• View in gallery

    Individual horse values of maximal ΔPL (A), RL (B), and EL (C) in study 1, 2, and 3 at baseline (n = 6 horses). Study 1 = Complete BAL with sedation. Study 2 = BAL without saline (0.9% NaCl) solution instillation but with sedation. Study 3 = BAL without saline solution instillation and without sedation.

  • View in gallery

    Mean ± SEM values of relative changes in RL at baseline (0 hours) and 3, 6, 12, 24, and 48 hours after the BAL or control procedures in study 1 (n = 6 horses; circles), study 2 (6; triangles), and study 3 (5; squares). *Significant (P < 0.05) difference between group mean value and group mean baseline value in study 1. †Significant (P < 0.05) time main effect at 3 hours. See Figure 1 for remainder of key.

  • View in gallery

    Bar graphs of individual horse values of the percentage variation in RL, compared with baseline, at 3 (graphs on the left) and 6 (graphs on the right) hours in study 1 (n = 6 horses), 2 (6), and 3 (5). See Figure 1 for remainder of key.

  • View in gallery

    Mean ± SEM values of relative changes in EL at baseline (0 hours) and 3, 6, 12, 24, and 48 hours after the BAL or control procedures in study 1 (n = 6 horses; circles), study 2 (6; triangles), and study 3 (5; squares). *Significant (P < 0.05) difference between group mean value and group mean baseline value in all studies. †Significant (P < 0.05) time main effect at 12 hours. See Figure 1 for remainder of key.

  • View in gallery

    Mean ± SEM values of relative changes in ΔPL at baseline (0 hours) and 3, 6, 12, 24, and 48 hours after the BAL or control procedures in study 1, 2, and 3. See Figures 1 and 4 for key.

  • 1.

    Leguillette R, Desevaux C, Lavoie JP. Effects of pentoxifylline on pulmonary function and results of cytologic examination of bronchoalveolar lavage fluid in horses with recurrent airway obstruction. Am J Vet Res 2002;63:459463.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Jackson CA, Berney C & Jefcoat AM, et al. Environment and prednisone interactions in the treatment of recurrent airway obstruction (heaves). Equine Vet J 2000;32:432438.

    • Search Google Scholar
    • Export Citation
  • 3.

    Robinson NE, Jackson C & Jefcoat A, et al. Efficacy of three corticosteroids for the treatment of heaves. Equine Vet J 2002;34:1722.

  • 4.

    Giguere S, Viel L & Lee E, et al. Cytokine induction in pulmonary airways of horses with heaves and effect of therapy with inhaled fluticasone propionate. Vet Immunol Immunopathol 2002;85:147158.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Sweeney CR, Rossier Y & Ziemer EL, et al. Effect of prior lavage on bronchoalveolar lavage fluid cell population of lavaged and unlavaged lung segments in horses. Am J Vet Res 1994;55:15011504.

    • Search Google Scholar
    • Export Citation
  • 6.

    Lavoie JP, Pascoe JR, Kurpershoek CJ. Effect of head and neck position on respiratory mechanics in horses sedated with xylazine. Am J Vet Res 1992;53:16521657.

    • Search Google Scholar
    • Export Citation
  • 7.

    Bates JH, Shardonofsky F, Stewart DE. The low-frequency dependence of respiratory system resistance and elastance in normal dogs. Respir Physiol 1989;78:369382.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Humbert M, Robinson DS & Assoufi B, et al. Safety of fiberoptic bronchoscopy in asthmatic and control subjects and effect on asthma control over two weeks. Thorax 1996;51:664669.

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    • Search Google Scholar
    • Export Citation
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    Hattotuwa K, Gamble EA & Jeffery PK, et al. Safety of bronchoscopy, biopsy, and BAL in research patients with COPD. Chest 2002;6:19091912.

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    • Search Google Scholar
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    Rogers DF, Barnes PJ. Opioid inhibition of neurally mediated mucus secretion in human bronchi. Lancet 1989;1:930932.

