What are the causes of respiratory failure in patients with pre-existing conditions such as Chronic Obstructive Pulmonary Disease (COPD), asthma, or cystic fibrosis?

Causes of Respiratory Failure

Respiratory failure develops through two fundamental mechanisms: lung failure causing hypoxemia (Type 1) or ventilatory pump failure causing hypercapnia (Type 2), with distinct underlying etiologies that must be identified to guide management. 1

Type 1 Respiratory Failure (Hypoxemic) - Primary Causes

Acute Respiratory Distress Syndrome (ARDS)

• ARDS represents the most severe form of acute lung injury, characterized by bilateral pulmonary infiltrates, increased pulmonary vascular permeability, and severe hypoxemia with mortality remaining 30-40% despite advances in care 1
• Triggered by diverse insults including sepsis, pneumonia, aspiration, trauma, and pancreatitis 1
• Classified by severity: mild (PaO₂/FiO₂ 200-300 mmHg), moderate (100-200 mmHg), or severe (≤100 mmHg) 1

Pneumonia and Pulmonary Infections

• Community-acquired and hospital-acquired pneumonia cause alveolar filling with inflammatory exudate, creating intrapulmonary shunting where blood bypasses ventilated alveoli entirely 1
• Severe childhood respiratory infections are associated with reduced lung function and increased respiratory symptoms in adulthood 2

Pulmonary Edema

• Fills alveoli with fluid, creating shunt physiology and severe V/Q mismatch 1
• Develops from increased pulmonary vascular permeability, increased hydrostatic pressures from resuscitation, and lowered oncotic pressure 1

Pulmonary Embolism

• Causes V/Q mismatch through increased dead space ventilation, diverting blood flow away from ventilated but unperfused lung regions 1

Pathophysiological Mechanisms

• Intrapulmonary shunting occurs when blood bypasses ventilated alveoli entirely, flowing through completely unventilated or fluid-filled lung units 1
• V/Q mismatch results from ventilation-perfusion abnormalities where some lung units receive inadequate ventilation relative to perfusion 1
• Diffusion impairment limits oxygen transfer across the alveolar-capillary membrane 1

Type 2 Respiratory Failure (Hypercapnic) - Primary Causes

COPD Exacerbations

• COPD exacerbations account for the majority of Type 2 respiratory failures 1
• Tobacco smoke is the major risk factor worldwide, though biomass cooking and heating in poorly ventilated dwellings also contribute 2
• Asthma may be a risk for development of chronic airflow limitation and COPD 2
• HIV infection accelerates onset of smoking-related emphysema and COPD 2
• Tuberculosis has been identified as both a risk factor for COPD and a potential comorbidity 2

Pathophysiological Mechanisms in COPD

• Increased airway resistance with flow-limited expiration during tidal breathing, initially with exercise then at rest 1
• Dynamic hyperinflation prevents expiration to relaxation volume, creating intrinsic PEEP (PEEPi) that acts as an inspiratory threshold load 1, 3
• Inspiratory muscle dysfunction related to impaired muscle function, with increased mechanical workload raising energy consumption 1, 3
• Severe V/Q abnormalities worsen during acute exacerbations 2

Neuromuscular Disorders

• Progressive ventilatory pump failure occurs in ALS, muscular dystrophy, and myasthenia gravis 1
• These conditions cause gradual deterioration of respiratory muscle strength, eventually leading to inability to maintain adequate alveolar ventilation 1
• Vital capacity <15 mL/kg suggests need for mechanical ventilation consideration 3

Chest Wall Disorders

• Obesity hypoventilation syndrome combines restrictive mechanics with central drive abnormalities 1
• Chest wall deformities including scoliosis and thoracoplasty impair ventilatory mechanics 1

Central Nervous System Depression

• Reduced central respiratory drive from medications, neurological injury, or metabolic derangements leads to alveolar hypoventilation 4

Pre-Existing Conditions as Risk Factors

COPD-Specific Considerations

• Concomitant chronic diseases occur frequently in COPD patients and independently affect mortality and hospitalizations 2
• Cardiovascular disease accounts for 26% of deaths in moderate-to-severe COPD, cancer 21%, with only 35% directly attributable to COPD 2
• Acute exacerbations may be caused by extrapulmonary mechanisms including systemic hypertension, acute heart decompensation, atrial fibrillation, and pulmonary embolism 2

Asthma

• Airway hyperresponsiveness is an independent predictor of COPD and respiratory mortality in population studies 2
• May indicate risk for excessive lung function decline in mild COPD 2

Cystic Fibrosis

• Abnormal ion transport due to CFTR dysfunction contributes to chronic inflammatory response and progressive airflow limitation 2
• Patients producing large volumes of sputum may have underlying bronchiectasis 2

Common Pitfalls in Identifying Causes

• Standard chest radiographs are poor predictors of oxygenation defect severity or clinical outcome, and classic ARDS findings may be asymmetric, patchy, or focal 1
• Chronic cough is often discounted by patients as a consequence of smoking and/or environmental exposures, delaying diagnosis 2
• Acute exacerbations of respiratory symptoms occur with significant frequency in smokers without COPD, suggesting they are not specific for COPD 2
• Supplemental oxygen can release hypoxic pulmonary vasoconstriction, potentially worsening V/Q mismatch in COPD exacerbations 5

Critical Assessment Framework

History Elements to Identify

• Exposure to risk factors: smoking, occupational exposures, biomass fuels 2
• Past medical history: asthma, childhood respiratory infections, HIV, tuberculosis 2
• Pattern of symptom development and exacerbation history 2
• Presence of comorbidities: heart disease, malignancies, neuromuscular disorders 2

Diagnostic Confirmation

• Spirometry is required to make the diagnosis of COPD; post-bronchodilator FEV₁/FVC <0.70 confirms persistent airflow limitation 2
• Arterial blood gas analysis distinguishes Type 1 (PaO₂ <8 kPa with normal/low PaCO₂) from Type 2 (PaCO₂ >6 kPa) 1, 3