Asthma Cough Research Articles

Effect of an NK1 receptor antagonist (CP-99,994) on hypertonic saline-induced bronchoconstriction and cough in male asthmatic subjects.

To investigate the role of NK1 receptors in the pathogenesis of bronchoconstriction and cough in asthma, we performed a randomized, double-blind, crossover study on the effects of a selective non-peptide tachykinin NK1 receptor antagonist (CP-99,994) on baseline measures of lung function and on hypertonic saline-induced bronchoconstriction and cough in 14 male subjects with mild asthma. CP-99,994 (250 micrograms/2 hours) and placebo were administered intravenously in 2-h infusions during consecutive visits 5 to 7 d apart. Specific airway resistance (SRaw) was measured and spirometry was performed at baseline and at 35 and 60 min. Next, hypertonic saline challenge was performed by delivering 10 breaths of saline of increasing concentration (0.9 to 7% in 1% increments at 5-min intervals) via an ultrasonic nebulizer until SRaw increased from baseline by 200% or 20 units, whichever was greater. Throughout the challenge cough was counted from a taped record made from two microphones placed close to the subject's larynx. We found that CP-99,994 did not significantly affect SRaw or spirometric measures of lung function during the first hour of infusion. Although CP-99,994 infusion markedly attenuated the bronchoconstrictor response to the saline challenge in two subjects, it did not significantly decrease the area under curves obtained for SRaw and cough during saline challenge for the group as a whole (p = 0.9 for SRaw;p = 0.8 for cough). We conclude that administration of 250 micrograms/kg of CP-99,994 over 2 h does not significantly inhibit hypertonic saline-induced bronchoconstriction or cough in subjects with mild asthma and does not have acute bronchodilator activity in these subjects.

抗アレルギー剤の咳ぜん息における有用性

抗アレルギー剤の咳ぜん息における有用性

A double-blind study of the efficacy of nedocromil sodium in the management of asthma in patients using high doses of bronchodilators

The effects of nedocromil sodium were assessed in 110 patients with asthma who experienced asthma symptoms despite the use of high doses of inhaled bronchodilators. During the baseline period, antiinflammatory agents were not permitted, and patients were treated with inhaled β-agonists on an as-needed basis. Patients who required 12 or more puffs of albuterol and experienced continuing asthma symptoms for 7 of the 14 baseline days were randomized to treatment groups. Subjects received either nedocromil sodium (4 mg) or placebo four times a day for 10 weeks. Statistically significant (p < 0.05) between-treatment differences (weeks 3 to 10), favoring nedocromil sodium, were determined for the asthma summary score, daytime asthma severity, asthmatic cough, morning peak flow rates, reduction of as-needed bronchodilator use, physician's assessment of asthma severity, and patient and physician opinions of treatment effectiveness. By trial end (week 10), sleep difficulty caused by asthma decreased 29% in the nedocromil sodium group and 4% in the placebo group (p = 0.006). Nedocromil sodium was well tolerated and improved asthma control while reducing the inhaled bronchodilator load of these patients with moderately severe asthma. (J ALLERGY CLIN IMMUNOL 1994;94:473-81.)

Poor agreement between reported and recorded nocturnal cough in asthma.

Reported presence or absence of night cough was compared with tape recorded cough in 15 children with perennial asthma (median age, 9 years; range, 7-14) who reported troublesome nocturnal symptoms. Measurements were made and diaries kept for 7 consecutive nights. Cough was reported on 66 of 105 (66%) and recorded on 93 (90%) available nights with poor overall agreement (Cohen's coefficient of assessment, kappa +0.30, range -0.17 to +1). The poor agreement between subjective and objective assessment of an important symptom of nocturnal asthma raises questions on the validity of symptom reporting and may in part explain the not infrequent disagreement between medical and patient assessment of disease severity.

Towards a quantitative description of asthmatic cough sounds

This study describes a method of quantitatively characterizing cough sounds using digital signal processing techniques. Differences between asthmatic and non-asthmatic cough sounds are presented. Coughs from 12 asthmatic and 5 non-asthmatic subjects were analysed. Cough sounds and flows were digitized, at a sampling rate of 5 kHz, before and after a free-running exercise test. Individual coughs were divided into two or three phases, corresponding to the initial glottal opening burst, the quieter middle phase, and (sometimes) the final closing burst. Standard signal processing techniques were then invoked to characterize the spectral and temporal shapes of the first two phases. Factor analysis indicated that the spectral shapes of the two phases are independent, with each being largely described by the degree of "peakedness" in the spectrum, and by the balance of energy between low and high frequencies. Both the duration of the initial burst and zero-crossing rates of the cough waveform (which indicates the "spectral balance") during each of the first two phases were smaller for asthmatic than for non-asthmatic coughs. Fewer asthmatic coughs contained a final burst. Discriminant analysis between the two groups gave classification error rates of 20-30%. The peak flow recorded during the cough was significantly smaller for asthmatics, and correlated very well with the peak flow recorded during forced expiration. Thus, significant differences exist between asthmatic and non-asthmatic cough sounds. An effective representation of the temporal structure of the cough sound is required to successfully characterize the cough.

Effect of controlled release salbutamol on nocturnal cough in asthma.