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    Krombach F, Fiehl E & Burkhardt D, et al. Short-term and long-term effects of serial bronchoalveolar lavages in a nonhuman primate model. Am J Respir Crit Care Med 1994;150:153158.

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Effects of the bronchoalveolar lavage procedure on lung function in horses with clinical exacerbation of recurrent airway obstruction

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  • 1 Départment de Sciences Cliniques, Faculté de Médecine Vétérinaire, Université de Montréal, St-Hyacinthe, QC J2S 7C6, Canada.
  • | 2 Départment de Sciences Cliniques, Faculté de Médecine Vétérinaire, Université de Montréal, St-Hyacinthe, QC J2S 7C6, Canada.

Abstract

Objective—To evaluate whether bronchoalveolar lavage (BAL) alters respiratory mechanics of horses with recurrent airway obstruction (ie, heaves) over a 48-hour period.

Animals—6 horses affected with heaves.

Procedures—Horses were subjected to a complete BAL procedure, which included sedation with xylazine and butorphanol, intratracheal administration of lidocaine, and instillation and aspiration of two 250-mL boluses of saline (0.9% NaCl) solution through an endoscope (study 1). To evaluate the effects of saline solution, horses were subjected to the same procedure without saline solution instillation and aspiration (study 2). Lastly, the endoscope was similarly introduced into the lower airways, without sedation or saline instillation and aspiration (study 3). Respiratory mechanics were performed at baseline (time 0) and at 3, 6, 12, 24, and 48 hours after each procedure.

Results—In study 1, BAL induced a significant decrease in pulmonary resistance lasting up to 6 hours. This may have resulted from clearance of mucus in large airways. We also observed a significant increase in lung elastance and transpulmonary pressure at 12 hours after BAL in all 3 studies, which may be attributed to a circadian effect.

Conclusions and Clinical Relevance—Our results indicate that the temporal effects of BAL procedures on lung mechanics should be taken into account when designing research protocols involving horses with heaves. Future studies should address the immediate effects of BAL on lung function.

Abstract

Objective—To evaluate whether bronchoalveolar lavage (BAL) alters respiratory mechanics of horses with recurrent airway obstruction (ie, heaves) over a 48-hour period.

Animals—6 horses affected with heaves.

Procedures—Horses were subjected to a complete BAL procedure, which included sedation with xylazine and butorphanol, intratracheal administration of lidocaine, and instillation and aspiration of two 250-mL boluses of saline (0.9% NaCl) solution through an endoscope (study 1). To evaluate the effects of saline solution, horses were subjected to the same procedure without saline solution instillation and aspiration (study 2). Lastly, the endoscope was similarly introduced into the lower airways, without sedation or saline instillation and aspiration (study 3). Respiratory mechanics were performed at baseline (time 0) and at 3, 6, 12, 24, and 48 hours after each procedure.

Results—In study 1, BAL induced a significant decrease in pulmonary resistance lasting up to 6 hours. This may have resulted from clearance of mucus in large airways. We also observed a significant increase in lung elastance and transpulmonary pressure at 12 hours after BAL in all 3 studies, which may be attributed to a circadian effect.

Conclusions and Clinical Relevance—Our results indicate that the temporal effects of BAL procedures on lung mechanics should be taken into account when designing research protocols involving horses with heaves. Future studies should address the immediate effects of BAL on lung function.

The BAL technique is a commonly used procedure for harvesting cells representative of the alveolar population. Cytologic evaluation of BAL fluid is commonly performed in clinical practice for the diagnosis of lower airway inflammation in horses and, occasionally, in horses with recurrent airway obstruction (ie, heaves) with labored respiration. Furthermore, sequential BAL procedures are important research tools when monitoring response to drug or evaluating the effects of changes in the environment of horses with lower airway inflammation such as heaves.1–4 Because BAL fluid and lung function are commonly assessed jointly in research studies, the effects of BAL on respiratory mechanics may introduce a bias in the results. To our knowledge, no data are available on the effects of BAL on lung mechanics over time and no consistent time between BAL procedures and measurements of lung mechanics has been established.

