Obesity Related Dyspnoea

Obesity related dyspnoea is breathlessness caused or worsened by excess body weight, which increases the mechanical load on the respiratory system and the oxygen demand of breathing, and is often compounded by deconditioning, cardiac disease, sleep disordered breathing, asthma and anxiety. It is the commonest cause of exertional breathlessness in people with a body mass index of 30 kg/m2 or more, and is a diagnosis made after other causes are excluded.

• Mechanisms:
  • Reduced chest wall compliance from fat on the chest, abdomen and diaphragm, with a fall in expiratory reserve volume and functional residual capacity (the most characteristic change), and sometimes airway closure at tidal breathing.
  • Increased respiratory work of breathing, with 3 to 4 times higher oxygen cost of breathing than in lean people at the same ventilation, and increased oxygen demand from a larger body mass.
  • Reduced respiratory muscle strength and endurance, and ventilation perfusion mismatch with hypoxaemia in the lung bases.
  • Systemic inflammation and airway hyperresponsiveness (obesity related asthma), reflux, and leptin resistance.
  • Associated disorders: obstructive sleep apnoea, obesity hypoventilation syndrome, heart failure with preserved ejection fraction, pulmonary hypertension, venous thromboembolism, coronary disease, and diabetes.
• Prevalence: obesity affects about 15 to 40% of adults depending on region, and about 30 to 40% of obese patients report breathlessness on exertion. Breathlessness increases with body mass index, especially above 35 to 40.
• Obesity hypoventilation syndrome is defined as a body mass index of 30 or more, daytime hypercapnia (partial pressure of carbon dioxide above 45 mmHg or 6 kPa) and sleep disordered breathing, without another cause of hypoventilation. It affects 10 to 20% of patients with obstructive sleep apnoea and obesity, and 30% of those with a body mass index above 40.
• Risk factors for severe disease: central (abdominal) obesity, body mass index above 40, male sex, older age, smoking, sleep apnoea, and sedentary lifestyle.

• Breathlessness on exertion (climbing stairs, walking uphill, carrying loads) and sometimes at rest, worse lying flat (reduced lung volumes) or bending forward, with decreased exercise capacity. The breathlessness often develops gradually over years.
• Associated symptoms: snoring, witnessed apnoeas, unrefreshing sleep, morning headaches, daytime sleepiness, fatigue, leg swelling, orthopnoea, reflux, wheeze, chest tightness, joint pain limiting activity, and low mood.
• Examination: a high body mass index and waist circumference (above 102 cm in men and 88 cm in women), a large neck circumference (above 43 cm in men and 41 cm in women), reduced chest wall movement, a crowded oropharynx, ankle oedema, and signs of right heart strain. Oxygen saturation may be reduced at rest in obesity hypoventilation (below 94%), with a plethoric complexion, cyanosis, raised jugular venous pressure and peripheral oedema in severe disease.
• Differential diagnosis: asthma, COPD, interstitial lung disease, heart failure, coronary disease, arrhythmia, pulmonary embolism and chronic thromboembolic disease, pulmonary hypertension, anaemia, thyroid disease, deconditioning, dysfunctional breathing, anxiety, neuromuscular weakness, pleural disease, and medicine effects (beta blockers, amiodarone, nitrofurantoin).
• Red flags: breathlessness at rest, oxygen saturation below 92%, exertional chest pain, syncope, haemoptysis, orthopnoea and paroxysmal nocturnal dyspnoea, leg swelling, unilateral leg swelling, rapid progression, hypercapnic features (morning headache, confusion, drowsiness, flapping tremor), and weight loss.
• Complications: respiratory failure, pulmonary hypertension and right heart failure (cor pulmonale), polycythaemia, perioperative complications, cardiovascular disease, reduced quality of life, and mortality.

• A systematic evaluation to exclude other causes and identify contributing conditions. Measure weight, height, body mass index, waist and neck circumference, blood pressure, oxygen saturation at rest and after walking, and perform full cardiorespiratory examination.
• Initial investigations: full blood count (polycythaemia, anaemia), thyroid function tests, glucose or HbA1c, lipid profile, liver and renal function, serum bicarbonate (a level of 27 mmol/L or more suggests chronic hypercapnia and prompts arterial blood gas testing), B-type natriuretic peptide (levels are lower in obesity, so a lower threshold, such as above 50 to 100 ng/L, is used to suspect heart failure), electrocardiogram, and chest X-ray.
• Spirometry and lung volumes: a normal or mildly reduced forced vital capacity and forced expiratory volume in 1 second with a preserved ratio (above 0.7), and a reduced expiratory reserve volume and functional residual capacity. A restrictive pattern with a low total lung capacity is seen only in severe obesity. The diffusing capacity is normal or slightly raised. Look for obstruction (asthma, COPD) with bronchodilator reversibility.
• Arterial blood gas on room air in patients with a serum bicarbonate of 27 mmol/L or more, a body mass index above 40, oxygen saturation below 94%, or sleep apnoea, to detect hypercapnia (partial pressure of carbon dioxide above 45 mmHg or 6 kPa).
• Echocardiography for heart failure with preserved ejection fraction (a normal ejection fraction with diastolic dysfunction and raised filling pressures) and pulmonary hypertension.
• Sleep study (home sleep apnoea test or polysomnography) for snoring, witnessed apnoea, sleepiness, or hypercapnia.
• Cardiopulmonary exercise testing for unexplained breathlessness, which shows reduced peak oxygen uptake relative to body weight, but normal when expressed per kilogram of lean mass, and a normal ventilatory reserve, an early rise in heart rate, and no cardiac or ventilatory limitation.
• CT pulmonary angiography or ventilation perfusion scan when thromboembolism is suspected, and CT of the chest for abnormal X-ray or interstitial disease.
• Assess for asthma (fractional exhaled nitric oxide, peak flow variability, bronchial challenge) because obesity related asthma is common and often over diagnosed.

