IV over 2 hours) or surgical/catheter embolectomy.

  • Intermediate-Risk (Submassive) PE: Normotensive with RV strain on echocardiogram/CT or elevated biomarkers (Troponin, BNP). Managed with anticoagulation and close monitoring; catheter-directed thrombolysis considered if deteriorating.

  • Low-Risk PE: Normotensive without RV strain or biomarker elevation. Managed with direct oral anticoagulants (DOACs: Apixaban, Rivaroxaban, Dabigatran, Edoxaban) or LMWH.

  • Anticoagulation Duration: 3 months for provoked VTE with transient risk factors; extended/indefinite for unprovoked VTE, recurrent VTE, or active malignancy.

Pulmonary Hypertension (PH)

• Essentials of Diagnosis:

  • Exertional dyspnea, fatigue, chest pain, syncope, loud pulmonary component of second heart sound ($\text{P}_2$), right ventricular heave, jugular venous distention, and lower extremity edema.

  • Hemodynamic Definition: Mean pulmonary arterial pressure (mPAP) > 20\,\text{mm Hg} measured by resting right heart catheterization.

• WSPH Etiologic Classification:

  • Group 1: Pulmonary Arterial Hypertension (PAH - Idiopathic, Heritable, Drug/Toxin, Scleroderma, HIV, Portal HTN, Congenital heart disease). Hemodynamics: mPAP > 20\,\text{mm Hg}, PCWP $\le 15\,\text{mm Hg}$, Pulmonary Vascular Resistance (PVR) $\ge 2\,\text{Wood units}$.

  • Group 2: PH secondary to Left Heart Disease (LV systolic/diastolic dysfunction, valvular disease).

  • Group 3: PH secondary to Lung Disease or Hypoxia (COPD, ILD, Sleep apnea, High altitude).

  • Group 4: PH secondary to Pulmonary Artery Obstructions (Chronic Thromboembolic Pulmonary Hypertension [CTEPH]).

  • Group 5: PH with Unclear/Multifactorial mechanisms (Sickle cell, sarcoidosis, ESKD).

• Targeted Pharmacotherapy for Group 1 PAH:

  • Endothelin Receptor Antagonists (ERA): Bosentan, Ambrisentan, Macitentan.

  • Phosphodiesterase-5 Inhibitors (PDE5I) & sGC Stimulators: Sildenafil, Tadalafil, Riociguat.

  • Prostacyclin Pathway Agents: Epoprostenol (IV), Treprostinil (IV/SC/Inhaled/PO), Iloprost (Inhaled), Selexipag (PO prostacyclin receptor agonist).

  • Activin Signaling Inhibitor: Sotatercept.

  • Initial Low/Intermediate Risk Group 1: Oral Dual Combination (ERA plus PDE5I).

  • High Risk Group 1: Triple Combination including Continuous IV/SC Prostacyclin infusion plus ERA and PDE5I.

  • Group 3 PH (ILD): Inhaled Treprostinil improves exercise capacity.

  • Group 4 CTEPH: Pulmonary Thromboendarterectomy (PTE) surgery or Riociguat.

ENVIRONMENTAL & OCCUPATIONAL LUNG DISORDERS

• Smoke Inhalation:

  • Systemic Toxicity: Carbon monoxide (CO) and Cyanide ($\text{HCN}$) poisoning. Managed with $100\%$ high-flow oxygen.

  • Upper Airway Thermal Injury: Mucosal edema causing inspiratory stridor within $18-24\,\text{hours}$. Managed with humidified oxygen, head elevation $30^\circ$, topical racemic epinephrine, Heliox, and early endotracheal intubation if severe.

  • Lower Airway Chemical Toxicity: Toxic aldehydes/acids trigger bronchorrhea, severe bronchospasm, mucosal sloughing, and ARDS within 1-2 days.

