A 38-year-old man is seen for evaluation of severe exertional dyspnoea. Two years ago, he had been able to play squash regularly, but he stopped 6 months ago because of dyspnoea and fatigue during exercise. He now reports dyspnoea after climbing one flight of stairs. He has no cough, sputum or wheeze. He smoked one pack of cigarettes a day for 10 years and quit 7 years ago. He has no allergies or pets, and has not travelled outside Europe or the USA. One of his six siblings died at age 25 with an unknown progressive lung ailment.
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1. What would you expect the patient’s FRC and residual volume (RV) to be?
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Correct answer:
The obstructive ventilatory defect (low ratio of FEV1/FVC) coupled with a reduced diffusing capacity for carbon monoxide would suggest emphysema. Emphysema is characterized by a reduction in lung elastic recoil, increased lung compliance and floppy airways. Therefore, FRC and residual volume (RV) are both likely to be elevated.
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2. Why is the cardiac point of maximal impulse (PMI) shifted to the midline?
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The hyperinflation of the lung and the increase in FRC pull the apex of the heart caudally and to the middle. This can be seen radiographically as a small midline heart. The ECG will show low voltage due to the increased amount of air between the heart and the chest wall, with an axis close to 90°. For a similar reason, the apex beat may be quiet.
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3. Why is the FVC low?
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Correct answer:
The forced vital capacity (FVC) is low because the RV is high. Airways close prematurely in emphysema, which increases RV. Furthermore, because of the marked decrease in maximal expiratory flow rate due to the decreased lung elastic recoil, patients’ spirometry traces may not plateau, indicating that the lung was still emptying at very low flow rates when the FVC manoeuvre was terminated.
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4. Why is the DLCO low?
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Diffusing capacity is influenced by the alveolar–capillary surface area for gas exchange. Emphysema is characterized by a loss of the alveolar–capillary units that are utilized for diffusion. There need not be a defect in transfer of gas from the alveolus to the capillary to reduce the DLCO; a reduction in surface area is adequate to cause abnormality.
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5. What will happen to the patient’s oxygenation with exercise? Why?
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With exercise, the patient’s oxygen saturation will fall because of the diffusion defect. With this magnitude of diffusion defect, the red cells have adequate time to equilibrate with alveolar oxygen as they traverse the alveolar–capillary membrane. However, during exercise, when cardiac output rises, red cells traverse the alveolar–capillary membrane at rest more quickly and do not equilibrate with alveolar oxygen tension at the end–capillary segment. This results in deoxygenated blood entering the systemic circulation when cardiac output is increased. This exercise-induced desaturation will be accentuated when alveolar oxygen is reduced, such as at high altitude. The threshold for significant oxygen desaturation with exercise is approximately DLCO <50% predicted.
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6. Why is the patient’s jugular venous pressure elevated?
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The patient probably has a component of pulmonary hypertension due to the emphysema. The loss of capillary units raises pulmonary vascular resistance and increases right heart work. Any degree of hypoxaemia during exercise will exacerbate the pulmonary hypertension by superimposing hypoxic pulmonary vasoconstriction on the already increased resistance.
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7. The patient probably has a component of pulmonary hypertension due to the emphysema. The loss of capillary units raises pulmonary vascular resistance and increases right heart work. Any degree of hypoxaemia during exercise will exacerbate the pulmonary hypertension by superimposing hypoxic pulmonary vasoconstriction on the already increased resistance.
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Correct answer:
The presence of early onset emphysema, the family history and the history of cigarette smoking make the diagnosis of α1–antitrypsin (AAT) deficiency most likely. He probably has the homozygous ZZ genotype that causes a marked reduction of AAT levels to less than 15% normal. The radiograph is consistent with panacinar emphysema and alveolar destruction predominantly at the bases. The lung destruction is due to release of proteolytic enzymes from neutrophils and other inflammatory cells in response to environmental stimuli. These enzymes are normally neutralized by the antiproteases in the lung to prevent lung destruction in the presence of mild inflammatory stimuli. In AAT deficiency, the proteases are not neutralized, and induce panacinar emphysema under ‘normal’ circumstances. Cigarette smoking induces a neutrophilic response in the lung that accelerates the decline of lung function in AAT deficiency. Intravenous replacement of AAT in patients with reduced lung function may slow the decline in FEV1.