Ethical considerations are more important when BAL is to be performed in heaves-affected horses during clinical exacerbation. These horses have marked changes in their lung function, which may deteriorate when performing a BAL under sedation. Moreover, findings in a previous study5 indicate that BAL can induce lower airway neutrophilia, which may further worsen inflammation and lung function of horses already having respiratory difficulties. The purpose of the study reported here was thus to evaluate whether the BAL procedure alters respiratory mechanics of horses with heaves over a 48-hour period.

Materials and Methods

Animals—Six adult heaves-affected horses (5 mares and 1 gelding) from our research herd were studied. Horses were mixed breeds and 8 to 18 years of age. Criteria for inclusion were a history of chronic, recurrent periods of labored breathing at rest; maximal changes in ΔPL of > 15 cm H2 O; > 15% neutrophils in BAL fluid on cytologic examination when horses were stabled; and results for CBC determination and serum biochemical analysis within the reference ranges of our laboratory. Thoracic radiographs were taken prior to the stabling to exclude concurrent pulmonary conditions. Endoscopic examination of the upper airways was also performed to exclude obstructive abnormalities. None of the horses had received treatments for heaves during the 3 months preceding the study.

Prior to the experiment, horses were conditioned to stand in stocks wearing a mask. The horses were stabled in the same barn for at least 3 weeks before the experiment, and the management remained the same throughout the study period. All experimental procedures were performed in accordance with the guidelines of the Canadian Council for Animal Care and were approved by the Animal Care Committee of the Faculty of Veterinary Medicine of the Université de Montréal.

Bronchoscopy and BAL—Bronchoalveolar lavages were performed in the morning (from 8:00 AM to 10:00 AM) by use of standard procedures for our laboratory.1 Briefly, horses were sedated with xylazinea (0.3 to 0.4 mg/kg, IV) followed 10 minutes later by butorphanolb (20 to 30 μg/kg, IV). Bronchoscopy was performed with a fiber-optic flexible endoscope (180 cm in length, 15 mm in diameter) inserted through the nares and directed down into the left lung until its tip was wedged in the bronchus. During the progression of the endoscope through the airway, several small boluses of a 0.5% solution of lidocaine hydrochloridec were administered (up to a maximal volume of 120 mL) to desensitize the airway mucosa. Once the endoscope was wedged in the bronchus, BAL was performed with two 250-mL boluses of sterile isotonic saline (0.9% NaCl) solution (at 37°C) rapidly instilled into the bronchus and aspirated via the endoscope's biopsy channel by use of a suction pump. The BAL fluid was collected into a siliconized glass jar and kept on ice until analysis. Total nucleated cells in BAL fluid samples were counted with a hemacytometer. Smears of the fluid were then prepared by centrifugation (at 90 × g for 5 minutes) of 100 μL of the BAL fluid and stained with a modified Wright solution. Differential counts were made on at least 400 cells; epithelial cells were not included in the differential count.

Respiratory mechanics measurements—Pulmonary function tests were performed on horses as described elsewhere.1 Briefly, flow rate was obtained by use of a heated pneumotachographd and associated differential pressure transducer.e The pneumotachograph was fitted to a mask placed and sealed over the nose of each horse so that the horse's nostrils were in line with the measuring equipment. During measurements, position of the head was set to minimize upper airway resistance.6 Electronic integration of the flow signal provided VT. For each experiment, the system was calibrated by forcing air at known flow rates (between 0 and 9 L/s) through the pneumotachograph with blower-rotameter equipment.

Transpulmonary pressure was obtained by use of a differential pressure transducerf that subtracted the esophageal pressure from the mask pressure. The esophageal pressure was measured with a balloon sealed over the end of a polyethylene catheter (inside diameter, 4.8 mm; outside diameter, 7.9 mm) placed in the distal third of the esophagus and distended with 3 mL of air. The pressure transducer was calibrated by use of a water manometer.

