Epidemiologic analysis of prenatal exposure to cough medicines containing dextromethorphan: no evidence of human teratogenicity

BACKGROUND: In a recent experimental study on chick embryos, Andaloro et al. (1998, Pediatr. Res. 43:1-7) observed a relationship between neural crest/neural tube defects (NTDs) and prenatal exposure to dextromethorphan. These authors made an extrapolation of their results to the human embryo, indicating that this drug could produce NTDs in humans. Rosenquist (1999, Teratology 60:58-60) based on the results of the epidemiologic study performed by Ferencz et al. (1997, Perspect. Pediatr. Cardiol. 5:50-162), concluded that dextromethorphan could cause congenital heart defects in humans. Because this drug is an over-the-counter drug, the suggestion of those authors has led to great controversy and public concern about the possible teratogenic effect of this drug on the human embryo. METHODS: We present the results of a case-control study by using logistic regression analyses on the effect of prenatal exposure to drugs containing dextromethorphan only, or in combination with other drugs, on human development. We mostly analyzed dextromethorphan. The study was designed in part as hypothesis confirmation for NTDs and congenital heart defects and, in part, as hypotheses generation by testing the association with many other congenital defects. RESULTS: The results do not show a relation between the occurrence of NTDs and heart defects or other defects with exposure to drugs containing dextromethorphan. CONCLUSIONS: The usual use of dextromethorphan in cough medications during pregnancy does not increase the risk for congenital defects.     

A portable automatic cough analyser in the ambulatory assessment of cough

Background  

Cough is one of the main symptoms of advanced lung disease. However, the efficacy of currently available treatment remains unsatisfactory. Research into the new antitussives requires an objective assessment of cough.     

Fictive cough in the cat.

Experiments were performed to determine whether cough could be elicited in paralyzed cats ventilated on a respiratory cycle-triggered pump. Midcollicular decerebrate cats were paralyzed and artificially ventilated on a phrenic-triggered pump. Phrenic and cranial iliohypogastric nerve efferent activities were recorded. Cough was elicited by electrical stimulation of the superior laryngeal nerve (SLN) or probing the intrathoracic trachea. Fictive coughs induced by electrical stimulation of the SLN or mechanical stimulation of the intrathoracic trachea consisted of large-amplitude bursts in phrenic discharge immediately followed by large bursts in cranial iliohypogastric discharge. During fictive cough, phrenic postinspiratory discharge was reduced relative to control cycles. Codeine (0.03-1 mg/kg iv) decreased both SLN- and probe-induced fictive cough. I conclude that fictive cough can be produced in paralyzed cats ventilated on a phrenic-triggered pump. Furthermore, fictive cough can be produced in the absence of afferent feedback associated with active expiration.     

Spectra of the voluntary first cough sounds

The voluntary cough sounds recorded according to Korpas and Sadlonova-Korpasova were sampled at a frequency of 20.000Hz and spectra of six consecutive windows of 50ms were estimated. To digitize signals an autotrigger mode was used. The subjects were healthy volunteers as well as patients with chronic bronchitis, asthma, bronchial carcinoma (growing intraluminarly in the 1st or in the 2nd or in the 3rd order bronchi), emphysema, laryngeal nerve paralyzis or laryngotomy. The duration of averaged cough sounds of patients was longer than that of healthy volunteers. The mean power of the spectra in the successive windows showed different patterns in the same group. In the third window of healthy volunteers (0.10 s-0.15 s) a high modulus broad bandwidth (between 1-2 kHz) spectrum was found which was considered as a bronchial "flute", and was probably related to the lowest resistance as well as to the velocity of airflow of cough manoeuvre. This pattern appeared with a delay and/or it was changed in the diseased groups compared to the healthy volunteers. Due to this delay, the spectra of the fifth window (0.20 s-0.25 s) showed somewhat higher harmonics (400-800 Hz) in the patients with chronic obstructive pulmonary diseases (COPD), carcinoma and laryngeal nerve paralyzis than in healthy volunteers. In emphysematous patients in the first (0.00-0.05 s), in the third (0.10-0.15 s) and in the fifth (0.20-0.25 s) windows the fundamental frequency was low (156-176 Hz) compared to that of the other groups. The paralyzed vocal cords functioning as an added resistance to the expiratory effort caused a phase-shift in the cough patterns, similarly to that seen in COPD patients. Due to the cannula, the spectra of patients having laryngotomy had a lot of high harmonics. They also had peaks nearly identical to that of bronchitic patients because they suffered from serious chronic bronchitis. It was found that by examination the cough spectra of series of voluntary cough sound signals it was possible to distinguish healthy volunteers from patients. This examination would therefore be useful for screening of bronchial diseases.