• E-Cigarette or Vaping Product-Associated Lung Injury (EVALI):

  • Linked to vaping THC/nicotine devices containing Vitamin E acetate. Presents with acute cough, dyspnea, chest pain, nausea, vomiting, diarrhea, and fever. Chest CT demonstrates bilateral ground-glass opacities with subpleural sparing. Rapidly responds to systemic corticosteroids.

• Occupational Pneumoconioses (Table 9-19):

  • Coal Worker's Pneumoconiosis: Coal dust macules ($2-5\,\text{mm}$) forming upper lung opacities; progresses to progressive massive fibrosis.

  • Silicosis: Inhalation of free crystalline silica ($0.3-5\,\mu\text{m}$) in sandblasters, stone cutters, and miners. Small rounded opacities throughout upper zones and pathognomonic "eggshell" calcification of hilar lymph nodes. Associated with a markedly increased risk of active Tuberculosis (mandatory TST/IGRA screening).

  • Asbestosis: Nodular interstitial fibrosis in shipyard, construction, and insulation workers > 15\,\text{years} post-exposure. Basilar linear streaking, honeycomb change, and pleural plaques on HRCT. Asbestos acts synergistically with cigarette smoking to cause bronchogenic carcinoma; also causes malignant pleural mesothelioma.

• Hypersensitivity Pneumonitis (Table 9-20):

  • Immune-mediated reaction to inhaled organic antigens (e.g., Farmer's lung [Saccharopolyspora rectivirgula in moldy hay], Bird fancier's lung [avian proteins]). Acute presentation: Fever, chills, cough, dyspnea $4-8\,\text{hours}$ post-exposure. HRCT displays mid-to-upper zone ground-glass opacities and air trapping. Managed via strict antigen avoidance and oral Prednisone.

• Medication-Induced Pulmonary Toxicity (Table 9-21):

  • Pulmonary Infiltration/Fibrosis: Amiodarone, Bleomycin, Methotrexate, Nitrofurantoin, Busulfan, Cyclophosphamide.

  • Immune Checkpoint Inhibitor Pneumonitis: Occurs in $5\%$ of patients receiving anti-PD-1/PD-L1 therapy; carries up to $20\%$ mortality if severe. Treated with drug cessation and high-dose corticosteroids.

• Radiation Lung Injury:

  • Radiation Pneumonitis: Acute exudative phase occurring $4-12\,\text{weeks}$ post-thoracic radiation. Insidious dry cough, dyspnea, fever, and sharp-bordered opacities conforming to radiation fields on CXR. Managed with oral Prednisone ($1\,\text{mg/kg/day}$).

  • Radiation Fibrosis: Chronic fibrotic phase occurring $6-12\,\text{months}$ post-radiation. Irreversible dense interstitial/pleural scarring; unhelpful response to steroids.

PLEURAL DISEASES

Pleural Effusion

• Classification via Light's Criteria (Effusion is an Exudate if $\ge 1$ criterion is met):

  1. Ratio of pleural fluid protein to serum protein > 0.5

  2. Ratio of pleural fluid LD to serum LD > 0.6

  3. Pleural fluid LD > 2/3 the upper limit of normal serum LD

• Transudative Causes: Heart failure (most common), cirrhosis with ascites, nephrotic syndrome, peritoneal dialysis, myxedema, acute atelectasis, superior vena cava obstruction.

• Exudative Causes & Fluid Features (Table 9-23):

  • Parapneumonic / Empyema: Neutrophilic predominance; Empyema confirmed by gross pus, positive Gram stain/culture, \text{pH} < 7.20, or glucose < 60\,\text{mg/dL}.

  • Malignancy: Turbid/bloody fluid; positive pleural cytology.

  • Tuberculosis: Lymphocytic predominance (> 50\%); elevated adenosine deaminase (ADA > 60\,\text{U/L}) or interferon-gamma.

  • Rheumatoid Arthritis: Very low glucose (< 30\,\text{mg/dL}), low pH (< 7.20), elevated rheumatoid factor, cholesterol crystals.

  • Esophageal Rupture: High pleural fluid amylase (salivary origin), \text{pH} < 6.0.