Signals from the transducers were amplified and passed through a digital-analogue converter to a computer equipped with a program for data acquisition and analysis.g Values of RL and EL were obtained by applying the data to the multiple regression equation for the single-compartment model of the lung.7 The coefficients of determination for the fit of the equation to the data were calculated for each breath. Respiratory rate data were also recorded. Signals were sampled at a frequency of 120 Hz for 100 seconds, and all valid breaths were used for analysis.

Experimental protocol—The design of the study was a crossover with 6 horses subjected to 3 treatment protocols (study 1, 2, and 3). In study 1, BAL procedures were performed on the 6 horses as already described immediately following respiratory mechanic baseline recording. Lung function was then measured 3, 6, 12, 24, and 48 hours later. To test the effect of saline solution instillation, a baseline respiratory mechanics analysis was performed, followed by bronchoscopy, as in study 1, except that no saline solution was instilled (study 2). For study 2, horses were sedated and the endoscope was inserted through the lower airway with instillation of local anesthetic solution as described, but once it was wedged in a lower bronchus, the endoscope was immediately retrieved. Lastly, to test the effects of sedation and insertion of the endoscope on lung function (study 3), the endoscope was similarly inserted through the airway with instillation of local anesthetic solution as described, but the procedure was performed on nonsedated horses. Once it reached a lower bronchus, the endoscope was withdrawn without injection of saline solution. Studies were performed in the order described, and a 2- to 4-week period elapsed between each study.

Statistical analysis— Baseline values of ΔPL,RL, and EL were compared by use of a repeated-measures ANOVA. Data were further analyzed by use of a repeated-measures ANOVA incorporating study group, horses, and time main effects as well as a group × time interaction effect. When a significant time effect was detected, values were compared with baseline by use of linear contrast of group means. When a significant group main effect or when group × time interaction was observed, values were compared with baseline value by use of contrasts for each group separately. Values of P ≤ 0.05 were considered significant.

Results

Animals—Bronchoalveolar lavage and respiratory mechanics procedures were well tolerated in all but 1 horse, which had intense coughing during bronchoscopy in study 3. One horse was removed from study 3 because it did not tolerate lung mechanics measurements and was at risk of injury to itself. Cytologic examination of BAL fluid samples revealed a high percentage of neutrophils in all horses (18% to 44%), confirming lower airway inflammation and the diagnosis of heaves in these horses.

Respiratory mechanics measurements—Consistent with the finding of labored breathing at rest, all horses had high values of ΔPL,RL, and EL at baseline. No significant difference was found in lung mechanics parameters between the baseline values of the 3 study periods (Figure 1). Values of ΔPL increased in 3 of the 6 horses over the 6-week study period, whereas lung mechanics improved in 2 horses. The lung function of 1 horse remained unchanged throughout the study period (Figure 1). No significant variation was found in VT and respiratory rate with time in the 3 studies (Table 1).

Figure 1—
Figure 1—

Individual horse values of maximal ΔPL (A), RL (B), and EL (C) in study 1, 2, and 3 at baseline (n = 6 horses). Study 1 = Complete BAL with sedation. Study 2 = BAL without saline (0.9% NaCl) solution instillation but with sedation. Study 3 = BAL without saline solution instillation and without sedation.

Citation: American Journal of Veterinary Research 67, 11; 10.2460/ajvr.67.11.1929

Table 1—

Mean ± SEM temporal values of VT and respiratory rate (f) in study 1 (n = 6 horses), study 2 (6), and study 3 (5).

