A 45-year-old woman is evaluated for fatigue and exertional dyspnea. She has had difficulty walking for more than 1 or 2 blocks without becoming short of breath. She uses 2 pillows to sleep. Past medical history is significant for hyperlipidemia, hypertension, and type 2 diabetes mellitus. The patient smoked a pack a day for 15 years but quit 10 years ago. She does not use alcohol or illicit drugs. Temperature is 36.7 C (98 F), blood pressure is 150/90 mm Hg, pulse is 80/min, and respirations are 16/min. BMI is 55 kg/m². On physical examination, jugular venous distension is difficult to visualize due to a thick neck. Lungs are clear to auscultation without wheezes or crackles. Heart sounds are distant. The abdomen is obese and nontender. There is trace bilateral lower-extremity edema. Neurological examination is within normal limits. Chest x-ray is of poor quality due to under-penetration but shows no obvious abnormalities. ECG shows low-voltage QRS complexes but no significant ST-segment or T-wave abnormalities. Laboratory results are as follows: Which of the following is the predominant cause of this patient's dyspnea?

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11ec25c8_d10a_90cc_bc81_f9461eddbd74_MD0003_00 Obesity hypoventilation syndrome (OHS) is defined as daytime hypercapnia (PaCO₂ >45 mm Hg) in an obese patient (BMI ≥30 kg/m², often >40 kg/m²) without another explanation for the hypercapnia. Most patients have coexisting obstructive sleep apnea with frequent apneic events and daytime hypersomnolence. Other features of OHS include dyspnea, polycythemia, respiratory acidosis with compensatory metabolic alkalosis, pulmonary hypertension, and cor pulmonale. Several mechanisms likely contribute to hypoventilation and resultant hypercapnia. Obesity reduces chest wall and lung compliance, leading to a decrease in tidal volumes and total lung capacity and an increase in airway resistance. As a result, higher levels of ventilatory drive are required to maintain normocapnia, but there is an inability to exhale excess CO₂ during the day (due to persistent restriction). This leads to CO₂ accumulation overnight, with subsequent chronic respiratory acidosis. Renal bicarbonate excretion is decreased as a compensatory mechanism; this blunts the ventilatory response to the increased CO₂ and contributes to hypoventilation. In sum, patients with OHS "can't breathe" (due to excess weight and altered lung mechanics) and "won't breathe" (due to decreased chemosensitivity to hypercapnia from persistent nocturnal hypoventilation). (Choice A) Airway inflammation and bronchospasm occur with reactive airway disease, which would cause wheezing or cough. (Choice C) Left ventricular contractile dysfunction results in systolic left heart failure. This patient is at risk for diastolic heart failure as a result of likely prolonged uncontrolled hypertension. However, she has clear lungs and minimal lower-extremity edema, making left-sided heart failure less likely. (Choice D) Neuromuscular dysfunction (eg, due to myasthenia gravis, amyotrophic lateral sclerosis, Guillain-Barré syndrome) can cause hypoventilation and dyspnea. However, this patient's elevated BMI and lack of neurologic signs or symptoms make OHS a more likely diagnosis. (Choice E) Ventilation/perfusion mismatch occurs in disease processes such as pulmonary embolism, pneumonia, and pulmonary edema. Hypoxemia with an elevated alveolar-arterial gradient should be present. Hypoventilation causes hypoxemia (PaO₂ is often <70 mm Hg), but the alveolar-arterial gradient remains normal. Educational objective: Obesity hypoventilation syndrome is defined by obesity (BMI ≥30 kg/m²), daytime hypercapnia (PaCO₂ >45 mm Hg), and alveolar hypoventilation. Arterial blood gas will show hypercapnia, hypoxemia, and respiratory acidosis as a result of altered lung mechanics due to obesity and hypoventilation. ² References: Obesity hypoventilation syndrome: a state-of-the-art review. (http://www.ncbi.nlm.nih.gov/pubmed/20875161) Chronic hypoventilation and its management. (http://www.ncbi.nlm.nih.gov/pubmed/23997060) Obesity hypoventilation syndrome--the big and the breathless (http://www.ncbi.nlm.nih.gov/pubmed/20609602)

A 45-Year-Old Woman Is Evaluated for Fatigue and Exertional Dyspnea