  • Chylothorax: Turbid milky supernatant; high triglycerides (> 110\,\text{mg/dL}) with presence of chylomicrons.

  • Hemothorax: Pleural fluid hematocrit to peripheral blood hematocrit ratio > 0.5.

• Interventional Management:

  • Complicated Parapneumonic Effusion & Empyema: Require tube thoracostomy drainage. Intrapleural Tissue Plasminogen Activator (tPA) combined with Deoxyribonuclease (DNase) instillation dissolves loculations and improves catheter drainage.

  • Hemothorax: Immediate tube thoracostomy to evacuate blood, prevent fibrothorax, and quantify ongoing bleeding.

Pneumothorax

• Classification:

  • Primary Spontaneous: Occurs in tall, thin young males (< 45\,\text{years}) without overt lung disease secondary to subpleural apical bleb rupture. Strongly linked to tobacco smoking.

  • Secondary Spontaneous: Complication of underlying pulmonary disease (COPD, CF, ILD, Pneumocystis pneumonia, catamenial).

  • Tension Pneumothorax: Life-threatening check-valve mechanism causing intrapleural pressure excess, lung collapse, ipsilateral hemithorax expansion, tracheal/mediastinal shift to the contralateral side, hypotension, and obstructive shock.

• Treatment Protocols:

  • Small, Asymptomatic Primary Spontaneous: Observation and high-flow oxygen administration (accelerates pleural air reabsorption).

  • Large or Symptomatic Primary Spontaneous: Needle aspiration or small-bore ($7-14\text{F}$) chest tube placement with a one-way Heimlich valve.

  • Secondary Spontaneous, Tension, or Ventilated Pneumothorax: Immediate tube thoracostomy. (Tension pneumothorax requires immediate emergency needle decompression prior to chest tube placement).

  • Indications for VATS Surgery & Pleurodesis: Recurrent spontaneous pneumothorax, bilateral pneumothorax, persistent air leak (> 3-5\,\text{days}), or first episode of secondary spontaneous pneumothorax.

DISORDERS OF CONTROL OF VENTILATION

• Obesity-Hypoventilation Syndrome (Pickwickian Syndrome):

  • Diagnostic Triad: $\text{BMI} \ge 30\,\text{kg/m}^2$, awake arterial chronic hypercapnia (\text{PaCO}_2 > 45\,\text{mm Hg} at sea level), and sleep-disordered breathing in the absence of an alternative hypoventilation cause.

  • Treatment: CPAP or noninvasive positive-pressure ventilation, weight reduction (incorporating GLP-1/GIP receptor agonists such as Tirzepatide), and avoidance of sedatives/opioids.

• Obstructive Sleep Apnea (OSA):

  • Risk Factors: Obesity, micrognathia, macroglossia, tonsillar hypertrophy, male sex, hypothyroidism, smoking.

  • Manifestations: Loud cyclical snoring, witnessed apneic pauses, choking/gasping awakenings, excessive daytime somnolence, morning headaches, hypertension.

  • Diagnosis: Overnight Polysomnography establishing an Apnea-Hypopnea Index (AHI) $\ge 5\,\text{events/hour}$ with clinical symptoms or $\ge 15\,\text{events/hour}$ without symptoms.

  • Management Options: Continuous Positive Airway Pressure (CPAP / APAP), weight loss, mandibular repositioning appliances, hypoglossal nerve stimulation, or surgical Uvulopalatopharyngoplasty (UPPP).

ACUTE RESPIRATORY FAILURE

• Definition: Arbitrarily defined as \text{PaO}_2 < 60\,\text{mm Hg} ($7.8\,\text{kPa}$) or \text{PaCO}_2 > 50\,\text{mm Hg} ($6.5\,\text{kPa}$).

• Respiratory Support Interventions:

  • High-Flow Nasal Cannula (HFNC): Delivers heated, humidified oxygen at high flows (up to $60\,\text{L/min}$) with adjustable $\text{FiO}_2$; washes out dead space $\text{CO}_2$ and reduces breathing work.