VariableTime before (0 h) and after BAL
0 h3 h6 h12 h24 h48 h
VT (L)
 Study 14.4 ± 0.24.2 ± 0.34.2 ± 0.34.3 ± 0.24.0 ± 0.24.5 ± 0.3
 Study 24.5 ± 0.44.3 ± 0.44.0 ± 0.34.5 ± 0.44.0 ± 0.34.0 ± 0.4
 Study 33.9 ± 0.54.2 ± 0.54.2 ± 0.54.2 ± 0.43.9 ± 0.43.9 ± 0.3
f (min−1)
 Study 120.4 ± 5.224.3 ± 5.125.1 ± 5.824.0 ± 5.520.5 ± 4.921.1 ± 5.0
 Study 223.0 ± 6.225.9 ± 7.426.8 ± 7.724.5 ± 7.324.3 ± 7.524.1 ± 7.1
 Study 325.6 ± 7.628.4 ± 8.027.5 ± 7.930.7 ± 7.725.9 ± 6.329.2 ± 8.2

Study 1 = Complete BAL with sedation. Study 2 = BAL without saline (0.9% NaCl) solution instillation but with sedation. Study 3 = BAL without saline solution instillation and without sedation.

A significant time main effect was observed in RL(Figure 2) when data from all groups were analyzed by use of a repeated-measure ANOVA. This finding was caused by a significant (P = 0.04) decrease in RL at 3 hours, compared with baseline values. Interestingly, when groups were analyzed separately, significant changes in RL over time were observed only in study 1 at 3 and 6 hours. Compared with baseline, 3 of 6 horses from study 1 had a decrease in RL ranging from 46% to 78%, whereas it improved mildly in 4 of 6 horses of study 2 (19% to 34%) and 2 of 5 horses of study 3 (13% to 25%; Figure 3). The improvement in RL was still present 6 hours after BAL for 4 horses in study 1 (range, 29% to 59%), whereas only 2 (18% and 26%) and 1 horses (27%) kept values of RL below baseline in study 2 and 3, respectively (Figure 3).

Figure 2—
Figure 2—

Mean ± SEM values of relative changes in RL at baseline (0 hours) and 3, 6, 12, 24, and 48 hours after the BAL or control procedures in study 1 (n = 6 horses; circles), study 2 (6; triangles), and study 3 (5; squares). *Significant (P < 0.05) difference between group mean value and group mean baseline value in study 1. †Significant (P < 0.05) time main effect at 3 hours. See Figure 1 for remainder of key.

Citation: American Journal of Veterinary Research 67, 11; 10.2460/ajvr.67.11.1929

Figure 3—
Figure 3—

Bar graphs of individual horse values of the percentage variation in RL, compared with baseline, at 3 (graphs on the left) and 6 (graphs on the right) hours in study 1 (n = 6 horses), 2 (6), and 3 (5). See Figure 1 for remainder of key.

Citation: American Journal of Veterinary Research 67, 11; 10.2460/ajvr.67.11.1929

A significant change was also found in EL (Figure 4) and ΔPL (Figure 5) over time in the 3 groups of horses. This was caused by a significant increase in EL and ΔPL at 12 hours after BAL or control procedures.

Figure 4—
Figure 4—

Mean ± SEM values of relative changes in EL at baseline (0 hours) and 3, 6, 12, 24, and 48 hours after the BAL or control procedures in study 1 (n = 6 horses; circles), study 2 (6; triangles), and study 3 (5; squares). *Significant (P < 0.05) difference between group mean value and group mean baseline value in all studies. †Significant (P < 0.05) time main effect at 12 hours. See Figure 1 for remainder of key.

Citation: American Journal of Veterinary Research 67, 11; 10.2460/ajvr.67.11.1929

Figure 5—
Figure 5—

Mean ± SEM values of relative changes in ΔPL at baseline (0 hours) and 3, 6, 12, 24, and 48 hours after the BAL or control procedures in study 1, 2, and 3. See Figures 1 and 4 for key.

Citation: American Journal of Veterinary Research 67, 11; 10.2460/ajvr.67.11.1929

Discussion

The main finding of our study is that BAL was associated with a decrease in RL for up to 6 hours following the procedure. This effect was associated with saline solution instillation, which suggests that saline solution may clear mucus secretions in the middle-sized and larger airways of horses affected with heaves. These results are of importance for clinicians when performing a BAL to confirm the diagnosis of heaves in horses with labored breathing at rest. Furthermore, these data should be taken into account when designing research protocols that combine BAL and lung mechanics measurements. This would be particularly critical when the temporal effects of drugs are being investigated in horses with heaves, as in the absence of proper placebo control horses, a beneficial effect could be wrongly attributed to the medication being evaluated.

