Airway and cough responsiveness and exhaled nitric oxide in non-smoking patients with stable chronic heart failure.

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Abstract
OBJECTIVE: To investigate the airway and cough responsiveness in non-smoking patients with stable chronic heart failure. Cough and wheeze, features associated with hyper-responsive airways, are not uncommon especially in decompensated chronic heart failure. Bronchial hyperresponsiveness has previously been demonstrated in chronic heart failure but this may have been confounded by smoking and acute decompensation. DESIGN: Case-control study. SETTING: Tertiary specialist hospital. PATIENTS AND INTERVENTIONS: Airway responsiveness to methacholine (a direct stimulant of smooth muscle in the airways), sodium metabisulphite (a putative stimulant of airway sensory nerves), and exercise was examined in 10 non-smoking patients with stable chronic heart failure (age 56.5 (3.2) (SEM) years; 7 men; radionuclide left ventricular ejection fraction 20.8 (2.9)%; radiographic cardiothoracic ratio 0.56 (0.02)). Exhaled nitric oxide, a product of the action of proinflammatory cytokines, was also measured to assess the contribution of local inflammation to airway responsiveness. The cough responses to low-concentration chloride solutions and to capsaicin were studied. Because all patients were receiving angiotensin-converting enzyme inhibitors, which may influence airway responsiveness and cough, 8 asymptomatic non-smoking controls taking angiotensin-converting enzyme inhibitors for essential hypertension were also studied (age 54.3 (2.8) years; 6 men; radiographic cardiothoracic ratio 0.46 (0.01)). RESULTS: The mean provocative concentration that induced a 20% decrease in forced expiratory volume in 1 second (FEV1) was 67.6 v 79.8 mg/ml (P = 0.71) for methacholine and 276.7 v 290.4 mg/ml (P = 0.79) for sodium metabisulphite in chronic heart failure patients and controls respectively. The change in FEV1 after maximal cardiopulmonary exercise testing was +1.44% in patients and +2.53% in controls (P = 0.47), indicating that there was no exercise-induced bronchospasm in either group (peak oxygen consumption was 16.9 (1.3) v 26.5 (2.3) ml/kg/min respectively, P < 0.01). Exhaled nitric oxide concentration was not increased in chronic heart failure (12.3 (1.7) v 16.2 (3.3) ppb, P = 0.32). The median cough counts after nebulised 0 mM and 37.5 mM chloride solutions were 2.5 v 1.0 (P = 0.6) and 5.5 v 5.5 (P = 0.5) respectively and the capsaicin concentration causing two or more coughs was 13.5 v 6.5 microM (P = 0.5). CONCLUSION: Airway hyper-responsiveness is not a predominant feature in non-smoking patients with stable chronic heart failure treated with, and tolerant to, angiotensin-converting enzyme inhibitors. It is unlikely to contribute to the exertional dyspnoea seen in these patients.