PULMONOLOGY

phosphodiesterase-4 inhibitors is to reduce inflammation by inhibiting of the breakdown of intracellular cyclic AMP. It is a once daily oral medication with no direct bronchodilator activity, although it has been shown to improve FEV1 in patients treated with salmeterol or tiotropium. Roflumilast reduces moderate and severe exacerbations treated with corticosteroids by 15 %-20% in patients with chronic bronchitis, severe to very severe COPD, and a history of exacerbations.

The effects on lung function are also seen when roflumilast is added to longacting bronchodilators. There are no direct comparison or add-on studies of roflumilast and inhaled corticosteroids. Phosphodiesterase-4 inhibitors should always be used in combination with at least one long-acting bronchodilator.

Phosphodiesterase-4 inhibitors have more adverse effects than inhaled medications for COPD. The most frequent adverse effects are nausea, reduced appetite, abdominal pain, diarrhoea, sleep disturbances, and headache.

Adverse effects led to increased withdrawal in clinical trials from the group receiving roflumilast. Adverse effects seem to occur early during treatment, are reversible, and diminish over time with continued treatment.

In controlled studies an average unexplained weight loss of two kilogramme has been seen and weight monitoring during treatment is advised as well as avoiding treatment with roflumilast in underweight patients. Roflumilast should also be used with caution in patients with depression. Roflumilast and theophylline should not be given together.

Oxygen therapy

The long-term administration of oxygen(> 15 hours per

day) to patients with chronic respiratory failure has been shown to increase survival in patients with severe resting hypoxemia. Long-term oxygen therapy is indicated for patients who have PaO 2 at or below 7.3 kPa( 55mmHg) or SaO 2 at or below 88 %, with or without hypercapnia confirmed twice over a three-week period.

Ventilatory support

Non-invasive ventilation( NIV) is increasingly used in patients with stable very severe COPD. Randomised controlled trials provide contradictory results regarding the clinical benefits of long-term NIV in patients with COPD and chronic hypercapnia, especially in terms of health status.

Surgical treatments

Lung volume reduction surgery( LVRS) is a surgical procedure in which parts of the lung are resected to reduce hyperinflation, making respiratory muscles more effective pressure generators by improving their mechanical efficiency( as measured by length / tension relationship, curvature of the diaphragm, and area of apposition).

In addition, an LVRS increase the elastic recoil pressure of the lung and thus improves expiratory flow rates and reduces exacerbations. The advantage of surgery over medical therapy is more significant among patients with predominantly upper-lobe emphysema and low exercise capacity prior to treatment.

A prospective economic analysis indicated that LVRS is costly relative to healthcare programmes not including surgery. In contrast to medical treatment, LVRS has been demonstrated to result in improved survival( 54 % versus 39.7 %) in severe emphysema patients with upper-lobe emphysema and low postrehabilitation exercise capacity.

In similar patients with high post-pulmonary rehabilitation

exercise capacity no difference in survival was noted after LVRS, although healthrelated quality of life and exercise capacity improved.

LVRS has been demonstrated to result in higher mortality than medical management in severe emphysema patients with an FEV1 ≤20 % predicted and either homogeneous emphysema on high resolution computed tomography or a diffusing capacity for carbon monoxide( DLco) ≤20 % predicted.

Lung transplantation

In appropriately selected patients with very severe COPD, lung transplantation has been shown to improve quality of life and functional capacity. The common complications seen in COPD patients after lung transplantation, apart from post-operative mortality, are acute rejection, bronchiolitis obliterans, opportunistic infections such as cytomegalovirus, fungal( candida, aspergillus, cryptococcus, pneumocystis) or bacterial( pseudomonas, staphylococcus species) infections, and lymphoproliferative disease. Lung transplantation is limited by the shortage of donor organs and costs. Criteria for referral for lung transplantation include COPD with a Body-mass index, airflow Obstruction, Dyspnea, and Exercise( BODE) index exceeding five.

Recommended criteria for listing include a BODE index of seven to ten and at least one of the following: History of exacerbation associated with acute hypercapnia( PaCO 2 > 6.7kPa [ 50mmHg ]), pulmonary hypertension, cor pulmonale, or both despite oxygen therapy and FEV1 < 20 % predicted with either DLco < 20 % predicted or homogenous distribution of emphysema.

Source: Global Strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. Updated 2016. SF

reduction by Roflumilast of moderate and severe exacerbations when treated with corticosteroids.

The Specialist Forum | Vol. 17 No. 4

May 2017 | 11