Eftects of B'reathing Warm Humidified Air on Bronchoconstriction Induced by Body Cooling and by Inhalation of Methacholine· Douglas 1. Horton, MD.; tmd w. Y.

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attacks can be precipitated both A withasthmatic exercise and cooling of the body.a.. cute

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Previously, we have demonstrated that exercise-induced asthma can be prevented by breathing warm humidified air at 37°C with 100 percent relative humidity during exercise.s.1 We have postulated that exercise-induced asthma is triggered by the loss of heat or water (or both) from the airways.s.e Since cooling of the airways has been observed with cooling of the body from exposure to cold,7-10 we have hypothesized that this cooling of the airways may also be responsible for the initiation of asthmatic attacks following exposure of the body to cold.a,. Asthmatic attac1cs can also be induced by inhalation of the parasympathomimetic substance, methacholine.'! Methacholine, like acetylcholine, stimulates the postsynaptic membrane of the neuromuscular junction, resulting in contraction of the smooth muscle of the airways. Thus, methacholine-induced bronchoconstriction may be distinct from the bronchoconstriction induced by exercise or body cooling and may be unrelated to cooling or dehydration of the airways. H cooling of the airways is responsible for bronchoconstriction induced by cooling of the body with ·From the National Jewish ~ital and Beseach Center (Dr. Horton) and the National ASthma Center (Dr. Chen), Denver. Supported in part by research grant HL-ill!6 from the National Institutes of Health. Manuscript received December 7; revision aooepted June 6. Reprint req1Iaf3: Dr. Chen, NtItiDnIIl &thmG CtmIer, 1999 ]ulitm Street, Deooer 80204

24 HOITOI. ClIO

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cold exposure, it follows that breathing wann humidified air may reduce the cooling of the airways and consequently lessen the bronchoconstriction. The present study was conducted to test this hypothesis by using warm humidified inspired air during exposure of the body to cold and during inhalation of methacholine in Patients with asthma.

MATERIALS AND METHODS Two groups of eight asthmatic patients who met the American 'Thoracic Society's definition of asthma1 2 were studied, with one group receiving body cooling and the other group iDhaling methacholine. In body cooling the patients were placed in a cold shower at a water temperature of 15°C for one minute (water output, 16 L/min); this was immediately followed by sitting 2 meters from an electric fan (Dayton model 4C 425) at high speed for another minute. Eight asthmatic patients underwent two body-eooling sessions in a random order. In one session the patient breathed warm humidified air at 37·C with 100 percent relative humidity during the exposure to cold and five minutes after the cooling by fan. In another session the patient breathed room air (23·C; 30 percent relative humidity) during and after the exposure to cold. 'The inspired air was delivered by a system shown in Figure I. The individual asthmatic patient was always tested at the same hour of the day and at a consistent time after his last dose of bronchodilator drugs. This was at least five hours following his last medication. Patients receiving altemate-day therapy with corticosteroids were tested on a day when they received no steroids. Prior to exposure to cold, the temperature of the skin and pulmonary functions were measured (baseline). After exposure to cold, the temperature of the skin was remeasured immediately following use of the fan, and the pulmonary fum'lions were remeasured five minutes after the termination