• Weight loss is the most effective treatment, which improves lung volumes, breathlessness, exercise capacity, sleep apnoea, asthma control, blood pressure and glucose.
  • Lifestyle programme: a daily energy deficit of 500 to 750 kcal (reduce intake to 1200 to 1500 kcal per day in women and 1500 to 1800 kcal in men), a diet of high protein and low refined carbohydrate, with dietitian support, and a target loss of 5 to 10% in 3 to 6 months, then maintenance. A 10% weight loss improves forced expiratory volume in 1 second and forced vital capacity by about 4 to 8%, and reduces breathlessness.
  • Physical activity: graded aerobic exercise (150 minutes per week of moderate intensity, starting at 10 minutes and building up), strength training, and water exercise for joint pain. Pulmonary rehabilitation improves exercise capacity and breathlessness.
  • Pharmacotherapy (body mass index of 30 or more, or 27 or more with comorbidity): semaglutide 0.25 mg subcutaneously once weekly for 4 weeks, increased every 4 weeks to 0.5 mg, 1 mg, 1.7 mg and 2.4 mg once weekly, or tirzepatide 2.5 mg subcutaneously once weekly for 4 weeks, then increased by 2.5 mg every 4 weeks to a maintenance dose of 5 to 15 mg weekly, or liraglutide 0.6 mg daily increased by 0.6 mg weekly to 3 mg daily, or orlistat 120 mg orally 3 times daily with meals. Expected weight loss is 5 to 10% with orlistat and liraglutide, about 15% with semaglutide 2.4 mg, and about 20% with tirzepatide at higher doses. Gastrointestinal adverse effects (nausea, vomiting, diarrhoea, constipation) are common, so give small meals, and avoid in pancreatitis, gallstone disease, and a history of medullary thyroid cancer or multiple endocrine neoplasia type 2. Stop in pregnancy.
  • Bariatric surgery (sleeve gastrectomy, gastric bypass) for body mass index of 40 or more, or 35 or more with comorbidity (sleep apnoea, type 2 diabetes, hypertension), or 30 or more with poorly controlled type 2 diabetes in specialist care. It produces 25 to 35% weight loss and large improvements in lung function and breathlessness.
• Treat contributing conditions:
  • Asthma: inhaled corticosteroid (budesonide 200 to 400 micrograms twice daily) with a long acting beta agonist when asthma is confirmed by objective tests, with weight loss. Avoid overtreatment.
  • Obstructive sleep apnoea: continuous positive airway pressure 4 to 20 cm of water, weight loss, and avoiding alcohol and sedatives.
  • Obesity hypoventilation syndrome: non-invasive ventilation (bilevel positive airway pressure, for example inspiratory pressure 15 to 20 cm of water and expiratory pressure 5 to 8 cm of water) or continuous positive airway pressure, started in a specialist sleep or ventilation service, with weight loss. Avoid oxygen therapy alone, and target oxygen saturation of 88 to 92% when oxygen is needed.
  • Heart failure with preserved ejection fraction: furosemide 20 to 40 mg orally once daily for congestion, empagliflozin 10 mg or dapagliflozin 10 mg once daily, blood pressure control, and weight loss.
  • Pulmonary hypertension and thromboembolic disease: specialist care, and anticoagulation for embolism (apixaban 10 mg 12 hourly for 7 days, then 5 mg 12 hourly, with higher body weight above 120 kg needing specialist advice).
  • Reflux: omeprazole 20 to 40 mg once daily, weight loss, and avoidance of late meals.
  • Anxiety and depression: cognitive behavioural therapy, with sertraline 25 to 50 mg daily where needed. Avoid medicines that cause weight gain where possible (some antidepressants, antipsychotics, steroids, sulfonylureas and insulin).
  • Anaemia, thyroid disease and other contributors: treat the cause.
• Breathing and positioning: upright positioning to ease breathing, a pillow or wedge for sleeping, diaphragmatic breathing, inspiratory muscle training, and avoiding tight clothes and binders.
• Avoid sedatives, opioids, and benzodiazepines, which can cause respiratory depression in obesity hypoventilation. Be careful with perioperative care: inform the anaesthetist, use regional anaesthesia, positive airway pressure after surgery, and extended monitoring.
• Special groups:
  • Pregnancy: monitor weight gain, treat sleep apnoea and asthma, avoid weight loss drugs, and exclude embolism and heart disease. Continuous positive airway pressure is safe.
  • Children and adolescents: family based lifestyle intervention, and assessment for asthma and sleep apnoea. Specialist pharmacotherapy (liraglutide or semaglutide) and bariatric surgery are available for severe obesity in selected adolescents.
  • Elderly: balance the weight loss with muscle preservation (protein 1.0 to 1.2 g/kg per day and resistance exercise), and treat heart and lung disease.
  • Renal impairment: adjust doses of drugs, with caution for orlistat and semaglutide for gastrointestinal losses.
  • Joint disease: low impact exercise (swimming, cycling), and analgesia.
• Follow up: review monthly during the early phase of weight loss, then every 3 to 6 months, with weight, symptoms, oxygen saturation, blood pressure, glucose, and bicarbonate. Refer to a respiratory or sleep physician for suspected hypoventilation, severe sleep apnoea, or unexplained hypoxia, and to a bariatric and obesity service when criteria are met.