Chronic idiopathic cough and iron deficiency

PURPOSE: Cough is more frequent in women than in men. Iron deficiency is present in 20% of women in industrialized countries, and in USA nearly 1/3 of women has virtually no iron stores. We investigated whether there is a link between iron deficiency and idiopathic cough. METHODS: We evaluated 16 healthy non-smoking women (mean age 38 ± 3 yrs) with chronic idiopathic cough, normal lung function tests, and no history of atopy, asthma or other bronchopulmonary diseases, and no symptoms and ENT evidence of gastroesophageal reflux. All had iron deficiency (serum ferritin 9.4 ± 0.9 ng/ml) and mild anemia (hemoglobin 11,6 ± 1,3 g/dl). The patients were examined before and after iron supplementation, provided that ferritin and hemoglobin were normal in the last two months. At both visits, the patients underwent measurement of spirometry, exhaled nitric oxide (FeNO), and histamine responsiveness of the extrathoracic airway (EA) (PC25MIF50) and of the bronchi (PC20FEV1), and histamine cough threshold (PC5coughs). Hyperresponsiveness (HR) was diagnosed when PC25MIF50 (EA-HR), PC20FEV1 (B-HR) and PC5coughs (cough-HR) were ≤; 8 mg/ml. RESULTS: During iron deficiency there was marked oral redness and soreness, with atrophy of oral mucosa and tongue papillae, and angular cheilosis; 9 patients had dysphonia. FeNO was normal in all the patients (14.9 ± 1.5 ppb). Histamine challenge showed B-HR in 4 women, EA-HR in 14 women, and cough-HR in 15 women. PC5coughs was closely related to PC25MIF50 (p<0.05). After iron supplementation, cough and signs and symptoms of pharyngolaryngitis were improved or resolved. Histamine thresholds were all significantly increased: PC20FEV1 from 18.8 ± 3.7 to 24.1 ± 3.8 mg/ml (p<0.01), PC25MIF50 from 6.2 ± 1.3 to 22.2 ± 3.6 mg/ml (p=0.001) and PC5coughs from 3.8 ± 1.3 to 17.8 ± 4.3 mg/ml (p<0.01). CONCLUSION: Chronic idiopathic cough in iron deficient women was strongly associated with EA-HR. Iron regulates the production of proinflammatory cytokines and its deficiency might favour upper airway inflammation and dysfunction.