CHEST, 75: 1, JANUARY, 1979

of the cooling by fan. The temperature of the skin \\ a5 determined with a thermistor probe (Yellow Springs Instrument Co. No. 421) and a telethermometer readout (Yellow Springs Instrument Co., model 44 TD). The temperatures were read on the left and right sides of the chest between the clavicle and the breast and on the center of the left and rigltt scapulae. The average of these four temperatures was recorded as the temperature of the skin. The thoracic gas volume and airway resistance (Raw) were measured in a pressure-variable body plethysmograph (Warren E. Collins, Inc. ). A wedge spirometer (Med-Sclence model 570) was . used to measure the forced vital capacity (FVC), the forced expiratory volume in one second (FEV1)' the forced expiratory flow during the middle half of the FVC (FEF25-751; formerly maximal midexpiratory flow), and the flow-volume curve. All measurements were completed within 15 minutes after the initiation of the cold shower. In the experiments involving challenge with inhaled methacholine, eight asthmatic patients participated in the study for two sessions. The medication, the hour of the day, and the procedure of challenge were identical in the two sessions, except that in one session the patient breathed the warm humidified air and the other breathed the room air. The sequence of the two sessions was randomly assigned. In a given patient the interval between the two sessions was no more than three days. The procedure for the challenge with inhaled methacholine followed the guidelines of the National Institute of Allergy and Infectious Disease's panel on standardization of bronchial inhalation challenge procedures,1I using the recommended increments in concentration of methacholine. The methacholine was administered by breathing flve breaths of a given concentration through a nebulizer (DeVilbiss No. 42 powered by a Mead-Johnson Mui-Myst). Each breath of methacholine was delivered from functional residual capacity

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to inspiratory capacity. The order of concentration given was (diluent control), 0.07, 0.15, 0.31, 0.62, 1.25, and 2.50 mg/ml. As long as there was less than a 20 percent faD in FEY1 from the diluent control baseline value, the next higher concentration of methacholine was given until a decrease in FEY1 of 20 percent or more was reached. This concentration of methacholine was recorded as the threshold concentration for the patient In both sessions the patient continued to breathe the specific inspired air delivered by a system shown in Figure 1 until the test was completed, except when performing maneuvers for measurement of pulmonary func· tion and when inhaling five breaths of diluent or methach0line. When a decrease of FEY1 was 20 percent or more of the diluent baseline level, the challenge was terminated, and a bronchodilator drug was administered. For experiments in· volving inhalation of methacholine, a pulmonary function analyzer (Medistor; Simlog Instruments) was used in the assessment of pulmonary function. Comparisons to locate specific sources of difference were performed by t-tests.

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RFsuLTS The exposure to cold resulted in a decrease in the temperature of the skin in all patients in both sessiODS of exposure. The decrease in the temperature of the skin was not significantly different (P > 0.1) on the day of breathing warm humidified air ( -6.2° C) or on the day of breathing ambient room air (-7.6°C). Results of the measurements of pulmonary function are shown in Table 1. During the breathing of ambient room air, the exposure to cold resulted in a significant decrease in FEV1 and FEF25-75S to an average of 75 percent and 64 percent of the precool-

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F'ICURE 1. System delivering inspired air. To achieve different types of inspired air, various units were used. For room air (23 ± l-C; 30 ± 5 percent relative humidity), air pump (AP) only was used; for warm humidified air (37 ± O.5-C; 100 percent relative humidity), humidifter ( H£), reservoir for prehumidified air (R), heater (Ht), water (W), and air pump were ued. Air flow controller (Fe) was able to regulate flow of air from zero to more than 100 L/min. Fine sponge filter of 1.2-cm thickness was installed at air pump. Air must pass through filter before entering thermally insulated conduit (I). He, Heating element; and C, heating element c0n-

troller.

CHEST, 75: 1, JANUARY, 1979

EFFECTS OF BREATHING WARII HUlllDIFIm AIR ON BRONCHOCONSTRICnON 25

ing baseline values, respectively, and a significant increase in the thoracic gas volume and Raw to an average of 132 percent and 214 percent of baseline values, respectively. In contrast, during the breathing of warm humidified air, the FEVI, FEF25-75S, and thoracic gas volume after exposure to cold did not show a significant change from baseline. The Raw after exposure to cold increased slightly but significantly to 114 percent of baseline. By comparing the two sessions after exposure to cold, the changes in the indices of pulmonary function are significantly less when breathing warm humidified air. In Table 2, the lowest threshold dose of inhaled methacholine producing a 20 percent or greater decrease in FEVI when breathing room air is compared to the corresponding value obtained when breathing warm humidified air. The amount of decrease in the baseline value for FEVI produced by that dose of methacholine is shown for each tyPe of inspired air. Also, the final threshold dose of inhaled methacholine for each type of inspired air is presented. When the percentage of the baseline value for FEVI is compared at the same concentration for each subject, there is no statistical difference between the room air and the warm humidiJied air. In four patients, there was no change in the threshold concentration of methacholine when breathing warm humidified air, as compared to breathing room air. In the remaining four patients the threshold dose of methacholine increased by one or two dilutions while breathing the warm humidified air. DIscuSSION

