The airway obstruction induced in the laboratory in stable asthmatics differed from that in the emergency room in duration of obstruction, severity of obstruc¬tion, and perhaps most importantly, in the degree of accompanying inflammation. The inflammatory response and release of mediators likely contribute to the alterations in breathing patterns and respiratory drive. The increase in breathing frequency that we have noted in the emergency room presentation of asthma and the lack of any such change in the laboratory implies that the inflammatory process, rather than the degree of bronchospasm, may be responsible for changes in respiratory rate.
At first glance, neither methacholine nor exercise would appear to be responsible for inducing acute inflammatory changes. Methacholine directly induces smooth muscle contraction. However, we acknowledge the possibility that methacholine could possibly stimulate irritant airway receptors by physical irritation of the mucosa, smooth muscle contraction in itself activating irritant receptors, and stimulation of a deflation reflex secondary to compression by contiguous hyper- inflated lungs.13 Similarly, in asthmatic patients, exercise results in thermal changes in the airways leading to sudden increases in blood supply to the bronchi, hyperemia and edema of the mucosa with subsequent airway narrowing,14 changes which could arguably be described as inflammatory. It remains unclear what clinical outcome these laboratory findings have on irritant airway receptors. Nevertheless, the duration and degree of inflammation in the airways of an asthmatic subject presenting to an emergency room and subsequent stimulation of intrapulmonary irritant receptors must exceed that which accompanies the acute, transient airflow limitation induced in the laboratory by methacholine or exercise.
Our observation of unchanged respiratory rate following methacholine inhalation appears to confirm earlier studies of ventilatory pattern following methacholine or histamine challenge in asthmatic subjects. Respiratory rate appears to be unchanged when bronchospasm is induced in this manner, but various changes in minute ventilation have been reported: some report an increase, others a decrease and still other observers report unchanged levels of ventilation. Tobin et al noted that the relief of bronchoconstriction in stable asthmatic subjects was not accompanied by any important changes in respiratory rate or minute ventilation. Our findings in laboratory- induced asthma are more similar to those of Chadha et al in that we noted no change in respiratory rate and a significant increase in minute ventilation derived mainly from an increased tidal volume. The reasons for such conflicting results among different research groups may be related to a variety of factors that include the differing degrees of bronchoconstriction induced, the use of mouthpieces and nose clips by some investigators, small sample size, or different populations (healthy volunteers, COPD or asthmatic patients). Our protocol was limited to asthmatic subjects, had a sample size larger than that reported in several of the other studies, and measured respiratory rate by a technique that did not require contact with the face or mouth. buy viagra professional
We thought that exercise, unlike methacholine, would be a more natural stimulant of bronchospasm in asthmatic subjects and might induce changes similar to those in spontaneously occurring asthma attacks. However, the pattern of changes in respiratory rate and minute ventilation following exercise were similar to those that we found following methacholine; that is, respiratory rate remained unchanged, while minute ventilation increased secondary to an increase in tidal volume.
We conclude that respiratory rate is increased in naturally occurring asthma but not when acute airways obstruction is induced transiently in the laboratory. In the former setting, respiratory rate is weakly correlated with spirometric measures of airflow obstruction, but the weakness of the correlation does not allow respiratory rate to be used as a substitute for spirometry.