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Study Title:

Vitamin B12 Deficiency and Chronic Cough

Study Abstract

Background: Chronic cough is characterized by sensory neuropathy. Vitamin B-12 (cobalamin) deficiency (Cbl-D) causes central and peripheral nervous system damage and has been implicated in sensory neuropathy and autonomic nervous system dysfunction.

Objective: We evaluated whether Cbl-D has a role in chronic, unexplained cough.

Design: Laryngeal threshold (histamine concentration that provokes a 25% decrease in the midinspiratory flow), bronchial threshold (histamine concentration that provokes a 20% decrease in the forced expiratory volume in 1 s), and cough threshold (histamine concentration that causes ≥5 coughs) in response to an inhaled histamine were assessed in 42 patients with chronic, unexplained cough [27 Cbl-D patients and 15 patients without Cbl-D (Cbl-N)] before and after intramuscular injections of cobalamin for 2 mo. Laryngeal, bronchial, and cough hyperresponsiveness was diagnosed when histamine concentration thresholds were ≤8 mg/mL. Seven Clb-D and 3 Cbl-N patients underwent an oropharyngeal biopsy before treatment.

Results: Cbl-D patients had a higher prevalence of laryngeal hyperresponsiveness than did Cbl-N patients (92.6% compared with 66.7%; P = 0.03), a thinner oropharyngeal epithelium [133.7 μm (95% CI: 95, 172 μm) compared with 230.8 μm (95% CI: 224, 237 μm), P = 0.002], a lower number of myelinated nerve fibers [2.25/mm2 (95% CI: 1.8, 2.7/mm2) compared with 3.44/mm2 (95% CI: 3, 3.8/mm2), P = 0.05], and a higher immunoreactive score for nerve growth factor (NGF) [6.7 (95% CI: 6, 7.3) compared with 2.8 (95% CI: 2.5, 3.1), P = 0.02]. After cobalamin supplementation, symptoms and laryngeal, bronchial, and cough thresholds were significantly improved in Cbl-D but not in Cbl-N patients.

Conclusions: This study suggests that Cbl-D may contribute to chronic cough by favoring sensory neuropathy as indicated by laryngeal hyperresponsiveness and increased NGF expression in pharyngeal biopsies of Cbl-D patients. Cbl-D should be considered among factors that sustain chronic cough, particularly when cough triggers cannot be identified.

Study Information

Caterina B Bucca, Beatrice Culla, Giuseppe Guida, Savino Sciascia, Graziella Bellone, Antonella Moretto, Enrico Heffler, Massimiliano Bugiani, Giovanni Rolla, and Luisa Brussino
Unexplained chronic cough and vitamin B-12 deficiency.
American Journal of Clinical Nutrition
2011 March
Department of Clinical Pathophysiology (CBB, GB, and AM) and Biomedical Science and Human Oncology.
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