The increase in EL at 12 hours was observed in all 3 studies and thus was not attributed to the BAL procedure. While a larger study would be needed to thoroughly evaluate the safety of the BAL, our results indicate that lung mechanics of heaves-affected horses do not deteriorate after a BAL is performed. In agreement with this finding, BAL has been found to be safe in humans with asthma and chronic obstructive pulmonary disease.8–10 However, the immediate effects of the BAL procedure on the respiratory mechanics and other vital parameters were not evaluated in our study and warrant future investigations.

The beneficial effect of the BAL procedure on RL observed at 3 and 6 hours in horses from study 1 appears to be the result of saline solution administration, as bronchoscopies performed with or without sedation were not associated with a decrease in RL. This improvement was likely the result of removal of mucus from the larger airway after saline solution instillation, thus decreasing resistance to airflow where it has the greatest velocity and is the most likely to become nonlaminar. In support of this hypothesis, changes were of a greater magnitude for RL than for EL, which are believed to reflect primarily the central and peripheral airways mechanics, respectively. The improvement in RL at 3 hours may also have been attributable, in part, to the expulsion of mucus from larger airways during the coughing episodes commonly observed while injecting the lidocaine solution or when the endoscope is withdrawn at the end of a BAL procedure. We did not record the number of coughs in the 3 studies; thus, we do not know if horses coughed more in study 1 than without saline solution instillation. Furthermore, results of previous studies indicate that xylazine and butorphanol have effects that can alter respiratory mechanics in horses. In fact, xylazine administration decreases RL for 30 minutes in ponies affected with heaves,11 butorphanol inhibits mucus secretion and plasma extravasation,12,13 and xylazine and butorphanol have an inhibitory effect on cholinergic and noncholinergic airway constriction.14–17 However, we did not measure any effect of sedation on lung function after baseline in study 2 (horses with sedation and bronchoscopy but no saline solution administration). Unfortunately, because of the short-term effects of xylazine on vital functions, previous studies11,18,19 on the respiratory effects of xylazine in horses did not perform measurements after > 30 minutes following drug administration, so we cannot compare our results with the measurements previously reported. A likely explanation for the lack of residual effects of sedative administration in study 2 is that the described effects of xylazine and butorphanol were probably gone by 3 hours after administration.

We also observed a significant increase in EL and transpulmonary pressure at 12 hours in the 3 studies, without associated changes in respiratory rate and VT. These changes may be the result of a circadian effect on lung mechanics, similar to the increase in EL measured at night in heaves-affected horses in a previous study.20 Alternative explanations for the changes in EL may be related to the trauma and subsequent inflammation created by the passage of the endoscope or local anesthetics on the airway epithelium. In support of this explanation, results of previous studies indicate that airway neutrophilia follows BAL procedures in horses,5 humans, and other species,21–23 but this effect is short-lived, and values returned to baseline 12 hours later, suggesting no damage ensued from the airway neutrophilia, which is in agreement with what has been described in other species.24 However, because an endoscopic examination was performed in all 3 groups, the design of our study does not allow for the distinction of a circadian effect from the effect of the passage of the endoscope to explain the observed increase in EL. Although unlikely, the attribution of this increase in EL to the passage of the endoscope would suggest that bronchoscopy might directly result in the deterioration of lung function in horses.

In conclusion, the BAL procedure resulted in a transient improvement in RL lasting at least 6 hours in some horses. This effect may have resulted from clearance of mucus in large airways and was followed by an increase in EL that could be the result of a circadian effect or of the passage of the endoscope into the lower airway. These findings should be taken into account in the design of research protocols when sequential lung function measurements are performed following a BAL procedure in horses with heaves.

ABBREVIATIONS

BAL

Bronchoalveolar lavage

ΔPL

Maximal difference in transpulmonary pressure

VT

Tidal volume

RL

Pulmonary resistance

EL

Pulmonary elastance

a.

