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. 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/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.

Incidence and remission of asthma: a retrospective study on the natural history of asthma in Italy.

BACKGROUND: The knowledge of the natural history of asthma from birth to adulthood could provide important clues for its cause and for the understanding of epidemiologic findings. OBJECTIVE: This study is aimed at assessing the incidence and remission of asthma from birth to the age of 44 years by using data from 18,873 subjects involved in a large, nationally representative, cross-sectional study carried out in Italy from 1998 through 2000. METHODS: The onset of asthma was defined as the age at the first attack, and remission was considered present when a subject was neither under treatment nor had experienced an asthma attack in the last 24 months. Person-years and survival techniques were used for the analysis. RESULTS: The average annual incidence rate for the 1953 to 2000 period was 2.56/1000 persons per year. Incidence peaked in boys less than 10 years of age (4.38/1000 persons per year) and in women 30 years of age or older (3.1/1000 persons per year) and showed a generational increase (incident rate ratio = 2.63 and 95% CI = 2.20-3.12 for 1974-1979 vs 1953-1958 birth cohort). The overall remission rate was 45.8% (41.6% in women and 49.5% in men, P <.001). Asthmatic patients in remission had an earlier age at onset (7.8 vs 15.9 years, P <.001) and a shorter duration of the disease (5.6 vs 16.1 years, P <.001) than patients with current asthma. The probability of remission was strongly (P <.001) and inversely related to the age at onset (62.8% and 15.0% in the <10- and > or =20-years age-at-onset groups, respectively). CONCLUSION: With respect to its natural history, asthma presents 2 different forms: early-onset asthma, which occurs early in childhood, affects mainly boys, and has a good prognosis, and late-onset asthma, which generally occurs during or after puberty, mainly affects women, and has a poor prognosis. The minority of patients with early-onset asthma who do not remit represents more than 35% of patients with current asthma in the general young adult population.