History
A 38-year-old man has presented to the emergency department with shortness of breath and wheeze. On arrival he was in extremis and unable to complete a full sentence. He was discharged from the hospital one week ago after acute severe exacerbation of chronic obstructive pulmonary disease (COPD), first diagnosed three years ago. This is his third casualty attendance over the past 12 months. He smokes five cigarettes a day. He is now awaiting investigation for deranged liver function tests. His father died of a chest disease in his 30s. He is taking salbutamol inhaler p.r.n.; tiotropium, 18 mg once daily;
Symbicort 6/200, 2 puffs daily; carbocisteine, 375 mg thrice daily; Uniphyllin Continus, 400 mg twice daily.
Examination
This man is visibly dyspnoeic with a respiratory rate of 32/min. His trachea is central, expansion of the chest poor but equal, and auscultation reveals widespread expiratory wheeze but no clinical sign of consolidation. A chest X-ray shows hyperinflated lung fields. Observations: heart rate 130/min, blood pressure 130/80 mmHg, SaO2 91 per cent on FiO2 0.4.
INVESTIGATIONS
Normal range
White cells 15.0 4–11 ¥ 109/L
Haemoglobin 13.0 13–18 g/dL
Platelets 150 150–400 ¥ 109/L
Sodium 140 135–145 mmol/L
Potassium 3.2 3.5–5.0 mmol/L
Urea 7.1 3.0–7.0 mmol/L
Creatinine 100 60–110 mmol/L
C-reactive protein 10 <5 mg/L
Bilirubin 50 5–25 mmol/L
Aspartate aminotransferase 49 8–40 IU/L Alkaline phosphatase 600 42–98 IU/L
Albumin 31 35–50 g/L
• What are the differential diagnoses?
• What is the appropriate initial management?
• What is the unifying diagnosis and how would you confirm it?
The main differential diagnoses for this man’s acute shortness of breath include asthma, acute exacerbation of COPD, pneumonia, and acute pulmonary oedema. Pneumothorax and pulmonary embolism should also be considered but are much less likely.
This man presented with type 2 respiratory acidosis and partially compensated metabolic alkalosis. His arterial blood gas result is worrying and needs urgent action: referral to the critical care service should be considered. As with all acutely unwell patients, airway, breathing and circulation should be managed accordingly and he should be nursed in a high-dependency area, with cardiorespiratory monitoring. Venous access should be established and a 12-lead ECG should be taken. A chest radiograph should be requested to look for acute pulmonary oedema, pneumothorax and pneumonia. In this case, the chest X-ray showed hyperexpanded lung fields.
The definition and treatment of acute exacerbation of COPD is well summarized by the NICE guideline CG12. The pharmacological management includes appropriate oxygen therapy, bronchodilators (b2 agonists, anticholinergics and theophyllines), steroids and antibiotics.
Oxygen is a drug and it should be given appropriately by selecting an appropriate deliv-ery device. Various types of mask are classified into variable (nasal cannulae, Hudson masks) and fixed-performance (Venturi masks, non-rebreathing reservoir masks, and masks delivering non-invasive ventilation). A fixed-performance device is so called because the fraction of inspired oxygen (FiO2) is known; it is commonly quoted as FiO2 or percentage oxygen (e.g. FiO2 0.4 = 40 per cent oxygen). For variable-performance devices the FiO2 is unknown, so it is impossible to prescribe FiO2 0.24 if oxygen is delivered by nasal cannulae; instead one should quote the amount of oxygen in litres delivered (e.g.
4 L oxygen via nasal cannulae). For variable-performance devices, the amount of FiO2 being received by the patient depends on, for example, the type of device and respiratory rate and tidal volume. A fixed-performance device should be used in patients at risk of type 2 respiratory failure. (Type 1 respiratory failure = PaO2 <8 kPa; type 2 = PaO2 <8 kPa and PaCO2 >6.7 kPa.) This may be difficult to predict and the key is to ensure hypoxia is corrected (PaO2 >8 kPa) and to perform frequent clinical assessment to look for clini-cal signs of CO2 narcosis and to perform sequential arterial blood gas sampling to look for interval changes in PaO2 and PaCO2 values. The usual practice is to perform arterial blood gas sampling 30 minutes after a change of FiO2 or device (if clinically appropriate).