Rompun, Bayer Animal Health, Toronto, ON, Canada.

b.

Torbugesic, Wyeth Canada, Guelph, ON, Canada.

c.

Xylocard 1, Astra Pharma Inc, Mississauga, ON, Canada.

d.

Fleisch No. 4, Oem Medical, Richmond, Va.

e.

Model 143PC03D, Micro switch, Honeywell, Scarborough, ON, Canada.

f.

Model HCXPM005D6V, Sensor Technics, Newport News, Va.

g.

Anadat and Labdat 5.1, RHT Infodat, Montreal, QC, Canada.

References

  • 1.

    Leguillette R, Desevaux C, Lavoie JP. Effects of pentoxifylline on pulmonary function and results of cytologic examination of bronchoalveolar lavage fluid in horses with recurrent airway obstruction. Am J Vet Res 2002;63:459463.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Jackson CA, Berney C & Jefcoat AM, et al. Environment and prednisone interactions in the treatment of recurrent airway obstruction (heaves). Equine Vet J 2000;32:432438.

    • Search Google Scholar
    • Export Citation
  • 3.

    Robinson NE, Jackson C & Jefcoat A, et al. Efficacy of three corticosteroids for the treatment of heaves. Equine Vet J 2002;34:1722.

  • 4.

    Giguere S, Viel L & Lee E, et al. Cytokine induction in pulmonary airways of horses with heaves and effect of therapy with inhaled fluticasone propionate. Vet Immunol Immunopathol 2002;85:147158.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Sweeney CR, Rossier Y & Ziemer EL, et al. Effect of prior lavage on bronchoalveolar lavage fluid cell population of lavaged and unlavaged lung segments in horses. Am J Vet Res 1994;55:15011504.

    • Search Google Scholar
    • Export Citation
  • 6.

    Lavoie JP, Pascoe JR, Kurpershoek CJ. Effect of head and neck position on respiratory mechanics in horses sedated with xylazine. Am J Vet Res 1992;53:16521657.

    • Search Google Scholar
    • Export Citation
  • 7.

    Bates JH, Shardonofsky F, Stewart DE. The low-frequency dependence of respiratory system resistance and elastance in normal dogs. Respir Physiol 1989;78:369382.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Humbert M, Robinson DS & Assoufi B, et al. Safety of fiberoptic bronchoscopy in asthmatic and control subjects and effect on asthma control over two weeks. Thorax 1996;51:664669.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Elston WJ, Whittaker AJ & Khan LW, et al. Safety of research bronchoscopy, biopsy and bronchoalveolar lavage in asthma. Eur Respir J 2004;24:375377.

  • 10.

    Hattotuwa K, Gamble EA & Jeffery PK, et al. Safety of bronchoscopy, biopsy, and BAL in research patients with COPD. Chest 2002;6:19091912.

  • 11.

    Broadstone RV, Gray PR & Robinson NE, et al. Effects of xylazine on airway function in ponies with recurrent airway obstruction. Am J Vet Res 1992;53:18131817.

    • Search Google Scholar
    • Export Citation
  • 12.

    Belvisi MG, Rogers DF, Barnes PJ. Neurogenic plasma extravasation: inhibition by morphine in guinea pig airways in vivo. J Appl Physiol 1989;66:268272.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13.

    Rogers DF, Barnes PJ. Opioid inhibition of neurally mediated mucus secretion in human bronchi. Lancet 1989;1:930932.

  • 14.

    LeBlanc PH, Eberhart SW, Robinson NE. In vitro effects of alpha 2-adrenergic receptor stimulation on cholinergic contractions of equine distal airways. Am J Vet Res 1993;54:788792.

    • Search Google Scholar
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Contributor Notes

Dr. Léguillette's present address is Faculty of Veterinary Medicine, University of Calgary, G380, 3330 Hospital Drive, NW Calgary, AB, T2N 4N1, Canada.

Supported by the Groupe de Recherche en Médecine Équine du Québec.

Address correspondence to Dr. Léguillette.