What are the etiologies of chronic respiratory failure?

Etiologies of Chronic Respiratory Failure

Chronic respiratory failure develops from three primary pathophysiological mechanisms: ventilatory pump failure (Type 2/hypercapnic), gas exchange failure (Type 1/hypoxemic), or a combination of both, with COPD being the most common cause overall. 1

Type 2 (Hypercapnic) Respiratory Failure Etiologies

Obstructive Lung Diseases

• COPD accounts for the majority of chronic hypercapnic respiratory failure cases, resulting from tobacco smoke exposure (the major risk factor worldwide) or biomass cooking/heating in poorly ventilated dwellings 1
• Dynamic hyperinflation prevents expiration to relaxation volume, creating intrinsic PEEP (PEEPi) that acts as an inspiratory threshold load, while severe V/Q abnormalities worsen gas exchange 1
• Asthma may progress to chronic airflow limitation and COPD, particularly with airway hyperresponsiveness as an independent predictor 1
• Bronchiectasis causes chronic airway inflammation and mucus retention leading to ventilatory failure 2

Neuromuscular Disorders

• Progressive ventilatory pump failure occurs in ALS, muscular dystrophy, myasthenia gravis, and acid maltase deficiency, where diaphragm involvement often precedes locomotor disability 3, 4
• Vital capacity <15 mL/kg or <1 L suggests need for mechanical ventilation consideration 5
• Respiratory muscle weakness and fatigue lead to chronic respiratory failure through inability to maintain adequate minute ventilation 3

Chest Wall Deformities

• Severe chest wall deformity including scoliosis and thoracoplasty restrict lung expansion and reduce ventilatory capacity 3, 4
• These restrictive mechanics combine with increased work of breathing to produce chronic hypoventilation 4

Obesity Hypoventilation Syndrome

• Combines restrictive mechanics from excess weight with central drive abnormalities, leading to chronic CO₂ retention 4
• The American Thoracic Society recommends long-term mechanical ventilation for this condition 5

Type 1 (Hypoxemic) Respiratory Failure Etiologies

Parenchymal Lung Diseases

• Interstitial lung diseases and pulmonary fibrosis cause chronic hypoxemia through diffusion limitation and V/Q mismatch 5
• Chronic lung disease of infancy (including bronchopulmonary dysplasia) leads to abnormal lung mechanics, air trapping, and chronic hypoxemia 3
• Severe childhood respiratory infections are associated with reduced lung function and increased respiratory symptoms in adulthood 1

Pulmonary Vascular Disease

• Chronic pulmonary hypertension increases right ventricular afterload through hypoxic vasoconstriction, vascular remodeling, and increased pulmonary vascular resistance 3
• Out-of-proportion pulmonary hypertension (mean PAP >40 mmHg) represents a distinct phenotype requiring specific management 3

Chronic Aspiration

• Gastroesophageal reflux and swallowing dysfunction cause recurrent aspiration, leading to pulmonary inflammation and chronic hypoxemia 3
• Pulmonary hyperinflation affects diaphragmatic configuration and lower esophageal sphincter function, perpetuating the cycle 3

Mixed Etiologies (Combined Type 1 and Type 2)

Cystic Fibrosis

• Chronic airway infection, mucus plugging, and progressive bronchiectasis lead to both ventilatory failure and gas exchange abnormalities 3
• Secretion clearance becomes a major limiting factor as disease progresses 3

COPD with Emphysema Predominance

• Emphysema with pulmonary hyperinflation causes both severe V/Q mismatch (hypoxemia) and dynamic hyperinflation (hypercapnia) 3
• Flow-limited expiration during tidal breathing initially occurs with exercise, then progresses to rest when FEV₁ falls below 1.0 L 5

Contributing Pathophysiological Mechanisms

Ventilatory Constraints

• Increased work of breathing from expiratory airflow obstruction and dynamic hyperinflation intensifies dyspnea and limits exercise capacity 3
• Respiratory muscle dysfunction results from inactivity-induced deconditioning, systemic inflammation, oxidative stress, blood gas disturbances, and corticosteroid use 3

Cardiac Dysfunction

• Right ventricular hypertrophy and failure develop from chronic pulmonary hypertension, compromising left ventricular filling through septal shifts 3
• Cardiovascular disease accounts for 26% of deaths in moderate-to-severe COPD patients 3

Peripheral Muscle Dysfunction

• Lower limb muscle dysfunction is frequent in chronic respiratory disease, with skeletal muscle alterations rendering muscles susceptible to contractile fatigue 3
• Increased lactic acid production at given exercise work rates contributes to exercise limitation and ventilatory demand 3

Nutritional and Inflammatory Factors

• Malnutrition causes delayed lung growth, respiratory muscle weakness, and susceptibility to diaphragmatic fatigue 3
• Persistent systemic inflammation and elevated CRP ≥5 mg/L independently predict mortality in chronic respiratory failure 2

Critical Diagnostic Thresholds

Chronic respiratory failure is defined by persistent impairment with PaO₂ <8 kPa (60 mmHg) and/or PaCO₂ >6 kPa (45 mmHg) that develops gradually with compensatory mechanisms. 5

• Post-bronchodilator FEV₁/FVC <0.70 confirms persistent airflow limitation in COPD 1
• Significant hypoxemia or hypercapnia is rare with FEV₁ >1.0 L in COPD 5
• Arterial blood gas analysis while breathing room air is required before any therapy changes 5