Aim: Biological therapies developed for severe asthma may have a role in COPD patients with asthma features.Method: We carried out a prospective, consecutive, cross-sectional analysis of 80 patients with severe COPD GOLD IV/D.Results: We studied 80 patients (48.8% female), aged 57.6 +/- 5.1 years, ex-smokers with 35.7 +/- 21.2 pack years, BMI 22.3 +/- 3.5 kg/m(2), FEV1 of 0.61 +/- 0.2 L (21.1 +/- 5.6% pred), pO(2) 52.4 +/- 8.4 mmHg, and BODE 6.9 +/- 1.7. 68% had > 2 moderate or severe exacerbations annually. 16.1% (5/31) patients showed FEV1 reversibility of > 12% and > 200 ml despite maximal therapy, 33% (15/45) had FENO >= 22.5 ppb, 33% (24/73) had serum IgE >= 100 I.E./ml and there was positive allergen sensitization in 51.5% (35/68). Blood eosinophilia of >= 150 cells/mu l was seen in 47% (35/74). Induced sputum showed eosinophilia of >= 2% in 56% (14/24) with respiratory pathogens in 63.8% (30/47). We identified 12 (15%) patients with asthma-COPD overlap. Of these, 10 (83.3%) had frequent exacerbations and these patients had significantly more severe exacerbations requiring NIV or ICU than those without asthma features (p < 0.005).Conclusion: We detected asthma features in a substantial subset of stable patients with severe COPD. Asthma features were associated with more severe exacerbation despite optimal COPD therapy, representing potential candidates for targeted therapy with anti- IgE or anti-IL5.