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