  • Noninvasive Positive-Pressure Ventilation (NIPPV): First-line therapy for hypercapnic respiratory failure secondary to acute COPD exacerbations.

  • Endotracheal Intubation Cuff Management: Maintain cuff inflation pressure < 20\,\text{mm Hg} ($20-30\,\text{cm H}_2\text{O}$) to limit mucosal ischemic injury.

  • Mechanical Ventilation Modes: Controlled Mechanical Ventilation (CMV / Assist-Control), Synchronized Intermittent Mandatory Ventilation (SIMV), Pressure Support Ventilation (PSV).

  • Volutrauma Prevention: Low tidal volume ventilation strategy ($6\,\text{mL/kg}$ of predicted body weight) to prevent alveolar overdistention.

ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS)

• Berlin Definition Criteria:

  1. Timing: Onset within 7 days of a known clinical insult or new/worsening respiratory symptoms.

  2. Imaging: New bilateral pulmonary opacities on CXR or CT not fully explained by effusions, collapse, or nodules.

  3. Origin of Edema: Respiratory failure not fully explained by heart failure or fluid overload.

  4. Oxygenation Impairment Tiers (measured with minimum $\text{PEEP} \ge 5\,\text{cm H}_2\text{O}$):

  • Mild ARDS: 200\,\text{mm Hg} < \text{PaO}_2/\text{FiO}_2 \le 300\,\text{mm Hg}

  • Moderate ARDS: 100\,\text{mm Hg} < \text{PaO}_2/\text{FiO}_2 \le 200\,\text{mm Hg}

  • Severe ARDS: $\text{PaO}_2/\text{FiO}_2 \le 100\,\text{mm Hg}$

• Pathophysiology: Diffuse injury to capillary endothelial and alveolar epithelial cells -> increased microvascular permeability -> protein-rich alveolar edema, surfactant inactivation, diffuse microatelectasis, severe $\text{V}/\text{Q}$ mismatching, and refractory hypoxemia.

• Evidence-Based Management Protocols:

  • Low Tidal Volume Ventilation Strategy: Target tidal volume of $6\,\text{mL/kg}$ ideal body weight (IBW) with plateau airway pressures maintained < 30\,\text{cm H}_2\text{O}. Reduces absolute mortality by $8.8\%$.

  • PEEP Optimization: Titrated to recruit collapsed alveoli while maintaining plateau pressure < 30\,\text{cm H}_2\text{O}.

  • Prone Positioning: Recommended for severe ARDS (\text{PaO}_2/\text{FiO}_2 < 150\,\text{mm Hg}) for $\ge 16\,\text{hours/day}$ to enhance alveolar recruitment and improve mortality.

  • Fluid Management: Conservative fluid protocol targeting lower central venous pressure (\text{CVP} < 4\,\text{mm Hg}) accelerates ventilator weaning.

  • Systemic Corticosteroids: Recommended by ATS guidelines to reduce mortality and duration of mechanical ventilation in early severe ARDS.

  • Extracorporeal Membrane Oxygenation (ECMO): Salvage therapy for severe refractory ARDS.

LUNG TRANSPLANTATION

• Candidate Selection: Advanced, progressive end-stage lung disease (ILD, COPD, Cystic Fibrosis, PAH) with a high 2-year mortality risk (> 50\%) despite maximal therapy. Absolute contraindications: Active malignancy, severe non-pulmonary organ dysfunction (cirrhosis, CKD, heart failure), active substance abuse/smoking, uncontrolled systemic infection, and medical noncompliance.

• Post-Transplant Care: Maintenance immunosuppression utilizing a 3-drug regimen: Calcineurin inhibitor (Tacrolimus) + Cell-cycle inhibitor (Mycophenolate mofetil) + Glucocorticoids.

• Prognosis: Median post-transplant survival is $\sim 7\,\text{years}$. Survival is superior in double-lung transplants and in recipients transplanted for cystic fibrosis.