The dose of oxygen should be chosen and titrated according to these results. For patients not at risk of type 2 respiratory failure, it is appropriate to aim for oxygen saturations of
>94 per cent (assessed on pulse oximeter and arterial blood gas sampling). For patients at risk of type 2 respiratory failure, it may be appropriate to aim for oxygen saturation of 88–92 per cent, depending on the clinical scenario. Oxygen should be maintained to
>8 kPa; below this level the total amount of oxygen available to tissues will be danger-ously variable and low as demonstrated by the haemoglobin oxygen dissociation curve.
Non-invasive ventilation in the form of bilevel positive airway pressure (BIPAP), deliv-ered via a face or nasal mask, has revolutionized the management of type 2 respiratory failure in COPD. The British Thoracic Society (BTS) has published a guideline on its use.
These patients should be ideally managed in critical-care units where access to mechani-cal ventilation is rapid. Bronchodilators could be delivered via BIPAP device concurrently which is useful in the treatment of acute exacerbation of COPD.
163 In acute severe exacerbation of COPD (or asthma), a ‘back to back’ nebulizers strategy is used. This is mainly for b2 agonists such as salbutamol. For salbutamol nebulizer it is probably better to prescribe a 2.5 mg rather than 5 mg dose to minimize the adren-ergic side-effects. To achieve equivalent bronchodilating effects, the low dose could be given more frequently. Salbutamol should rarely be given above 10 mg per hour. If this is needed, other bronchodilators or ventilation strategies should be considered because, beyond this dose, it may cause excessive tachycardia, peripheral vasodilation, hyperlac-tataemia and hypokalaemia. In order to achieve appropriate drug delivery, nebulizers should be driven by 8 L of air or oxygen; therefore in patients with type 2 respiratory failure it is important to notify nursing staff to deliver nebulizer therapy through medical air. If oxygen therapy is needed then it could be temporarily delivered via nasal cannu-lae. Patients taking oral theophylline therapy should have theophylline level measured at admission to determine whether it is subtherapeutic or at toxic level. This is particularly important if intravenous theophylline therapy is considered.
The decision to initiate antibiotics may be difficult at times when there is no sign of focal consolidation. It may be appropriate to initiate antibiotics if there is a change of sputum colour or frequency or clinical signs of sepsis. Steroids should be given in all severe COPD exacerbations.
This man was diagnosed with COPD at a very young age with a minimal smoking history.
It may be appropriate to review his case histories and previous lung function tests, chest imaging and bronchodilator reversibility tests to ensure this patient is not suffering from asthma rather than COPD. If COPD is confirmed then further investigation should be con-sidered. In the setting of a positive family history of early death due to chest disease and a history of deranged liver function tests, one should certainly consider a1-antitrypsin deficiency.
a1-Antitrypsin deficiency (A1AD) is a disease which has various phenotypes (designated M, S, ZZ). It is one of the most commonly inherited genetic disorders. MM confers 100 per cent protease inhibitor activity but ZZ is the most severe A1AD phenotype. The severity of lung disease differs even in siblings with the same allele. This is partially explained by environmental factors such as smoking and dust exposure; therefore it is paramount to educate patients with a1-antitrypsin deficiency not to smoke. Presentation (if not diagnosed through family screening) is often at the third or fourth decade with emphyse-matous lung changes out of proportion to smoking history. The emphyseemphyse-matous changes are predominately in the lower zones, in contrast to smoking-related emphysema, but it can affect all lung fields. Only a minority of homozygous A1AD develop severe liver dis-ease, but some patients may present with neonatal jaundice. Other organ manifestations of A1AD include relapsing panniculitis, vasculitis and glomerulonephritis. Treatment of A1AD is similar to standard COPD therapy with smoking cessation particularly empha-sized. a1-Antitrypsin is not routinely replaced. Lung and/or liver transplant may be options for some patients. A1AD patients should be managed at a specialist centre and their family should be offered genetic counselling.
KEY POINTS
• Acute exacerbation of COPD is a common acute medical emergency that should be recognized and treated promptly.
• a1-Antitrypsin deficiency is one of the most commonly inherited genetic disorders.
Smoking cessation is the key in halting its lung manifestations.
165