Unexplained chronic cough and vitamin B-12 deficiency.
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.


METHODS
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/mm(2) (95% CI: 1.8, 2.7/mm(2)) compared with 3.44/mm(2) (95% CI: 3, 3.8/mm(2)); 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.
Department of Clinical Pathophysiology, University of Turin, Turin, Italy. caterina.bucca@unito.it
Caterina B
CB
Bucca
Beatrice
B
Culla
Giuseppe
G
Guida
Savino
S
Sciascia
Graziella
G
Bellone
Antonella
A
Moretto
Enrico
E
Heffler
Massimiliano
M
Bugiani
Giovanni
G
Rolla
Luisa
L
Brussino
D000328:Adult; D001706:Biopsy; D003371:Cough / Q000209:etiology*; D003937:Diagnosis, Differential; D005260:Female; D006632:Histamine; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D020932:Nerve Growth Factor / Q000378:metabolism; D009960:Oropharynx / Q000294:innervation / Q000378:metabolism / Q000473:pathology; D011115:Polyneuropathies / Q000209:etiology; D012720:Severity of Illness Index; D014805:Vitamin B 12 / Q000097:blood / Q000627:therapeutic use*; D014806:Vitamin B 12 Deficiency / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
C502240:NGF protein, human; D006632:Histamine; D020932:Nerve Growth Factor; D014805:Vitamin B 12