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Mechanistic Deep Dive
Alveolar Gas Equation
- PAO2 = FiO2 Ã (PB - PH2O) - PaCO2/R
- R (respiratory quotient) â 0.8
- Sea level: PAO2 = 0.21 Ã (760 - 47) - PaCO2/0.8 = 150 - 1.25 Ã PaCO2
- Important for A-a gradient calculation
Diffusion Capacity (DLCO)
- Measures CO transfer
- â in: ILD, emphysema, pulmonary HTN, anemia
- â in: asthma, polycythemia, alveolar hemorrhage
- Corrected for hemoglobin
Ventilation Control
- Central chemoreceptors (medulla): respond to â PaCO2 / â pH in CSF
- Peripheral chemoreceptors (carotid + aortic bodies): respond to â PaO2 (mainly)
- Mechanoreceptors (lung stretch, J-receptors)
- Central pattern generator (medullary respiratory centers)
Cough Reflex
- Sensory: TRPV1, TRPA1, P2X3 receptors on vagal sensory nerves
- Central processing
- Motor: inspiration â glottic closure â forceful expiration
- P2X3 inhibition (gefapixant) blocks reflex
Recent Trials & Updates
COUGH-1 + COUGH-2 (2022) â Gefapixant
- Refractory chronic cough
- â Cough frequency
- FDA approved 2024
- Side effect: dysgeusia (taste alteration)
MK-7264 (Gefapixant) + Other P2X3 Inhibitors
- Sivopixant, eliapixant in trials
- Refractory cough treatment
2024 ATS/ERS/JRS/ALAT Dyspnea Update
- Refined definition
- Mechanism-based assessment
- Patient-reported outcome integration
CIRCO (2024) â Long COVID Dyspnea
- Microvascular dysfunction in long COVID
- Specific testing protocols
High-Yield Specialist Points
Refractory Chronic Cough
- Failed UACS + asthma + GERD trials
- Consider:
- Eosinophilic bronchitis (sputum eosinophils, ICS responsive)
- Bronchiectasis (HRCT)
- Chronic infection (NTM, fungal)
- Habit cough / tic
- Bordetella infection
- Neurogenic cough (laryngeal sensitivity)
- Treatment: gefapixant, nalbuphine, gabapentin, amitriptyline
Cough Hypersensitivity Syndrome
- Neurogenic etiology
- Triggered by mild stimuli (perfumes, temperature)
- Central sensitization
- Treatment: speech therapy, neuromodulators, gefapixant
Bronchodilator Reversibility Testing
- FEV1 improvement > 12% AND > 200 mL post-bronchodilator
- Asthma typically reversible
- COPD: < 12% reversibility
DLCO Pearls
- Corrected for Hgb
- â DLCO alone: pulmonary HTN, anemia
- â DLCO + obstruction: emphysema (>> COPD)
- â DLCO + restriction: ILD
- â DLCO: alveolar hemorrhage, polycythemia, asthma
Exercise-Induced Bronchospasm
- 70-80% of asthmatics
- Cold/dry air, exercise
- â FEV1 reduction after exercise
- Treatment: pre-exercise SABA, ICS daily
Pulse Oximeter Pitfalls
- Race-related inaccuracies (recently recognized)
- Dark skin â may overestimate SaO2
- 2024 FDA looking at this
- ABG remains gold standard
Capnography
- End-tidal CO2 (EtCO2)
- Useful for ventilation assessment
- Often used in procedural sedation, ICU
- â EtCO2: â cardiac output, hyperventilation
- â EtCO2: hypoventilation, â CO2 production
Six-Minute Walk Test (6MWT)
- Functional capacity
- < 300 m severely limited
- Distance + SpO2 + Borg dyspnea + HR
- Useful for ILD, PAH, COPD, HF, pre-transplant
Cardiopulmonary Exercise Testing (CPET)
- VO2 max gold standard for fitness
- Distinguishes cardiac vs pulmonary limitation
- Anaerobic threshold
- Wasserman 9-panel plot
Pearls
- 5 hypoxemia mechanisms; V/Q most common
- Shunt: no O2 response (key distinguisher)
- Hypoventilation: normal A-a gradient
- Chronic cough: UACS + asthma + GERD = 80-90%
- ACE inhibitor cough: 5-20%
- Refractory cough: gefapixant 2024 FDA
- Massive hemoptysis: bronchial artery embolization (definitive)
- DLCO: â in ILD, emphysema, PH; â in alveolar hemorrhage