A B S T R A C T Our purpose was to determine whether exposure to a realistic concentration of nitrogen dioxide (NO2) could increase the bronchial sensitivity of asthmatic patients to bronchoconstrictor agents. We established dose-response curves for changes in specific airway resistance (SRaw) in response to aerosolized carbachol in 20 asthmatics after each had spent 1 h in an exposure chamber breathing on one occasion unpolluted air and on a separate occasion 0.1 ppm N02: sequence of exposures to unpolluted air and to low levels of NO2 were randomized in a single-blind fashion. N02 induced a slight but significant increase in initial SRa. and enhanced the bronchoconstrictor effect of carbachol in 13 subjects: curves were shifted to the left and the mean dose of carbachol producing a twofold increase in initial SRaw was decreased from 0.66 mg to 0.36 mg (P < 0.001). In contrast, NO2 neither modified the initial SRaw nor the bronchoconstrictor effect of carbachol in seven subjects. In 4 out of the 20 subjects, exposure to a higher concentration of NO (0.2 ppm) yielded variable results.Potentiation of the carbachol bronchoconstrictor response by NO2 could not be related to any physical or clinical characteristics of the subjects tested. Although the mechanisms underlying the N02 effect remain controversial, the present results demonstrate that very low levels of NO. can adversely affect some asthmatics.

A single deep inspiration (DI) is commonly followed by transient airflow obstruction in asthmatic patients. In some patients, however, DI results in a sustained response which suggests that more than one mechanism may be responsible. We have studied the characteristics of the response to repeated DI, and their modification by various pharmacological agents, by measuring specific airway resistance (sRaw) in ten subjects who showed reproducible and consistent increases in sRaw after DI.

In anesthetized cats, with vagi cut and the spinal cord severed at the C8 level, phrenic motor and/or sensory discharge was recorded. Small afferent phrenic fibers were identified through their activation by lactic acid, hyperosmotic NaCl solution, or phenyl diguanide. They exhibited a spontaneous but irregular low-frequency discharge. Block of their conduction by procaine had no effect on eupneic motor phrenic activity. Large afferent phrenic fibers showed a spontaneous rhythmic discharge, and cold block (6 degrees C) of these fibers significantly prolonged the phrenic discharge time (Tphr) and total breath duration (TT) during eupnea. The stimulation of all afferent phrenic fibers lowered the impulse frequency of phrenic motoneurons (f impulses) and shortened both Tphr and TT. When the stimulation was performed during cold block all of the effects on phrenic output persisted, but changes in timing were less pronounced. Under procaine block, only the effects of phrenic nerve stimulation on Tphr persisted. These results suggest that both large and small afferent phrenic fibers control the inspiratory activity with a prominent role of small fibers on phrenic motoneuron impulse frequency.

Patient error in use of bronchodilator metered aerosols Aerosolised bronchodilator drugs in pressurised canisters delivering metered doses are widely used, easy to carry, and apparently easy to operate. The instructions with each canister are reasonably clear, stating that each puff must be deeply inhaled and the breath held afterwards. Since the drug intake depends mostly on the patient's ability to follow the instructions, we thought it was important to find out whether asthmatics used their aerosols correctly. Patients, methods, and resultsTwenty asthmatic patients (12 men, 8 women) with a mean age (±SD) of 44 8 + 15 1 were studied. All had been treated with bronchodilator sprays and knew how to operate them. They were not examined during an acute attack, although all of them had some bronchial obstruction when tested. They received no medication for 24 hours preccding the first test.Specific airway resistance (SRaw), which is the resistance corrected for lung volume,' was measured in a whole-body constant volume plethysmograph at a thoracic gas volume close to functional residual capacity, using the panting technique.2 Each subject was tested, by different procedures, on two successive days between 2 and 5 pm if the initial value of SRaw was comparable. On both days SRaw was measured before and 5 and 10 minutes after bronchodilator aerosol inhalation (salbutamol 100 jtg/puff in 10 patients and fenoterol 200 jug/puff in 10 others). Bronchodilatation was greatest after 10 minutes, therefore only measurements taken at that time were used.On the first day the patients were told to inhale two puffs of a bronchodilator spray in their customary way. On the second day two puffs of the same bronchodilator spray were administered by the physician. Wearing a nose clip, the patients opened their mouth wide, expired deeply, and then inspired deeply. One puff of drug was delivered at the beginning of the inspiration with the canister about 3 cm from the lips. After fully inspiring the patients closed their mouths and held their breath for four seconds. A second puff was administered in the same way. Repetition of the first-day procedure on different occasions by some patients showed there was no systematic error due to the tests not being randomised. The bronchodilatation achieved by the two procedures was similar in only 5 patients. In the 15 others it was greater when the aerosol was given by the physician. Observation showed that only the 5 patients in whom bronchodilatation was similar by both methods correctly inhaled (that is, at the beginning of a deep inspiration) on self-administration. Drugs administered by inhalation now play a major role in the treatment of bronchial asthma. It has been shown that some patients have difficulty inhaling drug aerosols from pressurised cannisters' and this may, of course, be a reason for treatment failure. The aim of this study was to find the number of patients attending an asthma clinic who were not using their inhalers satisfactorily, in spite of apparently adequate tuition i...

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