Sixteen asthmatic children completed a double blind placebo controlled crossover study of controlled release salbutamol (CRS) to assess its efficacy in controlling night time cough. Children with asthma were enrolled into the study on the basis of a history of persistent cough confirmed by two overnight tape recordings at home. Outcome was measured by two overnight tapes on each medication. Other treatment was unaffected. There was no significant fall in cough counts on CRS. Median scores were 14.5 and 12.0 coughing episodes per night for CRS and placebo respectively. Mean overnight oxygen saturation was identical in both treatment periods but morning peak flow showed a trend towards improvement on CRS. Treatment with CRS does not have a significant effect in control of night cough although it may improve objective measurements of lung function.

A Portable System for the Spectral Analysis of Cough Sounds in Asthma

A practical and portable method is described to analyze the sound spectra of coughs. The system is based upon a personal computer and simultaneously collects the sounds of cough heard both at the mouth and through the chest wall together with the airflow at the mouth produced during the cough. Subsequent analysis produce spectrographs of the cough sound linked to the corresponding airflow. The system will be used initially to examine the effects of exercise on the sound of cough in asthma. Further study of cough spectra in this way may be useful in the management of asthma either diagnostically or in the assessment of therapeutic interventions.

Bronchial hyperreactivity in patients who cough after receiving angiotensin converting enzyme inhibitors.

Angiotensin converting enzyme inhibitors cause cough in some patients, but the mechanism of this effect is not known. Six patients in whom these inhibitors had caused cough and a further two patients in whom they were suspected to have caused worsening of bronchial asthma were studied. Nine patients in whom angiotensin converting enzyme inhibitors had not been associated with cough served as controls. In the controls lung function and bronchial reactivity were measured once; for the study patients these and the cough index were measured twice before rechallenge for two weeks with an angiotensin enzyme inhibitor and once afterwards. Rechallenge with drug for two weeks caused a significant decrease in the mean concentration of histamine causing a 35% fall in airways conductance and a significant increase in the cough index. Patients with cough showed bronchial hyperactivity compared with the controls, which increased after rechallenge with the inhibitors. Cough associated with converting enzyme inhibitors may be a variant of the cough in asthma.

Nocturnal cough in asthma.

The timing of nocturnal cough and its association with change in ambient temperature was documented in 11 asthmatic children, median age 5.1 years, while they were receiving continuous prophylaxis. Studies were performed in their homes on three nights. A voice activated system with electronic time signal recorded coughing. Ambient temperature was recorded every five minutes throughout the night on a Grant Squirrel data logger. Ten children coughed on 27 nights with a median of six bouts of coughing a night (range 0-272). The cough rate in the two hours after going to bed was significantly higher than the cough rate in the middle of the night (2-4 am or 4-6 am). Peak coughing times were 7-9 pm and 6-8 am. The room temperature was lowest between 5 and 7 am. There were no significant differences between cough rates during periods of rapid temperature change (more than 1 degree C an hour). The timing of nocturnal cough observed in this study differed from the known basophase of circadian cycles described for adults and children.

Night cough counts and diary card scores in asthma.

A tape recording system for recording night cough in asthmatics at home is described. Objective cough counts and half hour periods containing cough did not correlate with diary card scores awarded to eight children on seven nights each. Night cough diary scores may mislead in the assessment of symptom severity.

Bradykinin stimulates afferent vagal C-fibers in intrapulmonary airways of dogs.

Bradykinin is released in the lungs in asthma and pulmonary anaphylaxis. It has negligible direct bronchoconstrictor effects in humans or dogs, but inhaled as aerosol it causes cough and reflex bronchoconstriction in asthmatics and some normal subjects. The afferent nerves responsible for these reflex effects have not been identified. We recorded vagal impulses in anesthetized dogs to determine whether lung afferents were stimulated by bradykinin. C-fiber endings in the intrapulmonary airways accessible from the systemic circulation were stimulated by bradykinin injected into the left atrium (0.5-1.0 micrograms/kg) or bronchial artery (1.5 micrograms), activity increasing 15-fold on average. C-fiber endings accessible from the pulmonary circulation were relatively insensitive to bradykinin. Bradykinin caused a small increase in firing of some rapidly adapting (irritant) receptors, but the effect appeared to be secondary to vascular changes. Bradykinin had variable effects on slowly adapting stretch receptors, but did not stimulate them directly. Thus vagally mediated sensory or reflex effects initiated by bradykinin in the lung are probably due to stimulation of "bronchial" C-fibers.

Alterations in Pulmonary Function Following Respiratory Viral Infection

Respiratory viral illness is a major cause of morbidity in both adults and children. This report focuses on both the acute and chronic effects on respiratory function of these ubiquitous infections. Infant airways are particularly vulnerable due to the relatively low conductance in immature peripheral airways. Bronchiolitis, caused predominantly by respiratory syncytial virus, is the most important of these viral illnesses and is emerging as a major risk factor for the subsequent development of obstructive airway disease in adults, possibly by interference with normal alveolar proliferation. The basic pathogenic mechanism involved in adult respiratory viral infection is bronchial hyperreactivity, presumably secondary to epithelial damage and resultant sensitization of rapidly adapting airway receptors. In addition, there may be virus-related alterations in the autonomic and humoral regulation of airway tone. Viral infections may alter the effects of common air pollutants on respiratory function.