The results indicate that breathing warm humidified air reduced the bronchoconstriction induced by cooling of the body, but not the bronchoconstriction induced by inhaled methacholine. Breathing cold "air in patients with respiratory disease was found to cause bronchoconsmction14.15 that can be blocked with atropine. IS It is well documented that aHerent parasympathetic nerve fibers richly innervate the mucous membranes, submucosal layers, and smooth muscles of the airways. II-IS Cooling these areas could trigger a neural reflex resulting in constriction of the lumen of the airways. This reftex constriction of the lumen of the airways induced by cold temperatures may be a defense mechanism in nature, since as the lumen is decreased, the volume of inspired air is reduced, and the severity of cooling is lessened.14 Both exercise-induced asthma and asthma induced by body cooling appear to be related to the cooling of the airways. With exercise, as ventilaljon

21 HORTOI, CHEN

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Data and Subject

FEV.. L 1 2 3 4 5 6 7 8 Mean FEF25-75%, Lisee 1 2 3 4 5 6 7 8

Mean

Thoracic gas volume, L 1 2 3 4 5 6 7 8

Mean

.

Warm Humidified Air &

Baseline

After Cold (Percent of Baseline)

Baseline

After Cold (Percent of Baseline)

1.95 1.65 2.45 2.78 2.84 1.77 1.87 2.68 2.25·

1.31 (67) 1.18 (72) 2.09 (85) 1.84 (66) 1.59 (56) 1.49 (84) 1.60 (86) 2.25 (84) 1.67 (75)·t

2.27 1.80 3.01 2.93 2.19 1.64 1.63 2.60 2.25

1.92 (85) 1.56 (87) 3.17 (105) 2.84 (97) 1.93 (88) 1.54 (94) 1.91 (117) 2.58 (99) 2.18 (97)t

1.39 1.04 2.32 2.50 1.82 1.35 1.45 2.54 1.80**

0.78 (56) 0.75 (72) 1.55 (67) 1.30 (52) 0.93 (51) 0.94 (70) 1.08 (74) 1.83 (72) 1.15 (64)··*

1.76 1.01 2.60 2.66 1.17 1.35 1.22 2.98 1.84

1.37 (78) 0.84 (83) 2.71 (104) 2.48 (93) 0.96 (82) 1.30 (96) 1.54 (126) 2.34 (79)

2.50 2.75 3.47 1.65 3.52 2.34 2.33 2.72 2.661

2.44 4.78 3.52 3.34 5.29 2.81 2.50 2.82 3.56

2.35 2.88 3.54 1.86 3.78 2.39 2.69 2.47 2.75

2.35 3.24 3.58 2.12 4.82 2.37 2.75 2.34 2.95

(100) (112) (101) (114) (128) (99) (102) (95) (106)

5.00 7.43 2.85 7.91 7.72 6.24 4.96 5.17 5.91

(122) (128) (120) (116) (126) (101) (85) (114) (114)U

Raw, em RIO /LIsee 1 4.32 2 5.90 3 2.18 4 5.67 5 2.42 6 6.20 4.80 7 8 4.59 4.51** Mean

(98) (174) (101) (202) (150) (120) (107) (104) (l32)§

4.08 5.82 2.38 6.80 6.13 6.17 5.83 4.52 9.08 (214)**t 5.221

10.43 (241) 13.76 (233) 5.46 (250) 12.28 (217) 8.24 (340) 9.11 (147) 6.41 (134) 6.97 (152)

1.69 (93)t

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Effects of breathing warm humidified air on bronchoconstriction induced by body cooling and by inhalation of methacholine.

Eftects of B'reathing Warm Humidified Air on Bronchoconstriction Induced by Body Cooling and by Inhalation of Methacholine· Douglas 1. Horton, MD.; tm...
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