It has been commonly accepted but poorly documented that in the presence of chronic asthma, patients may become adapted to the presence of their pulmonary dysfunction. They may, for instance, remain asymptomatic but taper their activities to a lower level; their degree of pulmonary dysfunction might possibly be grossly underestimated and their therapy less than optimal.
In keeping with this apparent blunting of perceptive ability with longstanding dysfunction, one might expect the perception of further acute fluctuations in the caliber of the airways to be similarly affected; however, the subjective nature of breathlessness has left the quantitation of this clinical impression essentially undocumented.
Studies utilizing externally applied loads to breathing and defining thresholds for detection of these loads have allowed quantitation of some sensations associated with breathing; however, external loading, while valuable in defining physiologic load-compensating mechanisms, is far from an ideal model of the pulmonary dysfunction seen in states of disease.
The present study was an attempt to further define the relationship between an intrinsic load to breathing (methacholine-induced asthma) and the subjective detection of this load. The study examines the sensitivity of individual asthmatic subjects in detecting acute fluctuations in pulmonary function on a number of occasions.
Materials and Methods
Ten subjects, each with asthma since childhood (read also about Childhood Asthma), agreed to undertake bronchoprovocation tests on a number of occasions. Our intention was to compare die changes in pulmonary function required to produce just noticeable symptoms on two specific occasions, once when initial pulmonary function was close to normal, and once when initial pulmonary function was modestly impaired, the subject being initially asymptomatic on each occasion.
Testing was performed in a 900-L variable-pressure plethysmograph. After initial indices of pulmonary function were measured, bronchoprovocation was continued until the subject indicated that tightness in the chest was just barely discernible (threshold point). Indices of pulmonary function were again measured, and the test ceased. The threshold point was thus a subjective determination. An attempt at standardization was made by the use of a visual analogue scale (unpublished data). If the subject felt more than “just noticeably tight,” the procedure was completed, but the results were not included for analysis.
The technique of bronchoprovocation was as follows: Aerosols were sequentially generated from freshly prepared solutions of methacholine hydrochloride (0.5, 1.25, 2.5, 5.0, and 10.0 mg/ml) in isotonic saline solution. Aerosols were generated by nebulizers (Bennett Vaponephrin) driven with an oxygen flow of 5 L/min. The subjects took a single vital capacity (VC) inhalation of the aerosol through a tube 1 inch in diameter in the wall of the plethysmograph (so as not to contaminate their environment) at three-minute intervals, until tightness in the chest was just sensed. Despite the standard method of administration, the subjects were instructed that the aerosols were randomized and that they might be given an aerosol of either isotonic saline solution or active drug. Lung volumes and indices of airway caliber were measured in the following manner. Two slow expirations from functional residual capacity (FRC) to residual volume (RV) were followed by two slow vital capacity (VC) maneuvers at 30-second intervals. The greatest value of each expired volume was used for calculations. After a one-minute rest, airway resistance (Raw) and thoracic gas volume at FRC were measured between two and five times, the average being used for calculations. Duplicate maneuvers for forced vital capacity (FVC) were then performed, allowing one-second forced expiratory volume (FEVj) to be measured and maximal expiratory flow-volume curves to be stored and photographed (the greatest of each was used for calculations). The maximal expiratory flow-volume curves were obtained by plotting expired flow against its electronically integrated signal (expired volume) on a storage oscilloscope (Tektronix 5310 N) and photographing the tracing. Maximal expiratory flow at 50 percent of the VC (Vmax50) and an index of the time constant of the lung (V/V25-75) were obtained from the maximal expiratory flow-volume curves. The V/V25-75 was taken as the slope of the straight line joining the points at 25 percent and 75 percent of VC on the maximal expiratory flow-volume curve.
Expiratory flow was measured with a Fleisch No. 4 pneumotachygraph and a pressure transducer (Hewlett-Packard P270), airway pressure with a pressure transducer (Hewlett-Packard 1280B), and plethysmographic pressure with a pressure transducer (Hewlett-Packard P270). All signals were recorded on a six-channel recorder (S. E. Laboratories 2005 U.V.).
Bronchoprovocation was commenced two minutes after the final baseline maneuver for FVC, in order to allow for possible changes after forced expirations. Predicted values for lung volumes, Raw, and Vmax50 were taken from the data of Goldman and Becklake, Pelzer and Thomson, and Chemiack and Raber, respectively.
The changes in pulmonary function needed to produce a threshold were compared on two occasions. Comparisons were made only if initial indices differed by an order (arbitrarily) of 25 percent or more.